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Novel Insights from Clinical Practice

Leptin Substitution Results in the Induction of Menstrual Cycles in an Adolescent with Leptin Deficiency and Hypogonadotropic Hypogonadism

von Schnurbein J.a · Moss A.a · Nagel S.A.a · Muehleder H.c · Debatin K.M.b · Farooqi I.S.d · Wabitsch M.a

Author affiliations

aDivision of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, and bDepartment of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany; cChildren’s Hospital Wels, Wels, Austria; dUniversity of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, UK

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Horm Res Paediatr 2012;77:127–133

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Article / Publication Details

First-Page Preview
Abstract of Novel Insights from Clinical Practice

Received: September 21, 2011
Accepted: December 20, 2011
Published online: February 14, 2012
Issue release date: April 2012

Number of Print Pages: 7
Number of Figures: 2
Number of Tables: 1

ISSN: 1663-2818 (Print)
eISSN: 1663-2826 (Online)

For additional information: https://www.karger.com/HRP

Abstract

Background: Leptin deficiency leads to midluteal-phase defect or reduced testicular volume in adults, despite normal gonadotropin levels. All children documented to date with leptin deficiency were prepubertal with physiologically low gonadotropins prior to therapy. A direct effect of leptin on pubertal development in a leptin-naive adolescent has not yet been shown. Methods: In 2010, we reported the first connatal leptin-deficient adolescent girl with clinically and chemically proven hypogonadotropic hypogonadism. In this study, we evaluated the effect of recombinant methionyl human leptin substitution. Results: Initially, the patient had prepubertal basal and stimulated luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, low growth hormone and insulin-like growth factor 1 (IGF1) levels and no pulsatile secretion of LH and FSH. After 11 weeks of therapy, basal and stimulated LH and FSH levels rose to pubertal values and nocturnal pulsatility was initiated. After 76 weeks of therapy, menstruation occurred at the age of 16.3 years. Pulsatile nocturnal growth hormone secretion, stimulated growth hormone secretion and IGF1 values also normalized. Conclusion: We describe here the first adolescent with hypogonadotropic hypogonadism due to connatal leptin deficiency. Leptin substitution led to a rapid induction of gonadotropin secretion and menarche. These data are further proof of the concept that leptin is needed for a timely maturation of the hypothalamic/pituitary/gonadal axis.

© 2012 S. Karger AG, Basel


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Article / Publication Details

First-Page Preview
Abstract of Novel Insights from Clinical Practice

Received: September 21, 2011
Accepted: December 20, 2011
Published online: February 14, 2012
Issue release date: April 2012

Number of Print Pages: 7
Number of Figures: 2
Number of Tables: 1

ISSN: 1663-2818 (Print)
eISSN: 1663-2826 (Online)

For additional information: https://www.karger.com/HRP


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