From the Guidelines
Cushing syndrome from exogenous steroid use should be managed by gradually tapering the steroid dose to minimize the risk of adrenal crisis, with the goal of using the lowest effective dose and considering steroid-sparing agents, as recommended by the most recent guidelines 1. The condition develops when patients take glucocorticoid medications like prednisone, dexamethasone, or hydrocortisone for extended periods, typically at doses exceeding 7.5 mg of prednisone daily (or equivalent) for more than 3 weeks. Key considerations in management include:
- Gradual tapering of the steroid dose to prevent adrenal crisis
- Use of the lowest effective dose for ongoing steroid therapy
- Consideration of steroid-sparing agents to reduce side effects
- Monitoring for complications like osteoporosis, diabetes, and hypertension
- Implementation of preventive measures, including calcium and vitamin D supplementation, blood glucose monitoring, and blood pressure control, as supported by evidence from studies on the metabolic effects of cortisol 1. The tapering schedule depends on treatment duration, with longer courses requiring slower tapers over weeks to months. For patients with Cushing's syndrome, the overall cardiovascular risk is substantial due to associated major risk factors such as diabetes mellitus, the metabolic syndrome, sleep apnea, obesity, and dyslipidemia, in addition to hypertension, as noted in a scientific statement from the American Heart Association 1. Recovery from symptoms typically begins within weeks of dose reduction but may take months to years for complete resolution of the hypothalamic-pituitary-adrenal axis function. It is essential to prioritize the management of Cushing syndrome from exogenous steroid use based on the most recent and highest-quality evidence, focusing on minimizing morbidity, mortality, and improving quality of life, as emphasized in the updated consensus on diagnosis and management of Cushing's disease 1.
From the FDA Drug Label
ADVERSE REACTIONS (listed alphabetically, under each subsection) The following adverse reactions have been reported with prednisone or other corticosteroids: ... development of cushingoid state, The development of Cushing's syndrome is a possible adverse reaction of exogenous steroid use, such as prednisone, as it can cause a cushingoid state 2.
- Key points:
- Cushing's syndrome is a potential side effect of long-term corticosteroid use.
- The risk of developing Cushing's syndrome increases with higher doses and longer duration of corticosteroid therapy.
- Patients on corticosteroids should be monitored for signs of Cushing's syndrome, such as weight gain, moon face, and buffalo hump.
From the Research
Cushing Syndrome from Exogenous Steroid Use
- Cushing syndrome is defined as a prolonged increase in plasma cortisol levels that is not due to a physiological etiology 3.
- The most frequent cause of Cushing syndrome is exogenous steroid use 3.
- Exogenous steroid use can lead to Cushing syndrome, which is associated with hyperglycemia, protein catabolism, immunosuppression, hypertension, weight gain, neurocognitive changes, and mood disorders 3, 4.
- Evaluation of patients with possible Cushing syndrome begins with ruling out exogenous steroid use 3.
- Screening for elevated cortisol is performed with a 24-hour urinary free cortisol test or late-night salivary cortisol test or by evaluating whether cortisol is suppressed the morning after an evening dexamethasone dose 3, 4, 5.
Diagnosis and Treatment
- Determining the etiology of Cushing syndrome is important as it affects management 4.
- The first-line therapy for all aetiologies of endogenous Cushing syndrome is surgical resection of the causal tissue 3, 4, 5.
- Medical therapy is essential in the management of patients with Cushing's syndrome when curative surgery has failed, surgery is not feasible, when awaiting radiation effect, and in recurrent cases of Cushing's syndrome 6.
- Steroidogenesis inhibitors have a rapid onset of action and are effective in reducing hypercortisolism, however, adverse effects, including adrenal insufficiency require very close patient monitoring 6.
Complications of Exogenous Steroid Use
- Exogenous steroid use can lead to secondary adrenal insufficiency, which can be profound and has not been well described 7.
- The interaction between ritonavir and exogenous steroid medications can lead to Cushing syndrome and secondary adrenal insufficiency 7.
- Patients with Cushing's syndrome due to exogenous steroid use require lifelong posttherapy monitoring to treat comorbidities and detect recurrence 5.