Making Endemic Goiter an American Disease, 1800-1820.

In 1800, American physician and naturalist Benjamin Smith Barton (1766-1815) published A Memoir Concerning the Disease of Goitre as it Prevails in Different Parts of North-America. The text documented the nature of the disease in the United States and highlighted how it differed from the ailment's presentation in European patients. While medical topographies were common during this period, Barton's goiter research and the steady stream of American goiter research that followed are worth special attention. This body of literature demonstrates how American physicians understood their relationship to transnational medical discussions and the unique perspective they brought to them. Goiter literature was common in European medical and travel writing during this period and intensely focused on the appearance of the disease in the mountains of Switzerland and Northern Italy. American goiter by its very appearance in non-mountainous regions of the United States contradicted nearly all of the received wisdom about the ailment's cause and potential cure. For two decades, American writers leveraged their own observations and local knowledge to challenge larger narratives in their field.

Thiocyanate in excess develops goiter followed by auto immune thyroid diseases even after effective salt iodization in a rural community of north east India.

PURPOSE: Salt iodization in Manipur of north-east India failed to prevent endemic goiter, therefore an in depth study carried out to evaluate thyroid functions of goitrous subjects in a randomly selected region. METHODS: Goiter survey conducted in children and women of reproductive ages by palpation followed by measurement of urinary iodine, thiocyanate and house-hold salt iodine to evaluate iodine nutritional status and consumption pattern of bamboo-shoots (BS). In all grade-2 goitrous subjects, free thyroxine, triiodothyronine, TSH, TPO and Tg antibodies, thyroid volume and echogenecity by ultrasonography and cytomorphology of thyroid by FNAC studied. RESULTS: Study population was 2486 children and 1506 women, goiter prevalence was 12.59% and 16.27% respectively; median urinary iodine and mean thiocyanate were 166 µg/l and 0.729 ± 0.408 mg/dl while salt iodine was ≥30 ppm. Serum thyroid hormones and TSH profiles of all grade-2 goitrous subjects showed 16.21% were subclinically hypothyroid, 2.16% overt hypothyroid, 4.86% subclinically hyperthyroid and 6.48% overt hyperthyroid, serum TPO- and Tg-antibodies found positive in 41.62%. Ultrasonographic results showed 24% had enlarged thyroid and 86.4% hypoechoic. Cytomorphological studies showed prevalence of colloid goiter (41.08%), lymphocytic thyroiditis (37.83%), Hashimoto's thyroiditis (8.10%), autoimmune thyroiditis (4.32%), sub-acute thyroiditis (2.16%) and 1.62% each papillary, medullary carcinoma, simple diffused hyperplasia and adenomoid nodular goiter. CONCLUSIONS: Grade-2 goitrous individuals in this mild goiter endemic region were affected by hypo- and hyperthyroidism with hypoechoic thyroid and thyroiditis. Thiocyanate that originates from BS even in presence of adequate iodine developed goiter and led goitrous population towards such diseases.

Boron - A potential goiterogen?

The iodine deficiency disorders (IDD) include a variety of disturbances such as decreased fertility, increased perinatal and infant mortality, impaired physical and intellectual development, mental retardation, cretinism, hypothyroidism, and endemic goiter (EG). The occurrence of the latter is determined by interplay between genetic and environmental factors. The major environmental factor is iodine status that is required for normal thyroid hormone synthesis. However, other factors like intake of micronutrients and goiterogens also have a significant impact. Essential and toxic trace elements both play a significant role in thyroid physiology. We hypothesize that in terms of overexposure boron may serve as a potential goiterogen. In particular, it is proposed that boron overload may impair thyroid physiology ultimately leading to goiter formation. Certain studies provide evidential support of the hypothesis. In particular, it has been demonstrated that serum and urinary B levels are characterized by a negative association with thyroid hormone levels in exposed subjects. Single indications on the potential efficiency of B in hypothyroidism also exist. Moreover, the levels of B were found to be interrelated with thyroid volume in children environmentally exposed to boron. Experimental studies also demonstrated a significant impact of boron on thyroid structure and hormone levels. Finally, the high rate of B cumulation in thyroid may also indicate that thyroid is the target for B activity. Chemical properties of iodine and boron also provide a background for certain competition. However, it is questionable whether these interactions may occur in the biological systems. Further clinical and experimental studies are required to support the hypothesis of the involvement of boron overexposure in goiter formation. If such association will be confirmed and the potential mechanisms elucidated, it will help to regulate the incidence of hypothyroidism and goiter in endemic regions with high boron levels in soil and water.

Lead, cadmium, manganese, cobalt, zinc and copper levels in whole blood of urban teenagers with non-toxic diffuse goiter.

The amount of lead (Pb), cadmium (Cd), manganese (Mn), cobalt (Co), zinc (Zn), and copper (Cu) present in whole blood of 118 teenagers were determined by atomic absorption spectrometry. The blood samples of 23 healthy teenagers were compared with the blood samples of 95 adolescents who were diagnosed with non-toxic diffuse goiter (NTDG). The study was aimed at examining whether in addition to mild iodine deficiency other trace elements could contribute to the development of non-toxic diffuse goiter. The results indicated that the levels of Pb, Cd and Mn in the blood samples of teenagers diagnosed with NTDG were higher than that in healthy children. Also, the results indicated that higher levels of metals were present in the blood samples with NTDG in adolescent patients who lived in areas with a higher amount of pollution.

Iodine-induced goitre and high prevalence of anaemia among Saharawi refugee women.

OBJECTIVE: The main objective was to assess iodine status (thyroid volume (Tvol) and urinary iodine concentration (UIC)) and their determinants in Saharawi refugee women. DESIGN: A cross-sectional survey was performed during January-February 2007. Tvol was measured by ultrasound and iodine concentration was analysed in spot urine samples and in household drinking water. Anthropometry and Hb concentration were measured and background variables were collected using pre-coded questionnaires. SETTING: The survey was undertaken in four long-term refugee camps in the Algerian desert. SUBJECTS: Non-pregnant women (n 394), 15-45 years old, randomly selected. RESULTS: Median (25th percentile-75th percentile (P25-P75)) UIC was 466 (294-725) µg/l. Seventy-four per cent had UIC above 300 µg/l and 46 % above 500 µg/l. Median (P25-P75) Tvol was 9·4 (7·4-12·0) ml and the goitre prevalence was 22 %. UIC was positively associated with iodine in drinking water and negatively associated with breast-feeding, and these two variables explained 28 % of the variation in UIC. The mean (sd) Hb level was 11·8 (2·4) g/dl. In total 46 % were anaemic with 14 %, 25 % and 7 %, classified with respectively mild, moderate and severe anaemia. CONCLUSIONS: The Saharawi women had high UIC, high levels of iodine in drinking water and increased Tvol and probably suffered from iodine-induced goitre. The high prevalence of anaemia is considered to be a severe public health concern. To what extent the excessive iodine intake and the anaemia have affected thyroid function is unknown and should be addressed in future studies.

Bocio endémico por exceso de yodo en la población escolarde los campos de refugiadosde la RASD (República Árabe Saharaui Democrática) / Endemic goiter associated with high iodine intake in primary high school children in the saharawi arab democratic republic

Al objetivar una elevada prevalencia de bocio en los niños saharauis que acuden a Asturias en los veranos, nos planteamos realizar un estudio en profundidad de este problema. En una muestra de 570 escolares de la República Árabe Saharaui Democrática (RASD) se realizó palpación del cuello, peso, talla, medición de T4, TSH y anticuerpos antiTPO en la sangre capilar y en muestras de orina para determinar el contenido en yodo, flúor y tiocianatos. Se determinó también el contenido de estas sustancias en el agua de bebida. Hallamos un 58,1 por ciento de bocio (un 7 por ciento de grado 2), con mayor prevalencia en las niñas (el 65,4 frente al 51,4 por ciento). La yoduria fue de 965 ñ 348 µg/l, sin diferencias entre sexos ni por grado de bocio. La función tiroidea fue normal en todos los niños, y los anticuerpos y los tiocianatos fueron normales. La concentración de yodo en el agua de bebida osciló entre 180 y 400 µg/l, con un alto contenido en flúor (0,7-1,5 mg/l).En resumen, describimos un área geográfica con elevada prevalencia de bocio (58 por ciento) entre sus escolares y una yoduria elevada (965 ñ 348 µg/l). El principal aporte de esas cantidades tan altas de yodo es el agua de bebida (entre 180 y 400 µg/l). La función tiroidea es normal, la autoinmunidad puede descartarse como etiología de esta endemia y no se demuestra la existencia de compuestos antitiroideos en el agua ni en la orina de los niños. Creemos que el bocio hallado en esta población puede ser de origen multifactorial: exceso de yodo y flúor, gran dureza del agua de bebida y posible contaminación ocasional de la misma (AU)

From naturally occurring goitrogens to the effects of anthropogenic endocrine disruptors on the thyroid in Slovakia.

The objective is to describe the effect of mandatory and well monitored prophylaxis of endemic goitre in Slovakia with the use of iodised salt for past 50 years and previous experimental attempts to assess a possible participation of naturally occurring goitrogens in the etiology of goitre. Previous observations by others showed a striking decrease of goitre prevalence in schoolchildren as early as few years after starting the prophylaxis in Slovakia and this success has been confirmed by a European study conducted by others in mid nineties. In the meantime, however, massive industrialisation of Slovakia and environmental negligence of the administration resulted in heavy airborne and mainly waterborne pollution of the food chain in certain areas around large chemical factories by industrial waste including polychlorinated biphenyls (PCB). Since Slovakia has been recently evaluated as an iodine replete country as based on the findings of the low thyroid volume by ultrasound and high urinary iodine, it became possible to evaluate the participation of factors different from iodine deficiency in the thyroid growth. Recent field surveys including an extensive international study PCBRISK repeatedly showed highly increased blood PCB level in subjects living in the polluted area and, at the same time, increased thyroid volume by ultrasound, increased frequency of positive thyroid antibodies and impaired glucose tolerance. (Ref. 59)

Traditional fermentation increases goitrogenic activity in pearl millet.

Epidemiological evidence suggests that millet might play a role in the etiology of endemic goiter. Recently, we showed that a traditional fermentation procedure of two pearl millet (Pennisetum americanum L. Lecke) cultivars grown in Sudan modified their effects on the weight of the thyroid gland and thyroid hormone profile in rats. In the present study, we report that this fermentation procedure reduced the ash contents of millet by about 40% and removed considerable amounts of Mg (>50%), Zn (27-39%) and K (45%). Other minerals (Ca, Fe, Cu) were not affected. Feeding of one fermented cultivar resulted in significant reduction in bone Mg and Zn contents, whereas feeding of the other fermented cultivar resulted in reduction of bone Mg only. Dietary Mg intake and bone Mg contents correlated negatively with serum T3. Groups fed the millet diets had higher serum Se level compared to those fed wheat or casein diets and feeding of fermented millet resulted in a further increase in serum Se level. Thus our data indicate that in rats the enhanced effects of millet on the thyroid induced by fermentation is likely related to removal of minerals from millet and/or chemical transformation of the goitrogens contained in millet.

[Verification and epidemiological study on endemic iodide-induced goiter in Jiangsu Old Yellow River flooded plain].

To verify the existence and reveal the epidemiological characteristics of endemic iodide-induced goiter in Jiangsu Old Yellow River flooded plain, 12 spots were selected in this survey. The results showed that the total goiter rate of 22.18% by palpation and 12.83% by B-ultrasound which surpassed the 5%-cutpoint-recommended jointly by WHO/UNICEF/ICCIDD. The urinary iodine median was 962 micrograms/L in 607 samples. The average 24 hours I31iodine-emissivity ratio was 4.6 +/- 0.3% with most of the serum TSH, T4, T3 within normal ranges. Of 1049 water samples in 65 towns, 771 had iodine content over 300 micrograms/L with water iodine concentration over 300 micrograms/L in 52 towns. These findings suggested that goiter in this plain had been endemic which related to excessive iodine in shallow well water. Heavy load of iodine over general population was noticed.

Problems of iodine and thiocyanate in domestic animals in goitrogenic areas of southern Poland.

High incidence of goitre in human together with low level of iodine in water and cow milk have been observed in Southern Poland (Table I). Therefore, iodine deficiency was considered as the only cause of goiter development. The correlation coefficient between iodine concentration in water and cow milk was r = 0.76 (Fig. 1) and indicate the possibility of iodine determination in milk instead of water. The iodine determination in milk reflects the level of iodine in water as well as in food, a negative correlation has been obtained between goitre incidence in human and iodine concentration in water (r = 0.43) (Fig. 2.). A low correlation coefficient suggest that iodine is not a solely factor responsible for goitre development. Studies on cows have indicated that thiocyanate may have effect on goitre development as well. There has been found higher concentration of thiocyanate (SCN) in blood plasma and in enlarged thyroids (Table II). Thiocyanate belongs to goitrogenic compounds and its main source are the plants of Brassica species widely cultivated in southern Poland. It has been found that cows fed with Brassica plants have high level of SCN both in blood and milk with no alteration of plasma iodine level. The transfer of iodine from plasma to milk is only slightly affected (Table III). The level of SCN in the thyroid depends on its plasma concentration; the calculated correlation coefficient is r = 0.88 (Fig. 3). Enhanced thyrotropin (TSH) secretion (during goitrogenesis) may be accompanied by increased accumulation of SCN in the thyroid (like iodide) and reduced oxidation to SO4 (unlike iodide) (Fig. 4). Therefore we postulated that TSH may be partly responsible for increased SCN level in goitrous thyroids. The question arise whether increased ingestion of SCN does really potentiate iodine deficiency and goitrogenic process in animals breeding in southern Poland. For explanation some additionally experiments were performed on laboratory animals. It have been observed that enhanced level of plasma SCN following feeding with Brassica plants increased proportionally the goitrogenic action as well as the accumulation of 131J by the thyroid and its conversion into organic form (Fig. 5). The latter data was confirmed by positive correlation between thyroxine and plasma SCN levels in sheep (r = 0.49), (Fig. 6) Thiocyanate like other monovalent anions suppress goitrogenic effect of propylthiouracil. However, anti-goitrogenic properties of SCN depends on normal iodine ingestion (Fig. 7).(ABSTRACT TRUNCATED AT 400 WORDS)

[Experimental and epidemiological studies on the interrelationship of thiocyanate and thyroid function]. / Experimentelle und epidemiologische Untersuchungen zu Wechselbeziehungen von Thiocyanat und Schilddrüsenfunktion.

The testing of a SCN- dose (32 mg NaSCN/kg oral 21 d long) which is about 100 fold above the alimentary SCN(-)-uptake on guinea pig has shown neither histologic/morphometrical nor clinical clue to thyrostatic effect. In 6 regions of the GDR (1,349 persons) has not been secured epidemiologically any relationship between SCN- serum level as well as SCN- urine level and goiter. The partly in the tendency low increase of SCN- level by patients with bland goiter was always under the levels of smokers without goiter, exceeded indeed the threshold of significance in the area of Werdau. In the industrial agglomeration areas the I(-)-SCN(-)-quotient at the most unfavourable cases ran to 3.5 (Halle, smoker, struma), was consequently close to the critical level of the goiter risk.

Antithyroid and goitrogenic effects of millet: role of C-glycosylflavones.

Pearl millet [Pennisetum millet (L.) leeke] is the main source of food energy for the rural poor in many areas of the semiarid tropics. Epidemiological evidence suggests that millet may play a role in the genesis of endemic goiter in these areas, and sparse experimental data in rats support this suspicion. This study was undertaken to determine in vivo in rats and in vitro using porcine thyroid slices and a thyroid peroxidase (TPO) assay the goitrogenic and antithyroid effects of millet diets, extracts of millet, and certain pure compounds contained therein. For use in these studies, whole grain millet was progressively dehulled to yield successively four bran and four flour fractions in which direct analyses revealed progressively lower concentrations of C-glycosylflavones. In vivo feeding of bran fraction 1, that richest in C-glycosylflavones, led to a significant increase in thyroid weight and antithyroid effects. Feeding of bran fraction 2, the next richest in C-glycosylflavones, produced similar, but less marked, changes. In vitro studies of 125I metabolism using porcine thyroid slices indicated that extracts of bran fractions 1 and 2 were most potent, producing changes similar to those produced by methimazole (MMI). At a concentration of 60 mumol/L, glucosylvitexin, the major C-glycosylflavone present in millet, had effects comparable to those of 1 mumol/L MMI. Similarly, in studies of porcine TPO, extracts of bran fraction 1 caused pronounced (85%) inhibition of enzyme activity, and progressively less inhibition was induced by extracts of bran fractions 2, 3, and 4. Overall, the TPO-inhibiting activities of the various millet fractions closely correlated with their C-glycosylflavone concentrations. Three C-glycosylflavones present concentrations. Three C-glycosylflavones present in millet, glucosylvitexin, glycosylorientin, and vitexin, also inhibited TPO activity. Thus, in vivo and in vitro studies revealed that millet diets rich in C-glycosylflavones produce goitrogenic and antithyroid effects similar to those of certain other antithyroid agents and small doses of MMI. We conclude that in areas of iodine deficiency in which millet is a major component of the diet, its ingestion may contribute to the genesis of endemic goiter.

Endemic goitre in central China caused by excessive iodine intake.

Thyroid status was examined in children from two villages in central China where the iodine concentrations in drinking water were 462.5 and 54 micrograms/l. Goitres were present in 65% (n = 120) and 15.4% (n = 51), respectively. All children in both groups were clinically euthyroid and neurologically normal. Growth measurements and intellectual performance were similar in the two groups. Children from the high-iodine village had a lower mean serum triiodothyronine and higher serum free thyroxine and serum thyroid-stimulating hormone concentrations than the children from the control village. 2 cases of overt hypothyroidism were detected in the high-iodine village.

In vitro measurement of antithyroid compounds and environmental goitrogens.

A specific, sensitive, and reproducible in vitro assay for antithyroid compounds and environmental goitrogens has been used to investigate antithyroid activity (AA) in small samples of water supplying 15 localities in endemic and nonendemic goiter areas of western Colombia. A significant positive correlation was observed between goiter prevalence and AA in water collected from the pipelines of these localities. Samples at the water source showed only borderline significance. No significant correlation was observed in waters between AA and total hardness (ppm) or concentrations of Ca, Mg, sulfates, chlorides, silicates, nitrates, and iodine. AA was also demonstrated by this in vitro assay in well water previously shown experimentally to be goitrogenic and that supplied the endemic goiter district of Candelaria town in western Colombia. In contrast, water from the well supplying the area of lower endemicity was found to possess little AA. These results provide experimental support for epidemiological observations that demonstrate a relationship between the sources of drinking water and goiter prevalence rates, and are consistent with previous findings indicating that organic antithyroid compounds contaminate water supplies in areas where goiter persists despite adequate iodine supplementation.

A goitrogenic agent from millet (Pennisetum typhoides) in Darfur Province, Western Sudan.

Serum samples from girls from an elementary school in Western Sudan with grades O, I and II/III goitre were examined for their thiocyanate, cysteine, thyroxine, TSH and T3 concentrations. The concentrations of thiocyanate in all girls was higher than that reported in the literature for Nigerians, but the concentrations of thiocyanate were nevertheless significantly elevated, and those of thyroxine significantly lowered in girls with grades I and II/III goitre as compared with grade O. There were no significant differences between any of the groups in the concentrations of cysteine or TSH and T3. The predominant staple food eaten in this area of Sudan is millet and evidence is produced that this contains a goitrogenic thionamide which could be a factor in causing the endemic goitre.

[Goitrogens of vegetable origin as possible aetiological factors in endemic goiter (author's transl)]. / Intervention de goitrigènes d'origine végétale dans l'étiologie du goitre endémique.

Ingestion of unsoaked cassava is followed by an increase of the thiocyanate production in men and in rats. Even a moderate increase of serum SCN concentration induces, in chronic conditions, a clearcut goitrogenic effect characterized by the aggravation of the effects of a preexisting iodine deficiency. The mechanism of the antithyroid action of SCN at low concentrations, lies in an acceleration of the exit rate of thyroidal iodide; this effect cannot be identified by the usual clinical investigation with Iodine131.

[Role of iodine and manganese in the etiology of endemic goiter in the Martuksk region of the Aktubinsk district]. / Rol' ioda i magrantsa v etiologii endemicheskogo zoba v Martukskom raione Aktiubinskoi oblasti.

Iodine deficiency in the external environment served as the main etiological factor of endemic goiter. Low iodine content in the soil (1.8-390 mg/kg) undoubtedly served as the cause of endemic goiter development. Water from the sources of the Martuksk district contained iodine in low concentration. Soils of the Martuksk district are characterized by an acute deficiency of mobile manganese. Manganese concentration in the arable soil layer (16.9-75.4 mg/kg) was regarded as reduced, this being characteristic of the foci of goiter endemia. Water manganese content (from 66 to 186 microgram/1, 99.45 +/- 10.6 microgram/1, on the average) was below the maximal permissible concentrations indicated in the International standard for drinking water. Iodine, manganese content in the soil, food products and in the water of the Martuksk district of the Aktyubinsk region indicated a reverse relationship between iodine and manganese content and the extent of endemic goiter spread.