ADDISON DISEASE

Addison disease denotes primary adrenal insufficiency of acquired etiology with gradual destruction of the adrenal cortex, while medulla is usually preserved.

Etiology: Autoimmune destruction of the adrenal glands is the commonest cause of Addison disease with frequent presence of autoantibodies against 21-hydroxylase enzyme.

Other causes include infections, e.g. tuberculosis and meningococcemia, drugs, e.g. ketoconazole and adrenal hemorrhage in sepsis, asphyxia or bleeding disorders. Waterhouse-Friderichsen syndrome denotes acute adrenal insufficiency following adrenal hemorrhage in meningococcemia.

Clinical presentation may be acute or insidious, depending on the etiology and severity/rapidity of acquired disease.

a. Chronic progressive adrenal insufficiency (Addison disease) usually presents in older children with:

• Signs of glucocorticoid deficiency, e.g. recurrent hypo­glycemia, vomiting, abdominal pain and failure to thrive.

• Signs of mineralocorticoid deficiency, e.g. salt craving, hypotension and muscular weakness.

• Signs of androgen deficiency, e.g. poor development of secondary sexual characteristics.

• Signs of compensatory ACTH excess, e.g. hyper­pigmentation of skin.

While all adrenocortical functions are lost in advanced disease, early cases may present with isolated cortisol deficiency.

b. Acute adrenal insufficiency (Adrenal crisis) is a life­threatening emergency, seen in septic/asphyxiated newborns, meningococcemia or acute stress states, e.g. infections, surgery, etc. These cases present with sudden vomiting, hypoglycemia, hypotension/shock and intractable biochemical abnormalities, e.g. hypo­natremia, hyperkalemia, etc.

D/D: Addison disease must be differentiated from other causes of adrenal insufficiency including genetic defects, e.g. CAH or adrenal hypoplasia congenital (DAX1 gene mutation) or secondary adrenal insufficiency due to pituitary or hypothalamic causes.

Diagnosis is based on:

• Low resting cortisol levels (lt;5 #956;g#8725;dl) which do not rise on ACTH stimulation test, i.e. measuring cortisol levels before and 30 or 60 minutes after 250 #956;g of cosyntropin (ACTH) by rapid intravenous infusion or Intramuscular injection. Normal resting levels that do not increase after administration of ACTH indicate absence of adrenocortical reserve, while low initial level followed by a significant response to ACTH indicate secondary adrenal insufficiency.

• Altered plasma ACTH levels to differentiate primary (#936;ACTH) from secondary (#936;ACTH) adrenal insuffi­ciency. Basal levels should be confirmed by stimulation tests.

• Tests for etiological diagnosis, e.g. CT/MRI of brain and abdomen, measurement of circulating antibodies in Addison disease and TB etiology.

• Other relevant tests for pituitary dysfunction in secondary disease.

Management: Acute adrenal crisis is a medical emergency, which requires intensively monitored fluid and electrolyte therapy along with IV hydrocortisone 50 mg#8725;m² immediately followed by 100 mg/m²/day in four divided doses. After the child is stable, life-long hormone replacement therapy is required as follows. as follows.

Chronic adrenal insufficiency or cases of acute adrenal crisis after recovery need life-long glucocorticoids (PO Hydrocortisone 10-12 mg/m²/dose q8hr) in minimum possible doses, which should be stepped-up during intercurrent infections or surgery. Mineralocorticoid (PO Fluorohydrocortisone 0.05-0.3 mg#8725;day) is necessary only in cases with aldosterone deficiency.

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