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Test ID: ACTH    
Adrenocorticotropic Hormone (ACTH), Plasma

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Useful For Suggests clinical disorders or settings where the test may be helpful

Determining the cause of hypercortisolism and hypocortisolism

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Adrenocorticotropic hormone (ACTH), the primary stimulator of adrenal cortisol production, is synthesized by the pituitary in response to corticotropin-releasing hormone (CRH), which is released by the hypothalamus. Plasma ACTH and cortisol levels exhibit peaks (6-8 a.m.) and nadirs (11 p.m.).

 

Cortisol, the main glucocorticoid, plays a central role in glucose metabolism and in the body's response to stress. Only a small percentage of circulating cortisol is biologically active (free form), with the majority of cortisol inactive (protein bound). Cortisol is inactivated in the liver and excreted in the urine as conjugated compounds (largely 17-hydroxysteroids). Urine free cortisol levels reflect circulating free plasma cortisol levels.

 

Disorders of cortisol production:

Hypercortisolism

-Cushing syndrome:

 - Cushing disease (pituitary ACTH-producing tumor)

 - Ectopic ACTH-producing tumor

 - Ectopic CRH

 - Adrenal cortisol-producing tumor

 - Adrenal hyperplasia (non-ACTH dependent, autonomous cortisol-producing adrenal nodules)

 

Hypocortisolism

-Addison disease-primary adrenal insufficiency

-Secondary adrenal insufficiency

-Pituitary insufficiency

-Hypothalamic insufficiency

-Congenital adrenal hyperplasia-defects in enzymes involved in cortisol synthesis

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

10-60 pg/mL (a.m. draws)

No established reference values for p.m. draws

Pediatric reference values are the same as adults, as confirmed by peer reviewed literature.

 

Petersen KE: ACTH in normal children and children with pituitary and adrenal diseases. I. Measurement in plasma by radioimmunoassay-basal values. Acta Paediatr Scand 1981;70:341-345

Interpretation Provides information to assist in interpretation of the test results

In a patient with hypocortisolism, an elevated adrenocorticotropic hormone (ACTH) indicates primary adrenal insufficiency, whereas a value that is not elevated is consistent with secondary adrenal insufficiency from a pituitary or hypothalamic cause.

 

In a patient with hypercortisolism (Cushing syndrome), a suppressed value is consistent with a cortisol-producing adrenal adenoma or carcinoma, primary adrenal micronodular hyperplasia, or exogenous corticosteroid use.

 

Normal or elevated ACTH in a patient with Cushing syndrome puts the patient in the ACTH-dependent Cushing syndrome category. This is due to either an ACTH-producing pituitary adenoma or ectopic production of ACTH (bronchial carcinoid, small cell lung cancer, others). Further diagnostic studies such as dexamethasone suppression testing, corticotropin-releasing hormone stimulation testing, petrosal sinus sampling, and imaging studies are usually necessary to define the ACTH source.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

In very rare instances of the ectopic adrenocorticotropic hormone (ACTH) syndrome, the elevated ACTH may be biologically active but not detected by the immunometric assay.

 

Patients taking glucocorticoids may have suppressed levels of ACTH with an apparent high level of cortisol. This may be due to cross-reactivity with the cortisol immunoassays. If exogenous Cushing is suspected, a cortisol level determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) (eg, COR / Cortisol, Serum, LC-MS/MS) should be used with the ACTH level for the interpretation.

Clinical Reference Provides recommendations for further in-depth reading of a clinical nature

1. Demers LM: In Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, 2006; pp 2014-2027

2. Petersen KE: ACTH in normal children and children with pituitary and adrenal diseases I. Measurement in plasma by radioimmunoassay-basal values. Acta Paediatr Scan 1981;70:341-345