Endocrine Abstracts

Objectives: Hypophosphatasia (HPP) is an inborn error of metabolism resulting from loss of function mutations in the tissue-nonspecific alkaline phosphatase (TNAP) gene. Asfotase alfa is an approved enzyme replacement therapy for HPP, while effective, it requires chronic multiple injections up to 6 times per week. We have developed a one-time gene therapy drug (ARU-2801: an adeno-associated viral vector expressing TNAP-D10) for HPP and examined the safety and effica...

G-protein subunit α-11 (Gα11), which is encoded by GNA11, plays a major role in calcium homeostasis by regulating parathyroid hormone (PTH) secretion, and germline loss-of-function mutations cause familial hypocalciuric hypercalcaemia type 2 (FHH2). Since Gα11 is ubiquitously expressed, we investigated whether FHH2 is associated with additional non-calcitropic phenotypes by analysing mice harbouring a homozygous germline deletion o...

A 24-year-old male was referred to endocrinology with multiple severe atraumatic vertebral fractures. In the preceding 10 years the patient had experienced a bimalleolar ankle fracture and numerous metacarpal and metatarsal breakages unrelated to trauma. There was no family history of osteoporosis and examination did not reveal any abnormalities in scleral colour, stature, dentition or facial/thoracic morphology. Dual-energy x-ray absorptiometry demonstrated severe densitometr...

Recent in-vitro studies have shown that vitamin D metabolites undergo conjugation reactions by sulfation and glucuronidation and may be important mechanisms for the inactivation, storage and excretion of analytes. However the circulating concentrations and clinical significance of phase II vitamin D conjugation is unclear as current analysis has almost exclusively been restricted to measuring their unconjugated metabolite forms. In this study we aimed to develop an analytical ...

Introduction: Primary hyperparathyroidism is a common endocrine disorder, surgery is curative. Patients with severe hypercalcemia receive cinacalcet or intravenous bisphosphonates as bridging. Intra-operative-parathyroid-hormone (IOPTH) measurement improves surgical accuracy. Bisphosphonates may increase PTH, while cinacalcet reduces it. The main aim was to assess the effect of zoledronate and cinacalcet on IOPTH.Method: Patients over 15-yo who underwent...

Heterozygous germline gain-of-function mutations of the extracellular calcium-sensing receptor (CaSR), a G-protein coupled receptor (GPCR), result in autosomal dominant hypocalcaemia type 1 (ADH1), which may cause symptomatic hypocalcaemia with low circulating parathyroid hormone (PTH) concentrations and hypercalciuria. Negative allosteric CaSR modulators, known as calcilytics, rectify the gain-of-function caused by CaSR mutations and are a potential targeted therapy for ADH1....