SAT-459 - A Modified Delphi Panel of US Endocrinologists to Align on Minimum Clinically Important Difference (MCID) in Glucocorticoid Dose and Other Key Uncertainties in Classic Congenital Adrenal Hyperplasia (CAH)

Objectives:
Classic congenital adrenal hyperplasia (CAH) is a rare autosomal recessive disorder, resulting in decreased or absent production of cortisol, and often decreased or absent aldosterone and increased adrenal androgens. Glucocorticoids (GCs) are needed for cortisol replacement in CAH and are used to manage androgen excess often at supraphysiologic doses, resulting in adverse consequences over a lifetime. While the value of reducing long-term supraphysiologic exposure to GCs is widely recognized, no consensus exists on the minimum clinically important difference (MCID) for GC dose reduction. This study aimed to align on: (1) the MCID for GC dose reduction; (2) the use of laboratory parameters for monitoring androgen control; (3) potential improvability of complications by reducing GC dose or adrenal androgen levels; and (4) GC dose down-titration practices.

Methods:
A two-round modified Delphi panel was conducted with CAH-treating endocrinologists. Round 1 used a structured survey; Round 2 was a virtual panel discussion to refine and reach consensus on pre-defined aspects of CAH management.

Results:
Twenty-four endocrinologists completed the survey, of which 10 attended the panel. Panelists had a mean of 20.8 years in practice and treated a median of 11 patients (IQR: 3-15) with CAH annually. 100% (n=10) consensus was achieved that a 2.5 mg/day reduction in GC dose in hydrocortisone equivalents (HCe) would lead to clinically meaningful long-term benefits; 70% (n=7) agreed that any GC dose reduction is clinically meaningful. Panelists emphasized individualizing management for each patient throughout all topics. All panelists (n=10) agreed that androstenedione (A4) could be an important biomarker in CAH management, but caution is advised as interpretation may be confounded by timing of blood draw, which varies based on time of day and GC dosing schedules. All panelists (n=10) agreed GC- and adrenal androgen-related clinical outcomes may exacerbate without GC dose or adrenal androgen reduction. All panelists who answered (n=9) agreed hypertension and pre-diabetes could improve by reducing GC dose; 89% (n=8) agreed obesity, acne, hirsutism, and sleep disorders could improve by reducing GC dose or adrenal androgen levels. Lastly, 90% (n=9) agreed that GC down-titration in routine practice would likely be slower than in clinical trials due to less frequent monitoring in the real world.

Conclusion:
This modified Delphi panel provides expert consensus on key aspects of care for patients with CAH. Notably, all panelists agreed that a 2.5 mg/day reduction in supraphysiologic GC dose (in HCe) represents a clinically meaningful reduction, and 70% agreed that any reduction is beneficial. These findings offer expert perspectives to help clinicians navigate individualized CAH care using novel therapies that reduce excess adrenal androgen levels, supraphysiologic GC doses, or both.

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