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

What is the treatment of Addison disease?

Treatment is replacing deficient hormones (cortisol ± Aldosterone). Cortisol replacement can be done with Prednisolone or hydrocortisone tablets. Aldosterone replacement is done with Fludorcortisone tablets. Patients with FGD/AAA syndrome need only cortisol replacement, while rest all patients require both cortisol and aldosterone replacement.

How to replace cortisol?

Prednisolone or hydrocortisone tablets. Prednisolone (5-7.5 mg) can be taken once a day early in the morning. Hydrocortisone (10-12 mg/m2/day) needs to be taken 2-3 times per day to mimic circadian rhythm. Dose needs to be increased at the time of stress to match increased requirement of cortisol hormone.

How to replace Aldosteorne?

Fludrocortisone tablets. It (100-150 mg/m2) has to be taken once a day early in the morning.

What are the side effects of the treatment & how to prevent it?

Cortisol (GC) over-replacement can lead to cushingoid symptoms (weight gain, fatigues, weakness, purple striae and mooning of face). Children are at risk of growth suppression, especially with prednisolone. Fludrocosrtisone (MC) over-replacement can lead to hypertension and hypokalemia. GC dose needs to be adjusted based on symptoms only. MC dose adjustment is based on Na, K and BP monitoring. It is always advisable to use hydrocortisone in children as compared to prednisolone to avoid higher growth suppressing potential of prednisolone.

What is an adrenal crisis?

Adrenal crisis is an emergency, where in immediate treatment is required to save the life. It happens when patients is under enormous stress and not on adequate replacement therapy. Patient will develop hypotension, low Na and high K and it is life threatening, if left untreated.

How to prevent adrenal crisis?

Patient has to understand that this is the life saving therapy which needs to be taken life-long and dose needs to be increased appropriately at the time of stress. Patient can wear a band (mentioning name of the illness, treatment in case of emergency, etc.) for identification during an episode of adrenal crisis. Injection hydrocortisone (100 mg/m2) can be given by intravenous/intramuscular route in case of emergency.