Endocrine Abstracts

Purpose: High serum prolactin concentrations have been associated with adverse health outcomes in some but not all studies. This study aimed to examine the morbidity and all-cause mortality associated with hyperprolactinaemia.Methods: A population-based matched cohort study in Tayside (Scotland, UK) from 1988 to 2014. Record-linkage technology (biochemistry, prescribing, hospital admissions, cancer registration, mat...

Introduction: Germline and somatic inactivating MEN1 variants are associated with a wide range of inherited and sporadic endocrine tumours. MEN1 encodes the tumour suppressor Menin, a ubiquitously expressed scaffold protein, implicated in multiple cellular processes including transcription, epigenetic regulation, and modulation of key signaling pathways. Despite intensive study, the mechanisms leading to endocrine tumorigenesis remain ill-defined, in part ref...

Introduction: The successful implementation of clinical genetic testing relies on accurate variant interpretation, as misclassification can result in significant harm to the patient and wider family. Missense single nucleotide variants (SNVs) pose a particular challenge, with current interpretation methods often unable to differentiate pathogenic variants from rare neutral variants, resulting in high numbers of variants of uncertain significance (VUS), and diagnostic uncertain...

Background: Advances in next-generation sequencing facilitate the simultaneous evaluation of large numbers of cancer predisposition genes (CPGs) in patients with cancer irrespective of family history or tumour phenotype. Several studies have reported the frequent occurrence of germline mutations in CPGs in patients with discordant cancer types raising the possibility of novel gene-cancer associations. The current study aimed to evaluate the significance of germline mutations i...

The epidemiology of hyperprolactinaemia is not well characterised in the literature. Using unique patient identifier we were able to link data from biochemistry, prescribing, hospital admissions, radiology, general registry office and maternity data. Observational data was collected for Tayside Scotland between 1993 and 2013. Any patient with a serum prolactin measurement >1000 mU/l or at least three prescriptions for a dopamine agonist were included. Patients who were pre...

Parafibromin is a tumour suppressor protein, encoded by the gene responsible for the hyperparathyroidism-jaw tumour (HPT-JT) syndrome, which is an autosomal dominant disorder, characterised by parathyroid tumours, ossifyfing fibromas, renal and uterine tumours. Parafibromin is a component of the polymerase-associated factor 1 (PAF1) complex and interacts directly with β-catenin, although these functions do not fully explain its role in tumourigenesis. To further investiga...

MicroRNAs are highly conserved non-coding RNAs that regulate diverse cellular processes. Altered microRNA expression is observed in many human cancers and microRNAs may have tumour suppressor or oncogenic properties. One group of putative tumour suppressor microRNAs is the let-7 family whose expression is reduced in several human tumours, and which inhibit the expression of several oncogenes including HMGA2 and K-Ras. Let-7 expression have also been observed to b...

Background: Establishing a genetic diagnosis in patients presenting with potential monogenic endocrine disorders can provide benefits for the individual and wider family. Next-generation sequencing (NGS) gene panels provide a time- and cost-efficient platform for testing. A Scottish NGS endocrine testing platform, comprising 30 genes (11 individual panels), was established in 2018. A national genomic test-directory provides eligibility criteria for testing, bu...

Introduction: Genomic testing is expected to become a part of mainstream testing in the not-too-distant future, with clinicians ordering genetics tests in the same way routine endocrine tests are requested today. Knowledge on how and what test to request needs to be gathered by a wide range of physicians. To support this, the Genomics Education Programme of NHS England is developing a resource for all endocrinologists to use in clinic as part it’s Genomic...

Background: Combination treatment with Levothyroxine (LT4) and Liothyronine (LT3) in primary hypothyroidism has been debated recently due to restrictions placed by local health boards. National guidance suggests that a short-term trial of combination LT4/LT3 treatment may be considered for individuals who report persistent symptoms despite adequate LT4 replacement.Method: We created a prescribing protocol for combined LT...