Acromegalic symptoms

Acromegalic symptoms

What is acromegaly ?

Acromegaly is a disorder which is insidious in onset and consist of constellation of signs and symptoms as a result of hypersecretion of growth hormone.

What are the causes of acromegaly ?

99% of acromegaly cases are associated with excess GH hormone secretion from pituitary adenoma. Other causes include pituitary somatotrophs hyperplasia that occur as a result ectopic GH hormone secretion from pancreatic tumor, bronchial carcinoid and hypothalamus ganglioneuroma.

What are the associated risk factor ?

6% cases of acromegaly is associated with MEN type 1 ( Multiple Endocrine Neoplasia type 1 )

How common is acromegaly ?

It is equally affect both male and female and it is common at the age range of 40 - 60 years old, with mean age of presentation of 44 years old. The incidence of acromegaly is around 3 - 5 per 1 000 000 annually and the prevalence is around 50 per 1 000 000 annually.

How does acromegaly present ?

The signs and symptoms of acromegaly predate the diagnosis of acromegaly by 4 - 6 years of diagnosis. The manifestation of signs and symptoms may associated with excess growth hormone production, local mass effect and hypopituitarism .

Patient generally complaints of wonky bite ( dental malocclusion ), increase in shoe size, increase in ring size and increase in glove size and curly hair.

The most common symptoms include sweating and headache which account for 80% of acromegaly symptoms, amenorrhea, reduced in libido, impotence, ( as a result of hyperprolactinemia) , develop hypothyroidism, hypoadrenalism and hypogonadism as a result of hypopituitarism. Patient may also develop akronparaesthesia ( upper and lower limb paraesthesia ) , athralgia, snoring as well as backache.

Signs of acromegaly

Hand - appositional bone growth as a result of elevation of growth hormone.Arms/hands appear to be large ( spade like shape ) , growth hormone will leads to soft tissue overgrowth and cartilage hypertrophy which leads to premature osteoarthritis and kyphoscoliosis. Temporomandibular joint arthritis may also present. Carpal tunnel syndrome and nerve entrapment syndrome may also present. The hand and palm appear to be oily and sweaty.

Feet - Enlargement of the feet ( the soles of the feet encroaching the dorsum of the feet )). As a result if excess GH hormone.

Face- Coarsening of the face, wide nasal bridge, prominent nasolabial fold, large ear, nose, tongue ( macroglossia ) and large lower jaw rather than the upper jaw which cause the teeth of the lower jaw to be widely separated and extended. ( prognathism ) .The patient may also present with big supraorbital ridges , frontal bossing, husky resonant voice due to laryngeal edema or thickening of the vocal cord. Patient may also present with obstructive sleep apnoea. Patient may also present with acanthosis nigricans and darkening of the skin. Scalp fold is extended but tether to the skin ( cutis verticis gyrata ).

Neck - Patient is presented with multinodular goitre.

Patient may also present with signs of local mass effect such as hypopituitarism or compression of optic chiasm which initially leads to bitemporal superior quadrantanopia which later progress to bitemporal hemianopia.

Acromegaly may present in pregnant women. Pregnancy appear to be normal. Glucose level needs to be monitor . Sign and symptoms of acromegaly may remit.

What is the pathology of acromegaly ?

Under microscopic evaluation the patient may present with somatotroph acidophilic of pituitary adenoma.

What is the investigation requires to detect acromegaly ?

Initial investigation

Random Growth hormone level in the blood is not reliable due to the pulsatile secretion of the growth hormone and the acromegalic level and normal peak level may overlap. Growth hormone level may increase in response of puberty, pregnancy and stress and sleep .

Growth hormone will stimulates the release of IGF - 1 from the liver. It is useful as an initial test to confirm the diagnosis of acromegaly. The IGF -1 also is influenced by puberty and pregnancy.

Oral glucose tolerance test ( OGTT ) is performed when the basal serum growth hormone level more than 0.4 mcg/l ( 1.2 mIU/l)

In oral glucose tolerance test , 50g or 75g of glucose is administrated orally. The growth hormone level and glucose level are then measured at 0 , 30,60 , 90, 120 , and 150 minutes. If the lowest growth hormone level is more than 1 mcg/l ( 3mIU/l) with rising glucose level than acromegaly is confirmed.

There is a chance of false positive result in cases where the patient suffer from hepatic, renal diseases, diabetes mellitus, and anorexia nervosa.

Blood glucose test - increase in blood glucose

Urea and electrolytes - increase in Ca2+ and phosphate

Anterior pituitary function test

Important to diagnose the present of hypopituitarism ( 9 am. cortisol , LH and FSH hormone levels are measured. Prolactin may raised as a result of stalk compression or co secretion.

Goldmann perimetry

Visual field and acuity test. To screen for bitemporal hemianopia which is a sign of acromegaly as a result of compression of optic chiasm.

MRI of the brain

MRI scan for pituitary fossa.Provide image if the pituitary tumor and optic chiasm compression.

Hand and feet x ray

Hand and feet x ray may reveals an increase in the joint space , tufting of the terminal phalanges and increase in the formation of osteophytes.

GhRH measurements

Rarely done.

How to treat acromegaly ?

The aim of treatment is to remove and prevent compression of the tumor by excising the lesion. The aim of treatment also involved reduction of growth hormone and IGF -1. The treatment involves :

  • surgical treatment
  • medical treatment
  • radiotherapy treatment

The surgical treatment involves hypophysectomy. Hypophysectomy is the only curative therapy. It is performed transsphenoidally. If the adenoma is less than 1 cm or if inaccessible , craniotomy is performed. Prior to surgery , the patient may require medical therapy to normalizes the growth hormone level.

The patient is put under general anesthetic. Image intensifier is used to visualize the sella through sphenoid .Later the lumbar subarachnoid drainage catheter is put to introduce saline solution onto subarachnoid space in hoping to lower the pituitary tumor into the field of operation. The sizes, shaped and location of the tumor are useful in determining the extent of the tumor resection. 60% of patient undergoes the surgery may present with normal baseline of growth hormone level after surgery. It is more common in microadenoma ( 40%- 90% ) rather than large invasive tumor ( 10% - 48% ) . However 13% may suffer diabetes after surgery.

The complication of the surgical treatment may includes nasoseptal perforation , CSF leak, infection ( meningitis ) , permanent diabetes mellitus and hypopituitarism.

The medical treatment includes:

Somatostatin analogues ( SSA)

Somatostatin analogue may includes octreotide ( sandostatin Lar IM monthly ) or lanreotide( somatuline LA ). Somatostatin analogue binds to and activates the somatostatin receptor of the pituitary tumor and inhibit the growth hormone secretion.

As a result suppression of growth hormone secretion and normalization of the IGF - 1in 50% -60% with shrinkage of the tumor.

The common side effects of SSA may includes abdominal pain, and irritation at the injection sites, abdominal discomfort, abdominal cramp, increase in loose stool , flatulence, steatorrhea and impaired glucose tolerance and increase incidence of gallstone. The main issues are the costs for monthly intramuscular injection.

Dopamine agonist

Dopamine agonist are cheaper and can be administered orally rather than SSA. Bromocriptine is a dopamine agonist with successful rates around 10% - 20% . The side effects of dopamine agonist may includes nausea, vomiting, constipation, Raynaud’s phenomenon, postural hypotension ( need to increase dose gradually, take it after meal ) and psychosis is a rare causes.

Cabergoline produces less dopaminergic side effects with successful rates are 30% - 40%.

Growth hormone antagonist

Growth hormone antagonist ( pegvisomant)

It is a recombinant growth hormone analogue. It is an alternative if the patient is intolerant or resistance to SSA. It doesn’t reduce growth hormone secretion but normalizes the IGF- 1in about 90%.


Radiotherapy is perform if the patient is unsuitable for surgery, suffer from residual disease after surgery, failure of medical therapy or adjunct therapy. Radiotherapy may takes 4 - 6 years to achieve full effect. During these latency period, medical therapy is also required. Side effect of radiotherapy may includes hypopituitarism, temporal lobe radiation injury, 2nd intracranial neoplasm and optic neuropathy.

What is the complication of acromegaly ?

The complication of acromegaly may include increase risk of colon cancer and colonoscopy is required.

Endocrine complications such as diabetes mellitus ( 15% ) and impaired glucose tolerance ( 40%) , hypercalcemia, hyperphosphataemia,hypertriglyceridemia, and gallstone formation.May present with symptoms of hyperprolactinemia.

Respiratory complication such as obstructive sleep apnea and cardiovascular complication that includes, hypertension, left ventricular hypertrophy, left ventricular dilation, congestive cardiac failure, cardiomyopathy and arrhythmias.Increase in growth hormone secretion, insulin resistance and blood pressure my induce fibrinogen synthesis and reduction in protein S which may leads to increase risk of stroke.

Psychologically- the patient will suffer from psychosis as a result from the side effects of dopamine agonist and depression.

Gigantism may develop if acromegaly develop before the fusion of the bony epiphyses.

What is the prognosis of acromegaly ?

The prognosis may be good if early diagnosis and treatment are done. Acromegalic patient if untreated may leads to two fold increase in mortality due to respiratory, cerebrovascular and cardiovascular complication. Reduction of growth hormone level back to baseline will reduce the mortality rates back as normal population.

pituitary adenoma the major cause of acromegaly
pituitary adenoma the major cause of acromegaly
large fingers
large fingers
macroglossia or large tongue
macroglossia or large tongue
changes in facial appearance
changes in facial appearance

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