A complex endocrine conundrum

Abstract

We describe a case of recurrent primary hyperparathyroidism, manifested as 3 metachronous parathyroid adenomata, in a 50 year-old woman who also had Hashimoto hypothyroidism, gastric gastrointestinal stromal tumour (GIST), cysts in liver and kidneys, 5 intestinal polyps (one of these a villous adenoma), diverticulitis and telangiectasia of lips. She did not have medullary thyroid carcinoma (MTC). Genetic analysis of the CDC73 gene [for Hyperparathyroidism-jaw tumor (HPT-JT)], MEN1 for Multiple Endocrine Neoplasia Type1, CDKN1B for MEN4, SDHB and SDHD for Paraganglioma/Pheochromocytoma susceptibility, VHL for von Hippel-Lindau Syndrome, BMPR1A and SMAD4 for Juvenile Polyposis Syndrome (JPS) (sequencing and MLPA), karyotype and array CGH (44 K) were all normal. She was found to be homozygous for a synonomous germline variant in exon 14 (p. Ser836Ser) of the RET oncogene. This RET variant is of unclear clinical significance, and has been previously reported both in normal individuals and in individuals with MTC. It is unlikely that homozygosity for the RET variant has been casual in the multiple pathologies that our patient has developed.