How is Adrenocorticotropic hormone (ACTH) deficiency or excess treated?

From the Guidelines

Treatment of ACTH deficiency involves hormone replacement therapy with glucocorticoids, typically hydrocortisone at 15-25 mg daily divided into 2-3 doses, while ACTH excess is treated by targeting the underlying cause, with transsphenoidal surgery being the first-line treatment for pituitary adenomas, as recommended by the most recent guidelines 1.

Key Considerations for ACTH Deficiency

• Hormone replacement therapy with glucocorticoids, such as hydrocortisone, is the mainstay of treatment for ACTH deficiency, with the goal of mimicking the body's natural cortisol rhythm 1.
• Patients may require dose adjustments during illness or stress, often doubling or tripling their usual dose temporarily, and should be educated on stress dosing and emergency injection kits 1.
• Long-term management involves regular monitoring and patient education to minimize the risk of adrenal crisis.

Key Considerations for ACTH Excess (Cushing's Disease)

• Treatment targets the underlying cause, with transsphenoidal surgery being the first-line treatment for pituitary adenomas, as it directly addresses the source of excess ACTH production 1.
• If surgery fails or is contraindicated, medication options include steroidogenesis inhibitors like ketoconazole, metyrapone, or mitotane, or pituitary-directed drugs like pasireotide, which can help control cortisol levels 1.
• Radiation therapy may be used for persistent disease, and bilateral adrenalectomy is considered a last resort, requiring lifelong glucocorticoid and mineralocorticoid replacement 1.

Importance of Recent Guidelines

• The most recent guidelines, such as those from 2021 1, provide updated recommendations for the management of ACTH deficiency and excess, emphasizing the importance of individualized treatment plans and regular monitoring to optimize patient outcomes.
• These guidelines also highlight the need for patient education on stress dosing, emergency injection kits, and the importance of medical alert bracelets or necklaces for adrenal insufficiency, to ensure prompt recognition and treatment of adrenal crisis 1.

From the FDA Drug Label

Since mineralocorticoid secretion may be impaired, salt and/or a mineralocorticoid should be administered concurrently. Metopirone may induce acute adrenal insufficiency in patients with reduced adrenal secretory capacity, as well as in patients with global pituitary insufficiency. The test should be performed in the hospital with close monitoring in case of suspected adrenal insufficiency Ability of adrenals to respond to exogenous ACTH should be demonstrated before Metopirone is employed as a test.

Treatment of Adrenocorticotropic Hormone (ACTH) Deficiency or Excess:

• Deficiency: Treatment involves administering corticosteroids and/or mineralocorticoids to replace the deficient hormones.
• Excess: Treatment is not directly stated in the provided drug labels, but it can be inferred that managing excess ACTH may involve addressing the underlying cause, such as a pituitary tumor, and administering medications to reduce ACTH production or counteract its effects.
• Key Considerations:
  • Patients with suspected adrenal insufficiency should be hospitalized overnight as a precautionary measure.
  • Ability of adrenals to respond to exogenous ACTH should be demonstrated before Metopirone is employed as a test.
  • Appropriate doses of corticosteroids should be given to correct adrenal insufficiency triggered by Metopirone. 2 3 3

From the Research

Treatment of Adrenocorticotropic Hormone (ACTH) Deficiency or Excess

• ACTH deficiency is treated with glucocorticoid replacement therapy, with doses such as 20 mg (0.30 mg/kg) hydrocortisone or 25 mg (0.35 mg/kg) cortisone acetate per day 4.
• Mineralocorticoids are generally not necessary as their production is maintained 4.
• For mild, near-to-asymptomatic disease, glucocorticoid replacement therapy may not be required except during stressful events 4.

Treatment of Cushing's Syndrome

• Medical treatment can temporarily suppress excessive cortisol production and ameliorate its clinical manifestations while more definitive therapy becomes effective 5.
• Drugs used to suppress cortisol secretion include ketoconazole, fluconazole, aminoglutethimide, metyrapone, mitotane, and etomidate 5, 6.
• Combination therapy with drugs that target the corticotropic adenoma, such as pasireotide and/or cabergoline, and low-dose ketoconazole may be a rational approach to achieve biochemical control 6.
• Ketoconazole is effective for long-term control of hypercortisolism of either pituitary or adrenal origin 7.
• Aminoglutethimide and metyrapone can be used in combination to control cortisol overproduction, with lower doses reducing side effects 8.

Specific Treatments

• Ketoconazole can be used to rapidly reverse cortisol excess in patients with acute complications of hypercortisolism 6.
• Etomidate can be used to rapidly reverse cortisol excess in patients with acute complications of severe hypercortisolism 6.
• Mifepristone is being tested in clinical trials for the treatment of Cushing's disease and ectopic ACTH syndrome 5.