Congenital Adrenal Hyperplasia with Non-functional Mutations in Both Alleles in a Clinically Unaffected Infant.

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.

Neonatal screening for congenital hypothyroidism.

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.

European Society for Paediatric Endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism.

OBJECTIVE: The aim was to formulate practice guidelines for the diagnosis and management of congenital hypothyroidism (CH). EVIDENCE: A systematic literature search was conducted to identify key articles relating to the screening, diagnosis, and management of CH. The evidence-based guidelines were developed with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system, describing both the strength of recommendations and the quality of evidence. In the absence of sufficient evidence, conclusions were based on expert opinion. CONSENSUS PROCESS: Thirty-two participants drawn from the European Society for Paediatric Endocrinology and five other major scientific societies in the field of pediatric endocrinology were allocated to working groups with assigned topics and specific questions. Each group searched the literature, evaluated the evidence, and developed a draft document. These papers were debated and finalized by each group before presentation to the full assembly for further discussion and agreement. RECOMMENDATIONS: The recommendations include: worldwide neonatal screening, approaches to assess the cause (including genotyping) and the severity of the disorder, the immediate initiation of appropriate L-T4 supplementation and frequent monitoring to ensure dose adjustments to keep thyroid hormone levels in the target ranges, a trial of treatment in patients suspected of transient CH, regular assessments of developmental and neurosensory functions, consulting health professionals as appropriate, and education about CH. The harmonization of diagnosis, management, and routine health surveillance would not only optimize patient outcomes, but should also facilitate epidemiological studies of the disorder. Individuals with CH require monitoring throughout their lives, particularly during early childhood and pregnancy.

European Society for Paediatric Endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism.

OBJECTIVE: The aim was to formulate practice guidelines for the diagnosis and management of congenital hypothyroidism (CH). EVIDENCE: A systematic literature search was conducted to identify key articles relating to the screening, diagnosis, and management of CH. The evidence-based guidelines were developed with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system, describing both the strength of recommendations and the quality of evidence. In the absence of sufficient evidence, conclusions were based on expert opinion. CONSENSUS PROCESS: Thirty-two participants drawn from the European Society for Paediatric Endocrinology and five other major scientific societies in the field of pediatric endocrinology were allocated to working groups with assigned topics and specific questions. Each group searched the literature, evaluated the evidence, and developed a draft document. These papers were debated and finalized by each group before presentation to the full assembly for further discussion and agreement. RECOMMENDATIONS: The recommendations include: worldwide neonatal screening, approaches to assess the cause (including genotyping) and the severity of the disorder, the immediate initiation of appropriate L-T4 supplementation and frequent monitoring to ensure dose adjustments to keep thyroid hormone levels in the target ranges, a trial of treatment in patients suspected of transient CH, regular assessments of developmental and neurosensory functions, consulting health professionals as appropriate, and education about CH. The harmonization of diagnosis, management, and routine health surveillance would not only optimize patient outcomes, but should also facilitate epidemiological studies of the disorder. Individuals with CH require monitoring throughout their lives, particularly during early childhood and pregnancy.

One-year evaluation of a neonatal screening program for cystic fibrosis in Switzerland.

BACKGROUND: From January 2011 onward, the Swiss newborn screening (NBS) program has included a test for cystic fibrosis (CF). In this study, we evaluate the first year of implementation of the CF-NBS program. METHODS: The CF-NBS program consists of testing in two steps: a heel prick sample is drawn (= Guthrie test) for measurement of immunoreactive trypsinogen (IRT) and for DNA screening. All children with a positive screening test are referred to a CF center for further diagnostic testing (sweat test and genetic analysis). After assessment in the CF center, the parents are given a questionnaire. All the results of the screening process and the parent questionnaires were centrally collected and evaluated. RESULTS: In 2011, 83 198 neonates were screened, 84 of whom (0.1%) had a positive screening result and were referred to a CF center. 30 of these 84 infants were finally diagnosed with CF (positive predictive value: 35.7%). There was an additional infant with CF and meconium ileus whose IRT value was normal. The 31 diagnosed children with CF correspond to an incidence of 1 : 2683. The average time from birth to genetically confirmed diagnosis was 34 days (range: 13-135). 91% of the parents were satisfied that their child had undergone screening. All infants receiving a diagnosis of CF went on to receive further professional care in a CF center. CONCLUSION: The suggested procedure for CF-NBS has been found effective in practice; there were no major problems with its implementation. It reached high acceptance among physicians and parents.

Newborn screening for cystic fibrosis in Switzerland--consequences after analysis of a 4 months pilot study.

BACKGROUND: Switzerland introduced newborn screening (NBS) for CF in 2011, using an IRT/DNA/IRT protocol. This paper describes the results of the first year and compares two versions of the protocol with different IRT cut-offs, particularly effects on recall rate, sensitivity and specificity. METHODS: IRT cut-offs were >45 ng/ml (99.0th percentile) in period 1 (months 1-4) and >50 ng/ml (99.2nd percentile) in period 2 (months 5-12). In period 2 we abstained from recalls when none of the 7 most common CF mutations were detected and IRT was <60 ng/ml. RESULTS: In periods 1 and 2, 26,535 and 56,663 tests were performed. Recall rates were 0.94% and 0.48%, respectively (p<0.001), PPV increased from 23% to 47% (p=0.024) and sensitivity was 90% and 100%. CONCLUSIONS: Raising initial IRT cut-off from the 99.0th to the 99.2nd percentile and abstaining from recalls for children with an IRT<60 ng/ml and carrying no major CFTR mutation significantly reduced the recall rate without affecting sensitivity.

Retrospective analysis of stored dried blood spots from children with cystic fibrosis and matched controls to assess the performance of a proposed newborn screening protocol in Switzerland.

BACKGROUND: Newborn screening (NBS) for Cystic Fibrosis (CF) has been introduced in many countries, but there is no ideal protocol suitable for all countries. This retrospective study was conducted to evaluate whether the planned two step CF NBS with immunoreactive trypsinogen (IRT) and 7 CFTR mutations would have detected all clinically diagnosed children with CF in Switzerland. METHODS: IRT was measured using AutoDELFIA Neonatal IRT-Kit in stored NBS cards. RESULTS: Between 2006 and 2009, 66 children with CF were reported, 4 of which were excluded for various reasons (born in another country, NBS at 6 months, no informed consent). 98% (61/62) had significantly higher IRT compared to matched control group. There was one false negative IRT result in an asymptomatic child with atypical CF (normal pancreatic function and sweat test). CONCLUSIONS: All children but one with atypical CF would have been detected with the planned two step protocol.

Postprandial changes of amino acid and acylcarnitine concentrations in dried blood samples.

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.

European best practice guidelines for cystic fibrosis neonatal screening.

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.

Children with congenital hypothyroidism: long-term intellectual outcome after early high-dose treatment.

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.

17-Hydroxyprogesterone in premature infants as a marker of intrauterine stress.

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<0.001) in AI infants. 17-OHP was even higher when intrauterine growth restriction was present (99.8 nmol/L). Antenatal steroids and mode of delivery did not significantly affect 17-OHP levels. CONCLUSIONS: Stress of relatively long duration, as in cases of PE, leads to a significant increase of 17-OHP level in preterm infants. The postnatal 17-OHP level may be considered as a measure for severity of intrauterine stress and might be used as an individualized indicator for earlier intensive care.

Prevalence of congenital adrenal hyperplasia among sudden infant death in the Czech Republic and Austria.

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.

Assessment of iodine status using dried blood spot thyroglobulin: development of reference material and establishment of an international reference range in iodine-sufficient children.

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 microg/liter, respectively. In the intervention, before introduction of iodized salt, median DBS-Tg was 49 microg/liter, and more than two thirds of children had DBS-Tg values greater than 40 microg/liter. After 5 and 10 months of iodized salt use, median DBS-Tg decreased to 13 and 8 microg/liter, respectively, and only 7 and 3% of children, respectively, had values greater than 40 microg/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.

Increasing the iodine concentration in the Swiss iodized salt program markedly improved iodine status in pregnant women and children: a 5-y prospective national study.

BACKGROUND: 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. OBJECTIVE: We evaluated Swiss iodine nutrition after the 1999 increase in the salt iodine concentration. DESIGN: 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. RESULTS: 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 (P < 0.01). Newborn thyrotropin concentrations >5 mU/L decreased from 2.9% in 1992-1998 (n = 259 035) to 1.7% in 1999-2004 (n = 218 665) (P < 0.0001). CONCLUSIONS: 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 concentrations >5 mU/L appears to be a sensitive indicator of iodine nutrition during pregnancy.

The effects of vitamin A deficiency and vitamin A supplementation on thyroid function in goitrous children.

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.

Dual fortification of salt with iodine and micronized ferric pyrophosphate: a randomized, double-blind, controlled trial.

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 microg I (as potassium iodate)/g salt and 2 mg Fe (as micronized ferric pyrophosphate; mean particle size = 2.5 microm)/g salt. After storage and acceptability trials, we compared the efficacy of the dual-fortified 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 approximately 18 mg Fe/d; iron absorption was estimated to be approximately 2%. 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.

Rapid relapse of thyroid dysfunction and goiter in school-age children after discontinuation of salt iodization.

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.

Quality control requirements in neonatal screening.

UNLABELLED: 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. CONCLUSIONS: 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.

Development of a dried whole-blood spot thyroglobulin assay and its evaluation as an indicator of thyroid status in goitrous children receiving iodized salt.

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.