Search Results
Search for other papers by A Chinoy in
Google Scholar
PubMed
Search for other papers by M Skae in
Google Scholar
PubMed
Search for other papers by A Babiker in
Google Scholar
PubMed
Search for other papers by D Kendall in
Google Scholar
PubMed
Search for other papers by M Z Mughal in
Google Scholar
PubMed
Search for other papers by R Padidela in
Google Scholar
PubMed
Background
Hypoparathyroidism is characterised by hypocalcaemia, and standard management is with an active vitamin D analogue and adequate oral calcium intake (dietary and/or supplements). Little is described in the literature about the impact of intercurrent illnesses on calcium homeostasis in children with hypoparathyroidism.
Methods
We describe three children with hypoparathyroidism in whom intercurrent illnesses led to hypocalcaemia and escalation of treatment with alfacalcidol (1-hydroxycholecalciferol) and calcium supplements.
Results
Three infants managed with standard treatment for hypoparathyroidism (two with homozygous mutations in GCMB2 gene and one with Sanjad-Sakati syndrome) developed symptomatic hypocalcaemia (two infants developed seizures) following respiratory or gastrointestinal illnesses. Substantial increases in alfacalcidol doses (up to three times their pre-illness doses) and calcium supplementation were required to achieve acceptable serum calcium concentrations. However, following resolution of illness, these children developed an increase in serum calcium and hypercalciuria, necessitating rapid reduction to pre-illness dosages of alfacalcidol and oral calcium supplementation.
Conclusion
Intercurrent illness may precipitate symptomatic hypocalcaemia in children with hypoparathyroidism, necessitating increase in dosages of alfacalcidol and calcium supplements. Close monitoring is required on resolution of the intercurrent illness, with timely reduction of dosages of active analogues of vitamin D and calcium supplements to prevent hypercalcaemia, hypercalciuria and nephrocalcinosis.
Search for other papers by Stefan Pilz in
Google Scholar
PubMed
Search for other papers by Armin Zittermann in
Google Scholar
PubMed
Search for other papers by Christian Trummer in
Google Scholar
PubMed
Search for other papers by Verena Theiler-Schwetz in
Google Scholar
PubMed
Search for other papers by Elisabeth Lerchbaum in
Google Scholar
PubMed
Search for other papers by Martin H Keppel in
Google Scholar
PubMed
Search for other papers by Martin R Grübler in
Google Scholar
PubMed
Medical Clinic V (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, Ruperto-Carola University of Heidelberg, Heidelberg, Germany
Synlab Medical Center of Human Genetics Mannheim, Mannheim, Germany
Search for other papers by Winfried März in
Google Scholar
PubMed
Search for other papers by Marlene Pandis in
Google Scholar
PubMed
Vitamin D testing and treatment is a subject of controversial scientific discussions, and it is challenging to navigate through the expanding vitamin D literature with heterogeneous and partially opposed opinions and recommendations. In this narrative review, we aim to provide an update on vitamin D guidelines and the current evidence on the role of vitamin D for human health with its subsequent implications for patient care and public health issues. Vitamin D is critical for bone and mineral metabolism, and it is established that vitamin D deficiency can cause rickets and osteomalacia. While many guidelines recommend target serum 25-hydroxyvitamin D (25[OH]D) concentrations of ≥50 nmol/L (20 ng/mL), the minimum consensus in the scientific community is that serum 25(OH)D concentrations below 25–30 nmol/L (10–12 ng/mL) must be prevented and treated. Using this latter threshold of serum 25(OH)D concentrations, it has been documented that there is a high worldwide prevalence of vitamin D deficiency that may require public health actions such as vitamin D food fortification. On the other hand, there is also reason for concern that an exploding rate of vitamin D testing and supplementation increases costs and might potentially be harmful. In the scientific debate on vitamin D, we should consider that nutrient trials differ from drug trials and that apart from the opposed positions regarding indications for vitamin D treatment we still have to better characterize the precise role of vitamin D for human health.
Search for other papers by Glenville Jones in
Google Scholar
PubMed
Vitamin D has many physiological functions including upregulation of intestinal calcium and phosphate absorption, mobilization of bone resorption, renal reabsorption of calcium as well as actions on a variety of pleiotropic functions. It is believed that many of the hormonal effects of vitamin D involve a 1,25-dihydroxyvitamin D3-vitamin D receptor-mediated transcriptional mechanism involving binding to the cellular chromatin and regulating hundreds of genes in many tissues. This comprehensive historical review provides a unique perspective of the many steps of the discovery of vitamin D and its deficiency disease, rickets, stretching from 1650 until the present. The overview is divided into four distinct historical phases which cover the major developments in the field and in the process highlighting the: (a) first recognition of rickets or vitamin D deficiency; (b) discovery of the nutritional factor, vitamin D and its chemical structure; (c) elucidation of vitamin D metabolites including the hormonal form, 1,25-dihydroxyvitamin D3; (d) delineation of the vitamin D cellular machinery, functions and vitamin D-related diseases which focused on understanding the mechanism of action of vitamin D in its many target cells.
Department of Nutrition, Institute of Life Sciences, Federal University of Juiz de Fora, Governador Valadares, Minas Gerais, Brazil
Department of Nutrition, Faculty of Health and Medical Sciences, University of Surrey, University of Surrey, Guildford, UK
Search for other papers by Marcela Moraes Mendes in
Google Scholar
PubMed
Search for other papers by Patricia Borges Botelho in
Google Scholar
PubMed
Search for other papers by Helena Ribeiro in
Google Scholar
PubMed
Vitamin D enhances calcium absorption and bone mineralisation, promotes maintenance of muscle function, and is crucial for musculoskeletal health. Low vitamin D status triggers secondary hyperparathyroidism, increases bone loss, and leads to muscle weakness. The primary physiologic function of vitamin D and its metabolites is maintaining calcium homeostasis for metabolic functioning, signal transduction, and neuromuscular activity. A considerable amount of human evidence supports the well-recognised contribution of adequate serum 25-hydroxyvitamin D concentrations for bone homeostasis maintenance and prevention and treatment strategies for osteoporosis when combined with adequate calcium intake. This paper aimed to review the literature published, mainly in the last 20 years, on the effect of vitamin D and its supplementation for musculoskeletal health in order to identify the aspects that remain unclear or controversial and therefore require further investigation and debate. There is a clear need for consistent data to establish realistic and meaningful recommendations of vitamin D status that consider different population groups and locations. Moreover, there is still a lack of consensus on thresholds for vitamin D deficiency and optimal status as well as toxicity, optimal intake of vitamin D, vitamin D supplement alone as a strategy to prevent fractures and falls, recommended sun exposure at different latitudes and for different skin pigmentations, and the extra skeletal effects of vitamin D.
Search for other papers by Gabriella Oliveira Lima in
Google Scholar
PubMed
Search for other papers by Alex Luiz Menezes da Silva in
Google Scholar
PubMed
Search for other papers by Julianne Elba Cunha Azevedo in
Google Scholar
PubMed
Search for other papers by Chirlene Pinheiro Nascimento in
Google Scholar
PubMed
Search for other papers by Luana Rodrigues Vieira in
Google Scholar
PubMed
Search for other papers by Akira Otake Hamoy in
Google Scholar
PubMed
Search for other papers by Luan Oliveira Ferreira in
Google Scholar
PubMed
Search for other papers by Verônica Regina Lobato Oliveira Bahia in
Google Scholar
PubMed
Search for other papers by Nilton Akio Muto in
Google Scholar
PubMed
Search for other papers by Dielly Catrina Favacho Lopes in
Google Scholar
PubMed
Search for other papers by Moisés Hamoy in
Google Scholar
PubMed
Low plasma levels of vitamin D causes bone mineral change that can precipitate osteopenia and osteoporosis and could aggravate autoimmune diseases, hypertension and diabetes. The demand for vitamin D supplementation becomes necessary; however, the consumption of vitamin D is not without risks, which its toxicity could have potentially serious consequences related to hypervitaminosis D, such as hypercalcemia and cerebral alterations. Thus, the present study describes the electroencephalographic changes caused by supraphysiological doses of vitamin D in the brain electrical dynamics and the electrocardiographic changes. After 4 days of treatment with vitamin D at a dose of 25,000 IU/kg, the serum calcium levels found were increased in comparison with the control group. The electrocorticogram analysis found a reduction in wave activity in the delta, theta, alpha and beta frequency bands. For ECG was observed changes with shortened QT follow-up, which could be related to serum calcium concentration. This study presented important evidence about the cerebral and cardiac alterations caused by high doses of vitamin D, indicating valuable parameters in the screening and decision-making process for diagnosing patients with symptoms suggestive of intoxication.
Search for other papers by Guido Zavatta in
Google Scholar
PubMed
Search for other papers by Bart L Clarke in
Google Scholar
PubMed
The first adjunctive hormone therapy for chronic hypoparathyroidism, recombinant human parathyroid hormone (1–84) (rhPTH(1–84)) was approved by the FDA in January 2015. Since the approval of rhPTH(1–84), growing interest has developed in other agents to treat this disorder in both the scientific community and among pharmaceutical companies. For several reasons, conventional therapy with calcium and activated vitamin D supplementation, magnesium supplementation as needed, and occasionally thiazide-type diuretic therapy remains the mainstay of treatment, while endocrinologists and patients are constantly challenged by limitations of conventional treatment. Serum calcium fluctuations, increased urinary calcium, hyperphosphatemia, and a constellation of symptoms that limit mental and physical functioning are frequently associated with conventional therapy. Understanding how conventional treatment and hormone therapy work in terms of pharmacokinetics and pharmacodynamics is key to effectively managing chronic hypoparathyroidism. Multiple questions remain regarding the effectiveness of PTH adjunctive therapy in preventing or slowing the onset and progression of the classical complications of hypoparathyroidism, such as chronic kidney disease, calcium-containing kidney stones, cataracts, or basal ganglia calcification. Several studies point toward an improvement in the quality of life during replacement therapy. This review will discuss current clinical and research challenges posed by treatment of chronic hypoparathyroidism.
Key points:
-
Conventional therapy with calcium and activated forms of vitamin D are currently the mainstays of treatment for most patients with chronic hypoparathyroidism.
-
Hormone therapy can be administered through FDA-approved once-daily rhPTH(1–84), or off-label multiple-daily injections of teriparatide. The former is the only FDA-approved drug, with safety and efficacy supported by a randomized placebo-controlled trial and open-label long-term extension trial data.
-
Twice-daily teriparatide has been used in children safely for up to 10 years.
-
New pharmacological options that replace the deficient hormone wi ll likely be available within the next few years.
Search for other papers by Johanna Öberg in
Google Scholar
PubMed
Search for other papers by Rolf Jorde in
Google Scholar
PubMed
Diagnostic Clinic, University Hospital of North Norway, Tromso, Norway
Search for other papers by Yngve Figenschau in
Google Scholar
PubMed
Search for other papers by Per Medbøe Thorsby in
Google Scholar
PubMed
Search for other papers by Sandra Rinne Dahl in
Google Scholar
PubMed
Search for other papers by Anne Winther in
Google Scholar
PubMed
Division of Internal Medicine, University Hospital of North Norway, Tromso, Norway
Search for other papers by Guri Grimnes in
Google Scholar
PubMed
Objective
Combined hormonal contraceptive (CHC) use has been associated with higher total 25-hydroxyvitamin D (25(OH)D) levels. Here, we investigate the relation between CHC use and vitamin D metabolism to elucidate its clinical interpretation.
Methods
The cross-sectional Fit Futures 1 included 1038 adolescents. Here, a subgroup of 182 girls with available 25(OH)D, 1,25-dihydroxyvitamin D (1,25(OH)2D), 24,25-dihydroxyvitamin D (24,25(OH)2D), vitamin D-binding protein (DBP) and measured free 25(OH)D levels, in addition to parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23), was investigated. Vitamin D metabolites were compared between girls using (CHC+) and not using CHC (CHC−). Further, the predictability of CHC on 25(OH)D levels was assessed in a multiple regression model including lifestyle factors. The ratios 1,25(OH)2D/25(OH)D and 24,25(OH)2D/25(OH)D (vitamin D metabolite ratio (VMR)) in relation to 25(OH)D were presented in scatterplots.
Results
CHC+ (n = 64; 35% of the girls) had higher 25(OH)D levels (mean ± s.d., 60.3 ± 22.2) nmol/L) than CHC- (n = 118; 41.8 ± 19.3 nmol/L), P -values <0.01. The differences in 25(OH)D levels between CHC+ and CHC− were attenuated but remained significant after the adjustment of lifestyle factors. CHC+ also had higher levels of 1,25(OH)2D, 24,25(OH)2D, DBP and calcium than CHC−, whereas 1,25(OH)2D/25(OH)D, PTH, FGF23 and albumin were significantly lower. Free 25(OH)D and VMR did not statistically differ, and both ratios appeared similar in relation to 25(OH)D, irrespective of CHC status.
Conclusion
This confirms a clinical impact of CHC on vitamin D levels in adolescents. Our observations are likely due to an increased DBP-concentration, whereas the free 25(OH)D appears unaltered.
Search for other papers by Barbara J Boucher in
Google Scholar
PubMed
Our knowledge of vitamin D has come a long way since the 100 years it took for doctors to accept, between 1860 and 1890, that both sunlight and cod liver oil (a well-known folk remedy) cured and prevented rickets. Vitamins D2/D3 were discovered exactly a hundred years ago, and over the last 50 years vitamin D has been found to have many effects on virtually all human tissues and not just on bone health, while mechanisms affecting the actions of vitamin D at the cellular level are increasingly understood, but deficiency persists globally. Observational studies in humans have shown that better provision of vitamin D is strongly associated, dose-wise, with reductions in current and future health risks in line with the known actions of vitamin D. Randomised controlled trials, commonly accepted as providing a ‘gold standard’ for assessing the efficacy of new forms of treatment, have frequently failed to provide supportive evidence for the expected health benefits of supplementation. Such RCTs, however, have used designs evolved for testing drugs while vitamin D is a nutrient; the appreciation of this difference is critical to identifying health benefits from existing RCT data and for improving future RCT design. This report aims, therefore, to provide a brief overview of the evidence for a range of non-bony health benefits of vitamin D repletion; to discuss specific aspects of vitamin D biology that can confound RCT design and how to allow for them.
Centre de Référence des Maladies Rares du Calcium et du Phosphore Filière de Santé Maladies Rares OSCAR, Paris, France
Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, INSERM, UMRS1138, Paris, France
Search for other papers by Jean-Philippe Bertocchio in
Google Scholar
PubMed
Search for other papers by Natalie Grosset in
Google Scholar
PubMed
Search for other papers by Lionel Groussin in
Google Scholar
PubMed
Search for other papers by Peter Kamenický in
Google Scholar
PubMed
Search for other papers by Fabrice Larceneux in
Google Scholar
PubMed
Search for other papers by Anne Lienhardt-Roussie in
Google Scholar
PubMed
Université Paris-Saclay, Inserm U1185, Physiologie et Physiopathologie Endocriniennes, Assistance Publique-Hôpitaux de Paris, Service d’Endocrinologie et Diabète de l’Enfant, Centre de Référence des Maladies Rares du Calcium et du Phosphore et Filière de Santé Maladies Rares OSCAR, Hôpital Bicêtre Paris Saclay, Le Kremlin-Bicêtre, France
Search for other papers by Agnès Linglart in
Google Scholar
PubMed
Centre de Référence des Maladies Rares du Calcium et du Phosphore Filière de Santé Maladies Rares OSCAR, Paris, France
Assistance Publique-Hôpitaux de Paris, Institut Necker-Enfants Malades, INSERM U1151 – CNRS UMR 8253, Paris, France
Search for other papers by Gérard Maruani in
Google Scholar
PubMed
Association Francophone de Chirurgie Endocrinienne (AFCE), France
Search for other papers by Eric Mirallie in
Google Scholar
PubMed
Search for other papers by François Pattou in
Google Scholar
PubMed
Search for other papers by Riyad N H Seervai in
Google Scholar
PubMed
Search for other papers by Coralie Sido in
Google Scholar
PubMed
Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Biochimie et Génétique Moléculaires, Paris, France
INSERM, U1169, Université Paris Sud, Hôpital Bicêtre, Le Kremlin Bicêtre, France
Search for other papers by Caroline Silve in
Google Scholar
PubMed
INSERM, U1418, CIC-EC, Hôpital Européen Georges Pompidou, Paris, France
Search for other papers by Aurélie Vilfaillot in
Google Scholar
PubMed
Search for other papers by Antoine Tabarin in
Google Scholar
PubMed
Search for other papers by Marie-Christine Vantyghem in
Google Scholar
PubMed
Centre de Référence des Maladies Rares du Calcium et du Phosphore Filière de Santé Maladies Rares OSCAR, Paris, France
Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, INSERM, UMRS1138, Paris, France
CNRS, ERL8228, Paris, France
Search for other papers by Pascal Houillier in
Google Scholar
PubMed
Search for other papers by the investigators of the Épi-Hypo study in
Google Scholar
PubMed
Context
Recent guidelines have provided recommendations for the care of patients with chronic hypoparathyroidism. Very little is known about actual physicians’ practices or their adherence to such guidelines.
Objective
To describe the physicians’ practice patterns and their compliance with international guidelines.
Design
The cohort studies included were Épi-Hypo (118 physicians and 107 patients, from September 2016 to December 2019) and ePatients (110 patients, November 2019).
Methods
Internet-based cohorts involving all settings at a nationwide level (France). Participants were (i) physicians treating patients with chronic hypoparathyroidism and patients with chronic hypoparathyroidism either participating in the (ii) Épi-Hypo study (Épi-Hypo 2019 patients), or (iii) Hypoparathyroidism France, the national representative association (ePatients).
Results
The physicians’ specialties were mainly endocrinology (61%), nephrology (28%), family medicine (2.5%), pediatrics (2.5%), rheumatology (2%), or miscellaneous (4%) and 45% were practicing in public universities. The median number of pharmaceutical drug classes prescribed was three per patient. The combination of active vitamin D and calcium salt was given to 59 and 58% of ePatients and Épi-Hypo 2019 patients, respectively. Eighty-five percent of ePatients and 87% of physicians reported monitoring plasma calcium concentrations at a steady state at least twice a year. In 32 and 26% of cases, respectively, ePatients and physicians reported being fully in accordance with international guidelines that recommend targeting symptoms, plasma calcium and phosphate values, and urine calcium excretion.
Conclusions
The care of patients with chronic hypoparathyroidism involves physicians with very different practices, so guidelines should include and target other specialists as well as endocrinologists. Full adherence to the guidelines is low in France.
Search for other papers by Stan Ursem in
Google Scholar
PubMed
Search for other papers by Vito Francic in
Google Scholar
PubMed
Search for other papers by Martin Keppel in
Google Scholar
PubMed
Search for other papers by Verena Schwetz in
Google Scholar
PubMed
Search for other papers by Christian Trummer in
Google Scholar
PubMed
Search for other papers by Marlene Pandis in
Google Scholar
PubMed
Search for other papers by Felix Aberer in
Google Scholar
PubMed
Search for other papers by Martin R Grübler in
Google Scholar
PubMed
Search for other papers by Nicolas D Verheyen in
Google Scholar
PubMed
Search for other papers by Winfried März in
Google Scholar
PubMed
Search for other papers by Andreas Tomaschitz in
Google Scholar
PubMed
Search for other papers by Stefan Pilz in
Google Scholar
PubMed
Search for other papers by Barbara Obermayer-Pietsch in
Google Scholar
PubMed
Department of Clinical Chemistry, Amsterdam Gastroenterology & Metabolism, Amsterdam UMC, University of Amsterdam, Endocrine Laboratory, Amsterdam, Netherlands
Search for other papers by Annemieke C Heijboer in
Google Scholar
PubMed
Objective
PTH can be oxidised in vivo, rendering it biologically inactive. Non-oxidised PTH (n-oxPTH) may therefore give a better image of the hormonal status of the patient. While vitamin D supplementation decreases total PTH (tPTH) concentration, the effect on n-oxPTH concentration is unexplored. We investigated the effect of vitamin D on n-oxPTH concentration in comparison to tPTH and compared the correlations between parameters of calcium, bone and lipid metabolism with n-oxPTH and tPTH.
Methods
N-oxPTH was measured in 108 vitamin D-insufficient (25(OH)D <75 nmol/L) hypertensive patients, treated with vitamin D (2800 IE daily) or placebo for 8 weeks in the Styrian Vitamin D Hypertension Trial (NCT02136771). We calculated the treatment effect and performed correlation analyses of n-oxPTH and tPTH with parameters of calcium, bone and lipid metabolism and oxidative stress.
Results
After treatment, compared to placebo, 25(OH)D concentrations increased, tPTH decreased by 9% (P < 0.001), n-oxPTH by 7% (P = 0.025) and the ratio of n-oxPTH/tPTH increased (P = 0.027). Changes in phosphate and HDL concentration correlated with changes in n-oxPTH, but not tPTH.
Conclusions
tPTH and n-oxPTH decrease upon vitamin D supplementation. Our study suggests that vitamin D supplementation reduces the oxidation of PTH, as we observed a small but significant increase in the non-oxidised proportion of PTH upon treatment. In addition, we found that changes in phosphate and HDL concentration showed a relationship with changes in n-oxPTH, but not tPTH. This may be explained by the biological activity of n-oxPTH. Further research should be carried out to establish the clinical relevance of n-oxPTH.
