Homozygous loss-of-function mutations in SLC26A7 cause goitrous congenital hypothyroidism.

Defects in genes mediating thyroid hormone biosynthesis result in dyshormonogenic congenital hypothyroidism (CH). Here, we report homozygous truncating mutations in SLC26A7 in 6 unrelated families with goitrous CH and show that goitrous hypothyroidism also occurs in Slc26a7-null mice. In both species, the gene is expressed predominantly in the thyroid gland, and loss of function is associated with impaired availability of iodine for thyroid hormone synthesis, partially corrected in mice by iodine supplementation. SLC26A7 is a member of the same transporter family as SLC26A4 (pendrin), an anion exchanger with affinity for iodide and chloride (among others), whose gene mutations cause congenital deafness and dyshormonogenic goiter. However, in contrast to pendrin, SLC26A7 does not mediate cellular iodide efflux and hearing in affected individuals is normal. We delineate a hitherto unrecognized role for SLC26A7 in thyroid hormone biosynthesis, for which the mechanism remains unclear.

Bócio em bovinos / Goiter in cattle

Bócio é o aumento não inflamatório e não neoplásico da glândula tireoide em animais adultos e recém-nascidos. Uma das principais causas envolvidas é a deficiência nutricional de iodo. Relata-se neste trabalho, a ocorrência de três surtos de bócio em bovinos. Na primeira propriedade (Propriedade A), 60 bezerros foram afetados, sendo que 20 morreram logo após o nascimento, 30 recuperaram-se e 10 permaneceram doentes e tiveram remissão dos sinais apenas após tratamento parenteral com iodo. Na segunda propriedade (Propriedade B) uma vaca e seu feto foram acometidos e na terceira (Propriedade C) dois bezerros foram afetados. Os principais sinais clínicos observados nos bezerros foram aumento de volume bilateral na região cervical ventral, emagrecimento, dificuldade respiratória, hipotricose e desenvolvimento corpóreo retardado. Na propriedade A foi relatada ainda a ocorrência de abortamentos. Macroscopicamente, os bezerros e o feto apresentavam tireoide aumentada, vermelho-escura, com vascularização evidente e edema subcutâneo cervical. No surto dois também foi observado, à necropsia, aumento de volume da glândula tireoide da vaca. Microscopicamente, a tiroide dos bezerros e do feto apresentava folículos tireoidianos hiperplásicos, heterogêneos, destituídos de coloide e com interstício acentuadamente vascularizado. A tireoide da vaca era semelhante à dos bezerros, no entanto, possuía quantidade maior de coloide. Em todos os casos a suplementação mineral era realizada por meio da mistura de sal mineral com sal branco. Na Propriedade A o sal branco era não iodado e misturado em partes iguais com o sal mineral. Na Propriedade B o sal também era misturado a um sal branco não iodado na proporção e 1:2, respectivamente. Na Propriedade C o sal mineral e o sal branco não iodado eram ofertados em cochos separados no campo e, segundo relato do proprietário, os animais priorizavam o consumo do sal branco. Em todas as propriedades acompanhadas foi recomendada a interrupção da adição de sal branco na mistura mineral e a administração de iodo aos bezerros acometidos. Após essas medidas não foram observados novos casos nas propriedades. Apesar de ser uma enfermidade bem conhecida, ainda são poucos os relatados de casos de bócios em bovinos no Brasil. Além disso, pouco se sabe sobre as reais deficiências minerais de cada região, e que simples orientações de manejo nutricional ainda são necessárias.(AU)

Goiter is a non-inflammatory and non-neoplastic enlargement of the thyroid gland in adults and neonates. One of the main causes involved is the nutritional deficiency of iodine. In this study three outbreaks of goiter in cattle are reported. In the first outbreak (Farm A) 60 calves were affected, of which 20 died soon after birth, 30 recovered and 10 remained sick. In the second outbreak (Farm B) a cow and its fetus were affected and in the third outbreak (Farm C) two calves were affected. The main clinical signs observed were bilaterally enlarged thyroid glands, weight loss, respiratory distress, hypotrichosis and myxedema. Additionally in the Farm A abortions were reported. Macroscopically the thyroid of the calves and fetus was enlarged, dark red with evident vascularization and cervical subcutaneous edema. In the Farm B the cow showed enlarged thyroid gland as well. Microscopically the calves and the fetus had hyperplastic and heterogeneous thyroid follicles with absence of colloid and vascularized interstitium. The thyroid of the cow was also hyperplastic, but had higher amount of colloid. In all outbreaks the mineral supplementation was performed by mixing non-iodized white salt with the mineral mixture. On the property A the white salt was non-iodized and mixed in equal parts with the mineral salt. At property B the salt was also mixed to a non-iodized white salt in ratio and 1:2, respectively. In the property C, mineral salt and non-iodized white salt were offered in separate troughs in the field, and according to the owner's report the animals prioritized the consumption of white salt. In all the monitored properties it was recommended to stop the addition of white salt in the mineral mixture and the administration of iodine to the affected calves. After these measurements no new cases were observed in the properties. Despite being a well-known disease, there are still few reported cases of goiter in cattle in Brazil. Moreover, little is known about the actual mineral deficiencies of each region, and that simple nutritional management guidelines are still needed.(AU)

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.

Iodine Deficiency in a Parenteral Nutrition-Dependent Adolescent With Intestinal Pseudo-Obstruction.

Routine supplementation of iodine in parenteral nutrition (PN) solutions is not current practice in the United States. In this case study, we describe an incidental finding of goiter in a long-term PN-dependent adolescent. With increased iodine screening, we then identified additional patients with undetectable urinary iodine concentrations in our population of children with short bowel receiving long-term PN. We hypothesize that 2 practice changes are possibly reducing iodine provision to long-term PN-dependent patients: transition to alcohol-based skin preparations and lipid minimization.

Hyperplastic goiter in two adult dairy cows.

Iodine excess and resultant hyperplastic goiter are well documented in neonatal ruminants, but little is reported on iodine excess in adult ruminants and associated histological changes of the thyroid gland. Two adult Holstein cows from a Michigan dairy herd that had lost several other animals had nonspecific clinical signs of illness and were submitted for necropsy. Thyroid glands of one of these 2 animals were grossly and markedly enlarged, and histologically, thyroid glands from both animals had regions of cystic nodular hyperplasia and follicular atrophy. Thyroid glands from both animals had markedly elevated iodine concentrations. Investigation into the potential source of excessive iodine on the farm revealed multiple sources of supplemental dietary iodine and probable uneven feed and mineral mixing. Based on the findings of this investigation, adult cattle could be susceptible to excessive doses of iodine. Possibility of previous iodine deficiency before supplementation period, with subsequent development and persistence of thyroid hyperplasia and cystic change, cannot be completely excluded. Current findings suggested that iodine excess in adult cattle can result in nodular hyperplastic goiter. Use of iodized salt in mineral supplements in adult dairy herds is common practice, and accidental excessive iodine supplement may be more common than reported. Recognizing gross and histological thyroid gland changes, consisting of concurrent cystic follicular hyperplasia, atrophy, and fibrosis should raise suspicion of iodine excess and/or prior deficiency in a cattle herd, and ancillary tests such as serum iodine measurements should be part of the diagnostic workup in suspected cases.

Goitre - causes, investigation and management.

BACKGROUND: Goitre refers to an enlarged thyroid. Common causes of goitre include autoimmune disease, thyroid nodules and iodine deficiency. OBJECTIVE: This article outlines the causes, investigation and management of goitre in the Australian general practice setting. DISCUSSION: Patients with goitre may be asymptomatic, or may present with compressive symptoms such as cough or dysphagia. Goitre may also present with symptoms due to associated hypothyroidism or hyperthyroidism. Thyroid stimulating hormone is the appropriate first test for all patients with goitre; if this hormone is low a radionuclide scan is helpful. Thyroid ultrasound has become an extension of physical examination and should be performed in all patients with goitre. Ultrasound can determine what nodules should be biopsied. Treatment options for goitre depend on the cause and the clinical picture and may include observation, iodine supplementation, thyroxine suppression, thionamide medication (carbimazole or propylthiouracil), radioactive iodine ablation and surgery.

[Iodine deficiency due to an abnormal diet]. / Jodiumdeficiëntie door afwijkend voedingspatroon.

BACKGROUND: In the past, iodine deficiency was an important cause of goitre and mental retardation. Since the introduction of iodised salt the incidence of iodine deficiency has declined enormously. CASE DESCRIPTION: An 8-year old girl had goitre for several months. Her diet was modified to take into account supposed food allergies. She never ate bread products and no salt was added to the food on the assumption that salt is harmful. The thyroid stimulating hormone (TSH) level was not abnormal, the free T4 value was reduced and the T3 value high to normal. Urine investigation indicated reduced iodine excretion. Echography demonstrated a diffusely enlarged thyroid. The iodine deficiency was successfully treated with oral iodine supplementation. CONCLUSION: This case report shows that iodine deficiency based on an inadequate iodine intake still occurs in the Netherlands. An increase in supposed allergies and subsequent decrease of iodine supplementation in the diet may lead to a higher frequency of this "forgotten" disease.

Aspectos patogênicos e clínicos do bócio multinodular / Pathogenic and clinical aspects of multinodular goiter

O bócio multinodular (BMN) é definido como um aumento da glândula tireóide secundário à proliferação multifocal de tireócitos e caracteriza-se pela heterogeneidade no crescimento e função das células foliculares. O BMN é considerado uma neoplasia benigna da tireóide. É uma doença comum, com aumento da prevalência em áreas com deficiência de iodo, sendo este o principal fator etiológico ambiental. A patogênese desta disfunção tireoidiana ainda não está inteiramente elucidada. Nesta revisão serão abordados os principais mecanismos envolvidos na patogênese, seguidos das implicações clínicas dessa patologia.

Multinodular goiter (MNG) is defined as an enlargement of the thyroid gland that is characterized by heterogeneity in growth and function of thyroid follicular cells. MNG is now considered a true thyroid neoplasm. It is a common disease, with higher prevalences in iodine deficiency areas. Iodine deficiency is the main environmental etiologic factor for MNG. The pathogenesis of multinodular goiter is not yet fully clarified. The purpose of this review is to summarize the current knowledge of MNG with respect to the pathology, etiologic and clinical characteristics.

[Current views on the etiopathogenesis of goiter in children]. / Wspólczesne poglady na etiopatogeneze wola u dzieci.

The most frequent cause of goiter in children is a deficit of iodine, leading to endemia of goiter in the regions with insufficient supplementation of this element. Goiter occurs also in the course of autoimmunological diseases of the thyroid gland (Hashimoto disease, Graves' disease), genetically-related disorders of thyroid hormones, biosynthesis/impaired biosynthesis of thyroid hormones. According to the theory of goiter pathogenesis, excessive enlargement of the thyroid gland is due to adaptation of follicle cells of the gland aiming at neutralizing the impaired synthesis of the thyroid hormones caused by various intrathyroid, environmental and genetic factors/agents. The mechanisms stimulating thyrocytes to hyperplasia or hypertrophy are very complex and still unknown in spite of having identified many physiological and pathogenetic factors connected with goiter.

[Prospective study on incidence of primary hyperparathyroidism in patients with goiter]. / Prospektywna ocena czestosci wystepowania pierwotnej nadczynnosci przytarczyc u chorych z wolem guzowatym.

UNLABELLED: Primary hyperparathyroidismus (PHPT) may coexist with goitre. Measurement of calcium concentration in blood serum is recommended before goiter operation. However, because of subclinical PHPT with normocalcemia this screening is insufficient for diagnosis of all PHPT cases. THE AIM: of the study is prospective evaluation of PHPT incidence in patients operated because of goitre. MATERIAL AND METHODS: The study was performed in group of 158 patients (145 women, 13 men) operated because of non-toxic goitre --115 patients--(SNN) and toxic--43 patients--(SNT). Calcium concentration (Ca), phosphorus concentration (P) and alkaline phosphatase activity (ALP) have been measured in all patients a day before operation. When this parameters has been out of normal range, parathormone concentration (PTH) was measured. PHPT was diagnosed, when PTH has been higher then normal range. Following Ca, P, ALP and PTH measurement was performed 3 months after operation to confirm or exclude the diagnosis of PHPT RESULTS: Values of Ca, P and ALP was out of normal range in 47 (37 with SNN and 10 with SNT) of 158 patients (29,7%). Higher PTH concentration (average 101,5 pg/ml) was in 16 of 47 patients (10, 1% of 158 patients). There was no hypercalcemia in any patient with PHPT PHPT was diagnosed in 12 (10,4%) patients with SNN and 4 (9,3%) with SNT. 12 patients were applied to following screening 3 months after operation. Among this patients value of Ca, P and ALP out of normal range was ascertained in 8 patients (66,7%). In 4 patients was higher PTH concentration. Increased PTH concentration and CA, P ALP concentration in normal range was observed in 1 patient three months after operation. In 5 of 12 (41,7%) patients was confirmed remaining PHPT although operation (average PTH 87,1 pg/ml). CONCLUSIONS: Primary hyperparathyroidismus coexist with similar incidence in patients with SNN and SNT Standard PHPT screening is proper because of PHPT incidence in up to 10% thyroid operated patients.

[131 iodine for the treatment of benign goiters]. / L'iode 131 comme traitement des goitres bénins.

INTRODUCTION: In order to evaluate the efficacy of 131 Iodine on goitre volume and on thyroid function, we studied a cohort of patients exhibiting a multinodular and toxic or non toxic goitre. METHODS: This retrospective study was conducted at the Marc Linquette clinic in Lille, in collaboration with the department of nuclear medicine. Thirty-eight patients treated with 131 Iodine were included from 1995 to 2001. Clinical examination and serum analyses including TSH, free T4 and T3, anti-thyroid peroxidase and anti-thyroglobulin antibodies and TSH-receptor antibodies measurements were conducted on inclusion and then at 3, 6, 12 and 72 months. The activity of 131 Iodine corresponded to a standard dose or was calculated according to Marinelli's method. We excluded patients who had not undergone assessment at the above-mentioned time schedules. RESULTS: The treatment was indicated in 30 patients presenting with a non compressive but toxic goitre, in 5 patients with a toxic compressive goitre and in 3 patients with a compressive but non-toxic goitre. Surgery had been excluded for all these patients because of their age, their cardiac status or because they had refused surgery after failure with prior partial thyroidectomy or medical treatment. Among the toxic goitres, TSH levels were low and T3 and T4 increased in 17 patients. In the 18 others, hyperthyroidism was manifested by an isolated decrease of TSH. The thyroid volume before treatment, assessed in 20 patients, was of 18 to 135 cm3 (mean: 53 cm3). Treatment consisted in administration of radioactivity of 3 to 30 mCi in 30 patients and standard activity of 20 to 25 mCi in 8. Functional efficacy with reduction in hyperthyroidism was noted after 3 months, and corrected in nearly all patients after 1 year, and morphological efficacy, with a mean decrease of 33.5% in the size of the goitres. No supplementary surgery was required, notably for the initially compressed goitres. Immediate and long term tolerance was satisfactory. CONCLUSION: Metabolic 131Iodine radiotherapy is effective for the functional and morphological treatment of goitres with good tolerance and few side effects. 131 Iodine is a reasonable alternative in cases with absolute or relative contraindication for surgery.

Equine goiter associated with excess dietary iodine.

Naturally occurring goiter cases are described in 2 newborn Arabian foals whose mares were supplemented with excess iodine during the final 24 w of the pregnancy. Six nursing foals and 2 mares were also affected clinically with thyroid hypertrophy. At least 12 times the maximum tolerable level of iodine supplementation was given, as the daily iodine intake for each mare was 299 mg. The prevalence of goiter cases was 2 and 9% in the mares and foals, respectively.

Hypothyroid goitre in a ram: chemical analysis gives indirect evidence for a structurally altered type of ovine thyroglobulin.

The thyroglobulin of a ram of the East Friesian milk sheep breed suffering from goitre was investigated by physico- and immunochemical methods. The respective ram was the only animal amongst the other sheep of the flock, that exhibited severe goitre, additionally showing depressed behaviour. Results of the thyroid-stimulating hormone response test were indicative of hypothyroidism. The dysfunction of the thyroid gland could be treated by additional iodine supplementation quite successfully, although all sheep had been given iodinated cattle salt throughout the course of the history. Without reducing conditions sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) of isolated thyroglobulin molecules of the ram and control sheep did not reveal different band patterns, but under reducing conditions different band patterns were evident for the respective animals: the ram's thyroglobulin displayed two main bands, those of healthy reference sheep only one. Both bands reacted equally with anti-thyroglobulin antibodies, even with those produced by immunizing rabbits with single bands. The reduced single thyroglobulin band of healthy sheep corresponded to a truncated form of that molecule, whereas the additional main band of the ram was a more resistant, intact thyroglobulin subunit, as was shown by mass spectrometry. In conclusion, results of physico- and immunochemical investigations gave evidence of a modification of thyroglobulin with suspected different iodine binding properties in the ram. The latter finding may have clinical relevance in similar cases in other species, as it is an example of the impact that a minor change in a protein molecule may have on a complete metabolic pathway. Additionally, it could be shown, that in the ovine species the generally found single main band of thyroglobulin after reduction is a truncated form and not an intact subunit. This truncation seems to be induced in vitro by the reductive sample pretreatment prior to SDS-PAGE.

Combating iodine deficiency: lessons from China, Indonesia, and Madagascar.

This study investigated the factors contributing to a successful and sustainable elimination of iodine-deficiency disorders, drawing from salt fortification experiences in China, Indonesia, and Madagascar. Government officials, salt farmers, salt producers, and wholesalers were interviewed to collect data during field visits. Analyses used in the study include simple correlation, and wherever data permit, regression. The study found that measures crucial for combating iodine deficiency include raising public awareness of the disorders, ensuring easy access to iodated salt, promoting compliance in the salt industry, and monitoring and enforcement. Factors that ensure a reliable supply of iodated salt are equally important as those that create the demand for it. Governments must ensure that surveillance and enforcement mechanisms are functioning right from the time that salt iodation is made compulsory. For sustainability during later years, the adequacy of iodine in iodated salt must be monitored, and incentives must be modified as needed to increase compliance rates in the salt industry. Once national coverage of iodated salt reaches over 90%, the government can concentrate on fine-tuning and targeting resources at areas with a low consumption of iodated salt. Elimination of micronutrient deficiencies has a long-term impact on public health; moreover, poorer segments of the population, who are more vulnerable to such deficiencies, have more to gain from fortification programs. Thus, lessons from the successful elimination of iodine-deficiency disorders are valuable for future similar micronutrient activities.

Does radioiodine therapy have an equal effect on substernal and cervical goiter volumes? Evaluation by magnetic resonance imaging.

Most often thyroidectomy is recommended in patients with large goiters. However, high-dose (131)I therapy may be used in case of contraindications to surgery. Large goiters are often partially located in the mediastinum. The aim of this study was to evaluate the impact of (131)I therapy on the cervical and the substernal goiter volume, separately. Fourteen patients (median age, 69 years; range, 52-86 years) with a large multinodular goiter (three hyperthyroid) and with a substernal extension greater than 15 mL were included. T1-weighted magnetic resonance (MR) estimates of the thyroid volume in the cervical and substernal compartments were obtained before and 1 year after high-dose (131)I therapy. The total goiter volumes ranged from 182 to 685 mL. The median substernal volume was 66 mL (fraction of total volume, 17.6%; range, 8.0%-78.9%). One year after treatment, the median substernal goiter volume was reduced by 29.2% (range, -6.1%-59.4%, mean: 26.1% +/- 6.0%), and the cervical goiter volume by 30.3% (range, 6.0%-75.4%, mean, 35.6 +/- 5.6%) compared to baseline values; p = 0.25 for difference in a regional effect. The volume reduction was unrelated to initial substernal goiter size. Likewise, deterioration of the inspiratory capacity did not correlate with the magnitude of the substernal goiter extension. In conclusion, high-dose (131)I therapy seems as effective in reducing the substernal as the cervical goiter volume. However, because the overall effect is modest, this therapy should primarily be considered for the patient with a high surgical risk.

Iodine-Induced hypothyroidism.

Iodine is an essential element for thyroid hormone synthesis. The thyroid gland has the capacity and holds the machinery to handle the iodine efficiently when the availability of iodine becomes scarce, as well as when iodine is available in excessive quantities. The latter situation is handled by the thyroid by acutely inhibiting the organification of iodine, the so-called acute Wolff-Chaikoff effect, by a mechanism not well understood 52 years after the original description. It is proposed that iodopeptide(s) are formed that temporarily inhibit thyroid peroxidase (TPO) mRNA and protein synthesis and, therefore, thyroglobulin iodinations. The Wolff-Chaikoff effect is an effective means of rejecting the large quantities of iodide and therefore preventing the thyroid from synthesizing large quantities of thyroid hormones. The acute Wolff-Chaikoff effect lasts for few a days and then, through the so-called "escape" phenomenon, the organification of intrathyroidal iodide resumes and the normal synthesis of thyroxine (T4) and triiodothyronine (T3) returns. This is achieved by decreasing the intrathyroidal inorganic iodine concentration by down regulation of the sodium iodine symporter (NIS) and therefore permits the TPO-H202 system to resume normal activity. However, in a few apparently normal individuals, in newborns and fetuses, in some patients with chronic systemic diseases, euthyroid patients with autoimmune thyroiditis, and Graves' disease patients previously treated with radioimmunoassay (RAI), surgery or antithyroid drugs, the escape from the inhibitory effect of large doses of iodides is not achieved and clinical or subclinical hypothyroidism ensues. Iodide-induced hypothyroidism has also been observed in patients with a history of postpartum thyroiditis, in euthyroid patients after a previous episode of subacute thyroiditis, and in patients treated with recombinant interferon-alpha who developed transient thyroid dysfunction during interferon-a treatment. The hypothyroidism is transient and thyroid function returns to normal in 2 to 3 weeks after iodide withdrawal, but transient T4 replacement therapy may be required in some patients. The patients who develop transient iodine-induced hypothyroidism must be followed long term thereafter because many will develop permanent primary hypothyroidism.

Goitre in Australia.

Goitre due to nodular thyroid disease is common. Most patients present with benign disease and are euthyroid at presentation, but careful clinical evaluation (thyroid function tests and fine needle biopsy) is essential to determine appropriate therapy. Thyroid hormone therapy should be reserved for hypothyroid patients and those with Hashimoto's thyroiditis. Iodine supplements are not beneficial. Indications for surgery are a malignant or atypical finding on fine needle biopsy, a recurrent cyst larger than 4 cm in diameter, or a goitre causing obstruction.