Cushing's Syndrome: A Quick Review

Definition: Clinical syndrome characterized by signs and symptoms of raised blood cortisol levels.

Etiologic classification:

• Pituitary Cushing's is Cushing's disease.

• ACTH dependence simply means if raised ACTH is the cause of raised cortisol.

• Feedback loop, more correctly negative feedback loop, implies if cortisol level influences ACTH level inversely. Ectopic Cushing's is caused my malignant cells that continuously proliferate and hence, continuously make ACTH, regardless of cortisol levels.

• Therapeutic administration of ACTH hormone for long periods can cause ACTH-dependent Cushing's. However, they are exceedingly rare (and hence, omitted from the whiteboard for simplicity).

(MCC= Most Common Cause ; B/L= Bilateral ; U/L=Unilateral)

Clinical Features:

CUSHINGOID

Central obesity, Cervical fat pads (with moon face and fish mouth = Cushingoid habitus), Collagen fiber weakness, Comedones (acne)
Ulcers (peptic)
Striae, Skin thinning & bruising
Hypertension, Hyperglycemia, Hirsutism
Immunosuppression, Infections
Necrosis (Avascular) of femoral head, Neuropsychiatric symptoms
Glucose intolerance, Growth retardation
Osteoporosis, Obesity
Impotence and menstrual abnormalities
Diabetes


Diagnosis:

High dose DXM or CRH don't bother ACTH or cortisol levels in Ectopic Cushing's as they're out of the feedback loop.

Other tests include:

• 24 hour urinalysis

• Midnight salivary cortisol

• 9 am cortisol

• Overnight low-dose DXM suppression test

• B/L inferior petrosal sinus sampling

• Electrolytes and routine CBC

(DXM=Dexamethasone)

Management:

• Iatrogenic: Withdraw steroids slowly.

• Pituitary: Trans-sphenoidal resection OR radical hypophysectomy, less commonly

• Adrenal: Surgical resection with post-op prednisolone OR medically treat with Metyrapone or Aminoglutethimide.

• Ectopic: Chemotherapy and Radiotherapy for small cell lung cancer OR surgical resection for carcinoids.

Let me know if anything needs clarification.

Happy studying!

-- Ashish Singh.