Cushing’s syndrome

Cushing’s syndrome refers to any causes of hypercortisolism.

Cushing’s disease specifically refers to 2n hypercortisolism due to excess ACTH by
pituitary adenoma. 

Etiology
1. Exogenous (iatrogenic)
 MCC of hypercortisolism
 Due to prolonged glucocorticoid thx
 Some traditional meds or tonics/jamu contains potent steroids usually for joint
pain → steroid-withdrawal arthralgia
2. Endogenous 
o Primary hypercortisolism = ACTH independent
 Adrenal gland makes too much cortisol → ACTH suppression
 Adrenal adenoma, carcinoma, macronodular adrenal
hyperplasia  
o Secondary hypercortisolism = due to high ACTH
a. Pituitary ACTH production = CUSHING’S DISEASE
o Pituitary adenoma → ACTH secretion 
b. Ectopic ACTH production 
o Paraneoplastic syndrome → ACTH secretion
 SCLC
 RCC

Clinical features
CUSHINGOID
 Cataracts
 Ulcers
 Skin (striae, bruising, thinning, ulcer)
o Impaired collagen synthesis → skin thinning
 Hirsutism
 HTN: often w hypokalemia and met alkalosis 
o High cortisol increases sensitivity of peripheral vessels to catecholamines
o At very high level, cortisol cross-react with mineralocorticoid receptors
(aldosterone is not increased) → increased water and sodium retention with
increased potassium excretion
 Infections
 Necrosis (femur head) - Due to inhibition of calcitriol synthesis by cortisol.
 Glycosuria
 Obesity, osteoporosis
 Immunosuppression
 Diabetes
o Diabetogenic effect of glucocorticoid → insulin resistance
 Muscle weakness with thin extremities - cortisol breaks down muscles to produce
amino acids for gluconeogenesis
 Moon facies, buffalo hump, truncal obesity - high insulin (due to high glucose)
increases fat storage centrally
o Supraclavicular fat pads are quite specific 
 Hyperpigmentation- in secondary hypercortisolism only!!! 
 o Esp in non-exposed area (palm creases, oral cavity)
o Excess ACTH → MSH is cleaved from same precursor as ACTH →
overproduce melanin
 Dyslipidemia - Cortisol increases lipolysis
 Decreased libido, irregular menstruation - due to inhibition of gonadotropin release

Diagnosis 
Lab test
 Hypernatremia, hypokalemia, met alkalosis (Due to the mineralocorticoid effect of
cortisol: ↑ water and sodium retention, ↑ K+ excretion, ↑ H+ excretion)
 Hyperglycemia- due to stimulation of gluconeogenesis enzymes (e.g., glucose-6-
phosphatase) and inhibition of glucose uptake in peripheral tissue
 Hyperlipidemia
 Leukocytosis (neutrophils*)
 Serum androgen: testosterone, DHEAS, androstenedione increased in F,
testosterone decreased in M.
 PRL, FSH, LH and pituitary fx 

To diagnose hypercortisolism 
**Diurnal cortisol = low in midnight, high in morning (that’s why we measure midnight
sample for screening, and early morning sample for dexa test!)
 ↑ 24hr urine cortisol: most accurate, but hard to do in clinical setting
 ↑ early morning serum cortisol following low dose dexamethasone test (1mg)
o A normal person w/o hypercortisolism will be suppressed at <50nmol/l
 Midnight salivary or serum cortisol
 Random cortisol is not useful except in exogenous Cushing’s when very low levels
found (traditional meds can contain dexa)
o