[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.

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.

Changes of urinary iodine excretion of newborns over a period of twenty years.

OBJECTIVE: The use of iodized salt is not mandatory in Hungary and supply is irregular since decades. The effect of this anomaly was studied on the neonatal urinary iodine excretion over a period of twenty years. DESIGN: Urinary iodine content of 286 newborns' samples was tested in different areas of Hungary in 1980, 1991, and 1999. METHODS: Colorimetric ceric ion-arsenious acid method based on Sandell-Kolthoff reaction was used for determination of urinary iodine content. Fitfy-one samples were excluded from evaluation because of suspicion of iodine contamination. RESULTS: Decreased iodine excretion was demonstrated in different areas and at various times over this period of twenty years in accordance with the results of other (schoolchildren, pregnants) surveys in Hungary. CONCLUSIONS: Iodine deficiency of newborns in these areas changed from year to year, documenting a fluctuating iodine intake. Universal salt iodization should be introduced throughout the country instead of the present "silent iodine prophylaxis" to prevent iodine deficiency, especially in the perinatal period.

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.

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.

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.

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.

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.

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.

Traditional fermentation increases goitrogenic activity in pearl millet.

Epidemiological evidence suggests that millet might play a role in the etiology of endemic goiter. Recently, we showed that a traditional fermentation procedure of two pearl millet (Pennisetum americanum L. Lecke) cultivars grown in Sudan modified their effects on the weight of the thyroid gland and thyroid hormone profile in rats. In the present study, we report that this fermentation procedure reduced the ash contents of millet by about 40% and removed considerable amounts of Mg (>50%), Zn (27-39%) and K (45%). Other minerals (Ca, Fe, Cu) were not affected. Feeding of one fermented cultivar resulted in significant reduction in bone Mg and Zn contents, whereas feeding of the other fermented cultivar resulted in reduction of bone Mg only. Dietary Mg intake and bone Mg contents correlated negatively with serum T3. Groups fed the millet diets had higher serum Se level compared to those fed wheat or casein diets and feeding of fermented millet resulted in a further increase in serum Se level. Thus our data indicate that in rats the enhanced effects of millet on the thyroid induced by fermentation is likely related to removal of minerals from millet and/or chemical transformation of the goitrogens contained in millet.

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.

Fairly elevated incidence of goiter with marginally low urinary iodine in adolescents living in the north-western part of Tunisia.

In order to study the etiology of endemic goiter in the north-western part of Tunisia, we examined 93 adolescents of this region. We measured urinary iodine concentrations, serum total thyroxine, total triiodothyronine, thyrotropin, thyroglobulin and antithyrogobulin antibody concentrations. The adolescents were questioned about their alimentary habits, the origin of their drinking water and the presence of known goiter(s) in their family. Among these adolescents, 49.5% of them had a goiter. Urinary iodine concentrations showed mild iodine deficiency. The serum determinations gave results within the reference ranges, without any significative differences between adolescents, with or without goiter. We found two risk factors: the age of adolescents, and the presence of a known goiter in the family. These results suggest that the actual prevention may not be adequate, or most likely that goitrogenic factors are to be looked for, especially in drinking water, since the majority of these adolescents drink no controlled water.

Control of iodine deficiency using iodination of water in a goitre endemic area.

Salt iodination is the method of choice for prevention of iodine deficiency in most parts of the world. However, establishment of such a program frequently involves considerable changes in the marketing and distribution patterns and requires years to achieve. This study was conducted to evaluate the efficiency of using well-defined water sources containing iodine-saturated silicon matrices for providing adequate iodine supply to an iodine deficient population in Kordofan State, Western Sudan. A system of water iodination using silicon matrices containing 30% sodium iodide placed in polyethylene baskets was used in four villages using either traditional wells or hand pumps. Before and every 6 months after iodination of water, urine and blood samples were obtained for determination of iodine and thyroid-related hormones, respectively. Goitre assessment on the village populations were performed at the start and 2 years later. Improvements in iodine status were recorded in all the study villages. The water iodine concentrations increased and a higher iodine content was observed in the hand pumps compared to the traditional wells. The median urinary iodine concentrations increased significantly, from 0.19, 0.20, 0.19, 0.11 to 1.20, 1.10, 0.37, 0.30 mumol/l in the four villages, respectively. The percentages of subjects with serum TSH above 4 mU/l were decreased from more than 30% before iodination to less than 15% at 2 years after iodine supply and the mean serum thyroxine hormone values rose. The rates of goitre decreased from 69% to less than 25%. The study shows that this system is effective, cheap, safe and practically applicable under conditions prevailing in rural areas in developing countries with iodine deficiency.

[Iodine deficiency in the Cirque of Salazie (Reunion Island). Analysis of nutritional causes and study of their consequences]. / Mise en evidence d'une carence iodée dans le Cirque de Salazie (Ille de la Réunion). Analyse de ses causes nutritionnelles et etude de ses conséquences.

Randomized subjects (n = 294), (35 young children, 6-30 months old--91 children 8.6 +/- 0.7 years, 116 teenagers 13.2 +/- 1.9 y--52 young women 28.5 +/- 6.1 y) leaving in a mountainous area of Reunion Island (Cirque de Salazie) were evaluated according to the following: a questionnaire related to food intake, cervical palpation for thyroid size evaluation and collections of urine and foods (natural and mineral water, breast and commercial milk and salt) for iodine measurement. Neonatal TSH of 308 new borns in Salazie were compared to TSH of 300 new-borns of Lille (France). The prevalence of goiter increases with age (0% in young children, 12.1% in children, 23.3% in teenagers, 38.4% in women) whereas median urinary iodine (microgram/dl) decreases in the same groups (12-7.8-5.6-4.2). The intake of milk and dairy products significantly decreases from children to adults. Neonatal TSH values are significantly higher in Salazie than in Lille (p < 0.005). Natural and mineral water, breast milk and salt contain little iodine. In conclusion iodine deficiency is present in this area of Reunion Island with a significant increment of neonatal TSH values.

Breastfeeding in Belgium: tentative evaluation based on neonatal screening cards.

In Belgium as in most developed countries, the proportions of breastfed to bottle-fed newborns is poorly known. A compilation of infant feeding information, available on cards which were completed at the time newborns were screened for inborn metabolic errors, indicates that in the years 1992 and 1993, 62.5 percent of infants were breastfed on day five of life. The data collected in this way were consistent for the years studied. Other countries may also be able to use screening cards to estimate breastfeeding initiation rates.

Human thyroglobulin reference material (CRM 457). 1st Part: Assessment of homogeneity, stability and immunoreactivity.

This paper describes the assessment of the homogeneity and stability of a purified and lyophilized human thyroglobulin (Tg), and characterizes its immunoreactivity. The purified and lyophilized Tg is intended to be used as a primary reference material to establish calibration of working serum based reference material. The programme involved the participation of 15 European laboratories and one laboratory from the United States. The homogeneity of the content of the ampoules was considered acceptable (< 9%). The stability was tested by accelerated temperature degradation showing predicted annual relative losses of 0.01% at -70 degrees C and 1.04% at -20 degrees C. The immunoreactivity of the Tg material as measured in different laboratories varied mostly according to the method used rather than the laboratory. The interlaboratory variability showed that the two commercial methods used in several laboratories (kit 1 and 2) had an interlaboratory variation (CV) of 15.9% (N = 5) and 7.1% (N = 3), respectively, whereas the total interlaboratory CV was 64.3% (N = 18). The immunoreactive Tg had dilution curves parallel with other Tg calibrators (those of the methods). Dilution curves of the Tg material after storage at various temperatures and time were parallel in both RIA and IRMA. In conclusion, we have prepared a Tg reference material which in extensive studies in several participating laboratories has demonstrated a sufficient homogeneity and stability as well as dilution curves parallel to the calibrators of all the immunoassays tested in the study. This reference material is considered the first step towards decreasing the interlaboratory variability between Tg immunoassays.

Human thyroglobulin reference material (CRM 457). 2nd Part: Physicochemical characterization and certification.

This report describes the characterization of a purified human thyroglobulin (Tg) reference material, and details the procedures used in its certification. The purified Tg is intended to be used as a primary reference material to establish calibration of working serum based reference material for immunoassay procedures. The programme involved the participation of 15 European laboratories and one laboratory from the United States. The physicochemical characterization showed by polyacrylamide gel electrophoresis and immunoblotting that the purified Tg had for the major part the expected molecular size of 660 kDa with traces of lower molecular forms. The amino acid composition was close to that demonstrated for the cDNA and the content of iodine was in keeping with a moderately to highly iodinated Tg. The mass concentration in reference material RM 457 is certified to be (0.324 +/- 0.018) g/L on the basis of protein determined by the Lowry method and supported by nitrogen determination, absorbance measurement, and amino acid analysis. This reference material is considered the first step towards decreasing the interlaboratory variability between Tg methods of measurement.