Endocrine Abstracts

Marshall-Smith syndrome (MSS) is a congenital disorder affecting skeletal and neural development, due to mutations in the nuclear factor I/X (NFIX) gene. NFIX encodes a ubiquitously expressed transcription factor that regulates the expression of viral and cellular genes. To identify novel genes that are misregulated by NFIX mutations, RNA sequencing and proteomics analyses were performed on mouse embryonic fibroblast (MEF) cells derived from a repres...

Diacylglycerol kinase delta (DGKD) has been implicated in calcium homeostasis and nephrolithiasis by genome-wide association studies. We have previously demonstrated that alterations in expression of DGKD cause biased calcium-sensing receptor (CaSR) signalling in vitro. To further elucidate the physiological role of DGKD we examined the biochemical phenotype of a Dgkd-haploinsufficient (+/-) mutant mouse developed by the International Mouse Phenotyping Consor...

Background: Studies have established a link between vitamin D deficiency and susceptibility to and severity of COVID-19. Our study aims to evaluate the role of vitamin D supplementation in intensive care units (ICU) in patients with COVID-19.Methods: We conducted a retrospective analysis of patients admitted to ICU in a large tertiary centre. Data on serum vitamin D concentration and supplementation, mortality, hospital and ICU stay, electrolyte replacem...

Objective: Remission rates in young people with Graves’ hyperthyroidism are <25% after a 2-yr course of thionamide antithyroid drug (ATD). Immunomodulatory agents might improve outcome by facilitating immune tolerance. We explored whether rituximab (RTX) would increase remission rates when administered with a short course of ATD.Design: This was an open label multi-centre single arm phase 2 trial in newly presenting young people (12-20y) with Gr...

Inactivating mutations in the thyroid hormone (TH) transporter monocarboxylate transporter 8 (MCT8) result in a severe form of psychomotor retardation (known as Allan-Herndon-Dudley syndrome, AHDS) due to compromised TH access to the CNS. Consequently, TH-dependent processes both during brain development and in the adult CNS such as adult hippocampal neurogenesis are impaired. Using mice deficient in Mct8, we recently demonstrated a diminished neurogenesis in the adult hippoca...

Background: To determine whether radioiodine remnant ablation (RRA) reduces cause-specific mortality (CSM) or tumor recurrence (TR) rates after bilateral thyroidectomy (BT) in low-risk adult papillary thyroid carcinoma (APTC) patients treated with curative intent, we compared outcome in 1836 stage I patients having BT alone with 832 having BT+RRA.Methods: THEN cohort (1966-1990) comprised 809 patients; 36% having RRA within 6 postoperative months. NOW co...

Dysregulation of sodium-iodide symporter (NIS) function is common in differentiated thyroid cancer, resulting in sub-optimal radioiodide therapy and poorer clinical outcome. Recent developments in identifying proteins that regulate the function of the sodium iodide symporter have highlighted two proteins involved in internalisation of NIS from the plasma membrane: AP-2 and moesin. Clathrin-mediated endocytosis (CME) of NIS is facilitated through the adaptor protein 2 (AP2) com...

Background: The Controlled Antenatal Thyroid Screening II (CATS) study, a large randomised trial of thyroxine supplementation for suboptimal gestational thyroid function (SGTF), reported a higher prevalence of elevated attention deficit hyperactivity disorder (ADHD) scores in 9 year-old children exposed to higher thyroid hormone (TH) in utero. Here we investigated if this was accompanied by altered neurodevelopment.Methods: 85 children aged 11-1...

Northern Ireland was one of the first participating sites for the UK screening programme for congenital hypothyroidism (CHT) started 40 years ago. This study aimed to explore any changing patterns in incidence over time. Enrolment in the programme has remained high throughout the 40 years (> 98%). The cut-off value for neonatal thyroid stimulating hormone (nTSH) on day 5-8 of life reduced in ~1995 from 10 mU/l to 8 mU/l to improve sensitivity and specificity. There was a s...

Context: Thyroid eye disease is disabling and disfiguring and has a substantial negative impact on quality of life. Medical therapies to reduce inflammation are widely used, but there is limited data from clinical trials beyond 6 months of follow-up. Methods: 3 year follow-up of a subset of the CIRTED trial (n = 68) which randomized patients to receive high-dose oral steroid with azathioprine/placebo and radiotherapy/sham radiotherapy. We compar...