Endocrine Abstracts

3-M syndrome is characterised by post-natal growth restriction. We have identified causative mutations in three genes CUL7, OBSL1 and CCDC8. CUL7, a component of an E3 ubiquitin ligase, has a binding domain for p53 and its reduction or absence has a major impact on growth and cell division. OBSL1 is postulated to have a role as a cytoskeletal adaptor, and was not recognised previously to be a growth regulator. The domain structure of CCDC8 predicts a possi...

Introduction: 131I-MIBG is a well-established treatment modality for patients with neuroendocrine tumours (NETs). Our centre has now accumulated over 10 years of experience with 131I-MIBG therapy, with long term data to evaluate effects on disease progress and other long term outcomes following therapy. Bone marrow effects of radionuclide therapy may include prolonged suppression, myelodysplasia or even frank leukaemia. Incidence is thought to be low, but...

Objective: To characterize patients with GH deficiency associated with lymphocytic hypophysitis (LyH).Method: Patients with a diagnosis of LyH were identified in the KIMS database. The responsible clinicians were asked to confirm the diagnosis and to provide more detailed information on the patient by filling in a questionnaire.Results: One hundred and fifty patients with a diagnosis of LyH were identified in the database and 100 c...

Background: 3-M syndrome is an autosomal recessive disorder characterized by pre- and post-natal growth restriction, normal intelligence and dysmorphic facial features. Mutations in the genes encoding Cullin 7 (CUL7) and Obscurin like-1 (OBSL1) have been shown to cause 3-M syndrome.Aims: To characterize CUL7 production and localization in a primary fibroblast cell line from a patient with 3-M syndrome due to a CUL7 mutation and to assess cell prol...

Patients with GHD have an, adverse body composition, insulin resistance, atherogenic lipid profile and impaired quality of life. We undertook a single centre retrospective audit of hypopituitary adults to quantify the long-term effects of dose-titrated GH replacement.The cohort comprised 53 patients defined as severely GHD using the GST (median peak GH 2.4 μ/l). Mean age 42±16.9 years, 23F, BMI 29.3±5.3 kg/m2. GH was titrated un...

The pre-receptor regulation of glucocorticoids is mediated by 11β-hydroxysteroid dehydrogenases (11β-HSD). The type 1 isoform is primarily responsible for the generation of active cortisol in tissues such as liver and adipose, whereas 11β-HSD2 regulates sodium and ion transport. Recently, we have shown the presence of functional 11β-HSD1 in the ciliary body of the eye where it is important in control of sodium transport, aqueous humour production and intrao...

Background: Diabetic gastroparesis is a disabling condition with no consistently effective treatment. Ghrelin infusion, in animal studies, increases gastric emptying and reverses post-operative ileus. We present the results of the first double-blind placebo-controlled cross-over study of ghrelin in gastric emptying in patients with diabetic gastroparesis....

BackgroundDiabetic gastroparesis is a disabling condition with no consistently effective treatment. Ghrelin infusion, in animal studies, increases gastric emptying and reverses post-operative ileus. We present the results of the first double-blind placebo-controlled cross-over study of ghrelin in gastric emptying in patients with diabetic gastroparesis.MethodsTen insulin requiring diabetic patients (5 men, 6 ...

Background: Growth Hormone (GH) and insulin-like growth factor 1 (IGF-1) are the biomarkers used to assess disease activity in acromegaly. Consensus guidelines from the Endocrine Society (2014) recommend a normal (age/sex-adjusted) IGF-1 in combination with a suppressed random GH<1 μg/l for biochemical remission. However, these results are discordant in some patients. The clinical significance of the IGF-1/GH dichotomy in the follow-up of these patients is unclear and...

Background: Acromegaly is characterised by growth hormone (GH) and insulin-like growth factor (IGF-1) hypersecretion. The disease is associated with increased cardiovascular, cerebrovascular and metabolic co-morbidities, resulting in excess mortality. A target GH <1 μg/l and normalised IGF-1 values correlate with mortality risk reduction. However, there is lack of consensus over which biomarker, GH or IGF-1, better predicts increased morbidity and/ or mortality.<p...