Permanent Primary Congenital Hypothyroidism Research Articles

Follow-up of infants with congenital hypothyroidism and low total thyroxine/thyroid stimulating hormone on newborn screen.

PurposeNewborn screening (NBS) methods to detect congenital hypothyroidism (CH) vary regarding whether total thyroxine (T4), thyroid stimulating hormone (TSH), or both are measured. Neonates with low T4 and normal or low TSH (lowT4/TSH) may only be detected by T4-inclusive methods or age-dependent repeat screens. Premature neonates and those with pituitary-hypothalamic disorders frequently manifest lowT4/TSH.MethodsThis is a retrospective case-study of newborns who were screen-positive for lowT4/TSH in Alabama in 2009–2016 using a combined T4 and TSH method and 2 routine NBS. The clinical, laboratory, and final diagnosis after 3 years were determined.ResultsOver 8 years, 225 infants were referred to our institution for evaluation and treatment of CH. Twelve infants were screen-positive for lowT4/TSH by first or second NBS. Four of the 12 infants had permanent CH (30%): 2 with primary and 2 with central etiologies. One infant with moderately severe central CH was only detected by the routine second NBS. Six of 7 premature infants had elevated TSH on serum confirmation labs consistent with a delay in hypothalamic-pituitary maturation, yet 2 of these patients were later established to have permanent primary CH. While most cases of lowT4/TSH resolved by 3 years of age, several neonates had extended periods of moderate to severe hypothyroxinemia prior to detection and treatment.ConclusionsOne third of the infants with lowT4/TSH on NBS in this study had permanent CH. These results emphasize the importance of T4-based assay methods, subsequent (repeat) screens and long-term follow-up in the management of neonates with lowT4/TSH on newborn screen.

Mutation screening in the genes PAX-8, NKX2-5, TSH-R, HES-1 in cohort of 63 Brazilian children with thyroid dysgenesis.

To evaluate the candidate genes PAX-8, NKX2-5, TSH-R and HES-1 in 63 confirmed cases of thyroid dysgenesis. Characterization of patients with congenital hypothyroidism into specific subtypes of thyroid dysgenesis with hormone levels (TT4 and TSH), thyroid ultrasound and scintigraphy. DNA was extracted from peripheral blood leukocytes and the genetic analysis was realized by investigating the presence of mutations in the transcription factor genes involved in thyroid development. No mutations were detected in any of the candidate genes. In situ thyroid gland represented 71.1% of all cases of permanent primary congenital hypothyroidism, followed by hypoplasia (9.6%), ectopia (78%), hemiagenesis (6.0%) and agenesis (5.5%). The highest neonatal screening TSH levels were in the agenesis group (p < 0.001). Thyroid dysgenesis is possibly a polygenic disorder and epigenetic factors could to be implicated in these pathogeneses.

Etiological evaluation of primary congenital hypothyroidism cases.

Primary congenital hypothyroidism is frequently seen endocrine disorder and one of the preventable cause of mental retardation. Aim of study was to evaluate the frequency of permanent/transient hypothyrodism, and to detect underlying reason to identfy any marker which carries potential to discriminate permanent/transient form. Forty eight cases older than 3 years of age, diagnosed as primary congenital hypothyroidism and started thyroxin therapy in newborn-period, and followed up between January 2007-June 2013 were included in the study. Thyroid hormon levels were evaluated and thyroid ultrasonography was performed in cases who are at the end of their 3 years of age, after 6 weeks of thyroxine free period. Thyroid sintigraphy was performed if serum thyroid-stimulating hormone was high (≥ 5 mIU/mL) and perchlorate discharge test was performed if uptake was normal or increased on sintigraphy. Cases with thyroid-stimulating hormone levels ≥ 5 mIU/mL were defined as permanent primary congenital hypothyroidism group and as transient primary congenital hypothyroidism group with normal thyroid hormones during 6 months. The mean age was 3.8±0.7 years. Mean diagnosis age was 16.6±6.5 days and 14 cases (29.2%) were diagnosed by screening program of Ministry of Health. There were 23 cases (14F, 9M) in permanent primary congenital hypothyroidism group and 12 (52.2%) of them were dysgenesis (8 hypoplasia, 4 ectopia), and 11 (47.8%) dyshormonogenesis. In transient primary congenital hypothyroidism group, there were 25 cases (17M, 8F). The mean thyroid-stimulating hormone levels at diagnosis were similar in two groups. The mean thyroxin dose in permanent primary congenital hypothyroidism group was significantly higher than transient group at the time of thyroxin cessation (2.1±0.7, 1.5±0.5 mg/kg/d, respectively, p=0.004). Thyroxin dose ≥1.6 mcg/kg/d was 72% sensitive and 69.6% specific for predicting permenant primary congenital hypothyroidism. Transient primary congenital hypothyroidism is more frequent than expected and found often in males in the primary congenital hypothyroidism cases, started thyroxin therapy in neonatal period. While fT4, thyroid-stimulating hormone, Tg levels at diagnosis do not predict transient/permenant primary congenital hypothyroidism, thyroxin dose before the therapy cessation at the age of 3 may make the distinction between transient/permenant primary congenital hypothyroidism.

Spectrum of extrathyroidal congenital malformations in a cohort of North Indian children with permanent primary congenital hypothyroidism

Background: Children with permanent primary congenital hypothyroidism (CH) are at increased risk for extrathyroidal congenital malformations (ECMs) as compared to normal child population. A wide variation in the prevalence of ECMs in CH has been reported previously with the reports from Turkey and India indicating a much higher prevalence (48%–59%) as compared to reports from other countries (2.1%–10.5%). Setting and Design: Pediatric Endocrinology Clinic of a large multispecialty hospital located in Northwest India. Retrospective study. Materials and Methods: Children diagnosed as permanent primary CH underwent evaluation for associated ECMs using echocardiography and abdominal and pelvic ultrasonography if clinically indicated. Results: The etiological diagnoses in 106 children (52 girls and 54 boys) with permanent CH were thyroid agenesis in 70 (66%), ectopia in 9 (8.5%), hypoplasia in 6 (5.5%), hypothyroidism with eutopic gland in 5 (4.7%), and dyshormonogenesis in 16 (15%) patients. Seven (7.42%) patients had associated ECMs. The majority (4, 3.7%) of ECMs were cardiac (ventricular septal defect in two patients and patent ductus arteriosus and transposition of great arteries in one each), while skeletal (congenital talipes equinovarus in two and hemivertebra in one patient) and genitourinary (splitting of the pelvicalyceal system in two patients) anomalies were seen in 3 (2.8%) and 2 (1.8%) patients, respectively. Conclusion: The prevalence of ECMs in children with permanent CH was much lower as compared to other cohorts from India. Further studies are needed to determine the underlying genetic and environmental factors to explain the drastic regional differences in the prevalence of ECMs in CH.

Loss-of-Function Variants in a Hungarian Cohort Reveal Structural Insights on TSH Receptor Maturation and Signaling.

Congenital hypothyroidism (CH) is one of the most common inborn endocrine disorders with genetic background. Despite the well-established newborn CH screening program in Hungary, no systematic examination of the underlying genetic alterations has been performed as yet. We aimed to explore TSH receptor (TSHR) mutations in a cohort of Hungarian patients with CH. Eighty-five unrelated patients with permanent primary CH, all diagnosed at newborn screening, were selected. Coding exons of the TSHR gene were sequenced and evaluated together with the thyroid-specific clinical parameters. Functional features of the novel mutations were experimentally examined, and their comparative molecular models were built. In four patients (one heterozygous and three compound heterozygous), seven TSHR mutations were identified. Among these, N432(1.50)D and P449(2.39)L are novel missense alterations. Importantly, the N432(1.50) residue is highly conserved among G protein-coupled receptors, and its function has not been examined yet in human glycoprotein hormone receptors. Our results indicate that the N432(1.50)D mutation disrupts important, architecture-stabilizing intramolecular interactions and ultimately leads to the complete intracellular retention of the receptor. On the other hand, P449(2.39) is located in the intracellular part of the receptor, which is important in G protein coupling. The P449(2.39)L mutation results in signaling impairment, with a more profound effect on the Gq/11 pathway. TSHR mutations are common among Hungarian patients with CH. The novel genetic alterations revealed an important structural role of the N432(1.50) and the P449(2.39) residues in receptor expression and signaling, respectively.

Sublingual thyroid ectopy: similarities and differences with Kallmann syndrome.

Permanent primary congenital hypothyroidism (CH), the commonest cause of preventable intellectual disability, is due to defects in the embryonic development of the thyroid in the vast majority of cases. These defects are collectively called thyroid dysgenesis. The thyroid may be absent (athyreosis) but, more commonly, a sublingual thyroid ectopy without lateral lobes, is the only thyroid tissue present. Such an ectopy presumably results from an arrest in the downward migration of the median anlage. Thyroid ectopy almost always occurs in a sporadic fashion. However, first-degree relatives are affected more often than chance alone would predict. On the other hand, almost all reported monozygotic twin pairs are discordant for thyroid ectopy. Current research is aimed at reconciling these contradictory epidemiological data. We propose a two-hit mechanism associating a germline predisposing factor with another genetic or epigenetic alteration within the ectopic thyroid tissue itself or, as in some forms of Kallmann syndrome, in the structures surrounding the thyroid during embryogenesis. Thyroid ectopy, a model for sporadic congenital malformations in humans, is also associated with congenital heart disease, and molecular mechanisms common to thyroid and heart development are being unraveled.

TSHRMutations as a Cause of Congenital Hypothyroidism in Japan: A Population-Based Genetic Epidemiology Study

The prevalence of congenital hypothyroidism (CH) associated with mutations in the TSH receptor gene (TSHR) has not been established. We examined the frequency of TSHR mutations among patients with permanent primary CH and in the general population in Japan. We enrolled 102 patients with permanent primary CH [70 with "moderate to severe CH" (TSH, >or=10 mU/liter) and 32 with "mild CH" (TSH, 5-10 mU/liter)], who were identified through newborn screening among 353,000 newborns born in Kanagawa prefecture from October 1979 to June 2006. These subjects were tested for TSHR mutations by PCR-based direct sequencing. We further characterized molecular functions of identified mutant TSHRs in vitro. We found three patients with moderate to severe CH who had biallelic mutations in TSHR and three patients with mild CH who had monoallelic mutations. Observed mutations included one previously characterized mutation (p.R450H) and three uncharacterized mutations (p.G132R, p.A204V, and p.D403N). In vitro experiments confirmed loss of functions of these four mutants. Among four mutations, p.R450H was particularly frequent: six of nine mutant alleles harbored p.R450H. All six alleles with p.R450H commonly carried a minor single nucleotide polymorphism, suggesting a founder effect. We estimated the prevalence of biallelic TSHR mutations to be 4.3% (three in 70) in Japanese patients with moderate to severe CH, and 1 in 118,000 (three in 353,000) in the general Japanese population. In Japan, TSHR mutations are relatively common among patients with CH, and a founder mutation (p.R450H) accounts for about 70% of mutants.

Clinical and Molecular Analysis of Thyroid Hypoplasia: A Population-Based Approach in Southern Brazil

Congenital hypothyroidism (CH) is mainly due to developmental abnormalities leading to thyroid dysgenesis (TD). TD encompasses very distinct morphologic subtypes of disease. This study examined and compared the phenotype in TD variants and searched for genetic alterations in sporadic thyroid hypoplasia (TH), the most misdiagnosed form of CH. This was a longitudinal study over a 14-year period (1990-2004). A continuous series of 353 children with TD was identified using thyroid function tests [thyroxine (T4) and TSH], scintigraphy, and ultrasound as diagnostic tools. Individual phenotypes were analyzed in 253 children with TD. Mutations in the most likely candidate genes were studied in 35 cases of TH. The overall birth prevalence of permanent CH was 1:4795. Ectopy represented 37% of all cases of permanent primary CH, dyshormonogenesis 28%, agenesis 24%, hypoplasia 10%, and hemiagenesis 1%. The lowest screening T4 level and the highest TSH level were in the agenetic group, followed by TH. The TH group had an improvement in the thyroid function showing less-severe phenotype with aging. In the molecular analysis, one patient was identified with a mutation in the PAX8 gene (155G>C; R52P); four patients had a heterozygous G>C substitution in position -569; two patients showed a (234C>A; P52T) or (2181C>G; D727E) polymorphic variants of the TSH-R gene; and one patient presented a novel heterozygous nonsynonymous substitution, 293G>A; S98N, in the NKX2.5 gene. The prevalence of CH was within the previously reported range of 1:3000-4000. Ectopy was the most common etiology. Clinical analysis revealed distinct hormonal patterns in TH subgroup when compared with other variants of TD, with genetic abnormalities identified only in few cases in the TSH-R, PAX8, and NKX2.5 genes.

TTF-2/FOXE1 gene polymorphisms in Sicilian patients with permanent primary congenital hypothyroidism

Thyroid transcription factor-2 (TTF-2/FOXE1) is a polyalanine domain protein that regulates thyroid embryogenesis, but very few patients with permanent primary congenital hypothyroidism (pCH) harbor germline mutations of this or other transcription factors that are involved in thyroid development that might explain the etiology of pCH. Variations within the polyalanine tract are found in a variety of genes and are often reported in association with malformation syndromes; pCH is frequently associated with thyroid malformations and extra-thyroidal malformations. Therefore, in this study we investigated whether alanine (Ala) length polymorphisms and non-polymorphic mutations of the TTF-2 gene in pCH patients might be involved in the pathogenesis of pCH. The entire coding region of the TTF-2 gene was analyzed in 57 Sicilian patients and 142 healthy controls. We found that the homozygous Ala14 polymorphism (Ala14/14) was less frequent in the pCH group than in the controls. In contrast, significantly more pCH patients than controls harbored the Ala16 polymorphism (Ala16/16 and Ala14/16). However, neither the Ala14/14 nor the Ala16 polymorphism was related to extra-thyroidal malformations. Two of the 57 patients carried Ala11/14 and Ala12/14, and one Ala14/14 patient also had the silent polymorphism 387 C/T (Leu129Leu). Other than known polymorphic variants we found no mutation in the TTF-2 gene. Therefore, this study demonstrates that mutations in the TTF-2 gene are rare in pCH patients and suggests that variations in the length of the Ala-tract could at least partially explain the etiology of pCH but not that of extra-thyroidal malformations.

High Prevalence of Extrathyroid Malformations in a Cohort of Brazilian Patients with Permanent Primary Congenital Hypothyroidism

The objective of this study was to evaluate the prevalence of major congenital malformations in a cohort of children with permanent primary congenital hypothyroidism (PCH). This cross-sectional study was conducted in 76 consecutive, unselected children with PCH recruited from a district hospital outpatient clinic. Malformations were identified by clinical examination. The prevalence of major congenital malformations in these patients was compared with the prevalence of malformations in children born at Hospital de Clínicas de Porto Alegre (HCPA). The etiology of hypothyroidism was established by scintigraphy and ultrasonography. Hypothyroidism was caused by thyroid dysgenesis in 67 patients (one case of hemiagenesis, 24 of ectopia, and 42 of agenesis); the gland was normally located and shaped in nine patients. Ten patients (13.2%) had major congenital malformations (1,316/10,000 patients), mostly cardiac. Malformations were observed only in patients with dysgenesis: thyroid agenesis (n = 7) and sub-lingual ectopic thyroid (n = 3). The prevalence of malformations was significantly higher (RR = 2.6; CI 95%: 1.3-4.8; p = 0.005) in this group than in HCPA newborns (509/10,000 patients). In conclusion, a high rate of extrathyroid congenital malformations, mostly cardiac, was found for patients with permanent PCH, especially thyroid dysgenesis. The present data support the existence of an association between CH and increased prevalence of congenital malformations.

Predictors of intellectual outcome in a cohort of Brazilian children with congenital hypothyroidism.

To identify predictors of intellectual development in a cohort of children with permanent primary congenital hypothyroidism. Cohort study with intellectual development as the outcome. Thirty-one consecutive newborns with permanent primary congenital hypothyroidism diagnosed by a screening programme were recruited from the outpatient clinic of a district hospital and underwent psychometric evaluation with the Wechsler Intelligence Scales after a minimum follow-up of 4 years. Eight of the 31 patients (25.8%) presented impaired intellectual development (full-scale intellectual quotient < 85), and one of them presented mental deficiency (full-scale intellectual quotient </= 69). The following were associated with worse prognosis: initial serum T4 levels </= 32.18 nmol/l, treatment beginning after 30 days of age, fewer than seven clinic visits during the first year of life, living in rural areas, nonintellectual parental occupation and little parental schooling. In a multiple regression analysis, only maternal schooling (B = 0.401; beta coefficient = 13.053, P = 0.063), number of clinic visits during the first year of life (B = 0.382; beta coefficient = 4.145, P = 0.047) and initial serum T4 (B = 0.287; beta coefficient = 1.336, P = 0.089) remained significantly associated with full-scale intelligence quotient scores. Maternal schooling, number of visits during the first year of life and baseline T4 levels were the main predictors of cognitive outcome in this cohort of patients.

Accuracy of ultrasonography to establish the diagnosis and aetiology of permanent primary congenital hypothyroidism.

To compare ultrasonography and 99mTc thyroid scintigraphy for the aetiologic diagnosis of permanent congenital hypothyroidism (CH). Eighty-eight consecutive patients with CH were recruited at an endocrinology outpatient clinic and submitted to high-frequency ultrasonography and to 99mTc scintigraphy. Seventy-six patients were diagnosed with permanent CH and 12 with transitory CH. The agreement between ultrasound and scintigraphy was very high (kappa coefficient = 0.866; P < 0.001) for the entire group. In permanent CH patients, ultrasonography identified 67 cases of dysgenesis (absence of thyroid gland in the usual anatomical location in 66 and hemiagenesis in one), and this diagnosis was confirmed by scintigraphy (absence of functional thyroid tissue in 43 and ectopia in 24). In the other nine permanent CH patients, the thyroid was in the usual anatomical location on ultrasonography but scintigraphy did not identify functional tissue in one patient. In the 12 transitory CH patients, a normally shaped thyroid was detected by ultrasound in the usual location, whereas scintigraphy showed absence of functional tissue in two identical twins and scarce concentration of isotope in a third patient. Ultrasonography is an accurate method to establish the presence of dysgenesis and might be used as the first imaging tool in patients with CH, whereas scintigraphy should be used mainly to distinguish agenesis from ectopia. Further examination is required to differentiate permanent CH with a normally located and shaped gland from transitory hypothyroidism.

Very low birth weight newborns do not need repeat screening for congenital hypothyroidism

Objective: To determine whether repeat screening for congenital hypothyroidism is necessary in newborns weighing <1500 g (very low birth weight [VLBW]). Study design: All VLBW infants born in the province of Québec between October 15, 1993, and October 15, 1994, had a second filter paper sample requested at 6 weeks of age to measure thyrotropin and thyroxine, in addition to these measurements for the routine screening sample. We then conducted a survey of all 4 academic pediatric endocrinology clinics in the province, inquiring about cases of permanent primary congenital hypothyroidism (PPCH) in children born weighing <1500 g or who may have been missed by neonatal screening. Results: Two specimens were obtained in 465 VLBW newborns. One case of mild transient hyperthyrotropinemia was identified. The survey identified 4 VLBW newborns with PPCH: 1 girl and 1 boy with dyshormonogenesis, 1 athyreotic girl, and 1 girl with thyroid ectopy. All 4 were detected by their initial filter paper specimens. The survey also identified 1 case of PPCH in a girl who had a normal neonatal screen and normal birth weight. Conclusions: VLBW newborns with PPCH can mount an appropriate thyrotropin response and do not need repeat screening for congenital hypothyroidism. (J Pediatr 2002;140:311-4)

Newborn screening for congenital hypothyroidism, Victoria, Australia, 1977-1997. Part 2: Treatment, progress and outcome.

A controlled longitudinal prospective study is reported of physical and neuropsychological progress up to 12 years in 152 children with congenital hypothyroidism (CH), detected by newborn screening in the Australian state of Victoria and born between the onset of screening in mid-1977 and December 1988. Linear growth of the CH children was normal. Throughout they were slightly heavier and the median head circumference was slightly larger compared with reference data. Those with thyroid aplasia required a marginally larger dose of thyroxine to achieve euthyroidism. Assessment of cognitive outcome in the children with permanent primary CH revealed the mean scores at 2, 5 and 8 years to be from 8.5 (p<0.001) to 10.2 (p<0.001) points lower than in a group of 60 euthyroid controls. However, there was large overlap and, of the affected children, only 10.1% at 2 years, 3.9% at 5 years and 6.8% at 8 years fell more than 2 SD below the means of the euthyroid controls. On univariate analysis, variables shown to have significant correlation with cognitive outcome at 8 years in the CH children were newborn activity, baseline TT4 and FTI, initial T4 dosage, socio-economic classification, maternal age, maternal education and presence of a serious accompanying disorder. On multiple regression analysis, significant variables were baseline bone age, maternal age and education, and presence of a serious accompanying disorder. No single thyroidal or extra-thyroidal variable could be identified to account for the discrepancy between the children with CH and the controls.

A search for the possible molecular mechanisms of thyroid dysgenesis: sex ratios and associated malformations.

Permanent primary congenital hypothyroidism (CH) can be caused by abnormal thyroid differentiation (athyreosis), migration (ectopy), or function (leading to goiter). Goiters follow an autosomal recessive pattern of inheritance, whereas ectopy and athyreosis are considered as a single sporadic entity with a female preponderance. On the other hand, a high prevalence of extrathyroidal malformations has been reported in CH, but without linking specific defects to specific types of CH. On the basis of TSH screening, 273 newborns were referred to an academic pediatric endocrinology clinic in the province of Quebec between 1988 and 1997. Of 230 patients with permanent primary CH who had scintigraphy at diagnosis, 141 had ectopy (104 girls), 36 had athyreosis (21 girls), 42 had goiter (18 girls), 10 (3 girls) had a normal scan, and 1 girl had hemiagenesis. Only in the ectopies was the proportion of girls significantly higher than 0.5 (P<0.001). Isolated cardiac malformations were observed in 7 patients (3.0%), a prevalence 5-fold higher than that in the general population; this was largely due to atrial and ventricular septal defects, which were only observed in ectopy and athyreosis. Our data suggest that the molecular mechanisms that lead to complete absence of thyroid differentiation or defective thyroid migration 1) may be similar, but are modulated by the genetic makeup of the embryo and/or the hormonal milieu of the fetus; and 2) may also be involved in septation of the embryonic heart.

Epidemiological of the Different Forms of Permanent Primary Congenital Hypothyroidism and Associated Malformations

Epidemiological of the Different Forms of Permanent Primary Congenital Hypothyroidism and Associated Malformations

Congenital hypothyroidism: increased incidence in Najran province, Saudi Arabia.

Neonatal screening for congenital hypothyroidism using cord serum thyroid-stimulating hormone (TSH) was initiated in Najran health region in September 1990. A total of 30810 newborn infants were screened by April 1995. Of the 24 infants with abnormal thyroid function tests on recall, 22 had permanent primary congenital hypothyroidism (incidence; 1:1400) and in two male siblings transient congenital hypothyroidism (incidence; 1:15400) was proved on follow-up. There was a significantly higher incidence of dyshormonogenesis. Eight (57 per cent) of the 14 infants who were adequately studied thyroid scan revealed ectopic glands with increased 99mTc uptake, while thyroid ectopy and aplasia were present only in three (22 per cent) infants each. Furthermore, goiter was evident clinically in two other patients.

Congenital hypothyroidism screening and the cutoff for thyrotropin measurement: recommendations from The Netherlands.

There is little agreement as to the optimal cutoff point for thyrotropin testing in primary thyroxine screening programs for congenital hypothyroidism. Most programs in the United States use a cutoff point of 10% of the lowest thyroxine values, whereas in the Netherlands a cutoff point of 20% is used. Therefore, the results of the Dutch program may provide valuable information about the optimal cutoff point. The frequency distribution of screening thyroxine values was studied in all cases of permanent primary congenital hypothyroidism (n = 481) detected in 1,601,603 screened children born during the period from January 1, 1981, to December 31, 1989, in the Netherlands. Programs using a 10% cutoff point would have missed 1.5% of cases. Above the 10% cutoff point, the marginal costs increase quite rapidly because of the escalating numbers of thyrotropin measurements necessary to detect one case of permanent primary congenital hypothyroidism: 20,000 in the range of 11% to 15% and 40,000 in the range of 16% to 20%. Based on these findings, a cutoff point of at least 10% is recommended.

Radionuclide imaging in primary permanent congenital hypothyroidism.

Thyroid scintigraphy was performed in 69 consecutive infants with permanent primary congenital hypothyroidism (CH) detected by systematic neonatal thyroid screening using a rectilinear scanner or a gamma camera 15 minutes after the intravenous injection of 250 microCi Tc-99m sodium pertechnetate, immediately after the infants were fed. Immobilization of the infant in a supine position with the neck in hyperextension was achieved by a vacuum cushion without any sedation. Thyroid scintigraphy showed thyroid ectopia in 43 of the 69 CH infants, thyroid agenesis in 19, and goiter in the last 7 infants, respectively. The images were easily interpretable in all cases, even in very small ectopic glands in the lingual area, as there was no interference with extra-thyroidal uptake of the tracer, especially by the salivary glands. Our experience indicates that thyroid scintigraphy in the CH newborns can be performed immediately at the time of diagnosis of CH without technical difficulties. As thyroid scintigraphy is the only procedure allowing the distinction between thyroid agenesis and ectopia, and as the neurointellectual prognosis might be lower in the former than in the latter situation, thyroid scintigraphy in CH newborns contributes not only to the diagnosis but also the prognosis of the disorder.