Endocrine Abstracts

Ligand binding by the calcium-sensing receptor (CaSR), which belongs to family C of the G-protein coupled receptor super-family, activates the phospholipase C-inositol triphosphate pathway and leads to an increase in intracellular calcium. CaSR inactivating mutations result in the hypercalcaemic disorders of familial benign hypocalciuric hypercalcaemia (FBHH) and neonatal severe primary hyperparathyroidism (NSHPT), whilst activating mutations result in the hypocalcaemic disord...

Mutations leading to haploinsufficiency of the dual zinc finger transcription factor GATA3 result in the hypoparathyroidism-deafness-renal dysplasia (HDR) syndrome which is an autosomal dominant disorder. We investigated 21 HDR probands and 14 patients with isolated hypoparathyroidism for GATA3 abnormalities. Venous blood was obtained after informed consent, as approved by the local ethical committee, and leukocyte DNA extracted. GATA3 specific primers were used for PCR amplif...

Introduction: Adult growth hormone deficiency (AGHD) is associated with target organ insensitivity to parathyroid hormone (PTH) and abnormal PTH circadian rhythm. In aging women with established osteoporosis, GH and insulin like growth factor -1 (IGF-1) concentrations are low and administration of GH has been shown to increase bone turnover and bone mineral density (BMD), but the mechanisms remain unclear. Consequently we investigated the effects of declining GH and IGF-1 conc...

Calcium-containing renal stones, which affect 7% of adults, may be associated with endocrine and metabolic disorders that include primary hyperparathyroidism, renal tubular acidosis, hypercalciuria and hyperoxaluria. In addition, ∼40% of patients with stones have a familial history, although the genetic defects remain to be elucidated. To facilitate this, we have established a mouse model for renal calcification, designated Rcalc1, and determined its chromosomal l...

Introduction: Oncogenic osteomalacia (OOM) is an uncommon disorder characterized by hyperphosphaturia, hypophosphatemia, decreased vitamin D3 serum levels, and osteomalacia. The paraneoplastic syndrome is driven by a small somatostatin receptor (sstr)-positive tumor that produces phosphatonins. While it is almost always difficult to detect the tumor by common imaging techniques, PET-CT using the radiotracer 68Ga-DOTANOC represents a novel diagnostic approach which f...

The injectable contraceptive depot medroxyprogesterone acetate (DMPA, Depo-Provera®) is used by over nine million women worldwide. It induces amenorrhoea, raising concern about effects on bone density. This study aims to ascertain if the skeletal effects of DMPA are age-specific and to identity the mechanisms through which DMPA acts on the skeleton. The study was approved by the local Ethics Committee. We recruited 100 pairs of women ages 18–25 and 35&#150...

Introduction: Secondary hyperparathyroidism (SHPT) is a major risk factor for the development of postoperative hypocalcaemia. Patients undergoing parathyroidectomy for SHPT receive alfacalcidol 4 mg once daily for three preoperative days as prophylaxis against postoperative hypocalcaemia.Objectives: The aims of the study were to establish whether the current protocol for prophylaxis of hypocalcaemia was effective and secondly to assess whether the introd...

Introduction: In young patients with Primary hyperparathyroidism, parathyroidectomy is the treatment of choice. Transient hypocalcaemia is common complication of parathyroidectomy but rarely potentially life threatening hungry bone syndrome (HBS) can develop. HBS is a state of hypocalcaemia, hypophosphataemia and tetany without concomitant hypoparathyroidism, and is caused by massive calcium deposition to the bone. Resulting hypocalcaemia can be severe and prolonged, requiring...

Introduction: The effect of oestrogens on the male skeleton has been demonstrated in a number of studies and oestradiol (E2) plays an important role in regulating bone mineral density (BMD). The concentration of bioavailable oestradiol (BE), rather than total oestradiol (TE), is associated with bone loss in elderly men.Oestradiol circulates in the bloodstream in one of three forms: bound to SHBG; bound to albumin; and unbound/free. The albumin-bound plus the free fraction comp...

The Hypoparathyroidism, Deafness and Renal dysplasia (HDR) syndrome is an autosomal dominant disorder caused by mutations in the dual zinc-finger transcription factor GATA-3. Gata3 heterozygous (+/−) knockout mice develop deafness, while Gata3 homozygous (−/−) mice, which are embryonically lethal at 11.5 to 12.5 days post-coitum (dpc), develop renal hypoplasia. The parathyroids have not been studied, and we therefore investigated these mice for ...

Introduction: Adult Growth Hormone Deficiency (AGHD) is associated with osteoporosis. Underlying mechanisms involved in the pathogenesis include reduced target-organ sensitivity to the effect of PTH. Growth Hormone Replacement (GHR) in AGHD leads to increased PTH target-organ sensitivity and consequently increased bone turnover and bone mineral density (BMD).Aims: We determined the effect of alendronate, given in addition to GHR, on PTH target-organ sens...

Kidney stones, which affect 5% of adults, are most frequently associated with hypercalciuria or hypercalcaemia. Furthermore, kidney stones may occur in families in ∼40% of patients, thereby implicating the involvement of genetic mechanisms. To further elucidate these, we have established a mouse model for renal calcification, designated Rcalc2, and determined its chromosomal localisation. Mice were kept in accordance with UK Home Office welfare guidelines and proj...

Human studies indicate that local glucocorticoid (GC) generation within osteoblasts plays a critical role in various bone diseases. Human osteoblasts express the enzyme 11b-hydroxysteroid dehydrogenase type 1 (11b-HSD1) that converts inactive GCs (cortisone, dehydrocorticosterone) to their active counterparts (cortisol, corticosterone). This activation capacity critically depends on expression of a cofactor generating enzyme hexose-6-phosphate dehydrogenase. Enzyme expression ...

Each year ∼700 patients undergo orthotopic liver transplant (OLT) in the UK. With excellent outcomes reported (1 and 5 year survivals of 90% and 70% respectively) increasing attention is paid to ensuring long-term wellbeing after transplantation. A large proportion of patients are diagnosed with osteoporosis and risk of fracture in the post-transplant period may be as high as 30% following transplant. The exact aetiology of this increase in fracture risk is unclear, alth...

Vitamin D toxicity is a recognised consequence of vitamin D therapy arising from prescription of pharmacological doses of vitamin D; biochemical monitoring is recommended for these patients. In contrast, patients taking low-dose calcium and vitamin D (Ca+D) supplements, commonly used to reduce the risk of osteoporosis, are not regarded as at risk of vitamin D toxicity, and biochemical monitoring is not routine. We report a patient taking Ca+D supplements who developed hypercal...

Thyroid hormone (T3) is an important regulator of skeletal development and bone turnover. Thyrotoxicosis is associated with accelerated growth, advanced bone age and osteoporosis. T3-action in bone is mediated mainly by T3-receptors (TRs). TRβPV mice harbour a dominant-negative mutation in the TRβ gene that impairs negative feedback control of the hypothalamic-pituitary-thyroid axis resulting in elevated thyroid hormone and TSH concentrations. TRβ<sup...