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"Cushing syndrome" clinical features signs symptoms

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Cushing Syndrome - Signs & Symptoms

Cushing syndrome results from chronic excess glucocorticoids, either from endogenous overproduction or exogenous steroid use. All the clinical features flow directly from the known actions of excess cortisol (and, in some causes, excess adrenal androgens).

Classic Body Habitus

Drawing of a woman with Cushing disease showing central obesity, buffalo hump, muscle wasting, and striae
Illustration from Costanzo Physiology 7e showing the characteristic body shape.
  • Central obesity - fat accumulates on the face, neck, trunk, and abdomen, while the limbs remain thin (due to increased lipolysis peripherally + muscle wasting)
  • Moon face - round, wide, plethoric face with fat deposition
  • Buffalo hump - fat pad deposited over the upper back/posterior neck
  • Supraclavicular fat pads
  • Thin extremities with proximal muscle weakness and wasting

Skin Changes (prominent and diagnostically useful)

These are described in detail by Andrews' Diseases of the Skin:
FeatureMechanism
Purplish/violaceous striae (abdomen, buttocks, thighs, breasts, upper arms)Loss of connective tissue from excess cortisol
Thin, fragile skin ("cigarette paper" wrinkling)Protein catabolism, reduced collagen
Easy bruising / ecchymosesSkin and capillary fragility
Liddle sign - skin tears off with adhesive tape removalExtreme skin fragility
Hypertrichosis / facial lanugo hair (especially in women)Excess adrenal androgens
AcneAndrogen excess
Facial plethora (cheeks, anterior neck, chest V)Increased RBC mass + skin thinning
Poor wound healingImpaired immune/fibroblast function
Scalp hair thinning (women)Androgen effects
Opportunistic fungal infections (dermatophyte, Pityrosporum)Immunosuppression
Occasionally: livedo reticularis, purpura, brownish pigmentationVariable
Women are affected 4 times more frequently than men in non-iatrogenic cases. Peak onset is in the 20s and 30s.

Metabolic & Systemic Features

  • Hypertension - cortisol has weak mineralocorticoid activity AND upregulates vascular alpha-1 adrenergic receptors, increasing responsiveness to catecholamines
  • Hyperglycemia / diabetes mellitus - cortisol promotes gluconeogenesis and insulin resistance; ~20% of patients develop frank DM
  • Hypokalemia - more pronounced in ectopic ACTH syndrome (where ACTH levels are very high)
  • Hyperlipidemia - central fat redistribution
  • Increased susceptibility to infections - immunosuppression

Musculoskeletal

  • Proximal myopathy - weakness of hip and shoulder girdle muscles (difficulty rising from a chair, climbing stairs)
  • Osteoporosis with back pain, vertebral compression fractures
  • Kyphosis of the dorsal spine (which can accentuate the buffalo hump)
  • Generalized arteriosclerosis with progressive prostration and limb/abdominal pains

Reproductive / Endocrine

  • Menstrual irregularities and amenorrhea in women (from androgen excess and HPA dysregulation)
  • Virilization in women - due to excess adrenal androgens
  • Loss of libido in both sexes
  • Hypogonadism

Neuropsychiatric

  • Depression, anxiety, emotional lability
  • Cognitive impairment
  • Sleep disturbance (loss of normal cortisol circadian rhythm)

Causes at a Glance

Flowchart of causes of Cushing syndrome - exogenous vs endogenous, ACTH-dependent vs independent
  • Exogenous (iatrogenic) steroids - most common overall
  • Cushing disease (pituitary ACTH-secreting adenoma) - ~70% of endogenous cases
  • Ectopic ACTH (usually malignant tumors, e.g. small cell lung) - ~10-15%
  • Primary adrenal (adenoma, carcinoma, PPNAD) - ~10%
  • Pseudo-Cushing syndrome - mimicked by alcohol abuse
Note: Cushing disease specifically refers to the pituitary-driven subtype; Cushing syndrome is the broader term for all causes of hypercortisolism.

Quick Diagnostic Clue

The overnight 1 mg dexamethasone suppression test is a rapid screen: cortisol below 50 nmol/L at 8 AM essentially rules out Cushing syndrome (except the iatrogenic form, where cortisol is already low due to adrenocortical suppression).
Sources: Andrews' Diseases of the Skin (9780323547536); Costanzo Physiology 7e (9780323793339); Campbell-Walsh-Wein Urology (9780323546423)
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