Clinical and Biochemical Characteristics of Severe Hypothyroidism Due to Autoimmune Thyroiditis in Children.

Introduction: In the majority of countries, autoimmune thyroiditis is the main cause of acquired hypothyroidism in children. Typically, the natural course of the disease is initially insidious and the diagnosis is incidental. There are some children who develop severe hypothyroidism without a proper diagnosis. The aim of the study was to analyze the clinical and biochemical profiles of children with severe primary hypothyroidism due to autoimmune thyroiditis. Materials and Methods: We analyzed the records of 354 patients diagnosed between 2009 and 2019 with autoimmune thyroiditis. Only patients with TSH above 100 µIU/mL, associated with decreased free thyroxine and the presence of antithyroid antibodies, were enrolled in the study. The analysis encompassed clinical symptoms, thyroid and biochemical status, bone age, and imaging. Results: Twenty-six children were enrolled in the study. The mean age at diagnosis was 10.26 ± 3.3 years, with a female preponderance of 1.8:1. The most frequent symptom was growth impairment (77%) and weight gain (58%). Goiters were present in 42% of patients. Less common findings were pituitary hypertrophy (four patients) and hypertrichosis (three patients). Median values at the time of diagnosis were TSH 454.3 uIU/ml (295.0-879.4), anti-TPO antibodies 1,090 IU/ml, and anti-Tg antibodies 195 IU/ml. Anti-TSHR ab were evaluated only in six out of the 26 patients. The characteristic biochemical profile was correlated with the grade of hypothyroidism, and the strongest correlations were found with CBC parameters, lipid profile, aminotransferases, and creatine. Conclusion: In children with severe hypothyroidism, the most sensitive symptoms are growth arrest and weight gain despite the fact that, in some children, the auxological parameters at presentation could be within normal values for the population. The specific biochemical profile closely correlates to the severity of thyroid hormone deficiency and involves mostly erythropoiesis, liver function, and kidney function. Pituitary enlargement should be considered in each child with severe hypothyroidism. It is necessary to conduct prospective studies evaluating the actual frequency of anti-TSHR antibodies and pituitary enlargement in children with extremely high TSH, especially those presenting without goiters.

Metastatic Tumor Burden and Loci as Predictors of First Line Sunitinib Treatment Efficacy in Patients with Renal Cell Carcinoma.

The aim of this study was to investigate the prognostic impact of baseline tumor burden and loci on the efficacy of first line renal cancer treatment with sunitinib. Baseline and on-treatment CT scans were evaluated. Both the Kaplan-Meier and Weibull modelling survival estimators have been used to describe sunitinib treatment response. Logistic regression was used to confirm associations between tumor site, burden and survival. Additionally, analysis of the metastases co-occurrence was conducted using the Bayesian inference on treated and external validation cohorts. 100 patients with metastatic clear cell renal cell carcinoma were treated with sunitinib in this study. Presence of metastases in the abdominal region (HR = 3.93), and the number of brain metastases correlate with shorter PFS, while the presence of thoracic metastases (HR = 0.47) with longer PFS. Localization of metastases in the abdominal region significantly impacts risk of metastases development in other locations including bone and brain metastases. Biology of metastases, in particular their localization, requires further molecular and clinical investigation.

Gastrointestinal Vascular Malformations in Patients with Turner's Syndrome: A Systematic Review of Case Reports.

BACKGROUND/AIM: There is a paucity of data on gastrointestinal (GI) vascular abnormalities in patients with Turner's syndrome (TS). Therefore, this literature review aimed to characterize the nature of GI vascular malformations in patients with TS, their localization in the GI tract, and their clinical and laboratory manifestations. METHODS: A systematic search for articles was conducted using Medline and Embase (until August 2017). A manual search of the references of the included papers was performed to identify any potential additional references. We also conducted a retrospective chart review of all patients with TS and GI bleeding who were hospitalized at our institution. RESULTS: A total of 29 articles published between 1947 and 2015 that described 39 cases were reviewed. Additionally, we included 2 patients who were hospitalized at our institution. The median age of patients with TS was 15 years (range: 0.1-57 years). Iron deficiency anaemia (35/40), haematochezia (15/37), and melaena (14/36) were the most common symptoms. Abnormal GI vessels occurred throughout the entire bowel, with a predilection for the small intestine (72%, 29/40). The most common abnormal vessels (65%, 24/37) were telangiectasias and dilated veins. CONCLUSION: Telangiectasias and dilated veins of the small intestine were the most commonly seen abnormal GI vessels in patients with TS.

The pre-treatment characteristics and evaluation of the effects of recombinant human growth hormone therapy in children with growth hormone deficiency and celiac disease or inflammatory bowel disease.

THE AIM OF THE STUDY: was to investigate the coincidence of growth hormone deficiency (GHD) and celiac disease (CD) or inflammatory bowel disease (IBD) in patients referred for short stature, and to evaluate the baseline anthropometric parameters and the effectiveness of recombinant human growth hormone (rhGH) therapy in the first year in those patients (GHD+CD/IBD subgroup) in comparison to patients with GHD without CD or IBD (GHD-CD/IBD subgroup). MATERIAL AND METHODS: The study was retrospective and included 2196 short patients (height SDS [Standard Deviation Score] ≤ -1.2). 1454 patients had height SDS ≤ -2. Twenty-nine patients suffered from CD or IBD. GHD was confirmed in 419 patients with height SDS ≤ -2. The coexistence of GHD and CD or IBD was found in seven patients (GHD+CD/IBD subgroup). RESULTS: At baseline the GHD-CD/IBD subgroup did not differ significantly in chronological age, height SDS, height velocity (HV) before rhGH therapy, body weight SDS, and body mass index SDS from the GHD+CD/IBD subgroup. The improvement in height SDS within the first year of rhGH therapy was higher in the GHD+CD/IBD subgroup than in the GHD-CD/IBD subgroup and the difference was statistically significant (p<0.05). HV in the first year of rhGH therapy was also significantly higher in the GHD+CD/IBD subgroup than in the GHD-CD/IBD subgroup (p < 0.05). CONCLUSIONS: In patients with chronic inflammatory disorders of the gastrointestinal tract, especially celiac disease, coexisting with GHD, rhGH therapy could be effective and should be administered together with therapy of primary gastrointestinal disease.

Graves' disease in children in the two decades following implementation of an iodine prophylaxis programme.

Grave's disease (GD) is a form of thyroid autoimmune disease characterised by hyperthyroidism. It is a rare clinical problem in paediatrics. Development of disease is the result of genetic susceptibility and some environmental factors. One of the best-documented environmental factors involved in thyroid autoimmunity is iodine excess. The aim of our study was to analyse the clinical course and response to pharmacological treatment in children diagnosed with Graves' disease in first two decades after mandatory salt iodination. Records of 94 children diagnosed with GD in the years 1998-2017 were analysed. Medical data of patients was compared between two decades following implementation of iodine prophylaxis: 1998-2007 (first-decade group - FDG) and 2008-2017 (second-decade group - SDG); 34 and 60 patients, respectively. Medical data of FDG was obtained from archival records and previous analysis performed in 2006. Data of 60 patients from SDG were obtained from currently available medical records. Results were statistically analysed using Microsoft Excel and Statistica 11 software. Results: In our study, after mandatory salt iodination, the tendency of an increase in newly diagnosed GD in children without family susceptibility was observed. The antibody profile indicates the significant contribution of the autoimmune process involving all thyroid antigens; therefore, the term "autoimmune hyperthyroidism" seems to be more appropriate than classical GD in this group of patients. The first-choice treatment with methimazole rarely causes adverse events during the therapy, and they have benign character.

Long-term response to sunitinib: everolimus treatment in metastatic clear cell renal cell carcinoma.

AIM: The study aim was to evaluate progression-free survival (PFS) and overall survival (OS) in patients with metastatic clear cell renal cell carcinoma on sunitinib (SU) and SU-everolimus treatment. PATIENTS & METHODS: After 7 years of enrollment and 9 years of follow-up, 193 consecutively presenting patients (151 men and 42 women) were treated. RESULTS: A total of 157 patients (81.3%) died and 36 patients (18.7%) survived. Median PFS in 193 SU-treated patients was 14.7 months and OS was 28.8 months. Median PFS was 13.98 months and median OS was 26.67 months in 175 patients treated with SU only or on SU-everolimus. CONCLUSION: The development of SU-induced hypothyroidism, hypertension, neutropenia and edema was a significant predictive and prognostic factor.

Mechanisms through which diabetes mellitus influences renal cell carcinoma development and treatment: A review of the literature.

Renal cell carcinoma (RCC) comprises 2­3% of all malignant tumors in adults. Many studies have established the key roles of smoking, hypertension and other components of metabolic syndrome in the occurrence of RCC. Diabetes mellitus (DM), one of the main consequences of metabolic syndrome, appears much more often in patients with RCC. The prognosis for patients suffering from both diabetes and RCC is worse than for those with kidney cancer only. Diabetes is linked to higher rate of recurrence and a greater number of distant metastases. These factors contribute to a reduction in overall survival (OS) and cause­specific survival (CSS). Diabetes can also occur as a paraneoplastic syndrome. Tyrosine kinase inhibitors (TKIs), which are agents used in the therapy of metastatic RCC, may have unexpected effects when administered to patients with diabetes. Studies and case reports have shown that they influence blood glucose levels (BGLs) in diabetic patients, sometimes causing dangerous episodes of hypoglycemia. Hyperinsulinemia and hyperglycemia can be considered independent carcinogenic factors, as they increase the amount of pro­inflammatory cytokines, reactive oxygen species and lipid peroxidation. TKIs have yet to be re­evaluated as to their safety of use in patients with diabetes.