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.