Endocrine Abstracts

Background: The incidence of germline pathogenic/likely pathogenic variants (P/LPV) is relatively well described in low grade well differentiated neuroendocrine tumors (NETs). However, germline findings in G3 NENs including grade 3 NETs (G3NET) and poorly differentiated neuroendocrine carcinoma (NEC) is gravely understudied, and guidance related to germline testing in G3NEN is lacking.Methods: An IRB approved, single institution, retrospective chart revi...

Background: Germline pathogenic or likely pathogenic (P/LP) variants occur in approximately 10% of NEN patients with recent data suggesting a higher frequency in pancreatic NENs or paraganglioma/pheochromocytoma (PPGL). However, identification of VUS can complicate interpretation of germline results, particularly when diverse populations are under study and the optimal gene panel size for testing remains unclear.Methods: A single-center retrospective cha...

New targeted drug strategies are urgently needed to improve radioiodine uptake and efficiently ablate thyroid cancer cells thereby minimising the risk of recurrent disease. High-throughput screening (HTS) offers a promising approach to identify new candidate drugs that will induce sodium iodide symporter (NIS) function to promote iodide uptake. However, significant progress has been limited by a lack of thyroid cell-based assays amenable to HTS. Here, we constructed a thyroid ...

J Mol Endocrinol October 1, 2015 55 81–94. DOI: 10.1530/JME-15-0119...

Hypoparathyroidism, a rare disorder characterized by absent or low levels of parathyroid hormone (PTH), often results from thyroid surgery. However, nonsurgical etiologies are present in >10% of patients. Data about this group of patients are limited.In this post hoc REPLACE (NCT00732615, EudraCT2008-005063-34) analysis, baseline characteristics and response to 50–100 μg/day rhPTH(1-84) in patients with postsurgical or nonsurgical ...

Although the vast majority of thyroid nodules are benign, evaluation by ultrasound-guided fine needle aspiration (FNA) biopsy is usually necessary to exclude underlying malignancy. Partially in recognition of reported variability in FNA sensitivity and specificity, the 2007 British Thyroid Association (BTA) guidelines recommended two benign results 3–6 months apart to exclude neoplasia. The 2014 BTA guidance states that a second FNA is not required for nodules with benign...

The role of the thyrotropin receptor (TSHR) in bone is unclear. TSHR-deficient mice have low bone mineral density (BMD) and focal osteosclerosis despite normal thyroid hormones (suggesting TSHR function, in bone, is important). Subclinical hypothyroidism (SH) has various aetiologies including thyroid autoimmunity (TA) and inactivating TSHR mutations (TSHR-M). In TSHR-deficiency & TSH-M elevated TSH compensates for reduced TSHR function, whereas in TA it compensates for red...

A new genetic disorder has recently been identified that results from mutation of THRA, encoding thyroid hormone receptor α1 (TRα1). Affected children have a high serum T3:T4 ratio, constipation and a variable intellectual deficit, but exhibit a consistently severe skeletal dysplasia. Similar to these patients, Thra1PV/+ mice harbour a mutation that disrupts the C-terminal α-helix of TRα1 and express a domi...

Mammalian genes display pulsatile transcription dynamics with bursts of expression occurring with variable duration and frequency. Using the human prolactin gene as a model of tissue specific gene regulation, we have characterised the transcription dynamics of this gene in cell lines, primary cells and pituitary tissue slices. Our data indicate that the tissue environment may have an important influence on cellular transcription activity. Cultures of cells from enzymatically d...

Introduction: Polycystic ovary syndrome (PCOS) is associated with obesity and increased cardiovascular (CV) risk markers.Objective: To assess the effects of 6 months treatment with liraglutide 1.8 mg od on obesity, and CV risk markers, particularly platelet function, in young obese women with PCOS compared to matched controls.Design: Interventional case–control study. Carotid intima-media wall thickness (cIMT) was measured by ...