What is Addison disease?

It is also known as primary adrenal insufficiency, wherein cortisol (with/without aldosterone) production is insufficient from the adrenal cortex. Hence, production of ACTH from the pituitary gland increases.

What are the symptoms of Addison disease?

Nausea, vomiting, anorexia, weight loss, hyperpigmentation of skin and mucosa, hypotension (low BP), hyponatremia (low Na), hyperkalemia (high K), hypoglycemia (low glucose). The symptoms are aggravated by illness/stress.

How to diagnose Addison disease?

In the presence of symptoms, low Na and high are sufficient for the diagnosis. Blood test to check ACTH and Cortisol levels can be required to confirm diagnosis in some doubtful cases. ACTH level has to be at least 2 times elevated then the upper limit of normal range. Cortisol level can be within the normal range (in the initial stages) because of an increased ACTH level (which stimulates cortisol production). Other investigations that may help in the diagnosis are high PRA (plasma renin activity) and low Aldosterone level. CT scan for the adrenal gland may be required to find out the etiology in acquired cases.

What are the causes of Addison disease?

Hereditary causes:

(a) Congenital adrenal hyperplasia (21 hydroxylase deficiency, 11 beta hydroxylase deficiency, 3 beta hydroxysteroid dehydratase deficiency, StAR deficiency, side chain cleavage enzyme deficiency, etc.) – most common cause

(b) Congenital adrenal hypoplasia (DAX 1 gene mutation, SF1 gene mutation, IMAGE syndrome, etc.)

(c) ACTH resistance syndromes (AAA syndrome, Familial glucocorticoid deficiency-FGD type 1, 2 and 3)

(d) X-linked Adrenoleukodystrophy (ALD)

Acquired causes:

(a) Autoimmune, isolated, as a part of polyglandular syndromes (APS 1 & 2) – most common cause in developed world

(b) Infections (e.g., Tuberculosis, histoplasmosis, etc.) – most common cause in developing world

(c) Infiltrative lesions (metastasis, lymphoma, etc.)

(d) Post surgical (bilateral adrenalectomy)

(e) Adrenal hemorrhage