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One of the key tasks for the persons in charge of a neonatal screening laboratory is the control and maintenance of the quality of analytical results. The process of examining every day hundreds of blood spot samples obtained from newborn babies in order to divide the population of neonates into a low risk group and a high risk group, presents several challenges with respect to organisation, analytical accuracy and precision and effectiveness in the recall and treatment procedures. Quality in neonatal screening is not determined solely by the analytical performance of the laboratory; all the steps of the neonatal screening “system” contribute to the overall quality and performance. Conclusion: programmes for the monitoring of the quality of neonatal screening have to be multidisciplinary and not restricted to the laboratory alone; not only analytical performance, but also the procedures used throughout the programme have to be monitored.

Until today, the mainstay of phenylketonuria (PKU) treatment is a phenylalanine (Phe)-restricted diet. Strict dietary treatment decreases flexibility and autonomy and still has a major impact on patients and their families. Compliance is often poor, particularly in adolescence. The aim of this study was to investigate the effect of the intake of fruits and vegetables containing Phe less than 100 mg/100g ('simplified diet'), as recommended by WHO for all individuals, instead of classical totally restricted diet on the course and treatment control of the disease in a well-characterized PKU cohort (n=80). All individual blood Phe measurements of each patient (1992-2009) were statistically analyzed before and after diet switch. Epidemiological data, age at diagnosis, PAH mutations, BH(4) responsiveness, as well as Phe control measurements and detailed diet information were tabulated in a local database. 62.5% had BH4 loading test and 40% had PAH analysis; 50/80 switched from classical to simplified diet, including 26 classical PKU, 13 moderate PKU, 7 mild PKU and 4 mild hyperphenylalaninemia (HPA). Median Phe levels on a simplified diet did not differ significantly to the median Phe levels on classical diet in all disease groups. Our results indicate that a simplified diet has no negative effect on blood Phe control in patients with hyperphenylalaninemia, independent of severity of the phenotype or the age at diet switch, over the period of 3 years. Thus, a simpler approach to dietary treatment of PKU available to all HPA patients is more likely to be accepted and adhered by patients and might also increase quality of life.

BACKGROUND Results in neonatal screening programs aiming at detection of congenital adrenal hyperplasia (CAH) can only report elevated levels of 17-hydroxy-progesterone (17-OHP), without being able to differentiate presence or absence of salt loss. AIM To predict presence or absence of salt loss in newborn infants with CAH. METHODS The first specimen of suspected CAH in samples sent from People's Democratic Republic of Laos (Lao PDR) was investigated for known mutations in CAH associated with salt loss. RESULTS Molecular genetic diagnosis revealed mutations associated with loss of function in both alleles; however, the infant was clinically unaffected even without any corticosteroid substitution therapy. CONCLUSIONS Although molecular genetic methods can theoretically predict loss of function in CAH, our infant was clinically unaffected even without therapy at 6 years of age. We speculate that in CAH, remaining enzyme activity can be sufficiently high, despite the presence of loss of function mutations, which do not affect infants clinically.

A pilot study was performed to investigate a clinical algorithm using serum-eosinophil cationic protein level (S-ECP) as an objective parameter for tapering the anti-inflammatory treatment in chronic childhood asthma. We studied 21 outpatient asthmatic children (6 girls and 15 boys, mean age 9 yr, range 3–12 yr, all with initial S-ECP ≥ 15 µg/l) over a period of 12 months at monthly intervals. At each visit a short history, clinical examination, blood sample for S-ECP and eosinophil count, lung function tests and drug compliance were assessed. According to the initial S-ECP, patients were allocated to two anti-inflammatory treatment groups: patients with S-ECP between 15 µg/l and 30 µg/l were treated with Budesonide 200 µg twice daily, while patients with S-ECP of 30 µg/l and above received Budesonide 400 µg twice daily. After this induction treatment the anti-inflammatory medication was tapered at monthly intervals according to actually measured S-ECP: patients with S-ECP

Context: Thyroglobulin (Tg) may be a valuable indicator of improving thyroid function in children after salt iodization. A recently developed Tg assay for use on dried whole blood spots (DBS) makes sampling practical, even in remote areas. Objective: The study aim was to develop a reference standard for DBS-Tg, establish an international reference range for DBS-Tg in iodine-sufficient children, and test the standardized DBS-Tg assay in an intervention trial. Design, Participants, and Interventions: Serum Tg reference material of the European Community Bureau of Reference (CRM-457) was adapted for DBS and its stability tested over 1 yr. DBS-Tg was determined in an international sample of 5- to 14-yr-old children (n = 700) who were euthyroid, anti-Tg antibody negative, and residing in areas of long-term iodine sufficiency. In a 10-month trial in iodine-deficient children, DBS-Tg and other indicators of iodine status were measured before and after introduction of iodized salt. Results: Stability of the CRM-457 Tg reference standard on DBS over 1 yr of storage at −20 and −50 C was acceptable. In the international sample of children, the third and 97th percentiles of DBS-Tg were 4 and 40 μg/liter, respectively. In the intervention, before introduction of iodized salt, median DBS-Tg was 49 μg/liter, and more than two thirds of children had DBS-Tg values greater than 40 μg/liter. After 5 and 10 months of iodized salt use, median DBS-Tg decreased to 13 and 8 μg/liter, respectively, and only 7 and 3% of children, respectively, had values greater than 40 μg/liter. DBS-Tg correlated well at baseline and 5 months with urinary iodine and thyroid volume. Conclusions: The availability of reference material and an international reference range facilitates the use of DBS-Tg for monitoring of iodine nutrition in school-age children.

Many industrialized countries struggle to maintain adequate iodine intake because of changes in dietary habits and the food supply. In Switzerland, because of declining iodine intakes in children and pregnant women, the iodine concentration in table salt was increased from 15 to 20 mg/kg.We evaluated Swiss iodine nutrition after the 1999 increase in the salt iodine concentration.In 1999 and 2004, a 3-stage probability proportionate-to-size cluster sampling was done to obtain a representative national sample of primary schoolchildren and pregnant women. Urine and household salt were collected for iodine measurement. The frequency of elevated thyrotropin concentrations found in the newborn screening program was evaluated before and after the increase.In 1999, median urinary iodine (UI) concentrations among children (n = 610) and pregnant women (n = 511) were 115 microg/L (range: 5-413 microg/L) and 138 microg/L (range: 5-1881 microg/L), respectively, which indicated marginal iodine status. In 2004, median UI concentrations among children (n = 386) and pregnant women (n = 279) were 141 microg/L (range: 0-516 microg/L) and 249 microg/L (range: 8-995 microg/L), respectively (P0.01). Newborn thyrotropin concentrations5 mU/L decreased from 2.9% in 1992-1998 (n = 259 035) to 1.7% in 1999-2004 (n = 218 665) (P0.0001).A 25% increase in iodine concentration in iodized table salt markedly improved iodine status in Switzerland, which showed the value of monitoring and adjusting iodine concentrations in national salt programs. The frequency of newborn thyrotropin concentrations5 mU/L appears to be a sensitive indicator of iodine nutrition during pregnancy.

Background: In many developing countries, children are at high risk for both goiter and anemia. In areas of subsistence farming in rural Africa, salt is one of the few regularly purchased food items and could be a good fortification vehicle for iodine and iron, provided that a stable yet bioavailable iron fortificant is used. Objective: We tested the efficacy of salt dual-fortified with iodine and micronized ferric pyrophosphate for reducing the prevalence of iodine and iron deficiencies in children. Design: In rural northern Morocco, we fortified local salt with 25 g I (as potassium iodate)/g salt and 2 mg Fe (as micronized ferric pyrophosphate; mean particle size 2.5 m)/g salt. After storage and acceptability trials, we compared the efficacy of the dualfortified salt (DFS) with that of iodized salt in a 10-mo, randomized, double-blind trial in iodine-deficient 6 –15-y-old children ( n 158) with a high prevalence of anemia. Results: After storage for 6 mo, there were no significant differences in iodine content or color lightness between the DFS and iodized salt. During the efficacy trial, the DFS provided 18 mg Fe/d; iron absorption was estimated to be2%. After 10 mo of treatment in the DFS group, mean hemoglobin increased by 16 g/L (P 0.01), iron status and body iron stores increased significantly ( P 0.01), and the prevalence of iron deficiency anemia decreased from 30% at baseline to 5% (P 0.001). In both groups, urinary iodine (P 0.001) and thyroid volume (P 0.01) improved significantly from baseline. Conclusion: A DFS containing iodine and micronized ferric pyrophosphate can be an effective fortification strategy in rural Africa. Am J Clin Nutr 2004;80:952–9.

BACKGROUND In programs to control iodine deficiency disorders (IDD), sustainability is a major concern. IDD has recently recurred in countries where salt iodization programs have lapsed. OBJECTIVE The objective of the study was to describe the evolution of thyroid dysfunction after the discontinuation of salt iodization in a cohort of children in an area of severe endemic goiter. DESIGN Moroccan children (aged 6-16 y, n = 159) with severe IDD received iodized salt (IS) for 1 y. Because of practical and financial constraints, including a lack of infrastructure and electricity at the production site, salt iodization abruptly ceased. The children were followed for another 14 mo, and concentrations of urinary iodine, thyrotropin, total thyroxine, and thyroglobulin and thyroid volume were measured. RESULTS Before iodization, median urinary iodine was 18 microg/L, 88% of children had elevated serum thyroglobulin concentrations, and 72% were goitrous. One year after the introduction of IS, median urinary iodine and thyroglobulin concentrations had normalized, mean thyroid volume had decreased by 34%, and median thyrotropin and mean total thyroxine concentrations were improved. Five months after the discontinuation of salt iodization, median urinary iodine had fallen to 20 microg/L. Fourteen months after the discontinuation of salt iodization, the rate of goiter was again similar to the rate before salt iodization; median thyrotropin and thyroglobulin concentrations were sharply higher than before the introduction of IS (P < 0.001); and the prevalence of hypothyroidism was 10%, compared with 3% before the introduction of IS (P < 0.001). CONCLUSIONS In IDD-affected areas, cessation of salt iodization is associated with a rapid deterioration of thyroid function in school-age children. These findings underline the importance of sustainability in IDD control and the vulnerability of children to even short-term lapses in IS programs.

BACKGROUND Serum thyroglobulin appears to be a sensitive marker of thyroid dysfunction in endemic goiter. However, its value as an indicator of thyroid status in children after the introduction of iodized salt has not been tested. OBJECTIVE The objective was to optimize and validate a thyroglobulin assay on dried whole blood spots and to evaluate thyroglobulin as an indicator of thyroid response to iodized salt. DESIGN A standardized, commercially available, sandwich fluoroimmunometric serum thyroglobulin assay was adapted for use on blood spots and validated in Swiss children. In a 1-y prospective study in 377 goitrous Moroccan children aged 6-15 y, the assay was used to measure thyroglobulin before and after the introduction of iodized salt. Urinary iodine, thyroid volume, thyrotropin, and thyroxine were measured, and regression was done with thyroglobulin as the dependent variable. RESULTS Correlation between the blood spot and serum assays was excellent (r = 0.98). The SD of the difference between the blood spot and serum assays was 3.8 micro g/L; the median CVs for the blood spot assay in controls and samples were 6.3% and 14.4%, respectively. Median thyroglobulin was 24.5 (range: 0-328.8) micro g/L at baseline and fell significantly after the introduction of iodized salt to 6.2 (0-83.1) and 4.4 (0-47.1) micro g/L at 5 and 12 mo, respectively (P < 0.0001). Regression of urinary iodine and thyroid volume on thyroglobulin was highly significant at baseline and at 5 mo (P < 0.001). CONCLUSION Thyroglobulin, measured in dried whole blood spots, may be a valuable indicator of improving thyroid function in children after supplementation with iodized salt.

Background/Aim: In children with Prader-Labhart-Willi syndrome (PWS), the insulin secretion is reduced, despite obesity, being ascribed to the growth hormone (GH) deficiency of hypothalamic origin. Besides, an increased prevalence of diabetes mellitus was described in this syndrome. Hence, we addressed the questions of how body composition and insulin secretion are interrelated and what impact GH therapy has on the carbohydrate metabolism in PWS. Methods: We measured weight, lean and fat mass (by dual-energy X-ray absorptiometry), triglycerides, HbA1c, and fasting insulin and glucose levels in 17 children (age range 1.5–14.6 years) with PWS to examine whether the carbohydrate metabolism is altered during 36 months of therapy with 8 mg GH/m2 body surface/week. In a subgroup of 8 children, the insulin secretion was longitudinally assayed during oral glucose tolerance at 0 and 12 months of therapy. Results: Before therapy, the insulin secretion was lower and markedly delayed as compared with reference data and did not rise during therapy. The glucose tolerance was impaired in 2 of 12 children examined by oral glucose tolerance test before therapy and normalized during therapy. Fasting insulin and insulin resistance being normal at the beginning, significantly increased at 12 months and returned to initial levels at 36 months of GH therapy. Fasting glucose as well as HbA1c and triglyceride levels were always normal. The fat mass before GH therapy was increased (39.5%) and dropped into the upper normal range (28.3%) during 3 years of therapy, being correlated with fasting insulin concentration and indices of insulin sensitivity before and after 1 year of therapy. Conclusions: Children with PWS are characterized by an intact insulin sensitivity with a decrease and a delay of insulin secretion, regardless of moderate obesity or GH treatment. In the present setting, the carbohydrate metabolism is not impaired by GH therapy, but by the excessively increased fat mass.

In many developing countries children are at high risk of both goiter and iron deficiency anemia. Iron deficiency adversely affects thyroid metabolism and may reduce the efficacy of iodine prophylaxis in areas of endemic goiter. Objective: The aim of this study was to determine whether iron supplementation in goitrous iron-deficient children would improve their response to iodized salt. Design: We conducted a randomized double-blind placebo-controlled trial in 5-14-y-old children in Cote dIvoire. Goitrous iron deficient children (n = 166) consuming iodized salt (10-30 mg I/kg salt at the household level) were supplemented with either iron (60 mg Fe/d 4 d/wk for 16 wk) or placebo. At 0 1 6 12 and 20 wk we measured hemoglobin serum ferritin serum transferring receptor whole-blood zinc protoporphyrin thyrotropin thyroxine urinary iodine and thyroid gland volume (by ultrasonography). Results: Hemoglobin and iron status at 20 wk were significantly better after iron treatment than after placebo (P < 0.05). At 20 wk the mean reduction in thyroid size in the iron-treated group was nearly twice that in the placebo group (x ± SD percentage change in thyroid volume from baseline: -22.8 ± 10.7% compared with -12.7 ± 10.1%; P < 0.01). At 20 wk goiter prevalence was 43% in the iron-treated group compared with 62% in the placebo group (P < 0.02). There was no significant differences between groups in whole-blood thyrotropin or serum thyroxine at baseline or during the intervention. Conclusions: Iron supplementation improves the efficacy of iodized salt in goitrous children with iron deficiency. A high prevalence of iron deficiency among children in areas of endemic goiter may reduce the effectiveness of iodine prophylaxis. (authors)

The possibility of measuring thyroid hormones from blood dried on filter paper opened the way to identifying neonates with congenital hypothyroidism (CH) already in the first days of life. Consequently the early initiation of adequate replacement therapy opened the way to an effective prevention of mental retardation. Timely and complete specimen collection, transport logistics, rapid analysis and communication of results are key points for the organization of a CH newborn screening program. Close collaboration between laboratory and treating specialists is necessary to ensure an adequate treatment and follow-up of babies identified by CH screening programs. Topics for further investigations remain in the fields of which forms of CH should be identified by screening (only severe or also very mild forms) and on the long-term outcome of the individuals identified by CH screening.

The possibility of measuring thyroid hormones from blood dried on filter paper opened the way to identifying neonates with congenital hypothyroidism (CH) already in the first days of life. Consequently the early initiation of adequate replacement therapy opened the way to an effective prevention of mental retardation. Timely and complete specimen collection, transport logistics, rapid analysis and communication of results are key points for the organization of a CH newborn screening program. Close collaboration between laboratory and treating specialists is necessary to ensure an adequate treatment and follow-up of babies identified by CH screening programs. Topics for further investigations remain in the fields of which forms of CH should be identified by screening (only severe or also very mild forms) and on the long-term outcome of the individuals identified by CH screening.

Background: Several countries with long-standing salt iodization programs, including Switzerland, have recently reported declining and/or low urinary iodine (UI) levels in their populations. In Switzerland, in response to studies indicating low UI levels in children and pregnant women, the salt iodine level was increased in 1998 from 15 to 20 mg/kg. Objective: Our objective was to evaluate iodine nutrition in a national sample of Swiss school children and pregnant women 8–16 months after the increase in the salt iodine level. Design: A 3-stage probability proportionate to size cluster sampling method was used to obtain a representative national sample of 600 children aged 6–12 y and 600 pregnant women. We then measured UI in both groups, thyrotropin (TSH) in pregnant women and thyroid volume by ultrasound to determine goiter prevalence in school children. Results: The median UI (range) of the children and pregnant women was 115 μg/l (5–413) and 138 μg/l (5–1881), respectively. The median blood TSH concentration (range) of pregnant women was 0.6 mU/l (0.2–2.1). Based on the current WHO/ICCIDD normative data for thyroid volume, none of the children were goitrous, using either age/sex-specific or BSA/sex-specific cutoffs. Conclusions: The iodine status of the Swiss population is once again adequate, illustrating the value of periodic monitoring and prudent adjustments to the iodine level in salt. This approach could serve as a model for countries struggling to maintain dietary iodine intake in the face of shifting dietary habits and changes in the food supply. Sponsorship: Swiss Foundation for Nutrition Research, Zurich, Switzerland; Foundation for Micronutrients in Medicine, Rapperswil, Switzerland; and Swiss Federal Institute of Technology in Zurich, Switzerland. European Journal of Clinical Nutrition (2001) 55, 162–166

Objectives In 1994, WHO/International Council for the Control of Iodine Deficiency Disorders recommended replacing the WHO 1960 four-grade goiter classification with a simplified two-grade system. The effect of this change in criteria on the estimation of goiter prevalence in field studies is unclear. In areas of mild iodine deficiency disorders (IDD) where goiters are small, ultrasound is preferable to palpation to estimate goiter prevalence. However, in areas of moderate to severe IDD, goiter screening by palpation may be an acceptable alternative to thyroid ultrasound. To address these two issues, we compared WHO 1960 and 1994 criteria with thyroid ultrasound for determination of goiter prevalence in areas of mild and severe IDD in Morocco. Design A cross-sectional study of 400 six- to 13-year-old children from two mountain villages (Ait M'hamed and Brikcha) in rural Morocco was carried out. Methods Urinary iodine concentration (UI), whole blood TSH and serum thyroxine were measured. Thyroid size was graded by inspection and palpation by two examiners using both WHO 1960 and 1994 criteria. Thyroid volume was determined by ultrasound. Variation between examiners and examination methods was assessed. Sensitivity and specificity of the two classification systems compared with ultrasound were calculated. Results Median UIs in Ait M'hamed and Brikcha were 183 and 24 microg/l respectively. In Ait M'hamed, using 1960 and 1994 criteria, goiter prevalence was 21 and 26% respectively, compared with 13% by ultrasound. In Brikcha, with 1960 and 1994 criteria, goiter prevalence was 64 and 67% respectively, compared with 64% by ultrasound. Agreement between observers was better with the 1994 criteria than with the 1960 criteria in Ait M'hamed (kappa=0.53 and 0.47 respectively), while in Brikcha observer agreement was similar with the two systems (kappa=0.67). Using either the 1994 or 1960 criteria, agreement with ultrasound was only moderate in Ait M'hamed (kappa=0.41-0.44), but good in Brikcha (kappa=0.55-0.64). Overall, compared with ultrasound, sensitivity increased 3-4% using 1994 criteria, while specificity decreased 4-5%. Conclusions The WHO 1994 criteria are simpler to use than the 1960 criteria and provide increased sensitivity with only a small reduction in specificity. Agreement between observers is better with the 1994 criteria than with the 1960 criteria, particularly in areas of mild IDD. Like the 1960 criteria, the 1994 criteria overestimate goiter prevalence in areas of mild IDD, compared with ultrasound. However, the 1994 palpation criteria provide an accurate estimate of goiter prevalence in areas of severe IDD, and may be an acceptable and affordable alternative to thyroid ultrasound in these areas.

Objectives: To determine the efficacy of oral iodized oil in goitrous children who are both selenium (Se) and iodine deficient; to investigate if Se status modifies the response of iodine deficient, goitrous children to oral supplementation with iodized oil. Design: A longitudinal intervention trial. Setting: Two rural villages in the western Cote d'Ivoire. Subjects: 51 goitrous non-anemic schoolchildren with both iodine and Se deficiency. Intervention: Each child received an oral dose of 0.4 ml iodized poppyseed oil containing 200 mg of iodine. They were followed for 1 y with measurements of urinary iodine (UI), thyrotropin (TSH), thyroxine (T4), and thyroid volume by ultrasound. Results: At baseline all children were goitrous and Se deficient; median UI was 29 μg/l and mean serum Se (s.d.) was 14.8 (10.7) μg/l. After receiving iodized oil, thyroid volume decreased significantly vs baseline at 10, 15, 30 and 50 weeks (P

The developing countries many children are at high risk of goiter and iron deficiency anemia. Because iron deficiency can have adverse effects on thyroid metabolism iron deficiency may influence the response to supplemental iodine in areas of endemic goiter. The aim of this study was to determine whether goitrous children with iron deficiency anemia would respond to oral iodine supplementation. A trial of oral iodine supplementation was carried out in an area of endemic goiter in western Cote dIvoire in goitrous children (n = 109) aged 6-12 y. Group 1 (n = 53) consisted of goitrous children who were not anemic. Group 2 (n = 56) consisted of goitrous children who had iron deficiency anemia. At baseline thyroid gland volume and urinary iodine thyrotropin and thyroxine were measured by using ultrasound. Each child received 200 mg I orally and was observed for 30 wk during which urinary iodine thyrotropin thyroxine hemoglobin and thyroid gland volume were measured. The prevalence of goiter at 30 wk was 12% in group 1 and 64% in group 2. The mean percentage change from baseline in thyroid volume 30 wk after administration of oral iodine was 245.1% in group 1 and 221.8% in group 2 (P < 0.001). Among the anemic children there was a strong correlation between the percentage decrease in thyroid volume and hemoglobin concentration (r/2 = 0.65). The therapeutic response to oral iodine was impaired in goitrous children with iron deficiency anemia suggesting that the presence of iron deficiency anemia in children limits the effectiveness of iodine intervention programs. (authors)

We investigated the feasibility and diagnostic utility of genotyping 9 CYP21 mutations, linked chromosome 6p markers, and a dimorphic X-Y marker from neonatal screening samples. Blood-impregnated filter papers (Guthrie cards) from 603 randomly chosen New Zealand neonates were genotyped blind to 17-hydroxyprogesterone (17-OHP) levels. Another 50 samples from Swiss and North American infants with correlative hormonal data were also genotyped. DNA was extracted, and gene-specific PCR was performed. CYP21 PCR products were subjected to ligase detection reaction, simultaneously analyzing 9 CYP21 mutations; PCR products of other genes were subjected to direct gel analysis. CYP21 genotyping indicated a heterozygote rate of 2.8% for classic mutations (excluding CYP21 deletions), and 2.0% for nonclassic mutations in New Zealanders. Ten full-term affected neonates showed a wide range of 17-OHP levels (15–1400 nmol/L). Sick or preterm infants or infants screened on the first day of life with high 17-OHP proved genet...

We have described previously in the Finnish population an inactivating point mutation (566C-->T) in the human FSH receptor (FSHR) gene. In women, this mutation causes hypergonadotropic ovarian failure with arrest of follicular maturation and infertility, whereas in men, there is variable suppression of spermatogenesis, but no absolute infertility. To determine whether the same FSHR mutation occurs in other populations, its frequency was determined in Finland, Switzerland, Denmark, and the Chinese population of Singapore. The mutation was screened for using genomic DNA extracted from whole blood or dried blood spots. Exon 7 of the FSHR gene was first amplified using a pair of biotinylated primers. The PCR products were then immobilized on streptavidin-coated microtitration wells and hybridized using short allele-specific oligonucleotide probes labeled with europium. Time-resolved fluorometry was used for europium signal detection. To test the reliability of this method, 40 isolated DNA samples and 35 dried blood spot samples were blindly tested for the 566C-->T FSHR mutation. The analyses yielded identical results with denaturing gradient gel electrophoresis and allele-specific restriction enzyme digestion of the same samples, thus demonstrating the reliability of the tested method. Automation of this procedure allows the screening of large numbers of samples, which was subsequently carried out to investigate the frequency of the 566C-->T mutation in the study populations. A total of 4981 samples from the above-mentioned 4 countries were analyzed. The frequency of the 566C-->T mutation was 0.96% for all Finnish samples (n=1976), with a strong enrichment of the mutant allele in the northeastern part of the country. Only 1 mutation carrier was identified in the samples from Switzerland (n=1162), whereas none was found in samples from Denmark (n=1094) and the Singapore Chinese (n=540). These results suggest that the 566C-->T mutation of the FSHR gene is enriched in Finland, but is uncommon in other populations.

BACKGROUND The serum-eosinophil cationic protein level (S-ECP) has been promoted as a biomarker of asthma that reflects the degree of bronchial eosinophilic inflammation. PATIENTS AND METHODS To investigate whether S-ECP is indeed a clinically useful objective parameter, especially in mild or moderate chronic childhood asthma, we studied 100 outpatient children with chronic asthma symptoms (63 boys and 37 girls, aged three to 15 years, median of age eight) and 25 controls (12 boys and 13 girls aged three to 15 years, median of age eight). Symptom scores, lung function parameters and atopy were compared with S-ECP determined by commercially available tests and eosinophils measured by an autoanalyser. RESULTS Asthma symptom scores in the patient group ranged between one and 13 (median of 8), S-ECP between 2.1 and 75.6 microg/l (median of 13.3 microg/ l), and eosinophils between 30/microl and 2002/microl (median of 314). Symptom scores and S-ECP were correlated significantly (P < 0.001) as were symptom scores and eosinophils (P = 0.001). S-ECPs were significantly higher in children with chronic asthma symptoms compared with non-asthmatic, non-atopic children (P = 0.005 for non-atopic chronic asthmatics and P < 0.001 for atopic asthmatics); similar results were found comparing eosinophils in these groups. There was no difference in S-ECP between atopic and non-atopic asthmatic children, but the 25 polysensitised asthmatic children especially with sensitisations to mite, pollen and pet allergens were found to have significantly higher S-ECP compared to 15 monosensitised children (P = 0.002). Similar results were found when correlating eosinophil numbers with atopy. Polysensitised (mite, pollen, pet) asthmatics had significantly higher eosinophil counts compared with monosensitised (pollen) asthmatics (P = 0.01); there was, however, a better discrimination between atopic and non-atopic asthmatics (P = 0.001). Non-asthmatic, non-atopic controls had significantly lower eosinophil counts compared with asthmatics (P < 0.001 for both non-atopic and atopic asthmatics). No correlation between S-ECP or eosinophils and any of the lung function parameters measured (FEV1, FEV1/FVC, MEF50, airway resistance and ITGV) was found. SUMMARY Our data thus indicate that 1) S-ECP is higher than normal in children with asthma symptoms and correlates with asthma symptom score. 2) S-ECP is better correlated to symptom score than to lung function parameters especially in children with mild and moderate asthma symptoms. 3) Raised S-ECP appears to reflect the extent of allergen sensitivity and may also reflect current allergen exposure. 4) Similar correlations were seen when measuring eosinophil number by an autoanalyser instead of S-ECP. CONCLUSIONS Although S-ECP and eosinophils are not diagnostic of asthma they are useful inflammation markers especially in the context of clinical studies. However, both methods are not yet suitable for use in daily practice because they require extensive procedures and special equipment.

It is well established that insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3) and insulin are low in growth hormone deficiency, but due to their dependence on nutrition, they are elevated in healthy obese children. As the presence of growth hormone deficiency in Prader-Labhart-Willi syndrome (PWS) is still controversial, we studied insulin, IGF-I and IGFBP-3 levels in 19 children with PWS (age range 0.5-14.6 years). Serum concentrations of insulin (SDS: -0.7+/-0.9, P = 0.01) and IGF-I (SDS: -0.7+/-0.8, P = 0.002) were low, but IGFBP-3 (SDS: -0.3+/-1.2, P = 0.2) was normal compared to normal weight age-matched children. Since children with PWS are typically obese, insulin, IGF-I and IGFBP-3 levels should be compared to normal obese children who present increased levels of these hormones. In comparison to data of healthy obese children reported in the literature, not only IGF-I, but also IGFBP-3 levels are low and fasting insulin levels even very low, suggesting a growth hormone deficiency.

Twelve children with documented Prader-Labhart-Willi syndrome were treated with human growth hormone (24 U/m2/week) during 1 year. The children were divided into three groups: group 1: overweight and prepubertal (n = 6, age 3.8-7.0 years); group 2: underweight and prepubertal (n = 3, age 0.6-4.1 years); group 3: pubertal (n = 3, age 9.2-14.6 years). In group 1, height increased from -1.7 SD to -0.6 SD, while weight decreased from 1.1 SD to 0.4 SD, with a dramatic drop in weight for height from 3.8 SD to 1.2 SD. Hand length increased from -1.5 SD to -0.4 SD and foot length from -2.5 SD to -1.4 SD. Body fat, measured by dual X-ray energy absorptiometry, dropped by a third, whereas muscle mass increased by a fourth. Physical capability (Wingate test) improved considerably. The children were reported to be much more active and capable. In group 2, similar changes were seen, but weight for height increased, probably because muscle mass increase exceeded fat mass decrease. Changes in group 3 were similar as in group 1, even though far less distinct. Conclusion: Growth hormone treatment in Prader-Labhart-Willi syndrome led to dramatic changes: distinct increase in growth velocity, height and muscle mass, as well as an improvement in physical performance. Fat mass and weight for height decreased in the initially overweight children, and weight for height increased in underweight children

The new genetic screening processor for newborn screening (GSP™) from PerkinElmer was extensively tested under routine conditions. The GSP is intended to fully process all newborn screening tests, apart from tandem mass spectrometry. For our evaluation we used all so far available tests for the GSP (TSH, 17-OHP, IRT, total-T4 and GALT). For all 5 tests we have determined specificity, limit of detection (LOD), limit of quantitation (LOQ), intra- and inter-assay variation, recovery, influence of EDTA and on-board stability of the reagents. Results were also compared with AutoDelfia and the Astoria Pacific Spot Check System (GALT). LOD and LOQ were 0.38 and 0.45 mU L−1 (blood) for TSH, 1.30 and 3.25 nmol L−1 (serum) for T4, 0.35 and 0.55 nmol L−1 (blood) for 17-OHP, 0.85 and 1.58 ng mL−1 (blood) for IRT and 2.6 and 3.6 U dL−1 (blood) for GALT. Mean recovery was 97.8–107.1%: intra-assay CVs 2.5–8.9; inter-assay CVs 5.7–11.0. On board stability was >37 days for the immunoassay. The dissolved GALT reagent is not stable at 4 °C, however if the reagent is removed from the GSP and stored at −18 °C, it is stable for 11 days. On board stability of the inducer is >140 days. The GSP is suitable for routine newborn screening. Compared to AutoDelfia, additional control procedures were included which increase the reliability of the system.

Most newborn screening laboratories use CE-marked or FDA-approved test-kits, like in routine clinical chemistry. National regulations require only minimal evaluation from the customer, if the test-kits are used as specified by the manufacturer. The microtiter-based kit-concept is often based on the perception, that the laboratory always processes whole microtiter plates. However, in the daily routine, this is rather a rare exception, which leads to much higher costs per newborn, compared to the costs per assay in the test-kits. In addition the amount of wasted resources is quite high. Performance of the Neonatal Total Galactose kit from Perkin Elmer was tested. We have determined specificity, limit of detection (LOD), limit of quantitation (LOQ), intra and inter assay variation, recovery, stability of measuring signal and reagents. Results were also compared with the Astoria Pacific Spot Check System. In addition, we had (by chance) the opportunity to test 2 kits, which were already expired for more than 3 years. LOD was 165 - 306 μmol/L and LOQ 475 - 703 μmol/L, depending on the definition of LOD/LOQ. Mean recovery was 112.8%, intra assay CVs were 11.3, 7.3, 4.0, and 3.0, and inter assay CVs 28.7, 15.9, 7.8, and 9.3, at 220, 590, 1200, and 2060 μmol/L respectively. Reconstituted and mixed reagents must be used within some hours, and were unstable even if stored at -20℃. However, if the reconstituted galactose substrate reagent and galactose oxidase reagent were only mixed according to the daily requirements, and the rest stored separately at -20℃, they were stable for at least 12 days. The performance of the expired test-kits did not differ from the others. The performance of the Total Galactose kit is comparable to other tests used for newborn screening. However, we could significantly reduce the costs per newborn and reduce unnecessary production of waste, by thorough validation and modification of the assay procedures.

In a Swiss screening programme for detection of congenital adrenal hyperplasia (CAH), 27 of over 120,000 newborns examined from 1992 to 1994 were further studied because of persistingly high 17 alpha hydroxyprogesterone (17OHP). Out of 27, 11 were later confirmed to have CAH by specific gas chromatography of urinary steroids and ACTH test at age 3-4 months. Of 27, 11 were born at term (7 confirmed 21-hydroxylase deficiency, one 11 beta-hydroxylase deficiency). Out of 27, 16 were preterm newborns. Of them, only 2 were confirmed to have CAH (one 21-, one 11 beta-hydroxylase deficiency). In 3 cases with high 17OHP, but later not confirmed CAH, what appeared to be a pregnanetriolone peak in the gas chromatograms was shown to be 3 beta, 15 beta, 17 alpha-pregnenetriol. This compound may be misleading in confirming the diagnosis of CAH. 15 beta-Hydroxylated compounds occur in fetuses, neonates, and amniotic fluid. Since human tissues do not have 15 beta-hydroxylating capacity, their origin is unclear. However, since some bacteria (Bacillus megatherium) and mycelial fungi (fusaria) are known to hydroxylate steroids in position 15 beta, it is likely that this compound is formed by micro-organisms in the enterohepatic circulation of newborns or their mothers.For the confirmation of the diagnosis of CAH in cases suspected by screening, later ACTH stimulation and specific steroid analysis are necessary.

Summary: Electrospray ionization tandem mass spectrometry is a widely applied method for the analysis of acylcarnitines in blood samples spotted on filter paper cards (Guthrie cards). When the filter paper cards are contaminated by EMLA cream, highly intense signals at m/z 221 and 235 are detected under ESI-MS/MS conditions, monitoring for precursors of m/z 85. These signals correspond to the active ingredients prilocaine and lidocaine in EMLA and overlap with the signals from the isotopically labelled internal standards (2H3)propionyl carnitine and (2H3)butyrylcarnitine. This interference prevents the proper quantification of the two short-chain acylcarnitines when samples are analysed without derivatization.

Introduction: Newborn screening for congenital adrenal hyperplasia (CAH) was introduced as a pilot program nationwide in Switzerland (two laboratories) and regionally in Berlin (one laboratory) during 1990. The coverage of all live-births has been >;99%. Methods: A total number of 89 129 newborns were screened by measuring the concentration of 17α-hydroxyprogesterone (17α-OHP) in dried filter paper blood spots taken between the third and fifth day of life. The method used was a sensitive fluoroimmunoassay (DELFIA), which does not require extraction of the samples. Results: Seven cases of CAH were discovered during the pilot study period. Four were females and three were males. Initially, there was a high number of recall examinations, mainly in preterm babies, when a cut-off value of 20 nmol/l blood was used. Subsequently, gestational age adjusted cut-off limits were established for preterm babies using as a limit the 97th percentile of the 17α-OHP concentrations of each group of gestational ages. Using these cut-off limits, the recall rate dropped to 0.2%. Discussion: Introduction of the age adjusted cut-off levels not only increases the cost benefit of screening for CAH by reducing the costs for clinical examinations and overhead expenses for the recall procedure, but also reduces the amount of parental anxiety that is produced by a positive screening result and by requests for an additional specimen.

A preliminary survey has been made of quality assurance programs in newborn screening. These have been summarized according to the contact information for the program, the distribution characteristics of the program, the reporting characteristics of the program and the analytes covered.

Blood sampling for newborn screening cannot be standardized as for example blood collection in adults after an overnight fast. Therefore the influence of postprandial changes and individual variation is valuable information for the assessment of sensitivity and specificity of newborn screening for certain disorders. We have analyzed 92 pairs of dried blood samples taken pre- and one hour postprandially, respectively. We have determined the mean increase in metabolite concentration and calculated its significance. Individual variation after an overnight fast in healthy adults (n = 3) was between 12 and 32% (SD). Postprandial increases of acylcarnitines were mostly not significant and not exceeding 10%. Postprandial increase of amino acids was highly significant for most proteinogenic amino acids, but not for all. With the collected data we were able to estimate that mainly decreased levels of methionine and, to a lesser extent, of free carnitine could be "masked" by postprandial increases of the respective metabolites, and could therefore lead to false negative results for the detection of disorders of cobalamin metabolism and carnitine transporter deficiency.

Eight growth-hormone-deficient children were treated with recombinant human GH (rhGH). Results of the short-term metabolic response to rhGH performed at the start of therapy during a 5-day introduction period and long-term results on growth were analyzed. We could not find any correlation between the effects on the short-term metabolic test and the growth response during long-term therapy, namely between the urea and insulin-like growth factor-I response during the short test and the increase in growth velocity. The short-term test is not a good predictor of the long-term response.

There is wide agreement on the benefits of NBS for CF in terms of lowered disease severity, decreased burden of care, and reduced costs. Risks are mainly associated with disclosure of carrier status and diagnostic uncertainty. When starting a NBS programme for CF it is important to take precautions in order to minimise avoidable risks and maximise benefits.In Europe more than 25 screening programmes have been developed, with quite marked variation in protocol design. However, given the wide geographic, ethnic, and economic variations, complete harmonisation of protocols is not appropriate. There is little evidence to support the use of IRT alone as a second tier, without involving DNA mutation analysis. However, if IRT/DNA testing does not lead to the desired specificity/sensitivity ratio in a population, a screening programme based on IRT/IRT may be used.Sweat chloride concentration remains the gold standard for discriminating between NBS false and true positives, but age-related changes in sweat chloride should be taken into account. CF phenotypes associated with less severe disease often have intermediate or normal sweat chloride concentrations. Programmes should include arrangements for counselling and management of infants where the diagnosis is not clear-cut.All newborns identified by NBS should be managed according to internationally accepted guidelines. CF centre care and the availability of necessary medication are essential prerequisites before the introduction of NBS programmes.Clear explanation to families of the process of screening and of implications of normal and abnormal results is central to the success of CF NBS programmes. Effective communication is especially important when parents are told that their child is affected or is a carrier. When establishing a NBS programme for CF, attention should be given to ensuring timely and appropriate processing of results, to minimise potential stress for families.

We aim to determine long-term intellectual outcome of adolescents with early high-dose treated congenital hypothyroidism (CH). Sixty-three prospectively followed children with CH were assessed at age of 14 y with the Wechsler Intelligence Scale for Children-Revised and compared with 175 healthy controls. Median age at onset of treatment was 9 d (range 5-18 d) and median starting dose of levothyroxine (L-T4) was 14.7 microg/kg/d (range 9.9-23.6 microg/kg/d). Full-scale intelligence quotient (IQ) was significantly lower than in controls after adjustment for socioeconomic status (SES) and gender (101.7 versus 111.4; p < 0.0001). Children with athyreosis had a lower performance IQ than those with dysgenesis (adjusted difference 7.6 IQ scores, p < 0.05). Lower initial thyroxine (T4) levels correlated with poorer IQ (r = 0.27, p = 0.04). Lower SES was associated with poorer IQ, in particular in children with CH (interaction, p = 0.03). Treatment during childhood was not related to IQ at age 14 y. Adolescents with CH manifest IQ deficits when compared with their peers despite early high-dose treatment and optimal substitution therapy throughout childhood. Those adolescents with athyreosis and lower SES are at particular risk for adverse outcome. Therefore, early detection of intellectual deficits is mandatory in children with CH.

AIMS: Amniotic infection (AI) and preeclampsia (PE), which are commonly the reason for prematurity, inflict stress of different duration on immature fetuses. Whether chronic stress, as reflected by intrauterine growth retardation, influences the level of 17-OH progesterone (17-OHP), was not previously examined. METHODS: We analyzed 17-OHP and TSH levels during neonatal screenings in the first hours of life of 90 premature infants born between 25 and 33 weeks of gestation in infants with AI (n=37) or with PE (n=53). Control of acute stress parameters was derived from umbilical arterial cord blood pH and base excess (BE). RESULTS: Mean 17-OHP levels of infants born to mothers with PE were 85.7 nmol/L compared to 54.6 nmol/L (P

Transdermal 17 beta-oestradiol administration (17 beta-E2), used mainly in menopausal women, allows a continuous 17 beta-E2 delivery through the skin into the systemic circulation, avoiding intestinal and hepatic passage. In order to explore whether transdermal 17 beta-E2 could be used for the induction of puberty, 17 beta-E2 patches with low dose delivery were administered in nine prepubertal girls with Turner syndrome (bone age greater than 10.5 years) for a mean period of 2.2 years. Treatment schedule: 5 micrograms/day for 6-9 months, 10 micrograms/day for 6-9 months, 25 micrograms/day for long-term substitution; addition of cyclic gestagen p.o. after 18-24 months. Breast development started within 3 months of therapy and menstruation occurred after 2 years. Growth rate increased from 3.2 to 5.0 cm/year during the 1st year of therapy, height prediction did not change. Serum oestradiol (E2) and urinary E2 conjugates increased proportionally with 17 beta-E2 doses, serum oestrone (E1) rose much less. The possibility to imitate time course, clinical events and hormonal changes of normal puberty, the absence of adverse drug reactions and the excellent acceptance and easy mode of application suggest that transdermal 17 beta-E2 is optimally suited for hormonal substitution in girls with hypogonadism.

Summary: Congenital adrenal hyperplasia is a group of autosomal recessive disorders resulting from the deficiency of one of the five enzymes required for the synthesis of cortisol in the adrenal cortex. The most frequent is steroid 21-hydroxylase deficiency, accounting for more than 90% of cases. Much has been learned about the genetics of the various clinical forms of 21-hydroxylase deficiency, and correlations between the genotype and the phenotype have been studied extensively. Gene-specific diagnosis is now feasible and neonatal screening and prenatal treatment have been widely implemented. This discussion will be limited to the most common form of congenital adrenal hyperplasia, with focus on the diagnostic advances in this disease

Objectives Newborn screening (NBS) for cystic fibrosis (CF) was introduced in Switzerland in 2011, based on IRT-DNA-IRT protocol. It aims to detect all children with classical CF, but to avoid identifying children with equivocal disease, called “CF screen positive, inconclusive diagnosis” (CFSPID). Here we evaluate the program describing the proportion of false negatives and the detection of CFSPID. Methods We analysed data from the national CF screening database, including all children born between January 2011 and November 2014. Children with positive screening results were referred to a CF centre for a sweat test and faecal elastase. We assessed initial IRT tests, screening results and the final diagnoses of the children. In addition, we determined the proportion of false negatively screened children and calculated the ratio CF:CFSPID. Results Within 4 years, 338,851 IRT tests were performed. In total, 364 children were screened positive and referred to a CF centre for further examination. 98 children (27% of 364) were diagnosed with CF, 13 (4%) had CFSPID, 250 (69%) were found to have no CF, and 3 (1%) were lost to follow up. In addition, 6 children with a negative screening result were clinically diagnosed with CF (5.8% false negatives – 6/104), one of them because a second heel prick test was never taken. The ratio CF:CFSPID overall was 8:1 [2011 9:1 (28/3); 2012 4:1 (26/6); 2013 21:1 (21/1) and 2014 8:1 (23/3)]. Conclusion The Swiss newborn screening program for CF performed well. False negative results are in the expected range and the ratio CF:CFSPID is acceptable. However, to increase the CF:CFSPID ratio further monitoring and adaptations are required.

This study aimed to estimate the number of infants who died of unrecognized congenital adrenal hyperplasia (CAH) in Austria and the Czech Republic within the past 13 years, before the introduction of adequate neonatal screening. The study was based on retrospective analysis of neonatal screening cards of 242 infants who died suddenly between 7 days and 12 months of age and whose cause of death could not be identified. 17-hydroxyprogesterone (17-OHP) was measured by fluoroimmunoassay and positive samples were subsequently genotyped. Three infants out of 242 may have had unrecognized CAH due to CYP21 (steroid 21-hydroxylase) gene defect. Their newborn 17-OHP levels and CYP21 genotypes were 706 nmol/l and del/conv//del/conv, 53 nmol/l and I2//I2, and 811 nmol/l and I2//Gln318stop, respectively. CAH due to CYP21 defect can lead to sudden unexpected death without prior symptoms typical for the condition. Hence, newborn screening would have prevented these deaths had it been available. In addition, we have shown that the I2 point mutation that is expected to lead to simple virilizing form may lead to a fatal outcome.

In developing countries, children are at high risk for both the iodine deficiency disorders (IDD) and vitamin A deficiency (VAD). The study aim was to determine the effects of VAD and vitamin A (VA) supplementation on thyroid function in an area of endemic goiter. In a double-blind, randomized, 10-month trial, Moroccan children with IDD and VAD (n = 138) were given iodized salt and either VA (200,000 IU) or placebo at 0 and 5 months. At 0, 5, and 10 months, measurements of VA status and thyroid function were made. At baseline, increasing VAD severity was a predictor of greater thyroid volume and higher concentrations of TSH and thyroglobulin (P < 0.001). In children with VAD, the odds ratio for goiter was 6.51 (95% confidence interval, 2.94, 14.41). VAD severity was also a strong predictor of higher concentrations of total T(4) (P < 0.001); the odds ratio for hypothyroidism in VAD was 0.06 (95% confidence interval, 0.03, 0.14). During the intervention, mean thyroglobulin, median TSH, and the goiter rate significantly decreased in the VA-treated group compared with those in the placebo group (P < 0.01). The findings indicate that VAD in severely IDD-affected children increases TSH stimulation and thyroid size and reduces the risk for hypothyroidism. This effect could be due to decreased VA-mediated suppression of the pituitary TSHbeta gene. In IDD- and VAD-affected children receiving iodized salt, concurrent VA supplementation improves iodine efficacy.

To determine if introduction of iodized salt induces thyroid autoimmunity in goitrous children, we conducted a prospective trial in iodine-deficient Moroccan schoolchildren (n = 323). Local salt was iodized at 25 microg iodine per gram of salt and distributed to households. Before introduction of iodized salt and at 10, 20, 40, and 52 weeks, we measured antithyroid peroxidase antibodies (TPO-Ab), antithyroglobulin antibodies (Tg-Ab), urinary iodine (UI), and thyroid hormones, and examined the thyroid using ultrasound. At baseline, median UI was 17 microg/L and the prevalence of goiter and hypothyroidism was 72% and 18%, respectively. Provision of iodized salt maintained median UI at 150-200 microg/L for the year (p0.0001). There was a significant increase in mean total thyroxine (T(4)) and a significant reduction in the prevalence of hypothyroidism (p0.001). There was a transient increase in the prevalence of detectable antibodies after introduction of iodized salt (p0.0001) with levels returning to baseline at 1 year. Only congruent with 1% of children had elevated TPO-Ab and none had elevated Tg-Ab over the course of the study, and no child with elevated TPO-Ab had abnormal thyrotropin (TSH) or T(4) concentrations. None developed clinical or ultrasonographic evidence of thyroid autoimmune disease and/or iodine-induced hypothyroidism or hyperthyroidism. Rapid introduction of iodized salt does not provoke significant thyroid autoimmunity in severely iodine-deficient children followed for 1 year.

Background: In many developing countries children are at high risk of both goiter and iron deficiency anemia. Objective: In a series of studies in northern Morocco we developed and tested a dual-fortified salt (DFS) containing iodine and microencapsulated iron. Design: To establish the DFS fortification concentration we measured salt intake by 3-d weighed food records and estimated iron bioavailability from the local diet by using published algorithms. We then formulated a DFS containing 25 aeg iodine/g salt (as potassium iodide) and 1 mg iron/g salt (as ferrous sulfate hydrate encapsulated with partially hydrogenated vegetable oil). After storage and acceptability trials we compared the efficacy of the DFS to that of iodized salt in a 9-mo randomized double-blind trial in iodine-deficient 6-15-y-old children (n=377). Results: Mean salt intake in school-age children was 7-12 g/d and estimated iron bioavailability from the local diet was 0.4-4.3%. After storage for 20 wk the DFS and iodized salt were not significantly different in iodine content and color stability was acceptable when the compounds were added to local meals. During the efficacy trial urinary iodine concentrations and thyroid volumes improved significantly (P < 0.001 an < 0.05 respectively) from baseline in both groups. At 40 wk mean hemoglobin concentrations in the DFS group had increased by 14 g/L (P

OBJECTIVE: In many developing countries, children are at high risk for both goiter and anemia. Iron (Fe) deficiency adversely effects thyroid metabolism and reduces efficacy of iodine prophylaxis in areas of endemic goiter. The study aim was to determine if co-fortification of iodized salt with Fe would improve efficacy of the iodine in goitrous children with a high prevalence of anemia. DESIGN AND METHODS: In a 9-month, randomized, double-blind trial, 6-15 year-old children (n=377) were given iodized salt (25 microg iodine/g salt) or dual-fortified salt with iodine (25 microg iodine/g salt) and Fe (1 mg Fe/g salt, as ferrous sulfate microencapsulated with partially hydrogenated vegetable oil). RESULTS: In the dual-fortified salt group, hemoglobin and Fe status improved significantly compared with the iodized salt group (P

Background/Aim: Since hyperandrogenism in simple obesity is assumed to arise from hyperinsulinism and/or increased insulin-like growth factor I (IGF-I) or leptin levels, we examined how in patients with Prader-Willi syndrome (PWS), the most frequent form of syndromal obesity, the accelerated adrenarche can be explained despite hypothalamic-pituitary insufficiency with low levels of insulin and IGF-I. Methods: In 23 children with PWS and a mean age of 5.6 years, height, weight, fat mass, fasting insulin concentration, insulin resistance (by HOMA-R; see text), and leptin and IGF-I levels were determined to test whether they explain the variance of the levels of dehydroepiandrosterone (DHEA) and its sulfate (DHEAS), of androstenedione, and of cortisol before and during 42 months of therapy with growth hormone. Results: The baseline DHEAS, DHEA, and androstenedione concentrations were increased as compared with age-related reference values, whereas the cortisol level was always normal. During growth hormone treatment, the DHEA concentration further rose, and the cortisol level decreased significantly. The insulin and IGF-I concentrations were low before therapy, while fat mass and leptin level were elevated. The hormonal covariates provided alone or together between 24 and 60% of the explanation for the variance of adrenal androgen levels, but the anthropometric variables did not correlate with them. Conclusions: In children with PWS, elevated androgen levels correlate with hormones that are usually associated with adiposity. However, the lack of direct correlations between disturbed body composition and androgen levels as well as the increased sensitivity to insulin and IGF-I are abnormalities specific to PWS, potentially caused by the underlying hypothalamic defect.

I. Valaskova1,2,3, J. Necasova1, R.M. Selingerova1, R. Spesna1, A. Holcikova4, L. Homola4, E. Pokojova5, R. Gaillyova1,2,3. 1University Hospital, Medical Genetics, Brno, Czech Republic; 2Masaryk University, Faculty of Medicine, Department of Biology, Brno, Czech Republic; 3Masaryk University, Faculty of Medicine, Department of Laboratory Methods, Brno, Czech Republic; 4University Hospital, Clinic of Pediatric Infectious Diseases, Brno, Czech Republic; 5University Hospital, Department of Pulmonary Diseases and Tuberculosis, Brno, Czech Republic