Endocrine Abstracts

Familial hypocalciuric hypercalcaemia type-3 (FHH3) is caused by loss-of-function mutations of the sigma subunit of adaptor protein-2 (AP2), a ubiquitously expressed heterotetrameric protein with a fundamental role in endocytosis of transmembrane proteins. FHH3-associated AP2σ mutations impair internalisation of calcium-sensing receptor (CaSR) giving rise to FHH. CaSR predominantly signals via Gαq/11 leading to intracellular calcium release, and activation...

Marshall-Smith syndrome (MSS) is a congenital disorder affecting skeletal and neural development due to mutations in the nuclear factor I/X (NFIX) gene. Of these mutations, 61% are small insertions/deletions, 12% are splice site mutations and 27% are large exonic deletions clustered in exons 6–10 of the NFIX gene. In order to derive a MSS mouse model, the N-ethyl-N-nitrosourea (ENU) mutagenesis DNA archive was screened ...

Introduction: Patients with primary adrenal insufficiency (PAI) and patients with congenital adrenal hyperplasia (CAH) receive life-long glucocorticoid (GC) replacement therapy. Today daily GC doses are still higher than the reported adrenal cortisol production rate, and are not able to reproduce the physiological secretion pattern. This might result in long-term morbidities such as osteoporosis. Until now no prospective trial was performed investigating the long-term effect o...

Familial hypocalciuric hypercalcaemia (FHH) is an autosomal dominant disorder characterised by hypercalcaemia and inappropriately low renal calcium excretion. FHH can be classified into three types: FHH1, caused by calcium-sensing receptor (CaSR) loss-of-function mutations, accounting for >65% of cases; FHH2, due to loss-of-function mutations of the G-protein α11 subunit (Gα11); and FHH3, resulting from loss-of-function mutations in the adap...

Importance: The major factor contributing to the high incidence of osteoporosis in older women is the reduction in estrogen synthesis. Isoflavones have a similar structure to 17-β estradiol and can act as selective estrogen receptor modulators.Objective: To determine the safety and effect of soy isoflavones on bone during early menopause.Design: Parallel, double blind, study.Setting: Secondary care resea...

Type 2 Diabetes Mellitus (T2DM) is associated with decreased bone quality and a higher prevalence of fractures. Sclerostin is an inhibitor of bone formation produced by osteocytes and its expression is elevated in serum of diabetic patients. We examined the effect of T2DM on bone architecture and sclerostin levels in a rat model of T2DM and the influence of hyperglycaemia on sclerostin production by bone cells in vitro. Bone architecture was measured by microCT in 14 ...

Intermittent PTH therapy is currently the only anabolic therapy for osteoporosis. As the mineralisation of the extracellular matrix of bone is essential for normal function it is vital that the effects of PTH on key regulators of mineralisation are uncovered. Ablation of Alpl, Phospho1 or Smpd3 results in skeletal hypomineralisation and as such this study examined the effects of bovine (b)PTH 1–34 on their expression. MC3T3 (clone-14) osteoblast-like cells display tempora...

Background: Although it is well established that subjects with type 2 diabetes (T2D) have an increased fracture risk, there have been conflicting reports on the relationship of T2D to bone mineral density (BMD). Such discrepancies could be due to failure to adjust for potential confounding factors which could influence BMD.Objectives: To assess the relationship between type 2 diabetes and BMD at the femoral neck and spine in diabetic and non-diabetic sub...

Background: Although sclerostin (SOST) and Dickkopf-related protein 1 (DKK1) are major regulators in bone metabolism, the associations between these soluble Wnt antagonists and osteoporotic fracture (OF) in Asians, who may have distinct biologic characteristics with Caucasians, are inconclusive. Furthermore, there have been no clinical studies separately considering non-vertebral and vertebral fractures in terms of the blood levels of SOST and DKK1.Metho...

Familial Benign Hypocalciuric Hypercalcaemia (FBHH) is a benign autosomal dominant condition characterised by elevated serum calcium and parathyroid hormone (PTH) and low urine calcium. It is a genetically heterogeneous disorder but the majority of cases (type 1 FBHH) can be shown to be due inactivating mutations in the Calcium Sensing Receptor (CASR). This is a guanine nucleotide-binding-protein (G-protein) coupled receptor that signals through the G-protein subunit α11 ...

Background: Circulating levels of total oestradiol (E2) decrease with age in adult males; the effect of altered E2 circadian rhythm is uncertain. We hypothesised that age-related changes in the circadian rhythm contribute to decreased BMD in older males and investigated this.Methods: Nineteen subjects were studied: six young-healthy (YH) males (mean age (years) 27.3±4.6) with normal BMD, eight older-healthy (OH) males (mean age...

Familial hypocalciuric hypercalcaemia (FHH) is a rare condition and can be mistaken for primary hyperparathyroidism (PHPT). Distinguishing this from the later is vital to avoid un-necessary surgery as this is a benign condition. Ca:Cr excretion ratio >0.01 in a spot urine is widely used to rule out FHH. However this was calculated from 24 h urine samples on the original studies.We present a case of 46-year-old lady who presented with symptomatic hype...

Aim: Pre-operative localisation of primary hyperparathyroidism (PHPT) has been based on ultrasound (US) of neck and MIBI scans with an expectation that solitary parathyroid adenomas (PA) would be localised with reasonable accuracy and sensitivity, to enable mini-parathyroidectomy. The aim of our audit was to assess the utility of both these imaging in patients with parathyroid adenoma.Method: Retrospective analysis was performed on all patients who had s...

A 25-year-old woman with hypertension was referred with 12 months history of watery right eye and slowly growing swelling in the lateral wall of the right orbit. On examination there was proptosis with superior and medial displacement of the right globe. CT scan of facial bones revealed a 3.5 cm swelling with internal cortical scalloping and calcification arising from the zygoma within the right lateral orbital wall. Further lucent lesions were identified in the frontal bone, ...

Aims: To define and identify patients who have ‘failed’ parathyroidectomy by a single surgeon. To explore common features of these cases to refine our pathways.Methods: This case note review began with a retrospective audit of 123 patients having neck exploration from January 2009 to May 2014. The dataset of clinicopathological information obtained from the electronic Trust records, was interrogated to identify patients fulfilling the following...

We report a case of a rare genetic condition of disordered bone turnover requiring complex multidisciplinary management.A 42-year-old lady presents with a 2-year history of worsening pain in both her legs and feet. She has a long standing history of structural equinus deformities worse on the right ankle and permanently walking on her toes. She also has fixed flexion deformities at both her knees. She normally is not able to weight bear and uses crutches...

Case report: A 29-year-old female with a 17-year history of severe enduring anorexia nervosa attended our unit. Osteoporosis was diagnosed aged 24 and she had developed a left calcaneal fracture after minimal trauma 3 weeks prior to presentation. Her bone mineral density at this time confirmed the presence of osteoporosis at the lumbar spine and total hip (T-score −3.3 and −2.9 respectively) and her body mass index was low at 15.1 kg/m2. She dec...

Primary hyperparathyroidism (PHPT) is not uncommon. It has varied presentations ranging from asymptomatic disease to the classical ‘stones, groans, and moans’. The incidence and prevalence of frank diabetes mellitus (DM) is significantly increased in patients with hypercalcaemia. It may be difficult to differentiate symptoms of hypercalcaemia from DM. We present a case of improved glycaemia in a patient with DM following removal of parathyroid adenoma.<p class="a...