What are the treatments for cortisol imbalance?

Treatment of Cortisol Imbalance

The treatment of cortisol imbalance depends on whether the patient has excess cortisol (Cushing syndrome) or cortisol deficiency (adrenal insufficiency), with specific therapies targeting the underlying cause and severity of symptoms.

Diagnostic Approach

• Morning cortisol levels (measured between 7:30-8:00 AM when cortisol is naturally highest) along with ACTH levels are essential for determining the type of cortisol imbalance 1
• Primary and secondary adrenal insufficiency can be distinguished by the relationship between ACTH and cortisol - low cortisol with high ACTH indicates primary adrenal insufficiency, while low cortisol with low ACTH suggests secondary adrenal insufficiency 2, 1
• For suspected Cushing syndrome, 24-hour urine cortisol measurement is recommended to confirm the diagnosis 2

Treatment of Cortisol Deficiency (Adrenal Insufficiency)

Primary Adrenal Insufficiency (Addison's Disease)

• Hormone replacement therapy is the cornerstone of treatment, with hydrocortisone 15-25 mg daily in divided doses (first dose immediately after waking, last dose not less than 6 hours before bedtime) 2
• Fludrocortisone (50-200 μg daily) should be added to replace mineralocorticoid function 2
• Patients should be advised to take salt and salty foods freely and avoid licorice and grapefruit juice 2
• All patients must wear medical alert identification, carry a steroid card, and receive education on managing illness and emergency situations 2

Secondary Adrenal Insufficiency

• Hydrocortisone replacement (same dosing as primary insufficiency) without fludrocortisone, as mineralocorticoid function is preserved 2
• Evaluate and treat any underlying pituitary or hypothalamic disorder 2

Adrenal Crisis Management

• Immediate administration of IV or IM hydrocortisone 100 mg followed by 100 mg every 6-8 hours until recovered 2
• Isotonic saline (0.9%) at an initial rate of 1 L/hour until hemodynamic improvement 2
• Identify and treat the underlying precipitant (often infection) 2

Treatment of Cortisol Excess (Cushing Syndrome)

Treatment Based on Etiology

Adrenal Adenoma

• Laparoscopic adrenalectomy is the treatment of choice 2
• Postoperative corticosteroid supplementation is required until recovery of the hypothalamic-pituitary-adrenal axis 2

Pituitary Tumor (Cushing Disease)

• Transsphenoidal surgery to remove the ACTH-producing pituitary tumor 2
• If surgery fails or is contraindicated, medical therapy or bilateral adrenalectomy may be considered 2

Ectopic ACTH Production

• Surgical removal of the ACTH-producing tumor when possible 2
• If the primary tumor is unresectable, bilateral laparoscopic adrenalectomy or medical management is recommended 2

Medical Management of Hypercortisolism

• Adrenostatic agents including ketoconazole (400-1200 mg/day) are most commonly used due to relatively tolerable toxicity profile 2
• Mitotane can be considered for more severe cases or adrenal carcinoma 2
• Octreotide may be considered for ectopic Cushing syndrome if the tumor is Octreoscan-positive 2

Special Considerations

Steroid Administration Timing

• The maximal activity of the adrenal cortex is between 2 AM and 8 AM, with minimal activity between 4 PM and midnight 3
• Exogenous corticosteroids suppress adrenocortical activity least when given at the time of maximal activity (morning) 3
• For long-term therapy, alternate day therapy may minimize side effects by allowing partial recovery of the HPA axis on off days 3

Monitoring and Follow-up

• Patients with adrenal insufficiency should be reviewed at least annually with assessment of weight, blood pressure, and serum electrolytes 2
• Monitor for development of new autoimmune disorders, particularly hypothyroidism 2
• Bone mineral density should be assessed every 3-5 years to monitor for osteoporosis 2

Complications Management

• Cardiovascular risk factors should be assessed and treated, as patients with Cushing syndrome have increased risk of myocardial infarction and stroke 2
• Bisphosphonates, vitamin D, and calcium supplementation should be considered for patients with bone mineral density loss 2
• Growth hormone deficiency may persist after treatment of Cushing syndrome and may require specific replacement therapy 2

Pitfalls and Caveats

• Never abruptly withdraw steroid therapy in patients with adrenal insufficiency or those on long-term corticosteroid treatment 3
• Stress dosing (2-3 times maintenance dose) is required during illness, surgery, or other physical stressors 2
• Patients on exogenous steroids for other conditions may develop secondary adrenal insufficiency, requiring careful tapering when discontinuing 2
• Morning cortisol testing in patients on corticosteroids is not diagnostic, as therapeutic steroids interfere with cortisol assays 1