Impact of Genetic Testing in Endocrinology Practice: A Single-Center Experience Focused on Lipid and Monogenic...

This study aims to describe the use and clinical impact of genetic testing in an academic endocrinology practice, including its effects on diagnosis, treatment selection, medication access, and downstream management.

This single-center, retrospective descriptive study evaluated probands in an adult academic endocrinology practice who underwent clinically indicated genetic testing. Genetic testing included next-generation sequencing panels and targeted Sanger sequencing. Polygenic risk scores for lipid traits were calculated using previously validated methods. Clinical utility and downstream management actions attributable to genetic results were also assessed.

Of 216 individuals tested, 187 met inclusion criteria. Most were evaluated for familial hypercholesterolemia (48.1%), hypertriglyceridemia (35.3%), or monogenic diabetes (21.9%). Overall, 123 individuals (65.8%) had a pathogenic or likely pathogenic variant (24.6%) and/or a high polygenic risk scores (≥75th percentile) (46.5%). Genetic test results were considered clinically helpful in 92.5% (95% CI 87.8-95.5) of cases, most commonly by clarifying diagnosis, prognosis, or eligibility for targeted therapies or coverage. A specific new clinical action beyond baseline management occurred in 17.6% (95% CI 12.9-23.7) of individuals, including treatment intensification or de-escalation, medication coverage approval, referral for surgery, or initiation of appropriate screening.

In a real-world academic endocrine practice, genetic testing frequently provided clinically meaningful information and led to direct changes in management. Utility varied by condition and available therapies. These findings support selective expansion of access to genetic testing and further development of standardized approaches for its integration into endocrine care.