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• W2024155454 abstract "Abstract Context: Idiopathic hypogonadotropic hypogonadism (IHH) with normal smell (normosmic IHH) or anosmia (Kallmann syndrome) is associated with defects in the production or action of GnRH. Accordingly, most IHH patients respond to physiological pulsatile GnRH replacement by normalizing serum LH, FSH, and testosterone (T) levels and achieving gametogenesis; some patients, however, show atypical responses. Interestingly, several IHH-associated genes are expressed in multiple compartments of the hypothalamic-pituitary-gonadal axis. Objective: The aim of the study was to investigate whether the clinical, biochemical, or genetic characteristics of IHH men with atypical responses to GnRH indicate alternative or additional defects in the hypothalamic-pituitary-gonadal axis. Subjects: We studied 90 IHH men undergoing long-term pulsatile GnRH treatment over 30 yr. Design and Setting: We conducted a retrospective study of response to GnRH at a Clinical Research Center. Interventions: Physiological regimens of pulsatile sc GnRH were administered for at least 12 months. Dose-response studies using iv GnRH pulses assessed the pituitary LH response. Main Outcome Measures: We measured serum T, LH, FSH, and inhibin B levels, sperm in ejaculate, and determined the sequence of IHH-associated genes. Results: Twenty-six percent of subjects displayed atypical responses to GnRH: 1) 10 remained hypogonadotropic and hypogonadal, demonstrating pituitary and testicular defects; 2) eight achieved spermatogenesis and normal T but only with hypergonadotropism, indicating impaired testicular responsiveness to gonadotropins; and 3) five remained azoospermic despite achieving adult testicular volumes and normal hormonal profiles, suggesting primary defects in spermatogenesis. Mutations were identified only in KAL1 across groups. Conclusion: In addition to hypothalamic GnRH deficiency, IHH men can have primary pituitary and/or testicular defects, which are unmasked by GnRH replacement." @default.
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• W2024155454 date "2010-06-01" @default.
• W2024155454 modified "2023-09-30" @default.
• W2024155454 title "Congenital Idiopathic Hypogonadotropic Hypogonadism: Evidence of Defects in the Hypothalamus, Pituitary, and Testes" @default.
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• W2024155454 doi "https://doi.org/10.1210/jc.2009-2582" @default.
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