OBJECTIVE:To describe the Dutch neonatal screening programme for congenital hypothyroidism (CH).DESIGN:Descriptive study.METHOD:Data on neonatal screening for CH in the period 1 January 1981 through 31 December 2011 were obtained from the Department for Vaccine Supply and Prevention Programmes of the Dutch National Institute for Public Health and the Environment (RIVM), laboratories and paediatricians to whom babies with abnormal screening results were referred. The screening procedure has been amended several times. In the period 1981-1994, only T4 and TSH were measured in heel prick blood, for example. From 1995, thyroxine-binding globulin (TBG) was added to the screening protocol.RESULTS:The participation rate was 99.7%. Before 1995 the sensitivity, specificity and positive predictive value were 94%, 99.51% and 6%, respectively. From 1995 these percentages were 98%, 99.85% and 21%, respectively. The total prevalence of CH was 1:2670 (prevalence of CH of thyroidal origin was 1:3100 and CH of central origin was 1:21,600). The percentages of patients with severe CH treated before day 15 in the periods 1981-1990, 1991-2000 and 2001-2011 were 24% (63/263), 63% (170/269) and 96% (176/184), respectively.CONCLUSION:The sensitivity and specificity of the screening procedure has considerably increased since 1995 compared with the period before 1995. In recent years patients with severe CH were treated considerably earlier than in the first years of the screening. Neonatal screening for CH may be considered as an important success for public health care.

To describe the Dutch neonatal screening programme for congenital hypothyroidism (CH). Descriptive study. Data on neonatal screening for CH in the period 1 January 1981 through 31 December 2011 were obtained from the Department for Vaccine Supply and Prevention Programmes of the Dutch National Institute for Public Health and the Environment (RIVM), laboratories and paediatricians to whom babies with abnormal screening results were referred. The screening procedure has been amended several times. In the period 1981-1994, only T4 and TSH were measured in heel prick blood, for example. From 1995, thyroxine-binding globulin (TBG) was added to the screening protocol. The participation rate was 99.7%. Before 1995 the sensitivity, specificity and positive predictive value were 94%, 99.51% and 6%, respectively. From 1995 these percentages were 98%, 99.85% and 21%, respectively. The total prevalence of CH was 1:2670 (prevalence of CH of thyroidal origin was 1:3100 and CH of central origin was 1:21,600). The percentages of patients with severe CH treated before day 15 in the periods 1981-1990, 1991-2000 and 2001-2011 were 24% (63/263), 63% (170/269) and 96% (176/184), respectively. The sensitivity and specificity of the screening procedure has considerably increased since 1995 compared with the period before 1995. In recent years patients with severe CH were treated considerably earlier than in the first years of the screening. Neonatal screening for CH may be considered as an important success for public health care

Doel Beschrijving van de Nederlandse neonatale screening op congenitale hypothyreoidie (CH). Opzet Descriptief onderzoek. Methode We verzamelden gegevens over de neonatale screening op CH in de periode 1 januari 1981-31 december 2011 van de Dienst Vaccinvoorziening en Preventieprogramma’s van het RIVM, van laboratoria en van kinderartsen naar wie pasgeborenen met een afwijkende uitslag werden verwezen. De screeningsprocedure werd verscheidene keren bijgesteld. In de periode 1981-1994 werden bijvoorbeeld alleen de waarden van T4 en TSH bepaald uit het hielprikkaartje. Vanaf 1995 werd ook de waarde van thyroxinebindend globuline (TBG) meegenomen. Resultaten De deelname was 99,7%. Tot 1995 was de sensitiviteit 94%, de specificiteit 99,51% en de positief voorspellende waarde 6%; vanaf 1995 was dit respectievelijk 98%, 99,85% en 21%. De totale prevalentie van CH was 1:2670 (prevalentie CH van thyreoidale oorsprong: 1:3100 en centrale CH: 1:21.600). De percentages kinderen met ernstige CH bij wie in de perioden 1981-1990, 1991-2000 en 2001-2011 voor de 15e levensdag met thyroxinebehandeling werd gestart, waren respectievelijk 24 (63/263), 63 (170/269) en 96 (176/184). Conclusie De sensitiviteit en specificiteit van het screeningsprogramma is vanaf 1995 aanzienlijk hoger dan voor 1995. In de recente jaren worden patienten met ernstige CH aanzienlijk vroeger behandeld dan in de beginjaren. De neonatale screening op CH kan als een belangrijk succes van de openbare gezondheidszorg worden beschouwd.

CONTEXT:The Dutch neonatal congenital hypothyroidism (CH) screening program detects infants with CH of central origin (CH-C). These infants have a high likelihood of multiple pituitary hormone deficiencies. ACTH deficiency especially poses an additional risk for brain damage and may be fatal.OBJECTIVE:Our objective was to evaluate different tools for assessment of the integrity of the hypothalamus-pituitary-adrenocortex (HPA) axis in young infants, aiming for a strategy for reliable and timely diagnosis.DESIGN, SETTING:This is a Dutch nationwide prospective study (enrollment 1994-1996). Patients were included if neonatal CH screening results were indicative of CH-C and HPA axis function could be tested within 6 months of birth.PATIENTS:Nine male and three female infants with CH-C and four infants with false-positive screening results or transient hypothyroidism were included in the study.MAIN OUTCOME MEASURES:CRH test results, multiple cortisol plasma concentrations, and cortisol excretion in 24-h urine were measured.RESULTS:Six (50%) of the CH-C patients had abnormal CRH test results. Three of them had discordant test results: impaired increase of plasma cortisol in response to CRH, despite substantial increase of plasma ACTH. The other three infants, with concordant impaired responses of both ACTH and cortisol to CRH, had a very low urinary cortisol excretion in comparison with the subjects with normal CRH test results.CONCLUSIONS:The CRH test proves to be a fast and reliable tool in the assessment of HPA axis (dys)function. It enables timely diagnosis in (asymptomatic) neonates at risk for serious morbidity and mortality. The discordant response type, which has not been described before, may be an early phase of HPA axis dysfunction. Alternatively, patients with this response type may constitute a separate pathogenetic subset of HPA axis-deficient patients.

CONTEXT:A shortage of thyroid hormone during prenatal life and the first years after birth results in a spectrum of neuropsychological disorders, depending on the duration and severity of the deficiency. In the case of congenital hypothyroidism of central origin (CH-C), the majority of patients have multiple pituitary hormone deficiencies (MPHD). This condition poses an additional threat to postnatal central nervous system development, primarily on account of neuroglycopenia due to ACTH/cortisol deficiency with or without additional GH deficiency. Therefore, in CH-C, rapid diagnosis is even more urgent than in congenital hypothyroidism of thyroidal origin.OBJECTIVE:In the assessment of hypothalamic-pituitary-thyroid function, we considered the pituitary response to iv administration of TRH (TRH test) pivotal. We evaluated the usefulness of the TRH test in a cohort of infants with neonatal congenital hypothyroidism screening results indicative of CH-C by analyzing the results within the framework of investigations of the anatomical and functional integrity of the hypothalamo-hypophyseal system.DESIGN AND SETTING:The study was a Dutch nationwide prospective study (1994-1996). Patients were included if neonatal congenital hypothyroidism screening results were indicative of CH-C and patients could be tested within 3 months of birth.PATIENTS:Ten male and five female infants with CH-C, detected by neonatal screening, and six infants with false-positive screening results, nonthyroidal illness, or transient hypothyroidism, were included in the study.MAIN OUTCOME MEASURES:Results of TRH tests, within the framework of extensive endocrinological examinations and cerebral magnetic resonance imaging, were measured.RESULTS:All patients with type 3 TSH responses to TRH had MPHD, and the majority (67%) of patients with type 2 responses had isolated TSH deficiency.CONCLUSIONS:The TRH test has a pivotal role in the diagnosis of TSH deficiency in young infants. Abnormal TRH test results, especially a type 3 response, urge immediate assessment of integral hypothalamic-pituitary function because the majority of patients have MPHD.

Context: Early recognition of gonadotropic dysfunction could enable well-timed growth and maturation and prevent damage to gonads and external genitalia. The adaptation of the Dutch neonatal screening program for congenital hypothyroidism in the mid 1990s resulted in enhanced detection of congenital hypothyroidism of central origin (CH-C), with high likelihood of multiple pituitary hormone deficiency, including gonadotropin (Gn) deficiency.Objective: We analyzed GnRH test results and baseline Gn and sex hormone measurements in 15 infants with CH-C to examine these diagnostic tools for assessment of the integrity of the hypothalamuspituitary-gonad axis in young infants.Design: In a nationwide prospective study (1994-1996), patients were referred to our department if neonatal CH screening results were indicative of CH-C. When CH-C was confirmed, GnRH tests and baseline Gn and sex hormone measurements took place at the age of 3 months, when euthyroid status had been accomplished by T-4 supplementation, and if necessary, cortisol supplementation was installed.Setting: The study took place at the Department of Pediatric Endocrinology, Emma Children's Hospital, Academic Medical Center, University of Amsterdam ( referral center).Patients: The study included 15 neonates (five girls and 10 boys) with CH-C, detected by neonatal screening, in whom investigation of the hypothalamus-pituitary-gonad axis could be performed at 3 months of age.Main Outcome Measures: Results of GnRH tests and baseline Gn and sex hormone measurements were assessed.Results: GnRH tests at 3 months of age showed a pattern indicative of endogenous GnRH stimulation in nine infants and a blunted response in six. Baseline Gn and sex hormone concentrations except estradiol (P = 0.053) were significantly different between responders and nonresponders.Conclusions: The GnRH test and baseline measurements of Gn and sex hormone serum concentrations at 3 months of age are promising options in the assessment of hypothalamic-pituitary-gonadal function in infants with CH-C of both sexes.

The case report by Hashimoto et al. 1 Hashimoto H Maruyama H Koshida R Okuda N Sato T. Central hypothyroidism resulting from pituitary suppression and peripheral thyrotoxicosis in a premature infant born to a mother with Graves disease. J Pediatr. 1995; 127: 809-811 Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar nicely shows different dynamics of thyroid-stimulating antibodies (TSAbs) compared with thyrotropin-binding inhibitory immunoglobulin. However, in our opinion, the authors' claim that their patient's central hypothyroidism is the result of the marked decrease of TSAb activity in comparison with inhibitory antibody activity is unfounded. But before we discuss the pathophysiologic implications, we believe we should express our great concern regarding the inconsistent and outdated method of treatment chosen to correct both hyperthyroidism and hypothyroidism.