What are the treatment options for cortisol imbalance?

Treatment Options for Cortisol Imbalance

The treatment of cortisol imbalance must be tailored to the specific underlying cause, with surgical intervention recommended for tumors causing Cushing syndrome and hormone replacement therapy with hydrocortisone 10-30 mg daily in divided doses for adrenal insufficiency.

Diagnosis of Cortisol Disorders

Hypercortisolism (Cushing Syndrome)

• Diagnosis confirmed by elevated 24-hour urinary cortisol levels 1
• Determine source through ACTH levels:
  • Elevated ACTH: Suggests pituitary tumor or ectopic source (lung, thyroid, pancreas, bowel)
  • Low/normal ACTH: Suggests adrenal source (adenoma or carcinoma)

Adrenal Insufficiency

• Diagnosis may involve:
  • Random plasma cortisol <10 μg/dl
  • Delta cortisol (change in baseline cortisol at 60 min of <9 μg/dl) after cosyntropin (250 μg) administration 1
• Primary vs. Secondary differentiation:
  • Primary: High ACTH, low cortisol, electrolyte abnormalities (↓Na, ↑K), hyperpigmentation
  • Secondary: Low ACTH, low cortisol, generally normal electrolytes, no hyperpigmentation 2

Treatment Approaches for Hypercortisolism

Surgical Management

• First-line treatment for tumor-related Cushing syndrome:
  • Pituitary tumors: Transsphenoidal surgery
  • Adrenal adenomas: Laparoscopic adrenalectomy
  • Ectopic tumors: Surgical removal when possible 1
  • Bilateral adrenalectomy for unresectable ectopic ACTH-producing tumors 1

Medical Management

• For mild disease or when surgery is contraindicated:

  • Adrenal steroidogenesis inhibitors are typically first-line due to reliable effectiveness 1:
    • Ketoconazole (400-1200 mg/day) - most commonly used due to availability and tolerable toxicity 1
    • Metyrapone - works within hours, inhibits 11-beta-hydroxylation in adrenal cortex 3
    • Osilodrostat - rapid normalization of cortisol 1

• For moderate-severe disease:

  • Combination of steroidogenesis inhibitors may be necessary 1
  • Mifepristone - blocks cortisol action at receptor level; useful for glucose control and hypertension 1
  • Pasireotide or cabergoline - may be preferred when tumor shrinkage is desired 1

• For severe, acute hypercortisolism:

  • Etomidate IV when oral medications cannot be taken 1
  • Consider bilateral adrenalectomy if medical therapy fails in severe cases 1

Monitoring During Treatment

• Serial measurements of urinary free cortisol and late-night salivary cortisol 1
• Monitor for side effects:
  • Ketoconazole: Hepatotoxicity, drug interactions
  • Metyrapone: Hypertension, hirsutism, acne
  • Mifepristone: Hypertension, hypokalemia, endometrial thickening 1

Treatment of Adrenal Insufficiency

Hormone Replacement Therapy

• Standard replacement:
  • Hydrocortisone 10-30 mg daily in divided doses (or equivalent prednisone 5-10 mg daily) 2
  • Morning doses should be higher than evening doses to mimic natural cortisol rhythm

Stress Dosing

• For minor illness/stress:

  • Double or triple maintenance dose 2
  • Taper back to maintenance over 5-10 days once stress resolves

• For severe stress/adrenal crisis:

  • Hydrocortisone 100 mg IV immediately, then 50-100 mg IV every 6 hours or 200 mg/day continuous infusion 2
  • Fluid resuscitation with normal saline (10-20 ml/kg; maximum 1,000 ml) 2

Critical Illness-Related Corticosteroid Insufficiency (CIRCI)

• For septic shock unresponsive to fluids and vasopressors:
  • IV hydrocortisone <400 mg/day for ≥3 days 1
• For early moderate to severe ARDS:
  • IV methylprednisolone 1 mg/kg/day (PaO2/FiO2 < 200 and within 14 days of onset) 1

Patient Education and Monitoring

• All patients with adrenal insufficiency require:
  • Education on stress dosing during illness
  • Emergency injectable steroids
  • Medical alert bracelet/card 2
• Monitor for side effects of long-term therapy:
  • Osteoporosis, hypertension, hyperglycemia, weight gain, lipodystrophy 2, 4

Special Considerations

• Reduced cortisol metabolism occurs during critical illness, which may lead to higher cortisol levels despite lower production 5
• Medications that induce CYP3A4 may increase hydrocortisone metabolism, requiring higher doses 2
• Cortisol levels may serve as a biomarker for mental disorder severity 6
• Pregnancy considerations: Metyrapone crosses placenta and may decrease fetal cortisol production 3