Monitoring for Treatment Effectiveness and Safety in Hypercortisolism Management

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Practical monitoring of patients on hypercortisolism treatment presents significant challenges, particularly with traditional markers such as 24-hour urinary-free cortisol collection, which suffers from poor patient adherence and collection accuracy. Most clinicians have moved toward a multimodal monitoring approach that balances safety concerns with therapeutic goals. Morning cortisol levels serve primarily as a safety measure to prevent overtreatment rather than as a therapeutic target, whereas late-night salivary cortisol provides a more practical assessment of treatment efficacy.

The monitoring strategy must account for the complex physiology of normal cortisol rhythm, which requires high morning levels and near-zero overnight values. Enzyme inhibitors such as osilodrostat can potentially flatten this natural rhythm, creating an artificial but not necessarily optimal cortisol pattern. The challenge lies in achieving adequate cortisol suppression without inducing adrenal insufficiency, requiring careful dose titration and frequent monitoring, especially during treatment initiation.

Clinical experience suggests that most practitioners are still developing optimal monitoring protocols for this emerging field. The approach typically involves periodic urinary-free cortisol measurements to ensure overall control, combined with regular morning cortisol checks to prevent dangerous overtreatment. The glucocorticoid receptor antagonist mifepristone offers some protection against adrenal crisis due to its mechanism of action, which allows the pituitary gland to increase ACTH production and drive cortisol levels up when needed. However, this can lead to secondary effects including hypertension and hypokalemia due to cortisol’s mineralocorticoid activity, requiring careful monitoring of blood pressure and electrolytes.