Endocrine Abstracts

Marshall-Smith syndrome (MSS) is a congenital disorder characterised by developmental delay, failure to thrive and skeletal abnormalities such as accelerated osseous development, osteopenia, bullet-shaped middle phalanges and kyphoscoliosis. MSS is caused by truncating or frameshift mutations of the nuclear factor I/X (NFIX) gene, which encodes a ubiquitously expressed transcription factor that regulates expression of viral and cellular genes, i...

Background: Teriparatide PTH(1-34) is an osteoanabolic agent used in the treatment of osteoporosis. Measurement of PTH(1-34) can be useful in osteoporosis treatment and in the diagnosis of pseudohypoparathyroidism (PHP) by confirming administration of PTH(1-34)Aims: 1) To assess PTH(1-34) profiles obtained using standard Forsteo treatment compared to using a novel oral administration. 2) To confirm the PTH(1-34) in a PHP patient re...

The hormonally active form of vitamin D, 1,25-dihydroxyvitamin D (1,25D) acting via the vitamin D receptor (VDR) is a potent transcriptional regulator, with effects on skeletal and extra-skeletal physiology. We have shown previously that skeletal responses to 1,25D also involve regulation of microRNAs (miRNAs); small non-coding RNAs with an emerging role in epigenetics. To assess the role of miRNAs in innate immune responses to 1,25D we utilised in v...

Heterotrimeric G-proteins are important molecular switches that transduce extracellular ligand-binding at G-protein-coupled receptors (GPCRs) to intracellular signals. G-protein alpha-subunits (Gα) have two domains, a helical and GTPase domain, which provide structural stability and mediate GTPase activity, respectively. Gain-of-function Gα mutations cause endocrine conditions including McCune-Albright Syndrome, due to Gαs mutations, and a...

The autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) syndrome is an autosomal recessive disorder characterized by immune deficiency and the autoimmune destruction of endocrine organs such as the parathyroids, adrenal cortex and ovaries. APECED is caused by biallelic germline mutations of the autoimmune regulator (AIRE) gene on chromosome 21q22.3, which is expressed in thymic medullary epithelial cells and plays a key role ...

The calcium-sensing receptor (CaSR) is a G-protein coupled receptor (GPCR) that maintains systemic calcium homeostasis by detecting alterations in extracellular calcium, which it transduces into signalling changes, mainly via the Gq/11 pathway, leading to a decrease in PTH secretion. The importance of CaSR is highlighted by studies of patients that harbour germline CaSR mutations, which lead to a gain of receptor function in autosomal dominant...

Background: Prevalence of FHH in hypercalcaemic patients with a raised PTH has been quoted as 1 in 20. Parathyroidectomy has no benefit and therefore it is important to exclude FHH prior to considering surgery.Objectives: The aim of our study was to idenitify hypercalcaemic patients with a 24 hour urine calcium creatinine ratio (Ca/Cr) between 0.01–0.02 with a view to propose a cut-off ratio of 0.015 which will provide optimal...

Background: Patients with hypoparathyroidism may present acutely with hypocalcaemia and these patients may have multiple admissions; however, data on the incidence of acute and recurrent acute hypoparathyroidism are scarce in the literature.Aim: We wished to determine: (1) the causes of severe hypocalcaemia amongst A&E attendances (2) the incidence of acute hypocalcaemia due to hypoparathyroidism amongst A&E attendances, and (3) the incidence of ...

Introduction: Nephrolithiasis and osteoporosis are more common in people with primary hyperparathyroidism (PHPT), although the clinical factors associated with this risk are not well characterised. Recent evidence has suggested parathyroid hormone concentration, but not calcium, is associated with mortality in PHPT.Methods: Retrospective analysis of all patients presenting to the Edinburgh Centre for Endocrinology & Diabetes wi...

There is concern about rapid reduction in bone mineral density (BMD) and early rebound vertebral fractures following discontinuation of denosumab. Our aim was to review local experience of discontinuation of denosumab, changes in BMD and fractures in patients with osteoporosis.Methods: A retrospective analysis was conducted for patients who discontinued denosumab between March 2011 & June 2016. Denosumab withdrawal(DW) was defi...

Reduced renal synthesis of 1,25-dihydroxyvitamin D (1,25(OH)2D) from 25-hydroxyvitamin D (25OHD) in end stage renal disease (ESRD) results in low serum 1,25(OH)2D. This appears to be due to reduced renal cell function and elevated serum fibroblast growth factor 23 (FGF23). Treatment strategies have therefore focussed on 1,25(OH)2D or its synthetic analogues, alfacalcidol or paricalcitol. However this overlooks 25-hydroxyv...

Method: We carried out a retrospective audit of baseline data for patients under our care with primary hyperparathyroidism on cinacalcet therapy, against the NHS England Clinical Commissioning Policy (July 2016). Patients with secondary hypercalcaemia due to end stage renal failure were excluded.Results: 40 patients were identified, 9 men and 31 women, with an age range of 32–89 years (median age 78). 3 patients were under 50 ...

Introduction: The performance of biochemical and imaging investigations in contributing towards successful surgical outcomes is not well characterised in PHPT.Methods: Retrospective analysis of all patients presenting to the Edinburgh Centre for Endocrinology & Diabetes with PHPT between 2006 and 2014 (n = 611). Parathyroid surgery was performed in 44.8%.Results: PTH was greater than 2x ULN in 34...

Introduction: Denosumab is a human monoclonal antibody against the receptor activator of nuclear factor-kB ligand, to reduce bone resorption by limiting maturation of osteoclasts. It has been approved for use in Scotland in patients with a bone mineral density (BMD) T-score of between −4 to 2.5 who are unable to take bisphosphonates. We aimed to analyze the effects of denosumab on BMD and fracture rate in a cohort of patients who have completed a 3-year cycle of...

Introduction: BONJ is a recognised complication of bisphosphonate treatment (both oral and intravenous). Data are sparse with the reported incidence of BONJ in the oral treatment of osteoporosis between 0.01% to 0.067% or alternatively described as 1.04 to 69 per 100,000 patient-years. This study aimed to estimate the incidence of BONJ in patients taking oral bisphosphonates as a treatment for osteoporosis.Methods: Forth Valley Hea...

Background: Management of PHPT includes successful localization of parathyroid adenoma(s) by nuclear imaging and ultrasound scans allowing focused or minimally invasive surgery. Our aim was to assess the accuracy of parathyroid imaging in surgically-treated patients with primary hyperparathyroidism (PHPT) by correlating the imaging findings with surgical findings and cure of hyperparathyroidism. We also compared the surgical outcomes in patients with con...

Introduction: The 4th International Workshop on asymptomatic primary hyperparathyroidism (PHPT) has set criteria for surgical intervention and suggests that a percentage of patients can be managed conservatively. Imaging is indicated only pre-operatively to determine the optimal surgical approach.Patients and methods: We completed an audit on the use of Sestamibi, clinical and biochemical data in patients with PHPT.<...

Background: Zoledronic acid infusions are licensed for the treatment of osteoporosis and other bone disorders. Hypocalcaemia, a common side effect, increases the risk of complications. The risk of hypocalcaemia is further increased by a deficiency in 25-OH Vitamin D (VD). Pre-dose screening (PDS) is necessary to detect sub-optimal levels of serum VD and adjusted calcium (AC) early to avoid delayed treatment.Objectives: Audit adhere...

: Ectopic parathyroid adenomas have a low imaging incidence quoted at 1.4% in patients undergoing investigation for primary hyperparathyroidism with a prevalence of 6–30%. These are reported to have a more clinically severe manifestation of the disease, frequently with higher calcium levels and bone disease. Remission due to parathyroid infarction is a rare occurrence. We report a 54-yr Afro-Carribean/mixed race female who presented with lethargy, weight loss and reduced ...

Introduction: Primary hyperparathyroidism is the most common cause of hypercalcemia in the ambulatory setting. Once the diagnosis has been confirmed, imaging of the parathyroid glands is performed locally with a combination of ultrasound scan (USS) and sestamibi/single-photon emission computed tomography (SPECT CT) to localise a parathyroid adenoma prior to surgery.Method: Data was collected on patients undergoing parathyroid surge...

Aim: To evaluate the prevalence of kidney stones and osteoporosis in a cohort of patients with a confirmed diagnosis of primary hyperparathyroidism (PHPT).Study Design: This retrospective study reviewed the clinical records of patients with a confirmed diagnosis of PHPT in a single tertiary referral centre for metabolic bone disease over a period of 6 years (January 2010 – December 2015).Patients: There ...

Chronic hypoparathyroidism (HypoPT) is a rare endocrine condition characterised by hypocalcaemia and deficient or absent parathyroid hormone. The recent European Society of Endocrinology Guidelines outline recommendations for treatment and monitoring of chronic HypoPT in adults. A Delphi panel was conducted to agree upon the characteristics that define ‘not adequately controlled on standard therapy’ where this relates to patients with chronic H...

We present the case and management of a 76 year old man who developed medication-related osteonecrosis of the jaw (MRONJ) as a result of 12 years of bisphosphonate and denosumab treatment for hypercalcaemia in the setting of metastatic parathyroid carcinoma.Within two years of his original parathyroidectomy, he had metastatic recurrence diagnosed with progressive hypercalcaemia; imaging revealed three pulmonary nodules consistent w...

The milk – alkali syndrome was well known in the pre-proton pump inhibitor era when remedies for peptic ulcer included a large amount of calcium and sodium bicarbonate resulting in hypercalcaemia, metabolic alkalosis and often acute kidney injury. In a study done from 1998 to 2003, milk alkali syndrome was the cause of hypercalcaemia in 8.8 percent of the cases which is a significant percentage, so awareness about it is important.<p class="abste...

Primary Hyperparathyroidism is one of the common endocrine disorders seen in an endocrine clinic. We retrospectively analysed patients referred with primary hyperparathyroidism over 1 yr (Oct 2013 - Sept 2014) and followed them over next 30 months. Patients with isolated secondary hyperparathyroidism were excluded. Few had secondary hyperparathyroidism in addition to primary hyperparathyroidism.50 patients with primary hyperparathy...

We report a 64-year old female with a background of T2DM, renal transplantation requiring ongoing glucocorticoids, and treated toxic multinodular goitre. Following a traumatic T11 fracture and significant osteoporosis risk factors (female, postmenopausal, T2DM, glucocorticoid-use, sarcoidosis, and previous thyrotoxicosis), she was started on bisphosphonate therapy in 2012 with good concordance. Bone densitometry at the time demonstrated lumbar T...

Severe Hypercalcaemia can present as a life threatening emergency requiring urgent measures to lower the calcium. Usually, this is associated with Primary Hyperparathyroidism. It can result in obtundation, oliguria, anuria, collapse or arrhythmias. It is important to act fast and decisively to prevent fatal complications.We describe a 39 year old gentleman who was a tennis coach, who was brought after he collapsed in his bathroom. ...