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Adrenorcortical Insufficiency: Addison’s Disease- Causes, Pathology, Clinical Features And Lab Investigations

Updated on February 11, 2014

Patches On Skin In Addison's Disease


Addison's Disease

Hypofunction of the adrenal cortex may be due to a primary disorder of the gland or secondary to hyposection of the trophic hormone.


Primary adrenocortical insufficiency: 1. Atrophy of the adrenal cortex due to autoimmune disorder,

2. Tuberculosis

3. Infiltration by metastatic carcinoma,

4. Hemochromatosis

5. Amyloidosis, and

6. Post-surgical (total or subtotal adrenalectomy).

Secondary adrenocortical insufficiency: Hypothalamic causes such as tumours of third ventricle, meningitis, encephalitis, injury to the base of the brain and corticosteroid therapy. Pituitary causes such as all causes of panhypopituitarism, especially tumours, basal meningitis, hypophysectomy or after irradiation. In the majority of cases of hypopituitarism, deficiency of gonadotropic and thyrotrophic hormones also coexist, but rarely isolated ACTH deficiency may occur.

Addison’s Disease- Primary Adrenal Cortical Insufficiency

Among diseases of the adrenal cortex, this is common. Autoimmune adrenal destruction (previously called idiopathic or primary atrophy) is more common in women. Antibodies against adrenal tissue may be demonstrable. Other autoimmune disorders like myxedema, diabetes (IDDM), Hashimoto’s disease, thyrotoxicosis, pernicious anemia, idiopathic ovarian failure and hypoparathyroidism may be associated. There is association between Addison’s disease and HLA-B38 and HLA-DR3.

Pathology: The adrenal glands show total cortical atrophy involving all three zones. The medulla is normal. In the primary form, histology shows lymphatic infiltration and increase in fibrous tissue. In the other types, evidence of the underlying disease may be demonstrable. In tuberculosis of the adrenals, evidence of tuberculosis elsewhere in the body may or may not be present. The major functional defect is marked reduction of glucocorticoids and mineralocorticoids and the clinical features are determined by the severity of these defects. Sex hormones are also reduced.

Laboratory Investigations:

  1. Hypoglycemia is common. Blood sugar falls further during periods of stress.
  2. Hyponatremia and hyperkalemia may occur sometimes. This is variable and, therefore, not of diagnostic importance.
  3. Plasma cortisol levels are low, and the diurnal rhythm is lost.
  4. Stimulation test- There is no response to ACTH stimulation in primary adrenal insufficiency. In secondary types, significant response occurs.
  5. Hypoadrenal subjects are very sensitive to the hypoglycemic effects of insulin and, therefore, this was used diagnostically. This test is not in vogue now.
  6. In Addison’s disease, plasma ACTH levels are high. In secondary hypoadrenalcorticism ACTH levels are low.

Addison's Disease manifestations


Clinical Manifestations

Generally, the onset is slow and may be unnoticed but many patients present for the first time in acute adrenal failure precipitated by stress. Initial symptoms may be vague such as weakness, tiredness, lethargy, weight loss and gastrointestinal upset. Sooner or later, dark pigmentation develops. When fully developed, the pigmentation is characteristic and in most cases, diagnostic of primary adrenal failure. Face, palms, extensor aspects of limbs, flexures and mucous membranes of the mouth, tongue and genitalia show pigmentation. In severe cases, the complexion becomes black. Pigmentation is mediated by the melanophore stimulating effect of ACTH and also secretion of melanophore stimulating hormone (MSH). Unlike primary hypoadrenalism, in the secondary type, there is no pigmentation. On the other hand, these subjects are pale and light coloured. Vitiligo is seen in some cases of Addison’s disease. Premature graying of hair may occur which reverts to normal with treatment. Women develop amenorrhea and men complain of impotence Addison’s disease confers abnormal sensitivity to drugs like morphine or pethidine. Hypoglycemia leads to extreme fatigue, sweating and coma. Cardiovascular abnormalities include hypotension and diminution in heart size, well demonstrable by x-ray. Psychiatric symptoms like depression or melancholia may be prominent in a few.

© 2014 Funom Theophilus Makama


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