From the Guidelines
Treatment for high cortisol after prolonged steroid use requires a gradual tapering of the steroid medication rather than abrupt discontinuation, as recommended by the British Society of Gastroenterology consensus guidelines 1. The tapering schedule depends on the specific steroid, dosage, and duration of use, but typically involves reducing the dose by 10-20% every 1-2 weeks under medical supervision. For example, if someone has been taking 20mg of prednisone daily for several months, their doctor might reduce it to 15mg for two weeks, then 10mg for two weeks, and so on until complete discontinuation.
During this process, the hypothalamic-pituitary-adrenal (HPA) axis needs time to recover its natural cortisol production, which may have been suppressed by external steroid use. Prolonged steroid use is associated with numerous side effects, including increased infection risk, osteoporosis, suppression of the hypothalamic-pituitary-adrenal axis, diabetes, weight gain, and cardiovascular disease 1.
Some key considerations for tapering steroid medication include:
- Reducing the dose gradually to minimize the risk of steroid withdrawal syndrome, which can include non-specific symptoms such as weakness, nausea, and arthralgia 1
- Monitoring cortisol levels regularly through blood or saliva testing to ensure the HPA axis is regaining function properly
- Providing supplementary treatments, such as adrenal support medications like hydrocortisone at physiologic doses, lifestyle modifications, and supplements, under the guidance of a healthcare provider.
It is essential to prioritize the patient's safety and well-being during the tapering process, as prolonged steroid use has been linked to increased mortality in patients with inflammatory bowel disease 1.
From the FDA Drug Label
Patients should be warned not to discontinue the use of corticosteroids abruptly or without medical supervision As prolonged use may cause adrenal insufficiency and make patients dependent on corticosteroids, they should advise any medical attendants that they are taking corticosteroids and they should seek medical advice at once should they develop an acute illness including fever or other signs of infection Following prolonged therapy, withdrawal of corticosteroids may result in symptoms of the corticosteroid withdrawal syndrome including, myalgia, arthralgia, and malaise.
The treatment for high cortisol after prolonged steroid use is not directly addressed in the provided drug labels. However, it is mentioned that prolonged use of corticosteroids can cause adrenal insufficiency and that withdrawal of corticosteroids may result in symptoms of the corticosteroid withdrawal syndrome.
- To minimize the risk of adverse effects, corticosteroids should be withdrawn gradually rather than abruptly 2.
- Medical supervision is necessary when discontinuing corticosteroid use to avoid complications such as adrenal insufficiency and corticosteroid withdrawal syndrome 2.
From the Research
Treatment Options for High Cortisol after Prolonged Steroid Use
- The treatment for high cortisol after prolonged steroid use typically involves the use of steroidogenesis inhibitors, such as ketoconazole and metyrapone, to reduce cortisol production 3, 4.
- Combination therapy with mitotane, metyrapone, and ketoconazole has been shown to be effective in controlling severe ACTH-dependent Cushing's syndrome 4.
- Etomidate, an anesthetic agent, has also been used as a steroidogenesis inhibitor to treat Cushing's syndrome, particularly in intensive care settings 5.
Mechanism of Action
- Ketoconazole inhibits the clearance of methylprednisolone and extends cortisol suppression beyond that produced by methylprednisolone alone 6.
- Metyrapone and ketoconazole combination therapy has been shown to rapidly control endocrine cancer-related life-threatening hypercortisolism 3.
- The use of ketoconazole and metyrapone can alter the urinary excretion of steroid metabolites, which can affect the reliability of urinary free cortisol immunoassay determinations 7.
Efficacy and Safety
- Combination therapy with mitotane, metyrapone, and ketoconazole has been shown to be effective in controlling severe ACTH-dependent Cushing's syndrome, with minimal side effects 4.
- Ketoconazole and metyrapone combination therapy has been shown to be well-tolerated and provides rapid control of endocrine cancer-related life-threatening hypercortisolism 3.
- However, the use of these medications can be limited by serious adverse side effects, such as gastrointestinal discomfort and elevated liver enzymes 4, 6.