Key Takeaways on Hypercortisolism Management

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The clinical approach to hypercortisolism management emphasizes the critical importance of high clinical suspicion, particularly in patients who do not fit the typical phenotype for difficult-to-control diabetes. The “start low, go slow” principle is fundamental to successful treatment, with particular attention needed for older patients who may require dosing as infrequently as 2 to 3 times per week initially. Patient education about expected withdrawal symptoms and the timeline for improvement is crucial for treatment adherence and success.

Screening should become routine practice for patients meeting specific criteria: those on multiple diabetes medications with poor control, particularly when combined with multiple antihypertensive agents. The screening process using dexamethasone suppression testing is simple and cost-effective yet dramatically underused in clinical practice. Primary care physicians play a crucial role in initial recognition and screening, even if they refer patients to specialists for treatment management. The big 4 clinical indicators—difficult-to-treat diabetes, hypertension, central obesity, and bone disease—should trigger screening consideration.

The field represents a paradigm shift toward precision medicine in endocrinology, moving beyond broad-spectrum treatments to targeted, biomarker-driven therapy. The prevalence of hypercortisolism in clinical practice is likely much higher than currently recognized, suggesting that inadequate screening rather than disease rarity explains the apparent low incidence. Successful management requires not only biochemical control but also attention to the psychological and quality-of-life improvements that often accompany treatment, as patients frequently experience resolution of depression, cognitive improvement, and enhanced overall well-being alongside metabolic improvements.