How are abnormal cortisol levels treated?

Treatment of Abnormal Cortisol Levels

The treatment of abnormal cortisol levels depends on the underlying cause, with surgical intervention being first-line for tumor-related hypercortisolism and hormone replacement therapy being essential for cortisol deficiency. 1

Hypercortisolism (Cushing Syndrome)

ACTH-Dependent Cushing Syndrome

• For pituitary tumors (Cushing's disease), surgical resection via transsphenoidal surgery is the first-line treatment 1
• For ectopic ACTH-producing tumors, surgical removal of the primary tumor is recommended when possible 1
• If the primary tumor is unresectable, options include:
  • Bilateral laparoscopic adrenalectomy 1
  • Medical management with adrenostatic agents 1

ACTH-Independent Cushing Syndrome

• For benign adrenal adenomas, laparoscopic adrenalectomy is recommended 1
• For malignant adrenal tumors, open adrenalectomy with removal of adjacent lymph nodes is recommended 1
• For bilateral adrenal hyperplasia:
  • If cortisol production is asymmetric, unilateral adrenalectomy of the most active side 1
  • If cortisol production is symmetric, medical management is indicated 1

Medical Management of Hypercortisolism

• Adrenostatic agents are the mainstay of medical therapy:
  • Ketoconazole (400-1200 mg/day) is most commonly used due to relatively tolerable toxicity profile 1
  • Mitotane is another option, particularly for adrenal carcinoma 1
  • Octreotide can be considered for ectopic Cushing syndrome if the tumor is Octreoscan-positive 1

Post-Surgical Management

• Postoperative corticosteroid supplementation is required until recovery of the hypothalamus-pituitary-adrenal (HPA) axis after adrenalectomy 1

Adrenal Insufficiency (Low Cortisol)

Primary Adrenal Insufficiency

• Glucocorticoid replacement: Hydrocortisone 15-25 mg daily in divided doses (typically 2/3 in morning, 1/3 in afternoon) 1, 2
• Mineralocorticoid replacement: Fludrocortisone (0.05-0.1 mg/day), adjusted based on volume status, sodium level, and renin response 1, 2

Secondary Adrenal Insufficiency

• Glucocorticoid replacement: Hydrocortisone 15-20 mg daily in divided doses 1, 2
• Mineralocorticoid replacement is usually not necessary in secondary adrenal insufficiency 1

Glucocorticoid-Induced Adrenal Insufficiency

• Gradual tapering of glucocorticoids to minimize secondary adrenocortical insufficiency 3
• Temporary hormone therapy during periods of stress 3

Special Considerations

Stress Dosing

• All patients with adrenal insufficiency need education on stress dosing for illness or physical stress 1, 2
• During acute illness or surgery, increase glucocorticoid dose (typically 2-3 times maintenance dose) 1
• Emergency injectable glucocorticoids (hydrocortisone 100 mg) should be prescribed to prevent adrenal crisis 2

Monitoring

• Regular follow-up of clinical symptoms and electrolytes 1
• For functioning tumors, follow-up imaging and biomarkers every 3-6 months 1

Patient Education

• Medical alert bracelet or necklace for adrenal insufficiency 1
• Education on steroid stress dosing and emergency injections 1
• Patients on immunosuppressant doses of corticosteroids should avoid exposure to chicken pox or measles 3

Common Pitfalls and Caveats

• Failure to recognize adrenal crisis, which can be life-threatening and requires immediate treatment with IV hydrocortisone and fluid resuscitation 1, 2
• Inadequate stress dosing during illness or surgery, which can precipitate adrenal crisis 1
• Overtreatment with glucocorticoids can lead to iatrogenic Cushing's syndrome (bruising, thin skin, edema, weight gain, hypertension, hyperglycemia) 1
• Failure to provide mineralocorticoid replacement in primary adrenal insufficiency 1, 2
• Abrupt discontinuation of glucocorticoids can lead to adrenal crisis; always taper gradually 3