Diagnosing Hypercortisolism

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After iatrogenic hypercortisolism due to exogenous glucocorticoid exposure is ruled out, there are 3 biochemical tests that can be used to test patients for endogenous hypercortisolism1

Tests for hypercortisolism

Tests Details Diagnostic range1
1-mg overnight dexamethasone suppression test (DST) Detects autonomous cortisol secretion in the blood2
  • Dynamic test that assesses responsiveness of the HPA axis to glucocorticoids1
>1.8 μg/dL
Late-night salivary cortisol (LNSC) Measures the free cortisol in the saliva at the time point when cortisol should be at its lowest level1
  • Detects the loss of diurnal rhythm1
>145 ng/dL
Urine free cortisol (UFC) Measures excretion of circulating unbound cortisol in the urine over 24 hours2
  • Detects the gross overproduction of cortisol over a period of time
>ULN for the assay

If tests are negative, retest in 6 months if signs and symptoms progress.1

Recommendations from screening guidelines:

“We suggest use of the 1-mg DST or late-night cortisol test, rather than UFC, in patients suspected of having mild Cushing syndrome.”—Endocrine Society1

“Given our objective of using tests with high sensitivity . . . we recommend use of the more stringent cutoff of 1.8 μg/dL.” —Endocrine Society1

“LNSC seems to be the best early predictor of recurrence of Cushing disease.”—AACE/ACE3

“Patients are screened for [mild Cushing syndrome] with a 1-mg overnight DST.”—AACE/AAES4

After an abnormal reading from initial tests and exclusion of other physiologic causes of excess cortisol (eg, pregnancy, obesity, diabetes), the Endocrine Society guidelines recommend the use of at least a second, different confirmatory test.1

AACE, American Association of Clinical Endocrinologists; AAES, American Association of Endocrine Surgeons; ACE, American College of Endocrinology; ULN, upper limit of normal.


  1. Nieman LK, Biller BMK, Findling JW, et al. The diagnosis of Cushing’s syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008;93(5):1526-1540.
  2. Arnaldi G, Angeli A, Atkinson AB, et al. Diagnosis and complications of Cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab. 2003;88(12):5593-5602.
  3. Fleseriu M, Hamrahian AH, Hoffman AR, Kelly DF, Katznelson L; for AACE Neuroendocrine and Pituitary Scientific Committee. American Association of Clinical Endocrinologists and American College of Endocrinology disease state clinical review: diagnosis of recurrence in Cushing’s disease. Endocr Pract. 2016;22(12):1436-1448.
  4. Zeiger MA, Thompson GB, Duh QY, et al. American Association of Clinical Endocrinologists and American Association of Endocrine Surgeons Medical Guidelines for the Management of Adrenal Incidentalomas. Endocr Pract. 2009;15(suppl 1):1-20.



Mifepristone is a potent antagonist of progesterone and cortisol via the progesterone and glucocorticoid (GR-II) receptors, respectively. The antiprogestational effects will result in the termination of pregnancy. Pregnancy must therefore be excluded before the initiation of treatment with Korlym and prevented during treatment and for one month after stopping treatment by the use of a nonhormonal medically acceptable method of contraception unless the patient has had a surgical sterilization, in which case no additional contraception is needed. Pregnancy must also be excluded if treatment is interrupted for more than 14 days in females of reproductive potential.


Administer once daily orally with a meal. The recommended starting dose is 300 mg once daily. Renal impairment: Do not exceed 600 mg once daily. Mild-to-moderate hepatic impairment: Do not exceed 600 mg once daily. Do not use in severe hepatic impairment. Based on clinical response and tolerability, the dose may be increased in 300-mg increments to a maximum of 1200 mg once daily. Do not exceed 20 mg/kg per day.

Concomitant use of Korlym with a strong CYP3A inhibitor resulted in a 38% increase in mean plasma concentration of mifepristone. For patients already being treated with a strong CYP3A inhibitor, start with a Korlym dose of 300 mg per day and titrate to a maximum of 600 mg per day if clinically indicated. When a strong CYP3A inhibitor is administered to patients already receiving Korlym, adjust the dose as follows: For patients receiving a daily dose of 600 mg, reduce the daily dose to 300 mg. Titrate to a maximum of 600 mg per day if clinically indicated. For patients receiving a daily dose of either 900 mg or 1200 mg, reduce the daily dose to 600 mg.


Pregnancy; use of simvastatin or lovastatin and CYP3A substrates with narrow therapeutic range; concurrent long-term corticosteroid use; women with history of unexplained vaginal bleeding; women with endometrial hyperplasia with atypia or endometrial carcinoma.


Adrenal insufficiency: Patients should be closely monitored for signs and symptoms of adrenal insufficiency.

Hypokalemia: Hypokalemia should be corrected prior to treatment and monitored for during treatment.

Vaginal bleeding and endometrial changes: Women may experience endometrial thickening or unexpected vaginal bleeding. Use with caution if the patient also has a hemorrhagic disorder or is on anticoagulant therapy.

QT interval prolongation: Avoid use with QT interval-prolonging drugs, or in patients with potassium channel variants resulting in a long QT interval.

Use of strong CYP3A inhibitors: Concomitant use increases mifepristone plasma levels. Adjust Korlym dose as described in Dosage and Administration. Use only when necessary and do not exceed a Korlym dose of 600 mg.


Most common adverse reactions in Cushing’s syndrome (≥20%): nausea, fatigue, headache, decreased blood potassium, arthralgia, vomiting, peripheral edema, hypertension, dizziness, decreased appetite, endometrial hypertrophy.


Drugs metabolized by CYP3A: Administer drugs that are metabolized by CYP3A at the lowest dose when used with Korlym.

CYP3A inhibitors: Caution should be used when Korlym is used with strong CYP3A inhibitors. Adjust Korlym dose as described in Dosage and Administration. Use only when necessary, and do not exceed a Korlym dose of 600 mg.

CYP3A inducers: Do not use Korlym with CYP3A inducers.

Drugs metabolized by CYP2C8/2C9: Use the lowest dose of CYP2C8/2C9 substrates when used with Korlym.

Drugs metabolized by CYP2B6: Use of Korlym should be done with caution with bupropion and efavirenz.

Hormonal contraceptives: Do not use with Korlym.


Nursing mothers: Discontinue drug or discontinue nursing.

Please see accompanying full Prescribing Information and Medication Guide.


Korlym® (mifepristone) is a cortisol receptor blocker indicated to control hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing’s syndrome who have type 2 diabetes mellitus or glucose intolerance and have failed surgery or are not candidates for surgery.

Important Limitations of Use

Do not use for the treatment of type 2 diabetes mellitus unrelated to endogenous Cushing’s syndrome.