From the Guidelines
Exogenous Cushing syndrome therapy, particularly in the context of glucocorticoid use for conditions like allergic bronchopulmonary aspergillosis (ABPA), should prioritize gradual tapering of the offending medication to minimize adrenal insufficiency risk, as evidenced by recent guidelines 1. When managing exogenous Cushing syndrome due to glucocorticoid therapy, it's crucial to consider the underlying condition that necessitated steroid treatment. The approach involves reducing the glucocorticoid dose to the lowest effective level, which can be achieved by tapering the dose slowly, typically by 10-20% every 1-2 weeks, to prevent adrenal insufficiency resulting from hypothalamic-pituitary-adrenal axis suppression 1.
Key considerations in the management of exogenous Cushing syndrome include:
- Gradual tapering of glucocorticoids to prevent adrenal insufficiency
- Monitoring for signs of the underlying disease flare-up and adrenal insufficiency symptoms
- Alternative-day dosing or switching to inhaled or topical steroids to minimize systemic effects
- Supportive measures such as calcium and vitamin D supplementation to prevent osteoporosis, weight management, blood pressure control, and blood glucose monitoring
It's also important to note that the recovery from exogenous Cushing syndrome can be prolonged, taking months to years after steroid discontinuation, with some features potentially being irreversible 1. The hypothalamic-pituitary-adrenal axis may require 6-12 months to fully recover after prolonged steroid use. In the context of ABPA, oral antifungal triazoles like itraconazole may offer an alternative to glucocorticoids, with a better safety profile but a slower trajectory to improvement 1.
Given the potential for exogenous Cushing’s syndrome with the use of methylprednisolone, especially when combined with oral itraconazole, careful consideration and monitoring are necessary 1. The decision to treat asymptomatic ABPA patients with systemic therapy should be individualized, taking into account the risk of progression to irreversible bronchiectasis and the potential benefits of treating underlying ABPA, even in the absence of symptoms 1.
From the FDA Drug Label
The diurnal rhythm of the HPA axis is lost in Cushing's disease, a syndrome of adrenocortical hyperfunction characterized by obesity with centripetal fat distribution, thinning of the skin with easy bruisability, muscle wasting with weakness, hypertension, latent diabetes, osteoporosis, electrolyte imbalance, etc The same clinical findings of hyperadrenocorticism may be noted during long-term pharmacologic dose corticoid therapy administered in conventional daily divided doses.
The use of exogenous corticosteroids can lead to Cushing's syndrome, a condition characterized by adrenocortical hyperfunction. To minimize the risk of Cushing's syndrome, alternate day therapy may be considered, which involves administering the corticosteroid every other morning to allow for re-establishment of normal hypothalamic-pituitary-adrenal (HPA) activity on the off-steroid day 2.
- Key points:
- Exogenous corticosteroids can suppress adrenocortical activity.
- Alternate day therapy may help minimize the risk of Cushing's syndrome.
- HPA axis disruption can lead to Cushing's syndrome. It is essential to individualize and tailor the therapy to each patient, weighing the benefit-risk ratio for each patient in whom corticoid therapy is being considered 2.
From the Research
Cushing Syndrome Exogenic Therapy
- Exogenic Cushing syndrome is caused by the use of exogenous steroids, which can lead to hypercortisolism 3.
- The management of Cushing syndrome begins with surgery to remove the source of excess endogenous cortisol production, followed by medication that includes adrenal steroidogenesis inhibitors, pituitary-targeted drugs, or glucocorticoid receptor blockers 3.
- Adrenally directed medical therapies, such as ketoconazole, metyrapone, osilodrostat, mitotane, and etomidate, can be used to inhibit adrenal steroidogenesis in patients with Cushing syndrome 4.
- Glucocorticoid withdrawal syndrome (GWS) can occur after treatment of endogenous Cushing syndrome, and its management requires careful glucocorticoid dosing and tapering, as well as monitoring for HPA axis recovery 5.
- Medical therapy to control hypercortisolism in adrenal Cushing's syndrome is currently not the first-line therapy, but it can be important in certain clinical scenarios, such as pre-surgical treatment or in patients who are not suitable candidates for surgery 6.
Treatment Options
- Adrenal steroidogenesis inhibitors, such as metyrapone, ketoconazole, and mifepristone, can be used to control hypercortisolism in patients with Cushing syndrome 6.
- Glucocorticoid receptor blockers, such as mifepristone, can also be used to treat Cushing syndrome 6.
- New drugs, such as levoketoconazole, osilidrostat, and relacorilant, are being tested in prospective trials and may become effective alternatives to common drugs 6.
- Mitotane can be used as a second-line therapy, but it is considered to have high toxicity 6.
- Etomidate has a special position as an emergency medication in severe hypercortisolism 6.
Management of Glucocorticoid Withdrawal Syndrome
- GWS can be difficult to differentiate from adrenal insufficiency and Cushing syndrome recurrence, which complicates glucocorticoid dosing and tapering regimens 5.
- Monitoring for HPA axis recovery requires both clinical and biochemical assessments 5.
- The most important intervention is reassurance to patients that GWS symptoms portend a favorable prognosis of sustained remission from Cushing syndrome, and GWS typically resolves as the HPA axis recovers 5.
- Gradual dose titration based primarily on symptoms is essential to maintain adherence and to eventually achieve disease control 5.