This assay may be significantly impacted by high-dose biotin (>5 mg dose) taken within previous 12 hours. High concentrations of biotin may lead to falsely decreased results. These concentrations may be found in patients taking over-the-counter supplements with biotin content much higher than nutritional requirements for biotin. Specimens should not be collected until at least 12 hours after the last dose.

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.^2,3 ACTH stimulates formation and secretion of glucocorticoids (especially cortisol) by the adrenal cortex. The glucocorticoid production is regulated by various factors.⁴ After stimulation (e.g. 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, hypopituitarism with ACTH deficiency and ectopic ACTH syndrome.^5,6 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. 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.

The Roche Diagnostics Elecsys ACTH assay employs two monoclonal antibodies specific for ACTH (9-12) and for the C-terminal region (ACTH 36-39). Due to common antigenic structure, the antibodies recognize intact biologically active ACTH 1-39 and the ACTH precursors POMC and pro-ACTH.³

References:
1. Reisch N, Reincke M, Bindlingmaier M.  Preanalytical stability of 
adrenocorticotropic hormone depends on time centrifugation rather than 
temperature.  Clin Chem 2007;53:358-359.

2. Cone RD. Anatomy and regulation of the central melanocortin system. 
Nature Neurosci 2005;8:571-578.

3. Talbot JA, Kane JW, White A. Analytical and clinical aspects of 
adrenocorticotrophin determination. Ann Clin Biochem 2003;40:453-471.

4. Jacobson L. Hypothalamic-pituitary-adrenocortical axis regulation. 
Endocrinol Metab Clin North Am 2005;34:271-292.

5. Beauregard C, Dickstein G, Lacroix A. Classic and recent etiologies 
of Cushing's syndrome: diagnosis and therapy. Treat Endocrinol 
2002;1:79-94.

6. Lindsay JR, Nieman LK. Differential diagnosis and imaging in 
Cushing's syndrome. Endocrinol Metab Clin North Am 2005;34:403-
421.