PBL: Iatrogenic Cushing’s Syndrome

Keywords:

• 40 y.o woman
• Has diabetes & hypertension for 6 months
• On oral hypoglycemia & antihypertensive medication
• Height: 165cm
• Weight: 85kg
• BMI: overweight/obese
• Moon shaped facies
• Truncal obesity
• Abdominal striae
• Diminished motor strength of proximal limb muscles
• Also on prolonged oral corticosteroid treatment for rheumatoid arthritis for 5 years
• Wanted to stop the cortocosteroid immediately, but disallowed by doctor.
• Lab investigation
  • Increased total serum cortisol
  • Increased free cortisol
  • Decreased serum ACTH

Hypothesis:

Iatrogenic Cushing’s syndrome

Additional Learning issues:

Pathophysiology of some Cushing’s disease clinical features

• Polyuria, polydipsia
• cortisol binds & inhibits ADh release
• Diabetes
• increased gluconeogenesis (opposite insulin action)
• Bruisability
• loss of subcutaneous collagen matrix, skin peels off easilty (liddle’s sign) –> susceptible to fungal infection
• Hirsutism
• due to ACTH increase
• cortiso binds to testosterone receptors –> increase androgen
• supress immune system
• decrease amount of circulating leukocytes & migration of tissue leukocytes
• lysis of lymphocyes
• Skin pigmentation
• Increase in ACTH
• Increased BP
• cortisol also causes increase in aldosterone, therefore there will be water retention.
• binds to receptors of the mineralocorticoid due to it’s similar chemical structure

Lab investigations of Cushing’s

• Serum Na+ increase
• cortisol binds to aldosterone receptor
• Na+ reabsorbed
• Serum K+ increase
• due to increased GFR & protein catabolism
• ACTH
• low in Cushing’s syndrome
• high in Cushing’s disease (pituitary defect)

Prolonged corticosteroid therapy (eg Rheumatoid arthritis, asthma)

Prolonged corticosteroid therapy will elevate cortisol level and cause Cushing’s syndrome. However, adbrupt discontinuation of the drug is also highly not recommendable because there will be a sudden sharp drop in cortisol levels in the body.

The treatment dosage must be slowly tapered off to allow the body to resume normal cortisol production. When this is done, much care must also be given to the underlying disease (Rheumatoid arthritis in this case), so that the disease wont worsen when the dosage is being reduced.

What are the drugs given for Cushing’s disease?

Ketoconazol

Mitotane

Metyrapone