Evolving Treatment Paradigms in Hypercortisolism: Integrating Emerging Evidence into Practice - Episode 6
Safety and Monitoring With Medical Management Options for Hypercortisolism
Panelists discuss how monitoring effectiveness requires tracking clinical parameters such as glucose and blood pressure rather than cortisol levels when using receptor antagonists while carefully managing expected adverse effects such as hypokalemia and the need for close glucose monitoring, especially in insulin-dependent patients.
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Monitoring treatment effectiveness varies significantly between steroidogenesis inhibitors and glucocorticoid receptor antagonists. With synthesis inhibitors, clinicians can track cortisol level reductions and titrate to normalize urinary-free cortisol, though Richard Auchus, MD, PhD, suggests this may represent a minimum effective dose. However, with receptor antagonists such as mifepristone, cortisol levels remain elevated or may increase, requiring clinical parameter monitoring instead. Key indicators include glucose improvement, blood pressure reduction, and weight loss, with glucose control typically improving immediately and weight loss taking longer to manifest.
The most significant adverse effects of glucocorticoid receptor antagonists include hypokalemia and hypertension, requiring proactive monitoring and management. Vivian Fonseca, MD, FRCP, recommends starting spironolactone prophylactically in all patients beginning mifepristone therapy, addressing both potassium depletion and blood pressure concerns simultaneously. Patient education about expected potassium drops prevents premature discontinuation when other physicians encounter low potassium levels. Clear documentation and communication with other health care providers ensures continuity of care and prevents inappropriate medication cessation.
Treatment selection depends on patient-specific factors including the underlying cause of hypercortisolism, comorbidities, and individual tolerance. Richard Auchus, MD, PhD, describes scenarios warranting therapy switches, such as vaginal bleeding with mifepristone in premenopausal women or adrenal insufficiency risk with synthesis inhibitors in patients with mild hypercortisolism. Drug interactions, QT prolongation risk, and individual medication tolerability all influence treatment decisions. The panel emphasizes that most medications are potent enough to use as monotherapy, avoiding the complexity of combination regimens while achieving effective cortisol control.
