Endocrine Abstracts

Case Report: A 49-year-old man presented with a two-year history of thyrotoxic symptoms for which he had been investigated on several occasions. He had a past medical history of dilated cardiomyopathy, which had been attributed to excess alcohol consumption, and had also suffered episodes of non-sustained ventricular tachycardia. His family history was strongly positive for autoimmune thyroid disease. Eventually, he was found to have an elevated fT4 (53 pmol/L, RR 12–22) ...

Congenital hypothyroidism (CH), occurs with a frequency of one in 3–4000 and is most commonly due (85%) to complete or partial failure of thyroid gland development (dysgenesis). Several transcription factors (TTF-1/Nkx2.1, TTF-2/FOXE1, PAX-8), are highly expressed in the developing rodent thyroid. We first showed that the FKHL15 gene is the human homologue of TTF-2, identifying a homozygous, loss-of-function, mutation in two siblings with CH, thyroid agenesis, clef...

Objectives: All known (>230) different mutations in thyroid hormone receptor β (TRβ) causing Resistance to Thyroid Hormone β (RTHβ), localise to three clusters within its hormone binding domain. Here, we report phenotypes and molecular studies in an unique family with RTHβ due to a mutation in the DNA binding domain (DBD) of TRβ.Methods: We ascertained clinical and biochemical features in four children and their parents ...

Background: Resistance to thyroid hormone (TH) beta (RTHβ), caused by mutations in THRB, is characterized by elevated serum (F)T4 accompanied by non-suppressed TSH concentrations. Disease features arise from variable resistance to TH action in tissues expressing Thyroid Hormone Receptor (TR) β (hypothalamus, pituitary, liver) and from thyrotoxic effects in tissues expressing TRα (heart, bone, brain). In symptomatic patients, treatment mainly involves be...

Context: Surgery is the first-line treatment option for thyrotropinomas, but medical therapy with somatostatin receptor ligands (SRL) may be used as neoadjuvant treatment and to facilitate safe surgery.Objectives: To determine the extent to which neoadjuvant SRL (i) corrects clinical, laboratory and tissue hyperthyroidism in thyrotropinomas, (ii) induces tumour shrinkage in macroadenomas, and (iii) aids microadenoma detection by 11C-methionine...

Introduction: Graves’ disease during pregnancy may cause maternal or neonatal complications, including arrhythmia, thyroid storm, congenital anomalies and neonatal thyroid dysfunction (TD). The optimal timing and frequency of TRAb measurement in pregnant women with a history of TD, and whether fetal monitoring could be limited to those with a strongly positive TRAb, is unclear.Methods: Retrospective case note review of women with elevated TRAb (>1 i...

Tumours caused by mutations in the SDH enzyme complex have a unique tumour metabolome due to a truncated citric acid cycle. The accumulation of the onco-metabolite succinate is believed to drive tumourigenesis. The aim was to investigate the role of MRI spectroscopy (H-MRS) to detect in vivo succinate elevations in suspected SDH deficient tumours including GIST, phaeochromocytoma/paraganglioma (PPGL) and pituitary adenomas (PA). Suitable patients were identified based...

Resistance to Thyroid Hormone alpha (RTHα) is characterised by tissue-selective hypothyroidism with near-normal thyroid function tests, and is due to thyroid receptor α gene mutations. We sought to correlate the clinical characteristics and response to thyroxine treatment of two RTHα patients with the properties of their defective TRα proteins.Clinical, biochemical and physiological parameters were assessed in each patient at baseline...

Background: Congenital, isolated, central, hypothyroidism (CCH), is rare and evades diagnosis on TSH-based congenital hypothyroidism screening programmes in the UK. Genetic ascertainment is therefore paramount in enabling prompt diagnosis and treatment of familial cases. Recognised causes include TSHB and IGSF1 gene defects, with only two previous reports of biallelic, highly disruptive (nonsense; R17X, in-frame deletion and missense; p.S115-T117del+T118), mu...

In patients with autoimmune Addison’s disease (AAD), exogenous glucocorticoid (GC) therapy is an imperfect substitute for physiological GC secretion; patients on long-term steroid replacement have increased morbidity, reduced life expectancy and poorer quality of life. Recent early-phase studieshave demonstrated that some endogenous steroidogenic function – Residual Adrenal Function (RAF) - is maintained at the point of diagnosis in a proportion of AAD patients; this...