Correlation between vitamin D levels and bone metabolism in children with cow’s milk allergy

Objective Research is limited regarding biochemical markers of bone metabolism among children with cow’s milk protein allergy (CMPA). We aimed to determine differences in vitamin D and bone metabolism markers between infants with CMPA and healthy infants and explore relationships between these in a cross-sectional study. Methods In total, we included 41 children diagnosed with CMPA and under systematic medical and nutritional care at our center, and 50 healthy children as a control group. We reviewed demographic and clinical characteristics and measured serum biomarkers. Results We found that serum 25-hydroxyvitamin D (25(OH)D) levels among infants in the CMPA group were significantly lower than those in the control group, and levels of bone-specific alkaline phosphatase (BALP), serum phosphorus, and serum calcitonin were reduced. Pearson correlation analysis showed that serum 25(OH)D concentrations in the CMPA group were negatively correlated with parathyroid hormone but not significantly correlated with calcitonin and BALP. Logistic regression showed that CMPA was a risk factor for vitamin D deficiency. Conclusions Our study indicated that CMPA was associated with disturbances in bone metabolism. Levels of vitamin D in children with CMPA were lower than those in healthy children. CMPA was a risk factor for vitamin D deficiency.

Unusual increase in carcinoembryonic antigen despite response to selpercatinib in two patients with medullary thyroid cancer

Introduction: Serum calcitonin (CT) and carcinoembryonic antigen (CEA) are valuable tumour markers in patients with medullary thyroid carcinoma (MTC). Both markers most often evolve in parallel after treatment. Selpercatinib (LOXO-292) is a highly selective RET kinase inhibitor indicated in advanced RET-mutant MTC patients. Case presentation: We report two observations of RET-mutant progressive metastatic and symptomatic MTC patients who were treated with selpercatinib. Patient 1, a 61-year-old man, presented dyspnoea and diarrhoea at selpercatinib initiation with large neck lymph nodes and lung metastases. Patient 2, a 76-year-old man, had acute discomfort with flush and diarrhoea, with small but diffuse bone and liver disease. Both patients had an objective response with rapid clinical improvement and RECIST 1.1 response (-90%) in patient 1. A rapid dramatic decrease in CT level was observed in both patients (-99% in both patients) while CEA levels gradually and sustainably increased after selpercatinib initiation (+207% at cycle 15 in patient 1 and + 835% at cycle 14 in patient 2). In both patients, FDG PET/CT did not show any abnormal uptake that could explain the CEA increase. Colonoscopy and oesogastric fibroscopy showed colonic polyposis with mild oesophagitis and gastritis in patient 1 and were normal in patient 2. Conclusion: These observations show an unusual and lasting increase in serum CEA in two MTC patients who exhibited an objective tumour response to selpercatinib. The mechanism behind this unexpected rise in CEA level remains unknown. The frequency of this evolving profile will be determined in further phase III studies.

Low Serum Calcitonin Gene-Related Peptide Level is Associated with Severity of Coronary Stenosis

Purpose: To evaluate the relationship between the serum calcitonin gene-related peptide (CGRP) level and severity of coronary stenosis. Methods: A total of 233 eligible patients who underwent coronary angiography were divided into two groups: a control and a coronary heart disease (CHD) group. The angiographic severity of coronary stenosis was evaluated by SYNTAX and Gensini scores. The incidence of major adverse cardiovascular events within two years was collected. Results: A negative correlation between serum CGRP levels and Gensini scores was observed in all patients (r=-0.352, p<0.001), the control group (r=-0.422, p<0.001) and the CHD group (r=-0.393, p<0.001). Serum CGRP levels were negatively associated with SYNTAX scores in the CHD group (r=-0.522, p<0.001). The area under the curve of CGRP for identifying high SYNTAX scores (>22) was 0.772 [95% confidence interval (CI): 0.673-0.870, p<0.001], and for identifying high Gensini scores was 0.744 (95% CI: 0.646-0.842, p<0.001). A CGRP concentration of 25.05 pg/ml was selected as the cutoff point. A low CGRP level (<25.05 pg/ml) was an independent predictor of severe coronary stenosis, a SYNTAX score >22 [odds ratio (OR) =5.819, 95% CI: 2.240-15.116; p<0.001] and a high Gensini score (>64) (OR=4.943, 95% CI: 2.020-12.095; p<0.001). The low CGRP group had a higher incidence of major adverse cardiovascular events within two years (11.1 vs. 3.1%, p=0.031). Conclusion: In coronary atherosclerosis patients without acute myocardial injury, serum CGRP levels were negatively associated with the severity of coronary stenosis.

Metastatic Lymph Node Ratio for Predicting Recurrence in Medullary Thyroid Cancer

The lymph node ratio (LNR) has been investigated as a prognostic factor in many different types of cancers, including differentiated thyroid cancer; however, reports regarding medullary thyroid cancer (MTC) are limited. Therefore, this study aims to evaluate LNR as a risk factor for structural recurrence in patients with MTC. Medical records of patients treated for MTC in a single tertiary center between 1995 and 2017 were retrospectively reviewed. LNR is defined as the number of metastatic lymph nodes or lymph node metastases (LNM) divided by the number of retrieved lymph nodes or lymph node yield (LNY). In the survival analysis, recurrence-free survival was defined as the time from the date of total thyroidectomy to recurrence or last follow-up. To identify risk factors influencing structural recurrence, univariable and multivariable Cox proportional hazard models were used. A total of 132 patients were enrolled. The mean age of study participants was 49.7 years, and 86 patients (65%) were women. Structural recurrence was identified in 39 patients at the end of the study period, and the median follow-up period was 8.7 years. In univariable analyses, gross extra thyroidal extension, N stage, postoperative serum calcitonin and carcinoembryonic antigen (CEA) levels, and LNR were significant (p < 0.05) predictors of structural recurrence. In multivariable analysis, postoperative serum calcitonin, postoperative serum CEA, and LNR were identified as a predictor of disease-free survival (p < 0.05). LNR can potentially predict structural recurrence as a quantitative evaluation tool for lymph node metastasis in patients with MTC.

Prognostic Value of Preoperative Serum Calcitonin Levels for Predicting the Recurrence of Medullary Thyroid Carcinoma

BackgroundSerum calcitonin level is a useful biomarker for predicting primary tumor size, the extent of lymph node, and distant metastasis in patients with medullary thyroid carcinoma (MTC). However, the association between preoperative serum calcitonin levels and long-term oncologic outcomes has not yet been established. The aims of this study were to determine the preoperative serum calcitonin cut-off value for predicting disease recurrence and to evaluate its prognostic value.MethodsPatients with MTC (n = 169) who were treated at a tertiary referral hospital in Korea between 1995 and 2019 were enrolled. To determine the preoperative serum calcitonin cut-off value for predicting structural recurrence, the maximum of the standardized log-rank statistics of all possible cut-off values was used. Multivariable Cox regression analysis was used to determine prognostic factors for disease-free survival.ResultsThe overall disease-free survival rate was 75.7%. The preoperative serum calcitonin cut-off value that predicted structural recurrence was 309 pg/mL. Preoperative serum calcitonin levels of &gt; 309 pg/mL were the strongest independent predictor of disease recurrence (hazard ratio (HR) 5.33, 95% confidence interval (85% CI) 1.67–16.96; P = 0.005). Lateral lymph node metastasis (HR 3.70, 95% CI 1.61–8.51; P = 0.002) and positive resection margins (HR 3.57, 95% CI 1.44–8.88; P = 0.006) were also significant predictors of disease recurrence.ConclusionsThe preoperative serum calcitonin cut-off value is useful in clinical practice. It is also the best predictive factor for disease-free survival. Preoperative serum calcitonin levels may help determine the optimal postoperative follow-up strategy for patients with MTC.

Medullary thyroid carcinoma in children: current state of the art and future perspectives

Medullary thyroid carcinoma (MTC) is a distinct type of malignant thyroid tumor in cell origin, biological behavior, and natural history. It accounts for 1.6% of all thyroid cancers and presents either sporadically or as a hereditary disease, the latter occurring as a part of multiple endocrine neoplasia (MEN) 2A and MEN2B syndromes or as a familial MTC disease with no other manifestations. The gene responsible for the hereditary form is the rearranged during transfection (RET) gene, a proto-oncogene located to human chromosome 10. Most pediatric MTC cases have been discovered after genetic testing investigations, leading to the concept of prophylactic surgery in presymptomatic patients. Therefore, the genetic status of the child, along with serum calcitonin levels and ultrasonographic findings, determine the appropriate age for prophylactic surgical intervention. Nevertheless, a diagnosis at an early stage of MTC warrants total thyroidectomy and central lymph node dissection with the addition of lateral/contralateral lymph node dissection depending on the tumor size, ultrasonographic evidence of neck disease, or calcitonin levels. Conversely, locally advanced/unresectable or metastatic MTC is primarily treated with multikinase inhibitors, while more specific RET inhibitors are being tested in clinical trials with promising results.

Serum calcitonin gene related peptide (CGRP) levels in migraine: A study on its clinical correlation and diagnostic efficacy

Migraine is a primary headache disorder marked by recurrent unilateral headache episodes. Calcitonin gene related peptide (CGRP) plays major role in migraine pathophysiology. CGRP is multifunctional, and its vasodilating activity within the central and peripheral blood vessels is one in all its primary functions. The intention is to prove serum calcitonin gene related peptide (CGRP) as an early diagnostic tool for migraine and the novelty is to correlate it with characteristics of migraine so that it helps in early initiation of treatment. Methods. 100 subjects including 90 patients with migraine and 10 with non-headache (NH) age-matched controls were prospectively recruited in our current study. The subjects were aged from 15- 50 years. The clinical assessment was made every month for the three months after the start of therapy. The subjects were compared based on the serum CGRP values. Serum CGRP concentrations were measured by using CGRP ELISA kit. Results. Out of total subjects selected, the maximum (23.3%) subjects were between age 26 and 30 years and least effected age group was 46-50 years (4.44%). Females’ predominance with 82% than males with 18%.Stress was major trigger occurring in 57% of cases. Throbbing pain with elevated CGRP levels 130.44±114.22 and p value (p = 0.01). The average CGRP levels was higher in test group 149.00±93.86 compared to control 61.30±24.37 with p value (p = 0.02). Conclusions. The serum CGRP levels were statistically more in migraine patients correlated with characteristics like throbbing type of pain, stress and inadequate sleep. Hence, the serum CGRP levels estimation can be considered as a diagnostic tool for migraine when the clinical character’s over lap or early in the course of migraine when all criteria for diagnosis are not yet fulfilled.

Medullary Thyroid Cancer: Case Series Reports and Literature Review

Background: Medullary thyroid carcinoma (MTC) is a rare neuro-endocrine tumor that arises from the C-cells of the thyroid. About 20- 25 % of MTC cases may be associated with hereditary syndromes like MEN 2A, MEN 2B and Familial MTC. The survival rate is related mainly to the age of the patient, stage of the disease and completion of the surgical resection. Methods: Retrospective review of 11 patients who were diagnosed with medullary thyroid cancer in our general surgery department during the period from 2011 to 2021. All patients had preoperative assessment including history taking, clinical examination, tumor marker (calcitonin and CEA), thyroid function testing, ultrasonography and FNAC. All patients underwent genetic assessment to exclude any underlying genetic mutation. Results: The mean age of diagnosis was 57.73 ± 16.45 years of age. Three patients were males and eight were females. All patients had total thyroidectomy, central and lateral neck dissection except one patient who had prophylactic thyroidectomy due to familial inherited RET mutation. Two patients had recurrence; both of them had high-stage tumor (T3 and T4) with multiple cervical lymph nodes metastasis. The sensitivity of serum calcitonin for the detection of MTC was about 98%. Patients, who had localized disease and underwent complete surgical resection, had good overall survival rates compared with patients with advanced disease. Conclusion: MTC represent a heterogeneous group of thyroid cancers. The overall survival is better than that of undifferentiated thyroid cancers. Complete resection of the thyroid tumor and any local or regional metastases provides the only cure for patients with MTC. Further researches are still needed to improve our understanding and management of MTC.

Impact of RET Screening on the Management of Multiple Endocrine Neoplasia Type 2A: 10 Years Experience and Follow-up in Three Families

Background: Multiple endocrine neoplasia type 2A (MEN 2A) is mainly caused by germline RET codon C634 mutation and is characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO), and hyperparathyroidism (HPTH). The early diagnosis and initial normative treatment are helpful for the long-term outcome of MEN2A. Methods: Three index cases and their 29 relatives from three families with MEN2A were included in this study. Genetic screening was performed on all participants. Demographic, clinical profiles, tumor histopathologic features, and follow-up records were systematically analyzed. Results: In total, RET C634Y mutation was identified in 10 individuals (10/32, 31.3%). Among them, 5 presented with MTC symptoms, whereas the other 5 did not show apparent clinical manifestation, and all were subjected to thyroidectomy with varying neck dissection. Compared to individuals in the former, the latter benefited greatly from RET screening with significantly younger age at diagnosis of MTC and surgery (18.1 ± 13.8 years vs. 39.0 ± 14.1 years, P =0.045), and less-aggressive MTC behavior (size: 0.74 vs. 2.82 cm, P =0.026; LN+/resected: 20.0% vs. 100.0%, P =0.048) and also lower recurrence rate of MTC (20.0% vs. 100.0%, P =0.048). The PHEO was identified in 6 of the 10 carriers (60.0%), and all had undergone adrenal-sparing surgery. During the 10 years of follow-up, one (16.7%) developed recurrence of PHEO. Conclusion: Integrated RET screening, serum calcitonin, and plasma metanephrine/normetanephrine levels can facilitate the early diagnosis and standardized MTC/PHEO surgery to improve the prognosis of MEN2A. Laparoscopic adrenal-sparing surgery prior to the bilateral total thyroidectomy is a preferred surgical approach for PHEO.

Breast metastasis from medullary thyroid carcinoma: a report of a case

Background Metastasis to the breast is rare. We herein report a patient with metastatic medullary thyroid carcinoma to the breast for whom measuring the calcitonin level was an important clue to the correct diagnosis. Case presentation A 54-year-old woman visited our hospital for the treatment of recurrent metastatic medullary thyroid carcinoma due to multiple endocrine neoplasia 2A and breast cancer. Positron emission tomography performed before the operation for metastatic medullary thyroid carcinoma recurrence in the neck showed the accumulation of 18F-fluorodeoxyglucose in the bilateral breast at sites other than the disease in the neck. Ultrasonography revealed multiple tumors in both breasts. A core needle biopsy of three breast tumors was performed. Microscopically, the tumor cells showed solid growth and did not show a tubular structure. She was diagnosed with triple-negative invasive ductal carcinoma. Post-operative positron emission tomography was performed as the serum calcitonin level increased after the operation. The accumulation of 18F-fluorodeoxyglucose in the bilateral breast tumors and lymph nodes in the neck was noted. The possibility of the breast tumors being metastasis of metastatic medullary thyroid carcinoma was considered. Needle aspiration was performed for three breast tumors. The calcitonin level of the washout fluid was measured and found to be ≥ 17,500 pg/mL. Immunohistochemistry showed that the tumor cells were calcitonin-positive and gross cystic disease fluid protein-15-negative. Vandetanib was started as recurrent metastatic medullary thyroid carcinoma with breast metastasis was finally diagnosed. The serum calcitonin level decreased after 1 month. Conclusion Although breast metastasis of medullary thyroid carcinoma is rare, a correct diagnosis is indispensable for appropriate treatment. When a breast tumor shows atypical morphological features for breast cancer according to the histopathology in a patient with a history of cancer, metastasis to the breast should be considered. Calcitonin measurement of the needle washout fluid was useful for confirming metastatic medullary thyroid carcinoma.