What is the treatment for abnormal cortisol levels (Hypercortisolism or Hypocortisolism)?

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Last updated: April 22, 2025View editorial policy

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From the Guidelines

For high cortisol levels, osilodrostat, metyrapone, or ketoconazole should be considered as the first-line treatment to rapidly normalize cortisol levels, as recommended by the most recent guideline update 1. When managing high cortisol levels, it's essential to consider the underlying cause and severity of the condition.

  • For patients with severe disease, the goal is to rapidly normalize cortisol levels, and medications like osilodrostat and metyrapone can achieve this within hours, while ketoconazole may take a few days 1.
  • Etomidate can also be used in hospitalized patients who cannot take oral medications, and combinations of steroidogenesis inhibitors may be necessary for patients with severe hypercortisolism 1.
  • In cases where hypercortisolism is very severe and unresponsive to medical therapy, bilateral adrenalectomy (BLA) should be considered to avoid worsening outcomes 1.
  • For patients with adrenal insufficiency, hydrocortisone replacement therapy is typically recommended, with a daily dose of 15-25 mg in divided doses, and fludrocortisone may also be necessary to manage mineralocorticoid deficiency 1.
  • It's crucial to monitor cortisol levels and adjust therapy as needed to achieve optimal outcomes and minimize the risk of adverse events.
  • Lifestyle modifications, such as regular exercise, adequate sleep, and a balanced diet, can also help normalize the hypothalamic-pituitary-adrenal axis and reduce cortisol production.
  • In addition to medical therapy, surgical removal of adrenal tumors or pituitary adenomas may be necessary to treat the underlying cause of excess cortisol production.
  • The choice of treatment should be individualized based on the patient's specific condition, medical history, and response to therapy, and should always prioritize minimizing morbidity, mortality, and improving quality of life.

From the FDA Drug Label

The initial dosage of hydrocortisone tablets may vary from 20 mg to 240 mg of hydrocortisone per day depending on the specific disease entity being treated.

  • Hydrocortisone is used to treat various conditions, and the dosage varies based on the disease being treated.
  • For cortisol levels, the dosage of hydrocortisone can range from 20 mg to 240 mg per day, depending on the individual's response and the specific condition being treated 2.
  • In cases of adrenal insufficiency, metyrapone is used as a diagnostic test, and hydrocortisone may be administered to treat the condition 3.

From the Research

Cortisol Level Management

To manage cortisol levels, several medications can be used, including:

  • Glucocorticoid replacement therapy, such as oral hydrocortisone, for patients with adrenal insufficiency 4
  • Adrenal steroidogenesis inhibitors, such as metyrapone, ketoconazole, and osilodrostat, to reduce cortisol production in patients with Cushing's syndrome 5, 6, 7, 8
  • Glucocorticoid receptor blockers, such as mifepristone, to block the effects of excess cortisol 5

Treatment Approaches

Treatment approaches for cortisol level management vary depending on the underlying condition:

  • For adrenal insufficiency, glucocorticoid replacement therapy is the standard treatment 4
  • For Cushing's syndrome, medical therapy may be used to control hypercortisolism, especially in cases where surgery is not feasible or has failed 5, 6, 7, 8
  • In severe cases of Cushing's syndrome, emergency treatment with oral metyrapone and/or ketoconazole or intravenous etomidate may be necessary 7

Medication Options

Several medications are available to manage cortisol levels, including:

  • Metyrapone: an adrenal steroidogenesis inhibitor used to reduce cortisol production 5, 6, 7, 8
  • Ketoconazole: an adrenal steroidogenesis inhibitor used to reduce cortisol production 5, 6, 7, 8
  • Osilodrostat: an adrenal steroidogenesis inhibitor approved for the treatment of Cushing's disease and Cushing's syndrome 6, 8
  • Etomidate: a medication used to rapidly lower cortisol levels in emergency situations 7, 8

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

What is the role of medical therapy in adrenal-dependent Cushing's syndrome?

Best practice & research. Clinical endocrinology & metabolism, 2020

Research

Updates in adrenal steroidogenesis inhibitors for Cushing's syndrome - A practical guide.

Best practice & research. Clinical endocrinology & metabolism, 2021

Research

Adrenally Directed Medical Therapies for Cushing Syndrome.

The Journal of clinical endocrinology and metabolism, 2021

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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