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Marie Reeberg Sass Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Nicolai Jacob Wewer Albrechtsen Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark

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Jens Pedersen Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Department of Endocrinology and Nephrology, Nordsjællands University Hospital, Hillerød, Denmark

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Kristine Juul Hare Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Nis Borbye-Lorenzen Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Center for Neonatal Screening, Department of Congenital Disorders, Statens Serum Institute, Copenhagen, Denmark

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Katalin Kiss Department of Pathology, Rigshospitalet, Copenhagen, Denmark

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Tina Vilsbøll Steno Diabetes Center Copenhagen, Gentofte, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark

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Filip Krag Knop Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Steno Diabetes Center Copenhagen, Gentofte, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark

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Steen Seier Poulsen Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Niklas Rye Jørgensen Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Jens Juul Holst Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Cathrine Ørskov Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Bolette Hartmann Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Objective:

Parathyroid hormone (PTH) is a key hormone in regulation of calcium homeostasis and its secretion is regulated by calcium. Secretion of PTH is attenuated during intake of nutrients, but the underlying mechanism(s) are unknown. We hypothesized that insulin acts as an acute regulator of PTH secretion.

Methods:

Intact PTH was measured in plasma from patients with T1D and matched healthy individuals during 4-h oral glucose tolerance tests (OGTT) and isoglycemic i.v. glucose infusions on 2 separate days. In addition, expression of insulin receptors on surgical specimens of parathyroid glands was assessed by immunochemistry (IHC) and quantitative PCR (qPCR).

Results:

The inhibition of PTH secretion was more pronounced in healthy individuals compared to patients with T1D during an OGTT (decrementalAUC0–240min: −5256 ± 3954 min × ng/L and −2408 ± 1435 min × ng/L, P = 0.030). Insulin levels correlated significantly and inversely with PTH levels, also after adjusting for levels of several gut hormones and BMI (P = 0.002). Expression of insulin receptors in human parathyroid glands was detected by both IHC and qPCR.

Conclusion:

Our study suggests that insulin may act as an acute regulator of PTH secretion in humans.

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Glenville Jones Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, Ontario, Canada

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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.

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Huma Qamar Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada
Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada

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Nandita Perumal Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada
Department of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada

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Eszter Papp Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada

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Alison D Gernand Department of Nutritional Sciences, Pennsylvania State University, University Park, Pennsylvania, USA

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Abdullah Al Mahmud Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research (icddr,b), Dhaka, Bangladesh

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Daniel E Roth Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada
Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada
Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada

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Intrauterine growth restriction (IUGR) reflects inadequate growth in-utero and is prevalent in low resource settings. This study aimed to assess the association of maternal delivery parathyroid hormone (PTH) – a regulator of bone turnover and calcium homeostasis – with newborn anthropometry, to identify regulators of PTH, and to delineate pathways by which maternal PTH regulates birth size using path analysis. This was a cross-sectional analysis of data from participants (n = 537) enrolled in the Maternal Vitamin D for Infant Growth trial in Dhaka, Bangladesh. Primary exposures were maternal delivery intact PTH (iPTH) or whole PTH (wPTH) and outcomes were gestational age- and sex-standardized z-scores for birth length (LAZ), weight (WAZ), and head circumference (HCAZ). Hypothesized regulators of PTH included calcium and protein intake, vitamin D, magnesium, fibroblast-like growth factor-23 (FGF23), and C-reactive protein. Maternal iPTH was not associated with birth size in linear regression analyses; however, in path analysis models, every SD increase in log(iPTH) was associated with 0.08SD (95% CI: 0.002, 0.162) higher LAZ. In linear regression and path analysis models, wPTH was positively associated with WAZ. Vitamin D suppressed PTH, while FGF23 was positively associated with PTH. In path analysis models, higher magnesium was negatively associated with LAZ; FGF23 was positively associated and protein intake was negatively associated with LAZ, WAZ, and HCAZ. Higher maternal PTH in late pregnancy is unlikely to contribute to IUGR. Future studies should investigate maternal FGF23, magnesium and protein intake as regulators of fetal growth, particularly in settings where food insecurity and IUGR are public health problems.

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Laura J Reid Edinburgh Centre for Endocrinology and Diabetes, Royal Infirmary of Edinburgh, Edinburgh, UK

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Bala Muthukrishnan Edinburgh Centre for Endocrinology and Diabetes, Royal Infirmary of Edinburgh, Edinburgh, UK

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Dilip Patel Department of Radiology, Royal Infirmary of Edinburgh, Edinburgh, UK

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Mike S Crane Department of Clinical Biochemistry, Royal Infirmary of Edinburgh, Edinburgh, UK

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Murat Akyol Department of Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK

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Andrew Thomson Department of Pathology, Royal Infirmary of Edinburgh, Edinburgh, UK

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Jonathan R Seckl Edinburgh Centre for Endocrinology and Diabetes, Royal Infirmary of Edinburgh, Edinburgh, UK
Centre for Cardiovascular Science, Queen’s Medical Research Unit, University of Edinburgh, Edinburgh, UK

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Fraser W Gibb Edinburgh Centre for Endocrinology and Diabetes, Royal Infirmary of Edinburgh, Edinburgh, UK

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Objective

Primary hyperparathyroidism (PHPT) is a common reason for referral to endocrinology but the evidence base guiding assessment is limited. We evaluated the clinical presentation, assessment and subsequent management in PHPT.

Design

Retrospective cohort study.

Patients

PHPT assessed between 2006 and 2014 (n = 611) in a university hospital.

Measurements

Symptoms, clinical features, biochemistry, neck radiology and surgical outcomes.

Results

Fatigue (23.8%), polyuria (15.6%) and polydipsia (14.9%) were associated with PHPT biochemistry. Bone fracture was present in 16.4% but was not associated with biochemistry. A history of nephrolithiasis (10.0%) was associated only with younger age (P = 0.006) and male gender (P = 0.037). Thiazide diuretic discontinuation was not associated with any subsequent change in calcium (P = 0.514). Urine calcium creatinine clearance ratio (CCCR) was <0.01 in 18.2% of patients with confirmed PHPT. Older age (P < 0.001) and lower PTH (P = 0.043) were associated with failure to locate an adenoma on ultrasound (44.0% of scans). When an adenoma was identified on ultrasound the lateralisation was correct in 94.5%. Non-curative surgery occurred in 8.2% and was greater in those requiring more than one neck imaging modality (OR 2.42, P = 0.035).

Conclusions

Clinical features associated with PHPT are not strongly related to biochemistry. Thiazide cessation does not appear to attenuate hypercalcaemia. PHPT remains the likeliest diagnosis in the presence of low CCCR. Ultrasound is highly discriminant when an adenoma is identified but surgical failure is more likely when more than one imaging modality is required.

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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.

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Mengting Yin Sichuan University West China Hospital, Chengdu, China

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Qianhui Liu Sichuan University West China Hospital, Chengdu, China

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Qingzhong Wang Jintang First People’s Hospital, West China Hospital Sichuan University Jingtang Hospital, Chengdu, China

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Yong He Sichuan University West China Hospital, Chengdu, China

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Haolan Song Sichuan University West China Hospital, Chengdu, China

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Xin Nie Sichuan University West China Hospital, Chengdu, China

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Guixing Li Sichuan University West China Hospital, Chengdu, China

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Background

The diagnosis of primary hyperparathyroidism (PHPT) remains a challenge because of increased asymptomatic PHPT or patients with normocalcaemic PHPT (NPHPT). In addition, some primary hospitals in China have no equipment to measure parathyroid hormone (PTH) levels. Therefore, an additional, simple, and inexpensive laboratory biochemical marker is urgently needed. The calcium/phosphate (Ca/P) ratio and chloride/phosphate (Cl/P) ratio have been proposed as suitable tools to diagnose PHPT in Europe; however, the Ca/P ratio has never been tested in China. We aimed to conduct a confirmatory study to explore the diagnostic performance of the Ca/P ratio for PHPT in China.

Methods

From January 2015 to December 2020, a total of 155 patients who underwent parathyroidectomy (143 PHPT patients and 12 NPHPT patients) and 153 controls were enrolled in this single-center , retrospective study. Serum calcium, phosphate, parathyroid hormone, 25-hydroxyvitamin vitamin D (25(OH) vitamin D), chloride, alanine transaminase (ALT), aspartate aminotransaminase (AST), estimated glomerular filtration rate (eGFR), and creatinine levels were recorded for all the study participants. Pairwise comparisons were made between groups, and the diagnostic performance of the Ca/P ratio was determined using receiver-operating characteristic (ROC) analysis.

Results

Patients with PHPT had a higher Ca/P ratio than controls (P < 0.001). A Ca/P ratio above 2.94 with a sensitivity of 95.5% and specificity of 98.7% can distinguish PHPT patients from healthy individuals. This index was positively correlated with the PTH level (r = 0.875, P < 0.001).

Conclusion

The Ca/P ratio is an ideal and inexpensive indicator for diagnosing PHPT in China when using a cut-off value of 2.94.

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Qian Wang Department of Thyroid and Neck Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Jiacheng Wang Department of Thyroid and Neck Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Yunhui Xin Department of Thyroid and Neck Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Ziyang He Department of Thyroid and Neck Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Xiang Zhou Department of Pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Xing Liu Department of Thyroid and Neck Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Teng Zhao Department of Thyroid and Neck Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Lihan He Department of Thyroid and Neck Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Hong Shen Department of Thyroid and Neck Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Mulan Jin Department of Pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Bojun Wei Department of Thyroid and Neck Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Background

Parathyroid carcinoma (PC), often misdiagnosed as a parathyroid adenoma (PA), is prone to local relapse due to the initial surgery being restricted to parathyroid lesions instead of en bloc resection of parathyroid lesions with negative incision margins. However, it is very challenging to distinguish PC from PA preoperatively; hence, this study investigated an effective biomarker for increasing accuracy in PC diagnosis.

Method

First, the differentially expressed circular RNAs between three PC tissues and three PA tissues were screened by high-throughput circular RNA sequencing, and the expression of hsa_circ_0005729 was verified by qRT-PCR in 14 patients with PC and 40 patients with PA. Secondly, the receiver operating characteristic curve and the area under the curve (AUC) were used to analyze the diagnostic efficiency of hsa_circ_0005729 in PC by combining with laboratory data. Thirdly, RNF138mRNA, the corresponding linear transcript of hsa_circ_0005729, was measured, and the relationship between hsa_circ_0005729 and RNF138 mRNA was analyzed in patients with PA and patients with PC.

Results

Hsa_circ_0005729 expression was significantly higher in patients with PC than in patients with PA. Serum calcium (P  = 0.045), alkaline phosphatase (ALP) (P  = 0.048), and creatinine levels (P  = 0.036) were significantly higher in patients with PC than in patients with PA. The AUC increased to 0.86 when hsa_circ_0005729 combined with serum calcium, creatinine, and ALP. In addition, hsa_circ_0005729 was positively correlated with RNF138 mRNA in patients with PA but not in patients with PC.

Conclusion

The novel circular RNA hsa_circ_0005729 was found to have a higher expression in patients with PC, indicating its usefulness for distinguishing PC from PA.

Open access
Heng Yeh Department of Emergency Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
College of Medicine, Chang Gung University, Taoyuan, Taiwan

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Hsuan Yeh College of Medicine, Chang Gung University, Taoyuan, Taiwan
Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan

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Chun-Cheng Chiang College of Medicine, Chang Gung University, Taoyuan, Taiwan
Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan

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Ju-Ching Yen College of Medicine, China Medical University, Taichung, Taiwan

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I-Kuan Wang College of Medicine, China Medical University, Taichung, Taiwan
Department of Nephrology, China Medical University Hospital, Taichung, Taiwan

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Shou-Hsuan Liu College of Medicine, Chang Gung University, Taoyuan, Taiwan
Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan

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Cheng-Chia Lee College of Medicine, Chang Gung University, Taoyuan, Taiwan
Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan

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Cheng-Hao Weng College of Medicine, Chang Gung University, Taoyuan, Taiwan
Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan

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Wen-Hung Huang College of Medicine, Chang Gung University, Taoyuan, Taiwan
Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan

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Ching-Wei Hsu College of Medicine, Chang Gung University, Taoyuan, Taiwan
Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan

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Tzung-Hai Yen College of Medicine, Chang Gung University, Taoyuan, Taiwan
Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan

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Secondary hyperparathyroidism (SHPT) is a common complication of end-stage kidney disease (ESKD). Hungry bone syndrome (HBS) occurs frequently in patients on maintenance dialysis receiving parathyroidectomy for refractory SHPT. However, there is scanty study investigating the clinical risk factors that predict postoperative HBS, and its outcome in peritoneal dialysis (PD) patients. We conducted a single-center retrospective study to analyze 66 PD patients who had undergone parathyroidectomy for secondary hyperparathyroidism at Chang Gung Memorial Hospital between 2009 and 2019. The patients were stratified into two groups based on the presence (n=47) or absence (n=19) of HBS after parathyroidectomy. Subtotal parathyroidectomy was the most common surgery performed (74.2%), followed by total parathyroidectomy with autoimplantation (25.8%). Pathological examination of all surgical specimens revealed parathyroid hyperplasia (100%). Patients with HBS had lower levels of postoperative nadir corrected calcium, higher alkaline phosphate (ALP), and higher potassium levels compared with patients without HBS (all P<0.05). A multivariate logistic regression model confirmed that lower preoperative serum calcium level (OR 0.354, 95% CI 0.133–0.940, P=0.037), higher ALP (OR 1.026, 95% CI 1.008–1.044, P=0.004), and higher potassium level (OR 6.894, 95% CI 1.806–26.317, P=0.005) were associated with HBS after parathyroidectomy. Patients were followed for 58.2±30.8 months after the surgery. There was no significant difference between HBS and non-HBS groups in persistence (P=0.496) or recurrence (P=1.000) of hyperparathyroidism. The overall mortality rate was 10.6% with no significant difference found between both groups (P=0.099). We concluded that HBS is a common complication (71.2%) of parathyroidectomy for SHPT and should be managed appropriately.

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Eeva M Ryhänen
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Ilkka Heiskanen
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Harri Sintonen Endocrinology, Department of Public Health, Group Administration, Helsinki University Hospital, University of Eastern Finland, Abdominal Center, University of Helsinki and Helsinki University Hospital, Post Box 340, FI-00290 Helsinki, Finland

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Matti J Välimäki
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Risto P Roine Endocrinology, Department of Public Health, Group Administration, Helsinki University Hospital, University of Eastern Finland, Abdominal Center, University of Helsinki and Helsinki University Hospital, Post Box 340, FI-00290 Helsinki, Finland
Endocrinology, Department of Public Health, Group Administration, Helsinki University Hospital, University of Eastern Finland, Abdominal Center, University of Helsinki and Helsinki University Hospital, Post Box 340, FI-00290 Helsinki, Finland
Endocrinology, Department of Public Health, Group Administration, Helsinki University Hospital, University of Eastern Finland, Abdominal Center, University of Helsinki and Helsinki University Hospital, Post Box 340, FI-00290 Helsinki, Finland

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Camilla Schalin-Jäntti
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Health-related quality of life (HRQoL) is frequently impaired in primary hyperparathyroidism (PHPT) but it is unclear if surgery is beneficial. The objective was to prospectively assess HRQoL in PHPT (n=124) with the 15D instrument before and after surgery, to compare it with that of a comparable sample of the general population (n=4295), and search for predictors of HRQoL and its change. HRQoL, and clinical and laboratory parameters were measured before and at 6 and 12 months after surgery. Regression techniques were used to search for predictors of HRQoL and gains from treatment. Before surgery, PHPT patients had significantly lower mean 15D score compared to controls (0.813 vs 0.904, P<0.001). Excretion, mental function, discomfort and symptoms, distress, depression, vitality, and sexual activity were most impaired (all P<0.001). Number of medications (P=0.001) and subjective symptoms (P<0.05) but not calcium or parathyroid hormone (PTH) predicted impaired HRQoL. Serum 25-hydroxyvitamin D (25OHD) was of borderline significance (P=0.051). Compared to baseline, mean 15D score improved significantly 6 months after surgery (0.813 vs 0.865, P<0.001) and the effect sustained at 1 year (0.878, P<0.001). The improvement was clinically important in 77.4% of patients (P<0.001). Educational level independently predicted improvement (P<0.005). HRQoL is severely impaired in PHPT but improves significantly after surgery. The 15D is a sensitive tool for assessing HRQoL and recognizing patients likely to benefit from surgery.

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Maria Angela D'amico Section of Human Morphology, Department of Medicine and Aging Sciences, G. d'Annunzio University of Chieti–Pescara, Via Dei Vestini 31, 66013 Chieti, Italy

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Barbara Ghinassi Section of Human Morphology, Department of Medicine and Aging Sciences, G. d'Annunzio University of Chieti–Pescara, Via Dei Vestini 31, 66013 Chieti, Italy

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Pascal Izzicupo Section of Human Morphology, Department of Medicine and Aging Sciences, G. d'Annunzio University of Chieti–Pescara, Via Dei Vestini 31, 66013 Chieti, Italy

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Lamberto Manzoli Section of Human Morphology, Department of Medicine and Aging Sciences, G. d'Annunzio University of Chieti–Pescara, Via Dei Vestini 31, 66013 Chieti, Italy

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A Di Baldassarre Section of Human Morphology, Department of Medicine and Aging Sciences, G. d'Annunzio University of Chieti–Pescara, Via Dei Vestini 31, 66013 Chieti, Italy

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Chromogranin A (CgA (CHGA)) is the major soluble protein co-stored and co-released with catecholamines and can function as a pro-hormone by giving rise to several bioactive peptides. This review summarizes the physiological functions, the pathogenic implications, and the recent use of these molecules as biomarkers in several pathological conditions. A thorough literature review of the electronic healthcare databases MEDLINE, from January 1985 to September 2013, was conducted to identify articles and studies concerned with CgA and its processing. The search strategies utilized keywords such as chromogranin A, vasostatins 1 and 2, chromofungin, chromacin, pancreastatin, catestatin, WE14, chromostatin, GE25, parastatin, and serpinin and was supplemented by the screening of references from included papers and review articles. A total of 209 English-language, peer-reviewed original articles or reviews were examined. The analysis of the retrospective literature suggested that CgA and its several bioactive fragments exert a broad spectrum of regulatory activities by influencing the endocrine, the cardiovascular, and the immune systems and by affecting the glucose or calcium homeostasis. As some peptides exert similar effects, but others elicit opposite responses, the regulation of the CgA processing is critical to maintain homeostasis, whereas an unbalanced production of peptides that exert opposing effects can have a pathogenic role in several diseases. These clinical implications entail that CgA and its derived peptides are now used as diagnostic and prognostic markers or to monitor the response to pharmacological intervention not only in endocrine tumors, but also in cardiovascular, inflammatory, and neuropsychiatric diseases.

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