Search Results

You are looking at 81 - 90 of 172 items for

  • Abstract: Bone x
  • Abstract: Mineral x
  • Abstract: Calcium x
  • Abstract: Hyperparathyroidism x
  • Abstract: Hypoparathyroidism x
  • Abstract: Skeleton x
Clear All Modify Search
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

Search for other papers by Jane Fletcher in
Google Scholar
PubMed
Close
,
Emma L Bishop Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK

Search for other papers by Emma L Bishop in
Google Scholar
PubMed
Close
,
Stephanie R Harrison Leeds Institute of Rheumatic and Musculoskeletal Medicine, Chapel Allerton Hospital, Leeds, UK

Search for other papers by Stephanie R Harrison in
Google Scholar
PubMed
Close
,
Amelia Swift School of Nursing, Institute of Clinical Sciences, University of Birmingham, Edgbaston, Birmingham, UK

Search for other papers by Amelia Swift in
Google Scholar
PubMed
Close
,
Sheldon C Cooper Gastroenterology Department, University Hospitals Birmingham NHS Trust, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham, UK

Search for other papers by Sheldon C Cooper in
Google Scholar
PubMed
Close
,
Sarah K Dimeloe Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK

Search for other papers by Sarah K Dimeloe in
Google Scholar
PubMed
Close
,
Karim Raza Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK

Search for other papers by Karim Raza in
Google Scholar
PubMed
Close
, and
Martin Hewison Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK

Search for other papers by Martin Hewison in
Google Scholar
PubMed
Close

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.

Open access
Mateo Amaya-Montoya School of Medicine, Universidad de los Andes, Bogotá, Colombia

Search for other papers by Mateo Amaya-Montoya in
Google Scholar
PubMed
Close
,
Daniela Duarte-Montero School of Medicine, Universidad de los Andes, Bogotá, Colombia

Search for other papers by Daniela Duarte-Montero in
Google Scholar
PubMed
Close
,
Luz D Nieves-Barreto School of Medicine, Universidad de los Andes, Bogotá, Colombia

Search for other papers by Luz D Nieves-Barreto in
Google Scholar
PubMed
Close
,
Angélica Montaño-Rodríguez School of Medicine, Universidad de los Andes, Bogotá, Colombia

Search for other papers by Angélica Montaño-Rodríguez in
Google Scholar
PubMed
Close
,
Eddy C Betancourt-Villamizar Team Foods, Bogotá, Colombia

Search for other papers by Eddy C Betancourt-Villamizar in
Google Scholar
PubMed
Close
,
María P Salazar-Ocampo School of Medicine, Universidad de los Andes, Bogotá, Colombia

Search for other papers by María P Salazar-Ocampo in
Google Scholar
PubMed
Close
, and
Carlos O Mendivil School of Medicine, Universidad de los Andes, Bogotá, Colombia
Fundación Santa Fe de Bogotá, Section of Endocrinology, Bogotá, Colombia

Search for other papers by Carlos O Mendivil in
Google Scholar
PubMed
Close

Data on dietary calcium and vitamin D intake from Latin America are scarce. We explored the main correlates and dietary sources of calcium and vitamin D in a probabilistic, population-based sample from Colombia. We studied 1554 participants aged 18–75 from five different geographical regions. Dietary intake was assessed by employing a 157-item semi-quantitative food frequency questionnaire and national and international food composition tables. Daily vitamin D intake decreased with increasing age, from 230 IU/day in the 18–39 age group to 184 IU/day in the 60–75 age group (P -trend < 0.001). Vitamin D intake was positively associated with socioeconomic status (SES) (196 IU/day in lowest vs 234 in highest SES, P-trend < 0.001), and with educational level (176 IU/day in lowest vs 226 in highest education level, P-trend < 0.001). Daily calcium intake also decreased with age, from 1376 mg/day in the 18–39 age group to 1120 mg/day in the 60–75 age group (P -trend < 0.001). Calcium intake was lowest among participants with only elementary education, but the absolute difference in calcium intake between extreme education categories was smaller than for vitamin D (1107 vs 1274 mg/day, P-trend = 0.023). Daily calcium intake did not correlate with SES (P -trend = 0.74). Eggs were the main source of overall vitamin D, albeit their contribution decreased with increasing age. Dairy products contributed at least 48% of dietary calcium in all subgroups, mostly from cheese-containing traditional foods. SES and education were the key correlates of vitamin D and calcium intake. These findings may contribute to shape public health interventions in Latin American countries.

Open access
Kelly Brewer Center for Molecular Oncology, University of Connecticut School of Medicine, Farmington, Connecticut, USA

Search for other papers by Kelly Brewer in
Google Scholar
PubMed
Close
,
Isabel Nip Center for Molecular Oncology, University of Connecticut School of Medicine, Farmington, Connecticut, USA

Search for other papers by Isabel Nip in
Google Scholar
PubMed
Close
,
Justin Bellizzi Center for Molecular Oncology, University of Connecticut School of Medicine, Farmington, Connecticut, USA

Search for other papers by Justin Bellizzi in
Google Scholar
PubMed
Close
,
Jessica Costa-Guda Center for Molecular Oncology, University of Connecticut School of Medicine, Farmington, Connecticut, USA
Center for Regenerative Medicine and Skeletal Development, Department of Reconstructive Sciences, University of Connecticut School of Dental Medicine, Farmington, Connecticut, USA

Search for other papers by Jessica Costa-Guda in
Google Scholar
PubMed
Close
, and
Andrew Arnold Center for Molecular Oncology, University of Connecticut School of Medicine, Farmington, Connecticut, USA
Division of Endocrinology and Metabolism, University of Connecticut School of Medicine, Farmington, Connecticut, USA

Search for other papers by Andrew Arnold in
Google Scholar
PubMed
Close

Objective

Primary hyperparathyroidism is most often caused by a sporadic single-gland parathyroid adenoma (PTA), a tumor type for which cyclin D1 is the only known and experimentally validated oncoprotein. However, the molecular origins of its frequent overexpression have remained mostly elusive. In this study, we explored a potential tumorigenic mechanism that could increase cyclin D1 stability through a defect in molecules responsible for its degradation.

Methods

We examined two tumor suppressor genes known to modulate cyclin D1 ubiquitination, PRKN and FBXO4 (FBX4), for evidence of classic two-hit tumor suppressor inactivation within a cohort of 82 PTA cases. We examined the cohort for intragenic inactivating and splice site mutations by Sanger sequencing and for locus-associated loss of heterozygosity (LOH) by microsatellite analysis.

Results

We identified no evidence of bi-allelic tumor suppressor inactivation of PRKN or FBXO4 via inactivating mutation or splice site perturbation, neither in combination with nor independent of LOH. Among the 82 cases, we encountered previously documented benign single nucleotide polymorphisms (SNPs) in 35 tumors at frequencies similar to those reported in the germlines of the general population. Eight cases exhibited intragenic LOH at the PRKN locus, in some cases extending to cover at least an additional 1.7 Mb of chromosome 6q25-26. FBXO4 was not affected by LOH.

Conclusion:

The absence of evidence for specific bi-allelic inactivation in PRKN and FBXO4 in this sizeable cohort suggests that these genes only rarely, if ever, serve as classic driver tumor suppressors responsible for the growth of PTAs.

Open access
Xiao-Ping Qi Department of Oncologic and Urologic Surgery, The 117th PLA Hospital, Wenzhou Medical University, Hangzhou, Zhejiang Province, China

Search for other papers by Xiao-Ping Qi in
Google Scholar
PubMed
Close
,
Jian-Zhong Peng Department of Dermatology, Hangzhou Third People’s Hospital, Hangzhou, Zhejiang Province, China

Search for other papers by Jian-Zhong Peng in
Google Scholar
PubMed
Close
,
Xiao-Wei Yang Department of Pediatrics, The First People’s Hospital of Wenling City, Wenling, Zhejiang Province, China

Search for other papers by Xiao-Wei Yang in
Google Scholar
PubMed
Close
,
Zhi-Lie Cao Department of Oncologic and Urologic Surgery, The 117th PLA Hospital, Wenzhou Medical University, Hangzhou, Zhejiang Province, China

Search for other papers by Zhi-Lie Cao in
Google Scholar
PubMed
Close
,
Xiu-Hua Yu Department of Oncologic and Urologic Surgery, The 117th PLA Hospital, Wenzhou Medical University, Hangzhou, Zhejiang Province, China

Search for other papers by Xiu-Hua Yu in
Google Scholar
PubMed
Close
,
Xu-Dong Fang Department of Oncologic and Urologic Surgery, The 117th PLA Hospital, Wenzhou Medical University, Hangzhou, Zhejiang Province, China

Search for other papers by Xu-Dong Fang in
Google Scholar
PubMed
Close
,
Da-Hong Zhang Department of Urologic Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang Province, China

Search for other papers by Da-Hong Zhang in
Google Scholar
PubMed
Close
, and
Jian-Qiang Zhao Department of Head and Neck Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province, China

Search for other papers by Jian-Qiang Zhao in
Google Scholar
PubMed
Close

Background

Cutaneous lichen amyloidosis (CLA) has been reported in some multiple endocrine neoplasia type 2A (MEN 2A) families affected by specific germline RET mutations C634F/G/R/W/Y or V804M, as a characteristic of the clinical manifestation in ‘MEN 2A with CLA’, one of four variants of MEN 2A, which was strictly located in the scapular region of the upper back.

Patient Findings

This study reports a large south-eastern Chinese pedigree with 17 individuals carrying the MEN 2A-harboring germline C611Y (c.1832G>A) RET mutation by Sanger sequencing. One individual presented MEN 2A-related clinical features, including typical CLA in the interscapular region; another individual exhibited neurological pruritus and scratching in the upper back but lacked CLA skin lesions. Both subjects presented with CLA or pruritic symptoms several years before the onset of medullary thyroid carcinoma (MTC) and/or pheochromocytoma. The remaining 15 RET mutation carriers did not exhibit CLA; of these, one presented with MTC and pheochromocytoma, nine with MTC only, two with elevated serum calcitonin and three younger subjects with normal serum calcitonin levels. This family’s clinical data revealed a later diagnosis of MTC (mean age, 45.9 (range: 23–73) years), a lower penetrance of pheochromocytoma (2/17, 11.8%) and CLA (1/17, 5.9%). However, no hyperparathyroidism and Hirschsprung disease were reported in this family.

Summary and Conclusions

This is the first description of a family with MEN 2A-related CLA due to a germline RET C611Y mutation, which might exhibit a novel and diversified genotype–phenotype spectrum in MEN 2A.

Open access
Elizaveta Mamedova Department of Neuroendocrinology and Bone Diseases, Endocrinology Research Center, Moscow, Russian Federation

Search for other papers by Elizaveta Mamedova in
Google Scholar
PubMed
Close
,
Natalya Mokrysheva Department of Parathyroid Diseases, Endocrinology Research Center, Moscow, Russian Federation

Search for other papers by Natalya Mokrysheva in
Google Scholar
PubMed
Close
,
Evgeny Vasilyev Department and Laboratory of Inherited Endocrine Disorders, Endocrinology Research Center, Moscow, Russian Federation

Search for other papers by Evgeny Vasilyev in
Google Scholar
PubMed
Close
,
Vasily Petrov Department and Laboratory of Inherited Endocrine Disorders, Endocrinology Research Center, Moscow, Russian Federation

Search for other papers by Vasily Petrov in
Google Scholar
PubMed
Close
,
Ekaterina Pigarova Department of Neuroendocrinology and Bone Diseases, Endocrinology Research Center, Moscow, Russian Federation

Search for other papers by Ekaterina Pigarova in
Google Scholar
PubMed
Close
,
Sergey Kuznetsov Department of Surgery, Endocrinology Research Center, Moscow, Russian Federation

Search for other papers by Sergey Kuznetsov in
Google Scholar
PubMed
Close
,
Nikolay Kuznetsov Department of Surgery, Endocrinology Research Center, Moscow, Russian Federation

Search for other papers by Nikolay Kuznetsov in
Google Scholar
PubMed
Close
,
Liudmila Rozhinskaya Department of Neuroendocrinology and Bone Diseases, Endocrinology Research Center, Moscow, Russian Federation

Search for other papers by Liudmila Rozhinskaya in
Google Scholar
PubMed
Close
,
Galina Melnichenko I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
Institute of Clinical Endocrinology, Endocrinology Research Center, Moscow, Russian Federation

Search for other papers by Galina Melnichenko in
Google Scholar
PubMed
Close
,
Ivan Dedov Endocrinology Research Center, Moscow, Russian Federation

Search for other papers by Ivan Dedov in
Google Scholar
PubMed
Close
, and
Anatoly Tiulpakov Department and Laboratory of Inherited Endocrine Disorders, Endocrinology Research Center, Moscow, Russian Federation

Search for other papers by Anatoly Tiulpakov in
Google Scholar
PubMed
Close

Background

Primary hyperparathyroidism (PHPT) is a relatively rare disorder among children, adolescents and young adults. Its development at an early age is suspicious for hereditary causes, though the need for routine genetic testing remains controversial.

Objective

To identify and describe hereditary forms of PHPT in patients with manifestation of the disease under 40 years of age.

Design

We enrolled 65 patients with PHPT diagnosed before 40 years of age. Ten of them had MEN1 mutation, and PHPT in them was the first manifestation of multiple endocrine neoplasia type 1 syndrome.

Methods

The other fifty-five patients underwent next-generation sequencing (NGS) of a custom-designed panel of genes, associated with PHPT (MEN1, CASR, CDC73, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2C, CDKN2D). In cases suspicious for gross CDC73 deletions multiplex ligation-dependent probe amplification was performed.

Results

NGS revealed six pathogenic or likely pathogenic germline sequence variants: four in CDC73 c.271C>T (p.Arg91*), c.496C>T (p.Gln166*), c.685A>T (p.Arg229*) and c.787C>T (p.Arg263Cys); one in CASR c.3145G>T (p.Glu1049*) and one in MEN1 c.784-9G>A. In two patients, MLPA confirmed gross CDC73 deletions. In total, 44 sporadic and 21 hereditary PHPT cases were identified. Parathyroid carcinomas and atypical parathyroid adenomas were present in 8/65 of young patients, in whom CDC73 mutations were found in 5/8.

Conclusions

Hereditary forms of PHPT can be identified in up to 1/3 of young patients with manifestation of the disease at <40 years of age. Parathyroid carcinomas or atypical parathyroid adenomas in young patients are frequently associated with CDC73 mutations.

Open access
Elena Pardi Endocrine Unit 2, Endocrinology Unit, Institute of Pathology, Department of Surgical, Department of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Pisa, Italy

Search for other papers by Elena Pardi in
Google Scholar
PubMed
Close
,
Stefano Mariotti Endocrine Unit 2, Endocrinology Unit, Institute of Pathology, Department of Surgical, Department of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Pisa, Italy

Search for other papers by Stefano Mariotti in
Google Scholar
PubMed
Close
,
Natalia S Pellegata Endocrine Unit 2, Endocrinology Unit, Institute of Pathology, Department of Surgical, Department of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Pisa, Italy

Search for other papers by Natalia S Pellegata in
Google Scholar
PubMed
Close
,
Katiuscia Benfini Endocrine Unit 2, Endocrinology Unit, Institute of Pathology, Department of Surgical, Department of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Pisa, Italy

Search for other papers by Katiuscia Benfini in
Google Scholar
PubMed
Close
,
Simona Borsari Endocrine Unit 2, Endocrinology Unit, Institute of Pathology, Department of Surgical, Department of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Pisa, Italy

Search for other papers by Simona Borsari in
Google Scholar
PubMed
Close
,
Federica Saponaro Endocrine Unit 2, Endocrinology Unit, Institute of Pathology, Department of Surgical, Department of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Pisa, Italy

Search for other papers by Federica Saponaro in
Google Scholar
PubMed
Close
,
Liborio Torregrossa Endocrine Unit 2, Endocrinology Unit, Institute of Pathology, Department of Surgical, Department of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Pisa, Italy

Search for other papers by Liborio Torregrossa in
Google Scholar
PubMed
Close
,
Antonello Cappai Endocrine Unit 2, Endocrinology Unit, Institute of Pathology, Department of Surgical, Department of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Pisa, Italy

Search for other papers by Antonello Cappai in
Google Scholar
PubMed
Close
,
Chiara Satta Endocrine Unit 2, Endocrinology Unit, Institute of Pathology, Department of Surgical, Department of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Pisa, Italy

Search for other papers by Chiara Satta in
Google Scholar
PubMed
Close
,
Marco Mastinu Endocrine Unit 2, Endocrinology Unit, Institute of Pathology, Department of Surgical, Department of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Pisa, Italy

Search for other papers by Marco Mastinu in
Google Scholar
PubMed
Close
,
Claudio Marcocci Endocrine Unit 2, Endocrinology Unit, Institute of Pathology, Department of Surgical, Department of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Pisa, Italy

Search for other papers by Claudio Marcocci in
Google Scholar
PubMed
Close
, and
Filomena Cetani Endocrine Unit 2, Endocrinology Unit, Institute of Pathology, Department of Surgical, Department of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Pisa, Italy

Search for other papers by Filomena Cetani in
Google Scholar
PubMed
Close

Inactivating germline mutations of the CDKN1B gene encoding the nuclear cyclin-dependent kinase inhibitor P27kip1 protein have been reported in patients with multiple endocrine neoplasia type 4 (MEN4), a MEN1-like phenotype without MEN1 mutations. The aim of this study was to characterize in vitro the germline CDKN1B mutation c.374_375delCT (S125X) we detected in a patient with MEN4. The proband was affected by primary hyperparathyroidism due to multiglandular parathyroid involvement and gastro–entero–pancreatic tumors. We carried out subcellular localization experiments by transfection with plasmid vectors expressing the WT or mutant CDKN1B cDNA into the eukaryotic human cervix adenocarcinoma (HeLa) and GH3 cell lines. Results from western blotting studies indicated that fusion proteins were expressed at equal levels. The mutated protein was shorter compared with the WT protein and lacked the highly conserved C-terminal domain, which includes the bipartite nuclear localization signal at amino acids 152/153 and 166/168. In HeLa and GH3 cells, WT P27 localized in the nucleus, whereas the P27_S125X protein was retained in the cytoplasm, predicting the loss of tumor-suppressive function. The proband's tumoral parathyroid tissue did not show allelic loss, because both WT and mutant alleles were determined to be present by sequencing the somatic DNA. Immunohistochemistry revealed a complete loss of nuclear expression of P27 in a parathyroid adenoma, which had been removed by the second surgery in the patient. In conclusion, our results confirm the pathogenic role of the c.374_375delCT CDKN1B germline mutation in a patient with MEN4.

Open access
Luchuan Li Department of Thyroid Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China

Search for other papers by Luchuan Li in
Google Scholar
PubMed
Close
,
Baoyuan Li Department of Thyroid Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China

Search for other papers by Baoyuan Li in
Google Scholar
PubMed
Close
,
Bin Lv Department of Thyroid Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China

Search for other papers by Bin Lv in
Google Scholar
PubMed
Close
,
Weili Liang Department of Thyroid Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China

Search for other papers by Weili Liang in
Google Scholar
PubMed
Close
,
Binbin Zhang Department of Thyroid Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China

Search for other papers by Binbin Zhang in
Google Scholar
PubMed
Close
,
Qingdong Zeng Department of Thyroid Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China

Search for other papers by Qingdong Zeng in
Google Scholar
PubMed
Close
,
Andrew G Turner Clinical and Health Sciences, University of South Australia, Adelaide, South Australia, Australia

Search for other papers by Andrew G Turner in
Google Scholar
PubMed
Close
, and
Lei Sheng Department of Thyroid Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China

Search for other papers by Lei Sheng in
Google Scholar
PubMed
Close

Background

Multiple studies have reported the increased incidence of thyroid cancer in patients with primary hyperparathyroidism (PHPT). However, the underlying risk factors of concomitant thyroid cancer in patients with PHPT remain unknown. The primary aim of this study was to examine the records of patients with PHPT to identify characteristics that correlated with the presence of coexisting thyroid nodules, and which may have an implication for the prediction of thyroid cancer.

Methods

Medical records of consecutive patients with PHPT (n = 318) were reviewed from January 2010 to September 2020 in two tertiary medical centers in China. Patient clinicopathological and biological data were collected and analyzed.

Results

Of a total of 318 patients with PHPT, 105 (33.0%) patients had thyroid nodules and 26 (8.2%) patients were concomitant with thyroid cancer. A total of 38 thyroid nodules taken from 26 patients were pathologically assessed to be well-differentiated papillary thyroid carcinoma (PTC), with 81% being papillary thyroid microcarcinoma (PTMC). In 79% (30/38) of these cancers, thyroid nodules were considered suspicious following preoperative ultrasound. Multinomial logistic regression analysis revealed that female gender was associated with increased risk of thyroid nodules (OR = 2.13, 95% CI: 1.13–3.99, P = 0.019), while lower log-transformed parathyroid hormone levels were an independent predictor of thyroid cancer in patients with PHPT (OR = 0.50, 95% CI: 0.26–0.93, P = 0.028).

Conclusion

In conclusion, we observed a relatively high prevalence of thyroid cancer in our cohort of Chinese patients with PHPT. Evaluation of thyroid nodules by preoperative ultrasound may be advisable in patients with PHPT, particularly for females and patients with modestly elevated serum parathyroid hormone levels.

Open access
Louise Vølund Larsen Department of ORL Head & Neck Surgery and Audiology, Odense University Hospital, Odense, Denmark

Search for other papers by Louise Vølund Larsen in
Google Scholar
PubMed
Close
,
Delphine Mirebeau-Prunier Laboratoire de Biochimie et Biologie Moléculaire, CHU Angers, Université d’Angers, UMR CNRS 6015, INSERM U1083, MITOVASC, Angers, France

Search for other papers by Delphine Mirebeau-Prunier in
Google Scholar
PubMed
Close
,
Tsuneo Imai Department of Breast & Endocrine Surgery, National Hospital Organization, Higashinagoya National Hospital

Search for other papers by Tsuneo Imai in
Google Scholar
PubMed
Close
,
Cristina Alvarez-Escola Endocrinology and Nutrition Department, University Hospital ‘La Paz’, Madrid, Spain

Search for other papers by Cristina Alvarez-Escola in
Google Scholar
PubMed
Close
,
Kornelia Hasse-Lazar Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland

Search for other papers by Kornelia Hasse-Lazar in
Google Scholar
PubMed
Close
,
Simona Censi Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy

Search for other papers by Simona Censi in
Google Scholar
PubMed
Close
,
Luciana A Castroneves Department of Endocrinology, Endocrine Oncology Unit, Instituto do Cancer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

Search for other papers by Luciana A Castroneves in
Google Scholar
PubMed
Close
,
Akihiro Sakurai Department of Medical Genetics and Genomics, Sapporo Medical University School of Medicine, Sapporo, Japan

Search for other papers by Akihiro Sakurai in
Google Scholar
PubMed
Close
,
Minoru Kihara Department of Surgery, Kuma Hospital, Kobe, Hyogo, Japan

Search for other papers by Minoru Kihara in
Google Scholar
PubMed
Close
,
Kiyomi Horiuchi Department of Breast and Endocrine Surgery, Tokyo Women’s Medical University, Tokyo, Japan

Search for other papers by Kiyomi Horiuchi in
Google Scholar
PubMed
Close
,
Véronique Dorine Barbu AP-HP, Sorbonne Université, Laboratoire Commun de Biologie et Génétique Moléculaires, Hôpital St Antoine & INSERM CRSA, Paris, France
Réseau TenGen, Marseille, France

Search for other papers by Véronique Dorine Barbu in
Google Scholar
PubMed
Close
,
Francoise Borson-Chazot Réseau TenGen, Marseille, France
Fédération d’Endocrinologie, Hospices Civils de Lyon, Université Lyon 1, France

Search for other papers by Francoise Borson-Chazot in
Google Scholar
PubMed
Close
,
Anne-Paule Gimenez-Roqueplo Réseau TenGen, Marseille, France
Service de Génétique, AP-HP, Hôpital européen Georges Pompidou, Paris, France
Université de Paris, PARCC, INSERM, Paris, France

Search for other papers by Anne-Paule Gimenez-Roqueplo in
Google Scholar
PubMed
Close
,
Pascal Pigny Réseau TenGen, Marseille, France
Laboratoire de Biochimie et Oncologie Moléculaire, CHU Lille, Lille, France

Search for other papers by Pascal Pigny in
Google Scholar
PubMed
Close
,
Stephane Pinson Réseau TenGen, Marseille, France
Laboratoire de Génétique Moléculaire, CHU Lyon, Lyon, France

Search for other papers by Stephane Pinson in
Google Scholar
PubMed
Close
,
Nelson Wohllk Endocrine Section, Hospital del Salvador, Santiago de Chile, Department of Medicine, University of Chile, Santiago, Chile

Search for other papers by Nelson Wohllk in
Google Scholar
PubMed
Close
,
Charis Eng Genomic Medicine Institute, Lerner Research Institute and Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA

Search for other papers by Charis Eng in
Google Scholar
PubMed
Close
,
Berna Imge Aydogan Department of Endocrinology And Metabolic Diseases, Ankara University School of Medicine, Ankara, Turkey

Search for other papers by Berna Imge Aydogan in
Google Scholar
PubMed
Close
,
Dhananjaya Saranath Department of Research Studies & Additional Projects, Cancer Patients Aid Association, Dr. Vithaldas Parmar Research & Medical Centre, Worli, Mumbai, India

Search for other papers by Dhananjaya Saranath in
Google Scholar
PubMed
Close
,
Sarka Dvorakova Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic

Search for other papers by Sarka Dvorakova in
Google Scholar
PubMed
Close
,
Frederic Castinetti Aix-Marseille Université, Institut National de la Santé et de la Recherche Médicale (INSERM), U1251, Marseille Medical Genetics (MMG), Marseille, France
Department of Endocrinology, Assistance Publique-Hôpitaux de Marseille (AP-HM), Hôpital de la Conception, Centre de Référence des Maladies Rares de l’hypophyse HYPO, Marseille, France

Search for other papers by Frederic Castinetti in
Google Scholar
PubMed
Close
,
Attila Patocs HAS-SE Momentum Hereditary Endocrine Tumors Research Group, Semmelweis University, Budapest, Hungary

Search for other papers by Attila Patocs in
Google Scholar
PubMed
Close
,
Damijan Bergant Department of Surgical Oncology, Institute of Oncology, Ljubljana, Slovenia

Search for other papers by Damijan Bergant in
Google Scholar
PubMed
Close
,
Thera P Links Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands

Search for other papers by Thera P Links in
Google Scholar
PubMed
Close
,
Mariola Peczkowska Department of Hypertension, Institute of Cardiology, Warsaw, Poland

Search for other papers by Mariola Peczkowska in
Google Scholar
PubMed
Close
,
Ana O Hoff Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands

Search for other papers by Ana O Hoff in
Google Scholar
PubMed
Close
,
Caterina Mian Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy

Search for other papers by Caterina Mian in
Google Scholar
PubMed
Close
,
Trisha Dwight Cancer Genetics, Kolling Institute, Royal North Shore Hospital and University of Sydney, Sydney, New South Wales, Australia

Search for other papers by Trisha Dwight in
Google Scholar
PubMed
Close
,
Barbara Jarzab Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland

Search for other papers by Barbara Jarzab in
Google Scholar
PubMed
Close
,
Hartmut P H Neumann Section for Preventive Medicine, Medical Center-University of Freiburg, Faculty of Medicine, Albert Ludwigs-University of Freiburg, Freiburg, Germany

Search for other papers by Hartmut P H Neumann in
Google Scholar
PubMed
Close
,
Mercedes Robledo Hereditary Endocrine Cancer Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain

Search for other papers by Mercedes Robledo in
Google Scholar
PubMed
Close
,
Shinya Uchino Department of Endocrine Surgery, Noguchi Thyroid Clinic and Hospital Foundation, Beppu, Oita, Japan

Search for other papers by Shinya Uchino in
Google Scholar
PubMed
Close
,
Anne Barlier Réseau TenGen, Marseille, France
Aix Marseille Univ, APHM, INSERM, MMG, Laboratory of Molecular Biology, Hospital La Conception, Marseille, France

Search for other papers by Anne Barlier in
Google Scholar
PubMed
Close
,
Christian Godballe Department of ORL Head & Neck Surgery and Audiology, Odense University Hospital, Odense, Denmark

Search for other papers by Christian Godballe in
Google Scholar
PubMed
Close
, and
Jes Sloth Mathiesen Department of ORL Head & Neck Surgery and Audiology, Odense University Hospital, Odense, Denmark
Department of Clinical Research, University of Southern Denmark, Odense, Denmark

Search for other papers by Jes Sloth Mathiesen in
Google Scholar
PubMed
Close

Objective

Multiple endocrine neoplasia type 2A (MEN 2A) is a rare syndrome caused by RET germline mutations and has been associated with primary hyperparathyroidism (PHPT) in up to 30% of cases. Recommendations on RET screening in patients with apparently sporadic PHPT are unclear. We aimed to estimate the prevalence of cases presenting with PHPT as first manifestation among MEN 2A index cases and to characterize the former cases.

Design and methods

An international retrospective multicenter study of 1085 MEN 2A index cases. Experts from MEN 2 centers all over the world were invited to participate. A total of 19 centers in 17 different countries provided registry data of index cases followed from 1974 to 2017.

Results

Ten cases presented with PHPT as their first manifestation of MEN 2A, yielding a prevalence of 0.9% (95% CI: 0.4–1.6). 9/10 cases were diagnosed with medullary thyroid carcinoma (MTC) in relation to parathyroid surgery and 1/10 was diagnosed 15 years after parathyroid surgery. 7/9 cases with full TNM data were node-positive at MTC diagnosis.

Conclusions

Our data suggest that the prevalence of MEN 2A index cases that present with PHPT as their first manifestation is very low. The majority of index cases presenting with PHPT as first manifestation have synchronous MTC and are often node-positive. Thus, our observations suggest that not performing RET mutation analysis in patients with apparently sporadic PHPT would result in an extremely low false-negative rate, if no other MEN 2A component, specifically MTC, are found during work-up or resection of PHPT.

Open access
Laura P B Elbers Department of Internal Medicine, Medical Center Slotervaart, Amsterdam, the Netherlands
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands

Search for other papers by Laura P B Elbers in
Google Scholar
PubMed
Close
,
Marije Wijnberge Department of Internal Medicine, Medical Center Slotervaart, Amsterdam, the Netherlands
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
Laboratory of Experimental Intensive Care and Anesthesiology, Academic Medical Center, University of Amsterdam, the Netherlands

Search for other papers by Marije Wijnberge in
Google Scholar
PubMed
Close
,
Joost C M Meijers Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
Department of Plasma Proteins, Sanquin Research, Amsterdam, the Netherlands

Search for other papers by Joost C M Meijers in
Google Scholar
PubMed
Close
,
Dennis C W Poland Clinical Chemistry Laboratory, Medical Center Slotervaart, Amsterdam, the Netherlands

Search for other papers by Dennis C W Poland in
Google Scholar
PubMed
Close
,
Dees P M Brandjes Department of Internal Medicine, Medical Center Slotervaart, Amsterdam, the Netherlands
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands

Search for other papers by Dees P M Brandjes in
Google Scholar
PubMed
Close
,
Eric Fliers Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands

Search for other papers by Eric Fliers in
Google Scholar
PubMed
Close
, and
Victor E A Gerdes Department of Internal Medicine, Medical Center Slotervaart, Amsterdam, the Netherlands
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands

Search for other papers by Victor E A Gerdes in
Google Scholar
PubMed
Close

Introduction

Abnormal coagulation tests have been observed in patients with primary hyperparathyroidism (HPT) suggesting a prothrombotic effect of parathyroid hormone (PTH). Vitamin D deficiency (VIDD) is the most frequent cause of secondary HPT. Aim of our study was to investigate the influence of HPT secondary to moderate-to-severe VIDD and vitamin D replacement on the coagulation and fibrinolysis system.

Subjects and methods

Prospective cohort study of patients with vitamin D <25 nmol/L with and without HPT, and a control group of patients on vitamin D suppletion. At baseline and after 2 months of vitamin D suppletion (900,000 IU in 2 months), endocrine and coagulation markers were measured.

Results

59 patients with VIDD of which 34 had secondary HPT and 36 controls were included. After 2 months of suppletion, vitamin D increased by 399% (VIDD with HPT), 442% (all patients with VIDD) and 6% (controls). PTH decreased by 34% (VIDD with HPT, P < 0.01 for decrease), 32% (all VIDD, P < 0.01) and increased by 8% in the controls (P-values: <0.01 for relative changes between VIDD with HPT or all VIDD patients vs controls). Relative changes in PT, aPTT, fibrinogen, Von Willebrand factor, factors VII, VIII and X, thrombin generation, TAFI, clot-lysis time and d-dimer were not different between patients with VIDD with HPT or all VIDD vs controls.

Discussion

Secondary HPT due to VIDD does not have a prothrombotic effect. In contrast with previous reports, PTH does not seem to influence coagulation or fibrinolysis, which is relevant because of the high prevalence of VIDD.

Open access
Magdaléna Fořtová Department of Medical Chemistry and Clinical Biochemistry, Charles University, Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic

Search for other papers by Magdaléna Fořtová in
Google Scholar
PubMed
Close
,
Lenka Hanousková Department of Medical Chemistry and Clinical Biochemistry, Charles University, Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic

Search for other papers by Lenka Hanousková in
Google Scholar
PubMed
Close
,
Martin Valkus Department of Medical Chemistry and Clinical Biochemistry, Charles University, Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic

Search for other papers by Martin Valkus in
Google Scholar
PubMed
Close
,
Jana Čepová Department of Medical Chemistry and Clinical Biochemistry, Charles University, Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic

Search for other papers by Jana Čepová in
Google Scholar
PubMed
Close
,
Richard Průša Department of Medical Chemistry and Clinical Biochemistry, Charles University, Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic

Search for other papers by Richard Průša in
Google Scholar
PubMed
Close
, and
Karel Kotaška Department of Medical Chemistry and Clinical Biochemistry, Charles University, Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic

Search for other papers by Karel Kotaška in
Google Scholar
PubMed
Close

Background

Fibroblast growth factor 23 (FGF23) is a key regulator of urine phosphate excretion. The aim of the study was to investigate the perioperative (intraoperative and postoperative) changes of plasma intact and C-terminal FGF23 (iFGF23, cFGF23) concentrations in patients with primary hyperparathyroidism (pHPT) submitted to surgery.

Materials and methods

The study involved 38 adult patients with pHPT caused by adenoma. Parathyroid hormone (PTH) levels were investigated intraoperatively (just before the incision and 10 min after adenoma excision). cFGF23, iFGF23, phosphate, estimated glomerular filtration rate (eGFR), and procollagen type 1 N-terminal propetide (P1NP) were measured intraoperatively and postoperatively (next day after the surgery).

Results

PTH levels decreased intraoperatively (13.10 pmol/L vs 4.17 pmol/L, P< 0.0001). FGF23 levels measured intraoperatively were at the upper level of reference interval. cFGF23 decreased postoperatively compared with the values measured just before the incision (cFGF23: 89.17 RU/mL vs 22.23 RU/mL, P< 0.0001). iFGF23 decreased as well, but the postoperative values were low. Postoperative inorganic phosphate values increased (1.03 mmol/L vs 0.8 mmol/L, P= 0.0025). We proved significant negative correlation of perioperative FGF23 with inorganic phosphate (cFGF23: Spearman’s r = −0.253, P= 0.0065; iFGF23: Spearman’s r = −0.245, P= 0.0085). We also found that FGF23 values just before incision correlated with eGFR (cystatin C) (cFGF23: Spearman’s r = −0.499, P= 0.0014; iFGF23: Spearman’s r = −0.413, P= 0.01).

Conclusion

Intraoperative iFGF23 and cFGF23 did not change despite PTH decreased significantly. cFGF23 and iFGF23 significantly decreased 1 day after parathyroidectomy and are associated with increase of inorganic phosphate in pHPT patients. cFGF23 and iFGF23 just before incision correlated with eGFR (cystatin C). Similar results found in both iFGF23 and cFGF23 suggest that each could substitute the other.

Open access