Central obesity, arterial hypertension, proximal muscle weakness, diabetes, oligomenorrhea, hirsutism, thin skin, and ecchymosis
Today, obesity is common. Anti-androgenic effects of Cushing syndrome can help differentiate it from obesity
+LR thin skin 112
+LR osteopenia 18
+LR ecchymoses 4
All 3 have a specificity of 95%
Prevalence of Cushing in obese/metabolic type patients 0.2%
24,000 cases of Cushing/12 million patients with metabolic syndrome = 0.2%
24 hour urinary free cortisol
2-forms: 1) unbound to protein or 2) cortisol unconjugated to sulfuric or hyaluronic acid
Unbound cortisol is filtered and reabsorbed. 3% remains in urine.
Should measure 24-hour urine creatinine with cortisol to ensure adequate collection
Repeat if creatinine is less than 1.5g/day for men and 1g/day in women
24-hour urine cortisol > 62mg/day has +LR 11
Dexamethasone Suppression test is used to differentiate ACTH dependent from ACTH independent Cushing syndrome.
This is now done by directly measuring ACTH levels
Should not be used to diagnose or screen for Cushing syndrome
Obese patients with depression will fail to suppress cortisol in response to dexamethasone challenge
For Cushingoid exam, but low or zero urinary free cortisol and suppressed ACTH levels suggests exogenous steroid and should prompt a review of medications.
ACTH-dependent Cushing syndrome can be due to pituitary secretion from an adenoma or ectopic secretion from a malignant source – typically in the chest.
Some experts recommend always doing petrosal sinus sampling due to the high prevalence of non-functioning pituitary adenomas and mortality associated with surgery. Some series report the prevalence of asymptomatic pituitary adenomas as high as 15-40%. Mortality associated with transsphenoidal micro-adenectomy is 1%.
ACTH-independent Cushing syndrome is usually caused by an adrenal neoplasm.
Characteristics of benign tumors: small (<5cm), <10 Hounsfield units, and have > 60% contrast washout at 15 minutes.
Benign tumors can be treated laparoscopically, while malignant tumors typically are resected with an open technique.