Adrenocorticotropic Hormone (ACTH), Plasma

ACTH is a hormone made by your pituitary gland that signals your adrenal glands to produce cortisol; measuring it in your blood helps your doctor determine whether a cortisol problem is coming from the pituitary, adrenal glands, or elsewhere. Results must always be interpreted alongside your cortisol level and the time your blood was drawn.

When elevated: Persistently elevated ACTH in the context of elevated cortisol raises concern for Cushing's disease (pituitary corticotroph adenoma) or ectopic ACTH syndrome from a neuroendocrine tumor, both of which carry significant morbidity including metabolic syndrome, osteoporosis, and cardiovascular risk. Markedly elevated ACTH (often >200 pg/mL) with low or normal cortisol is the biochemical hallmark of primary adrenal insufficiency, reflecting loss of negative feedback from a failing adrenal cortex. Chronic ACTH excess can also cause hyperpigmentation due to cross-reactivity with melanocortin receptors in the skin. When low: Suppressed or undetectable ACTH in the setting of low cortisol indicates secondary (pituitary) or tertiary (hypothalamic) adrenal insufficiency, which may result from pituitary pathology, prolonged exogenous glucocorticoid use, or hypothalamic dysfunction. Low ACTH with elevated cortisol strongly suggests an autonomous adrenal source of cortisol excess, such as an adrenal adenoma, carcinoma, or bilateral adrenal hyperplasia. Isolated low ACTH without clinical context is not diagnostic and requires correlation with dynamic testing and imaging.

ACTH is moderately relevant to athletes as a marker of HPA axis stress and recovery status. Chronic overtraining without adequate recovery can elevate cortisol and ACTH, potentially impairing adaptation and increasing injury risk; serial ACTH measurement alongside cortisol may help identify maladaptive training loads, though it is not a standard sports performance metric.