Cortisol Random

Order Code

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2655

Preferred Specimen

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• 2 mL serum collected in an SST tube.
• Allow the sample to clot in an upright position for at least 30 minutes, then centrifuge within 2 hours of collection.
• Refrigerate after processing.
• Important: Do not collect samples from patients on high-dose biotin therapy (>5 mg/day) until at least 8 hours after the last biotin dose.

ContainerType

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Serum separator tube

Alternate Specimen Requirements

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• 2 mL serum from a plain red top tube.
• Allow clotting in an upright position for at least 60 minutes, then centrifuge and transfer serum to a plastic transport tube within 2 hours.
• Clearly label tube as serum from a plain red top tube.
• Refrigerate after processing.
• Important: Avoid sample collection within 8 hours of high-dose biotin administration (>5 mg/day).

Minimum Volume

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Adult: 0.5 mL serum
Pediatric: 0.2 mL serum (does not allow for repeat or
additional testing).

Transport Temperature

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Refrigerated

Expected Turnaround Time

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1 day

Specimen Stability

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1 day room temperature; 4 days refrigerated; 1 year frozen. Allow only 1 freeze/thaw cycle

Methodology

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Roche COBAS Electrochemiluminescent Immunoassay (ECLIA)

Rejection Criteria

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• Plasma

Overview

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Cortisol, the primary adrenal glucocorticoid, is secreted by the adrenal glands under stimulation by pituitary adrenocorticotropic hormone (ACTH), which is regulated by hypothalamic corticotropin-releasing hormone (CRH). This regulatory system is known as the hypothalamic-pituitary-adrenal (HPA) axis, featuring a negative feedback loop.

Cortisol levels follow a circadian rhythm, peaking between 6 AM and 8 AM and reaching their lowest levels near midnight. In circulation, most cortisol is bound to cortisol-binding globulin (CBG) and albumin; less than 5% is free, which is the biologically active form. The free cortisol half-life is approximately 80 to 100 minutes. Cortisol plays vital roles in metabolism, immune regulation, and maintaining homeostasis. It is primarily inactivated in the liver, with metabolites excreted in urine.

Clinical Use

• If clinical suspicion remains high despite negative testing, repeat testing after six months is recommended.
• Serum cortisol testing helps diagnose hypercortisolism (e.g., Cushing syndrome) and hypocortisolism (e.g., Addison disease).
• Cortisol levels can vary rapidly due to stress, infection, medication, and time of day, so single random measurements may be misleading. Provocative or confirmatory testing is often required for accurate diagnosis.
• Cushing syndrome refers to any state of cortisol excess; Cushing disease specifically refers to excess ACTH secretion from a pituitary tumor.
• Exogenous glucocorticoid use is a common cause of Cushing syndrome and should be excluded by thorough history prior to testing.
• Initial screening may use serum, urine, or salivary cortisol; abnormal results warrant referral to endocrinology.

Clinical Significance

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• Screen for hypercortisolism (Cushing syndrome) or hypocortisolism (adrenal insufficiency; Addison disease)
• Part of the functional evaluation of the HPA (hypothalamic-pituitary-adrenal) axis
• Evaluate symptoms suggestive of cortisol excess (eg, hypertension, hyperglycemia, truncal obesity, purple striae on abdomen)
• Evaluate symptoms suggestive of cortisol deficiency (eg, fatigue, low blood pressure, weight loss, muscle weakness, abdominal pain)
• Evaluate symptoms suggestive of acute adrenal crisis (eg, hypotension, change in mental status, severe pain in lower back, vomiting and diarrhea)

Additional Information

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• The Endocrine Society (2008) recommends against using random cortisol or ACTH levels, urinary 17-ketosteroids, the insulin tolerance test, the loperamide test, or imaging for initial diagnosis of Cushing syndrome.
• Selection of initial tests depends on patient factors:
• For patients on antiepileptic drugs (e.g., phenytoin), urine free cortisol or salivary cortisol is preferred.
• In renal failure or adrenal incidentalomas, dexamethasone suppression testing (DST) is preferred over urine free cortisol.
• In pregnancy, urine free cortisol is recommended.

Interpretative Information

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Increased:

• Excess pituitary production of ACTH due to a pituitary adenoma (ie, Cushing Disease, most common)
• Adrenal gland overproduction (eg, solitary adrenal adenoma, nodular hyperplasia, rarely adrenal carcinoma)
• Ectopic ACTH-secreting tumor (eg, pancreas, lung, thyroid, thymus)
• Concurrent trauma, surgery, sepsis
• Depression
• Alcoholism
• Obesity
• Pregnancy or hormone therapy (due to increased cortisol binding globulin)
• Recent hydrocortisone (cortisol) or cortisone use

Decreased:

• Hypothalamic insufficiency
• Pituitary insufficiency
• Adrenal dysfunction (ie, Addison disease)
• Hypothyroidism
• Corticosteroid long-term use (suppresses endogenous cortisol production)
• Certain medications (eg, androgens, phenytoin)
• Sepsis (by decreasing cortisol binding globulin concentration)

Limitations

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• Single random values drawn under uncontrolled conditions have no diagnostic value.
• Cortisol levels may be physiologically increased during hypoglycemia, stress, and pregnancy, making interpretation of cortisol excess difficult.
• Cortisol levels may be falsely elevated following exogenous synthetic corticosteroid use (eg, prednisone, prednisolone).
• Aging may suppress both cortisol secretion and external manifestations of Cushing syndrome.
• Cushing syndrome may have normal urinary free cortisol levels, normal cortisol production rates, or normal nocturnal cortisol levels.
• Normal cortisol can be found with partial pituitary deficiency.
• Dexamethasone suppression tests (DST, both overnight and low-dose protocols) are associated with false positives in obesity, depression, certain antiepileptic drug use, and in 50% of women taking the oral contraceptives (due to increased CBG levels) (Nieman 2008).
• False negative results for the overnight DST may be seen in critically ill or nephrotic patients due to decreased concentrations of cortisol-binding globulin (Nieman, 2008).

References

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Diagnostic Role

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Cortisol excess or deficiency requires laboratory testing for accurate diagnosis. Establishing the correct diagnosis is complicated, however, by factors which affect cortisol levels and result in cortisol values overlapping the reference range. This makes the interpretation of a single value uncertain, especially if it falls within the normal range. Diagnostically useful cortisol measurements require standardized provocative testing protocols in which one or more preanalytic variables are held constant (Nieman 2008).

Clinical suspicion for high cortisol levels (Cushing syndrome) may arise in the setting of an adrenal incidentaloma compatible with adenoma; unusual features for a given age (osteoporosis and/or hypertension at a young age); multiple features predictive of Cushing syndrome (easy bruising, striae, proximal myopathy); or children with weight gain and decreasing growth velocity. In these settings, cortisol suppression testing with a 1 mg overnight or 48-hour, 2 mg/day dexamethasone suppression test is indicated (also appropriate is urine cortisol or late night salivary cortisol). If the test is abnormal or if suspicion remains high despite a normal test, referral to an endocrinologist is advised (Nieman 2008).

Clinical suspicion for low cortisol levels includes symptoms suggestive of corticosteroid deficiency (fatigue, low blood pressure, muscle weakness) or acute adrenal crisis (hypotension, change in mental status, hypoglycemia, electrolyte derangement). A history of prior corticosteroid use is helpful. The easiest screening test for adrenal insufficiency is the standardized cosyntropin ACTH stimulation test. It is very important to note that when adrenal crisis is suspected, emergent treatment is imperative to stabilize the patient. A blood specimen obtained for a random cortisol level may help suggest the diagnosis retrospectively, but awaiting the results should never delay treatment. Once the patient is stabilized, a formal endocrinology evaluation is appropriate (Griffing 2015).

Alias

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• Cortisol, serum
• Serum cortisol, random specimen

Test Setup Days

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Monday through Friday PM shift

CPT

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82533 LOINC: 2143-6

Reference Range

A.M.: 4.8-19.5 UG/DL
P.M.: 2.5-11.9 UG/DL
NOTE: FOR SHIFT WORKERS, THE A.M. CORTISOL RANGE GIVEN
ABOVE MAY BE USEFUL TO ASSESS THE CORTISOL AWAKENING
RESPONSE (CAR; THE CORTISOL DIURNAL PEAK, MEASURED WITHIN 2
HOURS OF AWAKENING) AND THE P.M. CORTISOL RANGE ABOVE MAY BE
USEFUL TO ASSESS THE EXPECTED DECLINE 8-10 HOURS AFTER
AWAKENING. HOWEVER, SHIFT WORKERS MAY EXPERIENCE EITHER AN
EXAGGERATED OR BLUNTED CAR DEPENDING UPON SHIFT TIMING AND
OTHER FACTORS. TO OPTIMIZE COMPARABILITY TO LITERATURE FOR
SUCH PATIENTS, CONSIDER REASSESSING AT LEAST 7 DAYS AFTER A
NON-SHIFT WORK PERIOD.
REF: T. STALDER ET AL. ASSESSMENT OF THE CORTISOL AWAKENING
RESPONSE: EXPERT CONSENSUS GUIDELINES.
PSYCHONEUROENDOCRINOLOGY 63 (2016) 414-432.

UNIT CODE	UNIT CODE NAME	ANALYTE	GENDER	AGE	REFERENCE RANGE	Units of Measure
2655	CORTISOL	COR	NOT SPECIFIED	ALL	SEE BELOW	UG/DL
2655	CORTISOL	COR	MALE	ALL	SEE BELOW	UG/DL
2655	CORTISOL	COR	FEMALE	ALL	SEE BELOW	UG/DL