The Effect of Vitamin D Supplementation on Hypothyroidism in the Randomized Controlled D-Health Trial.

Background: Hypothyroidism is common, and in iodine-sufficient areas, it is primarily caused by autoimmune destruction of the thyroid gland. Observational studies have consistently shown an inverse association between serum 25-hydroxyvitamin D concentration and autoimmune diseases; however, there is a lack of evidence from randomized controlled trials to support a benefit of vitamin D supplementation, particularly for autoimmune thyroid diseases. We, therefore, aimed to assess the effect of vitamin D supplementation on the incidence of hypothyroidism. Methods: We analyzed data from the D-Health Trial (n = 21,315), a randomized double-blind placebo-controlled trial of 60,000 international units per month of supplemental vitamin D3 among Australians aged 60 years and over. Hypothyroidism, a tertiary outcome of the D-Health Trial, was defined by treatment with levothyroxine, ascertained through linkage with the Australian Pharmaceutical Benefits Scheme. The outcome was time to first prescription of levothyroxine. We began follow-up at 12 months after randomization; people who had died or who had been dispensed levothyroxine during the first year were excluded. Flexible parametric survival models were used to assess the effect of vitamin D supplementation on hypothyroidism, overall and within strata defined by age, sex, body mass index, and predicted baseline vitamin D status. Results: We included 17,851 participants in the main analysis (vitamin D = 8939; placebo = 8912). During a median follow-up of 4.1 years (interquartile range 4.1-4.1), 293 participants developed hypothyroidism (vitamin D = 138 [1.5%]; placebo = 155 [1.7%]). Vitamin D supplementation did not significantly reduce the incidence of hypothyroidism (overall hazard ratio [HR] 0.89; 95% confidence interval [CI] 0.71-1.12). There was some suggestion of an effect in females (overall HR 0.78; CI 0.58-1.06) but not in males (overall HR 1.06; CI 0.74-1.50; p interaction 0.20). Conclusions: Vitamin D supplementation did not reduce the incidence of hypothyroidism overall; however, the possible beneficial effect observed in females warrants further investigation. Clinical Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12613000743763.

Prevalence and risk factors of hypothyroidism after universal salt iodisation: a large cross-sectional study from 31 provinces of China.

OBJECTIVES: To investigate the prevalence and risk factors of hypothyroidism after universal salt iodisation for 20 years in mainland China. DESIGN: Nationwide, cross-sectional survey. SETTING AND PARTICIPANTS: The Thyroid Disorders, Iodine Status and Diabetes epidemiological study included adults from 31 provinces of China. Data included demographic, physical characteristics, urine, serum thyroid-stimulating hormone (TSH), thyroid-peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb) and thyroid ultrasonography. Subclinical hypothyroidism (SCH) was classified into severe SCH (TSH >10 mU/L) and mild SCH (TSH 4.2-9.9 mU/L). A total of 78 470 (38 182 men and 40 288 women) participants were included in the final analysis. RESULTS: The prevalence of hypothyroidism was 13.95%. The prevalence rates of overt hypothyroidism (OH) and SCH were 1.02% and 13.93%, which mild SCH was significantly higher than severe SCH (12.18% vs 0.75%). Prevalence was higher in women than in men, and this gender difference was noted among all age groups. The prevalence of mild SCH, severe SCH and OH increases by 1.16%, 1.40% and 1.29% for every 10 years older. TPOAb or/and TgAb positive were significantly associated with OH and severe SCH (OR 15.9, p<0.001). However, SCH was positively correlated with increased urine iodine concentration, but this correlation was only in antibody-negative female patients. In non-autoimmune and male populations, there was a U-shaped relationship between severe SCH and OH and urine iodine concentration. CONCLUSIONS: Mild SCH is the most common form of hypothyroidism, which is related to iodine intake. Severe SCH is more similar to OH which autoimmune is the main cause. The various effects of iodine on hypothyroidism depend on thyroid autoimmune and gender.

[Endocrine side effects of radiation therapy: Diagnosis, prevention, and treatment]. / Effets secondaires endocriniens de la radiothérapie : diagnostic, prévention et traitements.

Endocrine complications after radiotherapy are usually delayed and require prolonged follow-up by the radiation oncologist. Endocrine glands are dispersed throughout the body and can be included in the radiation field of several tumors. As the symptomatology can sometimes be insidious and non-specific, their screening is based on a directed clinical examination but also on systematic hormonal assays. The thyroid gland is particularly radiosensitive, and hypothyroidism is generally observed for doses of more than 30Gy. After cervical irradiation, it is recommended to perform a TSH assay every 6 to 12months. The risk of secondary thyroid cancer only concerns children and exists even at low doses, systematic screening is required. The risk of pituitary insufficiency is dose-dependent, with different sensitivity for each axis. In children, the main concern is the early detection of somatotropic insufficiency in order to prevent the risk of short stature. Reproductive function can be impaired after receiving 4-6Gy requiring fertility preservation. Endocrine side effects can be treated to improve quality of life; therefore, we propose several approaches to be followed in order to promote screening and treatment.

Possible protective role of L-thyroxin on the parotid gland of adult male albino rat in carbimazole induced hypothyroidism: histological, histomorphometry, and ultrastructural study.

BACKGROUND: Thyroid disorders are among the most common metabolic disorders worldwide. Thyroid dysfunction affects salivary glands function, causing hyposalivation. It also provokes physiological and histological changes in parotid, submandibular, and in particular the sublingual gland. THE AIM OF THIS WORK: The aim of this work was to clarify the histological and ultrastructural changes that occur in the parotid gland following carbimazole-induced hypothyroidism in adult male albino rats. The study also aims to investigate the possible protective role of L-thyroxin supplementation on the rat parotid glands after long and short duration of hypothyroidism. MATERIAL AND METHODS: Fifty-five adult male albino rats of Sprague Dawley strain; were divided into four groups and eleven subgroups, five rats each. G І received nothing. G П given normal saline orally daily. G Ш (medical Hypothyroidism, short duration - long duration - recovery group) given Carbimazole orally by gastric tube in a dose of 0.05 mg/kg daily for 3,6 successive weeks for group (a, b) and for 6 successive weeks then were left without any medication for another 3 weeks in recovery group c. G IV-b, c (L-Thyroxine supplemented group, short duration-long duration) given Carbimazole orally daily for 3,6 successive weeks then L-thyroxine was given orally in a dose of (10 µg/100 g/B.W) daily for another 3 successive weeks. Animals were sacrificed 24 hours after the last dose of Carbimazole in G III-a, b and 3 weeks after stoppage the drug in G III-c. Animals were sacrificed 24 hours after the last dose of L- Thyroxine in G IV-b, c. The parotid specimens were processed for histopathological examination by light and electron microscopy. The medically induced Hypothyroidism resulted in significant parotid gland damage which was more obvious with longer duration; as follow: a) most of the acini had irregular outlines and were widely separated with narrow lumen and cytoplasmic vacuoles. b) some acinar cells contained ill defined, irregular, pyknotic or hyperchromatic nuclei. c)Vascular changes: dilated and engorged with blood. d) the interlobular and striated ducts appeared disrupted and dilated. e) extravasated blood with cellular infiltration were seen in the interstitial space. IN CONCLUSION: Thyroid hormones (THs) had a significant effect in protection of parotid gland against damage induced by carbimazole, as it preserved the normal histological architecture of the parotid gland. This beneficial effect of THs was mostly related to its antioxidant properties. The expression of BCL-2 has certain regularity in apoptosis after drug administration. Regulation of glandular atrophy and apoptosis are closely related. The molecular mechanism of the apoptosis of the gland is not clear, and further study is needed in the future.

Investigating the protective role of metformin on lithium-induced hypothyroidism.

Induction of oxidative stress events has been shown to be associated with lithium (Li) hypothyroidism induction. Metformin (MET) is a commonly used antidiabetic drug with multiple properties including antiproliferative activity, antioxidant potency, and is used in polycystic ovarian syndrome treatment. Here, in this study, we aimed to investigate the effect of different doses of MET on Li-induced hypothyroidism for elucidating its mechanism of action. The obtained results demonstrated the oxidative stress reduction in thyroid tissues upon MET treatment. Besides this, the biochemical analysis revealed a significant reduction in T3 and TSH levels (down to 2 ng/ml and 0.05 µU/ml, respectively) in coordination with an observable reduction in T4 level (up to 2.1 ng/ml). Also, a significant reduction in Li-related tissue damages including changes in the morphology and the size of follicles, rate of vascularity, detachment of follicular cells, inflammatory cells infiltration, and follicular cells hypertrophy and disruption was observed. Ultimately, regarding the significant improvement in thyroid tissues and valuable antioxidant activity determined in tissues treated with MET, it is concluded that MET co-administration with Li can significantly reduce the negative effects of Li and enhance the efficacy of Li therapy.

The impact of nutritional counseling on thyroid disorders in head and neck cancer patients after (chemo)radiotherapy: results from a prospective interventional trial.

OBJECTIVE: To analyze the impact of nutritional counseling on the development of hypothyroidism after (chemo)radiotherapy in head and neck cancer patients to propose a new normal tissue complication probability (NTCP) model. MATERIALS AND METHODS: At baseline, at the end of (chemo)radiotherapy, and during follow-up, thyroid-stimulating hormone (TSH) with free thyroxin (fT3 and fT4), nutritional status, and nutrient intake were prospectively analyzed in 46 out of 220 screened patients. Patients received (chemo)radiotherapy within an intervention (individual nutritional counseling every 2 weeks during therapy) and a control group (no nutritional counseling). RESULTS: Overall median follow-up was 16.5 [IQR: 12; 22] months. Fourteen patients (30.4%) presented with hypothyroidism after 13.5 [8.8; 17] months. During (chemo)radiotherapy, nutritional status worsened in the entire cohort: body mass index (p < 0.001) and fat-free mass index (p < 0.001) decreased, calorie deficit (p = 0.02) increased, and the baseline protein intake dropped (p = 0.028). The baseline selenium intake (p = 0.002) increased until the end of therapy. Application of the NTCP models by Rønjom, Cella, and Boomsma et al. resulted in good performance of all three models, with an AUC ranging from 0.76 to 0.78. Our newly developed NTCP model was based on baseline TSH and baseline ferritin. Model performance was good, receiving an AUC of 0.76 (95% CI: 0.61-0.87), with a sensitivity of 57.1% and specificity of 96.9% calculated for a Youden index of 0.73 (p = 0.004; area = 0.5). CONCLUSION: Baseline TSH and ferritin act as independent predictors for radiotherapy-associated hypothyroidism. The exclusion of such laboratory chemistry parameters in future NTCP models may result in poor model performance.

Levothyroxine Treatment and the Risk of Cardiac Arrhythmias - Focus on the Patient Submitted to Thyroid Surgery.

Levothyroxine (LT4) is used to treat frequently encountered endocrinopathies such as thyroid diseases. It is regularly used in clinical (overt) hypothyroidism cases and subclinical (latent) hypothyroidism cases in the last decade. Suppressive LT4 therapy is also part of the medical regimen used to manage thyroid malignancies after a thyroidectomy. LT4 treatment possesses dual effects: substituting new-onset thyroid hormone deficiency and suppressing the local and distant malignancy spreading in cancer. It is the practice to administer LT4 in less-than-high suppressive doses for growth control of thyroid nodules and goiter, even in patients with preserved thyroid function. Despite its approved safety for clinical use, LT4 can sometimes induce side-effects, more often recorded with patients under treatment with LT4 suppressive doses than in unintentionally LT4-overdosed patients. Cardiac arrhythmias and the deterioration of osteoporosis are the most frequently documented side-effects of LT4 therapy. It also lowers the threshold for the onset or aggravation of cardiac arrhythmias for patients with pre-existing heart diseases. To improve the quality of life in LT4-substituted patients, clinicians often prescribe higher doses of LT4 to reach low normal TSH levels to achieve cellular euthyroidism. In such circumstances, the risk of cardiac arrhythmias, particularly atrial fibrillation, increases, and the combined use of LT4 and triiodothyronine further complicates such risk. This review summarizes the relevant available data related to LT4 suppressive treatment and the associated risk of cardiac arrhythmia.

High-dose radiation exposure and hypothyroidism: aetiology, prevention and replacement therapy.

Without any doubt, high dose radiation exposure can induce hypothyroidism. However, there are open questions related to the mechanisms of its induction, corresponding dose thresholds and possible countermeasures. Therefore, this review addresses the aetiology, prevention and therapy of radiation induced hypothyroidism. External beam radiotherapy with several 10 Gy to the head and neck region and radioiodine therapy with several 100 Gy thyroid absorbed dose can destroy the thyroid gland and can induce autoantibodies against thyroid tissue. According to recent literature, clinical hypothyroidism is observed at threshold doses of ∼10 Gy after external beam radiotherapy and of ∼50 Gy after radioiodine therapy, children being more sensitive than adults. In children and adolescents exposed by the Chernobyl accident with mean thyroid absorbed doses of 500-800 mGy, subclinical hypothyroidism has been detected in 3%-6% of the cases with significant correlation to thyroid absorbed doses above 2.5 Gy. In case of nuclear emergencies, iodine thyroid blocking (ITB) is the method of choice to keep thyroid absorbed doses low. Large doses of stable iodine affect two different steps of internalization of radioiodine (transport and organification); perchlorate affecting the transport only may be an alternative to iodine. Administered before radioiodine incorporation, the effect of 100 mg iodide or more is still about 90% after 1 days, 80% after 2 days, and 50% or less after 3 days. If administered (too) late after exposure to radioiodine, the theoretically expected protective effect of ITB is about 50% after 6 h, 25% after 12 h, and about 6% after 24 h. In case of repeated or continuous exposure, repeated administration of 50 mg of iodide daily is indicated. If radiation-induced hypothyroidism cannot be avoided, thyroid hormone replacement therapy with individualized dosing and regular monitoring in order to maintain thyroid-stimulating hormone levels within the normal range ensures normal life expectancy.

Statin Use and Benefits of Thyroid Function: A Retrospective Cohort Study.

Purpose: Previous studies have suggested that cholesterol may influence thyroid function. Since statins are widely used for their cholesterol-lowering effect, we aimed to assess the association between statin use and thyroid function, and also to explore the role of the cholesterol-lowering effect in it. Methods: We performed a retrospective cohort study derived from REACTION study. Eligible subjects receiving statin therapy were included in the statin group, and sex-, age-, total cholesterol (TC)-, and thyroid function-matched participants without lipid-lowering therapy were included in the control group. The median follow-up time was three years. Outcomes of thyroid function were evaluated at the end of follow-up. We used multivariable regression models to assess the association between statin use and outcomes of thyroid function, and also performed mediation analyses to explore the role of cholesterol in it. Results: A total of 5,146 participants were screened, and 201 eligible subjects in the statin group and 201 well-matched subjects in the control group were analyzed. At the end of follow-up, TC and thyroid-stimulating hormone (TSH) levels in the statin group were lower than those in the control group (both p < 0.05), and the percentage of euthyroid subjects was higher in the statin group (88.06% vs. 76.12%, p = 0.002). The incidence rate of subclinical hypothyroidism (SCH) in euthyroid subjects was lower in the statin group (6.29% vs. 14.86%, p = 0.009), and the remission rate among subjects with SCH was higher in the statin group (50.00% vs. 15.38%, p = 0.008). In multivariable regression analyses, statin use was independently associated with lower TSH levels and higher odds to be euthyroid (OR 2.335, p = 0.004) at the end of follow-up. Mediation analyses showed the association between statin use and TSH levels were mediated by TC changes during follow-up. Conclusion: Statin use was associated with benefits of thyroid function, and TC changes serve as a mediator of the association between statin use and TSH levels. Further studies are needed to clarify the possible underlying mechanism.

Iodine supplementation for pregnant women: a cross-sectional national interventional study.

BACKGROUND: Although Iran has been considered iodine replete since 2000, the first national survey of iodine intake among Iranian pregnant women in 2014 indicated that despite the adequate intake of iodine by the general population, this vulnerable group has moderate iodine deficiency. Therefore, in this national cross-sectional interventional study, we aimed to assess the iodine intake and thyroid function of Iranian pregnant women 2 years after implementing national iodine supplementation for this vulnerable group. MATERIALS AND METHODS: In this cross-sectional study, we conducted a national interventional survey of pregnant women. A total of 1200 pregnant women (400 women from each trimester) from 12 provinces of Iran were recruited from the antenatal care clinics from October 2018 to March 2019. The median urinary iodine concentration (MUIC), as an indicator of iodine status in three spot urine samples, was measured, along with the serum total T4 (TT4), thyrotropin (TSH), thyroglobulin (Tg), thyroid peroxidase antibody (TPO-Ab), and iodine content of household salt. RESULTS: The mean age of the cohort was 28 ± 6.2 years, with the mean gestational age of 22.7 ± 13.0 weeks. The overall MUIC (IQR) of pregnant women was 188 µg/L (124.2-263 µg/L). Also, the MUICs in the three trimesters of pregnancy were 174 µg/L (110-254), 175 µg/L (116-251), and 165 µg/L (114-235), respectively. The MUICs ≥ 150, 100-149, and < 100 µg/L were found in 63, 19.8, and 16.2% of the subjects, respectively. The mean TT4 level was 12 ± 4.5 µg/dL, and the median (IQR) level of TSH was 2.37 mIU/L (1.66-3.18 mIU/L). According to our local reference range, 118 (10.5%) pregnant women had subclinical hypothyroidism, 6 (0.53%) women had isolated hypothyroxinemia, and 65 (5.7%) women were TPO-Ab positive. Also, the median (IQR) level of Tg was 10.08 µg/dL (5.7-20.4 µg/dL), and the median iodine content of household salt was 29.6 µg/g; the iodine content was ≥ 30 µg/g in 85% of household salt. The results showed that more than 95% of households were under iodized salt coverage. CONCLUSION: The results of this study indicated that iodine supplementation with at least 150 µg of iodine per day improved the iodine intake of pregnant women. Except for subclinical hypothyroidism, the prevalence of clinical hypothyroidism, clinical/subclinical thyrotoxicosis, TPO-Ab positivity, and isolated hypothyroxinemia decreased significantly, which emphasizes the importance of iodine supplementation during pregnancy.

T4-mediated rescue of aortic malformations in hypothyroid rats indicates maternal thyroid status can affect great vessel development.

Pexacerfont is a corticotrophin-releasing factor subtype 1 receptor (CRF-1) antagonist developed for potential treatment of anxiety and stress-related disorders. In male rats, pexacerfont caused hepatic enzyme induction leading to increased thyroxine (T4) clearance. When administered to pregnant rats on gestation day 6 to 15, pexacerfont at 300 mg/kg/day (30× mean AUC in humans at 100 mg/day) produced similar effects on thyroid homeostasis with serum T4 and thyroid-stimulating hormone levels that were 0.3-0.5× and 3.3-3.7× of controls, respectively. At this dose, fetuses of pexacerfont-treated dams presented findings associated with maternal hypothyroidism including growth retardation and increased skeletal alterations. Additionally, there were unexpected great vessel malformations that were mostly derived from the 4th pharyngeal arch artery in 5 (4.3%) fetuses from 3 (15.8%) litters. The etiology was unclear whether the vascular malformations were related to insufficient thyroid hormones or another mechanism. To better understand this relationship, pregnant rats were implanted with a subcutaneous L-thyroxine pellet designed to provide a sustained release of T4 throughout organogenesis in rat embryos (GD 6 to 15; the dosing period of pexacerfont). T4 supplementation produced a near euthyroid state in pexacerfont-treated dams and completely prevented the fetal vascular malformations. These results suggest maternal T4 levels during organogenesis may have a role in great vessel morphogenesis associated with patterning and/or regression of pharyngeal arch arteries. Although previous clinical reports have speculated a potential relationship between thyroid hormone homeostasis and early cardiovascular development, this is the first report to experimentally demonstrate this relationship in great vessel morphogenesis.

Long-term results of suppressing thyroid-stimulating hormone during radiotherapy to prevent primary hypothyroidism in medulloblastoma/PNET and Hodgkin lymphoma: a prospective cohort study.

Primary hypothyroidism commonly occurs after radiotherapy (RT), and coincides with increased circulating thyroid-stimulating hormone (TSH) levels.We tested therefore the protective effect of suppressing TSH with L-thyroxine during RT for medulloblastoma/PNET and Hodgkin lymphoma (HL) in a prospective cohort study. From1998 to 2001, a total of 37 euthyroid children with medulloblastoma/PNET plus 14 with HL, scheduled for craniospinal irradiation and mediastinum/neck radiotherapy, respectively, underwent thyroid ultrasound and free triiodothyronine (FT3), free thyroxine (FT4), and TSH evaluation at the beginning and end of craniospinal iiradiation. From 14 days before and up to the end of radiotherapy, patients were administered L-thyroxine checking every 3 days TSH to ensure a value < 0.3 µIU/mL. During follow-up, blood tests and ultrasound were repeated; primary hypothyroidism was considered an increased TSH level greater than normal range. Twenty-two/37 patients with medulloblastoma/PNET and all the 14 patients with HL were alive after a median 231 months from radiotherapy with 7/22 and 8/14 having correctly reached TSH levels < 0.3 µIU/mL and well matched for other variables. Twenty years on, hypothyroidism-free survival rates differed significantly, being 60% ± 15% and 15.6% ± 8.2% in TSH-suppressed vs. not-TSH suppressed patients, respectively (P = 0.001). These findings suggest that hypothyroidism could be durably prevented in two populations at risk of late RT sequelae, but it should be confirmed in a larger cohort.

Long-term results of suppressing thyroid-stimulating hormone during radiotherapy to prevent primary hypothyroidism in medulloblastoma/PNET and Hodgkin lymphoma: a prospective cohort study / 医学前沿

Primary hypothyroidism commonly occurs after radiotherapy (RT), and coincides with increased circulating thyroid-stimulating hormone (TSH) levels.We tested therefore the protective effect of suppressing TSH with L-thyroxine during RT for medulloblastoma/PNET and Hodgkin lymphoma (HL) in a prospective cohort study. From1998 to 2001, a total of 37 euthyroid children with medulloblastoma/PNET plus 14 with HL, scheduled for craniospinal irradiation and mediastinum/neck radiotherapy, respectively, underwent thyroid ultrasound and free triiodothyronine (FT3), free thyroxine (FT4), and TSH evaluation at the beginning and end of craniospinal iiradiation. From 14 days before and up to the end of radiotherapy, patients were administered L-thyroxine checking every 3 days TSH to ensure a value < 0.3 μIU/mL. During follow-up, blood tests and ultrasound were repeated; primary hypothyroidism was considered an increased TSH level greater than normal range. Twenty-two/37 patients with medulloblastoma/PNET and all the 14 patients with HL were alive after a median 231 months from radiotherapy with 7/22 and 8/14 having correctly reached TSH levels < 0.3 μIU/mL and well matched for other variables. Twenty years on, hypothyroidism-free survival rates differed significantly, being 60% ± 15% and 15.6% ± 8.2% in TSH-suppressed vs. not-TSH suppressed patients, respectively (P = 0.001). These findings suggest that hypothyroidism could be durably prevented in two populations at risk of late RT sequelae, but it should be confirmed in a larger cohort.

Does thyroid-sparing total laryngectomy decrease the risk of hypothyroidism?

BACKGROUND: Thyroid lobectomy is recommended with total laryngectomy for laryngeal cancer in the National Comprehensive Cancer Network ('NCCN') guidelines. However, it is associated with a 32-89 per cent risk of hypothyroidism, with or without adjuvant radiotherapy. OBJECTIVE: The study aimed to determine whether preserving the whole thyroid, compared to a single lobe, does indeed significantly lower the incidence of hypothyroidism in the setting of total laryngectomy. METHOD: A retrospective study was conducted at Groote Schuur Hospital in Cape Town, South Africa. RESULTS: Eighty-four patients met the inclusion criteria. The overall incidence of hypothyroidism was 45.2 per cent. The incidence of hypothyroidism was significantly reduced in patients who underwent thyroid-sparing total laryngectomy compared to hemithyroidectomy (p = 0.037). Adjuvant radiotherapy was associated with a higher incidence of hypothyroidism (p = 0.001). CONCLUSION: Thyroid-preserving laryngectomy should be advocated in carefully selected patients with advanced laryngeal carcinoma, as it reduces the incidence of hypothyroidism.

Interference on Iodine Uptake and Human Thyroid Function by Perchlorate-Contaminated Water and Food.

BACKGROUND: Perchlorate-induced natrium-iodide symporter (NIS) interference is a well-recognized thyroid disrupting mechanism. It is unclear, however, whether a chronic low-dose exposure to perchlorate delivered by food and drinks may cause thyroid dysfunction in the long term. Thus, the aim of this review was to overview and summarize literature results in order to clarify this issue. METHODS: Authors searched PubMed/MEDLINE, Scopus, Web of Science, institutional websites and Google until April 2020 for relevant information about the fundamental mechanism of the thyroid NIS interference induced by orally consumed perchlorate compounds and its clinical consequences. RESULTS: Food and drinking water should be considered relevant sources of perchlorate. Despite some controversies, cross-sectional studies demonstrated that perchlorate exposure affects thyroid hormone synthesis in infants, adolescents and adults, particularly in the case of underlying thyroid diseases and iodine insufficiency. An exaggerated exposure to perchlorate during pregnancy leads to a worse neurocognitive and behavioral development outcome in infants, regardless of maternal thyroid hormone levels. DISCUSSION AND CONCLUSION: The effects of a chronic low-dose perchlorate exposure on thyroid homeostasis remain still unclear, leading to concerns especially for highly sensitive patients. Specific studies are needed to clarify this issue, aiming to better define strategies of detection and prevention.

Risk of Iodine Deficiency in Extremely Low Gestational Age Newborns on Parenteral Nutrition.

Iodine is an essential component of thyroid hormones, which play a critical role in neurodevelopment. The iodine status of pregnant women and their newborns is not checked routinely. Extremely Low Gestational Age Newborns do not receive Iodine supplementation while on parenteral nutrition (PN). We measured urine iodine levels and thyroid function tests in 50 mother-infant dyads at birth, at 1 week, 1, 2, 3 months and near discharge. We correlated maternal and neonatal urine iodine levels with thyroid functions and measured iodine levels in milk and PN. In our study, 64% of mothers were iodine deficient at the time of delivery, their free T4 levels were 0.48 (0.41-0.54) ng/dL with normal thyroid-stimulating hormone (TSH). Iodine levels were thirty-fold higher in extremely low gestational age newborns (ELGAN) exposed to iodine comparing to full terms (p < 0.001), but this effect lasted <1 week. At 1 month of age, ELGAN on PN developed iodine deficiency (p = 0.017) and had high thyroglobulin levels of 187 (156-271) ng/mL. Iodine levels improved with enteral feeds by 2 months of age (p = 0.01). Iodine deficiency is prevalent among pregnant women and ELGAN; in particular, those on PN are at risk of hypothyroidism. Iodine supplementation during pregnancy and postnatally should be considered to avoid iodine deficiency.

A Lifestyle (Dietary) Intervention Reduces Tiredness in Children with Subclinical Hypothyroidism, a Randomized Controlled Trial.

PURPOSE: Subclinical hypothyroidism (SH) in children and adults is a subject for discussion in terms of whether to treat it or not with respect to the short-term clinical implications and consequences of SH and in the long term. If treatment with thyroxine supplementation is not indicated, no other treatment is available. We investigated whether a lifestyle (dietary) intervention improves or normalizes SH or decreases the presence of Thyroid Stimulating Hormone (TSH) and/or tiredness. Methods: We randomized children aged 1-12 years with SH to the control group (standard care = no treatment) or intervention group (dietary intervention). The dietary intervention consisted of green vegetables, beef, whole milk and butter for 6 months. The rest of the diet remained unchanged. We measured TSH, FreeT4, Lipid profile, Body Mass Index (BMI) and Pediatric Quality of Life (PedQL) multidimensional fatigue scale scores. Results: In total, 62 children were included. After 6 months, TSH decreased in both groups without a significant difference between the groups (p = 0.98). PedQL fatigue scores for sleep (p = 0.032) and total fatigue scores (p = 0.039) improved significantly in the intervention group, compared to the control group. No unfavorable effects occurred in the lipid profile or BMI. Conclusion: The lifestyle (dietary) intervention did not normalize SH and TSH levels, but it significantly reduced tiredness. These results suggest that children's well-being can be improved without medication.

Fine-needle aspiration with rapid parathyroid hormone assay to identify parathyroid gland in thyroidectomy.

To determine the levels of parathyroid hormone (PTH) in the fluids of various tissues for identification of parathyroid glands during thyroidectomy.Our study comprised 31 patients with thyroid cancer who underwent lobectomy with central compartment dissection at our hospital from October 2014 to February 2015. A total of 186 tissue samples, including 28 from parathyroid glands and 158 from non-parathyroid tissues, were obtained during the operations. Tissue fluids were collected via fine-needle aspiration to measure PTH levels; the tissue was punctured 3 times with a 26-gauge syringe needle and washed with 0.5 mL normal saline. Tissues were also prepared for pathological examination.PTH concentrations were significantly higher in parathyroid tissues than non-parathyroid tissues. None of the patients had irremediable parathyroid dysfunction after surgical resection.Use of fine-needle aspiration for quantification of PTH levels in tissue fluids rapidly, safely, and effectively identifies the parathyroid glands during thyroidectomy.

Model-based calculation of thyroid gland normal tissue complication probability in head and neck cancer patients after radiation therapy.

AIM: Primary hypothyroidism is one of the late complications that can occur after radiation therapy for malignant tumors in the head and neck region. The aim of this retrospective study was to show the validity of the Lyman-Kutcher-Burman (LKB) normal tissue complication model for thyroid gland based on clinical results. METHODS: Thyroid function was evaluated by measuring thyroid-stimulating hormone and free thyroxine serum levels before radiation therapy, 3 months after the beginning of radiation therapy, and afterwards at each follow-up visit. Cumulative incidence was calculated using the Kaplan-Meier method. Dose-volume histogram, total dose, fractionation schedule, total duration of the treatment, and other parameters were used for normal tissue complication probability calculation based on the LKB model. The model was evaluated after fitting with the three sets of parameters for grade 2 hypothyroidism: 1) "Emami," where n = 0.22; m = 0.26, and D50 = 80 Gy; 2) "mean dose," where n = 1; m = 0.27, and D50 = 60 Gy; and 3) "Lyman EUD," where n = 0.49; m = 0.24, and D50 = 60 Gy. A value 3.0 Gy was used for α/ß ratio RESULTS: Eighty-three patients treated with volumetric modulated arc therapy for head and neck cancers at the University Hospital Martin, Slovakia, from January 2014 to July 2017, were included in the retrospective study. Median follow-up was 1.2 years. Cumulative incidence of hypothyroidism grade 2 or higher after 12 and 24 months was 9.6 and 22.0%, respectively. Normal tissue complication probability values calculated with mean dose and Lyman EUD parameters showed the best correlation with our clinical findings. CONCLUSION: Empirically based modelling of normal tissue complication probability was valid for our cohort of patients. With carefully chosen parameters, the LKB model can be used for predicting the normal tissue complication probability value.

Efficacy and Safety of Long-Term Universal Salt Iodization on Thyroid Disorders: Epidemiological Evidence from 31 Provinces of Mainland China.

Background: Mandatory universal salt iodization (USI) has been implemented in China for 20 years. Although iodine deficiency disorders are effectively controlled, the risk of excess iodine have been debated. Methods: A nationally representative cross-sectional study with 78,470 enrolled participants, aged 18 years or older, from all 31 provincial regions of mainland China was performed. The participants were given a questionnaire and underwent B-mode ultrasonography of the thyroid. Serum concentrations of thyroid hormones, thyroid antibodies, and urine iodine concentration (UIC) were measured. Results: The median UIC of the adult population was 177.89 µg/L. The weighted prevalence of thyroid disorders in adults were as follows: 0.78% of overt hyperthyroidism, 0.44% of subclinical hyperthyroidism, 0.53% of Graves' disease, 1.02% of overt hypothyroidism, 12.93% of subclinical hypothyroidism, 14.19% of positive thyroid antibodies, 10.19% of positive thyroid peroxidase antibodies, 9.70% of positive thyroglobulin antibodies, 1.17% of goiter, and 20.43% of thyroid nodules. Iodine excess was only associated with higher odds of overt hyperthyroidism and subclinical hypothyroidism, while iodine deficiency was significantly associated with higher odds of most thyroid disorders. In addition, increased iodine intake was significantly associated with elevated serum thyrotropin levels but was inversely associated with thyroid antibodies and thyroid nodules. Conclusions: The long-term mandatory USI program with timely adjustments is successful in preventing iodine deficiency disorders, and it appears to be safe. The benefits outweigh the risks in a population with a stable median iodine intake level of up to 300 µg/L.