[The laboratory of pediatrics]. / Le laboratoire de pédiatrie.

A medical department in a university hospital has 3 duties: care, teaching, and research. Partnership between the department of pediatrics and a laboratory of pediatrics is therefore essential; they are complementary. The development of the laboratory requires constructive collaboration with the medical department, clinicians addressing questions to the laboratory, and the laboratory developing tools in order to provide answers. This clearly supposes that the necessary human and material resources are made available to the laboratory. The Laboratory of Pediatrics of the ULB, through its basic activity, exists and functions, but possibilities and ambitions are broader. With the aid of the department of pediatrics and of the university, the Laboratory should be able to consolidate the diversification of its activities and financial resources, and to extent the panel of services offered.

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.

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.

Blood spot follicle-stimulating hormone during early postnatal life in normal girls and Turner's syndrome.

Although FSH has previously been found to be elevated during infancy in agonadal subjects, it is not known whether perinatal FSH levels are also increased. Neonatal blood spot FSH levels were studied retrospectively in nine full term girls born with Turner's syndrome and compared with presumably normal full term girls born the same week. FSH was measured using a highly specific immunoradiometric assay adapted to blood spots collected at the time of systematic neonatal screening. On day 5-6 after birth, FSH was undetectable (< 1 IU/L) or low (1-4.4 IU/L) in normal girls. Among the nine patients with Turner's syndrome, five had FSH levels below 3 IU/L, and four showed slightly elevated levels, ranging from 4.3-10.9 IU/L. These differences in FSH secretion were not related to differences in karyotype. Among five patients studied longitudinally during the first 6 weeks of life, three showed increases in FSH levels to 14.9-15.9 IU/L during the second week of life. However, this increase was comparable to that seen in some normal girls sampled on a second occasion during the first weeks after birth. One patient with Turner's syndrome still had low FSH (2.5 IU/L) on day 23, but showed some increase to 8.5 IU/L on day 30. We conclude that 1) in Turner patients, perinatal changes in FSH secretion are similar to those in normal girls, although there is already a lack of feedback control by gonadal hormones on the hypothalamo-pituitary axis; and 2) the FSH assay cannot be used for neonatal screening of Turner's syndrome.

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.

Partial reversibility during late postpartum of thyroid abnormalities associated with pregnancy.

The aim of the present work was to assess during late postpartum the reversibility of thyroidal alterations associated with pregnancy. Thyroid function was reinvestigated 6 months after delivery in 100 randomly selected healthy women and thyroid volume was reevaluated 12 months after delivery in 10 other selected women. The subjects had previously been carefully followed during gestation as they were included in a prospective cohort investigation of the regulation of the thyroid during pregnancy, in an area with a limited dietary iodine intake (less than 100 micrograms/day in 85% of the women). Six months after delivery, an overall normalization of thyroid function was observed. However, an increase in the T3/T4 ratio, which was present in half the cases at delivery, was still evident 6 months postpartum, suggesting the persistence of relative iodine deficiency, probably prolonged in some women through breast-feeding. Furthermore, serum thyroglobulin levels, which were increased in half the women at delivery, remained abnormally high in 40% of them 6 months later. Twelve months after delivery thyroid volume, which had increased in average by 54% during pregnancy, had not reverted to the values found during early gestation. Moreover a goiter was still evident in 2/4 cases in whom it had developed during pregnancy. In conclusion, the present study indicates that pregnancy may constitute a prolonged stimulus for the thyroid and shows for the first time that the alterations associated with gestation are not limited to the period of pregnancy, being only partially reversible during late postpartum. In conditions with a limited iodine intake, pregnancy constitutes a risk for the maternal thyroid: goitrogenesis does occur and may be maintained after delivery. The glandular stress of pregnancy may therefore provide a clue to understanding the high prevalence of thyroid disorders in women. The present study provides additional arguments to suggest that iodine supply be increased during pregnancy but also after parturition, in particular in breast-feeding mothers.

Maternal and neonatal thyroid function at birth in an area of marginally low iodine intake.

Thyroid function was evaluated in cord serum of healthy full-term newborns and compared to that of mothers immediately after parturition. The study was carried out in an area without overt iodine deficiency, but with a marginal iodine supply (less than 100 micrograms/day in 80% of women). The aim of the study was to delineate the interrelationships between the thyroid statuses of mother and child at birth. Maternal thyroid function was characterized at delivery by relative hypothyroxinemia; increased T3/T4 ratios, indicating preferential T3 secretion; slightly increased TSH levels within the normal range in 97% of women; increased serum thyroglobulin (TG) values, which were above normal in 60% of women; and also goiter formation in almost 10% of women. The findings indicated glandular stimulation and confirmed our earlier reports that pregnancy constitutes a stress for the maternal thyroid economy, enhanced by the limited availability of iodine in the diet. By contrast, newborns showed a strikingly distinct pattern: there was no relative hypothyroxinemia and free T4 levels were significantly higher than in the respective mothers (19.4 vs. 14.7 pmol/L; P less than 0.001). In spite of these differences, however, mean neonatal TSH and TG levels were significantly higher than maternal values, respectively 6.0 vs. 1.9 mU/L for TSH (P less than 0.001) and 70 vs. 40 micrograms/L for TG (P less than 0.001). Furthermore, neonatal TG and TSH levels increased in parallel and were highly correlated with maternal data, suggesting a regulatory link between both thyroid economies. The results suggested that the common regulatory link is the limited availability of the iodine supply. In conclusion, the present study demonstrates that even in conditions with a marginally low iodine intake, pregnancy constitutes a stimulus for both the maternal and newborn thyroids. Changes in both groups are associated and the abnormalities in TSH and TG are amplified in the newborns. The TSH and TG alterations at birth in full-term healthy newborns, associated with similar alterations in maternal thyroid function, provide evidence for a common stimulatory factor, relative iodine deficiency. The data emphasize the hypersensitivity of neonatal thyroid function to marginal iodine deficiency and point to the need to increase the iodine supply in groups at risk, such as women during pregnancy, and also newborns in the perinatal period.

Pregnancy in patients with mild thyroid abnormalities: maternal and neonatal repercussions.

A prospective study was undertaken during pregnancy in 120 euthyroid women presenting with mild thyroid abnormalities (TA): 11 with a past history of thyroid disorder, 44 with goiter, 20 with nodules, and 45 with thyroid autoantibodies. The aims of the study were to assess whether the pattern of thyroid alterations during gestation was different in women with TA compared to that in healthy control pregnant subjects and to evaluate possible obstetrical and neonatal repercussions. The overall prevalence of underlying subtle thyroid abnormalities in the cohort was 17%, probably as the result of the environmental moderately low iodine intake. Despite the intrinsic heterogeneity of the four groups of women with TA, the adaptation of the thyroid to the stress of pregnancy was different from that of the control subjects. Noteworthy were 1) the marked elevation of serum thyroglobulin in women with past history of thyroid disorder, goiter and thyroid nodules; 2) the increase in goiter size in a third of the goitrous women, associated with biochemical evidence of functional stimulation of the gland; 3) the indirect evidence of partial thyroidal autonomy in goitrous patients; and 4) the increase in the number and size of thyroid nodules during gestation. Taken together, the data indicated that pregnancy was associated with a greater thyroidal risk in patients with TA compared to healthy subjects. In relation to thyroid autoimmunity, most patients remained euthyroid during gestation, but in a few cases, TSH was elevated at delivery, suggesting diminished thyroidal reserve. Also, 40% of newborns from mothers with thyroid autoimmunity had elevated thyroid peroxidase antibody titers at birth, and there was a highly significant correlation between maternal and neonatal thyroid peroxidase antibody titers. Finally, thyroid autoimmunity was clearly associated with an increased risk of spontaneous abortion (13.3 vs. 3.3%; P less than 0.001). Thyroid function in newborns from mothers with TA was normal and not different from that in controls; similarly, obstetrical features were similar in patients with TA and control subjects. In conclusion, pregnancy is associated with a greater thyroidal risk in women with TA, thereby emphasizing a potential link between pregnancy and thyroid disorders. It is recommended that patients with known, even subtle, thyroid abnormalities be closely monitored during pregnancy, in particular those with a goiter, nodules, or thyroid autoimmunity, especially in areas with a moderately low iodine intake, where the prevalence of mild thyroid disturbances is high.

Regulation of maternal thyroid during pregnancy.

A prospective study was undertaken in 606 healthy women during pregnancy to evaluate the changes occurring in maternal thyroid economy as a result of 1) the increased thyroid hormone-binding capacity of serum, 2) the effects of increased levels of hCG on TSH and on the thyroid, and 3) a marginally low iodine intake in the population (50-75 micrograms/day). Four main features were observed. First, thyroidal activity adjusted to the marked increase in serum T4-binding globulin: pregnancy was accompanied by an overall reduction in the T4/T4-binding globulin ratio, with lower free T4 and T3 levels, although in most cases free hormone levels remained within the normal range. The adjustment of thyroidal output of T4 and T3 did not occur similarly in all subjects. In approximately one third of the women, there was relative hypothyroxinemia, higher T3/T4 ratios (presumably indicating preferential T3 secretion), and higher, although normal, serum TSH concentrations. Second, high hCG levels were associated with thyroid stimulation, both functionally (lower serum TSH) and anatomically (increased thyroid size). The data are consistent with a TSH-like effect of hCG on the thyroid. Hence, regulation of the maternal thyroid is complex, resulting from both elevated hCG (mainly in the first half of gestation) and increasing TSH (mainly in the second half of gestation). Third, a significant increase in serum thyroglobulin levels was observed throughout gestation, especially during the last trimester. Fourth, increased thyroid volume was common, and goiter formation not uncommon (goiter was found in 9% of women at delivery). In conclusion, the alterations in maternal thyroid function during gestation are intricate and far from fully understood. In areas of marginally low iodine intake, gestation is associated in a significant number of women with relative hypothyroxinemia, increased thyroglobulin, and enlarged thyroid.

Endemic goiter with iodine sufficiency: a possible role for the consumption of pearl millet in the etiology of endemic goiter.

BACKGROUND: Deficiencies of iodine, iron, and vitamin A are the 3 most common micronutrient deficiencies in developing countries, although control programs, when properly implemented, can be effective. OBJECTIVE: We investigated these deficiencies and their possible interaction in preschool children in the southern Blue Nile area of Sudan. DESIGN: Goiter, signs of vitamin A deficiency, and biochemical markers of thyroid, vitamin A, and iron status were assessed in 984 children aged 1-6 y. RESULTS: The goiter rate was 22. 3%. The median urinary iodine concentration was 0.79 micromol/L and 19.3% of the children had a concentration >1.57 micromol/L. Although serum thyroxine and triiodothyronine concentrations were within reference ranges, the median thyrotropin concentration was 3.78 mIU/L and 44% of the children had thyrotropin concentrations above normal. The mean urinary thiocyanate concentration was high (259 +/- 121 micromol/L). The prevalences of Bitot spots and night blindness were 2.94% and 2.64%, respectively, and 32% of the subjects had serum retinol binding protein concentrations <15 mg/L. A significant positive correlation was observed between thyrotropin and retinol binding protein. Whereas 88% of the children had hemoglobin concentrations <1.86 mmol/L, only 13.5% had serum ferritin concentrations below the cutoff of 12 microg/L and 95% had serum transferrin concentrations above the cutoff of 2.50 g/L. CONCLUSIONS: Our results indicate that goiter is endemic in this region of Sudan despite iodine sufficiency and that both anemia and vitamin A deficiency are health problems in the area. Moreover, consumption of millet, vitamin A deficiency, and protein-energy malnutrition are possible etiologic factors in this endemic area.

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.

Validation of a simple, manual urinary iodine method for estimating the prevalence of iodine-deficiency disorders, and interlaboratory comparison with other methods.

The measurement of urinary iodine in population-based surveys provides a biological indicator of the severity of iodine-deficiency disorders. We describe the steps performed to validate a simple, inexpensive, manual urinary iodine acid digestion method, and compare the results using this method with those of other urinary iodine methods. Initially, basic performance characteristics were evaluated: the average recovery of added iodine was 100.4 +/- 8.7% (mean +/- SD), within-assay precision (CV) over the assay range 0-0.95 mumol/L (0-12 micrograms/dL) was < 6%, between-assay precision over the same range was < 12%, and assay sensitivity was 0.05 mumol/L (0.6 microgram/dL). There were no apparent effects on the method by thiocyanate, a known interfering substance. In a comparison with five other methods performed in four different laboratories, samples were collected to test the method performance over a wide range of urinary iodine values (0.04-3.7 mumol/L, or 0.5-47 micrograms/dL). There was a high correlation between all methods and the interpretation of the results was consistent. We conclude that the simple, manual acid digestion method is suitable for urinary iodine analysis.

Influence of dietary habits on thyroid status of a nomadic people, the Bororo shepherds, roaming a central African region affected by severe iodine deficiency.

OBJECTIVE: In contrast with the endemic goiter reported in several African countries, the nomadic Bororos of the Central African Republic have an unexpectedly low prevalence of goiter. This study was conducted to elucidate this puzzling observation. DESIGN: Thyroid function and iodine and thiocyanate intakes were evaluated in Bororos and inhabitants of the same area and compared with an Italian population. RESULTS: Urinary iodine concentrations indicated moderate iodine deficiency in the rural people and the Bororos. In the latter, no individual with clinical hypothyroidism was observed. Compared with the reference population, the Bororos had slightly lower thyroxine (T4) and free thyroxine (FT4), slightly increased tri-iodothyronine (T3) and T3/T4 ratio, slightly higher TSH, normal serum thyroglobulin, a prevalence of goiter of 17.1% and a higher urinary thiocyanate. The rural people showed striking differences: lower T4 and FT4, increased T3/T4 ratio, markedly increased TSH and thyroglobulin, a prevalence of goiter of 76.9% and a high urinary thiocyanate, indicating frequent consumption of cassava. A dietary survey indicated that the Bororos ingest large amounts of milk and related products but infrequently eat cassava. CONCLUSION: A minute difference in iodine deficiency between two populations induces totally different patterns of goiter and thyroid function. The reason for such a contrast probably involves differences in diet.

Belgian heart disease prevention project: comparison of self-reported smoking behaviour with serum thiocyanate concentrations.

At the end of a multifactorial cardiovascular preventive trial serum thiocyanate was measured in random samples of 1035 cases and 1087 controls. A cut-off point 0.45 mg/dl (77.6/mumol/l) gave a sensitivity of 82.1% among the cigarette smokers in the control group and a specificity of 91.0% among the non-smokers. When the intervention and control groups are compared in terms of self-reported smoking behaviour non-significant differences in mean thiocyanate concentration are observed for those who never smoked, ex-cigarette smokers, actual cigarette smokers, and in four different cigarette smoking categories. Our results fail to confirm the reported pessimistic views concerning the validity of self-reported smoking behaviour in subjects taking part in intervention trials.

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.

Biochemical thyroid profile in patients infected with the human immunodeficiency virus.

Over a 2-year period, thyroid function was studied in 102 patients infected with the human immunodeficiency virus (HIV) and in 102 age- and sex-matched controls with various infectious diseases. Biochemical abnormalities were observed in 1-20% of the patients, depending on thyroid indices, but thyroid disease (hypothyroidism) was diagnosed in only 1. Compared to controls, patients, especially those with the acquired immunodeficiency syndrome (AIDS), had a significant increase in serum thyroxine-binding globulin, a lower T3 and free thyroxine index, and a higher frequency of thyroglobulin antibodies.

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.

Iodine-induced hyperthyroidism: occurrence and epidemiology.

We have critically reviewed the available information on iodine-induced hyperthyroidism (IIH) from published sources and other reports as well as the experience of the authors in Tasmania, Zaire, Zimbabwe, and Brazil. Administration of iodine in almost any chemical form may induce an episode of thyrotoxicosis (IIH). This has been observed in epidemic incidence in several countries when iodine has been given as prophylaxis in a variety of vehicles, but the attack rate as recorded has been low. IIH is most commonly encountered in older persons with long standing nodular goiter and in regions of chronic iodine deficiency, but instances in the young have been recorded. It customarily occurs after an incremental rise in mean iodine intake in the course of programs for the prevention of iodine deficiency, or when iodine-containing drugs such as radiocontrast media or amiodarone are administered. The biological basis for IIH appears most often to be mutational events in thyroid cells that lead to autonomy of function. When the mass of cells with such an event becomes sufficient and iodine supply is increased, the subject may become thyrotoxic. These changes may occur in localized foci within the gland or in the process of nodule formation. IIH may also occur with an increase in iodine intake in those whose hyperthyroidism (Graves' disease) is not expressed because of iodine deficiency. The risks of IIH are principally to the elderly who may have heart disease, and to those who live in regions where there is limited access to medical care. More information is needed on the long-term health impact of IIH or "subclinical" IIH, especially in the course of prophylaxis programs with iodized salt or iodinated oil in regions where access to health care is limited.

Congenital central isolated hypothyroidism caused by a homozygous mutation in the TSH-beta subunit gene.

We report a Belgian girl born in 1983 with isolated thyrotropin (TSH) deficiency. Hypothyroidism without goiter was diagnosed at the age of 2 months, with extremely low total thyroxine (T4) at 0.3 microg/dL (4 nmol/L; N[normal]: 5.6-11.4 microg/dL). Basal TSH, only moderately elevated at 14.8 mU/L (N: 0-5.3; competitive radioimmunoassay, RIA), increased to 18.2 mU/L after thyrotropin-releasing hormone (TRH) stimulation, whereas prolactin increased normally. At age 15 years, after withdrawal of levothyroxine (LT4) therapy for 6 weeks, TRH stimulation slightly increased serum TSH using two immunometric assays, from less than 0.03 to 0.07 and from 0.2 to 0.3 (a monoclonal and polyclonal antibody), and from 1.9 to 4.1 mU/L using a polyclonal TSH antibody and iodinated recombinant TSH. Sequencing of the TSH-beta subunit gene revealed a homozygous single nucleotide deletion in codon 105 producing a frame shift that results in a truncated TSH-beta with nonhomologous 9 carboxyterminal amino acids and a loss of the 5 terminal residues. This mutation was previously reported in one Brazilian and two German families. The abnormal, and presumably biologically inactive, TSH can be detected in serum using appropriate antibodies. Its relatively small amount in serum is due to either reduced secretion or rapid degradation. The occurrence of the same mutation in three families of different ethnic origin suggests that this mutation may be prevalent in the population. Common ancestry or de novo mutations in a hot spot cannot be excluded. Finally, we must be aware that neonatal screening of congenital hypothyroidism based on blood spot TSH measurement will not detect this rare but severe genetic defect.

Quantification of urinary iodine: a need for revised thresholds.

OBJECTIVE: To compare different possibilities of reporting the iodine supply in the same urine samples. Indeed, in field studies, urinary iodine concentration (I/L: micro g I/L, micro mol I/L, I/creatinine: micro g I/g creatanine, micro mol I/mol creatinine) is more readily available than excretion (I/24h micro g I/24 h, micro mol I/24h). However, confusion exists regarding the comparability of iodine supply based upon I/L, I/creatinine and I/24h, which for decades have been regarded as biochemically equivalent. DESIGN: We compared I/24h, I/L and I/creatinine in accurate 24 h collections of urine and I/L and I/creatinine in 47 spot urine samples. PATIENTS: A total of 13 subjects (Bern n=7, Brussels n=6) collected a total of 110 precise 24 h urine collections (Bern n=63, Brussels n=47). The subjects from Brussels also took a spot sample at the beginning of each 24 h collection. RESULTS: Iodine supply in both places was mildly deficient according to the criteria of WHO; all but one collection indicated an intake of >0.39 micro mol I/24h (>50 micro g I/24h). The same data presented as I/creatinine (or I/L) indicated an iodine intake of <0.39 (<50 micro g I/24h) in 5% (24%) of the samples in Bern and 23% (57%) in Brussels. Similar findings were observed for 47 spot samples. Whatever the cut-off selected, I/creatinine and I/L were systematically lower than I/24h (P<0.0002). Creatinine showed smaller CV than volume but did not perform better in defining iodine intake. CONCLUSION: Considering I/24h as a reference, both I/creatinine and I/L clearly underestimate the iodine intake in subjects with adequate proteoenergetic intake. The significant deviations observed illustrate the urgent need for establishing separate ranges for I/24h, I/creatinine and I/L. In population studies, these deviations might even be larger.