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

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Lenka Hanousková Department of Medical Chemistry and Clinical Biochemistry, Charles University, Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic

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Martin Valkus Department of Medical Chemistry and Clinical Biochemistry, Charles University, Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic

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Jana Čepová Department of Medical Chemistry and Clinical Biochemistry, Charles University, Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic

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Richard Průša Department of Medical Chemistry and Clinical Biochemistry, Charles University, Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic

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Karel Kotaška Department of Medical Chemistry and Clinical Biochemistry, Charles University, Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic

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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.

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Hélène Singeisen Department of Internal Medicine, Endocrinology, Cantonal Hospital Thurgau, Münsterlingen, Switzerland

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Mariko Melanie Renzulli Institute of Radiology, Cantonal Hospital Thurgau, Frauenfeld, Switzerland

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Vojtech Pavlicek Department of Internal Medicine, Endocrinology, Cantonal Hospital Thurgau, Münsterlingen, Switzerland

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Pascal Probst Department of Surgery, Cantonal Hospital Thurgau, Frauenfeld, Switzerland

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Fabian Hauswirth Department of Surgery, Cantonal Hospital Thurgau, Münsterlingen, Switzerland

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Markus K Muller Department of Surgery, Cantonal Hospital Thurgau, Frauenfeld, Switzerland

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Magdalene Adamczyk Department of Pathology and Molecular Pathology, University Hospital Zurich and University of Zurich, Zurich, Switzerland

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Achim Weber Department of Pathology and Molecular Pathology, University Hospital Zurich and University of Zurich, Zurich, Switzerland

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Reto Martin Kaderli Department of Visceral Surgery and Medicine, Bern University Hospital, University of Bern, Bern, Switzerland

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Pietro Renzulli Department of Surgery, Cantonal Hospital Thurgau, Münsterlingen, Switzerland

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Objective

Multiple endocrine neoplasia type 4 (MEN4) is caused by a CDKN1B germline mutation first described in 2006. Its estimated prevalence is less than one per million. The aim of this study was to define the disease characteristics.

Methods

A systematic review was performed according to the PRISMA 2020 criteria. A literature search from January 2006 to August 2022 was done using MEDLINE® and Web of ScienceTM.

Results

Forty-eight symptomatic patients fulfilled the pre-defined eligibility criteria. Twenty-eight different CDKN1B variants, mostly missense (21/48, 44%) and frameshift mutations (17/48, 35%), were reported. The majority of patients were women (36/48, 75%). Men became symptomatic at a median age of 32.5 years (range 10–68, mean 33.7 ± 23), whereas the same event was recorded for women at a median age of 49.5 years (range 5–76, mean 44.8 ± 19.9) (P  = 0.25). The most frequently affected endocrine organ was the parathyroid gland (36/48, 75%; uniglandular disease 31/36, 86%), followed by the pituitary gland (21/48, 44%; hormone-secreting 16/21, 76%), the endocrine pancreas (7/48, 15%), and the thyroid gland (4/48, 8%). Tumors of the adrenal glands and thymus were found in three and two patients, respectively. The presenting first endocrine pathology concerned the parathyroid (27/48, 56%) and the pituitary gland (11/48, 23%). There were one (27/48, 56%), two (13/48, 27%), three (3/48, 6%), or four (5/48, 10%) syn- or metachronously affected endocrine organs in a single patient, respectively.

Conclusion

MEN4 is an extremely rare disease, which most frequently affects women around 50 years of age. Primary hyperparathyroidism as a uniglandular disease is the leading pathology.

Open access
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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Victor Jing-Wei Kang Departments of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan

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Bo-Ching Lee Departments of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan

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Jia-Zheng Huang Departments of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan

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Vin-Cent Wu Departments of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

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Yen-Hung Lin Departments of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

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Chin-Chen Chang Departments of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan

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TAIPAI group
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Primary aldosteronism (PA) is associated with urolithiasis as it causes hypercalciuria and hypocitraturia. However, the influence of different subtypes of PA on urinary stone formation remains unclear. This study aimed to evaluate the association between aldosterone-producing adenoma (APA) and the burden of urolithiasis in patients with PA. In the present study, we enrolled 312 patients with PA from a prospectively maintained database, of whom 179 had APA. Clinical, biochemical, and imaging data (including the presence, volume, and density of urinary stones on abdominal computed tomography) were compared between groups, with employment of propensity score matching (PSM) analysis to balance possible confounding factors. Kaplan–Meier analysis was used to estimate the acute renal colic event during follow-up. After PSM for age, sex, serum calcium, phosphate, blood urea nitrogen, creatinine, and uric acid, the APA and non-APA groups had 106 patients each. Patients with APA had higher serum intact parathyroid hormone (iPTH) (79.1 ± 45.0 vs 56.1 ± 30.3, P < 0.001) and a higher prevalence of urolithiasis (27.4% vs 12.3%, P = 0.006) than non-APA patients. During follow-up, a higher incidence of acute renal colic events was noted in the APA group than the non-APA group (P = 0.011); this association remained significant (P = 0.038) after adjustment for age and sex in Cox-regression analysis. Our data suggest that APA is associated with a heavier burden of urolithiasis and higher incidence of renal colic events compared to the non-APA subtype of PA.

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Charissa van Zwol-Janssens Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Aglaia Hage Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Kim van der Ham Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Birgitta K Velthuis Department of Radiology, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands

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Ricardo P J Budde Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands

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Maria P H Koster Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Arie Franx Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Bart C J M Fauser Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht & University of Utrecht, Utrecht, the Netherlands

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Eric Boersma Department of Cardiology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Daniel Bos Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Joop S E Laven Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Yvonne V Louwers Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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the CREW consortium
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the CREW consortium

Besides age, estrogen exposure plays a crucial role in changes in bone density (BD) in women. Premature ovarian insufficiency (POI) and polycystic ovary syndrome (PCOS) are conditions in reproductive-aged women in which the exposure to estrogen is substantially different. Women with a history of preeclampsia (PE) are expected to have normal estrogen exposure. Within the CREw-IMAGO study, we investigated if trabecular BD is different in these women because of differences in the duration of estrogen exposure. Trabecular BD was measured in thoracic vertebrae on coronary CT scans. Women with a reduced estrogen exposure (POI) have a lower BD compared to women with an intermediate exposure (PE) (mean difference (MD) −26.8, 95% CI −37.2 to −16.3). Women with a prolonged estrogen exposure (PCOS) have the highest BD (MD 15.0, 95% CI 4.3–25.7). These results support the hypothesis that the duration of estrogen exposure in these women is associated with trabecular BD.

Significance statement

Our results suggest that middle-aged women with PCOS have a higher BD and women with POI have a lower BD. We hypothesized that this is due to either a prolonged estrogen exposure, as seen in women with PCOS, or a reduced estrogen exposure, as in women with POI. In the counseling of women with reproductive disorders on long-term health issues, coronary CT provides a unique opportunity to assess both coronary artery calcium score for cardiovascular screening as well as trabecular BD.

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Liubov G Yanevskaya Almazov National Medical Research Centre, St. Petersburg, Russia

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Tatiana Karonova Almazov National Medical Research Centre, St. Petersburg, Russia
First Pavlov State Medical University, St. Petersburg, Russia

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Ilya V Sleptsov Saint-Petersburg State University N.I. Pirogov Clinic of High Medical Technologies, St. Petersburg, Russia

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Marina Evgenevna Boriskova First Pavlov State Medical University, St. Petersburg, Russia

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Aluza Ramilevna Bakhtiyarova Almazov National Medical Research Centre, St. Petersburg, Russia

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Roman A Chernikov Saint-Petersburg State University N.I. Pirogov Clinic of High Medical Technologies, St. Petersburg, Russia

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Karina Aleksandrovna Pogosian Almazov National Medical Research Centre, St. Petersburg, Russia

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Alena Timurovna Andreeva Almazov National Medical Research Centre, St. Petersburg, Russia

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Denis Andreevich Lebedev Almazov National Medical Research Centre, St. Petersburg, Russia

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Elena Nikolaevna Grineva Almazov National Medical Research Centre, St. Petersburg, Russia
First Pavlov State Medical University, St. Petersburg, Russia

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John P Bilezikian College of Physicians and Surgeons, Columbia University, New York, New York, USA

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Objective

The aim of our study was to investigate the distribution of the PHPT clinical manifestations and biochemical features in patients who underwent parathyroidectomy.

Materials and methods

Medical records of 449 patients from three Medical Centers (Saint-Petersburg, Russia), hospitalized during a period from 2011 to 2018, were reviewed. History and anthropometric data, laboratory results (iPTH, total and iCa, phosphorus, ALP, 24-h urinary calcium, 25(OH)D) and imaging data (ultrasonography, scintigraphy, CT/MRI scan, DXA) were analyzed.

Results

Three hundred ninety-four patients were included in the final analysis. Median age was 60 years with 94.2% being women. Symptomatic disease was evident in 222 (56.4%) patients, asymptomatic in 172 (43.6%). Skeletal involvement was more common for women, while frequency of other manifestations did not differ in both genders. There was no difference between symptomatic and asymptomatic patients in age. Serum iPTH level was higher in symptomatic patients (202.9 and 181.0 pg/mL, P = 0.022). Serum 25(OH)D level was estimated in few patients and negatively correlated with PTH (r = ¯0.294, P = 0.005), iCa (r = ¯0.268, P = 0.010) and total Ca (r = ¯0.284, P = 0.014) levels. Manifestations of CVD were observed in 67.7% of cases and affected equally both symptomatic and asymptomatic patients (70.7 and 63.4%, P = 0.076). Both age and BMI were higher in patients with CVD, whether or not they were symptomatic (62 and 53 years, P < 0.0001; 30.4 vs 26.0 kg/m2, P < 0.0001, respectively).

Conclusions

This experience illustrates that symptomatic phenotype is still the most common form of PHPT.

Open access
Fernanda A Correa Unidade de Endocrinologia do Desenvolvimento, Unidade de Endocrinologia Genética, Centre Hospitalier Universitaire Vaudois (CHUV), Division of Endocrinology, Laboratório de Hormônios e Genética Molecular LIM42

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Ericka B Trarbach Unidade de Endocrinologia do Desenvolvimento, Unidade de Endocrinologia Genética, Centre Hospitalier Universitaire Vaudois (CHUV), Division of Endocrinology, Laboratório de Hormônios e Genética Molecular LIM42

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Cintia Tusset Unidade de Endocrinologia do Desenvolvimento, Unidade de Endocrinologia Genética, Centre Hospitalier Universitaire Vaudois (CHUV), Division of Endocrinology, Laboratório de Hormônios e Genética Molecular LIM42

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Ana Claudia Latronico Unidade de Endocrinologia do Desenvolvimento, Unidade de Endocrinologia Genética, Centre Hospitalier Universitaire Vaudois (CHUV), Division of Endocrinology, Laboratório de Hormônios e Genética Molecular LIM42

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Luciana R Montenegro Unidade de Endocrinologia do Desenvolvimento, Unidade de Endocrinologia Genética, Centre Hospitalier Universitaire Vaudois (CHUV), Division of Endocrinology, Laboratório de Hormônios e Genética Molecular LIM42

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Luciani R Carvalho Unidade de Endocrinologia do Desenvolvimento, Unidade de Endocrinologia Genética, Centre Hospitalier Universitaire Vaudois (CHUV), Division of Endocrinology, Laboratório de Hormônios e Genética Molecular LIM42

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Marcela M Franca Unidade de Endocrinologia do Desenvolvimento, Unidade de Endocrinologia Genética, Centre Hospitalier Universitaire Vaudois (CHUV), Division of Endocrinology, Laboratório de Hormônios e Genética Molecular LIM42

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Aline P Otto Unidade de Endocrinologia do Desenvolvimento, Unidade de Endocrinologia Genética, Centre Hospitalier Universitaire Vaudois (CHUV), Division of Endocrinology, Laboratório de Hormônios e Genética Molecular LIM42

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Everlayny F Costalonga Unidade de Endocrinologia do Desenvolvimento, Unidade de Endocrinologia Genética, Centre Hospitalier Universitaire Vaudois (CHUV), Division of Endocrinology, Laboratório de Hormônios e Genética Molecular LIM42

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Vinicius N Brito Unidade de Endocrinologia do Desenvolvimento, Unidade de Endocrinologia Genética, Centre Hospitalier Universitaire Vaudois (CHUV), Division of Endocrinology, Laboratório de Hormônios e Genética Molecular LIM42

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Ana Paula Abreu Unidade de Endocrinologia do Desenvolvimento, Unidade de Endocrinologia Genética, Centre Hospitalier Universitaire Vaudois (CHUV), Division of Endocrinology, Laboratório de Hormônios e Genética Molecular LIM42

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Mirian Y Nishi Unidade de Endocrinologia do Desenvolvimento, Unidade de Endocrinologia Genética, Centre Hospitalier Universitaire Vaudois (CHUV), Division of Endocrinology, Laboratório de Hormônios e Genética Molecular LIM42

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Alexander A L Jorge Unidade de Endocrinologia do Desenvolvimento, Unidade de Endocrinologia Genética, Centre Hospitalier Universitaire Vaudois (CHUV), Division of Endocrinology, Laboratório de Hormônios e Genética Molecular LIM42

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Ivo J P Arnhold Unidade de Endocrinologia do Desenvolvimento, Unidade de Endocrinologia Genética, Centre Hospitalier Universitaire Vaudois (CHUV), Division of Endocrinology, Laboratório de Hormônios e Genética Molecular LIM42

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Yisrael Sidis Unidade de Endocrinologia do Desenvolvimento, Unidade de Endocrinologia Genética, Centre Hospitalier Universitaire Vaudois (CHUV), Division of Endocrinology, Laboratório de Hormônios e Genética Molecular LIM42

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Nelly Pitteloud Unidade de Endocrinologia do Desenvolvimento, Unidade de Endocrinologia Genética, Centre Hospitalier Universitaire Vaudois (CHUV), Division of Endocrinology, Laboratório de Hormônios e Genética Molecular LIM42

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Berenice B Mendonca Unidade de Endocrinologia do Desenvolvimento, Unidade de Endocrinologia Genética, Centre Hospitalier Universitaire Vaudois (CHUV), Division of Endocrinology, Laboratório de Hormônios e Genética Molecular LIM42

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The genetic aetiology of congenital hypopituitarism (CH) is not entirely elucidated. FGFR1 and PROKR2 loss-of-function mutations are classically involved in hypogonadotrophic hypogonadism (HH), however, due to the clinical and genetic overlap of HH and CH; these genes may also be involved in the pathogenesis of CH. Using a candidate gene approach, we screened 156 Brazilian patients with combined pituitary hormone deficiencies (CPHD) for loss-of-function mutations in FGFR1 and PROKR2. We identified three FGFR1 variants (p.Arg448Trp, p.Ser107Leu and p.Pro772Ser) in four unrelated patients (two males) and two PROKR2 variants (p.Arg85Cys and p.Arg248Glu) in two unrelated female patients. Five of the six patients harbouring the variants had a first-degree relative that was an unaffected carrier of it. Results of functional studies indicated that the new FGFR1 variant p.Arg448Trp is a loss-of-function variant, while p.Ser107Leu and p.Pro772Ser present signalling activity similar to the wild-type form. Regarding PROKR2 variants, results from previous functional studies indicated that p.Arg85Cys moderately compromises receptor signalling through both MAPK and Ca2 + pathways while p.Arg248Glu decreases calcium mobilization but has normal MAPK activity. The presence of loss-of-function variants of FGFR1 and PROKR2 in our patients with CPHD is indicative of an adjuvant and/or modifier effect of these rare variants on the phenotype. The presence of the same variants in unaffected relatives implies that they cannot solely cause the phenotype. Other associated genetic and/or environmental modifiers may play a role in the aetiology of this condition.

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Lasse Oinonen Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland

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Antti Tikkakoski Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland

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Jenni Koskela Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
Department of Internal Medicine, Tampere University Hospital, Tampere, Finland

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Arttu Eräranta Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland

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Mika Kähönen Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland

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Onni Niemelä Department of Laboratory Medicine and Medical Research Unit, Seinäjoki Central Hospital, Seinäjoki, Finland

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Jukka Mustonen Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
Department of Internal Medicine, Tampere University Hospital, Tampere, Finland

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Ilkka Pörsti Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
Department of Internal Medicine, Tampere University Hospital, Tampere, Finland

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Parathyroid hormone has been related with the risk of hypertension, but the matter remains controversial. We examined the association of parathyroid hormone with central blood pressure and its determinants in 622 normotensive or never-treated hypertensive subjects aged 19–72 years without diabetes, cardiovascular or renal disease, or cardiovascular medications. The methods were whole-body impedance cardiography and analyses of pulse wave and heart rate variability. Cardiovascular function was examined in sex-specific tertiles of plasma parathyroid hormone (mean concentrations 3.0, 4.3 and 6.5 pmol/L, respectively) during head-up tilt. Explanatory factors for haemodynamics were further investigated using linear regression analyses. Mean age was 45.0 (s.d. 11.7) years, BMI 26.8 (4.4) kg/m2, seated office blood pressure 141/90 (21/12) mmHg, and 309 subjects (49.7%) were male. Only five participants had elevated plasma parathyroid hormone and calcium concentrations. Highest tertile of parathyroid hormone presented with higher supine and upright aortic diastolic blood pressure (P < 0.01) and augmentation index (P < 0.01), and higher upright systemic vascular resistance (P < 0.05) than the lowest tertile. The tertiles did not present with differences in pulse wave velocity, cardiac output, or measures of heart rate variability. In linear regression analyses, parathyroid hormone was an independent explanatory factor for aortic systolic (P = 0.005) and diastolic (P = 0.002) blood pressure, augmentation index (P = 0.002), and systemic vascular resistance (P = 0.031). To conclude, parathyroid hormone was directly related to central blood pressure, wave reflection, and systemic vascular resistance in subjects without cardiovascular comorbidities and medications. Thus, parathyroid hormone may play a role in the pathophysiology of primary hypertension.

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Kaiyu Pan Department of Paediatrics, The First People's Hospital of Xiaoshan District, Hangzhou, Zhejiang, China

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Chengyue Zhang Xiangya School of Medicine, Central South University, Changsha, Hunan, China

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Xiaocong Yao Department of Osteoporosis, The First People's Hospital of Xiaoshan District, Hangzhou, Zhejiang, China

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Zhongxin Zhu Institute of Orthopaedics and Traumatology of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China

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Aim

Ensuring adequate calcium (Ca) intake during childhood and adolescence is critical to acquire good peak bone mass to prevent osteoporosis during older age. As one of the primary strategies to build and maintain healthy bones, we aimed to determine whether dietary Ca intake has an influence on bone mineral density (BMD) in children and adolescents.

Methods

We conducted a cross-sectional study composed of 10,092 individuals from the National Health and Nutrition Examination Survey (NHANES). Dietary Ca intake and total BMD were taken as independent and dependent variables, respectively. To evaluate the association between them, we conducted weighted multivariate linear regression models and smooth curve fittings.

Results

There was a significantly positive association between dietary Ca intake and total BMD. The strongest association was observed in 12–15 year old whites, 8–11 year old and 16–19 year old Mexican Americans, and 16–19 year old individuals from other race/ethnicity, in whom each quintile of Ca intake was increased. We also found that there were significant inflection points in females, blacks, and 12–15 year old adolescents group, which means that their total BMD would decrease when the dietary Ca intake was more than 2.6–2.8 g/d.

Conclusions

This cross-sectional study indicated that a considerable proportion of children and adolescents aged 8–19 years would attain greater total BMD if they increased their dietary Ca intake. However, higher dietary Ca intake (more than 2.6–2.8 g/d) is associated with lower total BMD in females, blacks, and 12–15 year old adolescents group.

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Matteo Scopel Medical Clinic III, Department of Medicine (DIMED), University Hospital of Padua, Padua, Italy

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Eugenio De Carlo Medical Clinic III, Department of Medicine (DIMED), University Hospital of Padua, Padua, Italy

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Francesca Bergamo Unit of Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy

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Sabina Murgioni Unit of Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy

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Riccardo Carandina Radiodiagnostic Unit, University Hospital of Padua, Padua, Italy

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Anna Rita Cervino Radiotherapy and Nuclear Medicine Unit, Istituto Oncologico Veneto IOV-IRCCS, Padua, Italy

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Marta Burei Radiotherapy and Nuclear Medicine Unit, Istituto Oncologico Veneto IOV-IRCCS, Padua, Italy

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Federica Vianello Radiotherapy and Nuclear Medicine Unit, Istituto Oncologico Veneto IOV-IRCCS, Padua, Italy

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Vittorina Zagonel Unit of Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy

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Matteo Fassan Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy

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Roberto Vettor Medical Clinic III, Department of Medicine (DIMED), University Hospital of Padua, Padua, Italy

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We considered 351 patients affected by neuroendocrine tumors (NETs), followed at the University Hospital of Padua and at the Veneto Oncological Institute. Of these, 72 (20.5%) suffered from bone metastases. The sample was divided according to the timing of presentation of bone metastases into synchronous (within 6 months of diagnosis of primary tumor) and metachronous (after 6 months). We collected data on the type and grading of the primary tumor and on the features of bone metastases. Our analysis shows that the group of synchronous metastases generally presents primary tumors with a higher degree of malignancy rather than the ones of the metachronous group. This is supported by the finding of a Ki-67 level in GEP-NETs, at the diagnosis of bone metastases, significantly higher in the synchronous group. Moreover, in low-grade NETs, chromogranin A values are higher in the patients with synchronous metastases, indicating a more burden of disease. The parameters of phospho-calcium metabolism are within the normal range, and we do not find significant differences between the groups. Serious bone complications are not frequent and are not correlated with the site of origin of the primary tumor. From the analysis of the survival curves of the total sample, a cumulative survival rate of 33% at 10 years emerges. The average survival is 80 months, higher than what is reported in the literature, while the median is 84 months. In our observation period, synchronous patients tend to have a worse prognosis than metachronous ones with 52-months survival rates of 58 and 86%.

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