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Drugs & Diseases > Laboratory Medicine
Serum Cortisol
Author: George T Griffing, MD; Chief Editor: Eric B Staros, MD more...
Sections Serum Cortisol
Reference Range
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Cortisol is the main adrenal glucocorticoid and plays a central role in glucose metabolism and in the body's response to stress. Adrenal cortisol production is regulated by adrenocorticotropic hormone (ACTH), which is synthesized by the pituitary gland in response to hypothalamic corticotropin-releasing hormone (CRH). Serum cortisol in turn inhibits the production of both CRH and ACTH (negative feed-back loop), and this system self-regulates to control the proper level of cortisol production. The coordinated stimulatory and inhibitory connections between CRH, ACTH, and cortisol are referred to as the hypothalamic-pituitary-adrenal (HPA) axis.
Free serum cortisol reference range
8 AM: 0.121-1.065 mcg/dL [1]
Total serum cortisol reference ranges
Adult/elderly [1] :
8 AM: 5-23 mcg/dL or 138-635 nmol/L (SI units)
4 PM: 3-13 mcg/dL or 83-359 nmol/L (SI units)
Child 1-16 years [1] :
8 AM: 3-21 mcg/dL
4 PM 3-10 mcg/dL
Newborn: 1-24 mcg/dL [1]
Urine (24-hour)
Adult/elderly: < 100 mcg/24 hr or < 276 nmol/day (SI units) [1]
Adolescent: 5-55 mcg/24 hr [1]
Child: 2-27 mcg/24 hr [1]
7 AM-9 AM: 100-750 ng/dL [1]
3 PM-5 PM: < 401 ng/dL [1]
11 PM-midnight: < 100 ng/dL [1]
Measurements of serum cortisol are used primarily in the diagnosis of hypercortisolism and hypocortisolism. Many extraneous factors can affect the serum cortisol including stress, time of day, and exogenous glucocorticoids. This makes the interpretation of a single value hazardous, and emphasizes the need for provocative testing.
Clinical states of cortisol excess (Cushing syndrome) are characterized by increased serum cortisol levels. [2, 3] Diagnostic tests are recommended to screen for hypercortisolism, but the easiest is the overnight low-dose dexamethasone suppression test. Dexamethasone (1 mg, ie, 2 tablets of 0.5 mg) are taken orally between 11 PM and midnight, and a single blood sample is drawn at 8 AM the next morning for assay of serum cortisol. A dose of 0.3 mg/m2 surface area can be used in children. The dexamethasone dose does not need to be adjusted in obese adults. [4, 5]
Hypocortisolism
Clinical states of cortisol deficiency (adrenal insufficiency) are characterized by decreased serum cortisol levels. The easiest screening test is the standard ACTH stimulation test. This test consists of measuring serum cortisol immediately before and approximately 60 minutes after intravenous injection of 250 mcg (one vial) of cosyntropin. Serum ACTH should also be drawn at baseline before administration of cosyntropin in order to distinguish primary from secondary adrenal insufficiency. [6, 7]
See the list below:
Container/tube: Red top
Specimen volume: 0.5 mL
Collection instructions: Include time of draw.
Reject sample due to gross hemolysis or visible lipemia.
Most cortisol circulates bound to cortisol-binding globulin (CBG-transcortin) and albumin. The most common cause of increased CBG is estrogen. Therefore, higher levels are found in women, pregnant women, and women undergoing estrogen therapy.
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.
Indications/Applications
Serum cortisol measurements are primarily used to diagnose states of cortisol excess (hypercortisolism) or deficiency (hypocortisolism).
Although hypercortisolism is uncommon, the signs and symptoms are common (eg, obesity, high blood pressure, increased blood glucose concentration).
Cushing syndrome (endogenous rather than exogenous from medication) results from overproduction of cortisol 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 and is most commonly seen in women in the third through the fifth decades of life. The onset is insidious and usually occurs 2-5 years before a clinical diagnosis is made.
Adrenal insufficiency results from underproduction of cortisol either as a result of primary adrenal disease or a deficiency of ACTH/CRH from pituitary/hypothalamic disease. The causes of hypocortisolism include Addison disease -primary adrenal insufficiency, pituitary insufficiency and/or hypothalamic insufficiency.
Acute stress (including hospitalization and surgery), alcoholism, depression, and many drugs (eg, exogenous cortisones, anticonvulsants) can interfere with normal diurnal variation, affect response to suppression/stimulation tests, and cause elevated baseline levels.
Patients taking some exogenous glucocorticoids (eg, prednisone) may have falsely increased cortisol levels because of cross-reactivity.
CBG levels may be increased in pregnancy and exogenous estrogens, resulting in higher cortisol levels.
An increased production of cortisol without true clinical manifestations of hypercortisolism (pseudo-Cushing syndrome) occurs with certain disorders including depression, alcoholism, anorexia nervosa, and others. In these cases, the overactivity of the hypothalamic-pituitary-adrenal axis is similar to Cushing syndrome.
Pagana KD, Pagana TJ, Pagana TN. Mosby's Diagnostic & Laboratory Test Reference. 14th ed. St. Louis, Mo: Elsevier; 2019.
Invitti C, Pecori Giraldi F, de Martin M, Cavagnini F. Diagnosis and management of Cushing's syndrome: results of an Italian multicentre study. Study Group of the Italian Society of Endocrinology on the Pathophysiology of the Hypothalamic-Pituitary-Adrenal Axis. J Clin Endocrinol Metab. 1999 Feb. 84(2):440-8. [Medline].
[Guideline] Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart PM, et al. The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008 May. 93(5):1526-40. [Medline]. [Full Text].
Blethen SL, Chasalow FI. Overnight dexamethasone suppression test: normal responses and the diagnosis of Cushing's syndrome. Steroids. 1989 Aug. 54(2):185-93. [Medline].
Wood PJ, Barth JH, Freedman DB, Perry L, Sheridan B. Evidence for the low dose dexamethasone suppression test to screen for Cushing's syndrome--recommendations for a protocol for biochemistry laboratories. Ann Clin Biochem. 1997 May. 34 ( Pt 3):222-9. [Medline].
Dickstein G, Shechner C, Nicholson WE, Rosner I, Shen-Orr Z, Adawi F. Adrenocorticotropin stimulation test: effects of basal cortisol level, time of day, and suggested new sensitive low dose test. J Clin Endocrinol Metab. 1991 Apr. 72(4):773-8. [Medline].
Crowley S, Hindmarsh PC, Holownia P, Honour JW, Brook CG. The use of low doses of ACTH in the investigation of adrenal function in man. J Endocrinol. 1991 Sep. 130(3):475-9. [Medline].
George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine
George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society
Eric B Staros, MD Associate Professor of Pathology, St Louis University School of Medicine; Director of Clinical Laboratories, Director of Cytopathology, Department of Pathology, St Louis University Hospital
Eric B Staros, MD is a member of the following medical societies: American Medical Association, American Society for Clinical Pathology, Association for Molecular Pathology, College of American Pathologists
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