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 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.

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.

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.

Effect of vaginal douching with povidone-iodine during early pregnancy on the iodine supply to mother and fetus.

Vaginal douching with polyvinylpyrrolidone iodine (PVP-I) during pregnancy results in maternal iodine overload and increases the iodine content of amniotic fluid. We evaluated the possible effects of this therapy on the thyroid of the fetus by investigating 62 women with a mean duration of amenorrhea of 20 weeks who solicited controlled abortion. Nineteen of them douched daily with PVP-I for 7 consecutive days before abortion (treated group). The other 43 women were not treated (control group). In both groups the iodine content was determined in the fetal thyroid and in amniotic fluid and maternal urine at the time of abortion. In addition, in the treated group the concentrations of iodine were also determined in amniotic fluid and urine before therapy and in urine after 4 days of therapy. There were no differences in the concentrations of iodine in urine and amniotic fluid in the control group and in the treated group before therapy. In the treated group urinary iodine increased from 6.1 +/- (SEM) 0.8 micrograms/dl before therapy to 91 +/- 20 micrograms/dl after 4 days and to 153 +/- 60 micrograms/dl after 7 days of therapy (p less than 0.001). In parallel, iodine in amniotic fluid increased from 1.2 +/- 0.2 micrograms/dl before therapy to 3.7 +/- 1.3 micrograms/dl after 7 days (p less than 0.05). In both groups the iodine content of the fetal thyroid increased with gestational age. However, it increased more rapidly in the treated group (from 1 to 7.7 micrograms) than in the control group (from 1 to 2.5 micrograms), p less than 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased recall rate at screening for congenital hypothyroidism in breast fed infants born to iodine overloaded mothers.

Skin disinfection with povidine-iodine (PVP-I) is widely used in obstetrics. We evaluated the influence of PVP-I in mothers at delivery on the serum thyroid stimulating hormone concentrations of their infants at the time of screening for congenital hypothyroidism. The study covered 4745 infants who were either breast fed (3659, 77%) or bottle fed (1086, 23%); 3086 (65%) of them were born to mothers with no iodine overload (controls) and 1659 (35%) to mothers with iodine overload. Compared with the control group, the breast and bottle fed infants born to mothers with iodide overload had a shift of neonatal thyroid stimulating hormone concentration towards high values. The shift was maximal in the breast fed infants with a 25 to 30 fold increase in the recall rate at screening for congenital hypothyroidism (serum thyroid stimulating hormone greater than 50 mU/l) while in the bottle fed infants, the recall rate was barely modified. In conclusion, the use of PVP-I in mothers at delivery induces a transient impairment of thyroid function in their infants, especially if breast fed. This situation is detrimental to screening for congenital hypothyroidism. Consequently PVP-I is not recommended in obstetrics.

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.

Prevention and treatment of endemic iodine-deficiency goiter by iodination of a municipal water supply.

A recently described method for the prevention and treatment of endemic iodine deficiency and goiter, introduction of iodine into a public water supply, was tested in Troina, a town of about 13,000 inhabitants in northeast Sicily. There, before initiation of the program, a goiter endemic of moderate severity was present, as evidenced by goiter prevalence of 55% in school children. Iodine deficiency in nongoitrous adults was indicated by daily urinary iodine excretion of 40.7 +/- 2.6 micrograms (mean +/- SE) and 24-h thyroid radioiodine uptake of 50.8 +/- 2.4%. Iodination of the water supply was initiated in November 1979 using a stream-splitting device that diverts a controlled fraction of the total water flow to a canister containing iodine crystals, where the water becomes saturated with iodine (approximately 300 mg/liter) before returning to the main stream. Except for a 15-month interruption during which governmental authorization of the program was being reconfirmed, treatment of the water has continued to the present time, initially at a level of 81 +/- 25 micrograms/liter (mean +/- SD) and since resumption at a level of 46.5 +/- 5 micrograms/liter. Iodination of the water was followed by a prompt and marked reduction in goiter prevalence, and by improvement in biochemical indices of iodine deficiency. By April 1983, overall goiter frequency in school children had declined to 6.1%, and large goiters (WHO Grade 2) had virtually disappeared. By January 1984, daily urinary iodine excretion had increased to 85.6 +/- 6.5 (SEM) micrograms and radioiodine uptake had decreased to 40.7 +/- 4.7%. Serum thyroid-related hormone concentrations were as follows (pretreatment vs. November-December 1983): T4, 5.8 +/- 0.3 vs. 8.4 +/- 0.3 microgram/dl; T3, 1.6 +/- 0.05 vs. 1.2 +/- 0.06 ng/ml; TSH, 3.7 +/- 0.2 vs. 2.2 +/- 0.1 microU/ml; all changes being statistically significant. By late 1983, serum T4, T3, and TSH values in Troina were almost identical to those in Catania, a community in which iodine deficiency is not present (goiter prevalence in school children, 2.2%). In contrast, in Troina serum T4 concentrations were significantly higher and serum TSH concentrations were significantly lower than those in Maniaci, a iodine-deficient town near Troina, in which the water was not iodinated. Iodinated water was well tolerated by the population of Troina, and no adverse effects of water iodination, including any increase in the frequency of hyperthyroidism, was observed. At present prices, the cost of the water iodination program in Troina would be approximately 4 cents (U.S.) per person per year.(ABSTRACT TRUNCATED AT 400 WORDS)

Increased risk of primary hypothyroidism in preterm infants.

Serum levels of thyroid stimulating hormone, thyroxine, triiodothyronine, free T4, thyroxine-binding globulin, reverse T3, and the TSH secretory areas and peak T3 after intravenous injection of 40 micrograms thyrotropin-releasing hormone were determined weekly from day 5 to 6 to 11 weeks of age in 42 unselected full-term and 61 preterm Belgian infants. The results on day 5 indicated a progressive deficit of thyroid function related to the degree of prematurity. In 92 infants this deficit progressively decreased with age and disappeared at 5 to 7 weeks. However, 11 infants developed biochemical evidence of overt but transient hypothyroidism. Belgian neonates are relatively iodine deficient, and this factor affects the constitution of iodine stores within the thyroid gland: (1) the urinary concentrations of iodine in the 103 infants studied in Belgium were markedly lower than in 30 infants from California; and (2) The iodine concentration of the thyroid gland in preterm infants who died during the 10 first days of life was almost three times lower in Brussels than in Toronto. The results indicate that, in Belgium, the effects of relative iodine deficiency on thyroid function are superimposed on and mask the physiologic state of tertiary hypothyroidism in prematurity.

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.

[Use of plasmapheresis in a case of Graves' disease with malignant ophthalmopathy (author's transl)]. / Exophtalmie maligne traitée par échange plasmatique. Rapport d'un cas.

A short trial with high doses of prednisolone to treat a 62 year-old woman with malignant ophthalmopathy due to Graves disease yielded an unsatisfactory improvement after 5-6 days. The authors decided therefore to use plasmapheresis, 4 plasma exchanges of 2.5 liters each associated with prednisolone (80 ng/day) and azathioprine (100 mg/day). This therapeutic approach resulted in a spectacular improvement obtained after less than 2 weeks: normalization of thyroid function, improvement of all ophthalmological indices confirmed by radiology (C.A.T.) of the retroocular region. The rapid and important improvement obtained after such a short period of time is in favor or the major role of plasmapheresis in this combined therapy of malignant Graves' ophthalmopathy.