How are abnormal cortisol levels treated?

From the Guidelines

Treatment for abnormal cortisol levels should prioritize addressing the underlying cause, with medications like osilodrostat and metyrapone being recommended for rapid normalization of cortisol in severe cases, as per the most recent guideline update 1. When it comes to treating abnormal cortisol levels, the approach depends on whether the levels are too high (Cushing's syndrome) or too low (adrenal insufficiency). For high cortisol, treatment focuses on addressing the underlying cause. If caused by long-term steroid medication use, doctors gradually reduce the dose. For pituitary tumors, surgical removal is often recommended, while adrenal tumors may require adrenalectomy.

• Medications like ketoconazole (400-1200 mg daily), mitotane (2-6 g daily), or metyrapone (250 mg every 6 hours) can block cortisol production when surgery isn't possible, with osilodrostat and metyrapone having the fastest action and being orally available 1.
• In cases of severe hypercortisolism, combinations of steroidogenesis inhibitors may be necessary, and if hypercortisolism is very severe and not responsive to optimized medical therapy, including combinations, bilateral adrenalectomy (BLA) should be considered to avoid worsening outcomes 1. For low cortisol, replacement therapy with hydrocortisone (15-25 mg daily in divided doses) or prednisone (5-7.5 mg daily) is standard.
• Patients typically take a higher dose in the morning and lower dose in the afternoon to mimic natural cortisol rhythm.
• Fludrocortisone (0.05-0.2 mg daily) may be added if aldosterone is also deficient. Treatment is lifelong for permanent conditions, and patients need to increase their medication during illness or stress.
• Regular monitoring of cortisol levels, electrolytes, and symptoms guides dosage adjustments, and proper treatment is essential as untreated cortisol abnormalities can lead to serious complications including cardiovascular problems, bone loss, infections, or adrenal crisis. The selection of medical therapy should consider factors such as the need for rapid normalization of cortisol, the presence of residual tumor, and the potential for tumor shrinkage, as well as drug intolerance, side effects, and concomitant comorbidities 1.

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. If after long-term therapy the drug is to be stopped, it is recommended that it be withdrawn gradually, rather than abruptly Drug-induced secondary adrenocortical insufficiency may be minimized by gradual reduction of dosage.

Abnormal cortisol levels are treated with hydrocortisone. The dosage may vary from 20 mg to 240 mg per day, depending on the specific disease entity being treated 2. It is essential to individualize the dosage based on the disease and the patient's response. If treatment is to be stopped after a long period, it is recommended to withdraw the drug gradually to minimize the risk of secondary adrenocortical insufficiency 2. Key considerations for treatment include:

• Disease entity: The dosage of hydrocortisone depends on the specific disease being treated.
• Patient response: The dosage should be adjusted based on the patient's response to treatment.
• Gradual withdrawal: Hydrocortisone should be withdrawn gradually to minimize the risk of secondary adrenocortical insufficiency.

From the Research

Treatment Options for Abnormal Cortisol Levels

Abnormal cortisol levels can be treated using various medical approaches. The following are some of the treatment options:

• Metyrapone therapy: This is a rapid-onset, long-term effective, and safe medical treatment for Cushing's syndrome patients, achieving urinary-free cortisol (UFC) normalization in 70% of patients 3.
• Ketoconazole treatment: This is an effective drug with acceptable side effects for treating Cushing's disease, with 49.3% of patients having normal urinary free cortisol (UFC) levels at the last follow-up 4.
• Combination therapy: Mitotane, metyrapone, and ketoconazole combination therapy is an effective alternative to rescue adrenalectomy for severe ACTH-dependent Cushing's syndrome, with all 11 patients experiencing a marked clinical improvement 5.

Efficacy of Treatment Options

The efficacy of these treatment options can be measured by their ability to normalize cortisol levels and improve clinical symptoms. For example:

• Metyrapone therapy has been shown to decrease UFC and late-night salivary cortisol (LNSC) levels quickly after the first month of treatment, with sustained UFC normalization up to 12 and 24 months 3.
• Ketoconazole treatment has been shown to have a significant decrease in UFC levels, with 25.6% of patients having at least a 50% decrease in UFC levels 4.
• Combination therapy with mitotane, metyrapone, and ketoconazole has been shown to rapidly decrease UFC excretion, with all 11 patients experiencing a marked clinical improvement 5.

Safety and Side Effects

The safety and side effects of these treatment options are also important considerations. For example:

• Metyrapone therapy has been shown to have few severe side effects, with half of the female patients complaining of hirsutism, and blood pressure not increased 3.
• Ketoconazole treatment has been shown to have mild and major increases in liver enzymes, but no fatal hepatitis was observed 4.
• Combination therapy with mitotane, metyrapone, and ketoconazole has been shown to have tolerable adverse effects, consisting mainly of gastrointestinal discomfort and a significant rise in total cholesterol and γ-glutamyl transferase levels 5.