Signs and Symptoms Percentage Prevalence

General Appearance

• Weight gain and obesity, manifesting as truncal obesity (90%)

• A rounded and puffy face ("moon facies") (75%)

• Dorsocervical ("buffalo hump") and supraclavicular fat accumulation

Skin Changes—From Atrophy of Dermis and Connective Tissue

• Skin striae ("stretch marks" that are usually red or purple in appearance and greater than 1 cm) (50%)

• Hyperpigmentation Metabolic

• Hyperglycemia that can range from impaired glucose tolerance (75%) to diabetes mellitus (20-50%)

• Hypokalemic alkalosis (from mineralocorticoid effect of cortisol) Cardiovascular

• Hypertension (from mineralocorticoid effect of cortisol) (85%)

• Patients are at risk of the cardiovascular complications of hypertension, hyperlip-idemia, and hyperglycemia

• Peripheral edema Genitourinary

• Menstrual irregularities (the most typical presentation is amenorrhea) (70%)

• Erectile dysfunction (85%) Other

• Psychiatric changes such as depression, emotional lability, psychosis, euphoria, anxiety, and decreased cognition (85%)

• Sleep disturbances

• Osteopenia (80%) and osteoporosis—usually affecting trabecular bone

• Linear growth impairment in children

• Proximal muscle weakness (65%)

• Avascular necrosis—more common in iatrogenic cases

• Glaucoma and cataracts

• Impaired wound healing and susceptibility to opportunistic infections

• Hypothyroidism

Laboratory Tests

• The diagnosis of Cushing's syndrome and its etiology is often complex and generally requires the involvement of endocrinologists and specialized testing centers.

• Initial screening tests to confirm the presence of hypercortisolism and differentiate Cushing's syndrome from conditions with similar presentations include 24-hour urinary free cortisol and overnight low-dose dexamethasone suppression test (DST; Table 45-6).

• The midnight plasma cortisol or combined dexamethasone suppression plus CRH test are less commonly used.

• Typically, a combination of at least two screening tests is used to establish the preliminary diagnosis.

• Once the diagnosis is confirmed, additional tests can be performed to determine the etiology.

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