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The article presents the discussion on revised recommendations for celiac disease (CD) screening and biopsy including consideration of a serology-based diagnostic approach. Topics include expanded section on skin disorders showing continuous glucose monitoring (CGM)-related and insulin pump-related skin issues; and screening for thyroid disease by measurement of TSH, anti-thyroid peroxidase antibodies and anti-thyroglobulin antibodies.

Our work aimed to study the influence of cholecalciferol on neurogenesis, neurotrophins and their receptors pathway-focused genes expression in patients with autoimmune thyroiditis and hypothyroidism. The pathway-specific PCR array (Neurotrophins and Receptors RT2 Profiler PCR Array, "QIAGEN", Germany) was used to identify and validate the neurogenesis regulatory genes expression in patients with thyroid pathology and control group. The results showed that in patients with autoimmune thyroiditis-caused primary hypothyroidism, the expression of BDNF, FAS, FGF2, HSPB1, IL10, NGF, NGFR, NRG1, NTF3, NTF4, TGFB1, and TP53 were increased after treatment with cholecalciferol and L-thyroxine. The mRNA levels of BAX, GDNF, CD40, FOS, GDNF, GFRA1, IL1B, and STAT3 were significantly decreased in patients with autoimmune thyroiditis-caused primary hypothyroidism after treatment with cholecalciferol and Lthyroxine compared to the patients who received only L-thyroxine. Therefore, the addition of vitamin D to standard therapy alters the transcriptional profile of blood cells in patients with primary hypothyroidism. [ABSTRACT FROM AUTHOR]

The thyroid hormone plays a vital role in the development and maturation of the nervous system not only during prenatal and perinatal age but also in adults. "Peripheral marker hypothesis" revealed that gene expression changes in some regions of the brain are reflected into the peripheral blood lymphocytes. The objective of the study was to investigate changes in the gene expression profile of neuropeptides and their receptors in patients with different forms of thyroid pathology. One hundred fifty-three patients with thyroid pathology were enrolled in the study. They were divided into three groups: group 1 included 16 patients with postoperative hypothyroidism, group 2 included 65 patients with hypothyroidism resulting from autoimmune thyroiditis (AIT), and group 3 included 72 patients with AIT and elevated levels of anti-thyroglobulin (anti-Tg) and anti-thyroid peroxidase (anti-TPO) antibodies in the serum. We used a pathway-specific polymerase chain reaction (PCR) array (RT² Profiler™ PCR Array Human Neurotrophins & Receptors, QIAGEN, Germany) to identify and verify neuropeptides and receptors pathway-focused gene expression in 12 individuals that were randomly selected from each group using real-time PCR. Our research identified that patients with postoperative hypothyroidism had a considerably increased expression of NPY1R, NTSR1, and NPY4R. The patients with hypothyroidism caused by autoimmune thyroiditis had considerably lower expression of NTSR1, while the expression of NPY1R increased. The mRNA levels of NPY2R and PNOC increased in the patients with elevated levels of autoantibodies anti-Tg and anti-TPO in the serum, and mRNA levels of NPY1R and NTSR1 decreased in this group of patients. [ABSTRACT FROM AUTHOR]

Aims: We aimed to analyze the relationship between epilepsy and glutamic acid decarboxylase autoantibodies (GADA) in patients with type 1 diabetes mellitus (T1DM) and the impact of GADA on demographic, clinical, and metabolic data in T1DM patients with epilepsy. Methods: We searched for patients with T1DM ≤20 years and GADA measurements, and within this group for patients with epilepsy. We formed groups: T1DM + Epilepsy + GADA positive; T1DM + Epilepsy + GADA negative; T1DM + GADA positive; T1DM + GADA negative. We used logistic regression to analyze the relationship between epilepsy and GADA with odds ratio adjusted for sex, duration of diabetes (DOD), and age at diabetes onset (ADO). We used logistic regression with odds ratio adjusted for DOD and ADO onset using epilepsy as a dependent variable and GADA, HbA1c, ketoacidosis, severe hypoglycemia (SH), sex, celiac disease, and autoimmune thyroiditis as independent variables. We conducted regression analyses adjusted for sex, DOD, and ADO to analyze differences in clinical/metabolic parameters between the groups. Results: Epilepsy was not more frequent in GADA‐positive patients (GPP). Logistic regression including all patients with GADA measurements showed that hypoglycemia with coma (HC) correlated with epilepsy when compared to no SH. We found no differences in clinical and metabolic data between GPP and GADA‐negative patients (GNP) with epilepsy. SH occurred more often in GPP with epilepsy in comparison to GPP without epilepsy. GNP with epilepsy had a higher rate of HC than GPP without epilepsy. Conclusion: We found no relationship between epilepsy and GADA. A relationship between T1DM and epilepsy might be explainable by SH. [ABSTRACT FROM AUTHOR]

Background: Autoimmune encephalitis is a new spectrum of autoimmune disorders of the central nervous system (CNS), which are characterized by pathogenic autoantibodies against neuronal surface antigens. Clinical presentations range from acute to subacute encephalopathy with neurological and psychiatric symptoms, and life-threatening autonomic dysfunction in severe cases. There exist no approved therapies nor is data available from controlled clinical trials. Patients are usually treated with diverse combinations of immunotherapy. However, effect of immunotherapy on antibody-producing cells and thus on levels of pathogenic autoantibodies is insufficient. Therefore, therapeutic response is sometimes prolonged with necessity of long-time intensive care treatment and also irreversible deficits occur in severe cases. This trial will investigate the efficacy and safety of bortezomib, a proteasome inhibitor known to selectively deplete plasma cells, in patients with severe autoimmune encephalitis who have been treated with rituximab with insufficient response.Methods: Generate-Boost is an investigator-initiated, multicenter, double-blinded, randomized controlled phase II trial which will be conducted in specialized neurological hospitals within the GENERATE (GErman NEtwork for Research on AuToimmune Encephalitis) network in Germany. Adult patients with severe autoimmune encephalitis (modified Rankin scale, mRS ≥ 3), autoantibodies against neuronal surface antigens, and pretreatment with rituximab are eligible for study participation. Fifty patients will be randomized 1:1 and undergo up to 3 cycles (each 21 days with 4 s. c. applications) of bortezomib or placebo. All patients will receive concomitant medication with dexamethasone, acyclovir and co-trimoxazole. The primary efficacy endpoint is the mRS score 17 weeks after first treatment application. Secondary endpoints are neurocognitive function, antibody titers, markers of neuronal cell damage, length of ICU/hospital stay, and mRS and Glasgow coma scale scores throughout the trial up to week 17. General and bortezomib-specific adverse events are monitored continuously.Discussion: The expected outcome of the study is to obtain first reliable data on a hypothesis-driven therapeutic option in severe and difficult-to-treat autoimmune encephalitis. If treatment with bortezomib is beneficial in these cases, this will be the basis for implementation in the current guidelines.Trial Registration: Clinicaltrials.gov , NCT03993262 . Registered June 20, 2019; German Clinical Trials Register, DRKS00017497. [ABSTRACT FROM AUTHOR]

Data regarding familial prevalence and recurrence risk ratio of autoimmune thyroid diseases (AITD) in Germany are lacking. The data from 179 German families of AITD patients encompassing 1 229 relatives were collected using standardized clinical and laboratory diagnostic criteria. Of this large collective, 86 AITD index cases with their 139 children and 106 AITD index cases with their 157 siblings were included. The familial prevalence was estimated by the recurrence risk ratio. This quotient indicates whether first degree relatives display an increased risk for developing AITD, compared with the general population. AITD were present in 14 % of children and 15 % of siblings of patients with AITD. Female gender was frequently affected in both off spring (female: male ratio = 3:1) and siblings (11:1). Daughters (19 % ) and sisters (24 % ) were more frequently affected than sons (7 % ) and brothers (3 % ). The risk for developing AITD was 16-fold and 15-fold increased in children and siblings, respectively, of patients with AITD. In particular, children and siblings of index cases with Hashimoto ’ s thyroiditis had a 32-fold and 21-fold increased risk, respectively, for developing immunthyroiditis. In comparison, the risk for developing Graves ’ disease was enhanced 7-fold in both children and siblings. The high prevalence of AITD in fi rst degree, foremost female, relatives of patients with AITD demonstrates the importance of family history for developing AITD. Hence, regular screening of children and siblings of patients with AITD for presence of immunethyroiditis is recommended. [ABSTRACT FROM AUTHOR]

Background: In adults, a significant impact of thyroid dysfunction and autoimmunity on health-related quality of life (HRQoL) and mental health is described. However, studies in children and adolescents are sparse, underpowered, and findings are ambiguous. Methods: Data from 759 German children and adolescents affected by thyroid disease [subclinical hypothyroidism: 331; subclinical hyperthyroidism: 276; overt hypothyroidism: 20; overt hyperthyroidism: 28; Hashimoto's thyroiditis (HT): 68; thyroid-peroxidase antibody (TPO)-AB positivity without apparent thyroid dysfunction: 61] and 7,293 healthy controls from a nationwide cross-sectional study ("The German Health Interview and Examination Survey for Children and Adolescents") were available. Self-assessed HRQoL (KINDL-R) and mental health (SDQ) were compared for each subgroup with healthy controls by analysis of covariance considering questionnaire-specific confounding factors. Thyroid parameters (TSH, fT4, fT3, TPO-AB levels, thyroid volume as well as urinary iodine excretion) were correlated with KINDL-R and SDQ scores employing multiple regression, likewise accounting for confounding factors. Results: The subsample of participants affected by overt hypothyroidism evidenced impaired mental health in comparison to healthy controls, but SDQ scores were within the normal range of normative data. Moreover, in no other subgroup, HRQoL or mental health were affected by thyroid disorders. Also, there was neither a significant relationship between any single biochemical parameter of thyroid function and HRQoL or mental health, nor did the combined thyroid parameters account for a significant proportion of variance in either outcome measure. Importantly, the present study was sufficiently powered to identify even small effects in children and adolescents affected by HT, subclinical hypothyroidism, and hyperthyroidism. Conclusions: In contrast to findings in adults, and especially in HT, there was no significant impairment of HRQoL or mental health in children and adolescents from the general pediatric population affected by thyroid disease. Moreover, mechanisms proposed to explain impaired mental health in thyroid dysfunction in adults do not pertain to children and adolescents in the present study., (Copyright © 2020 Hirtz, Keesen, Hölling, Hauffa, Hinney and Grasemann.)