Adrenal Disorders – Cushing’s Syndrome

Cushing’s Syndrome

• 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

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

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)