ArticleThe Journal of clinical endocrinology and metabolism2023
Altered Thyroid Feedback Loop in Klinefelter Syndrome: From Infancy Through the Transition to Adulthood.
Article in The Journal of clinical endocrinology and metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- Klinefelter syndrome beyond hypogonadism: multisystem manifestations and a framework for clinical surveillance.Frontiers in endocrinology · 2026Review
- Functional data analysis of FSH and inhibin B levels in four ovulatory cycles shows a changing oscillatory interaction during the follicular phase.Frontiers in endocrinology · 2026Article
- Continuity of care in Klinefelter syndrome: age-adapted modules for standardized clinical data collection (I-KS).Endocrine connections · 2025Article
- An Overview of Oxidative Stress in Sex Chromosome Aneuploidies in Pediatric Populations.Antioxidants (Basel, Switzerland) · 2025Review
- Evaluation of sleep disorders in children and adolescents affected by Klinefelter syndrome.European journal of pediatrics · 2025Article
- Case Report: Diabetic ketoacidosis in a patient with Klinefelter syndrome: a rare and complex presentation.Frontiers in endocrinology · 2025Article
- Total osteocalcin levels are independently associated with worse testicular function and a higher degree of hypothalamic-pituitary-gonadal axis activation in Klinefelter syndrome.Journal of endocrinological investigation · 2024Article
- From Klinefelter Syndrome to High Grade Aneuploidies: Expanding the Gene-dosage Effect of Supernumerary X Chromosomes.The Journal of clinical endocrinology and metabolism · 2024Article
- Klinefelter Syndrome: A Genetic Disorder Leading to Neuroendocrine Modifications and Psychopathological Vulnerabilities in Children-A Literature Review and Case Report.Children (Basel, Switzerland) · 2024Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
contextIt has been claimed that thyroid dysfunction contributes to the spectrum of Klinefelter syndrome (KS); however, studies are scarce.
objectiveIn a retrospective longitudinal study, we aimed at describing the hypothalamic-pituitary-thyroid (HPT) axis and thyroid ultrasonographic (US) appearance in patients with KS throughout the life span.
methodsA total of 254 patients with KS (25.9 ± 16.1 years) were classified according to their pubertal and gonadal status and compared with different groups of non-KS age-matched individuals with normal thyroid function, treated and untreated hypogonadism, or chronic lymphocytic thyroiditis. We assessed serum thyroid hormone levels, antithyroid antibodies, US thyroid parameters, and in vitro pituitary type 2 deiodinase (D2) expression and activity.
resultsThyroid autoimmunity was more prevalent among individuals with KS at all ages, although the antibody (Ab)-negative vs Ab-positive cohorts were not different. Signs of thyroid dysfunction (reduced volume, lower echogenicity, and increased inhomogeneity) were more prominent in KS than in euthyroid controls. Free thyroid hormones were lower in prepubertal, pubertal, and adult patients with KS, whereas thyrotropin values were lower only in adults. Peripheral sensitivity to thyroid hormones was unaltered in KS, suggesting a dysfunctional HPT axis. Testosterone (T) was the only factor associated with thyroid function and appearance. In vitro testing demonstrated an inhibitory effect of T on pituitary D2 expression and activity, supporting enhanced central sensing of circulating thyroid hormones in hypogonadism.
conclusionFrom infancy through adulthood, KS is characterized by increased morphofunctional abnormalities of the thyroid gland, combined with a central feedback dysregulation sustained by the effect of hypogonadism on D2 deiodinase.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.