Determining the cause of hypercortisolism and hypocortisolism
ACTH (Adrenocorticotropic Hormone)
Adrenal Corticotropin Hormone
Separate specimens should be submitted when multiple tests are ordered.
Patient Preparation: For the 12 hours before specimen collection do not take multivitamins or dietary supplements containing biotin (vitamin B7), which is commonly found in hair, skin, and nail supplements and multivitamins.
Supplies: Aliquot Tube, 5 mL (T465)
Collection Container/Tube: Ice-cooled, lavender top (EDTA)
Submission Container/Tube: Plastic, 5 mL, aliquot tube
Specimen Volume: 1 mL
1. Morning (6 a.m.-10:30 a.m.) specimen is desirable.
2. Collect with a pre-chilled lavender top (EDTA) tube and transport to the laboratory on ice.
3. Centrifuge at refrigerated temperature within 2 hours and immediately separate plasma from cells.
4. Immediately freeze plasma.
If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:
-General Request (T239)
-Oncology Test Request (T729)
|Specimen Type||Temperature||Time||Special Container|
|Plasma EDTA||Frozen (preferred)||28 days|
Determining the cause of hypercortisolism and hypocortisolism
Adrenocorticotropic hormone (ACTH) is synthesized by the pituitary in response to corticotropin-releasing hormone (CRH), which is released by the hypothalamus. ACTH stimulates adrenal cortisol production. Plasma ACTH and cortisol levels exhibit peaks (6-8 a.m.) and troughs (11 p.m.).
Disorders of cortisol production that might affect circulating ACTH concentrations include:
- 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)
-Addison disease-primary adrenal insufficiency
-Secondary adrenal insufficiency
-Congenital adrenal hyperplasia-defects in enzymes involved in cortisol synthesis
7.2-63 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
For SI unit Reference Values, see https://www.mayocliniclabs.com/order-tests/si-unit-conversion.html
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.
ACTH concentrations vary considerably depending on physiological conditions. Therefore, ACTH results should always be evaluated with simultaneously measured cortisol concentrations.
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.
Falsely elevated values may occur in plasma from patients who have developed human antimouse antibodies or heterophilic antibodies.
In rare cases, interference due to extremely high titers of antibodies to analyte-specific antibodies, streptavidin, or ruthenium can occur.
Under ACTH 1-24 medication, ACTH measurement is not recommended, due to negative interference with the sandwich 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, CINP / Cortisol, Serum, LC-MS/MS) should be used with the ACTH level for the interpretation.
Values obtained with different assay methods or kits may be different and cannot be used interchangeably. Test results cannot be interpreted as absolute evidence for the presence or absence of malignant disease.
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
Testing is performed on the Roche cobas. The Roche adrenocorticotropic hormone (ACTH) assay is a sandwich, electrochemiluminescence immunoassay that employs a biotinylated monoclonal ACTH-specific antibody and a monoclonal ACTH specific antibody labeled with a ruthenium complex. ACTH in the specimen reacts with both the biotinylated monoclonal ACTH-specific antibody and the monoclonal ACTH-specific antibody labeled with a ruthenium complex, forming a sandwich complex. Streptavidin-coated microparticles are added and the mixture incubates allowing the newly formed sandwich complex to become bound to the solid phase via the biotin streptavidin interaction. The reaction mixture is aspirated into the measuring cell where the microparticles are magnetically captured onto the surface of the electrode. Application of voltage to the electrode induces the chemiluminescent emission, which is then measured.
The 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 pro-opiomelanocortin (POMC) and pro-ACTH.(Package insert: Elecsys ACTH, Roche Diagnostics, Indianapolis, IN V 1.0, 05/2017)
Monday through Saturday
This test has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.