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      Calcitonin concentrations in patients with chronic kidney disease on hemodialysis in reference to parathyroidectomy

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          Abstract

          Objective

          Calcitonin is considered to be a biomarker of medullary thyroid carcinoma and C-cell hyperplasia, but calcitonin can also be elevated in about 30% of the patients with end-stage kidney disease. We reported preoperative calcitonin serum levels in 31 patients on hemodialysis before parathyroid surgery, evaluate influencing factors on calcitonin levels and determine postoperative calcitonin levels after parathyroid surgery.

          Results

          Median preoperative serum calcitonin was 8 pg/ml (range 2 to 165 pg/ml), serum calcitonin concentration declined postoperatively to 3 pg/ml (range 1 to 192 pg/ml). There was a strong positive correlation between pre- and postoperative serum calcitonin levels (r = 0.92; p > 0.01). Elevated preoperative serum calcitonin concentrations (more than 10 pg/ml) were found in 14 out of 32 dialysis-dependent patients (44%). Preoperative calcitonin levels of male patients were significantly higher than female patients. Hypercalcitoninemia showed a positive correlation to body mass index (p < 0.01). We found no correlation between preoperative calcitonin levels and patients’ age, duration of hemodialysis dependency, cinacalcet medication or preoperative concentrations of parathyroid hormone, creatinine and calcium. Basal calcitonin levels higher than 10 pg/ml are common in patients on dialysis. Male gender and morbid obesity are risk factors for hypercalcitoninemia. Calcitonin concentration decreases after parathyroid operation.

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          Preoperative calcitonin levels are predictive of tumor size and postoperative calcitonin normalization in medullary thyroid carcinoma. Groupe d'Etudes des Tumeurs a Calcitonine (GETC).

          Medullary thyroid carcinoma (MTC) is a calcitonin (CT)-secreting endocrine tumor. Although plasma CT level is a specific and sensitive marker of MTC, its preoperative usefulness in predicting tumor size and postoperative CT normalization has not been documented. From a nationwide database set up by the French CT Tumor Study Group, 226 MTC patients were selected according to the following criteria: preoperative CT level determination by an immunoradiometric assay (normal value, < 10 pg/mL) within the 6 months prior to surgery, total thyroidectomy and diagnosis of MTC ascertained by histological report including tumor size. Patients were 129 females and 97 males (female/male ratio, 1.3). One hundred and twelve patients (49.6%) had the sporadic variety of the disease, 74 (32.7%) had multiple endocrine neoplasia 2A, three (1.3%) had multiple endocrine neoplasia 2B, and 37 (16.4%) had familial MTC. Median age at diagnosis was 44.8 yr (range, 4.9-80.1 yr). Complete neck dissection was performed in 159 patients (70.4%). Postoperative CT normalization was ascertained by negative response of CT to pentagastrin stimulation (< 10 pg/mL) in 94 patients. Seventy-one patients were considered as not cured because of residual tumor tissue and/or elevated CT levels. Median tumor size was 11.0 mm (range, 0.2-80.0 mm), significantly larger in females (15.0 vs. 8.0 mm, P < 0.05), and in sporadic forms (15.0 vs. 7.0 mm, P < 0.05). Tumor size was significantly correlated (r2 = 0.52, P < 0.01) with preoperative CT levels, the relationship being more straight in familial (r2 = 0.71) than in sporadic (r2 = 0.36) forms. Furthermore, preoperative CT levels under 50 pg/mL appeared to be predictive of postoperative CT normalization (44 of 45 patients). However, higher CT levels did not mean absence of postoperative CT normalization (50 of 120 patients). We conclude that low preoperative CT levels are predictive of tumor size and postoperative CT normalization.
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            Calcitonin, the forgotten hormone: does it deserve to be forgotten?

            Calcitonin is a 32 amino acid hormone secreted by the C-cells of the thyroid gland. Calcitonin has been preserved during the transition from ocean-based life to land dwellers and is phylogenetically older than parathyroid hormone. Calcitonin secretion is stimulated by increases in the serum calcium concentration and calcitonin protects against the development of hypercalcemia. Calcitonin is also stimulated by gastrointestinal hormones such as gastrin. This has led to the unproven hypothesis that postprandial calcitonin stimulation could play a role in the deposition of calcium and phosphate in bone after feeding. However, no bone or other abnormalities have been described in states of calcitonin deficiency or excess except for diarrhea in a few patients with medullary thyroid carcinoma. Calcitonin is known to stimulate renal 1,25 (OH)2 vitamin D (1,25D) production at a site in the proximal tubule different from parathyroid hormone and hypophosphatemia. During pregnancy and lactation, both calcitonin and 1,25D are increased. The increases in calcitonin and 1,25D may be important in the transfer of maternal calcium to the fetus/infant and in the prevention and recovery of maternal bone loss. Calcitonin has an immediate effect on decreasing osteoclast activity and has been used for treatment of hypercalcemia. Recent studies in the calcitonin gene knockout mouse have shown increases in bone mass and bone formation. This last result together with the presence of calcitonin receptors on the osteocyte suggests that calcitonin could possibly affect osteocyte products which affect bone formation. In summary, a precise role for calcitonin remains elusive more than 50 years after its discovery.
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              Reference range of serum calcitonin levels in humans: influence of calcitonin assays, sex, age, and cigarette smoking.

              The objective of this study was to re-evaluate the adult C(T) reference values determined by five different immunoassays and by introducing criteria for selecting control subjects. A prospective multicenter study. Three hundred and seventy-five clinically euthyroid subjects. We used five different C(T) immunoassays. Sera were assayed for the concentration of TSH, gastrin, procalcitonin, urea, calcium, and anti-thyroperoxidase antibodies. Screening for the various potential causes of hypercalcitoninemia led to the exclusion of 23% of the sera. Our reference value analysis dealt with 287 subjects (142 men and 145 women). The proportion of samples in which no C(T) was detected varied from 56% (for assay D) to 88% (for assay C). We observed significant correlations (whose magnitude depended on the assay used) between C(T) levels and age or body mass index (BMI) (primarily in men). The distribution of C(T) levels showed that 4.7, 9.8, 2.5, 6.5, and 8.0% of the values were over 10 pg/ml respectively. These values corresponded essentially to samples from 11 male subjects (median age: 55 years), most of whom were smokers. The highest C(T) values were around twice as high in men than women, and were higher in smokers than non-smokers. Conclusion In clinical practice (and after having excluded the usual causes of raised C(T) levels), the interpretation of C(T) assay results must take into account i) the method used; ii) the patient's gender, age, and weight; and iii) the potential influence of cigarette smoking.
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                Author and article information

                Contributors
                Roza.Sabia@uniklinik-ulm.de
                Martin.Wagner@uniklinik-ulm.de
                Kristina.Susa@uni-ulm.de
                Johannes.Lemke@uniklinik-ulm.de
                Lars.Rothermund@kfh-dialyse.de
                Doris.Henne-Bruns@uniklinik-ulm.de
                +49 (0) 731 500 53501 , Andreas.Hillenbrand@uniklinik-ulm.de
                Journal
                BMC Res Notes
                BMC Res Notes
                BMC Research Notes
                BioMed Central (London )
                1756-0500
                19 July 2019
                19 July 2019
                2019
                : 12
                : 439
                Affiliations
                [1 ]GRID grid.410712.1, Department of Internal Medicine I, , University Hospital Ulm, ; Albert-Einstein-Allee 23, 89081 Ulm, Germany
                [2 ]GRID grid.410712.1, Department of General and Visceral Surgery, , University Hospital Ulm, ; Albert-Einstein-Allee 23, 89081 Ulm, Germany
                [3 ]KfH Kuratorium für Dialyse und Nierentransplantation e.V, KfH-Nierenzentrum, Erlenstraße 40, 89077 Ulm, Germany
                Article
                4479
                10.1186/s13104-019-4479-6
                6642600
                31324271
                1f3c35fa-5d0c-4937-afbb-9f66fbede70b
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 16 June 2019
                : 12 July 2019
                Categories
                Research Note
                Custom metadata
                © The Author(s) 2019

                Medicine
                calcitonin,hypercalcitoninemia,secondary hyperparathyroidism,renal insufficiency,parathyroid surgery

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