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  • Abstract: Hyperparathyroidism x
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  • Abstract: Vitamin D x
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Rasmus Reinke Department of Otorhinolaryngology, Head and Neck Surgery, Aarhus University Hospital, Aarhus, Denmark

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Stefano Christian Londero Department of Otorhinolaryngology, Head and Neck Surgery, Aarhus University Hospital, Aarhus, Denmark

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Martin Almquist Department of Surgery, Lund University Hospital, Lund, Sweden

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Lars Rejnmark Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark

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Lars Rolighed Department of Otorhinolaryngology, Head and Neck Surgery, Aarhus University Hospital, Aarhus, Denmark

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Objective

Total thyroidectomy is associated with a high risk of postoperative hypoparathyroidism, mainly due to the unintended surgical damage to the parathyroid glands or their blood supply. It is possible that surgeons who also perform parathyroid surgery see lower rates of postoperative hypoparathyroidism. In a single institution, we investigated the effects of restricting total thyroidectomy operations for Graves’ disease to two surgeons who performed both thyroid and parathyroid surgeries. We aimed to evaluate the rates of postoperative hypoparathyroidism in a 10-year period with primary attention toward patients with Graves’ disease.

Design

Retrospective cohort study from a single institution.

Methods

We defined the rate of permanent hypoparathyroidism after total thyroidectomy as the need for active vitamin D 6 months postoperatively. Between 2012 and 2016, seven surgeons performed all thyroidectomies. From January 2017, only surgeons also performing parathyroid surgery carried out thyroidectomies for Graves’ disease.

Results

We performed total thyroidectomy in 543 patients. The rate of permanent hypoparathyroidism decreased from 28% in 2012–2014 to 6% in 2020–2021. For patients with Graves’ disease, the rate of permanent hypoparathyroidism decreased from 36% (13 out of 36) in 2015–2016 to 2% (1 out of 56) in 2020–2021. In cancer patients, the rate of permanent hypoparathyroidism decreased from 30% (14 out of 46) in 2012–2014 to 10% (10 out of 51) in 2020–2021.

Conclusion

Restricting thyroidectomy to surgeons who also performed parathyroid operations reduced postoperative hypoparathyroidism markedly. Accordingly, we recommend centralisation of the most difficult thyroid operations to centres and surgeons with extensive experience in parathyroid surgery.

Significance statement

Thyroid surgery is performed by many different surgeons with marked differences in outcome. Indeed, the risk of postoperative permanent hypoparathyroidism may be very high in low-volume centres. This serious condition affects the quality of life and increases long-term morbidity and the patients develop a life-long dependency of medical treatments. We encountered a high risk of hypoparathyroidism after the operation for Graves’ disease and restricted the number of surgeons to two for these operations. Further, these surgeons were experienced in both thyroid and parathyroid surgeries. We show a dramatic reduction in postoperative hypoparathyroidism after this change. Accordingly, we recommend centralisation of total thyroidectomy to surgeons with experience in both thyroid and parathyroid procedures.

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Jane Fletcher Nutrition Nurses, University Hospitals Birmingham NHS Trust, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham, UK
School of Nursing, Institute of Clinical Sciences, University of Birmingham, Edgbaston, Birmingham, UK

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Emma L Bishop Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK

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Stephanie R Harrison Leeds Institute of Rheumatic and Musculoskeletal Medicine, Chapel Allerton Hospital, Leeds, UK

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Amelia Swift School of Nursing, Institute of Clinical Sciences, University of Birmingham, Edgbaston, Birmingham, UK

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Sheldon C Cooper Gastroenterology Department, University Hospitals Birmingham NHS Trust, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham, UK

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Sarah K Dimeloe Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK

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Karim Raza Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK

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Martin Hewison Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK

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Vitamin D has well-documented effects on calcium homeostasis and bone metabolism but recent studies suggest a much broader role for this secosteroid in human health. Key components of the vitamin D system, notably the vitamin D receptor (VDR) and the vitamin D-activating enzyme (1α-hydroxylase), are present in a wide array of tissues, notably macrophages, dendritic cells and T lymphocytes (T cells) from the immune system. Thus, serum 25-hydroxyvitamin D (25D) can be converted to hormonal 1,25-dihydroxyvitamin D (1,25D) within immune cells, and then interact with VDR and promote transcriptional and epigenomic responses in the same or neighbouring cells. These intracrine and paracrine effects of 1,25D have been shown to drive antibacterial or antiviral innate responses, as well as to attenuate inflammatory T cell adaptive immunity. Beyond these mechanistic observations, association studies have reported the correlation between low serum 25D levels and the risk and severity of human immune disorders including autoimmune diseases such as inflammatory bowel disease, multiple sclerosis, type 1 diabetes and rheumatoid arthritis. The proposed explanation for this is that decreased availability of 25D compromises immune cell synthesis of 1,25D leading to impaired innate immunity and over-exuberant inflammatory adaptive immunity. The aim of the current review is to explore the mechanistic basis for immunomodulatory effects of 25D and 1,25D in greater detail with specific emphasis on how vitamin D-deficiency (low serum levels of 25D) may lead to dysregulation of macrophage, dendritic cell and T cell function and increase the risk of inflammatory autoimmune disease.

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S Westra Department of Internal Medicine, Medical Centre Alkmaar, Alkmaar, the Netherlands

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Y H M Krul-Poel Department of Internal Medicine, Medical Centre Alkmaar, Alkmaar, the Netherlands

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H J van Wijland Department of General Practice, DIAZON, Alkmaar, the Netherlands

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M M ter Wee Department of Epidemiology and Biostatistics, VU Medical Centre, Amsterdam, the Netherlands

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F Stam Department of Internal Medicine, Medical Centre Alkmaar, Alkmaar, the Netherlands

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P Lips Department of Internal Medicine, Endocrine Section, VU Medical Centre, Amsterdam, the Netherlands

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F Pouwer Department of Medical and Clinical Psychology, Tilburg University, Tilburg, the Netherlands

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S Simsek Department of Internal Medicine, Medical Centre Alkmaar, Alkmaar, the Netherlands

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Objective

Increased levels of depressive symptoms, fatigue or pain (all dimensions of reduced health-related quality of life (HRQOL)) are common in people with type 2 diabetes mellitus (DM). Earlier studies have reported associations between low vitamin D status and fatigue and depressive symptoms. The aim of the present study was to examine the effects of vitamin D supplementation on dimensions of HRQOL in people with type 2 DM.

Design

Randomised, double-blind, placebo-controlled trial.

Methods

The effect of monthly cholecalciferol 50,000 IU vs placebo on HRQOL was assessed in 275 adults with type 2 DM derived from general practices. HRQOL at baseline and after six months using the Short Form 36 Health Survey (SF-36) was collected. Linear regression analyses were used to compare the change in HRQOL over time between the vitamin D and placebo group.

Results

187/275 (68%) completed baseline and follow-up SF-36 and were included in the analysis. Median serum 25-hydroxyvitamin D almost doubled in the intervention group compared to that in the placebo group (58.5–106.0 nmol/L vs 60.0–61.5 nmol/L, respectively). A small significant difference (adjusted B: −8.90; 95% CI: −17.16 to −0.65) between both groups was seen concerning the SF-36 domain role limitations due to physical problems in disadvantage of the vitamin D group.

Conclusions

Six months of vitamin D supplementation did not improve HRQOL in non-vitamin D-deficient people with type 2 DM managed on oral antidiabetic therapy.

Open access
Gabriella Oliveira Lima Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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Alex Luiz Menezes da Silva Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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Julianne Elba Cunha Azevedo Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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Chirlene Pinheiro Nascimento Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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Luana Rodrigues Vieira Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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Akira Otake Hamoy Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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Luan Oliveira Ferreira Laboratory of Experimental Neuropathology, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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Verônica Regina Lobato Oliveira Bahia Multidisciplinary Laboratory of Animal Morphology, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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Nilton Akio Muto Amazon Bioactive Compounds Valorization Center, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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Dielly Catrina Favacho Lopes Laboratory of Experimental Neuropathology, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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Moisés Hamoy Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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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.

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Mirjam M Oosterwerff Departments of Internal Medicine, Epidemiology and Biostatistics, Public and Occupational Health, Endocrine Section

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Rosa Meijnen Departments of Internal Medicine, Epidemiology and Biostatistics, Public and Occupational Health, Endocrine Section

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Natasja M Van Schoor Departments of Internal Medicine, Epidemiology and Biostatistics, Public and Occupational Health, Endocrine Section

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Dirk L Knol Departments of Internal Medicine, Epidemiology and Biostatistics, Public and Occupational Health, Endocrine Section

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Mark H H Kramer Departments of Internal Medicine, Epidemiology and Biostatistics, Public and Occupational Health, Endocrine Section

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Mireille N M Van Poppel Departments of Internal Medicine, Epidemiology and Biostatistics, Public and Occupational Health, Endocrine Section

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Paul Lips Departments of Internal Medicine, Epidemiology and Biostatistics, Public and Occupational Health, Endocrine Section

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E Marelise W Eekhoff Departments of Internal Medicine, Epidemiology and Biostatistics, Public and Occupational Health, Endocrine Section

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Vitamin D deficiency is highly prevalent among non-western immigrants in The Netherlands and associated with poor physical performance. The aim of this study was to assess the effect of vitamin D supplementation on physical performance, exercise capacity, and daily physical activity in vitamin D-deficient, overweight non-western immigrants. A randomized double-blind, placebo-controlled trial was conducted to assess the effect of vitamin D on physical performance. A total of 130 participants were included. Eligibility criteria included overweight (BMI >27 kg/m2), 25-hydroxy vitamin D (25(OH)D) ≤50 nmol/l, and an age range of 20–65 years. The intervention group received 1200 IU vitamin D3 daily for 4 months; the control group received placebo. Both groups received 500 mg calcium daily. Outcome measures included physical performance (physical performance score), exercise capacity (a 6-min walk test (6-MWT)), and daily physical activity (questionnaire and accelerometer). There was no significant effect on physical performance, exercise capacity, or physical activity in the intention to treat analysis. In an explorative post hoc analysis restricted to participants reaching a serum 25(OH)D concentration of >60 nmol/l after intervention, there was an improvement of 19 m in the 6-MWT compared with the control group (P=0.053). Moderate dose vitamin D supplementation did not significantly improve physical performance, exercise capacity, or physical activity. However, when 25(OH)D concentrations reached >60 nmol/l after intervention, there was a borderline significant improvement in exercise capacity. Although the clinical relevance is not clear, this is a promising result, as all participants were overweight and did not improve their overall activity levels.

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Göran Oleröd Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Lillemor Mattsson Hultén Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden

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Ola Hammarsten Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Eva Klingberg Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Purpose

Serum 25-hydroxy vitamin D [25(OH)D] varies greatly with season at northern latitudes. The purpose of this study was to determine if the seasonal variations in serum total 25(OH)D are followed by a concomitant variation in free 25(OH)D or if the variation is damped by alterations in the binding capacity of DBP.

Methods

Serum was collected from 540 healthy blood donors (60% men; mean age 41 ± 13 years) during 12 months and analyzed for total 25(OH)D, directly measured free 25(OH)D, vitamin D-binding protein (DBP) and albumin. Calculated free 25(OH)D was estimated.

Results

The UV-B radiation during the sampling month was positively correlated with the serum levels of total 25(OH)D (r = 0.355, P < 0.001), directly measured free (r = 0.336, P < 0.001) and calculated free 25(OH)D (r = 0.275, P < 0.001), but not with DBP and albumin. The percentage of free 25(OH)D was higher during the winter months than that during the summer months (0.020 ± 0.005% vs 0.019 ± 0.004%; P = 0.007) and higher in participants with a serum 25(OH)D below 25 nmol/L than that in participants with a serum 25(OH)D above 75 nmol/L (0.031 ± 0.007% vs 0.017 ± 0.003%; P < 0.001). iPTH was correlated with directly measured free 25(OH)D (r = −0.226; P < 0.001), but only weakly with calculated free 25(OH)D (r = −0.095; P = 0.027).

Conclusions

Directly measured free serum 25(OH)D was highly correlated with total serum 25(OH)D and followed the same seasonal variation, whereas the serum concentrations of DBP and albumin were stable. The fluctuation in free 25(OH)D was only marginally damped with an increase in the percentage of free 25(OH)D during the winter months and in participants with vitamin D deficiency.

Open access
Stan Ursem Department of Clinical Chemistry, Amsterdam Gastroenterology & Metabolism, Amsterdam UMC, Vrije Universiteit Amsterdam, Endocrine Laboratory, Amsterdam, Netherlands

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Vito Francic Division of Endocrinology and Diabetology, Department of Internal Medicine, Endocrinology Lab Platform, Medical University of Graz, Graz, Austria

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Martin Keppel University Institute for Medical and Chemical Laboratory Diagnostics, Paracelsus Medical University, Salzburg, Austria

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Verena Schwetz Division of Endocrinology and Diabetology, Department of Internal Medicine, Endocrinology Lab Platform, Medical University of Graz, Graz, Austria

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Christian Trummer Division of Endocrinology and Diabetology, Department of Internal Medicine, Endocrinology Lab Platform, Medical University of Graz, Graz, Austria

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Marlene Pandis Division of Endocrinology and Diabetology, Department of Internal Medicine, Endocrinology Lab Platform, Medical University of Graz, Graz, Austria

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Felix Aberer Division of Endocrinology and Diabetology, Department of Internal Medicine, Endocrinology Lab Platform, Medical University of Graz, Graz, Austria

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Martin R Grübler Division of Endocrinology and Diabetology, Department of Internal Medicine, Endocrinology Lab Platform, Medical University of Graz, Graz, Austria

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Nicolas D Verheyen Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

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Winfried März Synlab Academy, Synlab Holding Germany GmbH, München, Germany

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Andreas Tomaschitz Specialist Clinic of Rehabilitation Bad Gleichenberg, Bad Gleichenberg, Austria

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Stefan Pilz Division of Endocrinology and Diabetology, Department of Internal Medicine, Endocrinology Lab Platform, Medical University of Graz, Graz, Austria

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Barbara Obermayer-Pietsch Division of Endocrinology and Diabetology, Department of Internal Medicine, Endocrinology Lab Platform, Medical University of Graz, Graz, Austria

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Annemieke C Heijboer Department of Clinical Chemistry, Amsterdam Gastroenterology & Metabolism, Amsterdam UMC, Vrije Universiteit Amsterdam, Endocrine Laboratory, Amsterdam, Netherlands
Department of Clinical Chemistry, Amsterdam Gastroenterology & Metabolism, Amsterdam UMC, University of Amsterdam, Endocrine Laboratory, Amsterdam, Netherlands

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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.

Open access
Magdalena Zgliczyńska Department of Obstetrics, Perinatology and Neonatology, Centre of Postgraduate Medical Education, Cegłowska, Warsaw, Poland

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Magdalena Ostrowska Department of Endocrinology, Centre of Postgraduate Medical Education, Cegłowska, Warsaw, Poland

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Kinga Żebrowska Department of Obstetrics, Perinatology and Neonatology, Centre of Postgraduate Medical Education, Cegłowska, Warsaw, Poland

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Iwona Szymusik Department of Obstetrics, Perinatology and Neonatology, Centre of Postgraduate Medical Education, Cegłowska, Warsaw, Poland

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Konrad Kowalski Masdiag Sp. z o.o., Stefana Żeromskiego, Warsaw, Poland

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Dorota Leszczyńska Department of Endocrinology, Centre of Postgraduate Medical Education, Cegłowska, Warsaw, Poland

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Katarzyna Kosińska-Kaczyńska Department of Obstetrics, Perinatology and Neonatology, Centre of Postgraduate Medical Education, Cegłowska, Warsaw, Poland

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Objective

Vitamin D plays an important role during pregnancy. The aim was to compare vitamin D status in a group of singleton (SP) and twin pregnancies (TP) using two diagnostic methods: chemiluminescence immunoassay (CLIA) and liquid chromatography with tandem mass spectrometry (LC-MS/MS).

Design

This is a cross-sectional study.

Methods

The study was conducted in the population of SP and TP at the gestational age above 20 + 0 at the Bielanski Hospital in Warsaw, Poland, between October 2020 and January 2023. All patients had their venous blood samples collected and were given an original survey containing questions on demography and vitamin D supplementation.

Results

The study group included 53 Caucasian women with SP and 78 with TP aged from 21 to 47. Considering LC-MS/MS, patients with TP had lower concentrations of 25-hydroxyvitamin D (25(OH)D) than patients with SP. However, no significant difference was observed in the frequency of the occurrence of vitamin D deficiency (25(OH)D < 30 ng/mL). In both groups, the levels obtained with CLIA were significantly lower than in case of LC-MS/MS, however, strongly correlated. The intermethod agreement accounted for 52.4% and the Cohen’s kappa coefficient was 0.142.

Conclusions

The concentration of 25(OH)D in pregnant women depends on the type of gestation (SP/TP) and on the diagnostic methods used (CLIA/LC-MS/MS). Based on LC-MS/MS, the incidence of vitamin D deficiency was low in our group and no differences occurred in its frequency between SP and TP. The intermethod agreement between CLIA and LC-MS/MS on the detection of vitamin D deficiency was low.

Significance statement

This is the first study to compare the concentration of 25(OH)D levels between SP and TP using two methods: CLIA and the gold standard – LC-MS/MS. Based on LC-MS/MS, a low incidence of vitamin D deficiency was observed in our group, in which the vast majority of patients took cholecalciferol supplements. Moreover, there were no differences in its frequency between SP and TP. However, the 25(OH)D level was significantly lower in TP. The intermethod agreement between CLIA and LC-MS/MS on the detection of vitamin D deficiency was low, which is associated with substantial clinical implications.

Open access
Bingbing Wang Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA

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Mayra Cruz Ithier Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA

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Nataliya Parobchak Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA

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Stacy M Yadava Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA

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Jay Schulkin Department of Obstetrics, Gynecology, University of Washington, Seattle, Washington, USA

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Todd Rosen Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA

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Maternal vitamin D deficiency is linked to adverse pregnancy outcomes including spontaneous preterm birth (SPB). Placental corticotropin-releasing hormone (CRH) has been proposed to be part of a clock that governs the length of gestation in humans, with elevated maternal serum levels predicting early delivery. In this study, we test the hypothesis that vitamin D could contribute to the prevention of preterm labor by inhibiting CRH and other pro-labor mediators. The biological activity of vitamin D occurs via two pathways: non-genomic and genomic responses, both of which involve binding of 1,25-dihydroxyvitamin D (1,25(OH)2D), the active metabolite of vitamin D binding to the vitamin D receptor (VDR). By using chromatin immunoprecipitation followed by sequencing (ChIP-seq), we found that 1,25(OH)2D stimulates association of VDR with a number of miRNA genes including MIR181B2 and MIR26B, and their mature products miR-181b-5p and miR-26b-5p are predicted to target CRH and cyclooxygenase-2 (COX-2) mRNA at 3′-untranslated region (UTR), respectively. We performed RT-qPCR analysis to validate that expression of mature miR-181b-5p and miR-26b-5p in term human syncytiotrophoblast increased in response to treatment with 1,25(OH)2D. miR-181b-5p- or miR-26b-5p-mediated inhibition of CRH or COX-2 was further assessed by the use of miRNA mimics/inhibitors and a luciferase reporter assay. Taken together, this study has identified novel mechanisms by which vitamin D downregulates pro-labor genes and could lower the risk of preterm delivery.

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Gunjan Garg Departments of Endocrinology, Obstetrics and Gynecology, Biostatics

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Garima Kachhawa Departments of Endocrinology, Obstetrics and Gynecology, Biostatics

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Rekha Ramot Departments of Endocrinology, Obstetrics and Gynecology, Biostatics

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Rajesh Khadgawat Departments of Endocrinology, Obstetrics and Gynecology, Biostatics

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Nikhil Tandon Departments of Endocrinology, Obstetrics and Gynecology, Biostatics

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V Sreenivas Departments of Endocrinology, Obstetrics and Gynecology, Biostatics

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Alka Kriplani Departments of Endocrinology, Obstetrics and Gynecology, Biostatics

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N Gupta Departments of Endocrinology, Obstetrics and Gynecology, Biostatics

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To assess the effect of vitamin D supplementation on parameters of insulin sensitivity/resistance (IS/IR) and insulin secretion in subjects with polycystic ovarian syndrome (PCOS). A prospective double-blind randomized control trial was conducted to assess the effect of vitamin D on insulin kinetics in women with PCOS. The trial was conducted in a tertiary care research hospital. A total of 36 subjects with PCOS, aged 18–35 years, were included in this study. Vitamin D3 4000 IU/day versus placebo was given once a month for 6 months and both groups received metformin. IS (by whole-body IS index or Matsuda index), IR (by homeostasis model assessment IR (HOMA-IR)), and insulin secretion (by insulinogenic index; II30) were the main outcome measures. Secondary outcome included blood pressure (BP), lipid profile, disposition index (DI), and vascular stiffness. Out of 36 subjects who consented, 32 completed the study. Subjects were randomized into two groups: group A (n=15; metformin and vitamin D 4000 IU/day) or group B (n=17; metformin and placebo). Oral glucose tolerance tests with 75 g glucose were carried out at baseline and 6 months after supplementation. Hypovitaminosis D was observed in 93.8% of all subjects with mean serum 25 hydroxy vitamin D level of 7.30±4.45 ng/ml. After 6 months of vitamin D supplementation, there was no significant difference in any of the parameters of IS/IR (area under curve (AUC)–glucose, AUC–insulin, insulin:glucose ratio, HOMA-IR, Matsuda index, insulinogenic index, and DI), II30, and cardiovascular risk factors between the two groups. Supplementation of vitamin D, at a dose of 4000 IU/day for 6 months, did not have any significant effect on parameters of IS/IR and insulin secretion in subjects with PCOS.

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