Adrenal insufficiency
Also known as: hypocortisolism, Addison disease (primary form)
Adrenal insufficiency is a condition in which the adrenal glands produce too little cortisol, and sometimes too little aldosterone. It can be primary (adrenal gland failure, called Addison disease) or secondary to inadequate ACTH from the pituitary.
Adrenal insufficiency is inadequate production of adrenal cortex hormones — chiefly cortisol, and in some forms aldosterone as well. Cortisol is essential for maintaining blood pressure, blood glucose, and the body's response to stress, so its deficiency produces fatigue, weakness, weight loss, nausea, and hypotension that can progress to life-threatening adrenal crisis.
The condition is classified by where the axis fails. Primary adrenal insufficiency (Addison disease) results from destruction of the adrenal glands themselves — most often autoimmune in developed countries, with tuberculosis an important cause worldwide. Both cortisol and aldosterone are lost, and the pituitary responds with high ACTH. Because ACTH is processed from the same precursor as melanocyte-stimulating hormone, patients develop characteristic hyperpigmentation, along with hyperkalemia and hyponatremia from aldosterone loss. Secondary insufficiency stems from deficient pituitary ACTH — commonly after chronic exogenous corticosteroid use suppresses the axis — so ACTH is low, pigmentation is normal, and aldosterone is largely preserved because it is regulated by the renin-angiotensin system.
Distinguishing the forms is the clinical and exam-day skill: ACTH levels, potassium status, and skin findings separate primary from secondary disease, and abrupt steroid withdrawal is a classic trigger of acute crisis.
Adrenal insufficiency is high-yield endocrine pathology on the USMLE Step 1 exam, which tests the hormonal axis, lab patterns, and causes of each form. The NPTE-PT and NPTE-PTA exams cover it within endocrine and metabolic systems, emphasizing recognition of signs, symptoms, and implications for patient management.
Key takeaways
- Adrenal insufficiency is deficient cortisol production, with aldosterone also lost in primary disease.
- Primary (Addison disease) shows high ACTH, hyperpigmentation, hyperkalemia, and hyponatremia.
- Secondary insufficiency shows low ACTH, no hyperpigmentation, and preserved aldosterone.
- Chronic corticosteroid therapy suppresses ACTH, and abrupt withdrawal can precipitate adrenal crisis.
- USMLE Step 1 and the NPTE test distinguishing primary from secondary forms by labs and presentation.