Adrenocorticotropic Hormone (ACTH), Plasma

Pituitary function test useful in the differential diagnosis of Cushing syndrome, ectopic ACTH syndrome (eg, carcinoma of lung, islet cell tumors, carcinoid tumors, medullary carcinoma of thyroid), Addison disease, hypopituitarism, and ACTH-producing pituitary tumors (eg, Nelson syndrome)

ACTH secretion is pulsatile so multiple specimen collections may be required. Collection in nonsiliconized tubes can result in falsely low results as ACTH adheres to glass.

As with all tests containing monoclonal mouse antibodies, erroneous findings may be obtained from samples taken from patients who have been treated with monoclonal mouse antibodies or who have received them for diagnostic purposes.3 In rare cases, interference due to extremely high titers of antibodies to streptavidin and ruthenium can occur.3 The test contains additives, which minimize these effects.

Adrenocorticotropic hormone (ACTH), or corticotropin, is a peptide hormone consisting of 39 amino acids. It is produced in the anterior pituitary of the brain as part of the precursor molecule pro-opiomelanocortin (POMC). Tissue-specific cleavage results in ACTH and a range of related peptides.1,4

ACTH stimulates formation and secretion of glucocorticoids (especially cortisol) by the adrenal cortex. The glucocorticoid production is regulated by various factors.5-8 After stimulation (eg, by physical effort or by the internal body clock), the hypothalamus secretes CRH (corticotropin-releasing hormone). CRH acts on the pituitary, which in turn synthesizes and secretes ACTH. Finally, ACTH stimulates secretion of the glucocorticoids by the adrenals. High concentrations of glucocorticoids in the blood inhibit secretion of CRH and ACTH via a negative feedback mechanism.

ACTH concentrations show a diurnal variation with high levels in the morning and low levels in the evening; therefore, as with cortisol, it is important to know the collection time of the plasma sample for interpretation of the results.

Plasma ACTH measurements are useful in the differential diagnosis of pituitary Cushing's disease (ACTH hypersecretion), autonomous ACTH-producing pituitary tumors (eg, Nelson's syndrome), hypopituitarism with ACTH deficiency, and ectopic ACTH syndrome.9,10 In addition to cortisol measurements, ACTH determinations can be used together with functional or stimulation tests to diagnose the origin of glucocorticoid overproduction. Similarly, ACTH measurements can be employed to facilitate differential diagnosis of adrenocortical insufficiency (Addison's disease).

ACTH not produced by the pituitary gland is known as ectopic ACTH;11 this is often associated with small cell carcinoma of the lung. In rare cases, ectopic ACTH can be caused by thymic tumors, pancreatic adenocarcinomas, or bronchial carcinoids. These tumors often secrete ACTH precursors (POMC and pro-ACTH).

1. Talbot JA, Kane JW, White A. Analytical and clinical aspects of adrenocorticotrophin determination. Ann Clin Biochem. 2003 Sep; 40(Pt 5):453-471. PubMed 14503983

2. Reisch N, Renicke M, Bidlingmaier. Practical stability of adrenocorticotropic hormone depends on time to centrifugation rather than temperature. Clin Chem. 2007 Feb; 53(2):358-359.

3. ACTH on Elecsys 1010/2010 and Modular Analytics E170. [package insert]. 2007-07, V

4. Indianapolis, Ind: Roche Diagnostics; 2007. PubMed 2545177 4. Cone RD. Anatomy and regulation of the central melanocortin system. Nat Neurosci. 2005; 8(5):571-578. PubMed 15856065

5. Jacobson L. Hypothalamic-pituitary-adrenocortical axis regulation. Endocrinol Metab Clin North Am. 2005; 34(2):271-292. PubMed 15850842

6. Arlt W, Stewart PM. Adrenal corticosteroid biosynthesis, metabolism, and action. Endocrinol Metab Clin North Am. 2005; 34(2):293-313. PubMed 15850843

7. Lin L, Achermann JC. The adrenal. Horm Res. 2004; 62(Suppl 3):22-29. PubMed 15539795

8. Engelmann M, Landgraf R, Wotjak CT. The hypothalamic-neurohypophysial system regulates the hypothalamic-pituitary-adrenal axis under stress: An old concept revisited. Front Neuroendocrinol. 2004; 25(3-5):132-149. PubMed 15589266

9. Beauregard C, Dickstein G, Lacroix A. Classic and recent etiologies of Cushing's syndrome: Diagnosis and therapy. Treat Endocrinol. 2002; 1(2):79-94. PubMed 15765624

10. Lindsay JR, Nieman LK. Differential diagnosis and imaging in Cushing's syndrome. Endocrinol Metab Clin North Am. 2005; 34(2):403-421. PubMed 15850850

11. Oliver RL, Davis JR, White A. Characterization of ACTH-related peptides in ectopic Cushing's syndrome. Pituitary. 2003; 6(3):119-126. PubMed 14971736