Thyroid morphology in the population of the southeastern part of the Tassr

For the first time NA Tolmachev (1870) reported the presence of goiter in the population of Mamadyshsky. Cheboksary and Kozmodemyansk districts of the former. Kazan province.

The Amino Acid Transporter Mct10/Tat1 Is Important to Maintain the TSH Receptor at Its Canonical Basolateral Localization and Assures Regular Turnover of Thyroid Follicle Cells in Male Mice

Cathepsin K-mediated thyroglobulin proteolysis contributes to thyroid hormone (TH) liberation, while TH transporters like Mct8 and Mct10 ensure TH release from thyroid follicles into the blood circulation. Thus, thyroid stimulating hormone (TSH) released upon TH demand binds to TSH receptors of thyrocytes, where it triggers Gαq-mediated short-term effects like cathepsin-mediated thyroglobulin utilization, and Gαs-mediated long-term signaling responses like thyroglobulin biosynthesis and thyrocyte proliferation. As reported recently, mice lacking Mct8 and Mct10 on a cathepsin K-deficient background exhibit excessive thyroglobulin proteolysis hinting towards altered TSH receptor signaling. Indeed, a combination of canonical basolateral and non-canonical vesicular TSH receptor localization was observed in Ctsk−/−/Mct8−/y/Mct10−/− mice, which implies prolonged Gαs-mediated signaling since endo-lysosomal down-regulation of the TSH receptor was not detected. Inspection of single knockout genotypes revealed that the TSH receptor localizes basolaterally in Ctsk−/− and Mct8−/y mice, whereas its localization is restricted to vesicles in Mct10−/− thyrocytes. The additional lack of cathepsin K reverses this effect, because Ctsk−/−/Mct10−/− mice display TSH receptors basolaterally, thereby indicating that cathepsin K and Mct10 contribute to TSH receptor homeostasis by maintaining its canonical localization in thyrocytes. Moreover, Mct10−/− mice displayed reduced numbers of dead thyrocytes, while their thyroid gland morphology was comparable to wild-type controls. In contrast, Mct8−/y, Mct8−/y/Mct10−/−, and Ctsk−/−/Mct8−/y/Mct10−/− mice showed enlarged thyroid follicles and increased cell death, indicating that Mct8 deficiency results in altered thyroid morphology. We conclude that vesicular TSH receptor localization does not result in different thyroid tissue architecture; however, Mct10 deficiency possibly modulates TSH receptor signaling for regulating thyrocyte survival.

Complicated Relationship between Genetic Mutations and Phenotypic Characteristics in Transient and Permanent Congenital Hypothyroidism: Analysis of Pooled Literature Data

Purpose. Mutations and phenotypic characteristics remain unclear in patients with congenital hypothyroidism (CH), and no study concerning whether the outcome of transient CH (TCH) or permanent CH (PCH) is determined by mutations has been reported. Methods. We searched the literature up to April 2019. Eligible studies and data extraction were performed. We estimated the relationship between mutations and phenotypic characteristics in pooled patients with CH. Results. Two hundred forty-one cases were pooled from 41 eligible studies. The thyroid morphology, classification of mutated genes, and types of mutations were different between 94 patients with TCH and 147 patients with PCH. Heterozygous missense mutations prevailed in PAX8, TSHR, FOXE1, and NKX2-5, and patients with these mutated genes had a higher risk of PCH (OR = 37.38, 95% CI 5.04–277.21, P<0.001). TCH and PCH have equal shares in patients with mutated DUOX2 or DUOXA2. Dual-site and multisite mutations were frequently detected in DUOX2. High phenotypic heterogeneity was observed in mutated DUOX2 even in the same mutations. However, there was no relationship found between mutations and transient or permanent outcome in patients with mutated DUOX2. Conclusion. Transient or permanent outcomes were influenced by the biological function of mutated genes instead of types of mutations among patients with CH. Patients whose mutations were related to thyroid dysgenesis (TD) were more likely to have PCH. The relationship between mutations and phenotypic characteristics is complicated, and phenotypic characteristics may be affected by mutations and other factors.

Study of Vitamin D Level and Vitamin D Receptor Polymorphism in Hypothyroid Egyptian Patients

Purpose. The current study aimed at assessing vitamin D level and vitamin D receptor polymorphism in hypothyroid Egyptian patients and its effect on hypothyroidism and thyroid morphology, also to find a causal relation between vitamin D and hypothyroidism. Methods. This case-control study was conducted on 35 hypothyroid patients and 35 matched unrelated healthy controls. Total serum 25-hydroxyvitamin D3 and thyroid antibodies were measured using a human ELISA kit. Genotyping was performed by using real-time PCR. HOMA-IR was also calculated (fasting insulin in mIU/L × fasting glucose in mg/dL/405). All subjects were assessed for thyroid morphology by thyroid ultrasonography. Results. Vitamin D level was lower in hypothyroid patients than in control subjects. Vitamin D was also inversely related to TSH, HOMA-IR, and levels of anti-TG and anti-TPO. VDR polymorphism (Fok1 and Apa1) had no relation to TSH or vitamin D levels in both patients and control groups. Low vitamin D levels were associated with increased thyroid vascularity and nodularity; furthermore, vitamin D was inversely proportional to thyroid gland volume. Correlation of HOMA-IR with the levels of both anti-TG and anti-TPO in the 70 subjects proved that HOMA-IR was positively correlated to both antibodies. Conclusion. This study confirmed the association of vitamin D deficiency with hypothyroidism, thyroid autoimmunity, increased volume, nodularity, and vascularity of thyroid gland in hypothyroid patients as well as increased HOMA-IR. It proved the association between HOMA-IR and thyroid autoimmunity. The study proved no association between VDR polymorphisms (Fok1 and Apa1) with either vitamin D levels or TSH levels.

Basal Autophagy Deficiency Causes Thyroid Follicular Epithelial Cell Death in Mice

Autophagy is a catabolic process that involves the degradation of cellular components through the lysosomal machinery, relocating nutrients from unnecessary processes to more pivotal processes required for survival. It has been reported that systemic disruption of the Atg5 or Atg7 gene, a component of autophagy, is lethal and that its tissue-specific disruption causes tissue degeneration in several organs. However, the functional significance of autophagy in the thyroid glands remains unknown. Our preliminary data imply the possible involvement of dysfunctional autophagy in radiation-induced thyroid carcinogenesis. Therefore, we evaluated the effect of Atg5 gene knockout (KO) on thyroid morphology and function. To this end, Atg5flox/flox mice were crossed with TPO-Cre mice, yielding the thyroid follicular epithelial cell (thyrocyte)‒specific ATG5-deficient mice (Atg5thyr-KO/KO). Atg5 gene KO was confirmed by a lack of ATG5 expression, and disruption of autophagy was demonstrated by a decrease in microtubule-associated protein 1 light chain 3–II puncta and an increase in p62. Atg5thyr-KO/KO mice were born normally, and thyroid morphology, thyroid weights, and serum T4 and TSH levels were almost normal at 4 months. However, at 8 and 12 months, a decrease in the number of thyrocytes and an increase in TUNEL+-thyrocytes were observed in Atg5thyr-KO/KO mice even though thyroid function was still normal. The number of irregularly shaped (gourd-shaped) follicles was also increased. Excess oxidative stress was indicated by increased 8-hydroxy-2′-deoxyguanosine and 53BP1 foci in Atg5thyr-KO/KO mice. These data demonstrate that thyrocytes gradually undergo degradation/cell death in the absence of basal levels of autophagy, indicating that autophagy is critical for the quality control of thyrocytes.

Obesity-related thyroiditis in childhood: relationship with insulin resistance

Background Thyroid dysfunction is the most common hormonal abnormality in obesity. It should actually be considered as an adaptation response to fat excess. However, little has been reported on the morphology of the thyroid gland, and no data regarding the relationship between thyroid gland changes and metabolic parameters are available in obese adolescents. Objective The study aimed to evaluate the frequency of non-autoimmune thyroiditis in obese adolescents and compare the metabolic status of patients with or without thyroiditis. Methods A total of 218 obese children and 49 age-matched control healthy children were included. Thyroid ultrasonography (USG) was performed in all participants, as well as thyroid hormone levels, thyroid antibodies (Abs), lipid profile, homeostasis model assessment of insulin resistance (HOMA-IR) and high-sensitivity C-reactive protein (HsCRP) were determined. Obese children were divided into three groups according to the presence of thyroid autoantibodies and USG findings of thyroiditis (Group-1: Abs [−], normal thyroid morphology/Group-2: Abs [+], abnormal thyroid morphology/Group-3: Abs [−], abnormal thyroid morphology). The relationship between body mass index, metabolic parameters and thyroid gland status was analyzed. Results Seventy-two of 218 obese patients (33%) had non-autoimmune thyroiditis (Group-3). The rate of insulin resistance was significantly higher in Group-3 than in Group-1 (p = 0.024). Similarly, the frequency of metabolic syndrome (MS) was higher in Group-3 (44.3%) than in Group-1 (27.1%) (p = 0.014). Conclusions Obese adolescents with non-autoimmune thyroiditis had a higher incidence of insulin resistance. This finding supported the hypothesis that insulin resistance may have an effect on thyroid morphology. Further randomized trials investigating this relationship are required.

Toxicology of Repeated Iodine Thyroid Blocking in Adult Rat

Radioactive iodines emitted following nuclear accidents are responsible for the dramatic increase of the late-onset thyroid cancer. Until the Fukushima disaster, a single dose of potassium iodide (KI) has been considered as an efficient countermeasure. Indeed, recently it has been suggested that repeated administration of KI may be necessary to ensure adequate protection in case of protracted exposure. Whereas, the effect of a single dose of KI has largely been studied ensuring its safety, studies regarding adverse effects of repeated iodine thyroid blocking (ITB) administration are scarce. Our objective was to assess the long term overall impact of KI in adult rats after repeated intake. Adult Wistar rats were subjected to either KI or saline solution over eight days. Biochemical homeostasis, hormones level, autoimmunity status, thyroid morphology and thyroid transcriptome profile were analyzed thirty days after the discontinuation of KI administration. Biochemical parameters, plasma levels of TSH; thyroid hormones; anti-TPO and anti-Tg did not differ between treated and control rats, the thyroid histology was not affected by the treatment and no long term transcriptome signature attributable to the treatment was noticed. Based on these data, we conclude the safety of repeated KI intake in adult rats; these data are prominent and may contribute to the ongoing development of KI guidelines and marketing authorization.