Mahachoklertwattana P, Kaplan S L, Grumbach M M
Department of Pediatrics, University of California San Francisco 94143-0106.
J Clin Endocrinol Metab. 1993 Jul;77(1):118-24. doi: 10.1210/jcem.77.1.8325933.
The LHRH-secreting hypothalamic hamartoma (HH), a congenital malformation consisting of a heterotopic mass of nervous tissue that contains LHRH neurosecretory neurons attached to the tuber cinereum or the floor of the third ventricle, can cause true or central precocious puberty (TPP). We have suggested that it functions as an ectopic LHRH pulse generator independent of the central nervous system inhibitory mechanism that normally restrains the hypothalamic LHRH pulse generator. TPP associated with a hamartoma has all of the hormonal hallmarks of puberty, including a pubertal pattern of pulsatile LH and a pubertal plasma LH response to LHRH administration. Little is known about the natural history of HH. We present long term data on 10 children (5 females and 5 males) with TPP due to HH. Physical signs of puberty were observed at a mean age of 2.2 +/- 1.6 yr (range, 0.5-5.1). Two of 10 had a pedunculated mass, and 8 of 10 had a sessile mass. The hamartoma varied in diameter from 4-25 mm and did not change with time (3.5-8.7 yr). Four patients have a seizure disorder, 3 with gelastic seizures (1 with mental retardation) and 1 with tonic-clonic seizures. The shape of the hamartoma, sessile or pedunculated, did not correlate with the occurrence of seizures. At presentation with sexual precocity, the mean height SD for chronological age was +3.5 +/- 0.4, the mean height SD for bone age was -1.9 +/- 0.4, and the mean bone age SD for chronological age was +6.8 +/- 0.7. Baseline data were comparable to those of 10 females with idiopathic TPP. Nine of 10 HH patients and all idiopathic TPP patients were treated with a LHRH agonist. The response to therapy was excellent in both groups and indistinguishable. Nine of 10 HH children attend school regularly and, aside from those with seizures, have no neurological handicap. While surgical resection of the hamartoma has been recommended, it carries an increased risk of morbidity and mortality and, if removal is incomplete, does not arrest the sexual precocity. In our experience, LHRH agonist therapy for TPP due to HH is the preferable approach.
促黄体生成素释放激素（LHRH）分泌性下丘脑错构瘤（HH）是一种先天性畸形，由异位神经组织团块构成，其中含有附着于灰结节或第三脑室底部的LHRH神经分泌神经元，可导致真性或中枢性性早熟（TPP）。我们认为它起着异位LHRH脉冲发生器的作用，独立于正常情况下抑制下丘脑LHRH脉冲发生器的中枢神经系统抑制机制。与错构瘤相关的TPP具有青春期所有的激素特征，包括青春期促黄体生成素（LH）的脉冲式分泌模式以及青春期血浆LH对LHRH给药的反应。关于HH的自然病史知之甚少。我们提供了10例因HH导致TPP的儿童（5名女性和5名男性）的长期数据。青春期的体征在平均年龄2.2±1.6岁（范围0.5 - 5.1岁）时被观察到。10例中有2例有带蒂肿块，10例中有8例有扁平状肿块。错构瘤直径在4 - 25毫米之间，且随时间（3.5 - 8.7年）无变化。4例患者有癫痫发作障碍，3例有痴笑性癫痫（1例伴有智力障碍），1例有强直阵挛性癫痫。错构瘤的形状，扁平状或带蒂状，与癫痫发作的发生无关。在性早熟表现时，按实际年龄计算的平均身高标准差为 +3.5±0.4，按骨龄计算的平均身高标准差为 -1.9±0.4，按实际年龄计算的平均骨龄标准差为 +6.8±0.7。基线数据与10例特发性TPP女性的数据相当。10例HH患者中有9例以及所有特发性TPP患者均接受了LHRH激动剂治疗。两组对治疗的反应都很好且难以区分。10例HH儿童中有9例正常上学，除了那些有癫痫发作的儿童外，没有神经功能障碍。虽然有人建议手术切除错构瘤，但它会增加发病和死亡风险，而且如果切除不完全，不能阻止性早熟。根据我们的经验，对于因HH导致的TPP，LHRH激动剂治疗是更可取的方法。
