Rare disease month, day 1: Adrenal insufficiency (Addison’s disease)

Adrenal insufficiency is a condition defined by inadequate production of glucocorticoids. Other hormones, such as mineralocorticoids and androgens, may also be deficient. Adrenal insufficiency was first characterized by Thomas Addison in 1855. For this reason, adrenal insufficiency is often called Addison’s Disease, particularly the primary form.

Cortisol is the dominant glucocorticoid in humans and performs a wide array of essential functions. It is well known as a driver of stress response and modifies metabolic functions to lessen the impact of stress on the body. Its primary functions include increasing blood sugar, blood pressure, and heart rate; bronchodilation; and dampening immune response and inflammation. Patients with adrenal insufficiency are dependent upon replacement steroids and require them daily.

Common symptoms of adrenal insufficiency include fatigue, weakness, weight loss, low blood pressure (sometimes seen as orthostatic hypotension), anxiety, nausea, vomiting, diarrhea, sweating, and personality changes, among others. Darkening of the skin is often a clinical sign seen in primary adrenal insufficiency.

Adrenal insufficiency is life threatening and can be fatal. Prior to 1949, when synthetic cortisone became available, AI was universally fatal via adrenal crisis (also called Addisonian crisis). Adrenal crisis is the manifestation of critical cortisol deficiency. Symptoms can include fever; seizures; psychosis; severe abdominal, back and leg pain; fainting; vomiting and diarrhea; and dysregulation of electrolytes, including elevated potassium and calcium and low sodium. The only treatment for adrenal crisis is immediate corticosteroid replacement. Patients with adrenal insufficiency are recommended to always carry hydrocortisone for IM injection in the event of an emergency.

Primary adrenal insufficiency affects approximately 4.4-6 people per million. 80-90% of cases in developed countries result from autoimmune adrenalitis/ autoimmune Addison’s disease. This condition is sometimes seen as part of autoimmune polyendocrinopathy syndrome, in which several other endocrines are also impacted. Certain infections, such as histoplasmosis, coccidioiodomycosis, and tuberculosis; adrenoleukodystrophy; adrenal hyperplasia; and use of certain medications can cause primary adrenal insufficiency.

Secondary adrenal insufficiency affects approximately 150-280 people per million. It is most commonly caused by long term use of glucocorticoids which disrupts the HPA axis, the collective term for the hormonal system the body uses to regulate cortisol levels. Other causes for secondary AI include curing Cushing’s Syndrome, tumors of the hypothalamus, pituitary tumors, and trauma to or surgical removal of the pituitary. Complete cessation of glucocorticoids for up to a year is often necessary to trigger endogenous cortisol production but this cannot always be done safely. Many patients with secondary AI require replacement steroids for life.

Cortisol impacts mast cells in several ways, which have been rehashed extensively here and here.

For more information on adrenal insufficiency: http://www.nadf.us

 

Reference:

Charmandari E, et al. (2014) Adrenal insufficiency. The Lancet. (Seminar)