Evolving Treatment Paradigms in Hypercortisolism: Integrating Emerging Evidence into Practice - Episode 2
Distinguishing the Source of Hypercortisolism
Panelists discuss how hypercortisolism differs from classic Cushing syndrome and how 35% of patients in the CATALYST study had adrenal imaging abnormalities, emphasizing the importance of distinguishing between pituitary-dependent and adrenal-independent sources to guide appropriate treatment strategies.
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Richard Auchus, MD, PhD, clarifies the critical distinction between classical Cushing syndrome, with its characteristic physical manifestations, and the more subtle forms of hypercortisolism identified in CATALYST. He explains that although classical Cushing syndrome is rare (1 in 10,000), autonomous cortisol secretion from adrenal adenomas represents the largest population with hypercortisolism. These patients may not display the classic Cushingoid features but exhibit higher rates of diabetes, hypertension, and osteoporosis. The CATALYST study results found that 35% of patients with positive screening test results had adrenal imaging abnormalities, significantly higher than the 2% to 9% prevalence of adrenal adenomas in the general population.
The panel identifies key clinical patterns that should trigger suspicion for hypercortisolism, particularly what Ralph DeFronzo, MD, calls “the big 4”: difficult-to-control diabetes, hypertension, obesity, and severe osteoporosis with fractures. Kidney stones represent another important clinical clue. These patients have disease that often fails to respond to potent diabetes medications such as glucagon-like peptide-1 receptor agonists and SGLT2 inhibitors, which should raise immediate suspicion. The combination of multiple comorbidities, especially severe osteoporosis in the context of uncontrolled diabetes, should prompt clinicians to consider hypercortisolism screening.
Auchus explains that hypercortisolism exists on a spectrum, with different underlying causes requiring different treatment approaches. Some cases involve functional adrenal adenomas that can be surgically removed, whereas others represent nonneoplastic hypercortisolism secondary to chronic illness that perpetuates metabolic dysfunction. Understanding this spectrum is crucial for treatment planning, as surgical options may be available for some patients whereas others require medical management. The key insight is that regardless of the underlying cause, the metabolic consequences are significant and warrant treatment intervention.
