Endocrine Abstracts

Loss-of-function mutations of the calcium-sensing receptor (CaSR), a G-protein-coupled receptor (GPCR), result in familial hypocalciuric hypercalcaemia (FHH), a disorder of extracellular calcium homeostasis affecting the parathyroids and kidneys. However, around 35% of FHH patients do not have CaSR mutations. A form of FHH, designated FHH2, has been mapped to chromosome 19p. The GNA11 gene, encoding G-protein α11 (Gα11), a component of the CaSR sign...

Introduction: GH signalling is essential for post-natal linear bone growth. The systemic/local mechanisms responsible for GH action remain unclear as the importance of liver derived IGF1 on linear growth has recently been challenged.Aim: To unravel the underlying mechanisms of linear bone growth we exploited the suppressor of cytokine signalling-2 (SOCS2) KO mice which have enhanced linear growth despite normal systemic IGF1 and GH levels.<p class="a...

Dent’s disease is a renal proximal tubular Fanconi disorder characterised by generalised loss of solutes incuding insulin, glucose, PTH, amino acids and vitamin-D binding protein and is associated with rickets in 25% and phosphaturia in ~40% of patients. Dent’s disease is caused by mutations in the chloride/proton antiporter CLC-5, which, with megalin and cubilin has a role in receptor-mediated endocytosis and vesicle trafficking. To further elucidate the role of CLC...

GH is anabolic to the skeleton but its mode of action is unclear. Clues are available from the study of the suppressor of cytokine signalling-2 (SOCS2) KO mouse which has increased bone mass despite normal systemic IGF1 levels. Whilst suggesting direct GH effects on bone forming osteoblasts the precise signalling mechanisms remain unclear. The aims of this study were, therefore, to further detail the bone phenotype of SOCS2 KO mice and determine if GH promotes bone mass by mec...

Osteocytes make up >90% of bone cells, are embedded in mineralised matrix where they form a communication network. Osteocytes differentiate from osteoblasts, and are thought to be mechano-sensitive. They are very difficult to isolate leading to a dependence on cell lines for in vitro studies of osteocyte biology. There is thus a need to develop new methods to study these cells. Recent publications indicate that osteoblasts maintained in in vitro 3D collagen g...

Osteocytes differentiate from osteoblasts, are embedded in mineralised matrix and are critical regulators of bone remodelling. In vitro osteocyte models are currently limited to cell lines in monolayer, but these do not represent their 3D environment in vivo. We have recently shown that osteoblasts in 3D gels differentiate along the osteocytic pathway. Since retinoic acid (RA) has been shown to stimulate monolayer osteoblast/osteocyte differentiation, we have inv...

Dent’s disease, due to mutations in the chloride/proton antiporter, CLC-5, represents one form of familial hypophosphataemic rickets. Dent’s disease patients also have: low-molecular-weight-proteinuria; hypercalciuria with nephrolithiasis and renal failure; and urinary loss of parathyroid hormone and vitamin D-binding protein, due to defective receptor-mediated endocytosis within the renal proximal tubule. However, there is variability in these clinical phenotypes su...

GH is an important anabolic hormone involved in the regulation of longitudinal bone growth. However, acromegaly patients have a higher prevalence of vertebral fractures despite normal bone mineral density (BMD), suggesting that overexpression of GH has adverse effects on skeletal architecture and strength. We used giant bovine GH (bGH) transgenic mice to analyse the effects of high serum GH levels on bone architecture and mechanical strength. Five month-old hemizygous male bGH...

Objectives: Type 1 diabetes mellitus (T1DM) is associated with various autoimmune conditions including celiac disease. Both these conditions are independently and variably associated with risk of osteoporosis. The current study intended to study bone health parameters and factors affecting it in patients with T1DM with serological evidence of celiac disease (CD).Methods: A cross sectional study including 100 type one diabetes patients following up in our...

Articular cartilage maintenance and repair is regulated by numerous endocrine and paracrine factors. Investigation of molecular mechanisms underlying osteoarthritis (OA) is limited by inability to identify early stage disease and individuals at risk of progression. Susceptibility to OA is genetically determined and the availability of mice from the International Knockout Mouse Consortium with deletions of every known gene provides a unique opportunity to investigate its pathop...

Objectives: The current study intended to assess the impact of GH deficiency (GHD) on bone health after using various size corrections.Methods: Thirty prepubescent children with GHD (male:female=20:10, mean age– 9.4±3.5 years) were included in the study. Data on anthropometry and total body bone mineral content (TBBMC), bone area (TBBA) and lean body mass (TBLBM) by dual energy X ray absorptiometry were collected. Anthropometric Z scores...

Objective: The aim of the present study was to assess the association between vitamin D receptor (VDR) gene polymorphism and bone mass indices in Indian adolescent girls.Methods: The current study was a cross sectional one including 100 post menarcheal girls aged 15–18 years. Serum levels of ionized calcium, inorganic phosphorus, alkaline phosphatase, parathyroid hormone and 25 hydroxy vitamin D were measured. bone mineral content (BMC), bone area (...

Introduction: Osteogenesis imperfecta (OI) is a rare, heterogeneous, genetic connective tissue disorder that manifests clinically as bone fragility, brittleness and growth disorder. Effective diagnosis is important (although often challenging) to enable institution of early and effective multidisciplinary management.The case: A 19-year-old woman was referred to the Endocrine clinic at the Warwickshire Institute for the Study of Diabetes, Endocrinology an...

Objective: To determine effectiveness of supplementing vitamin D alone vs vitamin D+ calcium on bone mass accrual in underprivileged Indian premenarcheal girls.Methods: A double blind, matched pair, cluster randomization study was carried out in 200 premenarcheal girls (8–12 years) from three public schools. The participants were randomized into two clusters and were allocated to receive either vitamin D (Group A): 30 000 IU oral cholecalciferol eve...

Objective: To know the prevalence of primary hyperparathyroidism (PHPT) in urolithiasis and predictors of PHPT in urolithiasis.Methods: This cross sectional study was conducted between July 2005 and July 2012 in Department of Endocrinology and Urology at our hospital. In this study a total of 165 consecutive patients with urolithiasis with radioopaque stones were evaluated for clinical and biochemical profile. Stones retrieved were analyzed for type of s...

Introduction: Hyponatraemia, defined as serum sodium <135 mmol/l is commonest electrolyte abnormality and is frequently encountered in elderly population. It is associated with osteoporosis and falls and an independent risk factor for fractures. The reported 1-year mortality for fracture neck of femur is between 20 and 35%.Aim: To evaluate the impact of hyponatraemia on patients with fracture neck of femur compared to normonatraemia admitted to the h...

Background: Risperidone is a widely used antipsychotic, known to cause secondary hyperprolactinaemia. Hyperprolactinaemia is associated with erectile dysfunction, amenorrhea and reduced bone mineral density (BMD). However, there is insufficient information about the extent, severity and association between these side effects, particularly among the south Indian population.Aim and objectives: To estimate the prevalence of erectile dysfunction and amenorrh...

Increased life expectancy in patients with CF has brought about novel challenges in their care. Osteoporosis in CF is associated with significant morbidity and is an exclusion criterion for lung transplantation. Recent evidence suggests an association between dysglycaemia and low bone mineral density (BMD). We aimed to determine predictors of bone loss in a cohort of CF patients attending a tertiary referral centre and, in particular, if dysglycaemia is linked with low BMD.</p...

Patients with primary hyperparathyroidism (PHP) should have assessment of urinary calcium excretion as part of routine work up. This helps in the differential diagnosis of PHP in that urine calcium is low in familial benign hypocalciuric hypercalcaemia. Possible measures of calcium excretion include 24 h urine collection, spot sample for urine for urine calcium concentration and calcium/creatinine ratio (UCa/creat), and fractional excretion of calcium (FrExCa=urine calcium&#21...

Metabolic syndrome (MetS) is known to be associated with low levels of vitamin D. The association of vitamin D in postmenopausal women with MetS and osteoporosis has not been investigated. The aim of our investigation was to assess presence of MetS in postmenopausal women treated for osteoporosis.Metods: Fifty-nive women treated with weekly alendronate, vitamin D (Fosavance 5600, MSD) and calcium for 1 year were evaluated. The following parameters were a...

Neck ultrasound (US) can facilitate minimally invasive parathyroidectomy by providing fine anatomical detail of enlarged parathyroid adenomas in patients with primary hyperparathyroidism (PHPT). The role of neck MRI in US negative/equivocal cases remains unclear. We aimed to evaluate the performance of neck MRI in parathyroid tumour localisation in the setting of negative or equivocal neck US.We performed a retrospective review of a consecutive series of...

Background: The initial management of hypercalcaemia is well described: aggressive intravenous rehydration and subsequent intravenous bisphosphonates if required. Isolated case reports document the use of haemo/peritoneal dialysis and haemofiltration in the management of severe hypercalcaemia. We report three cases that required renal replacement therapy to treat severe hypercalcaemia.Case series: A 21-year-old male presented with abdominal pain and vomi...

This group has previously audited the effect of a protocol for investigation of primary hyperparathyroidism (PHP); the protocol stating that only patients meeting criteria for parathyroidectomy should have parathyroid imaging carried out. This showed a reduction in the number of radiological investigations (USS, CT, MRI and sestamibi scans) done in patients with primary hyperparathyroidism following introduction of this protocol.The aim of this audit was...

We look into total 67 patients with non-functioning pituitary adenoma and review their bone mineral density in association with age and gender, effect of radiotherapy and hormonal replacement.Age range: 5.97% (4 patients) are between 18 and 40 years, 43.28% (29 patient) between 41 and 60 years and 50.74% (34 patients) are between 61 and 86 years.Gender: 61.19% (41 patients) are male and 38.8% (26 patients) are female.<p class="...

Vitamin D deficiency with secondary hyperparathyroidism is common in South-east Asia. In contrast, primary hyperparathyroidism is relatively rare. We present a case of severe proximal myopathy with significant diagnostic delay.A 23-year-old lady presented with a 2 years history of lower back pain, radiating to both groins and upper thighs associated with recurrent falls. Her pain and weakness progressed insidiously leading to difficulty standing or walki...

Introduction: Primary hyperparathyroidism (PPTH) is a common referral to endocrine clinics with a clinical spectrum ranging from an asymptomatic state to a symptomatic disorder with or without end organ damage. We audited our management against the NIH guidelines which are endorsed by the Endocrine Society.Methods: There is no outpatient coding system to correctly identify all patients with primary hyperparathyroidism. We included patient on radiology da...

Introduction: In the year 2010, the Indian Council of Medical Research (ICMR) has published a normative data for mone mineral density (BMD) measured by dual energy X-ray absorptiometry (DXA) scanning. However, its impact on the diagnosis of osteoporosis when compared to currently used Caucasian database has not been analysed.Objectives: To study the effect of the newly generated ICMR database (ICMRD) on the diagnosis of osteoporosis compared with the Hol...

A 37-year-old woman presented with a short history of left arm pain. X-ray indicated a lytic lesion of the scapula. Calcium was elevated at 3.25 mmol/l (normal 2.2–2.6) with parathyroid hormone (PTH) 936 pg/ml (5–70). Upon questioning she reported nocturia, polydipsia and dyspepsia. Magnetic resonance imaging revealed brown tumours in the scapula, clavicle and hand. A superior parathyroid adenoma was excised with normalisation of calcium. Bone biopsy of the scapular ...

Introduction: Immobilization hypercalcemia (IH) is more common in children and adolescent due to increased rate of bone turnover and it usually develop 4–6 weeks post trauma but it can begin as early as 2 weeks and as late as six months. We report a patient who developed severer hypercalcemia after sustaining multiple fractures and immobilization.CaseA 24-year-old man was admitted for neurorehabilitation after road traffic acc...

Introduction: Cinacalcet acts at the calcium-sensing receptors on parathyroid cells to increase the sensitivity to circulating calcium concentrations. Studies have shown that this treatment is an effective means of managing hypercalcaemia in primary hyperparathyroidism.Aims: The aim of this study was to determine the outcomes of patients who had received cinacalcet for at least 3 months for primary hyperparathyroidism.Methods: We i...

Introduction: Osteoporosis is a silent disease and fractures pose enormous medical and financial burden on ageing individuals. Also subjects of younger age are at risk for subnormal bone mineral density when they have systemic disorders like rheumatoid arthritis or on long-term medications like corticosteroids. Preventive measures can be initiated if osteoporosis is diagnosed and treated before any fracture occurs. Even after the first fracture has occurred, there are effectiv...

Aim: The aim of this audit was to evaluate our adherence to current recommendations by Third International Workshop on the Management of Asymptomatic Primary Hyperthyroidism.Method: We audited 50 cases from our database of patients with PHPT diagnosed between 2007 and 2012.Results: 21/50 (42%) were referred for surgery with 19/21 operated. All referred patients had SESTA MIBI preoperative localisation scan. 19/21 had USS in additio...

Introduction: Vitamin D deficiency is increasingly being recognized as a metabolic disorder in temperate climates with various bone, cardiovascular and systemic manifestations. However topical, it is important to exclude tumour induced osteogenic osteomalacia as a possible aetiology in severe vitamin D deficiency when other risk factors (vegetarian diet, ethnicity, etc.) are absent. Early diagnosis of malignant tumors could be life saving and their resection may make this vita...

Introduction: Vitamin D deficiency is increasingly being recognized as a widely prevalent metabolic disorder in temperate climates with various systemic manifestations. However topical, it is important to exclude tumour induced osteogenic osteomalacia as a possible aetiology in severe vitamin D deficiency when other risk factors (vegetarian diet, ethnicity, etc.) are absent. Early diagnosis of malignant tumours could be life saving and their resection may make this vitamin D r...