Endocrine Abstracts

In response to hormone activation of the glucocorticoid receptor, GR responsive promoters move through a complex series of activity states, a phenomenon we term promoter progression. Genome-wide profiling of glucocorticoid receptor (GR) regulated loci reveals several classes of response, including genes that are transiently activated and genes that are transiently repressed. In contrast to the conventional paradigm of activation and repression, GR modulation of genome function...

IntroductionOnce thought to typify type 1 diabetes mellitus (T1DM), diabetic ketoacidosis (DKA) in people with type 2 diabetes mellitus (T2DM) is also now increasingly recognized. We explored the clinical and biochemical differences in DKA in the two types of diabetes.MethodsThis retrospective cohort study included all the DKA episodes from April 2014 to September 2020 at a large tertiary care centre in West ...

Section 1: Case history: A 60 year-old lady presented with a 4-year history of progressively increasing virilisation on the background of right salpingo-oophorectomy for ectopic pregnancy in 1984 (no histology available).Section 2: Investigations: Testosterone 23.6 nmol/l (NR < 1.7), LH 16 IU/l (7.7–58.5), FSH 33 IU/l (25.8–134.8), androstenedione 3.2 nmol/l (NR 1.4–14.3), DHEAs 1.2 umol/l (0.5–5.6), 17-OHP 2.7 nmol/l (1–4.5)...

Objectives: The crystal structures of the TSH receptor (TSHR) leucine rich repeat domain (LRD) bound to TSHR stimulating monoclonal autoantibody M22TM or to TSHR blocking monoclonal autoantibody K1-70TM and antibody free have been solved previously. Cryo-electron microscopy (cryo-EM) was now used to solve the structure of full length TSHR in complex with K1-70TM.Methods: Recombinant human TSHR expressed in CHO cells was i...

Background: High risk patients with differentiated thyroid cancer (DTC) undergoing radioiodine (I-131) treatment can be prepared by thyroid hormone withdrawal (THW) or with parenteral recombinant TSH (rhTSH). We compared two centres predominantly using THW or rhTSH to study the impact on radioiodine retention and length of hospital stay (LoHS).Methods: We retrospectively compared radioactivity at discharge following high dose I-131 therapy (3–5 GBq ...

High protein diets suppress appetite, but are difficult to adhere to. Understanding how the gut senses protein may identify mechanisms to drive satiety. Amino acid products of protein digestion are thought to be sensed by G protein coupled receptors in the gut, including the calcium sensing receptor (CaSR). Calcium ions are the major ligand of the CaSR, but aromatic amino acids, particularly L-phenylalanine (L-Phe), allosterically modulate CaSR activity....

Introduction: Worldwide the Short Synacthen Test (SST) is the most popular investigation for adrenal insufficiency (AI). Its invasivity make it resource-intensive. Salivary cortisol is a well-established alternative to serum. We have developed a non-invasive alternative to the SST, using a novel formulation of Synacthen (containing a drug enhancer, chitosan) administered nasally and utilising saliva to measure glucocorticoid response.Methods: Four open-l...

Transcription factors (TFs) regulate gene expression by interacting with chromatinized DNA response elements (REs). Access to these elements is dramatically restricted by chromatin organization, and modification of the nucleoprotein structure to allow factor binding is a key feature of cell selective gene regulation (Molecular Cell 29:611, 2008; Molecular Cell 43:145, 2011). Local transitions in chromatin access (often characterized as DNaseI hypersensitive sites (DHSs)) are o...

A 69-year-old woman was admitted with new uncontrolled diabetes, severe hypertension and bilateral leg oedema. Cushing’s syndrome was suspected when she developed resistant hypokalemic alkalosis on diuretic therapy. Detailed questioning also revealed a history of episodic sweating, palpitation and tremor.Investigation & management: ACTH-dependant Cushing’s syndrome was confirmed: Serum ACTH 516 ng/l; urine free cortisol 20 045 nmol/24 h; 09...

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by parathyroid, anterior pituitary and pancreatic islet tumours. Primary hyperparathyroidism is the first clinical manifestation in >85% of patients, although in some patients pancreatic and pituitary tumours may precede the occurrence of primary hyperparathyroidism. The earliest occurrence of MEN1-tumours has been reported at the age of 5 years following which the age-related penetr...