The following is a summary of “Phenotypic Profiling and Molecular Mechanisms in Hyperparathyroidism-jaw Tumor Syndrome,” published in the December 2023 issue of Endocrinology by Tora, et al.

Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is an inheritable primary hyperparathyroidism condition stemming from germline mutations in CDC73, responsible for parafibromin production and linked to an elevated risk of parathyroid cancer. Despite its clinical significance, there is a need for more guidance for managing afflicted individuals. The retrospective study sought to address this gap by comprehensively analyzing HPT-JT’s natural progression, genotype-histology correlations in parathyroid tumors, and the molecular consequences following CDC73 loss. For a study, researchers sought to delineate the natural course of HPT-JT, establish associations between genotypes, histology of parathyroid tumors, and parafibromin immunostaining, and elucidate the molecular changes ensuing CDC73 loss.

A total of 68 patients from 29 kindreds with HPT-JT were identified, with a median age at the last follow-up of 39 years. Analyses included an independent review of uterine tumors in 2 patients, parafibromin staining on parathyroid tumors from 19 patients, and RNA-sequencing on 21 parathyroid samples.

Of the patients, 81% developed primary hyperparathyroidism, and 31% of these cases progressed to parathyroid carcinoma. Uterine tumors were identified in 38% of females, and surgical resection revealed rare mixed epithelial-mesenchymal polypoid lesions in 50% of cases. Kidney tumors occurred in 6% of patients, with a predisposition in those with CDC73 variants at the p.M1 residue. Parafibromin staining did not align with tumor histology or genotype. RNA-sequencing highlighted significant associations with transmembrane receptor protein tyrosine kinase signaling, mesodermal commitment, and cell-cell adhesion in HPT-JT-related parathyroid tumors.

The study indicated that HPT-JT syndrome is marked by recurrent atypical adenomyomatous uterine polyps in women and a predisposition to kidney tumors in those with CDC73 variants at the p.M1 residue. The findings contributed valuable insights for the management of HPT-JT patients.

Source: academic.oup.com/jcem/article-abstract/108/12/3165/7204091?redirectedFrom=fulltext