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Publications

Journal Article Ahead of print

PubMed: 42875728 DOI: 10.1210/clinem/dgag426

Waist circumference outperforms cardiometabolic indices for identifying hypogonadism in Klinefelter Syndrome.

J Clin Endocrinol Metab

Authors: Andrea Graziani, Matteo Nardin, Giuseppe Grande, Riccardo Maria Pollis, Andrea Delbarba, Antonella Di Mambro, Riccardo Selice, Carlo Cappelli, Gian Paolo Fadini, Alberto Ferlin

Affiliations

  • Department of Medicine, University of Padua, 35128 Padua, Italy.
  • Unit of Andrology and Reproductive Medicine, Department of Systems Medicine, University Hospital of Padua, 35122 Padua, Italy.
  • Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Italy. Internal Medicine, Department of Medicine, Azienda Socio-Sanitaria Territoriale Spedali Civili, Piazzale Spedali Civili 1, 25123 Brescia, Italy.
  • Unit of Metabolic Diseases, Department of Medicine, University of Padua, Italy; Translation Specialistic Medicine "G.B. Morgagni", Curriculum "Endocrine and Metabolic Sciences", Italy.
  • Department of Medicine, Unit of Endocrinology and Metabolism, ASST Spedali Civili Brescia, Brescia, Italy.
  • Department of Medicine, University of Padua, Padua, Italy.
  • Veneto Institute of Molecular Medicine, Padua, Italy.

Abstract

CONTEXT

Klinefelter syndrome (KS) is characterized by primary hypogonadism and increased cardiometabolic risk. The utility of cardiometabolic indices remains unclear.

OBJECTIVE

To evaluate whether anthropometric and cardiometabolic indices provide incremental value beyond age for identifying hypogonadism in men with KS.

DESIGN AND SETTING

Retrospective cross-sectional cohort study at a tertiary referral center.

PATIENTS

580 patients with KS were evaluated. Analyses assessing biochemical hypogonadism were restricted to untreated patients with available calculated free testosterone (cFT) concentrations (n = 328).

MAIN OUTCOME MEASURES

Biochemical androgen deficiency was defined as cFT <0.220 nmol/L. Discriminative performance and incremental value of WC, LAP, TyG, and HOMA-IR were assessed using logistic regression, ROC analyses, reclassification analyses, decision curve analysis (DCA), and bootstrap validation.

RESULTS

Among untreated patients, 64.9% had biochemical hypogonadism. WC showed the highest discriminative ability (AUC 0.747) and slightly greater discrimination than cardiometabolic indices including LAP (AUC 0.704), HOMA-IR (AUC 0.681), and TyG index (AUC 0.612). In multivariable analyses adjusted for age, WC remained independently associated with hypogonadism (OR 1.05 per cm; p < 0.001). Age alone yielded an AUC of 0.744, which increased to 0.796 after addition of WC (p = 0.007), whereas addition of LAP resulted in only modest improvement (AUC 0.758). Addition of WC improved reclassification beyond age. DCA demonstrated consistent gains in clinical net benefit with inclusion of WC, whereas composite cardiometabolic indices provided limited additional utility.

CONCLUSIONS

In KS, WC provides incremental value beyond age for identifying hypogonadism, whereas composite cardiometabolic indices offer limited additional discriminatory value. These findings suggest that simple anthropometric assessment may support endocrine-metabolic stratification in KS.

MeSH

Hypogonadism, Testosterone, Klinefelter Syndrome, Waist Circumference