Istanbul Faculty of Medicine, Department of Pediatrics, Pediatric Endocrinology Unit, Istanbul University, Çapa 34093, Istanbul, Turkey.
Istanbul Faculty of Medicine, Department of Medical Genetics, Istanbul University, Istanbul, Turkey.
Hormones (Athens). 2018 Dec;17(4):581-588. doi: 10.1007/s42000-018-0079-4. Epub 2018 Nov 20.
Central precocious puberty (CPP) or early puberty (EP) is a rare entity in combined pituitary hormone deficiency (CPHD), the latter caused by mutations in pituitary transcription factor genes. The early onset of puberty in two patients with CPHD with POU1F1 gene mutation was evaluated. A 3-month-old boy was diagnosed with central hypothyroidism, and L-thyroxine was commenced. He was referred for the evaluation of short stature at 20 months of age. Anthropometric evaluation revealed severe short stature (- 6.1 SDS), and growth hormone (GH) and prolactin deficiencies were diagnosed. Homozygous POU1F1 gene mutation (c.731T>G, p. I244S) was also detected. Testicular enlargement and high luteinizing hormone (LH) levels were observed at 7 years and 9 months of age while he was on GH and L-thyroxine treatment. Due to rapid progression of puberty, gonadotropin-releasing hormone analogue (GnRHa) was initiated at 11.3 years of age. This patient recently turned 19.2 years old, and his final height was - 2.3 SDS. The second patient, a 6-month-old boy, was also referred for growth retardation. His height was - 2.7 SDS, and GH and thyroid-stimulating hormone (TSH) deficiencies were diagnosed. He also had homozygous (c.10C>T, p.Q4*) POU1F1 gene mutation. Onset of puberty was relatively early, at 10 years, with advanced bone age. He was on GnRHa treatment between 11.5 and 12.5 years of age. Recent evaluation of the patient was at 13.6 years of age, and he is still on levothyroxine and GH treatment. The relationship between the POU1F1 genotype and CPP or EP has not as yet been firmly established in humans. Animal studies have revealed that the Pou1f1 gene has a major effect on regulation of GnRH receptor function and the Gata2 gene. It has also been demonstrated that this gene controls gonadotrope evolution and prevents excess gonadotropin levels. Further studies are, however, needed to elucidate the relation between POU1F1 function and CPP.
中枢性性早熟（CPP）或早期性早熟（EP）在垂体激素缺乏症（CPHD）中较为罕见，后者是由垂体转录因子基因突变引起的。对两名患有 POU1F1 基因突变的 CPHD 患者的性早熟进行了评估。一名 3 个月大的男孩被诊断为中枢性甲状腺功能减退症，并开始服用左甲状腺素。他因 20 个月时的身材矮小而被转介评估。人体测量评估显示严重的身材矮小（-6.1 SDS），并诊断出生长激素（GH）和催乳素缺乏症。还检测到 POU1F1 基因的纯合突变（c.731T>G，p.I244S）。在接受 GH 和左甲状腺素治疗的同时，该男孩在 7 岁 9 个月时出现睾丸增大和高黄体生成素（LH）水平。由于性早熟快速进展，在 11.3 岁时开始使用促性腺激素释放激素类似物（GnRHa）。该患者最近年满 19 岁，其最终身高为-2.3 SDS。第二名患者为 6 个月大的男孩，也因生长迟缓而转介。他的身高为-2.7 SDS，诊断出 GH 和促甲状腺激素（TSH）缺乏症。他也有 POU1F1 基因的纯合突变（c.10C>T，p.Q4*）。性早熟的发病时间相对较早，为 10 岁，骨龄提前。他在 11.5 至 12.5 岁期间接受 GnRHa 治疗。最近对该患者的评估为 13.6 岁，他仍在接受左甲状腺素和 GH 治疗。POU1F1 基因型与 CPP 或 EP 之间的关系尚未在人类中得到明确证实。动物研究表明，Pou1f1 基因对 GnRH 受体功能和 Gata2 基因的调节有重大影响。还证明该基因控制促性腺激素细胞的进化并防止促性腺激素水平过高。然而，还需要进一步的研究来阐明 POU1F1 功能与 CPP 之间的关系。
