title: Gonadal function is associated with cardiometabolic health in pre-pubertal boys with Klinefelter syndrome.
abstract: The most common sex chromosome aneuploidy, Klinefelter syndrome (KS), is associated with primary gonadal failure and increased morbidity and mortality from cardiometabolic disorders in adulthood. Children with KS also have a high prevalence of metabolic syndrome (MetS) features. To assess the relationship of gonadal and cardiometabolic function in children with KS, we evaluated serum hormones [gonadotropins, inhibin B (INHB), anti-mullerian hormone (AMH), total testosterone (TT)], and features of MetS (waist circumference, fasting lipid panel, fasting blood glucose (FBG), and blood pressure) in 93 pre-pubertal boys with KS age 4-12 years (mean 7.7 ± 2.5 years). The cohort was grouped by age and tanner stage, and biomarkers were compared to normal ranges. A total of 80% of this pre-pubertal cohort had ≥1 feature of metabolic syndrome (MetS) and 11% had ≥3 features of MetS. Risk of MetS was independent of age and body mass index. Sertoli cell dysfunction was common with 18% having an INHB below the normal range. A low INHB was associated with higher FBG, triglycerides, LDL, and lower HDL (p < 0.05). An INHB <50 ng/dL yielded a sensitivity of 83% and a specificity of 79% for having ≥3 features of MetS. INHB and AMH positively correlated with each other (p < 0.001), and high AMH was protective of MetS. TT was below the lower limit of normal in 49% of subjects, with mean values significantly lower than expected (3.3 ng/dL vs. 4.9 ng/dL, p < 0.0001), however, no convincing relationship between TT and MetS was seen. In conclusion, gonadal and cardiometabolic dysfunction are prevalent in pre-pubertal boys with KS. Although the relationship of testosterone deficiency and MetS is well-known, this study is the first to report an association between impaired Sertoli cell function and cardiometabolic risk.
authors.affiliation: Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.|Section of Pediatric Endocrinology, Children's Hospital Colorado, Aurora, CO, USA.
authors.forename: S
authors.identifier: 0000-0002-0304-9550
authors.initials: S
authors.lastname: Davis
authors.affiliation: Hormone Biology and Metabolism, Hospital Cochin, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Lahlou
authors.affiliation: Department of Pediatrics, Thomas Jefferson University, Philadelphia, PA, USA.|A.I. DuPont Hospital for Children, Wilmington, DE, USA.
authors.forename: M
authors.initials: M
authors.lastname: Bardsley
authors.affiliation: Hormone Biology and Metabolism, Hospital Cochin, Paris, France.
authors.forename: M-C
authors.initials: MC
authors.lastname: Temple
authors.affiliation: Department of Pediatrics, Thomas Jefferson University, Philadelphia, PA, USA.|A.I. DuPont Hospital for Children, Wilmington, DE, USA.
authors.forename: K
authors.initials: K
authors.lastname: Kowal
authors.affiliation: Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.|Section of Pediatric Endocrinology, Children's Hospital Colorado, Aurora, CO, USA.
authors.forename: L
authors.initials: L
authors.lastname: Pyle
authors.affiliation: Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.|Section of Pediatric Endocrinology, Children's Hospital Colorado, Aurora, CO, USA.
authors.forename: P
authors.initials: P
authors.lastname: Zeitler
authors.affiliation: Department of Pediatrics, Thomas Jefferson University, Philadelphia, PA, USA.|A.I. DuPont Hospital for Children, Wilmington, DE, USA.
authors.forename: J
authors.initials: J
authors.lastname: Ross
mesh_terms: D054304:Anti-Mullerian Hormone / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007006:Hypogonadism / Q000097:blood / Q000503:physiopathology*; D007265:Inhibins / Q000097:blood; D007713:Klinefelter Syndrome / Q000097:blood / Q000503:physiopathology*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000503:physiopathology; D012708:Sertoli Cells / Q000378:metabolism; D013739:Testosterone / Q000097:blood*; D014280:Triglycerides / Q000097:blood; D055105:Waist Circumference / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D014280:Triglycerides; C422364:inhibin B; D013739:Testosterone; D007265:Inhibins; D054304:Anti-Mullerian Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone
keywords: 47,XXY; Klinefelter syndrome; anti-mullerian hormone; cardiometabolic; gonadal function; hypogonadism; inhibin B; metabolic syndrome; sex chromosome aneuploidy