HYPOPITUITARISM-DIAGNOSTIC CRITERIA AND TREATMENT (Growth Hormone deficiency and Pituitary dwarfism)

THE HYPOTHALAMIC – PITUITARY RELATIONSHIPS

HYPOTHALAMUS

The hypothalamus modulates the activity of the pituitary gland (hypophysis) via 2 distinct routes, one to the posterior and other to the anterior pituitary. The hypothalamus is connected with the posterior pituitary (neurohypophysis) by the supraopticohypophyseal nerve tract (peptidergic neurons). No nervous connection with the anterior pituitary (adenohypophysis) exists, but blood coursing through the hypothalamus gathers into a portal venous system which traverses the anterior pituitary and thus serves as a channel for direct transmission of the hypothalamic neurohormones. By these 2 routs, the hypothalamus is able to stimulate or release pituitary hormones.

Neurohypophyseal function.

The supraoptic and paraventricular nuclei of the hypothalamus secrete 2 octapeptide hormones – vasopressin and oxytocin. Both hormones are transported down axons bound as granules to carrier proteins, and are stored in the nerve endings of the posterior pituitary. They are released from these endings into the general circulation, where the granules dissociate, releasing free hormone and proteins.

Vasopressin (antidiuretic hormone, ADH) regulates water balance by stimulating resorption in the distal renal tubule. Secretion of ADH is controlled by increased osmotic pressure and decreased effective plasma volume.

Oxytocin stimulates uterine contractions (more so as pregnancy progresses), causes the myoepithelial cells of the breast to contract, expressing milk into the ducts. Secretion of oxytocin is controlled by suckling.

Adenohypophyseal function.

The hypothalamus plays an important role in hormone regulation by secreting a series of small peptides which stimulate or inhibit the synthesis and release of hormones by the anterior pituitary. Traditionally, these hypothalamic peptides have been known as releasing factors or ashypophysiotropic hormones (because they affect not only hormone release but also secretion). The neurons that secrete the hypothalamic peptides are located in the ventromedial nucleus nearby the median eminence. Secretion of these peptides is intimately related to the release of neurotransmitters by neurosecretory cells which are located in the same anatomical area (the best known neurotransmitters are the catecholamines dopamine and norepinephrine and the indoleamine serotonin).

The corticotropin-releasing hormone (CRH) stimulates the synthesis and release of corticotropin (ACTH) by the anterior pituitary.

The thyrotropin-releasing hormone (TRH) controls the secretion of thyrotropin (TSH) and also causes release of prolactin.

The gonadotropin-releasing hormone (GnRH), or luteinizing hormone-releasing hormone (LHRH) stimulates pituitary secretion of luteinizing hormone (LH) and to lesser extent that of follicle-stimulating hormone (FSH).

The growth-hormone-releasing hormone (GRH) stimulates and growth-hormone-inhibiting hormone (GIH, or somatotropin release-inhibiting factor (SRIF), or somatostatin) inhibits growth hormone (somatotropin) secretion from the anterior pituitary. GIH also inhibits insulin and glucagon secretion, gastrointestinal secretion of water, bicarbonate, pancreatic enzymes, gastric acid gastrin; glucose absorption and calcium transport.

The prolactin-inhibiting factor (PIF) controls prolactin secretion.

Hormone secretion  delivery to target cells  hormone recognition by receptors in target cells  biologic effect  hormone degradation  signal from target cells to slop further hormone secretion .
Hormone secretion delivery to target cells hormone recognition by receptors in target cells biologic effect hormone degradation signal from target cells to slop further hormone secretion . | Source
Hormone secretion  delivery to target cells  hormone recognition by receptors in target cells  biologic effect  hormone degradation  signal from target cells to slop further hormone secretion .
Hormone secretion delivery to target cells hormone recognition by receptors in target cells biologic effect hormone degradation signal from target cells to slop further hormone secretion . | Source

PITUITARY GLAND

The pituitary gland lies in a bony structure, the sella turcica, located at the base of the skull. The gland is a small organ about I cm long; it weighs 500 mg and is divided into two parts, anterior (adenohypophysis) and posterior (neurohypophysis). Both parts derive from the ectoderm, but their origins differ. The anterior pituitary originates from Rathke's pouch, an evagination from the roof of the embryonic oral region, whereas the posterior pituitary is formed from an extension of the floor of the third ventricle. Secretory granules can be demonstrated in the fetal pituitary by the end of the 12th week. The blood supply reaches the anterior pituitary through the superior hypophyseal artery (a branch or the internal carotid) and through the venous portal system, which originates in the median eminence and ends in the sinusoidal capillaries of the anterior lobe. Hypothalamic peptides reach the adenohypophysis by way of the portal system. Thin nerve fibers from the carotid plexus surround the arterioles.

The anterior pituitary secretes several important hormones, some of which in turn control hormone secretion by other glands: they are corticotropin (ACTH), somatotropin (growth hormone), prolactin, gonadotropins [follicle-stimulating (FSH) and luteinizing (LH) hormones], thyrotropin (TSH), and melanocyte-stimulating hormones (MSH).

FEEDBACK : Hormone secretion → delivery to target cells → hormone recognition by receptors in target cells → biologic effect → hormone degradation → signal from target cells to slop further hormone secretion .

ACTH stimulates adrenal growth and the secretion of cortisol. ACTH secretion is under dual control: by the hypothalamus through CRH (stress provokes serotonin secretion, and last stimulates secretion of GRH) and by adrenals through cortisol (by negative feedback). ACTH is secreted episodically, in a circadian pattern, with higher plasma concentrations in the early morning hours.

Somatotropin (growth hormone) stimulates protein synthesis and lipolysis, and increases blood glucose concentration (by decreasing of glucose utilization by the peripheral tissues and stimulating of hepatic gluconeogenesis). Somatotropin is under the control of GRH and GIH.

Prolactin function is initiation and maintenance of lactation. (Before pregnancy, the development and differentiation of the breast are influenced by estrogen, progesterone, and prolactin, but steroids are not effective in the absence of prolactin). Prolactin is under the control of TRH, PIF and physiologic stimulus for prolactin secretion is suckling.

Gonadotropins: FSH stimulates follicular growth in the female and spermatogenesis in the male;LH induces ovulation and maintains the corpus luteum after ovulation has occurred in the female and stimulates testosterone secretion by the Leydig cells of the testes.  Gonadotropins secretion is under dual control from the hypothalamus (GnRH production is stimulated by norepinephrine and inhibited by dopamine) and the gonads (feedback mechanism).

TSH stimulates the vascularity of the gland and the hypertrophy of the follicular cells, it also has extrathyroid actions, e.g. stimulation of lipolysis. TSH secretion is under the control of TRH and the thyroid hormones (feedback mechanism).

MSH stimulates hyperpigmentation. MSH secretion is under the control of ACTH.

Source
pituitary cysts are very common, with a frequency as high as 25 % in autopsy series. The cysts vary considerably in size. Some produce little change in the sella, while others may show moderate supraseliar extension or even massive sellar erosion
pituitary cysts are very common, with a frequency as high as 25 % in autopsy series. The cysts vary considerably in size. Some produce little change in the sella, while others may show moderate supraseliar extension or even massive sellar erosion
This photograph contrasts the residual viable pituitary (on the right) with the infarcted necrotic area (on the left). Notice the ghost architecture and the acellular area of infarction in this case of Sheehan'ssyndrome.
This photograph contrasts the residual viable pituitary (on the right) with the infarcted necrotic area (on the left). Notice the ghost architecture and the acellular area of infarction in this case of Sheehan'ssyndrome.
Weakness, dizziness, weight loss, and abdominal symptoms are secondary to decreased corlisol secretion by the adrenals. Symptoms of hypoglycemia may predominate. Dehydration, hypotension, and prostration may be found on physical examination
Weakness, dizziness, weight loss, and abdominal symptoms are secondary to decreased corlisol secretion by the adrenals. Symptoms of hypoglycemia may predominate. Dehydration, hypotension, and prostration may be found on physical examination | Source
The presence of pituitary insufficiency should be suspected from the history and physical examination  and confirmed by laboralory lesling. There are two types of diagnostic procedures: those designed to identify the cause of the problem (usually a r
The presence of pituitary insufficiency should be suspected from the history and physical examination and confirmed by laboralory lesling. There are two types of diagnostic procedures: those designed to identify the cause of the problem (usually a r
The sella turcica can be evaluated by plain x-ray films  of the skull, multidirectional polytomography, pneumoencephalography, computerized cranial axial tomography (CT scan), magneto  resonance investigation (MRI (pict.)) and cerebral angiography. P
The sella turcica can be evaluated by plain x-ray films of the skull, multidirectional polytomography, pneumoencephalography, computerized cranial axial tomography (CT scan), magneto resonance investigation (MRI (pict.)) and cerebral angiography. P
Cerebral angiography is useful in establishing the presence of parasellar lesions, determining the degree of suprasellar or parasellar extension of a pituitary tumor, excluding the presence of an aneurysm, and determining whether major vessels are in
Cerebral angiography is useful in establishing the presence of parasellar lesions, determining the degree of suprasellar or parasellar extension of a pituitary tumor, excluding the presence of an aneurysm, and determining whether major vessels are in

HYPOPITUITARISM

It is the syndrome, which is characterized by deficiency of one or more anterior pituitary hormones.

Etiology

Several pathologic processes may play an etiologic role in the development of the; syndrome:

1.     Tumors:

-         chromophobe adenomas can cause hypopituitarism by destroying the anterior pituitary cells that secrete the trophic hormones. Hormone deficiencies in order of frequency are growth-hormone, gonadotropins, TSH, ACTH, and prolaclin;

-         craniopharyngiomas arise from remnants of Rathke's pouch and can be either cystic or solid. This tumor is more common in younger people (with peak incidence in the second decade) who present with signs and symptoms of increased intracranial pressure; visual field defects, particularly bitemporal hemianopsia; hypogonadism; growth retardation; diabetes insipidus; and suprasellar calcifications;

-         pituitary cysts are very common, with a frequency as high as 25 % in autopsy series. The cysts vary considerably in size. Some produce little change in the sella, while others may show moderate supraseliar extension or even massive sellar erosion.

2.     Ischemia:

-         postpartum uterine hemorrhage (Sheehan's syndrome) is the most common cause of hypopituitarism in females. The clinical manifestations result from pituitary necrosis, which is believed to be caused by ischemia. Anterior pituitary hormone deficiencies appear during the puerperium. The neurohvpophysis is seldom affected. Failure to lactate and involution of the breasts are followed by loss of axillary and pubic hair. The amenorrhea of pregnancy persists and the symptoms of TSH and ACTH deficiency appear later. Although gonadotropins and growth-hormone deficiency may be the earliest to occur, there is variability in the order in which the hormones fail and in the type of hormones. affected.

-         less frequently, involvement of the vascular supply to the anterior piluitary in patients with diabetes mellitus, sickle-cell disease, and collagen vascular diseases can result in the development of pituitary insufficiency.

3.     Many cases of hypopiluilarism that were considered idiopalhic probably represent an autoimmuneprocess in which antipituiatary antibodies are present. Lymphocytic hypophysitis is a syndrome reported in women only during pregnancy or the postpartum period. Signs and symptoms resemble those seen in patients with pituitary tumors. Light microscopic studies reveal extensive cellular infiltration of the pituitary by lymphocytes. Antipituitary antibodies, particularly to prolactin, have been detected in some of the patients. The entity is considered to be autoimmune and it is associated with other endocrine autoimmune processes, notably chronic thyroiditis.

4.     Hypopituitarism frequently results from pituitary irradiation. Eighty-three % of patients who receive radiotherapy for tumors of the head and neck, usually 5000 rads, develop pituitary insufficiency. Hormone deficiencies may develop within a year or more after irradiation. The hypothalamus, the pituitary, or both may be affected.

5.     Infiltration of the pituitary gland by iron, histiocytes, or granulomatous processes is a relatively rare cause of hypopituitarism:

-         hemochromatosis;

-         histiocytosis;

-         sarcoidosis.

6.     Infectious processes:

-         tuberculosis;

-         bacteria;

-         fungus.

7.     Pituitary insufficiency can be caused by traumatic or surgical destruction of the hypothalamic-pituitary area.

Clinical presentation.

Many patients with pituitary tumors are asymptomatic, and the diagnosis is made accidentally by plain x-rays of the skull obtained. Usually, clinical manifestations of hypopituitarism are not present unless 75 % of the gland is destroyed.

Some patients present with signs and symptoms of increased intracranial pressure, such asheadaches, vomiting, and papilledema. Compression of the optic chiasm results in visual impairment, notably bitemporal hemianopsia.

In the classic case of hypopituitarism, clinical manifestations of ACTH, TSH, and gonadotropin deficiency are presen:

1.     Weakness, dizziness, weight loss, and abdominal symptoms are secondary to decreased corlisol secretion by the adrenals. Symptoms of hypoglycemia may predominate. Dehydration, hypotension, and prostration may be found on physical examination.

2.     Gonadotropin deficiency is responsible for decreased libido in patients of both sexes and for amenorrhea in females. Decreased libido, impotence, and hair loss are caused by testosterone deficiency, and amenorrhea is caused by estrogen deficiency. In males, a sallow complexion of the face, prominent wrinkles of the forehead, and loss of body hair, particularly pubic and axillary hair, may be very striking.

3.     Patients with unexplained anemia should be investigated for hypopituitarism. Erythropoiesis is hormone-dependent, and is particularly dependent upon testosterone, which stimulates erythropoietin production by the kidney.

4.     Secondary hypothyroidism is characterized by tiredness, cold intolerance, constipation, tingling and numbness of the extremities, and anorexia. Pale, dry skin and slow relaxation phase of the deep tendon reflexes are observed on examintion of the patient.

The symptoms of hypopituitarism mimic those of many diseases. The diagnosis can often be missed unless it is suspected. Watch for pituitary insufficiency:

1. In women who fail to lactate following pregnancy and delivery. (Involution of breasts and sparse axillary and pubic hair would suggest the diagnosis.)

2. In females with unexplained arnenorrhea, particularly if symptoms of ACTH and TSH deficiency or increased intracranial pressure are present.

3. In males with decreased libido and loss of axillary and pubic hair.

4. In patients with unexplained anemia.

5. In diabetic patients who experience a reduction in insulin requirements.

Diagnosis.

1. The presence of pituitary insufficiency should be suspected from the history and physical examination  and confirmed by laboralory lesling. There are two types of diagnostic procedures: those designed to identify the cause of the problem (usually a radiologic procedure) and those intended for evaluation of pituitary function.

2. Laboratory findings:

-         anemia, hypercholesterolemia, tendency to hypoglycemia;

-         hormonal assessment (decreased levels of pituitary and peripheral endocrine glands).

3. Instrumental investigations.

X-ray diagnosis of the abnormal sella turcica.

The sella turcica can be evaluated by plain x-ray films  of the skull, multidirectional polytomography, pneumoencephalography, computerized cranial axial tomography (CT scan),magneto – resonance investigation (MRI (pict.)) and cerebral angiography. Plain films of the sella are useful in evaluating patients for the possibility of a pituitary tumor. The sella may be abnormal in size, volume, or configuration. The upper limits of normal for sellar dimensions are length 17mm, depth 13mm, and width 15mm. Sellar enlargement is seen in 90 % of patients with endocrine deficiency caused by a pituitary tumor, but it may also be seen in patients with increased intracranial pressure, the empty sella syndrome, internal carotid artery aneurysm, primary hypothyroidism, and juxtasellar tumors. Likewise, a normal sella does not rule out pituitary pathology because microadenomas which are less than 1 cm in diameter may not be visualized.

Cerebral angiography is useful in establishing the presence of parasellar lesions, determining the degree of suprasellar or parasellar extension of a pituitary tumor, excluding the presence of an aneurysm, and determining whether major vessels are involved by the tumor.

Visual fields. A search for visual-field defects is important. Visual impairment in patients with hypopituitarism suggests the presence of a pituitary tumor compressing the optic chiasm. Bitemporal hemianopsia is the typical finding but other visual-field defects may be present. This ophthalmologic procedure can also help to monitor the response to therapy and to evaluate patients for possible tumor recurrences.

Treatment

The treatment of patients with pituitary insufficiency consists of

1)     eliminating the underlying cause and

2)     replacing the deficient hormones.

Pituitary tumors should be removed surgically, although irradiation and drug therapy (bromocriptine) are also available.

Hypothalamic peptides or pituitary hormones are not suitable for hormone replacement for several reasons:

(1) The human hormones are difficult to oblain in pure form;

(2) because of their nature and short halh-life they have to be given parenterally and frequently; and

(3) since they stimulate antibody formation, their activity is lost a few weeks after initiation of therapy.

Under these circumstances the usual practice is to administer the hormones produced by the target glands. They are available in pure form and are relatively inexpensive.

Adrenal insufficiency. Hydrocortisone is given orally in a total daily dose of 20 to 30 mg. Many physicians give one 20-mg tablet in the morning and half a tablet in the afternoon to try to stimulate the normal diurnal variation of plasma cortisol. This practice is not necessary, the local amount can be given as a -single dose in the morning. Other steroids with glucocorticoid activity can be used. Prednisone is preferred by some physicians because of its lower cost.

Hypothyroidism. Symptoms are easily controlled with synthetic l.-thyroxine. Most patients need 0.15 mg/day. In women the replacement dose is usually lower, and many do well on 0.1 mg/day.

Hypogonadism replacement with gonodal steroids is never indicated until puberty normally occurs. These agents in high doses can hasten bone maturation and epiphyseal closure, thereby limiting the height which may ultimately be reached.

In males testosterone therapy is recommended. (Testosterone enanthate, a long-acting preparation at a dose which is equiv alent to 50 to 100 mg/week. This is given as an intramuscular injection of 100 to 200 mg every 2 to 4 weeks. At the beginning of therapy, it is useful to administer 200 mg IM every 2 weeks until a good androgenic response is obtained. Side effects of testosterone include gynecomastia, acne, and occasionally hypertension, presumably secondary to stimulation of sodium retention by testosterone. The indications for testosterone therapy include decreased libido and anemia).Methyltestosterone or fluoxymesterone (10 to 40 mg/day) can also be used. They have the advantage of convenience, since they can be given orally, but development of cholesiatic jaundice and liver disease are potential problems with their use.

Premenupausal females with ovarian failure should be treated with estrogens. It can be ethinyl estradiol, which is administered orally in a dose of 0,025 to 0,05 mg once a day for 25 days of each month. Although this is the usual replacement dose. some patients may need a smaller or a larger dose. The benefits of estrogen therapy include return of menstruation, improvement of secondary sex characteristics such as skin texture and breast development, increased libido, and prevention of osteoporosis.

Side effects. Estrogen therapy is not without risk, e.g., the increased incidence of thrombophlebitis and pulmonary embolus. Hypertension, glucose intolerance, liver disease and hyperlipoproteinemia are also potential problems. There is also some controversial evidence that estrogens predispose to carcinoma of the endometrium, To minimize all these side effects, it is recommended that the minimum effective estrogen dose be used, that estrogens be prescribed cyclically rather than on an everyday basis, that periodic pelvic examinations be performed, and that an endometrial biopsy be done at the first sign of unexpected uterine bleeding.

Gross of a large chromophobe adenoma. Notice the location of the tumorin relation to the optic chiasm to explain visual field changes
Gross of a large chromophobe adenoma. Notice the location of the tumorin relation to the optic chiasm to explain visual field changes
Clinical features
Clinical features
haracterized by height more than 190 cm in women and 200 cm in men. Hypersecretion of GH prior to closure of epiphysis leads to proportional growth of bone; both length and width of bone are increased.
haracterized by height more than 190 cm in women and 200 cm in men. Hypersecretion of GH prior to closure of epiphysis leads to proportional growth of bone; both length and width of bone are increased. | Source
Klainfelters syndrome
Klainfelters syndrome
Marphan syndrome
Marphan syndrome
Bone overgrowth and soft tissue thickening lead to characteristic coarsening of the facial features. The hands are widened and the fingers become broad, requiring a larger  ring size. Similiar changes in the feet require a larger shoe size. This incr
Bone overgrowth and soft tissue thickening lead to characteristic coarsening of the facial features. The hands are widened and the fingers become broad, requiring a larger ring size. Similar changes in the feet require a larger shoe size. This incr
The sella turcica is enlarged  in at least 90 % of patients with acromegaly. (MRI , CT) Because of the slow progression of the disease, the sella is usually enlarged when the patient is first seen.
The sella turcica is enlarged in at least 90 % of patients with acromegaly. (MRI , CT) Because of the slow progression of the disease, the sella is usually enlarged when the patient is first seen.
Craniotomy is reserved for large tumors with suprasellar extension and involvement of the optic chiasm. Cryohypophysectomy (destruction of the pituitary by cold injury) can reduce the secretion of growth hormone without causing hypopituitarism in 88
Craniotomy is reserved for large tumors with suprasellar extension and involvement of the optic chiasm. Cryohypophysectomy (destruction of the pituitary by cold injury) can reduce the secretion of growth hormone without causing hypopituitarism in 88

GROWTH-HORMONE EXCESS

Increased secretion of growth hormone (GH) by pituitary tumors or increased sensitivity of peripheral tissues to GH leads to gigantism before puberty and to acromegaly after puberty.

Etiology

1.     Acidophilic adenoma of the pituitary.

2.     Chromophobe adenoma of the pituitary

3.     Ectopic GH-producing tumors. The signs and symptoms which appear in these patients are of two types:

1)     those secondary to the presence of tumor: mass effect (Headaches and visual impairment are present in 90 and 60 % of the patients respectively. Typically one finds bilateral loss of peripheral vision (bitemporal hemianopsia), which may be progressive.) and

2)     those secondary to increased circulating growth-hormone levels.

GIGANTISM

is characterized by height more than 190 cm in women and 200 cm in men. Hypersecretion of GH prior to closure of epiphysis leads to proportional growth of bone; both length and width of bone are increased.

Differential diagnosis have to be made with

- constitutional high height

           - Klainfelter’s syndrome

- Marphan syndrome

ACROMEGALY

GH hypersecretion after closure of epiphyses leads to periostal overgrowth and cortical thickening. Overgrowth of the mandible leads to protrusion of the jaw (prognatism). There is an overbite and the teeth become separated (diastema). Bone overgrowth and soft tissue thickening lead to characteristic coarsening of the facial features. The hands are widened and the fingers become broad, requiring a larger  ring size. Similiar changes in the feet require a larger shoe size. This increase in dimension of the acral (distal) parts of the body has led to the term acromegaly.

Hepatomegaly and cardiomegaly are consistent findings. Thyromegaly is present in about 25 % of the patients. Hyper- and hypothyroidism occurs rarely. The kidney may also become enlarged, and renal clearance of phosphate is frequently impaired.

Hypertension is present in 40 % of patients with acromegaly, although its cause is unknown. It is unclear whether the increase in blood pressure is caused by growth hormone per se or whether it is part of the generalized cardiovascular involvement seen in patients with the disease. Plasma renin may be high, normal, or low. The association of primary aldosteronism with acromegaly has been reported in a few cases.

Other manifestations of the disease are secondary to the abnormalities in glucose metabolism which result from growth-hormone excess. Thus, symptoms of diabetes mellitus, which include polyuria, polydipsia, polyphagia, and tiredness, may be present.

Increased perspiration is common among 90 % of patients. The skin is thickened, and females may note hypertrichosis.

Joint manifestations are common (70 %) in patients with acromegaly. In some patients, for example, arthralgias and arthritis may be the presenting complaints.

Amenorrhea, which occurs in as many as two-thirds of female patients, may be the chief com­plaint. Decreased libido is experienced by one-third of the patients.

Hyperfunction or deficiency of other pituitary trophic hormones may be present. Of note is the frequency among women with acromegaly (15 % of cases) of galactorrhea which is caused by increased secretion of prolactin by the pituitary tumor.

Diagnosis

The diagnosis of acromegaly is usually suspected from:

1)     the patient's history and

2)     physical examination (The head is large, the mandible is prominent, and the tongue is enlarged. The skin is thick and hard. Large hands and feet and increased subcutaneous tissue are evident on examination. Carpal tunnel syndrome occurs in as many as 44 % of the patients. Deformed joints can be confused with other arthritic syndromes.).

3)     The role of the laboratory is to assist in the confirmation of the diagnosis. Since the syndrome is caused by excessive growth-hormone production, one wants to demonstrate increased circulating levels of this hormone. An occasional blood sample drawn at 8 a.m. may be sufficient if the values are grossly elevated. Unfortunately, this procedure is not very reliable for two reasons:

-         some patients with acromegaly have normal growth-hormone concentrations, and

-          in normal subjects growth-hormone levels vary greatly. Stress, sleep, exercise, food ingestion, and diurnal variation can significantly affect growth-hormone concentrations. Thus, a normal serum growth-hormone level does not exclude acromegaly, and an elevated growth-hormone level does not always mean acromegaly.

To eliminate this problem one takes advantage of the concepts of feedback and autonomy to screen patients for acromegaly. Normally, glucose suppresses growth-hormone secretion. In patients with acromegaly the pituitary tumor is autonomous; that is, it does not respond to hyperglycemia. The recommended procedure consists of a glucose tolerance test with concomitant growth-hormone determinations; serum growth-hormone concentration falls in normal subjects 1 h after the oral glucose load. Patients with acromegaly not only have elevated values but also fail to suppress in response to glucose ingestion.

4)     Somatomedin-C, the tissue mediator of some of the effects of growth hor mone, has been measured by radioimmunoassay in the blood of patients with acromegaly. Because somalomedin-C binds to plasma protein, its serum concentrations are more stable than those of growth hormone. The values are evaluated in patients with acromegaly and they correlate well with growth hormone values 1 h post glucose administration.

5)     A paradoxical growth-hormone increase in response to TRH is seen in some patients with acromegaly, and when this abnormality is found, it can be used to follow the response to therapy.

6)     Glucose intolerance is seen in about 40 % of the patients. This information becomes available at the time the glucose tolerance test is ordered to obtain growth-hormone levels.

7)     An important part of the evaluation in patients with acromegaly is the search for visual-field defects. As mentioned earlier, because of the anatomical location of the tumor, the typical finding is the presence of bitemporal hemianopsia. However, other visual-field defects may be present.

8)     The sella turcica is enlarged  in at least 90 % of patients with acromegaly. (MRI , CT) Because of the slow progression of the disease, the sella is usually enlarged when the patient is first seen.

9)     One should also be interested in determining whether suprasellar extension of the tumor is present, and the best procedure for this purpose is computed tomography. This information can help the surgeon to decide what approach to use when removing the tumor.

Treatment.

Three therapeutic modalities—surgery, irradiation, and drugs—have been used to treat patients with acromegaly.

The surgical techniques of craniotomy, transsphenoidal hypophysectomy, and stereotaxic surgery, particularly cryosurgery, have been used to treat acromegaly, and all of them have met with some success.

At present, transsphenoidal hypophysectomy  is the procedure of choice. An incision is made in the inner aspect of the upper lip and the pituitary gland is entered through the nasal septum and the sphenoid sinus. With this procedure, improvement or cure of the acromegaly can be achieved in nearly 90 % of the patients. Advantages of transsphenoidal hypophysectomy, besides its effectiveness, include simplicity and low morbidity. Hypupituitarism and diabetes insipidus are extremely uncommon, since the re mainder of the pituitary gland is left intact. Perhaps the major difficulty of transsphenoidal hypophysectomy is the fact that some patients need a second operation because of recurrence of symptoms.

Craniotomy is reserved for large tumors with suprasellar extension and involvement of the optic chiasm. Cryohypophysectomy (destruction of the pituitary by cold injury) can reduce the secretion of growth hormone without causing hypopituitarism in 88 % of the patients.

External irradiation has been reported by some to control the activity of the disease in as many as 80 % of the patients, but other reports indicate that the procedure has not been too successful. One of the limitations is the amount of radioactivity that can be delivered, which should not exceed 5500 roentgens (R). Another difficulty with irradiation is its slow onset of action, the full effects requiring as long as 10 years to appear.

Irradiation with accelerated proton beams, which can be focused on the pituitary, delivers 10,000 or more rads without damaging the surrounding tissues. Results with this technique and those obtained with alpha particle irradiation are similar.

Drugs.

A dopaminergic agonist and ergot derivative, 2a-bromergocriptine (bromocriptine), causes a paradoxical inhibition of growth-hormone secretion in patients with acromegaly. In doses of 10 to 60 mg/day, the drug has induced clinical remissions in 73 % of the treated patients. However, return of normal growth-hormone suppressibility in response to glucose is seen in only 22 % of patients. Side effects include nausea, orthostatic hypotension, consti pation, digital vasospasm, and peptic ulcer.

 Precocious puberty
Precocious puberty

Contributors

Dr Andrei Lapyavko Andreivich. Department of Endocrinology- Ternopil State Medical University, Ternopil- Ukraine
Dr Andrei Lapyavko Andreivich. Department of Endocrinology- Ternopil State Medical University, Ternopil- Ukraine | Source
Source
Source
Source
Source
Source
Source
Source

PITUITARY DWARFISM (GROWTH FAILURE)

it is the disease caused by decreased secretion of GH by pituiatary gland or decreased sensitivity of peripheral tissues to this hormone and leads to growth retardation.

The height of adult men is less than 130 cm, and adult women is less than 120 cm.

Etiology

Children with pituitary dwarfism most commonly have either a craniopharyngioma  or no demonstratable etiology (idiopathic hypopituitarism). The latter is more frequent in males than in females. Before the diagnosis of pituitary dwarfism can be made, all other etiologies must be ruled out (look differential diagnosis).

Classification.

A.   Organic (trauma, neoplasms, infection).

B.    Idiopatic (primary or secondary, due to hypothalamic deficiency).

1.     Panhypopituitarism.

2.     Isolated GH deficiency (may be hereditary and transmitted as an autosomal recessive trait, in other instances a hereditary basis cannot be established).

Clinical manifestations

1.     Child is born with normal weight and height.

2.     Growth retardation can be observed since 3 – 4 years (the increasing of the height is not more than 1 cm per year.

3.     The patient, despite small size, has normal body proportions.

4.     Mental develoment is normal.

5.     Secondary hypothyroidism.

6.     Secondary adrenal insufficiency.

7.     Puberty will not appear because of a lack of gonadotropic hormons (secondary hypogonadism).

8.     The passport age is not corresponding with biologic age.

9.     In patients with isolated GH deficiency the patients have normal pituitary function (other than lack og GH), undergo normal puberty, and have normal reproductive capacity.

Diagnosis

Clinical picture (carefully recorded growth charts may disclose the time of onset of the disease); level of GH; X-ray examination of the skull and hands can be helpful in diagnosis.

Differential diagnosis have to be made with other causes of short stature:

I.                  Endocrine:

1.     Primordial (Lorrain – Levi) dwarfism (is an ill-defined diagnosis which presupposes normal hormonal activity in an individual with limited potential for tissue growth. Because the infants in this category are often small for gestation age, the term intrauterine dwarfism has also been used to designate those who have  growth retardation at birth. While patients with hypopituitarism are normal of size at birth (probably because of maternal Ghand somatomedin), patients with premordial dwarfism are already dwarfed at thus time because maternal somatomedin is not available or is ineffective. Characteristically, growth is slow from earliest infancy, although epiphyseal maturation and sexual development occur normally or at only a slightly retarded rate. No definite abnormalies have been reported. Intellect may be affected and other congenital anomalies may be present.)

2.     Hypothyroidism (primary or secondary)

3.     Precocious puberty.

4.     Cushing’s syndrome.

II.                Constitutional (normal variant) short stature  .

III.             Nonendocrine disorders (such as chronic disease, malabsorption syndromes, certain hematologic diseases, diseases involving the skeletal system are also common causes of growth retardation).

IV.            Psychosocial dwarfism (is associated with severe emotional deprivation, and is alleviated by the removal of the child from the adverse situation).

Treatment.

I.                   Balanced diet.

II.                Complex of physical exercises.

III.             Pharmacotherapy.

1.     GH (synthetic). Indications: a low level of GH or a low level of somatomedin in patients with biologic age less than 12 – 13 years and passport age more than 3 years.  Doses of 2 – 4 IU of GH given IM at nighttime three times a week for 2 – 3 months with 2 – 3 months break have accelerated the rate of linear growth, through often this therapeutic effect is not sustained.

2.     Anabolic steroids under the control of biologic (osteal) age.

3.     Thyroid replacement.

4.     Replacement with gonodal steroids is never indicated until puberty normally occurs. These agents in high doses can hasten bone maturation and epiphyseal closure, thereby limiting the height which may ultimately be reached.

5.     Vitamintherapy.

IV.            Surgical therapy (a craniopharyngioma presents special therapeutic problems, usually necessitating removal of tumor tissue or drainage of fluid from tumor cysts.

References

1.     The Merck Manual of Diagnosis and Therapy (fourteenth Edition)/ Robert Berkow and others. – published by Merck Sharp & Dohme Research Laboratories, 1982. – P. 987 – 992, 916 – 921. 990 – 997. 1032 – 1037, 1680 – 1681.

2.     Endocrinology (A Logical Approach for Clinicians (Second Edition)). William Jubiz.-New York: WC Graw-Hill Book, 1985. - P. 21 – 33. 34 – 38,52 – 63. 416 - 497.

3.     Manual of Endocrinology and Metabolism (Second Edition)/ Norman Lavin. – Little, Brown and Company.- Boston-New York-Toronto-London, 1994. -  P. 55 – 56. 179 - 274.

More by this Author


Comments 21 comments

D.Virtual.Doctor profile image

D.Virtual.Doctor 6 years ago from Europe Author

Hey guys! My 17th hub and clinical case been medically and rigorously analysed here. Is it not amazing?

The anterior pituitary synthesize and release several polypeptide and protein hormones. These influence a variety of metabolic processes essential for normal growth and development; they also maintain the normal structure and activity of several target glands.

Age and sex play an important role in the frequency of a given type of Cushing’s syndrome. Adrenal carcinoma is the cause in 65 % of patients younger than 15, nonpituitary ACTH secretion predominates in males, and 75 % of patients with pituitary – dependent Cushing’s syndrome are females.

The frequency of acromegaly among male and female is nearly equal. The gigantism appears more often in boys in prepubertal and pubertal period. Pituitary dwarfism, diabetes insipidus and syndrome of inappropriate ADH secretion a quiet rare but need early diagnosis and substitution therapy.


Virginia Mason Medical Center, WA 5 years ago

Posterior pituitary (Neurohypophysis)

Main article: Posterior pituitary

The posterior pituitary stores and releases:

Oxytocin, most of which is released from the paraventricular nucleus in the hypothalamus

Antidiuretic hormone (ADH, also known as vasopressin and AVP, arginine vasopressin), the majority of which is released from the supraoptic nucleus in the hypothalamus

Oxytocin is one of the few hormones to create a positive feedback loop. For example, uterine contractions stimulate the release of oxytocin from the posterior pituitary, which, in turn, increases uterine contractions. This positive feedback loop continues throughout labor.

[edit]Intermediate lobe

There is also an intermediate lobe in many animals, but is rudimentary in humans. For instance, in fish, it is believed to control physiological color change. In adult humans, it is just a thin layer of cells between the anterior and posterior pituitary. The intermediate lobe produces melanocyte-stimulating hormone (MSH), although this function is often (imprecisely) attributed to the anterior pituitary.

[edit]Variations among vertebrates

The pituitary gland is found in all vertebrates, but its structure varies between different groups.

The division of the pituitary described above is typical of mammals, and is also true, to varying degrees, of all tetrapods. However, only in mammals does the posterior pituitary have a compact shape. In lungfishes it is a relatively flat sheet of tissue lying above the anterior pituitary, and in amphibians, reptiles and birds, it becomes increasingly well developed. The intermediate lobe is generally not well developed in tetrapods, and is entirely absent in birds.[4]

Apart from lungfishes, the structure of the pituitary in fish is generally different from that in tetrapods. In general, the intermediate lobe tends to be well developed, and may equal the remainder of the anterior pituitary in size. The posterior lobe typically forms a sheet of tissue at the base of the pituitary stalk, and in most cases sends irregular finger-like projection into the tissue of the anterior pituitary, which lies directly beneath it. The anterior pituitary is typically divided into two regions, a more anterior rostral portion and a posterior proximal portion, but the boundary between the two is often not clearly marked. In elasmobranchs there is an additional, ventral lobe beneath the anterior pituitary proper.[4]

The arrangement in lampreys, which are amongst the most primitive of all fish, may indicate how the pituitary originally evolved in ancestral vertebrates. Here, the posterior pituitary is a simple flat sheet of tissue at the base of the brain, and there is no pituitary stalk. Rathke's pouch remains open to the outside, close to the nasal openings. Closely associated with the pouch are three distinct clusters of glandular tissue, corresponding to the intermediate lobe, and the rostral and proximal portions of the anterior pituitary. These various parts are separated by meningial membranes, suggesting that the pituitary of other vertebrates may have formed from the fusion of a number of separate, but closely associated, glands.[4]

Most fish also possess a urophysis, a neural secretory gland very similar in form to the posterior pituitary, but located in the tail and associated with the spinal cord. This may have a function in osmoregulation.


University Health Network 5 years ago

A pituitary tumor is an abnormal growth in the pituitary gland, the part of the brain that regulates the body's balance of hormones.

Causes

Most pituitary tumors are noncancerous (benign). Up to 20% of people have pituitary tumors. However, many of these tumors do not cause symptoms and are never diagnosed during the person's lifetime.

The pituitary gland is a pea-sized endocrine gland located at the base of the brain. The pituitary helps control the release of hormones from other endocrine glands, such as the thyroid and adrenal glands. The pituitary also releases hormones that directly affect body tissues, such as bones and the breast's milk glands. These hormones include:

Adrenocorticotropic hormone (ACTH)

Growth hormone (GH)

Prolactin

Thyroid-stimulating hormone (TSH)

As the tumor grows, hormone-releasing cells of the pituitary may be damaged, causing hypopituitarism.

The causes of pituitary tumors are unknown. However, some are part of a hereditary disorder called multiple endocrine neoplasia I (MEN I).

Other types of tumors that can be found in the same part of the head as a pituitary tumor:

Craniopharyngiomas

Cysts

Germinomas

Tumors that have spread from cancer in another part of the body (metastatic tumors)

Back to TopSymptoms

Most pituitary tumors produce too much of one or more hormones. As a result, symptoms of one or more of the following conditions can occur:

Hyperthyroidism

Cushing syndrome

Gigantism or acromegaly

Nipple discharge

Symptoms caused by pressure from a larger pituitary tumor may include:

Headache

Lethargy

Nasal drainage

Nausea and vomiting

Problems with the sense of smell

Visual changes

Double vision

Drooping eyelids

Visual field loss

Rarely, these symptoms may occur suddenly and can be severe.

Back to TopExams and Tests

Your health care provider will perform a physical examination. The provider will note any problems with double vision and visual field, such as a loss of peripheral vision or the ability to see in certain areas.

Endocrine function tests include:

Cortisol levels:

Dexamethasone suppression test

Urine cortisol test

Follicle-stimulating hormone (FSH) levels

Insulin growth factor-1 (IGF-1) levels

Luteinizing hormone (LH) levels

Serum prolactin levels

Testosterone/estradiol levels

Thyroid hormone levels:

Free T4 test

TSH test

Tests that help confirm the diagnosis include the following:

Formal visual field testing

MRI of head

Back to TopTreatment

Pituitary tumors are usually not cancerous and therefore won't spread to other areas of the body. However, as they grow, they may place pressure on important nerves and blood vessels.

Surgery to remove the tumor is often necessary, especially if the tumor is pressing on the optic nerves, which could cause blindness.

Most of the time, pituitary tumors can be removed through the nose and sinuses. However, some tumors cannot be removed this way and will need to be removed through the skull (transcranial).

Radiation therapy may be used to shrink the tumor, either in combination with surgery or for people who cannot have surgery.

The following medications may shrink certain types of tumors:

Bromocriptine or cabergoline are the first-line therapy for tumors that release prolactin. These drugs decrease prolactin levels and shrink the tumor.

Ocreotide or pegvisomant is sometimes used for tumors that release growth hormone, especially when surgery is unlikely to result in a cure.

Back to TopSupport Groups

The Pituitary Network Association -- www.pituitary.org

Back to TopOutlook (Prognosis)

If the tumor can be surgically removed, the outlook is fair to good, depending upon whether the entire tumor is removed.

Back to TopPossible Complications

The most serious complication is blindness. This can occur if the optic nerve is seriously damaged.

The tumor or its removal may cause permanent hormone imbalances. The affected hormones may need to be replaced.

Back to TopWhen to Contact a Medical Professional

Call your health care provider if you develop any symptoms of a pituitary tumor.

Back to TopReferences

Melmed S, Kleinberg D. Anterior pituitary. In: Kronenberg HM, Melmed S, Polonsky KS, Larsen PR. Williams Textbook of Endocrinology . 11th ed. Philadelphia, PA: Saunders Elsevier; 2008:chap 8.

http://health.nytimes.com/health/guides/disease/pi...


Bc Children's Hospital 5 years ago

What is the Pituitary Gland?

The pituitary gland is a pea-sized gland located at the base of the skull between the optic nerves. The pituitary gland secretes hormones. Hormones are chemicals that travel through our blood stream. The pituitary is sometimes referred to as the "master gland" as it controls hormone functions such as our temperature, thyroid activity, growth during childhood, urine production, testosterone production in males and ovulation and estrogen production in females. In effect the gland functions as our thermostat that controls all other glands that are responsible for hormone secretion. The gland is a critical part of our ability to respond to the environment most often without our knowledge.

The pituitary gland actually functions as two separate compartments an anterior portion (adenohypohysis-hormone producing) and the posterior gland (neurohypophysis). The anterior gland actually is made of separate collection of individual cells that act as functional units (it is useful to consider them as individual factories) that are dedicated to produce a specific regulatory hormone messenger or factor. These factors are secreted in response to the outside environment and the internal bodily responses to this environment. These pituitary factors then travel through a rich blood work network into the blood stream and eventually reach their specific target gland. They then stimulate the target gland to produce the appropriate type and amount of hormone so the body can respond to the environment correctly.

Similar to the cortisol factory there are additional factories:

Growth Hormone

Prolactin

Gonadotropin ("sex hormones")

Thyroid

These five axes (factories) function as the anterior pituitary gland neuroendocrine unit. If any one of these factories become excited and start to overproduce their respective hormonal factor the net result is excess production of the final hormone product. So in the above example, if the cortisol cells (corticotrophs) loose their ability to respond to the normal stimuli from the environment and hypothalamus and develop their own independent, uncontrolled autonomous secretion they will produce more cortisol than the body requires. In return the adrenal gland will be over stimulated and secrete unregulated and unneeded catecholomines (stress chemicals). The net result is excess production of these important chemicals that raise the blood pressure and drive the heart in order to respond to stress when needed and can cause the body and internal organs to be stressed when there is no need. The consequences of overdriving the internal organs of the body can be life threatening. Often these cells that overproduce their respective hormone will clump together within a given area of the pituitary gland creating a true factory of over production – pituitary tumor.

In addition to these five factories (cell lines) that produce hormones the anterior pituitary gland also contains remnants of the parent cells from which each of these individual cells came from. Specifically as the pituitary gland was formed the anterior gland contained a parent cell (pituicyte) which if you will was a parent cell. During embryological development this parent cells grew and matured into a series of daughter cells. Each of these daughter cells differentiated or learned to secrete a specific type of hormone eventually resulting in one of the five factory cells. In about 20% of the cases in fact the parent cell (which has not yet learned to secrete anything) grows excessively creating a collection or clump—pituitary tumor. This clump can grow and in the process create pressure on adjacent structures. Therefore these nonsecreting tumors create a problem for the patient not from excess hormone production but rather because of pressure on adjacent structures.

What are the adjacent structures?

If the pressure is exerted on the other members of the pituitary gland directly it impairs their ability to secrete their specific hormone – pituitary dysfunction. Among the most sensitive factories are the sex hormones (gonadotropins). If the pituitary tumor grows sideways (fat tumor) it will compress the cavernous sinus. This structure is an important cave located on either side of the gland that is continues a channel for blood to drain out of the brain, the carotid artery to supply the brain, and the cranial nerve that move the eyes. Fortunately, dysfunction of these critical structures is a rare and late event in most cases. However it is more likely that the gland will grow tall or upward (tall tumor). Often it will extend out of the bony structure that houses the pituitary gland (sella – named after the Turkish saddle). It will then grow through the thin "saran wrap" – like membrane (diaghrama) that separates the pituitary fossa or sella from the brain. It will then start to grow upward and start to push on the junction of the optic nerves where they cross (optic chiasm). When this happens the vision becomes compromised. The pattern of vision loss is a reflection of the compression at the site of crossing and so the patient develops blind spots along both temple regions.

Both tumors that secrete hormones (functional tumors) and tumors that do not (non-functional tumors) can create this pressure or mass effect. More often it is these nonfunctional tumors that present with visual loss. In order for visual loss to occur the tumor has to be larger and grown through the confines of the sella and upward to the optic chiasm. These tumors are generally larger. The functional tumors often present when they are smaller because they have created a syndrome of excess production that prompts the patient to get help often before the vision is compressed.

from

http://www.neurosurgery.pitt.edu/minc/skullbase/pi...


Wisconsin Health and Hospital Association 5 years ago

Other tumors

In a few patients, acromegaly is caused not by pituitary tumors but by tumors of the pancreas, lungs, and adrenal glands. These tumors also lead to an excess of GH, either because they produce GH themselves or, more frequently, because they produce GHRH (Growth Hormone Releasing Hormone), the hormone that stimulates the pituitary to make GH. In these patients, the excess GHRH can be measured in the blood and establishes that the cause of the acromegaly is not due to a pituitary defect. When these non-pituitary tumors are surgically removed, GH levels fall and the symptoms of acromegaly improve.

In patients with GHRH-producing, non-pituitary tumors, the pituitary still may be enlarged and may be mistaken for a tumor. Therefore, it is important that physicians carefully analyze all "pituitary tumors" removed from patients with acromegaly in order not to overlook the possibility that a tumor elsewhere in the body is causing the disorder.

[edit]Pituitary gigantism

This condition of growth hormone excess is rare in children and is referred to as pituitary gigantism, because the excessive growth hormone produces excessive growth of bones and the child can achieve excessive height; from 2.1 to 2.7 m (6'11" to 8'11") in stature by adulthood if left untreated. As an affected child becomes an adult, many of the adult problems can gradually develop. The distinction between gigantism (occurring in children) and acromegaly (occurring in adults) can be made by the occurrence of the adenoma in relation to the closure of the epiphyses. If elevated growth hormone levels occur before the closure of the epiphyses (i.e. in prepubertal children), then gigantism ensues. If it occurs after the closure of the epiphyses (i.e., in adults) then acromegaly ensues.

[edit]Diagnosis

Frequent blood sampling with serum GH measurement shows that in normal subjects (left panel) GH can fluctuate between undetectable levels (most of the time) and peaks of up to 30 ?g/l (90 mIU/l), owing to the episodic nature of GH secretion, while in patients with acromegaly (an example is given on right panel), GH hypersecretion is continuous and GH never returns to undetectable levels.

Magnetic resonance image of a pituitary macroadenoma that caused acromegaly with compression of the optic chiasm.

Site of action of the different therapeutic tools in acromegaly. Surgery, radiotherapy, somatostatin analogues and dopamine agonists act at the level of the pituitary adenoma, while GH-receptor antagonists act in periphery by blocking the growth hormone receptor and thus impairing the effects of GH on the different tissues.

If acromegaly is suspected, medical imaging and medical laboratory investigations are generally used together to confirm or rule out the presence of this condition.

IGF1 provides the most sensitive and useful lab test for the diagnosis of acromegaly. A single value of the Growth hormone (GH) is not useful in view of its pulsatality (levels in the blood vary greatly even in healthy individuals). GH levels taken 2 hours after a 75 or 100 gram glucose tolerance test are helpful in the diagnosis: GH levels are suppressed below 1 ?g/L in normal people, and levels higher than this cutoff are confirmatory of acromegaly.

Other pituitary hormones have to be assessed to address the secretory effects of the tumor as well as the mass effect of the tumor on the normal pituitary gland. They include TSH (thyroid stimulating hormone), gonadotropic hormones (FSH,LH), ACTH (adrenocorticotropic hormone), prolactin.

An MRI of the brain focusing on the sella turcica after gadolinium administration allows for clear delineation of the pituitary and the hypothalamus and the location of the tumor.

[edit]Treatment

The goals of treatment are to reduce GH production to normal levels, to relieve the pressure that the growing pituitary tumor exerts on the surrounding brain areas, to preserve normal pituitary function, and to reverse or ameliorate the symptoms of acromegaly. Currently, treatment options include surgical removal of the tumor, drug therapy, and radiation therapy of the pituitary.

Surgery is a rapid and effective treatment, of which there are two alternative methods. The first method, a procedure known as Endonasal Transphenoidal surgery, involves the surgeon reaching the pituitary through an incision in the nasal cavity wall. The wall is reached by passing through the nostrils with microsurgical instruments. The second method is Transsphenoidal surgery during which an incision is made into the gum beneath the upper lip. Further incisions are made to cut through the septum to reach the nasal cavity, where the pituitary is located. Endonasal Transphenoidal surgery is a less invasive procedure with a shorter recovery time than the older method of Transphenoidal surgery, and the likelihood of removing the entire tumor is greater with reduced side-effects. Consequently, Endonasal Transphenoidal surgery is often used as a first option, with Transphenoidal and other treatments, such as, medicinal therapy or radiostatic neurosurgery being used to reduce the remaining adverse effects of the remaining tumor.

These procedures normally relieve the pressure on the surrounding brain regions and lead to a lowering of GH levels. If the surgery is successful, facial appearance and soft tissue swelling improve within a few days. Surgery is most successful in patients with blood GH levels below 40 ng/ml before the operation and with pituitary tumors no larger than 10 mm in diameter. Success depends on the skill and experience of the surgeon. The success rate also depends on what level of GH is defined as a cure. The best measure of surgical success is normalization of GH and IGF-1 levels. Ideally, GH should be less than 2 ng/ml after an oral glucose load. A review of GH levels in 1,360 patients worldwide immediately after surgery revealed that 60 percent had random GH levels below 5 ng/ml. Complications of surgery may include cerebrospinal fluid leaks, meningitis, or damage to the surrounding normal pituitary tissue, requiring lifelong pituitary hormone replacement.

Even when surgery is successful and hormone levels return to normal, patients must be carefully monitored for years for possible recurrence. More commonly, hormone levels may improve, but not return completely to normal. These patients may then require additional treatment, usually with medications.

The primary current medical treatment of acromegaly is to use somatostatin analogues -- octreotide (Sandostatin) or lanreotide (Somatuline). These somatostatin analogues are synthetic forms of a brain hormone, somatostatin, which stops GH production. The long-acting forms of these drugs must be injected every 2 to 4 weeks for effective treatment. Most patients with acromegaly respond to this medication. In many patients, GH levels fall within one hour and headaches improve within minutes after the injection. Several studies have shown that octreotide and lanreotide are effective for long-term treatment. Octreotide and lanreotide have also been used successfully to treat patients with acromegaly caused by non-pituitary tumors.

Somatostatin analogues are also sometimes used to shrink large tumors before surgery.

Because octreotide inhibits gastrointestinal and pancreatic function, long-term use causes digestive problems such as loose stools, nausea, and gas in one third of patients. In addition, approximately 25 percent of patients develop gallstones, which are usually asymptomatic. In rare cases, octreotide treatment can cause diabetes. On the other hand, scientists have found that in some acromegaly patients who already have diabetes, octreotide can reduce the need for insulin and improve blood sugar control.

For those who are unresponsive to somatostatin analogues, or for whom they are otherwise contraindicated, it is possible to treat using one of the dopamine agonists, Bromocriptine (Parlodel) or Cabergoline. These have the advantage of being tablets rather than injections, and cost considerably less. These drugs can also be used as an adjunct to somatostatin analogue therapy. They are most effective in those whose pituitary tu


Women & Infants Hospital of Rhode Island 5 years ago

Complications

Severe headache

Arthritis and carpal tunnel syndrome

Enlarged heart

Hypertension

Diabetes mellitus

Heart failure

Kidney failure

Compression of the optic chiasm leading to loss of vision in the outer visual fields (typically bitemporal hemianopia)

Increased palmar sweating and sebum production over the face (seborrhea) are clinical indicators of active growth hormone (GH) producing pituitary tumors. These symptoms can also be used to monitor the activity of the tumor after surgery although biochemical monitoring is confirmatory.

[edit]Pseudoacromegaly

Pseudoacromegaly is a condition with the usual acromegaloid features but without an increase in growth hormone and IGF-1. It is frequently associated with insulin resistance.[5] Cases have been reported due to minoxidil at an unusually high dose.[6]

[edit]Notable cases

Famous patients, all but three (Abraham Lincoln, Maurice Tillet and Antonio Silva) standing in excess of 2.00 metres (6.6 feet):

Abraham Lincoln,(February 12, 1809 – April 15, 1865) the 16th President of the United States, was debated at several occasions to have Marfan's syndrome and also Acromegaly.[7][8] He grew to 1.93 m (6 ft. 4 in) in height and generally weighed less than 82 kg (180 lb). His legs and arms were disproportionately long for his body, which, when seated, was about the length of an average six-footer.[clarification needed] Lincoln's body growth and energic constitution show gross evidence of pituitary hyperactivity and gonadal hypoactivity. He was a long, thin baby at birth, with unusually long, thin arms and legs.

André the Giant, wrestler and actor [9][10] 2.13 m (7') tall after back surgery; his original wrestling stats listed him at 2.23 m (7'4"). He died at the age of 46. (He chose not to be treated and died from cardiac complications of the disease.)

Richard Kiel, Jaws from the James Bond Movies and Mr. Larson in Happy Gilmore.[11]

Rondo Hatton, character horror actor in the '30s and '40s[12]

Pio Pico, the last Mexican Governor of California (1801–1894), manifested acromegaly without gigantism between at least 1847 and 1858. Some time after 1858 signs of the growth hormone-producing tumor disappeared along with all the secondary effects the tumor had caused in him. He looked normal in his 90's.[13] His remarkable recovery is likely an example of spontaneous selective pituitary tumor apoplexy.[14]

Sir Archibald Levin Smith (1836–1901), British judge,[15]

Paul Wight, wrestler, also known as "The Big Show" or "The Giant".[16]

James McLeay, professional SANFL player, suffers from low grade acromegaly, 2.1 m, 120 kilograms.[17]

Nikolay Valuev, professional boxer and former World title holder, 2.13m (7'0"), 141 kg (311 pounds).[18]

Carel Struycken, Actor, 2.13m (7'0").[19]

Primo Carnera, professional boxer and World Heavyweight champion, 216 cm (85 in).[20]

Maurice Tillet (1903 – August 4, 1954) French professional wrestler.

[edit]Fictional

It has been suggested that the character 'Punch' from Punch and Judy was originally a caricature of an Acromegaly sufferer.[21]

A non-obvious case of acromegaly, where the patient presented with, in addition to large hands, insomnia, hunger and high blood pressure, was described in the diagnosis column of the New York Times

http://en.wikipedia.org/wiki/Acromegaly


Memorial Hermann Northeast Hospital 5 years ago

What is acromegaly?

Acromegaly is a hormonal disorder that results from too much growth hormone (GH) in the body. The pituitary, a small gland in the brain, makes GH. In acromegaly, the pituitary produces excessive amounts of GH. Usually the excess GH comes from benign, or noncancerous, tumors on the pituitary. These benign tumors are called adenomas.

Acromegaly is most often diagnosed in middle-aged adults, although symptoms can appear at any age. If not treated, acromegaly can result in serious illness and premature death. Acromegaly is treatable in most patients, but because of its slow and often “sneaky” onset, it often is not diagnosed early or correctly. The most serious health consequences of acromegaly are type 2 diabetes, high blood pressure, increased risk of cardiovascular disease, and arthritis. Patients with acromegaly are also at increased risk for colon polyps, which may develop into colon cancer if not removed.

When GH-producing tumors occur in childhood, the disease that results is called gigantism rather than acromegaly. A child’s height is determined by the length of the so-called long bones in the legs. In response to GH, these bones grow in length at the growth plates—areas near either end of the bone. Growth plates fuse after puberty, so the excessive GH production in adults does not result in increased height. However, prolonged exposure to excess GH before the growth plates fuse causes increased growth of the long bones and thus increased height. Pediatricians may become concerned about this possibility if a child’s growth rate suddenly and markedly increases beyond what would be predicted by previous growth and how tall the child’s parents are.

[Top]

What are the symptoms of acromegaly?

The name acromegaly comes from the Greek words for “extremities” and “enlargement,” reflecting one of its most common symptoms—the abnormal growth of the hands and feet. Swelling of the hands and feet is often an early feature, with patients noticing a change in ring or shoe size, particularly shoe width. Gradually, bone changes alter the patient’s facial features: The brow and lower jaw protrude, the nasal bone enlarges, and the teeth space out.

Overgrowth of bone and cartilage often leads to arthritis. When tissue thickens, it may trap nerves, causing carpal tunnel syndrome, which results in numbness and weakness of the hands. Body organs, including the heart, may enlarge.

Other symptoms of acromegaly include

joint aches

thick, coarse, oily skin

skin tags

enlarged lips, nose, and tongue

deepening of the voice due to enlarged sinuses and vocal cords

sleep apnea—breaks in breathing during sleep due to obstruction of the airway

excessive sweating and skin odor

fatigue and weakness

headaches

impaired vision

abnormalities of the menstrual cycle and sometimes breast discharge in women

erectile dysfunction in men

decreased libido

[Top]

What causes acromegaly?

Acromegaly is caused by prolonged overproduction of GH by the pituitary gland. The pituitary produces several important hormones that control body functions such as growth and development, reproduction, and metabolism. But hormones never seem to act simply and directly. They usually “cascade” or flow in a series, affecting each other’s production or release into the bloodstream.

GH is part of a cascade of hormones that, as the name implies, regulates the physical growth of the body. This cascade begins in a part of the brain called the hypothalamus. The hypothalamus makes hormones that regulate the pituitary. One of the hormones in the GH series, or “axis,” is growth hormone-releasing hormone (GHRH), which stimulates the pituitary gland to produce GH.

Secretion of GH by the pituitary into the bloodstream stimulates the liver to produce another hormone called insulin-like growth factor I (IGF-I). IGF-I is what actually causes tissue growth in the body. High levels of IGF-I, in turn, signal the pituitary to reduce GH production.

The hypothalamus makes another hormone called somatostatin, which inhibits GH production and release. Normally, GHRH, somatostatin, GH, and IGF-I levels in the body are tightly regulated by each other and by sleep, exercise, stress, food intake, and blood sugar levels. If the pituitary continues to make GH independent of the normal regulatory mechanisms, the level of IGF-I continues to rise, leading to bone overgrowth and organ enlargement. High levels of IGF-I also cause changes in glucose (sugar) and lipid (fat) metabolism and can lead to diabetes, high blood pressure, and heart disease.

Pituitary Tumors

In more than 95 percent of people with acromegaly, a benign tumor of the pituitary gland, called an adenoma, produces excess GH. Pituitary tumors are labeled either micro- or macro-adenomas, depending on their size. Most GH-secreting tumors are macro-adenomas, meaning they are larger than 1 centimeter. Depending on their location, these larger tumors may compress surrounding brain structures. For example, a tumor growing upward may affect the optic chiasm—where the optic nerves cross—leading to visual problems and vision loss. If the tumor grows to the side, it may enter an area of the brain called the cavernous sinus where there are many nerves, potentially damaging them.

Compression of the surrounding normal pituitary tissue can alter production of other hormones. These hormonal shifts can lead to changes in menstruation and breast discharge in women and erectile dysfunction in men. If the tumor affects the part of the pituitary that controls the thyroid—another hormone-producing gland—then thyroid hormones may decrease. Too little thyroid hormone can cause weight gain, fatigue, and hair and skin changes. If the tumor affects the part of the pituitary that controls the adrenal gland, the hormone cortisol may decrease. Too little cortisol can cause weight loss, dizziness, fatigue, low blood pressure, and nausea.

Some GH-secreting tumors may also secrete too much of other pituitary hormones. For example, they may produce prolactin, the hormone that stimulates the mammary glands to produce milk. Rarely, adenomas may produce thyroid-stimulating hormone. Doctors should assess all pituitary hormones in people with acromegaly.

Rates of GH production and the aggressiveness of the tumor vary greatly among people with adenomas. Some adenomas grow slowly and symptoms of GH excess are often not noticed for many years. Other adenomas grow more rapidly and invade surrounding brain areas or the venous sinuses, which are located near the pituitary gland. Younger patients tend to have more aggressive tumors. Regardless of size, these tumors are always benign.

Most pituitary tumors develop spontaneously and are not genetically inherited. They are the result of a genetic alteration in a single pituitary cell, which leads to increased cell division and tumor formation. This genetic change, or mutation, is not present at birth, but happens later in life. The mutation occurs in a gene that regulates the transmission of chemical signals within pituitary cells. It permanently switches on the signal that tells the cell to divide and secrete GH. The events within the cell that cause disordered pituitary cell growth and GH oversecretion currently are the subject of intensive research.

http://endocrine.niddk.nih.gov/pubs/acro/acro.htm


University of Tokyo Hospital 5 years ago

Medical Therapy

Medical therapy is most often used if surgery does not result in a cure and sometimes to shrink large tumors before surgery. Three medication groups are used to treat acromegaly.

Somatostatin analogs (SSAs) are the first medication group used to treat acromegaly. They shut off GH production and are effective in lowering GH and IGF-I levels in 50 to 70 percent of patients. SSAs also reduce tumor size in around 0 to 50 percent of patients but only to a modest degree. Several studies have shown that SSAs are safe and effective for long-term treatment and in treating patients with acromegaly caused by nonpituitary tumors. Long-acting SSAs are given by intramuscular injection once a month.

Digestive problems—such as loose stools, nausea, and gas—are a side effect in about half of people taking SSAs. However, the effects are usually temporary and rarely severe. About 10 to 20 percent of patients develop gallstones, but the gallstones do not usually cause symptoms. In rare cases, treatment can result in elevated blood glucose levels. More commonly, SSAs reduce the need for insulin and improve blood glucose control in some people with acromegaly who already have diabetes.

The second medication group is the GH receptor antagonists (GHRAs), which interfere with the action of GH. They normalize IGF-I levels in more than 90 percent of patients. They do not, however, lower GH levels. Given once a day through injection, GHRAs are usually well-tolerated by patients. The long-term effects of these drugs on tumor growth are still under study. Side effects can include headaches, fatigue, and abnormal liver function.

Dopamine agonists make up the third medication group. These drugs are not as effective as the other medications at lowering GH or IGF-I levels, and they normalize IGF-I levels in only a minority of patients. Dopamine agonists are sometimes effective in patients who have mild degrees of excess GH and have both acromegaly and hyperprolactinemia—too much of the hormone prolactin. Dopamine agonists can be used in combination with SSAs. Side effects can include nausea, headache, and lightheadedness.

Agonist: A drug that binds to a receptor of a cell and triggers a response by the cell, mimicking the action of a naturally occurring substance.

Antagonist: A chemical that acts within the body to reduce the physiological activity of another chemical substance or hormone.

Radiation Therapy

Radiation therapy is usually reserved for people who have some tumor remaining after surgery and do not respond to medications. Because radiation leads to a slow lowering of GH and IGF-I levels, these patients often also receive medication to lower hormone levels. The full effect of this therapy may not occur for many years.

The two types of radiation delivery are conventional and stereotactic. Conventional radiation delivery targets the tumor with external beams but can damage surrounding tissue. The treatment delivers small doses of radiation multiple times over 4 to 6 weeks, giving normal tissue time to heal between treatments.

Stereotactic delivery allows precise targeting of a high-dose beam of radiation at the tumor from varying angles. The patient must wear a rigid head frame to keep the head still. The types of stereotactic radiation delivery currently available are proton beam, linear accelerator (LINAC), and gamma knife. With stereotactic delivery, the tumor must be at least 5 mm from the optic chiasm to prevent radiation damage. This treatment can sometimes be done in a single session, reducing the risk of damage to surrounding tissue.

All forms of radiation therapy cause a gradual decline in production of other pituitary hormones over time, resulting in the need for hormone replacement in most patients. Radiation also can impair a patient’s fertility. Vision loss and brain injury are rare complications. Rarely, secondary tumors can develop many years later in areas that were in the path of the radiation beam.

[Top]

Which treatment for acromegaly is most effective?

No single treatment is effective for all patients. Treatment should be individualized, and often combined, depending on patient characteristics such as age and tumor size.

If the tumor has not yet invaded surrounding nonpituitary tissues, removal of the pituitary adenoma by an experienced neurosurgeon is usually the first choice. Even if a cure is not possible, surgery may be performed if the patient has symptoms of neurological problems such as loss of peripheral vision or cranial nerve problems. After surgery, hormone levels are measured to determine whether a cure has been achieved. This determination can take up to 8 weeks because IGF-I lasts a long time in the body’s circulation. If cured, a patient must be monitored for a long time for increasing GH levels.

If surgery does not normalize hormone levels or a relapse occurs, an endocrinologist should recommend additional drug therapy. With each medication, long-term therapy is necessary because their withdrawal can lead to rising GH levels and tumor re-expansion.

Radiation therapy is generally reserved for patients whose tumors are not completely removed by surgery, who are not good candidates for surgery because of other health problems, or who do not respond adequately to surgery and medication.

Points to Remember

Acromegaly is a hormonal disorder that results from too much growth hormone (GH) in the body.

In most people with acromegaly, a benign tumor of the pituitary gland produces excess GH.

Common features of acromegaly include abnormal growth of the hands and feet; bone growth in the face that leads to a protruding lower jaw and brow and an enlarged nasal bone; joint aches; thick, coarse, oily skin; and enlarged lips, nose, and tongue.

Acromegaly can cause sleep apnea, fatigue and weakness, headaches, impaired vision, menstrual abnormalities in women, and erectile dysfunction in men.

Acromegaly is diagnosed through a blood test. Magnetic resonance imaging (MRI) of the pituitary is then used to locate and detect the size of the tumor causing GH overproduction.

The first line of treatment is usually surgical removal of the tumor. Medication or radiation may be used instead of or in addition to surgery.

[Top]

Hope through Research

Researchers continue to study treatment options for people with acromegaly. Studies are examining the safety and effectiveness of different types, dosages, dosing schedules, and combinations of somatostatin analogs and GH receptor antagonists, both before and after transsphenoidal surgery. Another study is evaluating the effects of GH replacement in adults with a history of acromegaly who are now growth hormone deficient. Other research seeks to identify new genes that predispose people to endocrine tumors.

http://endocrine.niddk.nih.gov/pubs/acro/acro.htm


Children's Hospital of The King's Daughters 5 years ago

Acromegaly

Acromegaly is a chronic metabolic disorder in which there is too much growth hormone and the body tissues gradually enlarge.

Causes

Acromegaly occurs in about 6 of every 100,000 adults. It is caused by abnormal production of growth hormone after the skeleton and other organs finish growing.

Excessive production of growth hormone in children causes gigantism rather than acromegaly.

The cause of the increased growth hormone release is usually a noncancerous (benign) tumor of the pituitary gland. The pituitary gland, which is located just below the brain, controls the production and release of several different hormones, including growth hormone.

Symptoms

Body odor

Carpal tunnel syndrome

Decreased muscle strength (weakness)

Easy fatigue

Enlarged bones of the face

Enlarged feet

Enlarged hands

Enlarged glands in the skin (sebaceous glands)

Enlarged jaw (prognathism) and tongue

Excessive height (when excess growth hormone production begins in childhood)

Excessive sweating

Headache

Hoarseness

Joint pain

Limited joint movement

Sleep apnea

Swelling of the bony areas around a joint

Thickening of the skin, skin tags

Widely spaced teeth

Widened fingers or toes due to skin overgrowth with swelling, redness, and pain

Other symptoms that may occur with this disease:

Excess hair growth in females

Weight gain (unintentional)

Exams and Tests

High growth hormone level

High insulin-like growth factor 1 (IGF-1) level

Spine x-ray shows abnormal bone growth

Pituitary MRI may show a pituitary tumor

Echocardiogram may show an enlarged heart, leaky mitral valve, or leaky aortic valve

This disease may also change the results of the following tests:

Fasting plasma glucose

Glucose tolerance test

Treatment

Surgery to remove the pituitary tumor causing this condition corrects the abnormal growth hormone secretion in most patients. This surgery may not be available to patients in remote locations, so travel to a larger metropolitan area may be necessary for treatment.

Radiation of the pituitary gland is used for people who do not respond to the surgical treatment. However, the reduction in growth hormone levels after radiation is very slow.

The following medications may be used to treat acromegaly:

Octreotide (Sandostatin) or bromocriptine (Parlodel) may control growth hormone release in some people.

Pegvisomant (Somavert) directly blocks the effects of growth hormone, and has been shown to improve symptoms of acromegaly.

These medications may be used before surgery, or when surgery is not possible.

After treatment, periodic evaluation is necessary to ensure that the pituitary gland is working normally. Yearly evaluations are recommended.

Outlook (Prognosis)

Pituitary surgery is successful in most patients, depending on the size of the tumor and the experience of the surgeon.

Without treatment the symptoms will get worse, and the risk of cardiovascular disease increases.

Possible Complications

Arthritis

Cardiovascular disease

Carpal tunnel syndrome

Colonic polyps

Glucose intolerance or diabetes

High blood pressure

Hypopituitarism

Sleep apnea

Spinal cord compression

Uterine fibroids

Vision abnormalities

When to Contact a Medical Professional

Call your health care provider if you have symptoms of acromegaly, or if your symptoms do not improve with treatment.

Prevention

There are no methods to prevent the condition, but early treatment may prevent complications of the disease from getting worse.

Alternative Names

Somatotroph adenoma; Growth hormone excess; Pituitary giant

http://www.nlm.nih.gov/medlineplus/ency/article/00...


Children's Hospital of Wisconsin 5 years ago

Gigantism, also known as giantism (from Greek gigas, gigantas "giant"), is a condition characterized by excessive growth and height significantly above average. This condition is caused by an over production of human growth hormone.[1]

Contents [hide]

1 Terminology

2 See also

3 References

4 External links

[edit]Terminology

The term is typically applied to those whose height is not just in the upper 1% of the population but several standard deviations above mean for persons of the same sex, age, and ethnic ancestry. The term is seldom applied to those who are simply "tall" or "above average" whose heights appear to be the healthy result of normal genetics and nutrition. It is usually caused by a tumor on the pituitary gland on the brain. It causes growth of the hands, face, and feet.[2]

Other names somewhat obsolete for this pathology are hypersomia (Greek: hyper over the normal level; soma body) and somatomegaly (Greek; soma body, object pronoun somatos of the body; megas, megalos great). In the past, while many of them were social outcasts because of their height, some (usually unintentionally) found employment in Friedrich Wilhelm I's famous Potsdam Giants regiment.

Many of those who have been identified with gigantism have suffered from multiple health problems involving their circulatory or skeletal system.

[edit]See also

Acromegaly

Deep-sea gigantism

Growth hormone

Island gigantism

List of humans with gigantism

List of tallest people

Local gigantism

Megafauna

Nephilim

Overgrowth syndrome

Dwarfism

from

http://en.wikipedia.org/wiki/Gigantism


Washington University Physicians 5 years ago

Gigantism refers to abnormally high linear growth due to excessive action of insulin-like growth factor-I (IGF-I) while the epiphyseal growth plates are open during childhood. Acromegaly is the same disorder of IGF-I excess when it occurs after the growth plate cartilage fuses in adulthood. Gigantism is a nonspecific term that refers to any standing height more than 2 standard deviations above the mean for the person's sex, age, and Tanner stage (ie, height Z score >+2). These disorders are placed along a spectrum of IGF-I hypersecretion, wherein the developmental stage when such excess originates determine the principal manifestations. The onset of IGF-I hypersecretion in childhood or late adolescence results in tall stature. This article focuses on IGF-I excess with an onset during childhood.

The most remarkable example of a person with gigantism was Robert Wadlow, called the Alton giant, who stood 8 feet 11 inches tall at the time of his death in his mid-20s (see image below). A more recent person, widely known for his wrestling and movie roles, was Andre Roussimoff, or Andre the Giant. He was 6 feet 3 inches tall at age 12 years and reached a height of 7 feet 4 inches by adulthood.

Image shows the coauthor with a statue of Robert Wadlow, who was called the Alton giant. He was the tallest person ever recorded and was 8 feet 11 inches tall at the time of his death.

More recently, scientific breakthroughs in the molecular, genetic, and hormonal basis of growth hormone (GH) excess have provided important insights into the pathogenesis, prognosis, and treatment of this exceedingly rare disease.

Pathophysiology

Causes of excess IGF-I action may be divided into 3 categories: (1) those originating from primary GH excess released from the pituitary; (2) those caused by increased GH-releasing hormone (GHRH) secretion or hypothalamic dysregulation; and (3) hypothetically, those related to the excessive production of IGF-binding protein, which prolongs the half-life of circulating IGF-I.

By far, most people with giantism have GH-secreting pituitary adenomas or hyperplasia. Although gigantism is typically an isolated disorder, rare cases occur as a feature of other conditions, such as multiple endocrine neoplasia (MEN) type I, McCune-Albright syndrome (MAS), neurofibromatosis, tuberous sclerosis, or Carney complex.

Approximately 20% of patients with gigantism have MAS (the triad of precocious puberty, café au lait spots, fibrous dysplasia) and may have either pituitary hyperplasia or adenomas (see following image).

Photograph shows a 12-year-old boy with McCune-Albright syndrome. His growth-hormone excess manifested as tall stature, coarse facial features, and macrocephaly.

Frequency

United States

Gigantism is extremely rare, with approximately 100 reported cases to date. Acromegaly is more common than giantism, with an incidence of 3-4 cases per million people per year and a prevalence of 40-70 cases per million population.

Mortality/Morbidity

Because of the small number of people with gigantism, mortality and morbidity rates for this disease during childhood are unknown.

For individuals with acromegaly, the mortality rate is 2-3 times that of the general population. Successful treatment, with normalization of IGF-I levels, may be associated with a return to normal life expectancy. For persons with acromegaly, the most frequent causes of death are cardiovascular and respiratory complications.

Researchers disagree on whether malignancy is a significant cause of increased mortality. Although benign tumors (including uterine myomas, prostatic hypertrophy, and skin tags) are frequently encountered in acromegaly, documentation for overall prevalence of malignancies in patients with acromegaly remains controversial. Most studies suggest that as many as 30% of patients may have a premalignant colon polyp at diagnosis, and as many as 5% may have a colonic malignancy. However, the long-term effect of colonic lesions on morbidity and mortality has not been established.

No clear evidence supports an increased risk for lung, breast, or prostate cancer. As a significant cause of morbidity, sleep apnea may be both obstructive and central.

Race

No predilection has been reported.

Sex

IGF-I excess equally affects men and women.

In a series of 12 children, GH-secreting adenomas occurred with a female-to-male ratio of 1:2. Given the small size of this series, these disorders are unlikely to show a sex bias during childhood.

Age

Gigantism may begin at any age before epiphyseal fusion. The mean age for onset of acromegaly is in the third decade of life. For acromegaly, the delay from the insidious onset of symptoms to diagnosis is 5-15 years, with a mean delay of 8.7 years.

Clinical

History

The presentation of patients with gigantism is usually dramatic, unlike the insidious onset of acromegaly in adults. Reasons for this difference include the close monitoring of growth in children and their relatively responsive growth-plate cartilage. Children with gigantism have few soft-tissue effects (eg, peripheral edema, coarse facial features) because of their rapid linear growth.

Longitudinal acceleration of linear growth secondary to IGF-I excess is the cardinal clinical feature of gigantism.

Tumor mass may cause headaches, visual changes due to optic nerve compression, and hypopituitarism.

A common finding from pituitary GH excess is hyperprolactinemia, which manifests in childhood because mammosomatotrophs are the most common type of GH-secreting cells involved in childhood gigantism.

http://emedicine.medscape.com/article/925446-overv...


Universitätsklinikum Dusseldorf 5 years ago

All growth parameters are affected, although not necessarily symmetrically. Over time, IGF-I excess is characterized by progressive cosmetic disfigurement and systemic organ manifestations. Physical manifestations include the following:

Tall stature

Mild-to-moderate obesity (common)

Macrocephaly (may precede linear growth)

Soft-tissue hypertrophy

Exaggerated growth of the hands and feet with thick fingers and toes

Coarse facial features

Frontal bossing

Prognathism

Hyperhidrosis

Osteoarthritis (a late feature of IGF-I excess)

Peripheral neuropathies (eg, carpel tunnel syndrome)

Cardiovascular disease (eg, cardiac hypertrophy, hypertension, left ventricular hypertrophy) if IGF-I excess is prolonged

Benign tumors, including uterine myomas, prostatic hypertrophy, colon polyps, and skin tags, which are frequently in acromegaly (Documentation of a high prevalence of malignancies in patients with acromegaly remains controversial.)

Frequently associated endocrinopathies (eg, hypogonadism, diabetes and/or impaired glucose tolerance, hyperprolactinemia)

Causes

Despite diverse pathophysiologic mechanisms, the final common abnormality is IGF-I excess. Elevated tissue levels of free IGF-I, which is produced primarily in hepatocytes in response to excess GH, mediate most if not all growth-related outcomes in gigantism. Transgenic mice that overexpress GH, GHRH, or IGF-I had dramatically accelerated somatic growth compared with control litter mates. One acromegalic patient had low serum GH levels and elevated serum total IGF-I levels; this finding implicates IGF-I as the key pathologic factor in this disease. Serum levels of IGF-I are consistently elevated in patients with acromegaly and, therefore, are used to monitor treatment success.

The conditions described below can cause IGF-I oversecretion.

Primary pituitary GH excess: In most individuals with GH excess, the underlying anomaly is a benign pituitary tumor composed of somatotrophs (GH-secreting cells) or mammosomatotrophs (GH-secreting and prolactin [PRL]-secreting cells) in the form of a pituitary microadenoma or an macroadenoma. The adenomas are most characteristically well-demarcated and confined to the anterior lobe of the pituitary gland. In some people with GH excess, the tumor spreads outside the sella, invading the sphenoid bone, optic nerves, and brain. GH-secreting tumors are more likely to be locally invasive or aggressive in pediatric patients than in adults.

Gs-alpha (Gsa) mutation: G proteins play an integral role in postligand signal transduction in many endocrine cells by stimulating adenyl cyclase, resulting in an accumulation of cyclic adenosine monophosphate (cAMP) and subsequent gene transcription. About 20% of patients with gigantism have MAS and pituitary hyperplasia or adenomas. Activating mutations of the stimulatory Gsa protein have been found in the pituitary lesions in MAS and are believed to cause the other glandular adenomas observed. Point mutations found in several tissues affected in MAS involve a single amino-acid substitution in codon 201 (exon 8) or 227 (exon 9) of the gene for Gsa. Somatic point mutations have been identified in somatotrophs of less than 40% of sporadic GH-secreting pituitary adenomas. The resulting oncogene (gsp) is thought to induce tumorigenesis by persistently activating adenyl cyclase, with subsequent GH hypersecretion.

Loss of band 11q13 heterozygosity: Loss of heterozygosity at the site of a putative tumor-suppressor gene on chromosome band 11q13 was first identified in tumors from patients with MEN type I and GH excess. Loss of heterozygosity at band 11q13 has also been observed in all types of sporadically occurring pituitary adenomas. It is associated with an increased propensity for tumoral invasiveness and biologic activity.

Abnormality at Carney loci on chromosomes 2 and 17: Carney complex is characterized by myxomas, endocrine tumors, and spotty pigmentation. It is transmitted as an autosomal dominant trait. About 8% of affected individuals have GH-producing pituitary adenomas. The causative gene for this disease was mapped to chromosome bands 2p16 and 17q22-24. Germline mutations in PRKAR1A (which encodes for the protein kinase A type I-alpha regulatory subunit, an apparent tumor-suppressor gene on chromosome arm 17q) were detected in several families with Carney complex.

Secondary GH excess: Causes of secondary GH excess include increased secretion of GHRH due to an intracranial or ectopic source and dysregulation of the hypothalamic-pituitary-GH axis.

GHRH excess: Hypothalamic GHRH excess is postulated as a cause for gigantism, possibly secondary to an activating mutation in hypothalamic GHRH neurons. Excess GHRH secretion may be due to an intracranial or ectopic tumor. Several well-documented incidents of hypothalamic GHRH excess demonstrated intracranial gangliocytomas associated with gigantism or acromegaly. Ectopic GHRH-secreting tumors have included carcinoid, pancreatic islet-cell, and bronchial neoplasms. Prolonged tumoral secretion of GHRH leads to pituitary hyperplasia, with or without adenomatous transformation, that increases levels of GH and other adenohypophyseal peptides.

Disruption of somatostatin tone: Tumoral infiltration into somatostatinergic pathways are hypothesized to be the basis for GH excess in rare incidents of gigantism associated with neurofibromatosis and optic glioma or astrocytomas.


Palo Alto Medical Foundation 5 years ago

Laboratory Studies

Serum IGF-I determination is a sensitive screening test for acromegaly.

An excellent linear dose-response correlation between serum IGF-I levels and 24-hour integrated GH secretion has been demonstrated. Elevated IGF-I values in a patient whose symptoms prompt appropriate clinical suspicion almost always indicates GH excess.

Potential confusion may arise in the evaluation of healthy adolescents because IGF-I levels can be substantially higher during puberty than during adulthood. Always compare the patient's measurement with age-matched and sex-matched IGF-I reference ranges published in the literature or established for the specific testing laboratory.

A single GH measurement is inadequate. Because GH is secreted in a pulsatile manner, use of a random GH measurement can lead to a false-positive or false-negative result.

The free serum IGF-I level can also be diagnostic, but testing this level not necessary because this test is relatively expensive and unavailable to most clinicians.

An elevated serum insulin-like growth factor binding protein-3 (IGFBP-3) level may suggest the diagnosis of GH excess, although the diagnostic use of IGFBP-3 results for gigantism requires further study. In patients with confirmed somatotroph adenomas, increased IGFBP-3 levels are reported to be a sensitive marker of GH elevations and may be elevated even if total IGF-I levels are in the reference range.

An inability to suppress serum GH level during an oral glucose-tolerance test (OGTT) is the criterion standard for diagnosing GH excess. Failure to suppress serum GH levels to less than 5 ng/dL within 3 hours after a 1.75-g/kg oral glucose challenge (not to exceed 75 g) is diagnostic of pituitary GH excess.

Imaging Studies

If laboratory findings suggest GH excess, obtain an MRI to confirm the presence of a pituitary adenoma. In rare cases, a pituitary mass may not be identified because of an occult pituitary microadenoma or an ectopic tumor.

CT scanning is an acceptable imaging study if MRI is unavailable.

Chest or abdominal imaging may reveal the rare ectopic GH-secreting or GHRH-secreting tumor.

Other Tests

Although testing with an intravenous administration of thyrotropin-releasing hormone (TRH) is not necessary to make the diagnosis, 50-80% of patients with GH excess have a paradoxic rise in GH levels after the challenge.

Circulating GHRH blood levels may confirm peripheral ectopic GHRH secretion in the presence of an ectopic tumor. However, in the presence of a hypothalamic GHRH-secreting tumor, circulating GHRH levels may be normal.

Histologic Findings

Mammosomatotrophs are the most common type of GH-secreting cells involved in childhood gigantism.

Coexistence of both GH and PRL in the secretory granules of the tumor cells is clearly demonstrated on immunohistochemical staining.

http://emedicine.medscape.com/article/925446-diagn...


St. Joseph's Health Care London 5 years ago

Treatment

Medical Care

Surgery clearly fails to cure a notable number of patients with IGF-I excess. Therefore, medical therapy has taken on an important role in treating these patients. The most remarkable recent progress in treating this disorder has been in medical therapy. Well-tolerated, long-acting somatostatin analogs and dopamine agonists improve adherence and efficacy.

The goals of medical therapy goals are the following:

Remove or shrink the pituitary mass

Restore GH secretory patterns to normal

Restore serum total IGF-I and IGFBP-3 levels to normal

Retain normal pituitary secretion of other hormones

Prevent recurrence of disease

Somatostatin analogs are highly effective in treating patients with GH excess.

Octreotide suppresses serum GH level to less than 2.5 mcg/L in 65% of patients with acromegaly and normalizes circulating IGF-I levels in 70% of patients.

Studies of patients with GH excess for longer than 14 years demonstrated that effects of octreotide are well sustained over time.

Tumor shrinkage, although generally modest, also occurs with octreotide.

Consistent GH suppression was achieved with a continuous subcutaneous pump infusion of octreotide in a pubertal boy with pituitary gigantism.

New long-acting formulations, including long-acting octreotide and lanreotide, were recently demonstrated to produce consistent GH and IGF-I suppression in patients with acromegaly with once-monthly or biweekly intramuscular depot injections.

Sustained-released preparations have not been tested in children.

Dopamine agonists (eg, bromocriptine, cabergoline) bind to pituitary dopamine type 2 (D2) receptors and suppress GH secretion, although their precise mechanism of action remains unclear.

PRL levels are often adequately suppressed. However, circulating GH and IGF-I levels rarely normalize with this therapy. Less than 20% of patients achieve GH levels less than 5 ng/mL, and less than 10% achieve normal IGF-I levels.

Tumor shrinkage occurs in a few patients.

Dopamine agonists are generally used as adjuvant medical treatments for GH excess, and their effectiveness may be added to that of octreotide.

Although long-acting formulations are available, no data about the long-term control of GH and IGF-I with these agents are available.

Tests of a novel hepatic GH-receptor antagonist (pegvisomant [Somavert]) demonstrated effective suppression of GH and IGF-I levels in patients with acromegaly due to pituitary tumors or ectopic GHRH hypersecretion.

Normalization of IGF-I levels occurs in as many as 90% of patients treated daily with this drug for 3 months.

Long-term studies are underway, but pegvisomant has not been tested in children.

Surgical Care

For well-circumscribed pituitary adenomas, transsphenoidal surgery to completely remove the tumor is the treatment of choice, and it may be curative.

The likelihood of a surgical cure greatly depends on the surgeons' expertise and on the size and extension of the mass.

Intraoperative GH measurements can improve the results of tumor resection.

Transsphenoidal surgery to resect tumors is as safe in children as it is in adults.

A transcranial approach is sometimes necessary.

The primary goal of treatment is to normalize GH levels.

As determined by using GH assays available to date, GH levels should be normalized (50% of the points measured during the day) in all patients.

Because this change is impractical to test, GH levels (


Faculty of Medicine Ramathibodi Hospital 5 years ago

Further Outpatient Care

Evaluate long-term efficacy of surgery and radiotherapy by using anatomic tools, including MRI and visual-field evaluation.

After surgery and after the start of medical treatment, perform biochemical assessment at 6-12 weeks; normalization of IGF-I levels may occur several months later.

All patients with a history of GH excess require periodic life-long evaluation.

In one series, the long-term recurrence rate for GH-secreting adenomas in children was 13.3% after surgery.1

Complications

Hypopituitarism may develop as the result of the pituitary mass or as a complication of surgery or radiation therapy.

Treat pituitary failure with appropriate hormone-replacement therapy.

Patient Education

For excellent patient education resources, visit eMedicine's Acromegaly Center. Also, see eMedicine's patient education articles Acromegaly, Acromegaly FAQs, and Understanding Acromegaly Medications.

Also, refer patients to the Hormone Foundation for additional information.

Miscellaneous

Medicolegal Pitfalls

Failure to recognize and treat coexisting hyperprolactinemia

Failure to diagnose associated conditions, such as cardiovascular disease, tumors (eg, colon polyps, benign prostatic hypertrophy), and diabetes

Failure to monitor for and detect tumoral recurrence after surgical treatment

http://emedicine.medscape.com/article/925446-follo...


Psychiatric Research Institute New York State 5 years ago

Gigantism is abnormally large growth due to an excess of growth hormone during childhood, before the bone growth plates have closed.

Causes

The most common cause of too much growth hormone release is a noncancerous (benign) tumor of the pituitary gland. Other causes include:

Carney complex

McCune-Albright syndrome (MAS)

Multiple endocrine neoplasia type 1 (MEN-1)

Neurofibromatosis

If excess growth hormone occurs after normal bone growth has stopped, the condition is known as acromegaly.

Gigantism is very rare.

Symptoms

The child will grow in height, as well as in the muscles and organs. This excessive growth makes the child extremely large for his or her age.

Other symptoms include:

Delayed puberty

Double vision or difficulty with side (peripheral) vision

Frontal bossing and a prominent jaw

Headache

Increased sweating

Irregular periods (menstruation)

Large hands and feet with thick fingers and toes

Release of breast milk

Thickening of the facial features

Weakness

Exams and Tests

CT or MRI scan of the head showing pituitary tumor

Failure to suppress serum growth hormone (GH) levels after an oral glucose challenge (maximum 75g)

High prolactin levels

Increased insulin growth factor-I (IGF-I) levels

Damage to the pituitary may lead to low levels of other hormones, including:

Cortisol

Estradiol (girls)

Testosterone (boys)

Thyroid hormone

Treatment

In pituitary tumors with well-defined borders, surgery is the treatment of choice and can cure many cases.

For situations in which surgery cannot completely remove the tumor, medication is the treatment of choice. The most effective medications are somatostatin analogs (such as octreotide or long-acting lanreotide), which reduce growth hormone release.

Dopamine agonists (bromocriptine mesylate, cabergoline) have also been used to reduce growth hormone release, but these are generally less effective. Pegvisomant, a medication that blocks the effect of growth hormone, may be used.

Radiation therapy has also been used to bring growth hormone levels to normal. However, it can take 5 - 10 years for the full effects to be seen and almost always leads to low levels of other pituitary hormones.

Radiation has also been linked to learning disabilities, obesity, and emotional changes in children. Most experts will use radiation only if surgery and medication fail.

Outlook (Prognosis)

Pituitary surgery is usually successful in limiting growth hormone production.

Possible Complications

Delayed puberty

Surgery and radiation can both lead to low levels of other pituitary hormones, which can cause:

Adrenal insufficiency

Diabetes insipidus (rarely)

Hypogonadism

Hypothyroidism

When to Contact a Medical Professional

Call your health care provider if your child has signs of excessive growth.

Alternative Names

Giantism

http://www.nlm.nih.gov/medlineplus/ency/article/00...


University of Colorado Hospital 5 years ago

Hypopituitarism is a clinical syndrome of deficiency in pituitary hormone production. This may result from disorders involving the pituitary gland, hypothalamus, or surrounding structures. Panhypopituitarism refers to involvement of all pituitary hormones; however, only one or more pituitary hormones are often involved, resulting in partial hypopituitarism. Pituitary hormones of clinical significance include adrenocorticotropic hormone (ACTH, ie, corticotropin), follicle-stimulating hormone (FSH), luteinizing hormone (LH), growth hormone (GH), prolactin, thyroid-stimulating hormone (TSH, ie, thyrotropin), and antidiuretic hormone (ADH).

Recent studies

Li et al examined the efficacy of using magnetic resonance imaging (MRI) scans in children to examine pituitary function and to characterize such function in patients with multiple pituitary hormone deficiencies. The study included 96 pituitary hormone-deficient children and 90 controls. The authors used MRI findings from the hypothalamic-pituitary region to divide the hormone-deficient patients into 5 stages. Based on serum concentrations of ACTH, cortisol, GH, insulinlike growth factor-1 (IGF-1), free thyroxine (FT4), TSH, FSH, LH, testosterone, estradiol, and prolactin in the patients and controls, a positive correlation was found between the MRI-based stages and the number of pituitary hormone deficiencies in patients. The authors concluded that MRI findings can be correlated with pituitary function and can provide evidence of multiple pituitary hormone deficiencies.1

Pathophysiology

When pituitary hormone production is impaired, target gland hormone production is reduced because of a lack of trophic stimulus. Normally, subphysiologic target hormone levels stimulate the pituitary gland to increase trophic hormone production; however, in hypopituitarism, the pituitary gland response is absent, suboptimal, or inappropriate with biologically inert hormone production. This results in progressive secondary failure of the target glands. Patients with hypopituitarism typically present with low target hormone levels accompanied by low levels of the corresponding trophic hormone.

The trophic hormone level may appear to be within the reference range with a corresponding subphysiologic target hormone level. Such a trophic hormone level would be inappropriately low for the subphysiologic target hormone level. Sometimes, the assayed trophic hormone level may be biologically inert.

Mortality/Morbidity

Four retrospective studies from the United Kingdom and Sweden show that mortality is increased by 1.3- to 2.2-fold in hypopituitarism compared to age- and sex-matched cohorts.2 Morbidity is variable and may result from hormone deficiency or underlying disease. Underlying disorders, such as tumors, intracranial lesions, or systemic disease, may be asymptomatic or result in morbidity that masks the hormone deficiency. Note the following:

Deficiency of ACTH with adrenal crisis or TSH with myxedema may be life threatening.

GH deficiency causes more morbidity in children than in adults.

Sudden compromise of ACTH production may result in more profound morbidity than slowly progressive deficiency.

Gonadotropin deficiency with hypogonadism may cause morbidity insidiously.

Morbidity is more profound in congenital hypopituitarism.

Race

No racial predilection exists.

Sex

Postpartum hypopituitarism causes an overall increase in the prevalence of hypopituitarism in women.

Age

All ages are affected.

Clinical

History

Presentation varies from asymptomatic to acute collapse, depending on the etiology, rapidity of onset, and predominant hormones involved.

Initially, a patient with any hormone deficiency may be asymptomatic. Individuals with the following deficiencies present with the indicated condition:

ACTH deficiency -Adrenal insufficiency

TSH deficiency -Hypothyroidism

Gonadotropin deficiency -Hypogonadism

GH deficiency - Individuals with GH deficiency present with failure to thrive and short stature in children. Most adults are asymptomatic, but some may experience fatigue and weakness.

ADH deficiency - Polyuria and polydipsia

Other presenting features may be attributable to the underlying cause. A patient with a space-occupying lesion may present with headaches or visual field deficits. A patient with large lesions involving the hypothalamus may present with polydipsia and syndrome of inappropriate secretion of antidiuretic hormone (SIADH).

Physical

Physical examination findings may be normal in subtle presentations. Patients may present with features attributable to deficiency of target hormones, including hypothyroidism, adrenal insufficiency, hypogonadism, and failure to thrive.

Causes

Note the following causes:

Tumors3 -Craniopharyngiomas, pituitary adenomas

Infiltrative processes -Sarcoidosis, histiocytosis X, hemochromatosis

Infections -Tuberculosis, syphilis, meningitis

Ischemia and infarction - Sheehan syndrome, apoplexy

Empty sella syndrome

Iatrogenic - Radiation,4,5 surgery, withholding previous chronic glucocorticoid replacement

Trauma to the hypophysis

Congenital -Kallmann syndrome

Autoimmune - Lymphocytic hypophysitis6

Transsphenoidal adenomectomy - In a study of 435 patients who underwent endonasal transsphenoidal adenomectomy, Fatemi et al found that hypopituitarism developed in 5.5% of these individuals.7 The results indicated that the likelihood of hypopituitarism development after transsphenoidal adenoma removal is higher when the tumor is larger than 20 mm.

http://emedicine.medscape.com/article/122287-overv...


Orthopaedic Surgery and Sports Medicine At The University of Washington 5 years ago

Laboratory Studies

Hormonal studies should be performed in pairs of target gland and their respective stimulatory pituitary hormone for proper interpretation, as follows8 :

ACTH and Cortrosyn stimulation test

TSH and thyroxine

FSH, LH, and either estradiol or testosterone (as appropriate for sex)

Prolactin

GH provocative testing

Imaging Studies

MRI or computed tomography (CT) scanning of the pituitary1,9

Other Tests

Other tests to ascertain the likely underlying etiology are indicated by the patient's presentation.

Procedures

Cortrosyn stimulation testing

Histologic Findings

Findings depend on etiology (eg, tumors, infiltrations, infections, empty sella).

http://emedicine.medscape.com/article/122287-diagn...


D.Virtual.Doctor profile image

D.Virtual.Doctor 5 years ago from Europe Author

woooooooooooooow! I was expecting this for a long time. I miss you guys and all your contributions. I have gone through most of it and they are indeed great contributions to this clinical case. Keep on writing, I need your experienced knowledge on such cases.


Yvon Codere 4 years ago

I have marfan syndrome with aneurysme and valves abnormalities, coartation of the aorta et retina deteachment and fatigue and weakness, sleep apnea, haital hernia. But also a a deficiency with free testosterone. Your articles appears to be useful


D.Virtual.Doctor profile image

D.Virtual.Doctor 4 years ago from Europe Author

Thanks a lot Yvon Codere

    Sign in or sign up and post using a HubPages Network account.

    0 of 8192 characters used
    Post Comment

    No HTML is allowed in comments, but URLs will be hyperlinked. Comments are not for promoting your articles or other sites.


    Click to Rate This Article
    working