Table 1Signs and Symptoms of Cushing's Syndrome
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 |
Table 2Caveats and Restrictions for Tests Used to Screen for Hypercortisolism
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 |
Table 3Conditions Associated with Hypercortisolism Not Caused by Cushing's Syndrome
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 |
|