Endocrine Abstracts

The PTEN gene is a tumour suppressor gene with high risk of breast, thyroid, endometrial, colorectal, kidney tumours and melanoma, mucocutaneous lesions, macular pigmentation, and macrocephaly. Germ line heterozygous pathogenic variants in this gene leads to a spectrum of disease now called PTEN hamartoma tumour syndrome (PHTS). Cowden syndrome (the predominant phenotype of PHTS) is estimated to affect 1:200,000 individuals - however it may be under-diagnosed. Guidelines for screening and management of this disease, published by the UK Cancer Genetic Group in May 2017, advised annual thyroid ultrasound screening from age 16 years. An 11-year-old boy (Case 1) who was previously well with no significant family history, presented with epistaxis and was incidentally noted to have thyroid enlargement. He was found to have multiple thyroid nodules (causing tracheal shift), this together with frontal bossing and moderate hypertrophy of gingivae suggested a diagnosis of Cowden syndrome. This was confirmed with a heterozygous pathogenic variant c.632dupG p(Cys211TrpfsTer32) in the PTEN gene. Case 1 underwent first a hemi-thyroidectomy aged 12 and then total thyroidectomy, with histology returning follicular carcinoma. Case 1’s monochorionic identical twin brother (Case 2) had similar clinical features and he was subsequently found to have the same pathogenic genetic variant. Case 2 underwent total thyroidectomy, aged 13, but on histology, found to have a follicular variant of papillary thyroid carcinoma. Neither child had any evidence of any metastasis. The brothers are both being followed up in a surveillance clinic to undergo further screening for other tumour development risk. Cascade genetic testing confirmed the PTEN pathogenic variant had arisen de novo. Case 1 and 2 are monochorionic identical twins with an identical pathogenic PTEN genetic variant, raised in the same environment. Despite this, they developed different types of thyroid tumours at the age 12 and 13 years. They require ongoing thyroid cancer follow-up according to the MDT recommendations and will continue with PTEN screening into adulthood. These cases suggest that thyroid screening in patients with PTEN hamartoma syndrome would be of benefit earlier than currently advised.