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Measurement of ACTH, CRH, and other hypothalamic and pituitary peptides

Lynnette K Nieman, MD
Section Editor
André Lacroix, MD
Deputy Editor
Kathryn A Martin, MD


Measurements of plasma corticotropin (ACTH) are extremely useful in the diagnosis of both Cushing's syndrome and adrenal insufficiency. In contrast, corticotropin-releasing hormone (CRH) is rarely measured in peripheral plasma or serum because the concentrations are much lower than and do not correlate well with those in the hypothalamic-hypophysial portal plasma. This is because of contribution from nonhypothalamic sources (eg, the gastrointestinal tract). The measurement of ACTH, CRH, and other related hypothalamic and pituitary peptides will be reviewed here. The approaches to the diagnosis of Cushing's syndrome and adrenal insufficiency are discussed separately. (See "Establishing the diagnosis of Cushing's syndrome" and "Diagnosis of adrenal insufficiency in adults".)


The current commercially available two-site immunometric assays have an analytical sensitivity between 0.6 and 9 pg/mL (0.12 to 19.8 pmol/L) [1]. However, performance differs between assays and should be considered when interpreting patient results [2,3]. Furthermore, the most common platform immunoassay in use in the United States gives significantly different results in the critical range of 9 to 118 pg/mL (2 to 26.2 pmol/L) compared with a gold standard immunometric assay [4].

Normal values — Plasma corticotropin (ACTH) concentrations are usually between 10 and 60 pg/mL (2.2 and 13.3 pmol/L) at 8 AM. The values decrease during the waking hours and are usually less than 20 pg/mL (4.5 pmol/L) at 4 PM and less than 10 pg/mL (2.2 pmol/L), usually less than 5 pg/mL (1.1 pmol/L), within one hour after the usual time of falling sleep. This circadian rhythm in plasma ACTH concentrations is the cause of the parallel changes in cortisol secretion by the adrenal glands and the resulting rhythm in serum cortisol concentrations.

Interpretation — The time of day at which the sample is taken is an important determinant of the utility of the measurement of plasma ACTH, which is often best interpreted with a simultaneous measurement of serum cortisol.

In evaluating patients with adrenal insufficiency, measurements should be made in the morning, if possible, when plasma ACTH and serum cortisol concentrations are usually at their highest value [5] (see "Diagnosis of adrenal insufficiency in adults"). However, in urgent or emergent evaluation of patients with potential adrenal insufficiency (eg, in the intensive care unit or emergency department), blood samples should be drawn at any time before administration of glucocorticoid therapy.

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Literature review current through: Nov 2017. | This topic last updated: Jul 05, 2017.
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