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Diabetes, Endocrine and Obesity Branch, The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD, USA.
Copyright © 2018 Korean Endocrine Society
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
CONFLICTS OF INTEREST: HRA Pharma provided research funding to National Institutes of Health for investigation of metyrapone and mifepristone under a Cooperative Research and Development Agreement.
Test | Caveat | When can the test be used despite the caveat? | Verifying the result |
---|---|---|---|
All tests | May be falsely normal in a patient with cyclic Cushing's syndrome [1011] | If the pre-test probability is high based on history and physical examination, repeat testing at intervals or when patient feels worst. | Review caveats for each test below |
UFC | May be falsely increased with fluid intake >5 L/day [12] | If subjects reduce intake | Measure volume; if volume is high, ask about intake |
May be falsely increased or decreased with incorrect collection | Measure creatinine, which should be ± 15% from day to day; check volume | ||
Will be decreased in the setting of renal impairment [13] | Use with caution with GFR 30–50 mL/min: accept as valid only elevated values. | ||
1 mg DST | May be falsely normal in Cushing's disease patients, presumably because of slow drug metabolism [14] | Measure dexamethasone; if in range expected of an 8 mg dose, consider Cushing's disease | |
May be falsely abnormal in patients with elevated CBG (2° oral estrogen) or in those with fast metabolism of dexamethasone [8] | Fewest false positive results in patients not taking medications that interact with CYP3A4 [15] | Measure dexamethasone level; if low, increase dose to achieve correct level | |
Measure CBG; if high discontinue estrogen for 4–6 weeks | |||
Salivary cortisol | May be falsely abnormal in older men and women, and in hypertensive or diabetic patients [1617] | If used in these populations, consider accepting only normal results | |
May be falsely abnormal in individuals with variable sleeping times (e.g., shift workers) | If used in this population, consider accepting only normal results |
Condition | Factors affecting hypercortisolism |
---|---|
Exercise | Described in individuals exercising nearly daily at close to maximal VO2 [18] |
Hypothalamic amenorrhea | Described in women under stress or after weight loss [19] |
Pregnancy | Occurs in late second and third trimester [20] |
Uncontrolled diabetes | |
Sleep apnea | Seen in untreated subjects; remits with treatment [21] |
Pain | |
Alcoholism | Associated with increased UFC and abnormal DST [22] |
Psychiatric disorders | |
Stress | |
Extreme obesity |
Systemic |
Fatigue or hypomania (may alternate) |
Growth retardation (in children) |
Increased weight from baseline |
Insomnia |
Vivid dreams |
Skin, adipose, hair |
Abnormal adipose in dorsocervical, supraclavicular, temporal areas |
Striae, especially if >1 cm width and purple |
Thin skin, especially at <40 years |
Hyperpigmentation, typically over joints, in scars, buccal and vaginal mucosa and perioral |
Hirsutism (women) |
Balding (women) |
Acne, especially if new |
Poor wound healing |
Increased bruising |
Flushed ruddy face |
Psychiatric/Cognitive |
Accentuation of previous (or new) personality/psychiatric disorder |
Increased irritability |
Decreased memory |
Decreased cognitive ability |
Infectious |
Increased number of infections |
Metabolic/Renal |
Glucose intolerance/diabetes |
Increased incidence of stones |
Cardiovascular/Thrombotic |
Hypertension |
Increased incidence cerebrovascular accident |
Increased incidence myocardial infarction |
Increased clotting |
Edema |
Reproductive |
Decreased libido |
Delayed or stuttering puberty (children) |
Infertility |
Hypogonadism |
Opthalmologic |
Central serous chorioretinopathy |
Musculoskeletal |
Proximal muscle weakness |
Back pain |
Decreased bone mineral density/fracture |
Test | Caveat | When can the test be used despite the caveat? | Verifying the result |
---|---|---|---|
All tests | May be falsely normal in a patient with cyclic Cushing's syndrome [ | If the pre-test probability is high based on history and physical examination, repeat testing at intervals or when patient feels worst. | Review caveats for each test below |
UFC | May be falsely increased with fluid intake >5 L/day [ | If subjects reduce intake | Measure volume; if volume is high, ask about intake |
May be falsely increased or decreased with incorrect collection | Measure creatinine, which should be ± 15% from day to day; check volume | ||
Will be decreased in the setting of renal impairment [ | Use with caution with GFR 30–50 mL/min: accept as valid only elevated values. | ||
1 mg DST | May be falsely normal in Cushing's disease patients, presumably because of slow drug metabolism [ | Measure dexamethasone; if in range expected of an 8 mg dose, consider Cushing's disease | |
May be falsely abnormal in patients with elevated CBG (2° oral estrogen) or in those with fast metabolism of dexamethasone [ | Fewest false positive results in patients not taking medications that interact with CYP3A4 [ | Measure dexamethasone level; if low, increase dose to achieve correct level | |
Measure CBG; if high discontinue estrogen for 4–6 weeks | |||
Salivary cortisol | May be falsely abnormal in older men and women, and in hypertensive or diabetic patients [ | If used in these populations, consider accepting only normal results | |
May be falsely abnormal in individuals with variable sleeping times (e.g., shift workers) | If used in this population, consider accepting only normal results |
Condition | Factors affecting hypercortisolism |
---|---|
Exercise | Described in individuals exercising nearly daily at close to maximal VO2 [ |
Hypothalamic amenorrhea | Described in women under stress or after weight loss [19] |
Pregnancy | Occurs in late second and third trimester [ |
Uncontrolled diabetes | |
Sleep apnea | Seen in untreated subjects; remits with treatment [ |
Pain | |
Alcoholism | Associated with increased UFC and abnormal DST [ |
Psychiatric disorders | |
Stress | |
Extreme obesity |
Those that occur at an unusual age (fractures, hypertension, failure to progress in puberty, memory and cognitive changes) are more likely to reflect underlying hypercortisolism. Progressive accumulation of features over time also is more suggestive than a few features at one point in time.
UFC, urine free cortisol; GFR, glomerular filtration rate; 1 mg DST, 1 mg overnight dexamethasone suppression test; CBG, corticosteroid-binding globulin.
UFC, urine free cortisol; DST, dexamethasone suppression test.