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Test ID: CORT Cortisol, Serum

Reporting Name

Cortisol, S

Useful For

Discrimination between primary and secondary adrenal insufficiency


Differential diagnosis of Cushing syndrome


This test is not recommended for evaluating response to metyrapone.

Clinical Information

Cortisol, the main glucocorticoid (representing 75%-90% of the plasma corticoids), plays a central role in glucose metabolism and in the body's response to stress.


Cortisol levels are regulated by adrenocorticotropic hormone (ACTH), which is synthesized by the pituitary in response to corticotropin-releasing hormone (CRH). CRH is released in a cyclic fashion by the hypothalamus, resulting in diurnal peaks (6 a.m.-8 a.m.) and nadirs (11 p.m.) in plasma ACTH and cortisol levels.


The majority of cortisol circulates bound to cortisol-binding globulin (CBG-transcortin) and albumin. Normally, less than 5% of circulating cortisol is free (unbound). The "free" cortisol is the physiologically active form. Free cortisol is filterable by the renal glomerulus.


Although hypercortisolism is uncommon, the signs and symptoms are common (eg, obesity, high blood pressure, increased blood glucose concentration). The most common cause of increased plasma cortisol levels in women is a high circulating concentration of estrogen (eg, estrogen therapy, pregnancy) resulting in increased concentration of cortisol-binding globulin.


Spontaneous Cushing syndrome results from overproduction of glucocorticoids as a result of either primary adrenal disease (adenoma, carcinoma, or nodular hyperplasia) or an excess of ACTH (from a pituitary tumor or an ectopic source). ACTH-dependent Cushing syndrome due to a pituitary corticotroph adenoma is the most frequently diagnosed subtype; most commonly seen in women in the third through the fifth decades of life. The onset is insidious and usually occurs 2 to 5 years before a clinical diagnosis is made.


Causes of hypocortisolism are:

-Addison disease-primary adrenal insufficiency

-Secondary adrenal insufficiency:

--Pituitary insufficiency

--Hypothalamic insufficiency

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


In primary adrenal insufficiency, adrenocorticotropic hormone (ACTH) levels are increased, and cortisol levels are decreased; in secondary adrenal insufficiency, both ACTH and cortisol levels are decreased.


When symptoms of glucocorticoid deficiency are present and the 8 a.m. plasma cortisol value is less than 10 mcg/dL (or the 24-hour urinary free cortisol value is <50 mcg/24 hours), further studies are needed to establish the diagnosis. First, the basal plasma ACTH concentration should be measured, followed by the short cosyntropin stimulation test. Other frequently used tests are the metyrapone, and insulin-induced hypoglycemia test. Consult the Endocrine Testing Center at 800-533-1710 extension 4-2148 for testing information and interpretation of test results.


Cushing syndrome is characterized by increased serum cortisol levels. However, the 24-hour urinary free cortisol excretion is the preferred screening test for Cushing syndrome, specifically CORTU / Cortisol, Free, 24 Hour, Urine, which utilizes high-performance liquid chromatography/triple quadrupole-mass spectrometry (LC-MS/MS). A normal result makes the diagnosis unlikely.


When cortisol measurement by immunoassay gives results that are not consistent with clinical symptoms, or if patients are known to or suspected of taking exogenous synthetic steroids, consider testing by LC-MS/MS; see CINP / Cortisol, Serum, LC-MS/MS, Serum. For confirming the presence of synthetic steroids, order SGSS / Synthetic Glucocorticoid Screen, Serum.

Analytic Time

Same day/1 day

Day(s) and Time(s) Performed

Monday through Friday; 5 a.m.-12 a.m.

Saturday; 6 a.m.-6 p.m.

Clinical Reference

1. Findling JW, Raff H: Diagnosis and differential diagnosis of Cushing's syndrome. Endocrinol Metab Clin. North Am 2001;30(3):729-747

2. Buchman AL: Side effects of corticosteroid therapy. J Clin Gastroenterol. 2001;33(4):289-294

3. Rifai N, Horvath AR, Wittwer eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 6th ed. Elsevier; 2018

Method Name

Immunoenzymatic Assay

Specimen Type


Advisory Information

The preferred screening test for Cushing syndrome measures 24-hour urinary free cortisol. Order CORTU / Cortisol, Free, 24 Hour, Urine.


For confirming the presence of synthetic steroids, order SGSS / Synthetic Glucocorticoid Screen, Serum.


For patients taking exogenous glucocorticoids, order CORTU / Cortisol, Free, 24 Hour, Urine


For evaluating response to metyrapone, order DCORT / 11-Deoxycortisol Serum.


For evaluation of congenital adrenal hyperplasia, order DCORT / 11-Deoxycortisol Serum; OHPG / 17-Hydroxyprogesterone, Serum; and DHEA_ / Dehydroepiandrosterone (DHEA), Serum, which provide a better, accurate, and specific determination of the enzyme deficiency.

Specimen Required

Collection Container/Tube:

Preferred: Serum gel

Acceptable: Red top

Submission Container/Tube: Plastic vial

Specimen Volume: 0.6 mL

Collection Instructions:

1. Morning (8 a.m.) and afternoon (4 p.m.) specimens are preferred.

2. Serum gel tubes should be centrifuged within 2 hours of collection.

3. Red-top tubes should be centrifuged and the serum aliquoted into a plastic vial within 2 hours of collection.

Additional Information:

1. Include time of collection.

2. If multiple specimens are collected, send separate order for each specimen.

Specimen Minimum Volume

0.5 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Serum Refrigerated (preferred) 7 days
  Frozen  7 days

Reference Values

a.m.: 7-25 mcg/dL

p.m.: 2-14 mcg/dL


For SI unit Reference Values, see

Test Classification

This test has been cleared, approved or is exempt by the U.S. 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.

CPT Code Information


LOINC Code Information

Test ID Test Order Name Order LOINC Value
CORT Cortisol, S 87429-7


Result ID Test Result Name Result LOINC Value
CORTP Cortisol, S 83088-5
CAM AM Result 9813-7
CPM PM Result 9812-9
Mayo Clinic Laboratories | Endocrinology Catalog Additional Information: