Primary adrenal insufficiency (Addison’s disease) is defined by failure of adrenal glands to provide sufficient quantities of glucocorticoid, mineralocorticoid, and androgen hormones. It is most commonly caused by bilateral adrenal destruction from autoimmune disease. Secondary adrenal insufficiency is defined as an ACTH deficiency due to either a failure of ACTH or CRH production from hypothalamic-pituitary disease (e.g., pituitary surgery, Sheehan’s syndrome) or a suppression of the hypothalamic-pituitary axis (e.g., exogenous glucocorticoids).
A major distinction between primary and secondary is that mineralocorticoid deficiency is associated with primary disease whereas it is not with secondary disease. In secondary disease, only ACTH is deficient and the renin-angiotensin-aldosterone axis is intact. This difference in salt and water balance leads to different clinical presentations.
- CBC: normochromic, normocytic anemia, relative lymphocytosis with increased eosinophil count
- Acid-base: Mild metabolic acidosis
- Renal function: Prerenal azotemia
- Primary disease: Hyponatremia and hyperkalemia (aldosterone deficiency) due to salt wasting from mineralocorticoid deficiency
- Secondary disease: Hyponatremia alone. This is due to ADH mediated free water retention. Glucocorticoid deficiency induces a “relative volume” deficiency promoting ADH secretion.
- Stewart PM, Krone NP. The Adrenal Cortex. In: Melmed S, Williams RH. Williams Textbook of Endocrinology. Saunders; 2011.
- Barthel A, Willenberg HS, et al. Adrenal Insufficiency. In: Jameson JL, Groot LJ. Endocrinology: Adult and Pediatric. Saunders; 2015.
Defined by: Eric Lin, MD