Serum Calcitonin Levels Research Articles

Dapagliflozin Attenuates Hyperglycemia Related Osteoporosis in ZDF Rats by Alleviating Hypercalciuria.

Recent studies showed that in patients with type 2 diabetes mellitus (T2DM), Sodium-dependent glucose transporters 2 inhibitor (SGLT2I) may cause potential adverse effects on skeleton such as increasing the risk of fracture. This risk is possibly mediated by effects induced by all SGLT2I class drugs but whether Dapagliflozin aggravates osteoporosis in patients with T2DM remains controversial. Therefore, we designed this study to explore how Dapagliflozin affects the metabolism and the quality of bone in. T2DM animal models The effect of Dapagliflozin on skeleton was evaluated on male ZDF (Zucker Diabetic Fatty) rats—a rat model of diet induced spontaneous T2DM. Dapagliflozin was administrated via gavage at the dosage of 1.0 mg/kg/day. Bone tissue mineral density and the microarchitecture of tibiae were measured with micro-CT and biomechanics characteristic of the femora were tested using a three-point bending test. Serum bone biomarkers and other metabolic parameters were also tested via ELISA or other assays. Our results found that diabetic rats demonstrated symptoms of osteoporosis and Dapagliflozin could help to alleviate these defections caused by diabetes. Compared to the negative controls, the serum CT (calcitonin) level in ZDF rats as well as the uric calcium and phosphate levels were elevated, and these symptoms were alleviated by Dapagliflozin. Tibiae of Dapagliflozin treated rats demonstrated decreased cortical tissue mineral density while trabecular tissue mineral density and mean bone mineral density received a rise when compared to the matched controls. ZDF rats also showed defections in femora stiffness which could be relieved by Dapagliflozin administration. The mechanism of Dapagliflozin affecting bone quality is possibly connected to the suppression of serum calcitonin and excretion of calcium via urine rose by hyperglycemia. In conclusion, Dapagliflozin can prevent osteoporosis in ZDF rats by alleviating hypercalciuria.

Association between calcium-phosphorus balance and adolescent idiopathic scoliosis: A meta-analysis

Study designA systematic review and meta-analysis. ObjectiveThe objective of this meta-analysis was to evaluate the association between calcium-phosphorus balance and adolescent idiopathic scoliosis (AIS). MethodsDatabases, including PubMed, OVID database, Web of Science, CBM database and CNKI database were searched for the relevant case control studies and cross-sectional studies. Two authors selected studies and extracted data independently. Data analysis was performed by Review Manager Software 5.0. Subgroup analysis was performed on the serum level of vitamin D according to gender and menstruation. ResultsFive studies were included, with a total of 646 cases of AIS and 791 controls. AIS group had a lower serum level of vitamin D compared to control group [MD = −6.74, 95% CI (−9.47, −4.00)]. Gender and menstruation condition were thought to have no effect on the primary outcome of vitamin D level by subgroup analysis [MD = −5.97, 95% CI (7.61, −4.34)]. The AIS group had a lower calcium level [SMD= −0.77, 95% CI (−1.51, −0.02)] and calcitonin level compared to control group. There was no statistical difference in phosphorus level [SMD=0.5, 95% CI (−0.46, 0.57)] and parathyroid hormone level [SMD = −0.11, 95% CI (−0.54, −0.31)]. Meanwhile, the observational indexes, including serum levels of calcium, phosphorus, parathyroid hormone and calcitonin were within normal limits. ConclusionVitamin D deficiency may be involved in the pathogenesis of AIS by influencing the regulation of calcium-phosphors metabolism on human bone. Therefore, we suggest to screen vitamin D level in AIS patients. Level of EvidenceLevel III, Therapeutic Study

F-18-Dopa Positron Emission Tomography/Computed Tomography Is More Sensitive Than Whole-Body Magnetic Resonance Imaging for the Localization of Persistent/Recurrent Disease of Medullary Thyroid Cancer Patients.

Background: Elevated postoperative serum calcitonin (Ctn) level indicates persistent/recurrent disease in patients with medullary thyroid carcinoma (MTC). Its location is a challenge. The aim of our study was to compare the disease detection rates of F-18-Dopa (fluoro dihydroxyphenylalanine) positron emission tomography (PET)/computed tomography (CT), whole-body (WB) magnetic resonance imaging (MRI), F-18-FDG (fluorodeoxyglucose) PET/CT, WB CT scanning, neck ultrasonography, and bone scintigraphy in MTC patients with increased Ctn levels and unknown localization of the source. Methods: We compared the independent reading of each imaging procedure with a reference assessment for structural disease defined by pathology or concordance between two imagings or with subsequent follow-up. The detection rate of each imaging modality was determined in per patient, per organ, and per lesion analysis. Results: Thirty-six consecutive patients (21 females, mean age: 57 years, sporadic MTC in 26 cases, median serum Ctn level: 760 pg/mL; range: 21-10,121) were analyzed. The reference assessment localized disease in 24 (64%) patients with 74 lesions detected in the thyroid bed (8), in neck lymph nodes (15), mediastinal lymph nodes (6), lungs (1), liver (2), bones (3), and other site (1). At the patient level, the detection rates were 64% (CI 0.48-0.80) for F-18-Dopa PET/CT with early acquisitions, 40% (CI 0.24-0.56) for F-18-FDG PET/CT, 40% (CI 0.24-0.56) for WB MRI, and 48% (CI 0.31-0.66) for WB CT scan. Conclusions: In MTC patients with increased Ctn and no known distant metastases, F-18-Dopa PET/CT is more sensitive to detect structural disease than any other imaging modality, including WB MRI.

RET S409Y Germline Mutation and Associated Medullary Thyroid Carcinoma.

Background: Inherited medullary thyroid carcinoma (MTC) is primarily caused by RET mutations that are commonly localized in exons 5, 8, 10, 11, and 13-16. In this study, we report pedigrees for individuals with MTC that harbor a germline S409Y variant within exon 6 of the RET proto-oncogene. Methods: Targeted sequencing was used to diagnose four apparently sporadic MTC index cases carrying the germline RET S409Y (c.1226 C>A) variant. Subsequently, 27 relatives of these individuals underwent clinical and genetic assessments and/or thyroid surgery. Furthermore, in silico analyses and in vitro assays were performed to predict or verify the potential oncogenic activity of the S409Y variant. Results: Overall, 15 of 31 participants were found to carry the RET S409Y variant. Of these, 6 presented with isolated MTC (mean age 50.2 years; range 41-75 years), of which 3 presented with neck lymph node metastases and 2 presented with distant liver or lung metastases. Among the remaining 9 carriers, 3 (mean age 56 years; range 41-76 years) had elevated serum calcium-stimulated calcitonin (sCtn) or concurrent marginally elevated serum calcitonin (Ctn) levels, whereas the other 6 (mean age 37.5 years; range 14-52 years) exhibited typical Ctn/sCtn levels (p < 0.05). None of the 15 carriers in these 4 families presented clinical evidence of pheochromocytoma, hyperparathyroidism, or Hirschsprung's disease. In silico analyses revealed that S409Y was a "possibly damaging" mutation that could affect the RET protein inter-domain interface. An in vitro assay revealed that the phosphorylation level of RET tyrosine 905 was relatively higher in the RET S409Y mutant than in wild-type (WT) RET. Moreover, transfection of HEK 293 cells with S409Y enhanced the phosphorylation activity of AKT, ERK pathways, and it increased cell proliferation compared with WT RET, but to a lesser degree than that for the RET C618Y and C634Y mutations. Conclusions: This study demonstrates that the novel germline RET S409Y variant is likely pathogenic and is associated with lower penetrance of MTC than that for the C618Y and C634Y mutations. Individuals with S409Y should be managed using a personalized approach, and additionally, "at-risk" family members should be evaluated. Additional studies are needed to elucidate the correlation between the S409Y mutation and multiple endocrine neoplasia type 2-specific tumors.

RET Proto-oncogene Gene Mutation Is Related to Cervical Lymph Node Metastasis in Medullary Thyroid Carcinoma.

RET proto-oncogene (RET) mutations were proved to be related to the development of medullary thyroid carcinoma (MTC). We aimed to analyze the role of RET mutations in cervical lymph node metastasis in patients with MTC. Forty-nine patients with preoperatively diagnosed MTC by fine-needle aspiration cytology (FNAC) who underwent bilateral total thyroidectomy with cervical lymphadenectomy were included. Postoperative RET gene test and pathological analysis were performed with the surgical specimens; serum calcitonin (Ctn) and carcinoembryonic antigen (CEA) levels were tested pre- and postoperatively, to evaluate the association between RET mutations and cervical lymph node metastasis in MTC. In these 49 patients, the RET mutation rates of Exon 11, Exon 10, Exon 11&13, Exon 13, and Exon 16 were 20.4%, 4.1%, 38.8%, 22.4%, and 0%, respectively. The lymph node metastasis rates of patients with RET mutation in the central and lateral compartments were 71.4% and 64.3%, respectively, versus 28.6% and 14.3% of patients without RET mutation. The preoperative basal serum levels of Ctn (234.8 ± 188.4 vs. 44.4 ± 27.5, p< 0.01) and postoperative Ctn (49.8 ± 86.4 vs. 3.7 ± 2.2, p= 0.001) in MTC patients with RET mutations were significantly higher than those in MTC patients without RET mutation. In addition, the preoperative (50.2 ± 76.7 vs. 7.4 ± 6.8, p= 0.001) and postoperative serum levels of CEA (13.2 ± 19.5 vs. 1.3 ± 1.6, p< 0.01) in MTC patients with RET mutations were significantly higher than those in MTC patients without RET mutation (p< 0.05). RET mutation was related to cervical lymph node metastasis in patients with MTC, especially the mutation in Exon 11&13. Patients with RET mutation in Exon 11&13 might be regarded as the predictor for prophylactic ipsilateral total cervical lymphadenectomy even without clear evidence of lateral cervical lymph node metastasis.

Diagnostic value of fine needle aspiration cytology combined with serum calcitonin for medullary thyroid carcinoma

Objective To investigate the value of fine-needle aspiration cytology (FNAC) combined with serum calcitonin in the diagnosis of medullary thyroid carcinoma (MTC). Methods Retrospective analysis of the serum calcitonin and FANC results in 17 cases of MTC confirmed by pathological examination. The diagnostic value of the two methods alone and in combination for MTC were compared. Results 13 of the 17 MTC patients (13/17, 76.5%) underwent fine needle aspiration biopsy before surgery, 11 cases (11/13, 84.6%) diagnosed as thyroid malignant tumor, 7 of whom were diagnosed or suspected of MTC (7/13, 53.8%). Serum calcitonin levels increased in different degrees in 16 patients. The sensitivity of the two methods combined in the diagnosis of MTC was 92.3% (12/13). Conclusions FNAC is an important diagnostic method for the evaluation of thyroid nodules, but it is not sensitive to the diagnosis of MTC. Serum calcitonin is highly sensitive but not universally available. Compared with FNAC alone, FNAC combined with the serum calcitonin examination may significantly improve the detection rate of MTC preoperative and reduce missed diagnosis. Key words: Ultrasonography; Biopsy, fine-needle; Calcitonin; Thyroid neoplasms; Carcinoma, medullary

Case report: Can a patient with an active cancer receive a kidney transplant?

Introduction: An active cancer is an absolute contraindication for kidney transplantation and a frequent cause of wait-list patient exclusion for long periods. Waiting time for kidney transplantation after the cancer diagnosis/treatment depends on multiple factors such as type of cancer, stage, histological type, prognosis, and physicians’ opinions. Case description: In this study, we describe a case of a 52-year-old man with medullary thyroid carcinoma classified as T1N1bM0 stage IV-A, who received a human leukocyte antigen identical living donor kidney transplantation despite not being biochemically cured. He received maintenance immunosuppression with tacrolimus, prednisone, and mycophenolic acid, switched to everolimus plus prednisone after 8 months. After 5 years, kidney function is excellent and there is no structural recurrence of the disease on imaging tests, although serum calcitonin levels remain elevated but stable. Conclusion: This is the first report that exposes the case of a patient with an active thyroid neoplasm receiving kidney transplantation. The good prognosis of the active neoplasm and the fact of having an identical human leukocyte antigen optimal donor made us proceed with the transplant with an excellent 5-year outcome.

Bone metabolism markers and hungry bone syndrome after parathyroidectomy in dialysis patients with secondary hyperparathyroidism.

To explore the short-term variation in bone metabolic markers and the characteristics of hungry bone syndrome (HBS) after parathyroidectomy (PTX) with forearm autotransplantation in uremic patients with secondary hyperparathyroidism (SHPT) and to provide a basis for the pathogenesis, diagnosis and treatment of metabolic bone disease in SHPT. A total of 115 patients with SHPT receiving PTX from July 2015 to December 2017, hospitalized at the First Affiliated Hospital of Nanjing Medical University, were enrolled in our study. We retrospectively analyzed the baseline clinical data, the levels of bone metabolism markers before and on the third day after PTX, and the risk factors predicting HBS. Preoperative baseline data showed that the levels of bone metabolic markers such as bone metabolism-regulating hormones: iPTH, calcitonin (CT); bone formation markers: phosphatase (ALP), osteocalcin (OC); bone resorption markers: type I collagen cross-linked N-telopeptides (NTX), type I collagen cross-linked C-telopeptides (CTX), tartrate-resistant acid phosphatase 5b (TRAP-5b) were all increased compared to normal levels. The levels of postoperative serum iPTH, CT, CTX and TRAP-5b decreased significantly compared to preoperative levels, while the levels of OC and ALP increased significantly. Of the 115 patients, 101 (87.8%) developed HBS after PTX. High preoperative serum ALP and low preoperative serum calcium level independently predicted the occurrence of HBS. Younger preoperative age, high preoperative serum ALP and iPTH level independently predicted the severity of HBS. In severe SHPT, both bone formation and resorption were active, which suggested the presence of high-turnover bone diseases characterized by up-regulation of osteoclasts-osteoblasts functionally coupling activation in the patients. PTX could promote osteoblast activity and reduce osteoclast activity. HBS was common after PTX. Preoperative higher serum ALP and lower calcium were independent predictors of the occurrence of HBS. Younger patients with higher preoperative ALP and PTH may need to closely monitor serum calcium levels and intensive calcium supplementation after PTX.

Effect of age and Gender on Fasting and Food-Stimulated Levels of Calcitonin, Parathyroid, and Gastrin Hormones in Healthy Adults

Objective: To investigate the effect of age and gender on basal and food-stimulated serum calcitonin (CT), parathyroid hormone (PTH), and gastrin levels among healthy adults. Methods: Ninety-six healthy adults (76 men and 20 women) aged between 21 and 43 years were recruited. Serum CT, PTH, and gastrin levels were measured after a 9-hour overnight fast, and 1 and 3 hours postprandially. Results: PTH levels decreased early and increased late after feeding. This change was significant in men but not in women. CT levels increased in response to food intake in men but not in women. Gastrin levels were significantly increased after feeding in both men and women. Mean basal and food stimulated CT, PTH, and gastrin levels did not significantly differ between genders. Fasting and post-prandial PTH levels were higher while gastrin levels were lower in older subjects (>30 years old) compared to younger subjects (≤30 years old). Fasting and postprandial CT levels were not significantly different between age groups. Conclusion: Age had a significant effect on fasting and food-stimulated PTH and gastrin hormone levels. The effect of age on PTH levels was independent of baseline vitamin D levels. Men showed significant changes in CT and PTH levels in response to feeding compared to women, although the mean hormone levels were not significantly different between men and women. Abbreviations: CT = calcitonin; MTC = medullary thyroid carcinoma; PTH = parathyroid hormone; SD = standard deviation.

Present status of prophylactic thyroidectomy in pediatric multiple endocrine neoplasia 2: a nationwide survey in Japan 1997-2017.

Background In Japan, prophylactic thyroidectomy involves out-of-pocket expense. The American Thyroid Association (ATA) recommends prophylactic thyroidectomy for medullary thyroid carcinoma (MTC) during early childhood in patients with multiple endocrine neoplasia type 2 (MEN2). The ATA reports a high frequency of postoperative complications in childhood, which also influenced the delay of prophylactic thyroidectomy in Japan. Methods This retrospective study of multiple medical centers in Japan included individuals aged <20 years diagnosed with germline RET mutations between 1997 and 2017. The onset and onset possibility were defined based on confirmed lesions or calcitonin levels. The definition of risk and prophylactic thyroidectomy were based on the ATA 2015 revised guideline. Results Twenty-one patients with MEN2 were enrolled (highest risk, n = 5; high risk, n = 5; and moderate risk, n = 11). The cumulative incidence of the onset/onset possibility reached 50% at 5 and 8 years and 100% at 9 years and 17 years in high- and moderate-risk patients, respectively. Of 7 patients with MEN2A, 71% underwent prophylactic thyroidectomy. Only one 5-year-old patient (C634Y) had increased serum calcitonin level after prophylactic thyroidectomy in the MEN2A group. The only permanent complication, which did not occur in patients who underwent total thyroidectomy alone, was hypoparathyroidism (33% of patients). This permanent complication occurred with clinically developed MTC. No permanent postoperative complications occurred in patients aged 5-6 years. Conclusions Prophylactic thyroidectomy reduces recurrence and postoperative complications in pediatric patients with MEN2. Early thyroidectomy based on only calcitonin level could possibly reduce thyroidectomy delay.

Calcitonin negative Medullary Thyroid Carcinoma: a challenging diagnosis or a medical dilemma?

BackgroundMedullary thyroid carcinoma is a neuroendocrine tumor belonging form a malignant growth of the thyroid parafollicular C-cells, representing from 1 to 10% of all thyroid cancer. The biochemical activity of medullary thyroid carcinoma includes the production of calcitonin and carcinoembryogenic antigen, which are sensitive tumor markers, facilitating the diagnosis, follow-up and prognostication. The diagnosis is reached through the identification of high basal calcitonin serum level or after pentagastrin stimulation test. Medullary thyroid carcinoma is able to produce other relevant biomarkers as procalcitonin, carcinoembryionic antigen and chromogranin A. In Literature are described few cases of medullary thyroid carcinoma without elevation of serum calcitonin, an extremely rare event. The aim of this study was to analyse the presentation, the main features and therapeutic management of medullary thyroid carcinoma associated with negative serum calcitonin levels.MethodsUsing the PubMed database, a systematic review of the current Literature was carried out, up to February 2018. Finally, nineteen articles met our inclusion criteria and were selected according to the modified Newcastle-Ottawa scale.ResultsFourty-nine patients with definitive pathology confirming medullary thyroid carcinoma and with calcitonin serum level in the normal range were identified (24 female, 24 male and not reported gender in 1 case). Mean age was 51.7 years. Serum calcitonin levels were reported for 20 patients with a mean value of 8.66 pg/mL and a range of 0.8–38 pg/mL. Despite the low or undetectable calcitonin serum level, at immunochemistry in almost the half of the cases reported by the Authors, the tumors presented diffuse or focal positivity for calcitonin and carcinoembryionic antigen, while was reported a chromogranin A positivity in 41 of the 43 tested patients.ConclusionsCalcitonin negative medullary thyroid carcinoma is an extremely rare pathology. The diagnosis and the surveillance is often challenging and delayed, due to the lack of elevation of serum markers as calcitonin and carcinoembryionic antigen. Further studies are needed, to better define options for management of non secretory medullary thyroid carcinoma and to identify new and reliable biomarkers associated to diagnosis and relapse of this medical dilemma.

Dynamics of serum phosphorus, calcium, and hormones during egg laying cycle in Hy-Line Brown laying hens

Understanding serum dynamic patterns of P, Ca, and P-Ca metabolism related hormones would help us in developing feeding strategies that can be used to reduce dietary inorganic P input and decrease P excretion in laying hens. In the current study, Hy-Line Brown laying hens (35-wk-old, n = 15) were fed with a corn-soybean meal-based commercial laying hen diet containing 0.24% non-phytate P, 3.59% Ca, 2,040IU/kg vitamin D3, 2,500 FTU/kg phytase, 2,636kcal/kg ME, and 15.9% crude protein. Blood samples from each laying hen were collected immediately after the first oviposition; 3, 6, 9, 12, 15, 18, and 21h after the first oviposition; and immediately after the second oviposition. As a result, after the first oviposition, serum P and Ca levels of the laying hens were gradually increased, peaked in 6h, and then gradually decreased all the way down until the second oviposition. Similarly, serum fibroblast growth factor 23 (FGF-23) level was gradually increased after the first oviposition, but peaked in 9h, and then gradually decreased all the way down until the second oviposition. Serum 1,25-dihydroxy-cholecalciferol [1,25(OD)2D3] level was linearly and quadratically decreased during the egg laying cycle we observed. The serum levels of parathyroid hormone, calcitonin, and alkaline phosphatase were erratically fluctuated during the egg laying cycle in patterns that are very different from that of serum P, Ca, FGF-23, and 1,25(OD)2D3. In conclusion, the result that serum FGF-23 peaked after serum P indicates that the dynamics in serum FGF-23 levels might be driven by serum P levels during the egg laying cycle.

SUN-595 Chronic Diarrhea as a Manifestation of Medullary Thyroid Cancer

Background: Tumor secretion of calcitonin (Ct), Ct gene-related peptide, or other substances can cause diarrhea in patients with advanced medullary thyroid cancer (MTC). We report 3 patients with chronic diarrhea due to MTC in whom the diagnosis was delayed. Case 1: A 26-year-old man reported to Gastroenterology (GI) clinic with a 6-month history of diarrhea. An extensive work-up was performed including upper and lower endoscopies that were unrevealing. A diagnosis of chronic diarrhea of unknown etiology was made and patient received symptomatic treatment. Six months later the patient lost about 16 pounds of weight; a chest CT was performed showing a left thyroid mass with cervical lymphadenopathy and skeletal metastases. Biopsy of the thyroid mass confirmed MTC. Serum calcitonin (Ct) level was 52894 ng/L (ref <10). Additional tests (serum VIP, somatostatin, glucagon, pancreatic polypeptide, neurotensin, and gastrin levels) were normal. Two months post thyroidectomy and lymph node dissection, Ct level was 447 ng/L and diarrhea improved. Subsequently serum Ct started rising and imaging studies showed extensive metastases and presently patient is treated with tyrosine kinase inhibitors. Case 2: A 27-year-old woman was referred to GI clinic with a 3-month history of diarrhea. Upper endoscopy and colonoscopy were noncontributory. Detailed laboratory evaluations were normal and a diagnosis of irritable bowel syndrome was made. One month later, thyroid nodules were detected and biopsy of the thyroid nodule revealed MTC. Serum Ct was 2890 ng/L. Patient underwent total thyroidectomy and histology confirmed MTC with metastasis. Two months later, serum Ct was 490 ng/L with improvement in diarrhea and reduced loperamide dosage. Case 3: A 38-year-old man was referred to GI clinic with a 4-month history of diarrhea. Patient underwent a detailed evaluation and was treated with loperamide and tincture of opium with partial improvements. Three months later, a physical examination revealed a 4-cm left thyroid nodule and biopsy suggested MTC. Serum Ct level was 4088 ng/L. Patient underwent total thyroidectomy and lymph node dissection. Histology confirmed MTC. Two months postoperatively, serum Ct level normalized and diarrhea completely resolved. Discussion The link between tumor humoral secretion and diarrhea is well established in patients with MTC as diarrhea is more frequent with metastatic disease and immediately improves after resection of the tumor. The improvement in diarrhea was seen in our patients postoperatively. Diarrhea may result from a secretory process induced by elevated circulating Ct or other substances such as prostaglandin or serotonin. Other proposed mechanisms include decreased absorption in the colon secondary to motor disturbances. In conclusion, MTC should be considered when evaluating chronic diarrhea.

Time to calcitonin normalization after surgery for node-negative and node-positive medullary thyroid cancer

It remains unclear when postoperative serum calcitonin levels should be measured in patients with medullary thyroid cancer (MTC) and, specifically, whether this decision should be based on the preoperative calcitonin level or nodal status. A cohort of patients with previously untreated MTC was studied. Kaplan-Meier analyses, stratified by preoperative calcitonin level, nodal status and number of nodal metastases, were performed to determine time to calcitonin normalization after initial surgery, with statistical analysis by means of the log rank test. Some 213 patients with node-negative and 182 with node-positive MTC were included in the study. Postoperative calcitonin levels normalized in a mean of 3·5 versus 3·7 days respectively among patients with preoperative calcitonin levels of 10-100 pg/ml (P = 0·815); 4·8 versus 5·3 days in those with preoperative calcitonin levels of 100·1-500 pg/ml (P = 0·026); 5·3 versus 9·9 days in patients with preoperative calcitonin levels of 500·1-1000 pg/ml (P = 0·004); and 6·6 versus 57·7 days among those with preoperative calcitonin levels exceeding 1000 pg/ml (P < 0·001). Calcitonin levels normalized in a mean of 4·7 days when nodal metastasis was not present, 5·2 days in those with one to five nodal metastases, 7·0 days in patients with six to ten nodal metastases, and 57·1 days among patients with more than ten nodal metastases. Postoperative calcitonin normalization curves paralleled each other in patients with node-negative MTC, but diverged in those with node-positive disease and with more nodal metastases. Calcitonin levels typically normalize within 1 week; and within a fortnight in those with node-positive MTC and preoperative calcitonin levels of 500·1-1000 pg/ml. With node-positive MTC and preoperative calcitonin levels exceeding 1000 pg/ml, and with more than ten nodal metastases, calcitonin normalization takes longer.

Hypercalcitoninaemia in pseudohypo-parathyroidism type 1A and type 1B.

SummaryPseudohypoparathyroidism (PHP) is a heterogeneous group of rare endocrine disorders characterised by normal renal function and renal resistance to the action of the parathyroid hormone. Type 1A (PHP1A), which is the most common variant, also include developmental and skeletal defects named as Albright hereditary osteodystrophy (AHO). We present two cases, a 54- and a 33-year-old male diagnosed with PHP who were referred to us for persistently high levels of serum calcitonin. AHO and multinodular goitre were present in the 54-year-old male, while the second patient was free of skeletal deformities and his thyroid gland was of normal size and without nodular appearance. We performed GNAS molecular analysis (methylation status and copy number analysis by MS-MLPA) in genomic DNA samples for both patients. The analysis revealed a novel missense variant c.131T>G p.(Leu44Pro) affecting GNAS exon 1, in the patient with the clinical diagnosis of PHP1A. This amino acid change appears to be in accordance with the clinical diagnosis of the patient. The genomic DNA analysis of the second patient revealed the presence of the recurrent 3-kb deletion affecting the imprinting control region localised in the STX16 region associated with the loss of methylation (LOM) at the GNAS A/B differentially methylated region and consistent with the diagnosis of an autosomal dominant form of PHP type 1B (PHP1B). In conclusion, hypercalcitoninaemia may be encountered in PHP1A and PHP1B even in the absence of thyroid pathology.Learning points:We describe a novel missense variant c.131T>G p.(Leu44Pro) affecting GNAS exon 1 as the cause of PHP1A.Hypercalcitoninaemia in PHP1A is considered an associated resistance to calcitonin, as suggested by the generalised impairment of Gsα-mediated hormone signalling. GNAS methylation defects, as in type PHP1B, without thyroid pathology can also present with hypercalcitoninaemia.

Effects of nicotine on markers of bone turnover in ovariectomized rats.

IntroductionOsteoporosis is characterized by low bone mass and density, as well as change in microarchitecture of bone tissue leading to decreased bone strength. In vitro research shows nicotine can increase osteoblast activity and proliferation, also suppress osteoclast activity. Therefore we explore nicotine anti-resorptive property by in vivo true experimental and randomized posttest only controlled group research that was conducted in 18-20 weeks old Rattus norvegicus.MethodsTwenty-five female rats were divided into five groups, with 5 rats per group. The first group represented normal rats (Sham), while the second to fifth group underwent bilateral ovariectomy. The second group serves as positive control group (ovariectomy-only/OVX). The third to fifth group serve as dose 1 (P1-0.25mg/kg), dose 2 (P2-0.5 mg/kg), and Dose 3 (P3-0.75 mg/kg) treatment group receiving daily per-oral nicotine for 28 days, started 3 weeks post- ovariectomy. After 28 days treatment, the serum was checked.ResultsNicotine has dose-dependent manner on serum osteocalcin and serum DPD level. Level of osteocalcin in P2 group was significantly lower (Mann-Whitney, p = 0.008) compared to OVX group (59.4% lower). Level of DPD in all group was not significantly different (ANOVA, p < 0.05) but shows lowest level in P2 group. For serum calcitonin level, there's no significant different between groups.ConclusionNicotine at right low-dose might be able to inhibit osteoclast activity, thus open a possibility of anti-resorptive property of nicotine.

Tumor cells may circulate in medullary thyroid cancer patients independently of serum calcitonin.

Early detection of tumor relapse is a major issue in patients with medullary thyroid carcinoma. Calcitonin has been reported as a sensitive and accurate marker for recurrence of medullary thyroid carcinoma after thyroidectomy. Recent evidence nevertheless reveals pitfalls in calcitonin immunoassays due to the presence of heterophilic antibodies or macroaggregates. Calcitonin can also remain undetectable despite metastasis of rare tumor cells in thyroidectomized patients. In this context, we designed a sensitive and specific technique to identify calcitonin-positive circulating tumor cells (CTC) in medullary thyroid carcinoma. We demonstrate that calcitonin-positive CTCs are present in the peripheral blood of medullary carcinoma patients following complete thyroidectomy. Unexpectedly, the presence of CTCs could be identified up to 12 years after surgery even in the absence of detectable levels of serum calcitonin.

The RET C611Y mutation causes MEN 2A and associated cutaneous

BackgroundCutaneous 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 FindingsThis 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 ConclusionsThis 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.

18F]DOPA PET/ceCT in diagnosis and staging of primary medullary thyroid carcinoma prior to surgery

PurposeMedullary thyroid carcinoma (MTC) is characterized by a high rate of metastasis. In this study we evaluated the ability of [18F]DOPA PET/ceCT to stage MTC in patients with suspicious thyroid nodules and pathologically elevated serum calcitonin (Ctn) levels prior to total thyroidectomy and lymph node (LN) dissection.MethodsA group of 32 patients with sonographically suspicious thyroid nodules and pathologically elevated basal Ctn (bCtn) and stimulated Ctn (sCtn) levels underwent DOPA PET/ceCT prior to surgery. Postoperative histology served as the standard of reference for ultrasonography and DOPA PET/ceCT region-based LN staging. Univariate and multivariate regression analyses as well as receiver operating characteristic analysis were used to evaluate the correlations between preoperative and histological parameters and postoperative tumour persistence or relapse.ResultsPrimary MTC was histologically verified in all patients. Of the 32 patients, 28 showed increased DOPA decarboxylase activity in the primary tumour (sensitivity 88%, mean SUVmax 10.5). Undetected tumours were exclusively staged pT1a. The sensitivities of DOPA PET in the detection of central and lateral metastatic neck LN were 53% and 73%, in contrast to 20% and 39%, respectively, for neck ultrasonography. Preoperative bCtn and carcinoembryonic antigen levels as well as cN1b status and the number of involved neck regions on DOPA PET/ceCT were predictive of postoperative tumour persistence/relapse in the univariate regression analysis (P < 0.05). Only DOPA PET/ceCT cN1b status remained significant in the multivariate analysis (P = 0.016, relative risk 4.02).ConclusionThis study revealed that DOPA PET/ceCT has high sensitivity in the detection of primary MTC and superior sensitivity in the detection of LN metastases compared to ultrasonography. DOPA PET/ceCT identification of N1b status predicts postoperative tumour persistence. Thus, implementation of a DOPA-guided LN dissection might improve surgical success.

Elevated level of serum calcitonin of unknown origin

Elevated level of serum calcitonin of unknown origin