Endocrine Abstracts

Introduction: Mixed gonadal dysgenesis (MGD) is a rare form of difference in sex development (DSD) characterised by mosaic karyotype of 45,X/46,XY and dysgenetic gonads. Gender dysphoria can be associated, the frequency of which is unknown. We describe 2 cases of MGD with gender dysphoria and the conundrum around pubertal induction.Case 1: An 8-year-old, reared as a girl, presented with longstanding concerns about appear...

VKK Chatterjee, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom AbstractKrishna Chatterjee graduated from Cambridge and completed his clinical training in Oxford. He first trained in endocrinology at Hammersmith Hospital, London and subsequently undertook research in the Thyroid Unit at Massachusetts General Hospital, Boston. In 1990, he returned to Cambridge as a Wellcome Senior Clinical Res...

Introduction: Thyroid function tests are frequently undertaken in children with non-specific symptoms suggestive of thyroid dysfunction. Infrequently, susceptibility of automated thyroid hormone assays to interference may generate misleading results, with the potential for inappropriate diagnosis and management. We report an unusual case with apparent subclinical hyperthyroidism, due to negative interference in particular TSH assay platforms, with an underlying genetic basis.<...

Objectives: Patients with homozygous 6Ψ mutations have GH insensitivity (GHI). We previously described spectrum of clinical and biochemical phenotypes of 11 6Ψ patients (David et al. JCEM 2007;92:655) and now report 9 additional patients. Response to rhIGF-I therapy has not previously been assessed.Methods: 20 6Ψ patients (12 M, 11 families, mean age 4.0±2.2 year) were diagnosed genetically in our centre. Continuous ...

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...

Objectives: Noonan Syndrome (NS) is an autosomal dominant multi-system disorder characterised by short stature (SS), distinctive facial features and cardiovascular abnormalities. Mutations in multiple genes regulating the RAS-MAPK pathway have been identified in NS including 5 recently described novel LZTR1 variants. We identified 2 novel LZTR1 variants in patients with features of growth hormone insensitivity and NS. The molecular function of LZTR1 ...

Introduction: Growth Hormone Insensitivity (GHI) is characterised by a triad of short stature (SS), IGF-1 deficiency and normal/high GH levels. ‘Classical’ GHI due to homozygous exonic GHR mutations results in extreme SS with dysmorphic and metabolic abnormalities. Heterozygous exon 9 GHR mutations are rare and exert dominant negative effects due to impairment of GHR dimerization/downstream signalling associated with a milder GHI phenotype. Only sev...

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...