Supplementary Material for: A Review of Pituitary Duplication and First Report of Associated Precocious Puberty in a Boy

Introduction:
Pituitary duplication is a rare congenital malformation, with fewer than 80 cases reported in the literature. It is often associated with midline malformations but can also occur in isolation. Central precocious puberty (CPP) is the most common endocrinological manifestation, but to date this has only ever been reported in female patients.
Case Report:
A 9-year-old boy presented with precocious puberty. His medical history was notable for ventricular septal defect. Physical examination showed Tanner stage P3 G2, a growth rate of 10 cm/year, and bone age of 12.5 years. A GnRH test confirmed CPP. Pituitary function was otherwise normal. MRI revealed ectopic pituitary duplication with two separate stalks, two ectopic posterior pituitary, tuberomammillary fusion, and vascular anomalies involving the basilar artery and vertebral vessels. The patient was treated with GnRH agonist therapy, which normalized growth and slowed bone maturation. Whole exome sequencing did not identify any pathogenic variants.
Conclusion:
This is the first reported case of CPP in a male with pituitary duplication. The findings highlight the need for awareness of endocrine dysfunction, including CPP, in patients with pituitary malformations. The gender disparity of CPP in pituitary duplication remains unexplained, and further research into genetic and molecular mechanisms, notably Sonic Hedgehog signaling, is required to understand this association.

引言：
垂体重复畸形是一种罕见的先天性发育畸形，目前文献报道的病例不足80例。该畸形常伴发中线结构发育异常，但也可单独出现。中枢性性早熟（Central precocious puberty, CPP）是其最常见的内分泌临床表现，但截至目前，此类病例仅见于女性患者。

病例报告：
一名9岁男性患儿因性早熟就诊，既往史提示存在室间隔缺损。体格检查显示其Tanner分期为P3 G2，年生长速率为10 cm，骨龄达12.5岁。促性腺激素释放激素（Gonadotropin-Releasing Hormone, GnRH）激发试验证实为中枢性性早熟。其余垂体功能检测结果均正常。磁共振成像（Magnetic Resonance Imaging, MRI）显示异位垂体重复畸形，伴两条独立的垂体柄、两处异位垂体后叶、乳头体融合，以及累及基底动脉与椎血管的血管异常。予患者促性腺激素释放激素激动剂治疗后，其生长速率恢复正常，骨成熟进程得以延缓。全外显子组测序未检出任何致病性变异。

结论：
本病例为首例报道的伴垂体重复畸形的男性中枢性性早熟病例。本研究结果提示，对于垂体发育畸形患者，需警惕包括中枢性性早熟在内的内分泌功能异常。垂体重复畸形伴中枢性性早熟的性别差异机制至今尚未阐明，需进一步开展遗传学与分子机制研究，尤其是音猬因子（Sonic Hedgehog）信号通路相关研究，以明确二者的关联。