Pierre Bourdoux

Iodine deficiency, other trace elements, and goitrogenic factors in the etiopathogeny of iodine deficiency disorders (IDD)

Severe goiter, cretinism, and the other iodine deficiency disorders (IDD) have their main cause in the lack of availability of iodine from the soil linked to a severe limitation of food exchanges. Apart from the degrees of severity of the iodine deficiency, the frequencies and symptomatologies of cretinism and the other IDD are influenced by other goitrogenic factors and trace elements. Thiocyanate overload originating from consumption of poorly detoxified cassava is such deficiency. Very recently, a severe selenium deficiency has also been associated with IDD in the human population, whereas in animals, it has been proven to play a role in thyroid function either through a thyroidal or extrathyroidal mechanism. The former involves oxidative damages mediated by free radicals, whereas the latter implies an inhibition of the deiodinase responsible for the utilization of T4 into T3. One concludes that:1.Goiter has a multifactorial origin2.IDD are an important public health problem; and3.IDD are a good model to study the effects of other trace elements whose actions in many human metabolisms have been somewhat underestimated.

Reversibility of severe hypothyroidism with supplementary iodine in patients with endemic cretinism.

The reversibility of thyroid dysfunction in children with endemic cretinism treated with supplemental iodine is unknown. To study this question we conducted a five-month follow-up of 51 patients with cretinism (age 14 and below), who were randomly assigned to treatment (0.5 ml of intramuscular iodized oil) and control groups. The geometric mean initial serum level of thyrotropin (223 microU per milliliter; SD, 97 to 513) and the mean (+/- SD) initial serum level of thyroxine (1.0 +/- 1.2 micrograms per deciliter) indicated that all patients had severe hypothyroidism. Within one month after receiving the iodized oil, 13 of 14 of the younger patients (less than 4 years) and 1 of 9 of the older patients (4 to 14 years; P less than 0.001) had thyrotropin values below 20 microU per milliliter. Five months after treatment, the levels of thyrotropin had decreased and those of thyroxine had increased in all children, but greater changes occurred in the 13 younger patients than in the 14 older patients. The mean levels of thyrotropin were 2 microU per milliliter (SD, 0.6 to 6) vs. 38 microU per milliliter (SD, 11 to 132; P less than 0.001), and the mean (+/- SD) levels of thyroxine were 13.1 +/- 2.8 vs. 8.1 +/- 4.6 micrograms per deciliter (P less than 0.001). In the untreated group, 3 of the 9 younger patients and none of the 15 older patients recovered normal thyroid function within five months. We conclude that iodine supplementation restored a biochemically euthyroid state in all younger children with cretinism but only some of the older children. In addition, some younger patients became euthyroid without iodine supplementation.

The epidemiology of iodine-deficiency disorders in relation to goitrogenic factors and thyroid-stimulating-hormone regulation.

In children aged 5-7 y from goiter-endemic areas in Ubangi, Zaire, and Ntcheu, Malawi, mean serum thyroxin (T4) concentrations were 53 +/- 49 vs 81 +/- 33 nmol/L (P < 0.05), and thyroid-stimulating hormone (TSH) values were 24.3 +/- 9.6 vs 4.5 +/- 3.3 mU/L respectively (P < 0.01); mean urinary iodine concentrations were 0.14 +/- 0.02 vs 0.09 +/- 0.02 mumol/L, and mean thiocyanate concentrations were 0.33 +/- 0.05 vs 0.17 +/- 0.05 nmol/L, respectively (P < 0.05). Mean serum selenium concentrations were 0.343 +/- 0.176 mumol/L in Ubangi and 0.437 +/- 0.178 mumol/L in Ntcheu (P < 0.05). In two groups of 11 adolescent girls from Ubangi, the mean values for excretion of urinary iodine were 1.31 +/- 0.14 and 0.58 +/- 0.17 mumol/L (P < 0.05) after a meal of cassava or a control meal of rice, respectively. In euthyroid subjects from Ubangi, mean serum TSH for a given serum T4 was approximately twice as high for children aged < 15 y than for those aged 16-25 y. The high frequency of myxedematous cretins observed in Ubangi very probably result from both severe iodine and selenium deficiency together with thiocyanate overload.

Superiority of thyrotropin to thyroxine as a tool in the screening for congenital hypothyroidism by the filter paper spot technique.

The effects of storage on the assessment of thyroxine (T4) and thyrotropin (TSH) were evaluated in blood spots collected on filter paper according to the methods commonly used in screening for congenital hypothyroidism. Comparisons were made with serum values obtained simultaneously in the same subjects. In samples stored at room temperature a clear-cut decrease in T4 was observed after 24 hours while TSH was stable for at least 15 days. Spot samples collected in an area of severe endemic goiter in Africa and analyzed in Brussels displayed a systematic decrease in T4 (up to 133 nmol/l) while TSH was fairly stable. Spot samples collected in Belgium were stored at -18 degrees C and were reassayed after 1 year; they did not show any significant change in TSH but a systematic decrease in T4. We conclude that spot TSH is the tool of choice in screening for congenital hypothyroidism particularly in developing countries and that spot T4 should not be used for field studies or under any circumstances in which assays cannot be performed very soon after blood collection.

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.

The goitrogenic effect of two Sudanese pearl millet cultivars in rats

Abstract Pearl millet ( Pennisetum americanum L. Lecke) is the staple food in many goiter areas in the west of Sudan while wheat is an additional staple food in low goiter areas. Epidemiological evidence from these areas suggests that although iodine deficiency is the major cause of goiter, millet consumption may play a role in goiter causation. This study was designed to determine in rats the possible goitrogenic and antithyroid effects of two millet cultivars, Bayoda and Balady, consumed in two endemic goiter areas with different goiter prevalence rates in the west of Sudan. Both fermented and unfermented forms of the two cultivars of millet were included in the study. Whole grain millet and wheat used in this experiment were only fortified with iodine with an amount supplying recommended dietary requirements. Feeding the two millet cultivars unfermented was associated with serum thyroid hormones comparable with the wheat reference while feeding the Balady cultivar (consumed in the area of low goiter prevalence) unfermented was associated with significant enlargement of the thyroid gland. Fermentation, was associated with the same trend of changes in both cultivars: enlargement of the thyroid gland and increased serum T4, T3 and TSH. Compared to the wheat reference group, fermentation of the cultivars was associated with increased serum T3 and T4 (only Bayoda) and significant further enlargement of the thyroid gland (only Balady). Among the animals that consumed millet (two way analysis), those receiving fermented millet showed increased serum T4, T3 and TSH compared to those which received unfermented millet. Nutritional inadequacies reflected in impaired growth, and enlarged heart and kidneys were more pronounced in animals fed millet diets than in those fed the wheat reference diet. In conclusion, in rats, the consumption of millet interferes with thyroid function; the consumption of Balady seems to induce an enlargement of the gland whereas the consumption of Bayoda causes modifications in the pattern of thyroid hormones.