• Clinical science

Adrenal insufficiency


Adrenal insufficiency refers to the decreased production of adrenocortical hormones (glucocorticoids, mineralocorticoids, and adrenal androgens). Primary adrenal insufficiency (Addison disease) is caused by a disorder of the adrenal glands. The most frequent cause of primary adrenal insufficiency by far is autoimmune adrenalitis, which may occur sporadically or as a manifestation of polyglandular autoimmune syndromes. Secondary adrenal insufficiency is the result of decreased production of ACTH (adrenocorticotropic hormone). Decreased levels of ACTH are seen following prolonged glucocorticoid therapy or in pituitary/hypothalamic diseases. Patients with long-standing adrenal insufficiency may present with postural hypotension, nausea, vomiting, weight loss, anorexia, lethargy, depression, and/or chronic hyponatremia. Female patients also present with loss of libido as a result of hypoandrogenism. Patients with primary adrenal insufficiency also tend to develop hyperpigmentation of the skin, mild hyperkalemia, and metabolic acidosis. Serum cortisol levels that remain low even after the administration of exogenous ACTH (ACTH stimulation test) confirm the diagnosis of adrenal insufficiency. Glucocorticoid replacement therapy with hydrocortisone is required for all forms of adrenal insufficiency. The dose of glucocorticoids should be increased during periods of stress (e.g., surgery, trauma, infections) in order to prevent an adrenal crisis, a severe, acute type of adrenal insufficiency that presents with fever, impaired consciousness, severe abdominal pain, and hypovolemic shock. Adrenal crisis is life-threatening and should be treated immediately with high doses of hydrocortisone and intravenous fluids.


Primary adrenal insufficiency (Addison disease)

Primary adrenal insufficiency is caused by conditions that directly damage the adrenal gland.

Secondary adrenal insufficiency

Secondary adrenal insufficiency is caused by conditions that decrease ACTH production (impaired hypothalamic-pituitary-adrenal axis).

Secondary adrenal insufficiency is far more common than primary adrenal insufficiency!




Clinical features

Hormone insufficiency Clinical and/or biochemical features Primary adrenal insufficiency Secondary adrenal insufficiency


  • Hypotension


  • Weight loss, anorexia, lethargy, and/or depression
  • Intestinal complaints (nausea, vomiting, and/or diarrhea)
  • Hypotension
Hypoandrogenism (among female patients only)
  • Loss of libido
  • Loss of axillary and pubic hair
Elevated ACTH
  • Hyperpigmentation of areas that are not normally exposed to sunlight (e.g., palmar creases, mucous membrane of the oral cavity)

Most cases of adrenal insufficiency are subclinical and only become apparent during periods of stress (e.g., surgery, trauma, infections), when the cortisol requirement is higher!


Diagnosis of adrenal insufficiency

Identifying the underlying cause of adrenal insufficiency


If the dose of glucocorticoids is not increased during periods of stress (e.g., surgery, febrile infections, trauma), the patient may develop an adrenal crisis!

Adrenal crisis (Addisonian crisis)

Adrenal crisis can be life-threatening. Therefore, treatment with high doses of hydrocortisone should be started immediately without waiting for diagnostic confirmation of hypocortisolism!

Autoimmune polyendocrine syndromes

Adrenal insufficiency is the most common endocrinopathy in patients with polyglandular autoimmune syndrome (present in over 50% of cases)!