Overview of adrenal insufficiency

The adrenal glands produce hormones in the:

• adrenal cortex
  • glucocorticoids (eg cortisol)
  • mineralocorticoids (eg aldosterone)
  • androgens (eg dehydroepiandrosterone [DHEA])
• adrenal medulla
  • catecholamines (eg adrenaline).

Adrenal insufficiency refers to insufficient production of glucocorticoids and mineralocorticoids by the adrenal cortex; androgen production may also be insufficient. Adrenal insufficiency typically only occurs if both adrenal glands are affected.

Primary adrenal insufficiency (also known as Addison disease) is usually caused by autoimmune-related atrophy of the adrenal cortex; other causes include infection, metastatic cancer and some drugs.

Secondary adrenal insufficiency occurs when a pituitary or hypothalamic disorder causes a deficiency of adrenocorticotrophic hormone (ACTH); see Hypopituitarism.

In children, adrenal insufficiency is usually caused by either a genetic disorder (eg congenital adrenal hyperplasia, adrenoleukodystrophy, other rarer mutations such as SF-1) or an autoimmune disorder (affecting only the adrenal glands, or part of an autoimmune polyglandular syndrome).

The hallmarks of primary adrenal insufficiency are fatigue, anorexia and weight loss, postural hypotension, and skin and mucosal hyperpigmentation. Hyperpigmentation may be absent if adrenal insufficiency develops rapidly. Hyperkalaemia and hyponatraemia are common, but their absence does not exclude primary adrenal insufficiency.

A diagnosis of primary adrenal insufficiency is confirmed by the combination of:

• a positive short Synacthen test (ie an absent or severely blunted plasma cortisol response to tetracosactide [tetracosactrin] 30 to 60 minutes after injection)
• elevated ACTH
• elevated plasma renin (measured by direct concentration or plasma renin activity).

In patients with adrenal insufficiency, acute stress such as illness or surgery can precipitate acute cortisol deficiency and adrenal crisis. Adrenal crisis can present with features that mimic sepsis, including nausea, vomiting, diarrhoea, hypoglycaemia and hypercalcaemia, and is a medical emergency; see Adrenal crisis.