[Crises of public health, medicine, society?]. / Crises de la santé publique, de la médecine, de la société?

Public health is in crisis. Apart from temporary factors, this crisis could have also its origin in theoretical and conceptual insufficiencies relative to the definition of this scientific domain. Organisational and institutional conditions needed for the strengthening of public health are discussed in relation with the localization of its production sites, taking into account the needed synthesis or consensus to reach and in view of the larger and valuable intellectual traditions to which it belongs. The crisis of public health is only part of a crisis of medicine and of our modern societies.

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.

Selenium deficiency mitigates hypothyroxinemia in iodine-deficient subjects.

Studies were performed to assess the role of combined selenium and iodine deficiency in the etiology of endemic myxedematous cretinism in a population in Zaire. One effect of selenium deficiency may be to lower glutathione peroxidase activity in the thyroid gland, thus allowing hydrogen peroxide produced during thyroid hormone synthesis to be cytotoxic. In selenium-and-iodine-deficient humans, selenium supplementation may aggravate hypothyroidism by stimulating thyroxin metabolism by the selenoenzyme type I iodothyronine 5'-deiodinase. Selenium supplementation is thus not indicated without iodine or thyroid hormone supplementation in cases of combined selenium and iodine deficiencies.

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.

Effect of selenium supplementation in hypothyroid subjects of an iodine and selenium deficient area: the possible danger of indiscriminate supplementation of iodine-deficient subjects with selenium.

Selenium and seleno dependent glutathione peroxidase (GPX) deficiency has been described in endemias of myxedematous cretinism. In northern Zaire, a selenium supplementation trial has been conducted. Beside correcting the GPX activity, two months of selenium supplementation was shown to modify the serum thyroid hormones parameters in clinically euthyroid subjects and to induce a dramatic fall of the already impaired thyroid function in clinically hypothyroid subjects. These results further support a role of selenium in thyroid hormone metabolism. In an iodine deficient area, this selenium deficiency could lead to opposite clinical consequences: protect the general population and the fetus against iodine deficiency and brain damage; and in turn, favour the degenerative process of the thyroid gland leading to myxoedematous cretinism.

Iodine and selenium deficiency associated with cretinism in northern Zaire.

Selenium status was determined in an endemic-goiter area and in a control area of Zaire. Compared with the reference values of a noniodine-deficient area, serum selenium in subjects living in the core of the northern Zaire endemic-goiter belt (Karawa villages) was seven times lower in 52 school-children and similarly low in 23 cretins; erythrocyte glutathione peroxidase (RBC-GPX) was five times lower in schoolchildren and still two times lower in cretins (P = 0.004). In a less severely iodine-deficient city of the same endemia (Businga), selenium status was moderately altered. RBC-GPX activity was linearly associated with serum selenium concentration up to a value of 1140 nmol/L and leveled off at approximately 15 U/g Hb at greater selenium concentration. At Karawa villages, selenium supplementation normalized both the serum selenium and the RBC-GPX. This combined iodine and selenium deficiency could be associated with the elevated frequency of endemic myxedematous cretinism in Central Africa.

[Excess of thiocyanate and selenium deficiency: cofactors in the etiology of endemic goiter and cretinism in North Zaire]. / Surcharge en thiocyanate et carence en sélénium: des cofacteurs dans l'étiologie du goitre et du crétinisme endémiques au Nord-Zaïre.

Endemic goitre is accompanied by a spectrum of iodine deficiency disorders (IDD). From work undertaken by CEMUBAC in Ubangui Zaïre, the role of thiocyanate overload is recalled while this work demonstrates for the first time in man an action of selenium supplementation (and thus deficiency) on thyroid function in iodine deficient areas. The extreme severity of the selenium deficiency may intervene either on the central and/or peripheral deiodination of thyroxine, or on the synthesis of the thyroid hormones. Together with thiocyanate overload, selenium deficiency may be responsible of the high frequency of myxedematous cretins in Zaïre.

The respective effects of serum thyroxine and triiodothyronine on serum thyrotropin and lipid parameters in endemic juvenile hypothyroidism.

The respective effects of serum total T4 concentration and of serum total T3 concentration on serum TSH concentration and on lipid parameters were compared in 84 7- to 16-year-old children of the Northern Zaire goitre endemia classified in group A (T4 greater than 77 nmol/l and T3 greater than 1.69 nmol/l), B (low T4, normal T3) and C (low T4, low T3). Mean serum TSH level was normal in group A (2.3 mU/l), it raised to 39.4 mU/l in group B (p less than 0.001) and to 166.3 mU/l in group C (p less than 0.001 vs A and B). Low density lipoprotein cholesterol and apoprotein B were increased in group B vs A (p less than 0.05) and in group C vs A (p less than 0.001) and B (p less than 0.001 for apoprotein B; not significant for cholesterol). High density lipoprotein cholesterol and apoprotein A1 were similar in the three groups. Mean serum triglyceride level, not different in groups A and B, was doubled in group C (p less than 0.001). Multiple regression analysis showed that serum TSH, apoprotein B, and triglyceride levels were influenced by both thyroid hormones concentrations with a predominant effect of serum T4 on the first two parameters and of serum T3 on the last one. In conclusion, low serum T4 with normal T3 concentrations resulted in an increase in serum TSH and in an altered lipid metabolism; it clearly represented an hypothyroid state.

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.

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.

Fetal hypothyroidism and maternal thyroid status in severe endemic goiter.

The relationship between maternal thyroid function and newborn thyroid function was studied in a region of very severe endemic goiter (Ubangi, Republic of Zaïre). T4, T3, and TSH concentrations were measured in the sera of 56 mothers (at the time of delivery) and 60 newborns (in the cord). The results obtained in these groups (untreated) were compared with those obtained in two control groups, comprising 53 mothers whose iodine deficiency had been corrected by the injection of iodized oil and 68 neonates born to such mothers. The results show that the mean (+/- SEM) T4 serum concentration (micrograms per dl) was 11.5 +/- 0.7 in the untreated mothers compared with 15.7 +/- 0.7 in the treated mothers (P less than 0.001), and 9.4 +/- 0.8 in the untreated newborns compared with 12.4 +/- 0.5 in the newborns of treated mothers (P less than 0.01). The values observed for the mean T3 serum concentrations (nanograms per dl) in the same groups were 171 +/- 10 and 154 +/- 9 (mothers; P greater than 0.05) and 68 +/- 6 and 55 +/- 6 (newborns; P greater than 0.05); the mean TSH serum concentrations (microunits per ml) were 8.7 (7.6 - 9.9) and 5.4 (4.9 - 5.9; mothers; P less than 0.001) and 19.6 (16.6 - 23.2) and 6.4 (5.8 - 7.0; newborns; P less than 0.001). The proportion of untreated newborns, i.e. 40%, with individual TSH values deviating by more than 2 SDS above the mean of the treated newborns is much greater than the corresponding proportion, i.e. 15%, of untreated mothers in relation to the treated ones. In 6 out of 34 untreated newborns, definite biochemical signs of congenital hypothyroidism were observed. Correlation coefficients were calculated between the untreated subjects. A positive correlation coefficient of 0.80 (P less than 0.001) was observed between the serum T4 concentrations of the mothers and those of the newborns, and one of 0.61 (P less than 0.001) was observed between their respective serum TSH values. Significant inverse correlations were observed between maternal serum T4 and cord serum TSH (-0.79; P less than 0.001) and between cord T4 concentrations and maternal TSH concentrations (-0.57; P less than 0.01). No definite trend is observed between the variations of serum T3 on one hand, and those of serum T4 or serum TSH on the other hand. Out of 51 mothers in whom serum T4 was determined, 11 showed values below 8 micrograms /dl; the newborns of those mothers showed very low serum T4 values (5.5 +/- 1.6 micrograms/100 ml) and extremely high serum TSH levels [144 (98-210) microU/ml]. It is concluded that, contrary to the situation observed in physiological conditions, maternal thyroid function in regions of severe endemic goiter is a good indicator of newborn thyroid function. The reasons for this probably lie in the influence of environmental factors acting simultaneously on the mother and the fetus.

Strategy of goitre and cretinism control in Central Africa.

Goitre prevalence in Ubangi Mongala (north-western Zaïre) ranges from 27 to 60 per cent in the male population and from 48 to 78 per cent in the female population; the prevalence of cretinism ranges between 0.7 and 7.6 per cent. This severe endemia affects 1.5 million inhabitants and constitutes a major public health problem. If administered to an entire population, single injections of slowly resorbable iodized oil can reduce goitre prevalence substantially, correct the iodine deficiency and restore normal thyroid function for a period of 3 to 7 years, depending on the parameter considered. The cost of programme of endemic goitre prevention based on this method can be estimated at 0.07 US dollars per person and per year of protection. A strategy of goitre and cretinism control in Central Africa, using iodized oil in an attack phase and iodized salt in a follow-up phase, is proposed. The organization of this programme will be dovetailed into other public health activities and will strengthen the basic health service framework.

PIP: Goiter prevalence in Ubangi Mongala (northwest Zaire) ranges from 27-60% in the male population and from 48-78% in the female population; the prevalence of cretinism ranges from 0.7-7.6%. The severe endemia affects 1.5 million inhabitants and constitutes a major public health problem. If administered to an entire population, single injections of slowly resorbable iodized oil can reduce goiter prevalence substantially, correct the iodine deficiency, and restore normal thyroid function for a period of 3-7 years, depending on the parameter considered. The cost of such a program of endemic goiter prevention based on this method can be estimated at 0.07 US dollars/person/year of protection. A strategy of goiter and cretinism control in Central Africa, using iodized oil in an attack phase and iodized salt in a follow-up phase is proposed. The organization of this program will be dovetailed into other public health activities and will strengthen the basic health service framework.

Incidence of ischaemic heart disease in two cohorts of Belgian clerks.

A study during a five-year period has been conducted on the incidence of ischaemic heart disease (IHD) among two cohorts of Belgian employees who were free of IHD at entry. As regards the final outcome these incidences differ significantly. The chief difference between the two cohorts is their systolic blood pressure. These pressure differences may be attributed to differences in the level of work pressure. The increased work pressure in Cohort I might account, through stress, for the greater incidence of sudden death or myocardial infarction.