Adrenocorticotropic Hormone (ACTH)

Adrenocorticotropic Hormone (ACTH), also known as corticotropin, is ordered with serum cortisol to assess adrenal cortical dysfunction and overall HPA axis integrity. The test helps distinguish Cushing disease (pituitary ACTH excess) from ACTH-independent Cushing syndrome and ectopic ACTH production, and it is used to evaluate secondary and tertiary adrenal insufficiency. ACTH measurement is also applied to monitor response after surgical or other therapy for ACTH-secreting tumors and to track for recurrence.

Anterior pituitary corticotrophs secrete ACTH in response to hypothalamic corticotropin‑releasing hormone (CRH). ACTH drives adrenal cortisol biosynthesis, supports adrenal androgen production, and at physiologic concentrations has minimal direct effect on aldosterone. Circulating ACTH displays a diurnal rhythm and rises with stress, exercise, sleep, and pregnancy. Patterns of ACTH and cortisol help resolve the cause of cortisol excess. In ACTH‑independent Cushing syndrome due to adrenal neoplasia, elevated cortisol suppresses ACTH. In Cushing disease caused by a pituitary adenoma, chronic ACTH overproduction produces bilateral adrenal hyperplasia with concomitant elevation of ACTH and cortisol and increased urinary free cortisol and 17‑ketosteroids. Ectopic ACTH secretion by nonpituitary tumors—commonly bronchial carcinoma and thymoma, and less often medullary thyroid carcinoma or neoplasms of the ovary, breast, stomach, or colon—results in high ACTH with adrenal hyperplasia and cortisol excess. CRH stimulation testing typically elicits a rise in ACTH in pituitary Cushing disease but produces minimal or no ACTH response with ectopic ACTH production. In primary adrenal insufficiency (Addison disease) from adrenal destruction, glucocorticoids, mineralocorticoids, and androgens are low, with compensatory elevation of ACTH and disruption of its normal rhythm. Secondary or tertiary adrenal insufficiency due to pituitary or hypothalamic disease features reduced ACTH with secondary adrenal hypoplasia or atrophy; CRH testing can help differentiate pituitary from hypothalamic causes. Nelson syndrome denotes a pituitary tumor with markedly elevated ACTH and secondary adrenal insufficiency after bilateral adrenalectomy for Cushing disease. Measurement of ACTH together with cortisol is integral to evaluation of disorders of the hypothalamic–pituitary–adrenal axis.