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It is well established that iodine supplementation is effective in correcting iodine deficiency and reducing goiter prevalence. In Italy, legislation has allowed the production of iodized salt since 1972, but its consumption is on a voluntary basis. In the present study, the efficacy of legislative measures that made compulsory the availability of iodized salt in foodstores has been evaluated. Urinary iodine excretion and thyroid size, scored according to Pan American Health Organization recommendations, were determined prior to (1981) and 10 years after (1991) the introduction of legislative measures in the whole schoolchildren population residing in a restricted area of the Tuscan Appennines. Moreover, in 1991, thyroid volume was determined by ultrasonography. In 1981, mean urinary iodine excretion was 47.1 +/- 22.4 mg/kg creatinine (0.412 mumol/l) and goiter prevalence was 60%, indicating a moderate iodine deficiency. Eighty of the families subsequently used iodized salt on a regular basis; as a result of this excellent compliance, in 1991 the mean urinary iodine excretion increased to 129.7 +/- 73 mg/kg creatinine (1.24 mumol/l) and goiter prevalence dropped to 8.1%. The results of this study underline the effectiveness of iodine prophylaxis in correcting iodine deficiency and abating endemic goiter in schoolchildren, and suggest that implementation of measures that make compulsory the availability of iodized salt in foodstores overcomes the fact that there is no law governing the exclusive production and trading of iodized salt.

In the treatment of endemic goitre, the concept of giving levothyroxine in combination with iodine offers a promising therapeutic approach by influencing not only TSH secretion but also intrathyroidal iodine content. However, little is known about the doses of iodine necessary to correct intrathyroidal iodine deficiency. To get more information on this important issue, we conducted a prospective, double-blind study on the effect of a monotherapy with 500 micrograms iodide/day and a combined treatment with 100 micrograms levothyroxine and 100 micrograms iodide/day on thyroid iodine concentration as measured by fluorescence scintigraphy. In a group of 12 patients, a 4-month treatment with 100 micrograms levothyroxine and 100 micrograms iodide/day did not significantly affect thyroid iodine concentration (0.35 +/- 0.14 vs 0.37 +/- 0.11 mg/g). The application of 500 micrograms iodide/day in these patients during a second 4-month period resulted in a sharp increase in thyroid iodine concentration from 0.37 +/- 0.11 to 0.61 +/- 0.14 mg/g (p less than 0.01). Another group of 8 patients first treated with 500 micrograms iodide/day also showed a significant increase in iodine concentration from 0.35 +/- 0.14 to 0.65 +/- 0.20 mg/g (p less than 0.01). After switching to the combination regimen during a second 4-month period, thyroid iodine concentration slightly decreased, particularly in those patients with high iodine concentrations after monotherapy with iodide (0.65 +/- 0.20 vs 0.50 +/- 0.12 mg/g, p less than 0.05). In conclusion, treatment with 500 micrograms iodide/day could sharply increase thyroid iodine concentration in patients with endemic goitre. In contrast, a combination of 100 micrograms levothyroxine and 100 micrograms iodide/day had no significant effect on thyroid iodine concentration.

In 1956, a study of the iodine metabolism in endemic goitre was made on a group of inhabitants of the Aland Islands, an autonomous province of Finland. The number of Alanders studied was 130. In a follow-up study 25 years later, 101 still living subjects from the original study could be traced. 17 of them had become hyperthyroid, 7 had been operated on for non-toxic goitre, and 4 had become hypothyroid. There was no correlation between thyroid hormone excretion values in 1956 and subsequent hyperthyroidism. Rheumatoid arthritis was overrepresented in the goitre group compared with the group without goitres, as well as compared with statistical figures on the frequency of rheumatic disease among the population in general of Aland and of Finland as a whole.

A survey of endemic goitre in the island of S. Miguel (the Azores) was performed. The prevalence of goitre in school-children varied between 11 and 41%. In the most affected region, 16% of the adult males and 48% of the women had goitre, in some cases grade 3. The median urinary excretion of iodine was very low in school-children, varying between 10 and 49 micrograms I/g creatinine. The reasons for such a low iodine intake in the population of this oceanic island are the scarcity of fish in the diet and, possibly, the leaching of the soil of its iodine content due to high pluviosity.

To investigate further the possible causes of the difference in goitre frequency between the rural and urban areas of Darfur region in the Sudan, urinary iodine excretion (UIE) and thyroid hormone concentrations were measured in 97 goitrous and 31 non-goitrous subjects from rural Darfur, 62 goitrous subjects from urban Darfur and 37 non-goitrous subjects from Khartoum. The mean UIE was equally low in goitrous subjects from rural Darfur (56.2 +/- 43.1 micrograms/g creatinine) and urban Darfur (46.3 +/- 20.7 micrograms/g creatinine) and both values were lower than that in the non-goitrous subjects from Khartoum (83.6 +/- 41.9 micrograms/g creatinine). Subjects from rural Darfur also had lower mean serum thyroxine and higher triiodothyronine and thyroid stimulating hormone levels. The mean serum thiocyanate level of 3.2 mg/l in goitrous subjects from rural Darfur was significantly higher than the values of 1.8 ng/ml in goitrous subjects from urban Darfur (P less than 0.001) and 1.7 mg/l in non-goitrous subjects from Khartoum (P less than 0.001). It is concluded that the additional contribution of goitrogenic factors in rural Darfur induces thyroid anomalies to a greater degree than are most likely caused by the iodine deficiency alone in subjects from urban Darfur.

Iodine prophylaxis was introduced to the moderately severe goitre endemic area in Salta, Argentina, in 1963. All thyroidectomies from a 20 year period were reviewed, and 148 thyroid malignancies carefully studied. The period from 5 to 15 years after iodization was associated with a lower frequency of follicular carcinomas and a higher frequency of papillary carcinomas than the period before and up to 5 years after prophylaxis. Lymphoid infiltration in the non-tumorous thyroid was relatively infrequent before iodine prophylaxis: it was much higher in each of the post-prophylaxis periods. These results, in agreement with other studies, support the view that an increased iodine intake is associated with an increased incidence of papillary carcinoma of the thyroid and thyroiditis.

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.

Since goitre prevalence increases sharply during the first two decades of life, age-related changes in the adaptation of the thyroid to iodine deficiency may occur. In order to study this, we have measured serum levels of TSH, T4 and T3 in 247 subjects (age range 5 to 60 years) living in an endemic goitre area of North Algeria (group A) and in 64 control subjects living in the non-iodine deficient city of Algiers (group B). TRH tests were also performed in 88 subjects from the goitrous area and in 30 controls. Patients from group A had significantly higher serum TSH and T3 and lower serum T4 than those from group B. Analysis of group A by age groups revealed significantly higher TSH concentrations in the 2-9 years group and a moderate but significant decrease in the group from 50-59 years. No significant changes were demonstrated for T4 and T3. In the goitrous area, the response of TSH to TRH was exaggerated and prolonged. delta TSH20 was inversely correlated with age. The different age groups showed a significantly progressive and continuous decrease of delta TSH20, delta TSH60, delta TSH120 from age 10-19 to age 50-59 years. Our findings thus show a sharp increase of TSH during the first decades of life, which coincides with the phase of maximal growth of the thyroid gland. These results suggest that TSH plays a definite role in the genesis of endemic goitre. The subsequent progressive decrease of TSH secretion and reserve, with unchanged T4 and T3, imply a gradual development of autonomous activity in longstanding multinodular goitre.