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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., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Published by Elsevier Inc.)

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., (Copyright © 2023. Published by Elsevier Masson SAS.)

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., (© 2022 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

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., (Copyright © 2022. Published by Elsevier Masson SAS.)

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., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., Competing Interests: SB has been an invited speaker for Lo.Li. Pharma, which provided us with pure MI, but had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer SMF declared a shared affiliation with the authors AA and PF to the handling editor at time of review., (Copyright © 2021 Benvenga, Micali, Ieni, Antonelli, Fallahi, Pallio, Irrera, Squadrito, Picciolo, Puzzolo and Minutoli.)

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.

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.

Introduction: Epoprostenol, a synthetic prostaglandin I2 (PGI 2 ) 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.

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., (Copyright © 2018 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

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 (β = 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.

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.

Occurrence and mode of action of potentially relevant goitrogens in human nutrition and their mode of action (MOA) are reviewed, with special focus on the anionic iodine uptake inhibitors perchlorate (PER), thiocyanate (SCN) and nitrate (NO3). Epidemiological studies suggest persistent halogenated organic contaminants and phthalates as well as certain antimicrobials to deserve increased attention. This also applies to natural goitrogens, including polyphenols and glucosinolates, food constituents with limited data density concerning human exposure. Glucosinolates present in animal feed are presumed to contribute to SCN transfer into milk and milk products. PER, SCN and NO3 are well-investigated environmental goitrogens in terms of MOA and relative potency. There is compelling evidence from biomarker monitoring that the exposure to the goitrogens SCN and NO3 via human nutrition exceeds that of PER by orders of magnitude. The day-to-day variation in dietary intake of these substances (and of iodide) is concluded to entail corresponding variations in thyroidal iodide uptake, not considered as adverse to health or toxicologically relevant. Such normal variability of nutritional goitrogen uptake provides an obvious explanation for the variability in radioactive iodine uptake (RAIU) measurements observed in healthy individuals. Based on available data, a 20 % change in the thyroidal uptake of iodide is derived as threshold value for a biologically meaningful change induced by perchlorate and other goitrogens with the same MOA. We propose this value to be used as the critical effect size or benchmark response in benchmark dose analysis of human RAIU data. The resulting BMDL20 is 0.0165 mg/kg bw/day or 16.5 μg/kg bw/day. Applying a factor of 4, to allow for inter-human differences in toxicokinetics, leads to a TDI for perchlorate of 4 μg/kg bw/day.

A 27-year-old gravid 1 at 27 weeks 6 days with a history of hypothyroidism had an ultrasound that demonstrated a 3.9 × 3.2 × 3.3-cm well-circumscribed anterior neck mass, an extended fetal head, and polyhydramnios. Further characterization by magnetic resonance imaging (MRI) showed a fetal goiter. During her evaluation for the underlying cause of the fetal goiter, the patient revealed she was taking nutritional iodine supplements for treatment of her hypothyroidism. She was ingesting 62.5 times the recommended amount of daily iodine in pregnancy. The excessive iodine consumption caused suppression of the fetal thyroid hormone production, resulting in hypothyroidism and goiter formation. After the iodine supplement was discontinued, the fetal goiter decreased in size. At delivery, the airway was not compromised. The infant was found to have reversible hypothyroidism and bilateral hearing loss postnatally. This case illustrates the importance of examining for iatrogenic causes for fetal anomalies, especially in unregulated nutritional supplements., (Copyright © 2016 by the American Academy of Pediatrics.)

This paper applies probabilistic risk assessment in quantifying risks from cumulative and aggregate risk pathways for selected goitrogens in water and food. Results show that the percentages of individuals with a Hazard Index (HI) value above 1 ranges between 30% and 50% both with and without serum half-life correction when a traditional regulatory assessment approach based on establishment of a No Observed Effects Level (NOEL) is used. When an exposure-response curve is instead used and a threshold of 50% inhibition is assumed, 1.1% or less of the population exceeds an HI value of 1 with no serum half-life correction, rising to as high as 11% when serum half-life correction is applied. If 0% to 5% threshold for iodide uptake inhibition is assumed for production of adverse effects, the percentage of the population with an HI above 1 is 46.2% or less with no serum half-life correction, and 47.2% or less when serum half-life correction is applied. The probabilistic analysis shows that while there are exposed groups for whom perchlorate exposures are the primary cause of individuals having HI values above 1, these constitute significantly less than 1% of the population. Instead, the potential risk from exposure to goitrogens is dominated by nitrates without serum half-life correction and thiocyanates with serum half-life correction, suggesting public health protection is better accomplished by a focus on these and other goitrogens expect in highly limited cases where waterborne perchlorate is at unusually high concentrations.

Iodine deficiency can impair the reproductive performance of livestock and affect perinatal mortality of offspring, yet diagnosis of deficiency is complicated and guidelines for I supplementation are imprecise. We challenged pasture-grazing pregnant ewes with a long-acting I supplement and a goitrogenic forage, then monitored their I status during gestation and lactation and in their lambs from birth to weaning. Approximately 46 d into gestation, 376 ewes were assigned to 6 groups comprising 3 supplementation levels × 2 diet regimens. On d 0 the groups received an intramuscular injection of iodized oil providing 0, 300, or 400 mg of I. They grazed until d 23, then half of each supplementation group were fed brassica kale until d 85, then all groups returned to pasture for lambing (parturition approximately d 99) and remained there until weaning (d 192). Serum total I concentration (STIC) was measured repeatedly in 8 'monitor' ewes per group and in their lambs and in milk sampled postpartum. Severity of goiter was determined as the thyroid-weight:birth-weight (TW:BW) ratio in 82 newborn dead lambs. Mean ± SE STIC for all ewes was initially 42 ± 2 (range 24 to 105) µg/L. Diet did not affect I concentrations in ewe serum or milk. Responses to iodized oil were proportional to dose level; STIC increased to approximately 150 and 240 µg/L for the 300- and 400-mg I groups and remained greater than 0-mg I groups for 161 d (P < 0.05). Milk contained 26, 271, and 425 µg I/L for the 0-, 300-, and 400-mg I groups, respectively. Mean STIC of lambs from supplemented ewes did not differ by diet; concentrations for the 300- and 400-mg I groups were 237 and 287 µg I/L at birth, and by weaning all groups were similar (62 ± 3 µg/L). Lamb STIC measured at birth correlated with exposure to I in utero (R(2) = 0.59), which was estimated from the area under the curve (AUC) of ewe STIC measured during the last 99 d of gestation. Thyroid enlargement in lambs affecting the TW:BW ratio was a sensitive indicator of maternal nutrition, being greater with kale feeding (1.27 vs. 0.51 g/kg) and lesser with I supplementation (0.35 vs. 1.44 g/kg). Results support the use of STIC as a biochemical criterion. It was sensitive to the effects of I supplementation with responses in ewes and lambs proportional to dose level and it reflected the relationship between ewe and lamb I metabolism. However STIC did not discriminate between groups of ewes fed pasture vs. goitrogenic forage during pregnancy.

A 69-year-old man presented with a 6-week history of shortness of breath on exertion, unintentional weight loss, altered bowel habits and lethargy. He was diagnosed with atrial fibrillation 2 years previously and started on amiodarone and warfarin. He subsequently reverted to sinus rhythm and his medication was stopped 1 year prior to presentation. He denied history of thyroid dysfunction. On examination, he had a small firm goitre of grade I. His skin was warm and sweaty. Thyroid function tests showed him to be thyrotoxic. He was started on carbimazole 20 mg; however, he further became significantly thyrotoxic. Given the severity of his presentation and lack of any clinical or biochemical improvement, oral prednisolone 30 mg once daily was coadministered. His symptoms subsequently resolved and he became euthyroid. The prednisolone was tapered down and stopped while the carbimazole was incrementally reduced to 10 mg daily., (2014 BMJ Publishing Group Ltd.)

Since 1963 lithium treatment has been the best proven long-term pharmacotherapy for bipolar disorder (BD), both in the prevention of depressive and manic episodes, along with the reduction of the suicide risk. Thyroid gland and the hypothalamic-pituitary-thyroid (HPT) axis play a role in the pathophysiology, clinical course and treatment of BD. The influence of lithium on the thyroid gland is one of the key side effects in the long-term therapy with this drug. Lithium is accumulated in the thyroid gland at 3 to 4-fold higher concentrations as compared to its plasma levels. Its administration results in the reduced production with release inhibition of thyroid hormones, altering the immune processes of this gland. The most common thyroid side effects associated with long-term lithium treatment are goiter and hypothyroidism. Hyperthyroidism is a rare complication of lithium therapy. Lithium may also induce an increase in the thyroid autoimmunity, especially if such change had been present before lithium treatment producing structural changes in this gland. This paper reviews the management of complications described above as well as recommendations for monitoring of thyroid function in patients receiving long-term lithium treatment are discussed.

Thyroid disfunction affects negatively emotional stability and worsens the clinical course of bipolar affective disorder. The main stabilizer used in this illness, lithium carbonate has numerous effects on the physiology of the thyroid, with the most significant being the inhibition of thyroid hormone release that may occur at therapeutic levels. These dysfunctions have also been reported most frequently in bipolar patients not undergoing treatment with lithium, and was not completely explained by the effects of this drug. Apart from the numerous medical complications and mood disturbances, the cognitive or perceptual system may also be affected. In fact, the presence of thyroid disease increases the rates of obsessive compulsive disorder, phobias, panic disorder, major depressive disorder, cyclothymia, or bipolar disorder. In severe cases of hypothyroidism, the clinical symptoms and signs can be similar to a melancholic depression or dementia. It is therefore important to know well all these possible complications in daily clinical practice. This review will cover the main thyroid dysfunctions present in bipolar patients, whether ot not produced by treatment with lithium carbonate, and will provide a series of recommendations for clinical management., (Copyright © 2013 SEP y SEPB. Published by Elsevier España. All rights reserved.)

Although thyroid-stimulating hormone (TSH) is known to be a major regulator of thyroid hormone biosynthesis and thyroid growth, insulin-like growth factor 1 (IGF-1) is required for mediating thyrocyte growth in concert with TSH in vitro. We generated mice with thyrocyte-selective ablation of IGF-1 receptor (TIGF1RKO) to explore the role of IGF-1 receptor signaling on thyroid function and growth. In 5-wk-old TIGF1RKO mice, serum thyroxine (T4) concentrations were decreased by 30% in concert with a 43% down-regulation of the monocarboxylate transporter 8 (MCT8), which is involved in T4 secretion. Despite a 3.5-fold increase in circulating concentrations of TSH, thyroid architecture and size were normal. Furthermore, thyrocyte area was increased by 40% in WT thyroids after 10 d TSH injection, but this effect was absent in TSH-injected TIGF1RKO mice. WT mice treated with methimazole and sodium perchlorate for 2 or 6 wk exhibited pronounced goiter development (2.0 and 5.4-fold, respectively), but in TIGF1RKO mice, goiter development was completely abrogated. These data reveal an essential role for IGF-1 receptor signaling in the regulation of thyroid function and TSH-stimulated goitrogenesis.

This report describes the onset of goiter in several species of shark following the addition of ozone to a touch pool. A detailed description of a female brown-banded bamboo shark (Chiloscyllium punctatum) that was presented with multinodular goiter is provided. Four other brown-banded bamboo sharks and 11 white-spotted bamboo sharks (Chiloscyllium plagiosum) housed in the same system developed clinical disease consistent with goiter, but two zebra bullhead sharks (Heterodontus zebra) did not. Plasma thyroxine (T4) concentration was 4.64 ng/ml before euthanasia, consistent with a diagnosis of hypothyroidism. The sharks had been chronically exposed to mean (+/- standard error) NO3-N concentrations of 35 +/- 5.12 mg/L before ozonation of the system. Ozonation of aquarium water causes a reduction in environmental iodide, which is required for thyroid hormone synthesis. Nitrate is goitrogenic and would further decrease I- absorption by competitive inhibition. Multinodular goiter is consistent with goiter caused by chronic iodide deficiency. Understanding the interaction between water chemistry and goiter development is critical to development of elasmobranch health management systems.

Endemic fluorosis is a serious problem in public health. Previous studies have indicated that patients with thyroid goiters usually live in fluoride-affected areas. However, the mechanism of goitrogenesis caused independently by fluoride is still unclear. The principle objective of this study was to investigate the possible roles of nitric oxide (NO) and vascular endothelial growth factor (VEGF) in the genesis of fluoride-induced nodular goiters. Eighty SD rats (40 males and 40 females) at the age of 4 weeks were used to establish animal models via fluoride-supplemented drinking water. These rats were randomly divided into four groups of 20. Group 1 was used as the control and were given deionized water. Group 2 (LF), group 3 (MF), and group 4 (HF) were given deionized water containing 50mg/L, 100mg/L, and 200mg/L of sodium fluoride (NaF), respectively. Thyroid samples were collected on day 150. Pathological observation was performed to evaluate structural changes in the thyroid gland. The expression of VEGF mRNA in the thyroid glands was assessed by reverse transcriptional PCR. The serum NO level was analyzed by spectrometric methods. In addition, immunohistochemistry was conducted to evaluate expression and deposition of VEGF in the thyroid gland. The results showed that the average relative weight of the thyroid glands of rats in the fluoride-treated groups was significantly higher than that in control rats (p<0.05). The proliferation and dilatation of capillary blood vessels, enlarged follicles with excessive colloid, and obvious nodules were found in the thyroid glands of fluoride-treated rats. Compared to the control group, the expression of VEGF mRNA in the thyroid gland and the serum NO levels in the fluoride-treated groups were significantly increased (p<0.05). Furthermore, the deposition of VEGF in epithelial and follicular cells of the thyroid gland was significantly higher in fluoride-treated groups than in the control group. These results suggested that abnormal expression of VEGF induced by fluoride can lead to the proliferation of vascular endothelial cells in the thyroid gland. Accordingly, VEGF oversecreted locally by vascular endothelial cells might contribute to the proliferation of epithelial and follicular cells, resulting in the formation of hyperplastic nodules and enlargement of the thyroid gland. Furthermore, we proposed that there might be a positive feedback mechanism between NO and VEGF expression in fluoride-induced goiter formation. It was concluded that angiogenic and vasodilative factors such as VEGF and NO must be involved in fluoride-induced thyroid goitrogenesis., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Introduction: The present study aims to evaluate the incidence, types, timing and risk factors in amiodarone (AMD)-induced thyroid dysfunction., Material and Methods: The study comprised 229 patients from an iodine-replete area (115 women, 114 men, mean age 63.8 ± 9.2 years), chronically treated with AMD. The cases were clinically investigated prior to, and during treatment, by thyroid 2D and color Doppler flow sonography, thyroid function tests (TSH, FT3, FT4), and antithyroid antibodies., Results: Of 88 patients (38.4%) who developed thyroid dysfunction, 47 (20.5%) presented AMD-induced thyrotoxicosis (AIT) and 41 (17.9%) AMD-induced hypothyroidism (AIH). There is an evident prevalence of subclinical AIH (29 cases), compared to subclinical AIT (three cases). Regarding clinical forms, these prevailed in AIT (44 patients) (p 〈 0.001, Fisher's exact test). Thyrotoxic patients were classified in pathogenic types as follows: 11 cases as type 1, 15 cases as type 2, and 21 cases as mixed form. The most important risk factor for the development of thyroid dysfunction was represented by the underlying thyroid pathology. The patients with previous thyroid abnormalities (diffuse or nodular goitre and/or positive antithyroid antibodies) developed earlier thyroid dysfunction compared to those with an apparently normal thyroid gland. The thyroid dysfunction occurrence was heterogeneous (4-84 months). Thyrotoxicosis involved especially young ages, while AIH affected later years.The daily dose, the duration of the treatment and the cumulative dose of AMD do not represent risk factors in thyroid dysfunction development. The determination of serum AMD and desethylamiodarone concentrations does not offer benefits in the diagnosis and treatment of thyroid dysfunction., Conclusions: In the present study, the incidence of AIH was similar to that reported in iodine-replete areas. The incidence of AIT was higher that previously reported, a fact underlining the importance of the proper screening and monitoring of patients. Cases with previous thyroid morphologic and/or immunologic abnormalities require frequent monitoring.

Amiodarone treatment is associated with the occurrence of thyroid dysfunction. The aim was to determine the incidence of amiodarone-induced thyroid dysfunctions and the influence of gender, age, treatment duration, goiter, thyroid antibodies, thyroid echogenicity and family history on their appearance. Of 248 consecutive patients, 144 males and 104 females, referred to thyroid status screening, 16% were with clinical dysfunction, 21% with sub-clinical dysfunction and 63% were euthyroid. The presence of goiter and thyroid peroxidase antibodies were the significant individual predictive factors for the occurrence of clinical dysfunction, and in the multivariate regression model, the presence of goiter was a significant predictive factor with the prognostic value of 80%. For sub-clinical dysfunction, the significant individual predictive factors were female gender and the presence of goiter, as well as in the multivariate regression model, with the prognostic value of 74.5% for female gender and 77.5 % for the presence of goiter. It is necessary to check the thyroid status both before and during amiodarone treatment. Administration of other anti-arrhythmic drugs and/or more frequent check-ups of the thyroid status should be taken into consideration in patients at higher risk, i.e. women with positive thyroid peroxidase antibodies and goiter.

Elasmobranch susceptibility to goiter formation in captive environments has been well documented. Until recently, most public aquariums operated under the belief that the etiology of goiter in elasmobranchs was nutritional and specifically caused by insufficient dietary iodine. Recent studies have demonstrated that high environmental nitrate (NO3-N) inhibits the ability of the thyroid gland to utilize available iodide, resulting in thyroid gland overstimulation by thyroid stimulating hormone and ultimately leading to the development of goiter. The objective of this study was to evaluate the effects of high environmental nitrate concentrations on thyroid function in juvenile whitespotted bamboo sharks Chiloscyllium plagiosum. In July 2008, five juveniles (80-150 g) were exposed to a low-nitrate environment (NO3-N concentration < 1 mg/L of water) and five were exposed to an elevated-nitrate environment (NO3-N = 70 mg/L) for 29 d in a flow-through natural seawater system. Nitrate exposure did not affect growth rates (e.g., weight, length, and condition factor) and did not alter free plasma thyroxine concentrations during the 29-d experimental period. However, histological examination of thyroid glands from sharks exposed to elevated nitrate revealed the development of diffuse hyperplastic goiter. With increasing restrictions on water use, most modern aquaria operate as recirculating systems, which results in higher and more chronic nitrate exposure for captive animals. Goiter is one of the most common health problems in captive elasmobranchs, and this study suggests that nitrate exposure is an important factor in the etiology of this disease.

Maternal overtreatment with antithyroid drugs can induce fetal goitrous hypothyroidism. This condition can have a critical effect on pregnancy outcome, as well as on fetal growth and neurological development. The purpose of this Review is to clarify if and how fetal goitrous hypothyroidism can be prevented, and how to react when prevention has failed. Understanding the importance of pregnancy-related changes in maternal thyroid status when treating a pregnant woman is crucial to preventing fetal goitrous hypothyroidism. Maternal levels of free T(4) are the most consistent indication of maternal and fetal thyroid status. In patients with fetal goitrous hypothyroidism, intra-amniotic levothyroxine injections improve fetal outcome. The best way to avoid maternal overtreatment with antithyroid drugs is to monitor closely the maternal thyroid status, especially estimates of free T(4) levels.

Background: We have demonstrated that the administration of delta-iodolactone (i.e., 5-iodo-delta lactone) of arachidonic acid (IL-delta), a mediator in thyroid autoregulation, prevents goiter induction by methylmercaptoimidazol (MMI) in rats. Other studies have shown that transforming growth factor beta-1 (TGF-beta1) mimics some of the actions of excess iodide, but its participation in autoregulation is disputed. The present studies were performed to test the hypotheses that IL-delta decreases thyroid growth by inhibition of cell proliferation and/or by stimulation of apoptosis due to oxidative stress, that TGF-beta is stimulated by an excess of iodide and by IL-delta, and that c-Myc and c-Fos expression are upregulated during goiter induction and downregulated during goiter inhibition., Methods: Rats were treated with MMI alone or together with iodide or IL-delta. Thyroid weight, cell number, cell proliferation, apoptosis, and oxidative stress were determined. Proliferating cell nuclear antigen (PCNA), TGF-beta1, TGF-beta3, c-Myc, and c-Fos were measured by Western blot., Results: MMI caused a progressive increase in thyroid weight accompanied by an increase in cell number, asymmetry of the ploidy histograms, and PCNA, c-Fos, and c-Myc expression. In addition, an early increase of apoptosis was observed. Peroxides as well as glutathione peroxidase and catalase activities were also increased in goitrous animals. The inhibitory action of IL-delta on goiter formation was accompanied by the inhibition of cell proliferation evidenced by a significant decrease in cell number, PCNA expression, and asymmetry of the ploidy histograms. A transient stimulation of apoptosis after 7 days of treatment was also observed. MMI administration stimulated TGF-beta1 but not TGF-beta3 synthesis. IL-delta alone caused a slight increase of TGF-beta3 but not TGF-beta1, whereas potassium iodide (KI) stimulated both isoforms and MMI reversed KI effect on TGF-beta1 expression but not on TGF-beta3., Conclusions: The goiter inhibitory action of IL-delta is due to the inhibition of cell proliferation and the transient stimulation of apoptosis. This latter action does not involve oxidative stress. TGF-beta1 does not play a role in the autoregulatory pathway mediated by IL-delta. Iodide stimulates TGF-beta3 without the need of being organified. These results suggest that there may be more than one pathway involved in the autoregulatory mechanism.

Fetal thyroid dysfunction is a well-recognized cause of secondary cardiac disease, including arrhythmias and hydrops fetalis, but has not previously been reported to mimic structural heart disease. We describe a case of fetal goiter presenting as suspected anomalous pulmonary venous connection and highlight lessons for the obstetrician and pediatric cardiologist with regard to imaging as well as communication.

Catechins are flavonoids found in abundance in green tea, have elicited high interest due to their beneficial effects on health. Though flavonoids have been reported to have an antithyroid effect and also to be goitrogenic there have been no reports about the effect of green tea on rat thyroid. The present study was designed to examine whether high doses of green tea has any harmful effect on thyroid physiology. For this purpose green tea extract was administered orally to male albino rats for 30 days at doses of 1.25 g%, 2.5 g% and 5.0 g%, respectively. Similarly, pure catechin was administered at doses of 25, 50 and 100mg/kg body weight which is equivalent to above doses of green tea extract. Lower body weight gain associated with marked hypertrophy and/or hyperplasia of the follicles was noted in the high dose of green tea and catechin treated groups. Decreased activity of thyroid peroxidase and 5'-deiodinase I and substantially elevated thyroidal Na,K+ATPase activity have been observed. Moreover, serum T3 and T4 levels were found to reduce followed by significant elevation of serum TSH. Taken together, these results suggest that catechin present in green tea extract might behave as antithyroid agent and possibly the consumption of green tea at high dose could alter thyroid function adversely., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

One in 200 people receive lithium for treatment of bipolar disorder. The common clinical side effects of the drug are goitre in up to 40% and hypothyroidism in about 20%. Lithium increases thyroid autoimmunity if present before therapy. Treatment with levothyroxine is effective and lithium therapy should not be stopped. Lithium may cause hyperthyroidism due to thyroiditis or rarely Graves' disease. As lithium inhibits thyroid hormone release from the thyroid gland it can be used as an adjunct therapy in the management of severe hyperthyroidism. It also increases thyroidal radioiodine retention and may be effective in reducing administered activity in hyperthyroidism. There is no clinical benefit of lithium therapy in thyroid cancer. More research is required on the cellular proliferative effects of lithium as well as its impact on the immune system.

Objectives: In this retrospective study, we reviewed the data from patients who had total thyroidectomy for benign thyroid disease and evaluated the safety of this surgery., Patients and Methods: Three hundred and twenty three patients (49 males, 274 females; mean age 42.6+/-14.1 years; range 13 to 80 years) who underwent total thyroidectomy between 2002 and 2008 were included in the study. In the preoperative studies, patients with suspicion of thyroid cancer were excluded. Indications for total thyroidectomy, cancer incidence and complication rates were evaluated. Two hundred and eighty three patients (87.6%) were operated on due to bilateral multinodular goiter, 17 (5.3%) due to toxic goiter, 23 (7.1%) due to thyroiditis., Results: In our study, it was found that the incidences of permanent recurrent laryngeal nerve palsy and permanent hypoparathyroidism were 0.6% and 1.86%, respectively. Postoperative hemorrhage requiring repeat surgery occurred in 0.6% of the patients. There was no recurrence during follow-up., Conclusion: The present study shows that total thyroidectomy is a safe procedure with a low incidence of permanent complications. Total thyroidectomy is an acceptable surgical alternative for benign multinodular or diffuse goiters.

Aims: Propylthiouracil (PTU) is presently considered to be the treatment of choice for hyperthyroidism in pregnancy. It is known to cross the human placenta, and therefore may affect the fetus. The major aims of this study were to evaluate the rate of major anomalies and to report the rate of fetal goitre, accompanied by hypothyroidism, in fetuses/ newborns of mothers after in utero exposure to PTU., Methods: Prospective observational controlled cohort study of PTU-exposed pregnancies of women counselled by the Israeli Teratology Information Service between the years 1994 and 2004 compared with women exposed to nonteratogens., Results: We followed up 115 PTU-exposed pregnancies and 1141 controls. The rate of major anomalies was comparable between the groups [PTU 1/80 (1.3%), control 34/1066 (3.2%), P= 0.507]. Hypothyroidism was found in 9.5% of fetuses/neonates (56.8% of whom with goitre). Hyperthyroidism, possibly resulting from maternal disease, was found in 10.3%. Goitres prenatally diagnosed by ultrasound were successfully treated in utero by maternal dose adjustment. In most cases neonatal thyroid functions normalized during the first month of life without any treatment. Median neonatal birth weight was lower [PTU 3145 g (2655-3537) vs. control 3300 g (2968-3600), P= 0.018]., Conclusions: PTU does not seem to be a major human teratogen. However, it could cause fetal/neonatal hypothyroidism with or without goitre. Fetal thyroid size monitoring and neonatal thyroid function tests are important for appropriate prevention and treatment.

Objective: To investigate the inhibitory effects of Kangjia Pill (KJP) on the cell proliferation in rat goiter model induced by methimazole (MMI)., Methods: Fifty-six Wistar rats were randomly divided into four groups: the normal group, MMI model group (MMI), low dose of KJP group (LKJP), and high dose of KJP (HKJP). Except the normal group (20 rats), the other groups (12 rats in each) were given 0.04% (w/v) MMI through the drinking water until the end of the experiment. One week later, the rats in the LKJP and HKJP groups were given KJP by gastrogavage at the dose of 250 mg/(kg x d) and 1,000 mg/(kg x d), respectively for 12 weeks. The relative thyroid weight (mg/100 g body weight) of each rat was accessed. The expression of proliferating cell nuclear antigen (PCNA) was determined by immunohistochemistry, and the correlation analysis between the PCNA positive thyrocytes and the relative thyroid weight was performed. The expressions of PCNA and cyclin D1 were examined with Western blotting., Results: After KJP treatment for 12 weeks, compared with the MMI group, the relative thyroid weight of the HKJP group decreased significantly, and the positive thyrocyte populations of PCNA in the two KJP groups reduced markedly (all P<0.05). The correlation analysis showed that PCNA was closely correlated with thyrocyte proliferation (r=0.685, P<0.05). KJP significantly decreased the protein expression of PCNA and cyclin D1 in the thyroid specimens (P<0.05), the high dose showed better effects., Conclusion: KJP played a therapeutic role via inhibiting cell proliferation in the rat goitrous glands.

Premature newborns are particularly vulnerable to iatrogenic hypothyroidism due to iodine exposure, usually through skin absorption of iodine-containing disinfectants or intravenous administration of iodinated contrast agents. We report here a case of severe iatrogenic hypothyroidism with goiter and cholestasis, discovered six weeks after a contrast enema using sodium ioxitalamate, an iodinated contrast agent. Prematurity, intrauterine growth retardation, and enteral feeding intolerance could explain why this complication occurred after contrast enema. Our observations suggest that indications of contrast enema in neonates need to be carefully considered, and when necessary, thyroid function should be monitored, especially in very premature infants.

Objective: To demonstrate the direct stimulation of thyroid tissue in the absence of thyroid-stimulating immunoglobulin after exposure to epoprostenol., Methods: Seronegative thyrotoxicosis, diffuse goiter, and homogeneous uptake on thyroid scintigraphy were noted in a patient with pulmonary arterial hypertension (PAH) being treated with intravenously administered epoprostenol (prostaglandin I2 or PGI2). More cases with similar characteristics were identified on review of the thyroid function in patients with PAH who were treated with this medication. Fifty-four adult patients with PAH were studied. The study subjects were divided into 2 groups based on whether they were treated with PGI2 or not. Thyroid functions were reviewed, and the prevalence of thyroid disease was assessed. We then compared the prevalence of hyperthyroidism in our study subjects with the prevalence of hyperthyroidism in the general female population using data from published studies., Results: We noted a high prevalence (3 of 45 or 6.7%) of thyroid-stimulating immunoglobulin-negative thyrotoxicosis in adults with preexisting PAH being treated with epoprostenol (PGI2) in the absence of other mechanisms or drugs to explain the hyperthyroidism. The prevalence of hyperthyroidism in our study population was significantly greater (P<.01 by X2 analysis) than that in the general female population in other published reports., Conclusion: The data suggest that epoprostenol is a medication associated with stimulation of thyroid tissue, goiter formation, and hyperthyroidism. Patients receiving this drug need to undergo close follow-up for the development of thyrotoxicosis and goiter.

C cells are primarily known for producing calcitonin, a hypocalcemic and hypophosphatemic hormone. Nevertheless, besides their role in calcium homeostasis, C cells may be involved in the intrathyroidal regulation of follicular cells, suggesting a possible interrelationship between the two endocrine populations. If this premise is true, massive changes induced by different agents in the activity of follicular cells may also affect calcitonin-producing cells. To investigate the behaviour of C cells in those circumstances, we have experimentally induced two opposite functional thyroid states. We hyperstimulated the follicular cells using a goitrogen (propylthiouracil), and we suppressed thyroid hormone synthesis by oral administration of thyroxine. In both scenarios, we measured T(4), TSH, calcitonin, and calcium serum levels. We also completely sectioned the thyroid gland, specifically immunostained the C cells, and rigorously quantified this endocrine population. In hypothyroid rats, not only follicular cells but also C cells displayed hyperplastic and hypertrophic changes as well as increased calcitonin levels. When exogenous thyroxine was administered to the rats, the opposite effect was noted as a decrease in the number and size of C cells, as well as decreased calcitonin levels. Additionally, we noted that the two cell types maintain the same numerical relation (10 +/- 2.5 follicular cells per C cell), independent of the functional activity of the thyroid gland. Considering that TSH serum levels are increased in hypothyroid rats and decreased in thyroxine-treated rats, we discuss the potential involvement of thyrotropin in the observed results.

Despite evidence for a conserved role of thyroid-stimulating hormone (TSH) in regulating vertebrate thyroid function, molecular data on thyroid responses to TSH are mainly limited to mammalian species. In this study, we examined histological and molecular changes in the thyroid of Xenopus laevis tadpoles during a 12-day treatment with 20mg/l perchlorate (PER) and 50mg/l ethylenethiourea (ETU). Inhibition of thyroid hormone (TH) synthesis by PER and ETU was evident from developmental retardation, reduced expression of TH-regulated genes and up-regulation of tshb-A mRNA. Thyroid histopathology revealed goiters with strikingly different follicular morphologies following PER and ETU treatment. Using real-time PCR, we analyzed thyroids sampled on day 12 for differential expression of 60 candidate genes. Further temporal analyses were performed for a subset of 14 genes. Relative to the control, PER and ETU treatment modulated the expression of 51 and 49 transcripts, respectively. Particularly genes related to TH synthesis and protein metabolism were similarly affected by PER and ETU. However, several genes were differentially expressed in PER- and ETU-treated tadpoles. Specifically, goiter formation in the PER treatment was associated with low expression of genes related to DNA replication but high expression of negative growth regulators. Results from this work provide for the first time a characterization of gene expression profiles during goitrogenesis in a non-mammalian vertebrate model. Overall, our data suggest that, in addition to TSH over-stimulation, further mechanisms related to the mode of goitrogen action contribute to the regulation of thyroid gene expression.

Necropsy and histopathologic examination of three Great Cormorants (Phalacrocorax carbo) shot in Niigata, central Japan, revealed goitrous changes in the thyroids. Thyroids had a hypertrophic follicular epithelium, loss or deficiency of luminal colloid, occasional small follicles suggesting hyperplasia, and occasional collapsed follicles. Irregularly shaped follicles were frequent, and hyperemia, deposition of dark pigment, and sporadic lymphoid aggregates were also seen. Chemical analysis simultaneously conducted showed higher than normal levels of dioxins in the liver, muscle, and fat, i.e., polychlorinated dibenzo-dioxins, polychlorinated dibenzo-furans, and coplanar polychlorinated biphenyls. The present results, together with those of relevant previous studies, strongly suggest an association between these pollutants and thyroid lesions in the Great Cormorant.

Two siblings born to a mother with Wilson's disease, who was taking D-penicillamine, developed transient goitrous hypothyroidism. A prospective evaluation of 5 patients with Wilson's disease taking and not taking D-penicillamine for as long as 9.5 years showed subclinical hypothyroidism. D-penicillamine probably inhibited thyroperoxidase activity in utero in healthy infants and during childhood in patients with Wilson's disease.

Objective: The aim of the present study was to analyze the influence of nitrate as a possible alimentary goitrogen on thyroid volume in a previously iodine-deficient area., Design: Population based cross-sectional epidemiologic survey., Participants: Data of 3772 participants (20-79 years) of the Study of Health in Pomerania without diagnosed thyroid disorders were analyzed. EVALUATION AND MEASUREMENTS: The nitrate concentration in spot urine was determined by ion chromatography. High nitrate levels were defined as urine nitrate concentrations exceeding the 75th percentile for the investigated population. Thyroid structure and size were measured by ultrasound. Subjects were divided into two groups with absence or presence of high urine nitrate concentrations. Comparisons between groups were made using the chi(2)-test or the Student's t-test. Multivariable analyses were done by logistic regression and ANOVA (analysis of variance). Odds ratios and their 95% confidence intervals as well as adjusted means (standard error) were calculated., Results: In the whole population, the mean urine nitrate level was 53.1+/-0.8mg/l. The 75th percentile of urine nitrate concentrations was 69.0mg/l, indicating that the renal excretion of nitrate is at a low level. The proportion of goiter in subjects with and without high urine nitrate concentrations was 35.5% and 34.7%, respectively (p=0.69). Analyses considering age, sex and further potential confounders could not identify an association between the exposure variable and the risk of goiter., Conclusion: The low level of the alimentary nitrate intake does not influence the thyroid volume in a population with currently sufficient alimentary intake of iodine.