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Leptin Substitution Results in the Induction of Menstrual Cycles in an Adolescent with Leptin Deficiency and Hypogonadotropic Hypogonadism.
MedLine Citation:
PMID:  22343341     Owner:  NLM     Status:  Publisher    
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.
J von Schnurbein; A Moss; S A Nagel; H Muehleder; K M Debatin; I S Farooqi; M Wabitsch
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-2-14
Journal Detail:
Title:  Hormone research in paediatrics     Volume:  -     ISSN:  1663-2826     ISO Abbreviation:  -     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-2-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101525157     Medline TA:  Horm Res Paediatr     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 S. Karger AG, Basel.
Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
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