2-iodohexadecanal induces autophagy during goiter involution.

BACKGROUND: Iodine plays an important role in thyroid physiology and biochemistry. The thyroid is capable of producing different iodolipids such as 2-iodohexadecanal (2-IHDA). Data from different laboratories have shown that 2-IHDA inhibits several thyroid parameters and it has been postulated as intermediary on the action of iodide function. OBJECTIVE: To explore different mechanisms involved during the involution of the hyperplastic thyroid gland of Wistar rats towards normality induced by 2-IHDA. METHODS: Goiter was induced by the administration of MMI for 10 days, then the treatment was discontinued and Wistar rats were injected with 2-IHDA or KI. RESULTS: During involution, 2-IHDA treatment reduced PCNA expression compared to spontaneous involution. KI treatment caused an increase of Caspase-3 activity and TUNEL-positive cells. In contrast, 2-IHDA failed to alter this value but induced an increase of LC3B expression. KI but not 2-IHDA led to an increase in peroxides levels, catalase and glutathione peroxidase activity. CONCLUSIONS: We demonstrated that 2-IHDA, in contrast to iodide, did not lead to an increase in oxidative stress or apoptosis induction, indicating that the involution triggered by 2-IHDA in Wistar rats, is primarily due to the inhibition of cell proliferation and the induction of autophagy.

Iatrogenic endocrine complications of lithium therapy.

Lithium is a cation, similar to sodium and potassium, affecting ion transport. It is used in the medical field as a treatment of bipolar disorders. The main endocrine complications of lithium treatment affect thyroid and parathyroid glands, in association with renal complications. Thyroid adverse effects, which are more frequent in women, comprise hypothyroidism, goiter, or sometimes hyperthyroidism, through interference with the iodine symporter. The increase in thyroid volume is early. Prevalence of goiter is 4 times higher than in the general population and hypothyroidism (8-20%) more frequent in case of pre-existing thyroid autoimmunity. Hyperthyroidism likely to worsen mood is reported in 5% of cases but the causal link to lithium is unproven. An increase in serum calcium and PTH occurs in 30% of cases, as lithium stimulates parathyroid cell proliferation by activating the Wnt pathway. The risk of hyperparathyroidism, by adenoma and especially by hyperplasia, is 5 times higher than in the general population, with the particularity of frequent low urine calcium by action on the calcium-sensing receptor (CaSR). Renal complications include risk of acute or chronic renal failure and nephrogenic diabetes insipidus, which is a factor for hypernatremia and hypercalcemia through dehydration. Nephrogenic diabetes insipidus is not always reversible after lithium therapy discontinuation. Metabolically, weight gain can be observed, but rather less than with other psychotropic drugs, and lithium does not in itself induce diabetes. At pituitary level, corticotropic activation is frequent, but implicating the disease rather than lithium. Lithium treatment induces little or no hyperprolactinemia. Regular monitoring of serum calcium, the ionogram, creatinine and TSH is recommended in lithium treatment.

Use of thyroid hormones in hypothyroid and euthyroid patients: A THESIS questionnaire survey of UK endocrinologists.

OBJECTIVE: Management of hypothyroidism is controversial because of medication cost pressures and scientific uncertainty on how to address treatment dissatisfaction experienced by some patients. The objective was to investigate the experience and preferences of UK endocrinologists in use of thyroid hormones. DESIGN: Web-based survey. PATIENTS: UK endocrinologists were invited to participate. MEASUREMENTS: Responses to questionnaire. RESULTS: The response rate was 21% (272/1295). While levothyroxine monotherapy is regarded as the treatment of choice for hypothyroidism, 51% of respondents stated that combined treatment with levothyroxine and liothyronine could be considered for levothyroxine-treated patients whose symptoms persist despite normalisation of serum thyroid stimulating hormone (TSH) concentration. However, only 40% are currently prescribing such treatment, and just 23% would consider taking it themselves. A small minority prescribe desiccated thyroid extract, and those most likely to do so are aged over 60 years. Most respondents stated that they have no influence over brand or formulation of levothyroxine dispensed to their patients and expect no major differences in efficacy between different formulations. A total of 9% would prescribe levothyroxine for euthyroid enlarging goitre, and 29% for euthyroid female infertility with high titre thyroid peroxidase antibodies, despite recent trials finding no benefit. CONCLUSIONS: UK endocrine practice in management of hypothyroidism is broadly in line with international guidance. However, a minority of respondents would consider thyroid hormone supplementation in euthyroid individuals for female infertility, enlarging goitre, and other indications in which evidence of efficacy is lacking. Willingness to consider prescribing combined levothyroxine and liothyronine, for hypothyroid symptoms which persist despite normalised TSH, has increased in comparison to previous international surveys, despite inconsistent evidence of benefit.

Use of GLP-1 Receptor Agonists and Occurrence of Thyroid Disorders: a Meta-Analysis of Randomized Controlled Trials.

The association between glucagon-like peptide-1 (GLP-1) receptor agonists and the risk of various kinds of thyroid disorders remains uncertain. We aimed to evaluate the relationship between the use of GLP-1 receptor agonists and the occurrence of 6 kinds of thyroid disorders. We searched PubMed (MEDLINE), EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) and Web of Science from database inception to 31 October 2021 to identify eligible randomized controlled trials (RCTs). We performed meta-analysis using a random-effects model to calculate risk ratios (RRs) and 95% confidence intervals (CIs). A total of 45 trials were included in the meta-analysis. Compared with placebo or other interventions, GLP-1 receptor agonists' use showed an association with an increased risk of overall thyroid disorders (RR 1.28, 95% CI 1.03-1.60). However, GLP-1 receptor agonists had no significant effects on the occurrence of thyroid cancer (RR 1.30, 95% CI 0.86-1.97), hyperthyroidism (RR 1.19, 95% CI 0.61-2.35), hypothyroidism (RR 1.22, 95% CI 0.80-1.87), thyroiditis (RR 1.83, 95% CI 0.51-6.57), thyroid mass (RR 1.17, 95% CI 0.43-3.20), and goiter (RR 1.17, 95% CI 0.74-1.86). Subgroup analyses and meta-regression analyses showed that underlying diseases, type of control, and trial durations were not related to the effect of GLP-1 receptor agonists on overall thyroid disorders (all P subgroup > 0.05). In conclusion, GLP-1 receptor agonists did not increase or decrease the risk of thyroid cancer, hyperthyroidism, hypothyroidism, thyroiditis, thyroid mass and goiter. However, due to the low incidence of these diseases, these findings need to be examined further. Systematic Review Registration: PROSPERO https://www.crd.york.ac.uk/prospero/, identifier: CRD42021289121.

What an endocrinologist should know for patients receiving lithium therapy.

Lithium is an efficient treatment of bipolar disorder. Besides renal insufficiency, many endocrine side effects are described such as the occurrence of thyroid disorders, hypercalcaemia and nephrogenic diabetes insipidus. Lithium inhibits the secretion of thyroid hormones. The prevalence of goiter is 4 times more common in Lithium-treated patients compared as to the general population. Hypothyroidism (8-20%) is more frequent in women and in case of pre-existing thyroid autoimmunity. Grave's disease and other hyperthyroidisms are sometimes reported. Lithium stimulates the proliferation of parathyroid cells by activating the Wnt pathway. An increase in serum calcium and PTH is described in patients treated with Lithium with a 4 to 6-fold higher risk of primary hyperparathyroidism than in the general population. Nevertheless, 24-hour urine calcium is not often increased, and the phenotype can mimic a hypercalcemia-hypocalciuria syndrome that may regress with Lithium discontinuation. Surgery should be cautious since parathyroid hyperplasia is more common than parathyroid adenoma. Nephrogenic diabetes insipidus is frequently reported and may be debilitating, sometimes intricated with severe dehydration, hypernatremia, and acute renal insufficiency. Nephrogenic diabetes insipidus is not generally reversible after Lithium discontinuation, especially in patients who have chronic kidney disease due to interstitial tubule nephritis. In conclusion, clinical assessment (goiter, diuresis) and biological monitoring of serum calcium, sodium creatinine, TSH and lithium are recommended in patients receiving Lithium therapy. The risk of Lithium discontinuation in case of side effects should be weighed against the psychological risk, and must be discussed with the psychiatrist.

Tiroiditis subaguda y tirotoxicosis posterior a vacuna contra SARS-CoV-2: reporte de 2 casos / Subacute thyroiditis and thyrotoxicosis after SARS-CoV-2 vaccine: report of 2 cases

La enfermedad por coronavirus SARS-CoV-2 que surgió en el año 2019 (COVID-19), ha obligado al rápido desarrollo de vacunas para prevenir su propagación e intentar controlar la pandemia. Dentro de las vacunas desarrolladas, las primeras en ser aprobadas con una tecnología nueva en el campo de la vacunación, fueron las vacunas basadas en ARNm (ácido ribonucleico mensajero), que lograron tasas de efectividad cercanas al 95 % para la prevención de la enfermedad COVID-19 grave. Los eventos adversos comunes son reacciones locales leves, pero ha habido varios informes de pacientes que desarrollaron tiroiditis subaguda y disfunción tiroidea después de recibir la vacuna contra SARS-CoV-2. Este artículo presenta dos casos de tiroiditis subaguda poco después de recibir la vacuna contra COVID-19

The SARS-CoV-2 coronavirus disease which emerged in 2019 (COVID-19), has forced the rapid development of vaccines to prevent the spread of infection and attempt to control the pandemic. Among the vaccines developed, one of the first to be approved with a new technology in the field of vaccination, was the mRNA (messenger ribonucleic acid) vaccine, with rates of effectiveness close to 95% for the prevention of severe COVID-19 disease. Common adverse events are mild local reactions, but there have been some reports of patients developing sub-acute thyroiditis and thyroid dysfunction after receiving the SARS-CoV-2 vaccine. This article presents two case reports of subacute thyroiditis shortly after receiving the COVID-19 vaccine

The Association of Myo-Inositol and Selenium Contrasts Cadmium-Induced Thyroid C Cell Hyperplasia and Hypertrophy in Mice.

Previous studies have demonstrated that, in addition to inducing structural changes in thyroid follicles, cadmium (Cd) increased the number of C cells. We examined the effects of myo-inositol (MI), seleno-L-methionine (Se), MI + Se, and resveratrol on C cells of mice exposed to cadmium chloride (Cd Cl2), as no data are currently available on the possible protective effects of these molecules. In contrast, we have previously shown this protective effect against CdCl2 on the thyroid follicles of mice. Ninety-eight C57 BL/6J adult male mice were divided into 14 groups of seven mice each: (i) 0.9% NaCl (vehicle; 1 ml/kg/day i.p.); (ii) Se (0.2 mg/kg/day per os); (iii) Se (0.4 mg/kg/day per os); (iv) MI (360 mg/kg/day per os); (v) Se (0.2 mg/kg/day) + MI; (vi) Se (0.4 mg/kg/day) + MI; (vii) resveratrol (20 mg/kg); (viii) CdCl2 (2 mg/kg/day i.p.) + vehicle; (ix) CdCl2 + Se (0.2 mg/kg/day); (x) CdCl2 + Se (0.4 mg/kg/day); (xi) CdCl2 + MI; (xii) CdCl2 + Se (0.2 mg/kg/day) + MI; (xiii) CdCl2 + Se (0.4 mg/kg/day) + MI; (xiv) CdCl2 + resveratrol (20 mg/kg). After 14 days, thyroids were processed for histological, immunohistochemical, and morphometric evaluation. Compared to vehicle, Cd significantly decreased follicle mean diameter, increased CT-positive cells number, area and cytoplasmic density, and caused the disappearance of TUNEL-positive C cells, namely, the disappearance of C cells undergoing apoptosis. Se at either 0.2 or 0.4 mg/kg/day failed to significantly increase follicular mean diameter, mildly decreased CT-positive cells number, area and cytoplasmic density, and was ineffective on TUNEL-positive C cells. Instead, MI alone increased significantly follicular mean diameter and TUNEL-positive cells number, and decreased significantly CT-positive cells number, area and cytoplasmic density. MI + Se 0.2 mg/kg/day or MI + Se 0.4 mg/kg/day administration improved all five indices more markedly. Indeed, follicular mean diameter and TUNEL-positive cells number increased significantly, while CT-positive cells number, area and cytoplasmic density decreased significantly. Thus, all five indices overlapped those observed in vehicle-treated mice. Resveratrol improved significantly all the considered parameters, with a magnitude comparable to that of MI alone. In conclusion, the association Myo + Se is effective in protecting the mouse thyroid from the Cd-induced hyperplasia and hypertrophy of C cells. This benefit adds to that exerted by Myo + Se on thyrocytes and testis.

MicroRNA expression profiles of the thyroid after goiter formation and involution in rats under different iodine regimens.

BACKGROUND: Thyroid damage occurs during experimental iodine-deficient goiter and involution with iodine supplementation. This study investigated the dynamic microRNAs (miRNAs) expression profiles in iodine-deficient thyroids during adequate and excessive iodine supplementation. METHODS: Twenty-four female Wistar rats were randomly divided into control, low-iodine (LI), LI-1I, and LI-2I groups. The LI-1I and LI-2I groups were fed a LI diet for 12 weeks, followed by a onefold (adequate) or twofold (excessive) physiological dose of iodine for 4 weeks to induce involution. The miRNA expression profiles were evaluated and the potential functions of the differentially expressed miRNAs identified were explored. RESULTS: In the LI group, 20 miRNAs were downregulated and 8 were upregulated. After involution, 21 miRNAs recovered to the control group levels in the LI-1I group, which was more than the 17 that recovered in the LI-2I group. In addition, 8 new differentially expressed miRNAs were identified in the LI-1I group, which was less than the 13 found in the LI-2I group. Bioinformatics analyses indicated that all differentially expressed miRNAs were involved in different processes and pathways, such as autoimmune thyroid disease and the Ras signaling pathway. CONCLUSION: Differentially expressed miRNAs are involved in iodine-deficient goiter formation and involution. Supplementation with adequate, not excessive, iodine may be more beneficial to restore homeostasis.

Effect of lithium carbonate on the function of the thyroid gland: mechanism of action and clinical implications.

Lithium carbonate, a drug known for more than 100 years, has been successfully used as a psychiatric medication. Currently, it is a commonly used drug to treat patients with unipolar and bipolar depression, and for the prophylaxis of bipolar disorders and acute mania. Lithium salts may cause the development of goiter, hypothyroidism, or rarely hyperthyroidism. The present review examined the current state of knowledge on the effect of lithium carbonate on the thyroid gland. The Pubmed database and Google Scholar were searched for articles related to the effects of lithium therapy on the thyroid gland function published up to February 2020. Studies that examined the mechanism of action of lithium at the molecular level, including pharmacokinetics, and focused on its effects on the thyroid gland were included. Lithium as a mood-stabilizing drug has a complex mechanism of action. Because of the active transport of Na+/I- ions, lithium, despite its concentration gradient, is accumulated in the thyroid gland at a concentration 3 - 4 times higher than that in the plasma. It can inhibit the formation of colloid in thyrocytes, change the structure of thyroglobulin, weaken the iodination of tyrosines, and disrupt their coupling. In addition, it reduces the clearance of free thyroxine in the serum, thereby indirectly reducing the activity of 5-deiodinase type 1 and 2 and reducing the deiodination of these hormones in the liver. Taken together, this review provides recommendations for monitoring the thyroid gland in patients who require long-term lithium therapy. Prior to the initiation of lithium therapy, thyroid ultrasound should be performed, and the levels of thyroid hormones (fT3 and fT4), TSH, and antithyroid peroxidase and antithyroglobulin antibodies should be measured. If the patient shows normal thyroid function, TSH level measurement and thyroid ultrasound should be performed at 6- to 12-month intervals for long term.

Animals in Iodine Deficiency or Sulfadimethoxine Models of Thyroid Damage Are Differently Affected by the Consumption of Brassica Sprouts.

The study was primarily aimed at investigating the effect of brassica sprout consumption, namely rutabaga (Brassica napus L. var. napobrassica) sprouts (R) generally recognized as antithyroid agent due to its goitrogenic substance content, on hematological, biochemical, and immunological parameters in rats. Sprouts were tested alone and in a combination with other antithyroid factors, such as iodine deficiency (RDI) and sulfadimethoxine (RS). The expression of the heme oxygenase-1 (HO-1) gene in the thyroid as a stress-inducible protein was determined. The thermographic analysis was also estimated. The intake of rutabaga sprouts by healthy rats did not reveal any significant, harmful effect on the thyroid function. Both body temperature and expression of HO-1 remained unchanged in response to the consumed sprouts. In animals with hypothyroidism, rutabaga sprouts enhanced the negative effect of iodine deficiency or sulfadimethoxine ingestion on the organism by increasing the WBC (RDI), TNF-α (RS), creatinine (RS), and triglyceride (RDI and RS) levels, as well as decreasing PLT (RS) level. Moreover, rutabaga sprout consumption by rats with iodine deficiency and sulfadimethoxine decreased their body temperature. Additionally, the concomitant administration of sprouts and iodine depletion significantly reduced the expression of HO-1 in the thyroid. The results may prove useful in confirming rutabaga sprout consumption to be safe, though the seeds of this vegetable provide a well-known antithyroid agent. Our results have shown that rutabaga sprout consumption may be also a factor that enhances the negative clinical features only when combined with iodine deficiency and sulfadimethoxine ingestion.

Thyroid Dysfunction in Patients with Pulmonary Artery Hypertension (PAH): The Effect of Therapies Affecting the Prostanoid Pathway.

INTRODUCTION: Epoprostenol, a synthetic prostaglandin I2 (PGI2) analog, has been the mainstay of treatment for severe pulmonary arterial hypertension (PAH) for the last two decades. Treprostinil, another synthetic prostaglandin analog, and selexipag, an oral selective Inositol Phosphate (IP) prostacyclin receptor agonist, have also been approved for treatment of PAH. Prostacyclin and its analogs cause a variety of side effects in patients with PAH; however, thyroid dysfunction is rarely reported. METHODS: After treating an index case of thyroid dysfunction occurring after initiation of epoprostenol, we reviewed our databases of PAH patients treated with epoprostenol, treprostinil or selexipag to identify the occurrence of this association. RESULTS: We identified six cases of thyroid dysfunction in our cohort: five after initiation of an intravenous prostacyclin (epoprostenol) and one after initiation of an oral prostacyclin receptor agonist (selexipag). Four of the patients presented with hyperthyroidism and two with a large autoimmune goiter. Graves' disease was seen in three patients, Hashimoto's disease in two patients and thyrotoxicosis in one patient. CONCLUSION: Therapy with medications targeting the prostacyclin pathway is a potential risk factor for the development of symptomatic thyroid disease.

Case Series: Minocycline-Associated Thyroiditis.

INTRODUCTION: Minocycline, a member of the tetracycline class of antibiotics, has been associated with benign thyroid pigmentation but reports of thyroid dysfunction are sparse. METHODS: Cases were selected via an inquiry of the electronic medical records for patients with thyroid dysfunction and the use of a tetracycline antibiotic. Non-autoimmune thyroiditis was defined as abnormally low or suppressed thyroid-stimulating hormone (TSH, <0.3 µIU/mL), elevated free thyroxine or total thyroxine, and undetectable antithyroid antibodies. RESULTS: Nine cases of thyroiditis without autoimmunity were identified out of 423 reviewed patients. Cases of thyroiditis occurred in adolescents ages 14-17 years who had been taking minocycline for 6 months to 4 years. In all cases, minocycline was prescribed for the treatment of acne. Four of the 9 received treatment for thyrotoxicosis with a ß-blocker (in 3 cases) and/or antithyroid drug (in 2 cases). Thyroiditis was symptomatic in all but one individual who presented with painless goiter. All thyroiditis was transient and resolved after a median of 4.5 months (range 2-5 months). In one case, thyroiditis was followed by transient hypothyroidism. DISCUSSION: Minocycline is known to cause thyroid abnormalities, although it has not been definitively linked to thyroid dysfunction. Here, we report 9 cases of non-autoimmune thyroiditis in adolescents receiving minocycline for acne. We recommend that minocycline exposure be considered in the differential diagnosis for thyroiditis and that patients receiving minocycline be counseled regarding the risk of thyroid dysfunction.

Effect of Reduction in Iodine Content of Edible Salt on the Iodine Status of the Chinese Population.

OBJECTIVE: The aim of this study was to evaluate the impact of the revised Chinese National Standard GB26878-2011 'Iodine Content in Edible Salt' on the iodine status among the Chinese population. METHODS: In 2011 and 2014, the probability proportionate to size sampling (PPS) was used in each Chinese province to obtain the representative data. In each sampling unit, school children aged 8-10 years and pregnant women were selected. Key indicators included urinary iodine concentration (UIC), thyroid volume (TV), and the iodine content in edible household salt. RESULTS: The median urinary iodine concentration (MUIC) decreased between 2011 and 2014 from 238.6 to 197.9 µg/L in school-age children. The number of provinces with iodine excess decreased to zero. The proportion of children whose UIC was > 300 µg/L was 18.8% and decreased to 11% compared with 29.8% in 2011. There was no significant difference in UIC < 50 µg/L between 2014 (4.3%) and 2011 (3.7%) (P > 0.05). The MUIC among pregnant women in 2014 was more concentrated between 110 and 230 µg/L. The goiter rate among children aged 8-10 years was unchanged, both the goiter rate of 2011 and 2014 remaining below 5%, in view of the sustainable elimination of iodine deficiency disorders. CONCLUSION: The National Standard GB26878-2011 'Iodine Content in Edible Salt' that was introduced in March 2012 resulted in an overall improvement in iodine status, reducing the risk of excessive iodine intake in the Chinese population.

Iodine-Induced Fetal Hypothyroidism: Diagnosis and Treatment with Intra-Amniotic Levothyroxine.

BACKGROUND: Iodine is necessary for fetal thyroid development. Excess maternal intake of iodine can cause fetal hypothyroidism due to the inability to escape from the Wolff-Chaikoff effect in utero. CASE REPORT: We report a case of fetal hypothyroid goiter secondary to inadvertent excess maternal iodine ingestion from infertility supplements. The fetus was successfully treated with intra-amniotic levothyroxine injections. Serial fetal blood sampling confirmed fetal escape from the Wolff-Chaikoff effect in the mid third trimester. Early hearing test and neurodevelopmental milestones were normal. CONCLUSION: Intra-amniotic treatment of fetal hypothyroidism may decrease the rate of impaired neurodevelopment and sensorineural hearing loss.

Adverse effects on thyroid of Chinese children exposed to long-term iodine excess: optimal and safe Tolerable Upper Intake Levels of iodine for 7- to 14-y-old children.

Background: The adverse effects of iodine excess on the thyroid in children are not well understood, and the Tolerable Upper Intake Level for iodine in children is unclear. Objective: The aims of this study were to assess the effects of chronic long-term iodine excess on thyroid function in children and to explore the safe Tolerable Upper Intake Level of iodine in Chinese children. Design: A multistage cross-sectional study was conducted in 2224 children from areas with adequate to excessive iodine content in drinking water. Repeated samples of 24-h urine and spot urine samples were collected to estimate habitual daily iodine intakes of children. The thyroid volume in children was measured and blood samples were collected to determine thyroid function. Results: The habitual iodine intake of children was 298 µg/d (range: 186-437 µg/d). The total goiter rate was 9.7%, 232 (11.2%) children had hyperthyrotropinemia, and 232 (11.2%) children had thyroglobulin (Tg) concentrations >40 µg/L. The prevalence of hyperthyrotropinemia was >10% in children at iodine intakes of 200-300 µg/d. Tg concentrations increased with increased iodine intake (ß = 0.5; 95% CI: 0.4, 0.6), and the prevalence of Tg >40 µg/L was >3% in all iodine-intake groups. Multivariate logistic regression analysis indicated that the risk of total goiter significantly increased at iodine intakes ≥250-299 µg/d in 7- to 10-y-old children (OR: 8.8; 95% CI: 2.3, 34.0) and at iodine intakes ≥300-399 µg/d in 11- to 14-y-old children (OR: 5.2; 95% CI: 1.5, 18.3). However, there were no consistent differences in the risk of hyperthyrotropinemia and Tg >40 µg/L in children between different iodine-intake groups. Conclusions: Thyroid volume and goiter appear to be more sensitive indicators of thyroid stress than thyrotropin and Tg in children with long-term excess iodine intakes. We recommend 250 and 300 µg/d as safe Tolerable Upper Intake Levels of iodine for children aged 7-10 y and 11-14 y, respectively. This trial was registered at www.clinicaltrials.gov as NCT02915536.

Fetal goitrous hypothyroidism treated by intra-amniotic levothyroxine administration: case report and review of the literature.

BACKGROUND: Fetal goitrous hypothyroidism is mainly caused by maternal treatment of Graves' disease. Fetal goiter sometimes compresses the trachea and esophagus and may cause polyhydramnios, preterm labor, complications of labor and delivery, and neonatal respiratory disorder. CASE PRESENTATION: We report a case of fetal goitrous hypothyroidism in which the mother had Graves' disease, which was treated with propylthiouracil. Intra-amniotic levothyroxine (L-T4) administration was performed, and the fetal goiter decreased in size. A female infant was delivered without goiter and complications. Thyroid function was within the normal range. CONCLUSIONS: Previous reports on fetal goitrous hypothyroidism that was treated with intra-amniotic L-T4 showed that patients who had intra-amniotic L-T4 administration were likely to have a good outcome compared with patients who did not have L-T4. Thyroid function of the mother and fetus should be carefully monitored and treated appropriately.

Effect of excess iodine intake on thyroid diseases in different populations: A systematic review and meta-analyses including observational studies.

BACKGROUND: Although several reports concerning the association of iodine excess and thyroid disease have appeared, no systematic review of the association between iodine excess intake and thyroid diseases, especially hyperthyroidism and hypothyroidism, has yet been reported. METHOD: We conducted a systematic search of Ovid MEDLINE, PubMed, Cochrane Central Register of Controlled Trials databases, Ichushi-Web and CiNii database for intervention trials and observational studies. Search terms were constructed from related words for excess AND iodine intake or excretion AND thyroid hormones or diseases AND study designs. After considering the qualitative heterogeneity among studies, a meta-analysis was conducted and odds ratios and 95% confidence intervals (CI) were estimated in random-effects models. A protocol was registered with PROSPERO (No. CRD42015028081). RESULTS: 50 articles were included, including three intervention trials, six case-control studies, six follow-up studies and 35 cross-sectional studies. Three cross-sectional studies in adults included in meta-analysis. Odds ratio of overt and subclinical hypothyroidism between excess and adequate populations were 2.78 (CI:1.47 to 5.27) and 2.03 (CI:1.58 to 2.62) in adults, respectively. Source of excess iodine status was mainly iodized salt or water in included studies. CONCLUSION: Although universal salt iodization has improved goiter rates, chronic exposure to excess iodine from water or poorly monitored salt are risk factors for hypothyroidism in free-living populations. Monitoring of both iodine concentration in salt as well as the iodine concentration in local drinking water are essential to preventing thyroid diseases. Hypothyroidism should be also carefully monitored in areas with excess iodine. Because of the low quality and limited number of included studies, further evidence and review are required.