Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Eythstrasse 24, Ulm, Germany.
Horm Res Paediatr. 2012;77(2):127-33. doi: 10.1159/000336003. Epub 2012 Feb 14.
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.
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.
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.
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.
尽管促性腺激素水平正常，但瘦素缺乏会导致成年人黄体中期缺陷或睾丸体积减小。迄今为止，所有记录在案的瘦素缺乏症患儿在接受治疗前均处于青春期前，其促性腺激素生理性降低。瘦素对青春期前未接受过瘦素治疗的青少年青春期发育的直接影响尚未得到证实。
2010 年，我们报道了首例先天性瘦素缺乏的青春期前女孩，其具有临床和化学证实的促性腺激素低下性性腺功能减退症。在这项研究中，我们评估了重组甲硫氨酸人瘦素替代治疗的效果。
最初，患者的基础和刺激黄体生成素（LH）和卵泡刺激素（FSH）水平处于青春期前水平，生长激素和胰岛素样生长因子 1（IGF1）水平较低，且 LH 和 FSH 无脉冲分泌。治疗 11 周后，基础和刺激 LH 和 FSH 水平升高至青春期水平，并开始出现夜间脉冲式分泌。治疗 76 周后，该患者于 16.3 岁时出现月经初潮。夜间脉冲式生长激素分泌、刺激生长激素分泌和 IGF1 值也恢复正常。
我们在此描述了首例因先天性瘦素缺乏导致的促性腺激素低下性性腺功能减退症的青春期前患者。瘦素替代治疗可迅速诱导促性腺激素分泌和初潮。这些数据进一步证明了瘦素对于下丘脑-垂体-性腺轴及时成熟是必需的。
