Supplementary Material for: Central Precocious Puberty due to Hypothalamic Hamartomas Correlates with Anatomic Features but Not with Expression of GnRH, TGFα, or <i>KISS1</i>

<i>Background/Aims:</i> Hypothalamic hamartomas are the most common identifiable cause of central precocious puberty (CPP). Hamartoma characteristics proposed to be associated with CPP include specific anatomic features and expression of molecules such as gonadotropin-releasing hormone (GnRH), transforming growth factor α (TGFα), and <i>GRM1A</i>, which encodes the type 1 metabotropic glutamate receptor α isoform. We sought to determine whether hamartomas that cause CPP could be distinguished by anatomic features, expression of these molecules, or expression of <i>KISS1</i>, whose products signal through the receptor GPR54 to stimulate GnRH release. <i>Methods:</i> Clinical records and radiologic images were reviewed for 18 patients who underwent hamartoma resection for intractable seizures; 7 had precocious puberty. Resected tissue was examined for expression of GnRH, GnRH receptor (GnRHR), TGFα, <i>KISS1</i>, <i>GPR54</i>, and <i>GRM1A</i>. <i>Results:</i> Hypothalamic hamartomas associated with CPP were more likely to contact the infundibulum or tuber cinereum and were larger than hamartomas not associated with CPP. GnRH, TGFα, and GnRHR were expressed by all hamartomas studied. Expression of <i>KISS1</i>, <i>GPR54</i>, and <i>GRM1A</i> did not differ significantly between hamartomas associated and not associated with CPP. <i>Conclusion:</i> Anatomic features rather than expression patterns of candidate molecules distinguish hypothalamic hamartomas that are associated with CPP from those that are not.

<i>背景/目的：</i> 下丘脑错构瘤（Hypothalamic hamartomas）是目前已明确的中枢性性早熟（central precocious puberty, CPP）最常见病因。既往认为与CPP相关的错构瘤特征包括特定解剖学特征，以及促性腺激素释放激素（gonadotropin-releasing hormone, GnRH）、转化生长因子α（transforming growth factor α, TGFα）和编码1型代谢型谷氨酸受体α亚型的<i>GRM1A</i>等分子的表达情况。本研究旨在明确导致CPP的错构瘤是否可通过解剖学特征、上述分子的表达模式，或<i>KISS1</i>（其编码产物通过GPR54受体介导信号通路以刺激GnRH释放）的表达水平进行区分。
<i>方法：</i> 回顾性分析18例因难治性癫痫接受错构瘤切除术患者的临床病历与影像学资料，其中7例合并性早熟。对切除的错构瘤组织进行检测，分析其GnRH、促性腺激素释放激素受体（GnRH receptor, GnRHR）、TGFα、<i>KISS1</i>、<i>GPR54</i>及<i>GRM1A</i>的表达情况。
<i>结果：</i> 与CPP相关的下丘脑错构瘤更易累及漏斗部（infundibulum）或灰结节（tuber cinereum），且体积较未合并CPP的错构瘤更大。所有纳入研究的错构瘤均表达GnRH、TGFα及GnRHR。<i>KISS1</i>、<i>GPR54</i>及<i>GRM1A</i>的表达水平在合并与未合并CPP的错构瘤中无显著差异。
<i>结论：</i> 与CPP相关的下丘脑错构瘤与未合并CPP者的区分依据为解剖学特征，而非候选分子的表达谱。