Selenium decreases thyroglobulin concentrations but does not affect the increased thyroxine-to-triiodothyronine ratio in children with congenital hypothyroidism.

Compared with euthyroid controls, patients with congenital hypothyroidism (CH) who are receiving L-T(4) treatment show elevated serum TSH relative to serum T(4) concentrations and increased T(4)/T(3) ratio. These abnormalities could be the consequence of impaired activity of the selenoenzymes deiodinases on which patients with CH rely to convert the ingested L-T(4) into active T(3). Eighteen patients (0.5-15.4 yr), diagnosed with CH in infancy, received selenomethionine (SeM, 20-60 microg selenium/day) for 3 months. The study took place in Belgium, a country where selenium intake is borderline. Compared with the values observed in age- and sex-matched euthyroid controls, patients with CH had decreased selenium, thyroglobulin and T(3) concentrations and increased TSH, reverse T(3), and T(4) concentrations and T(4)/T(3) ratio at baseline. Selenium supplementation caused a 74% increase in plasma selenium values but did not affect the activity of the selenoenzyme glutathione peroxidase used as a marker of selenium status. SeM abolished the TSH difference observed between CH patients and euthyroid controls at baseline and caused a significant decrease in thyroglobulin values. Thyroid hormone concentrations were not affected by SeM. In conclusion, our data suggest that selenium is not a limiting factor for peripheral T(4)-to-T(3) conversion in CH patients. In contrast, we find indirect evidence that SeM improves thyroid hormones feedback at the hypothalamo-pituitary level and decreases stimulation of the residual thyroid tissue, possibly suggesting greater intracellular T(4)-to-T(3) conversion.

Prevalence of zinc deficiency and its clinical relevance among hospitalised elderly.

Zinc is an essential trace element, and constituent of many metallo-enzymes required for normal metabolism. Age may be associated with altered metallothionein metabolism related to changes in zinc metabolism. The objectives of this study were: (i) to assess the prevalence of zinc deficiency among hospitalised elderly patients; (ii) to define the social, functional, pathological and nutritional characteristics of zinc deficient elderly hospitalised patients; and (iii) to assess the relationship between the zinc status and humoral immune function among hospitalised elderly patients. Fifty consecutive patients underwent comprehensive geriatric assessments included evaluations of the medical (index of the severity of the disease(s)), psychiatric (Geriatric depression scale (GDS)), therapeutic, social, functional (Katz's scale), and nutritional problems (Mini Nutritional Assessment (MNA) and biochemical markers (zinc, albumin, prealbumin (PAB), cholesterol) before their discharge. Fourteen patients (28%) presented a zinc concentrations lower than 10.7 micromol/l, this value is usually considered as the cut-off level below which a zinc deficient status is possible. Higher proportions of respiratory infections, cardiac failure, and depression were observed among zinc deficient patients as compared with the group of patients with normal zinc status. The other parameters of comprehensive geriatric assessment did not allow to discriminate the zinc deficient patients. The only slight differences (which remained unsignificant) concerned the prealbumin levels which tended to be higher in the group of patients presenting normal zinc status than in the group with poor zinc status (0.208+/-0.062 versus 0.171+/-0.068 g/l respectively, P=0.06), and the IgG2 levels which tended to be lower in the group of patients with normal zinc status than in the group presenting poor zinc status (2.77+/-1.91 versus 4.06+/-2.56, respectively, P=0.057). A negative correlation was observed between the Zn concentrations and the IgG2 levels (Spearman R=-0.311, P=0.028). To the best of our knowledge, this is the first study presenting zinc status according to a comprehensive geriatric assessment among European hospitalised geriatric patients. We decided to perform this study to known whom of our patients needed to be supplemented with zinc administration. Considering the low energy intake of hospitalised patients (confirmed here in regards of the nutritional assessment), and the insufficient trace element density in European foods, the relevance of providing medical supplements or enriched foods to this population has to be evaluated. Although most of the current diseases may be relevant to long-term interactions between nutrition and ageing, certain states observed in the elderly, like impaired immune and cognitive functions, could still benefit from an appropriate nutritional supplementation.

Autonomy in endemic goiter.

The occurrence of hyperthyroidism in many individuals after introduction of iodine prophylaxis in endemic goiter areas can have dramatic consequences for the affected individuals. It indicates that in such individuals the increase of serum thyroid hormone level in response to iodine supplementation does not exert its normal negative feedback on thyroid activity, ie, that in such individuals some thyroid tissue has become autonomous. In this short review we summarize what is known about the possible mechanisms, cause, diagnosis, and consequences of thyroid autonomy.

The use of sugar as a vehicle for iodine fortification in endemic iodine deficiency.

The use of sugar as a vehicle for iodine supplementation was explored in a study of iodine deficiency in the Sudan. A survey of sugar consumption was conducted and established a widespread and uniform intake of sugar in all ages with no differences among socio-economic groups. The daily intake among adults varied from 48 g to 78 g as examined in five different geographical areas in the country. Iodinated sugar was produced by addition to sugar solution prior to crystallisation in an evapocrystallizer or sprayed on the conveyor of cured sugar before it entered the dryers. Subsequently, the iodinated sugar was given to members of 18 and 60 families in a mildly (urinary iodine < 5.1 micrograms/dl) and moderately (urinary iodine < 3 micrograms/dl) iodine deficient areas, respectively, over a 1-month and a 6-month period, respectively. In both tests, improvements were recorded, i.e. the rates of goitre decreased, urinary iodine levels increased significantly (from 5.1 to 14.4 micrograms/dl and from 3 to 9.8 micrograms/dl, respectively) and thyroid hormones values rose. No side effects were noted. The results indicate that fortification of sugar with iodine may serve as a new alternative approach in attempts to eradicate iodine deficiency related disorders in endemic areas.

The effects of different doses of oral iodized oil on goiter size, urinary iodine, and thyroid-related hormones.

The prevention of iodine deficiency is still a worldwide concern. This study, conducted in Soja in western Sudan, was carried out to evaluate the effects of a dose of iodized oil sufficient enough to give maximum protection against goiter and provide an acceptable iodine supply without side-effects over a sufficiently long period of time. Adult goitrous subjects (n = 117) were randomly assigned to three groups, A, B, and C, and received a single oral dose of 200, 400, or 800 mg iodine, respectively. Urine and blood samples were collected at the start of the study and monitored for 1 yr. In the 3 groups, mean serum T4 and median urinary iodine and serum TSH values were restored to reference limits, and these were maintained for about 1 yr. In each treatment group, about two thirds of the subjects displayed a reduction in goiter size, and the 400- and 800-mg doses were not more efficient than the 200-mg dose to accomplish normalization of thyroid hormone values. A temporary rise in TSH was noted 1 week after iodine administration in 1, 3, and 10 subjects, respectively, and 1, 0, and 3 subjects showed biochemical signs of thyrotoxicosis during the year after treatment with the 3 different doses. The data indicate that oral administration of 200 mg iodine is effective and acceptable for treating iodine deficiency in adults for 1 yr. Because of the risks of side-effects and the shortage of medical resources, higher doses are not recommended.

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.

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 that this goitrogenic factor aggravates a relative or a severe iodine 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 origin; 2. IDD are an important public health problem; and 3. IDD are a good model to study the effects of other trace elements whose actions in many human metabolisms have been somewhat underestimated.

Efficacy of low oral doses of iodized oil in the control of iodine deficiency in Zaire.

BACKGROUND: About one billion people worldwide are at risk for iodine deficiency. Despite existing programs of prophylaxis, the prevention of iodine deficiency is still a challenge throughout the developing world. We studied the efficacy of low doses of iodized oil in an area of severe iodine deficiency in Zaire. METHODS: Seventy-five subjects with visible goiter were randomly assigned to receive a single oral dose of placebo or either 0.1 or 0.25 ml of iodized oil, corresponding to 0, 47, and 118 mg of iodine, respectively. The mean ages of the subjects in the three groups were 23, 22, and 22 years, respectively, and the ratios of males to females were 0.25, 0.32, and 0.19. Efficacy was assessed by evaluating goiter size and measuring urinary iodine and serum thyroid hormone concentrations for 12 months. RESULTS: Goiter size decreased in most of the subjects who received either dose of iodized oil. Their urinary iodine concentrations were normal for six to nine months and their serum thyroxine and thyrotropin concentrations were nearly all normal throughout the study period. There were no side effects, even in subjects whose serum thyroxine concentrations had initially been low. In the placebo group, neither goiter size nor any of the biochemical values changed. CONCLUSIONS: The oral administration of a single small dose of iodized oil is capable of correcting iodine deficiency for about a year. This method of supplementation is likely to be more effective, efficient, and acceptable than the administration of either intramuscular or large oral doses of iodized oil.

Contribution of thyroid ultrasound and serum calcitonin to the diagnosis of congenital hypothyroidism.

UNLABELLED: To elucidate the role of thyroid ultrasound (TU) in the diagnosis of congenital hypothyroidism (CH), we compared 1) TU and thyroid scintigraphy (TS) in 6 CH newborns and 2) TU results in the 6 CH newborns, in 8 newborns with "false positive" results at screening, in 13 CH children aged 2 mo to 12 yr treated since the neonatal period and in 235 controls aged 0-12 yr. RESULTS: 1) In all 6 CH newborns with no thyroid uptake at TS, TU evidenced small posterior hyperechogenic masses in the thyroid area [Vol: 322 +/- 180 (SD) mm3]; 2) In all normal controls and in the 8 "false positive" cases at screening TU showed normal thyroid structures. The thyroid volume was 831 +/- 383 mm3 in normal newborns and progressively increased with age. In the older CH children, TU also demonstrated the hyperechogenic masses, but their volume barely increased with age: as a consequence, the difference between the volume of the masses in CH patients and the thyroid tissue in controls, already significant in newborns (p less than 0.01), markedly increased with age. The exact nature of these masses is unknown; they could represent poorly vascularized ultimobranchial remnants containing the calcitonin - secreting cells: this hypothesis is supported by our finding that serum concentrations of calcitonin (measured by a sensitive extraction method) (mean +/- SD, pg/ml) were lower in the CH patients (2.9 +/- 1.5) than in controls (13.0 +/- 6.9; p less than 0.001) at birth. In conclusion, in all cases of CH, TU showed abnormal structures in the thyroid area. TU and TS provide complementary information in the diagnosis of CH, and TU should be routinely performed in all newborns suspected of CH to avoid unnecessary use of TS in unaffected infants.

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.

Regional variations of iodine nutrition and thyroid function during the neonatal period in Europe.

In order to evaluate further the possibility that transient hypothyroidism and hyperthyrotropinemia in newborn infants could result from a state of relative iodine deficiency, the urinary concentration of iodine, used as an index of the dietary intake of iodine was determined in casual urine samples collected in 1,076 full-term infants aged 3-6 days in 16 cities in 10 different European countries and in Toronto, Canada. In addition, the results obtained by programs of systematic neonatal screening for congenital hypothyroidism in the same areas were compared. There were marked regional differences in iodine nutrition during the neonatal period in Europe (median urinary iodine: 16.2 micrograms/dl in Rotterdam, the Netherlands, and 1.1 micrograms/dl in Freiburg, FRG. A low iodine supply in newborn populations was accompanied by, and probably explained, an elevated frequency of transient disorders of thyroid function in young infants. Iodine prophylaxis is urgently needed in some European countries not only for the prevention of goiter, but mostly for the prevention of impairment of thyroid function during the critical period of brain development.

Endemic infantile hypothyroidism in a severe endemic goitre area of central Africa.

Thyroid function and exposure to dietary goitrogenic factors (iodine deficiency and thiocyanate overload) were studied at birth and from birth to 7 years in 200 neonates and 347 children living in the severe endemic goitre area of Ubangi, Northern Zaire. Serum T4 was at the lower limit of normal at birth (104 +/- 4 nmol/l) and stayed at that level during the first year of life (123 +/- 9) (NS), but decreased to 75 +/- 8 (P less than 0.001) at 2-4 years and to 62 +/- 6 (P less than 0.001) at 5-7 years of age. Mean serum FT4 decreased from 10.4 +/- 0.9 pmol/l during the first year to 8.2 +/- 1.0 (NS) at 2-4 years (NS) and to 7.7 +/- 0.9 (P less than 0.05) at 5-7 years. Mean serum TSH was 10.4 (8.4-12.9) mU/l (geometric mean +/- 1 SEM) during the first year, 10.1 (7.5-13.7) (NS) at 2-4 years and 24.3 (18.5-31.9) (P less than 0.05) at 5-7 years. Mean serum T3 was 3.23 +/- 0.12 nmol/l during the first year and remained stable thereafter. The frequencies of low T4 (T4 less than 77 nmol/l), high TSH TSH (TSH greater than 50 mU/l), and low T4 and T3 (T3 less than 1.69 nmol/l) were twice as high at 5-7 years as in the first year (respectively 65%, 42% and 15%). The urinary iodide concentration of the children was stable and low throughout the study period. By contrast, serum thiocyanate concentration which was high at birth (129 +/- 5 mumol/l) decreased to normal values between 3 and 12 months of age and increased again during and after weaning (1 to 3 years of age) to reach a value of 138 mumol/l which was comparable to that observed in adults in the same area. Thiocyanate concentration was high (133 +/- 7 mumol/l) in the mothers' serum but low in the mothers' milk (57 +/- 3 mumol/l) (P less than 0.001). Multivariate analysis showed that both iodine deficiency and thiocyanate overload were explanatory factors of the serum levels of T4, FT4 and TSH in children. In conclusion, our results show that infantile hypothyroidism is much more frequent at 5-7 years of age than at birth or during the first year of life. The deterioration in thyroid function during and after weaning is linked to persistent iodine deficiency accompanied by an increase in thiocyanate overload. The variability in the age of onset, the severity, and the duration of infantile hypothyroidism might explain the wide range of psychomotor and physical abnormalities observed in a large proportion of subjects in this area.

PIP: Thyroid function and exposure to dietary goitrogenic factors (iodine deficiency and thiocyanate overload) were studied at birth and from birth to 7 years in 200 neonates and 347 children living in the severe endemic goiter area of Ubangi, Northern Zaire. Serum T4 was at the lower limit of normal at birth (104 +or- 4 nmol/1) and stayed at that level during the 1st year of life (123 +or- 9) (NS), but decreased to 75 +or- 8 (P0.001) at 2-4 years and to 62 +or- 6 (P.001) at 5-7 years of age. Mean serum FT4 decreased from 10.4 +or- 0.9 pmol/1 during the 1st year to 8.2 +or- 1.0 (NS) at 2-4 years (NS) and to 7.7 +or- 0.9 (P0.05) at 5-7 years. Mean serum TSH was 10.4 (8.4-12.9) mU/1 (geometric mean +or- 1 SEM) during the 1st year, 10.1 (7.5-13.7) (NS) at 2-4 years, and 24.3 (18.5-31.9) (P0.05) at 5-7 years. Mean serum T3 was 3.23 +or- 0.12 nmol/1 during the 1st year and remained stable thereafter. The frequencies of low T4 (T477 nmol/1), high TSH TSH (TSH50 mU/1), and low T4 and T3 (T31.69 nmol/1) were twice as high at 5-7 years as in the 1st year 65%, 42%, and 15%, respectively). The urinary iodide concentration of the children was stable and low throughout the study period. By contrast, serum thiocyanate concentration which was high at birth (129 +or- 5 cmol/1) decreased to normal values between 3-12 months of age and increased again during and after weaning (1-3 years of age) to reach a value of 138 umol/1 which was comparable to that observed in adults in the same area. Thiocyanate concentration was high (133 +or- 7 umol/1) in the mothers' serum but low in the mothers' milk (57 +or- 3 umol/1) (P0.001). Multivariate analysis showed that both iodine deficiency and thiocyanate overload were explanatory factors of the serum levels of T4, FT4, and TSH in children. The results show that infantile hypothyroidism is more frequent at 5-7 years of age than at birth or during the 1st year of life. The deterioration in thyroid function during and after weaning is linked to persistent iodine deficiency accompanied by an increase in thiocyanate overload. Variability in age at onset, severity, and duration of infantile hypothyroidism might explain the wide range of psychomotor and physical abnormalities observed in a lage proportion of subject, in this area.