What are the treatments for cortisol imbalance?

Treatment of Cortisol Imbalance

Treatment depends entirely on whether cortisol is too high (hypercortisolism/Cushing syndrome) or too low (adrenal insufficiency), with surgical removal being the definitive treatment for most cortisol-producing tumors and lifelong hormone replacement being mandatory for cortisol deficiency.

Hypercortisolism (Cushing Syndrome)

Surgical Management

Laparoscopic adrenalectomy is the definitive treatment for benign adrenal adenomas causing Cushing syndrome 1. The surgical approach depends on the underlying cause:

• ACTH-independent (adrenal source): Remove the affected adrenal gland via laparoscopic adrenalectomy when feasible 1
• Malignant tumors: Open adrenalectomy is required for tumors >5 cm, those with irregular margins, local invasion, or heterogeneous appearance to prevent rupture 1
• Ectopic ACTH-producing tumors: Remove the primary tumor if resectable; if unresectable, perform bilateral laparoscopic adrenalectomy 1
• Bilateral multinodular hyperplasia: Perform adrenal vein sampling to assess cortisol production asymmetry; if asymmetric, remove the most active side; if symmetric, use medical management 1

Critical postoperative consideration: All patients require corticosteroid supplementation after adrenalectomy until the hypothalamus-pituitary-adrenal (HPA) axis recovers 1.

Medical Management of Hypercortisolism

When surgery is not feasible or as bridge therapy, use adrenostatic agents 1:

• Ketoconazole 400-1200 mg/day: Most commonly used due to easy availability and relatively tolerable toxicity profile 1
• Mitotane: Alternative adrenostatic agent 1
• Octreotide: Consider for ectopic Cushing syndrome if tumor is Octreoscan-positive, though less effective for controlling ectopic ACTH secretion 1

Symptomatic Management

Treat complications of hypercortisolism including hypertension, hyperglycemia, hypokalemia, and muscle atrophy 1.

Long-term Complications Requiring Monitoring

Even after remission, patients face persistent risks 1:

• Cardiovascular disease: Screen for hypertension, heart failure, and atherosclerotic disease as standardized mortality ratio remains elevated (4.1-16 in active disease) 1
• Bone disease: Vertebral fractures occur in 30-50% of patients; consider bisphosphonates, vitamin D, and calcium supplementation even after remission 1
• Growth hormone deficiency: Prevalence ranges from 50-60% within 2 years post-surgery to 8-13% after 2 years; consider GH replacement for persistent deficiency affecting bone, muscle, and quality of life 1

Hypocortisolism (Adrenal Insufficiency)

Maintenance Replacement Therapy

Most patients with primary adrenal insufficiency should take hydrocortisone 15-25 mg daily (or cortisone acetate 18.75-31.25 mg) in split doses, with the first dose immediately after waking and the last dose at least 6 hours before bedtime 1. In children, use 6-10 mg/m² of body surface area 1.

Dosing schedule to mimic diurnal rhythm 1:

• Give 2/3 of total dose in the morning upon waking
• Give 1/3 in early afternoon
• Avoid dosing within 6 hours of bedtime 1

Mineralocorticoid replacement for primary adrenal insufficiency: Most patients require fludrocortisone 50-200 µg as a single daily dose 1. Children and younger adults may require higher doses 1. Adjust based on volume status, sodium level, and renin response (target upper half of reference range) 1.

Alternative glucocorticoid: Prednisone 5-10 mg daily can be used, with 20 mg hydrocortisone equivalent to 5 mg prednisone 1, 2. However, hydrocortisone is preferred as it allows recreation of the diurnal cortisol rhythm 1.

Stress Dosing

For moderate illness (Grade 2): Double or triple the maintenance dose (hydrocortisone 30-50 mg total or prednisone 20 mg daily) for 2 days, then return to maintenance 1.

For severe illness or surgery 1:

• Minor procedures: 100 mg hydrocortisone IM just before procedure
• Moderate surgery: 100 mg hydrocortisone IM before procedure, then double oral dose for 24 hours
• Major surgery: 100 mg hydrocortisone IV before procedure, continue 100 mg every 6-8 hours

Adrenal Crisis Management

Adrenal crisis is a medical emergency requiring immediate treatment without waiting for diagnostic confirmation 1:

1. Draw blood for cortisol, ACTH, electrolytes, glucose before treatment but do not delay therapy 1
2. Hydrocortisone 100 mg IV bolus immediately, followed by 100 mg every 6-8 hours 1
3. Isotonic saline (0.9%) at 1 L/hour initially until hemodynamic improvement, then continue at slower rate for 24-48 hours 1
4. Taper to oral maintenance over 1-3 days once stable 1
5. Restart fludrocortisone when hydrocortisone dose falls below 50 mg/day 1

Essential Patient Education

All patients with adrenal insufficiency must 1:

• Wear medical alert identification jewelry
• Carry a steroid emergency card
• Have supplies for self-injection of parenteral hydrocortisone
• Receive education on stress dosing for sick days
• Know when to seek emergency medical attention
• Understand how to adjust doses during minor to moderate concurrent illnesses

Monitoring

Annual follow-up should include 1:

• Assessment of health, well-being, and weight
• Blood pressure measurement
• Serum electrolytes
• Screening for new autoimmune disorders (particularly hypothyroidism)
• Bone mineral density every 3-5 years to assess for complications of glucocorticoid therapy 1

Common Pitfalls

• Never abruptly discontinue corticosteroid therapy—always taper gradually 2
• Do not rely solely on morning cortisol levels—normal basal cortisol with elevated ACTH can still indicate early primary adrenal insufficiency 3
• Avoid long-acting steroids like dexamethasone for replacement therapy—they produce prolonged adrenal suppression and are not suitable for alternate-day therapy 2
• Remember that patients on chronic glucocorticoids for other conditions will have suppressed morning cortisol—this represents iatrogenic secondary adrenal insufficiency 1