Cushing’s Syndrome

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  • Chronic hypercortisolism due to excessive production of cortisol
  • 20-40 years of age
  • 3 times higher frequency in women
  1. Pituitary Cushing’s syndrome
  2. Adrenal Cushing’s syndrome
  3. Ectopic Cushing’s syndrome
  4. Iatrogenic Cushing’s syndrome

Pituitary Cushing’s syndrome (60-70%)

  • Cushing’s disease
  • Excessive ACTH, due to
    • Pituitary lesion: corticotroph adenoma, multiple corticotroph microadenoma
    • hypothalamic origin: excessive CRH secretion –> pituitary ACTH
  • Excessive ACTH will act on adrenal cortex and cause: bilateral cortical hyperplasia
  • DX: Dexamethasone

Adrenal Cushing’s syndrome (20-25%)

  • Low ACTH levels, High Cortisol levels
  • Disease in 1 or both adrenal glands
    • Adrenal lesions: Adrenal cortical adenoma, carcinoma, cortical hyperplasia
  • No response to high dose of glucocorticoids (?)

Ectopic Cushing’s syndrome (10-15%)

  • High ACTH levels
  • Ectopic ACTH secretions from non-endocrine tumours
    • Oat cell carcinoma (lung)
    • Lung cancer
    • Malignant thymoma
    • Pancreatic tumour
  • ACTH act on adrenal cortex releasing cortisol
  • Dexamethasone does not suppress cortisol secretion (acts on pituitary only)

Iatrogenic Cushing’s syndrome

  • Prolonged therapeutic administration of high doses of glucocorticoids/ACTH
  • Used in organ transplant recipients & autoimmune diseases.

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Clinical features

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Refer Adrenal Steroid Hormones to understand action of glucocorticoid on body causing the clinical features.

  • Truncal obesity, thin extremities
  • Buffalo hump (fat over shoulders)
  • Moon face (rounded oedematous face)
  • Muscle wasting
  • Muscle weakness – hypokalemia
  • Growth retardation in children & adolescents
  • Atrophy of subcutaneous tissue – purple striae of abdominal wall & ecchymoses. Loss of subcutaneous collagen matrix, increased skin fragility, skin peels off readily (Liddle’s sign) & subjected to fungal infection.
  • Excess androgen – hirsutims, increased sebum, acne, scalp hair regression, irregular menstrual cycle
  • Male: impotence, decreased libido
  • Enhanced bone resorption – osteoporosis
  • Polycythemia, neutrophilia, lumphopenia, eosinopenia
  • hypertension, oedema & congestive heart failure
  • Psychiatric: depression, psychosis, irritability
  • Depressed immunity

image Abdominal striae

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ACTH dependent (Cushing’s disease) (60%)

  • pituitary origin / ectopic ACTH
  • Mostly pituitary ACTH
  • 15% ectopic ACTH, 50% Small cell carcionoma of the lungs
  • Prominent features: hypokalemia, hypoglycemia & muscle wasting.

ACTH independent (25%)

  • Adrenal origin
  • Adenomas – slow growing , pure hypercortisolism (only cortisol)
  • Carcinomas – larger, more cortisol precursors & adrenal androgens
  • Micronodular hyperplasia – rare, common in young adults, autosomal dominant, asso. with pituitary & testicular lesions.

Diagnosis of Cushing’s syndrome

Obtain 2 late-night salivary cortisol tests (at it’s lowest level due to it’s diurnal rhythm)

Results:

  • Both normal: Cushing’s unlikely
  • Discordant/equivocal results – repeat or confirm with 1mg overnight low-dose dexamethasone suppression test/ UFC
  • Both abnormal: Cushing’s likely – confirm with 1mg overnight low-dose dexamethasone suppression test/ UFC

Low-dose dexamethasone test explained in different post. (link)

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