Morphological abnormalities in children with thyroidal congenital hypothyroidism.

Several groups of investigators have reported an increased incidence of congenital anomalies in patients with congenital hypothyroidism. Furthermore, in patients with congenital hypothyroidism and mutations in genes known to be involved in thyroid development, specific extra-thyroidal abnormalities have been observed. The goal of the present study was to gain insight in the types and patterns of morphological characteristics depending on the type of congenital hypothyroidism of thyroidal origin (CH-T).

Role of corticotropin-releasing hormone testing in assessment of hypothalamic-pituitary-adrenal axis function in infants with congenital central hypothyroidism.

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.

Role of the thyrotropin-releasing hormone stimulation test in diagnosis of congenital central hypothyroidism in infants.

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.

Loss of integrity of thyroid morphology and function in children born to mothers with inadequately treated Graves' disease.

Context: Central congenital hypothyroidism (CH-C) in neonates born to mothers with inadequately treated Graves' disease usually needs T(4) supplementation. The thyroid and its regulatory system have not yet been extensively studied after T(4) withdrawal, until we observed disintegrated thyroid glands in some patients.

Objective: The aim was to study the occurrence and pathogenesis of disintegrated thyroid glands in CH-C patients.

Neonatal screening for congenital hypothyroidism in the Netherlands: cognitive and motor outcome at 10 years of age.

Context: Patients with thyroidal congenital hypothyroidism (CH-T) born in The Netherlands in 1981-1982 showed persistent intellectual and motor deficits during childhood and adulthood, despite initiation of T(4) supplementation at a median age of 28 d after birth.

Objective: The present study examined whether advancement of treatment initiation to 20 d had resulted in improved cognitive and motor outcome.

Design/setting/patients: In 82 Dutch CH-T patients, born in 1992 to 1993 and treated at a median age of 20 d (mean, 22 d; range, 2-73 d), cognitive and motor outcome was assessed (mean age, 10.

Early assessment of hypothalamic-pituitary-gonadal function in patients with congenital hypothyroidism of central origin.

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 hypothalamus-pituitary-gonad axis in young infants.

Comorbidity, hospitalization, and medication use and their influence on mental and motor development of young infants with Down syndrome.

Objective: Young infants with Down syndrome have an increased occurrence of several well-known medical conditions such as congenital heart and gastrointestinal disease. The aim of this study was to establish consequences like hospitalization and medication use rates and to determine their possible influence on early neurodevelopment.

Patients And Methods: This study compared 2 years of thyroxine treatment with placebo in 196 neonates with Down syndrome who were included in a previously reported randomized clinical trial.

Median nerve conduction velocity and central conduction time measured with somatosensory evoked potentials in thyroxine-treated infants with Down syndrome.

Objective: The aim of this study was to determine whether thyroxine treatment would improve nerve conduction in infants with Down syndrome.

Methods: A single-center, nationwide, randomized, double-blind, clinical trial was performed. Neonates with Down syndrome were assigned randomly to thyroxine (N = 99) or placebo (N = 97) treatment for 2 years.

Trisomy 21 causes persistent congenital hypothyroidism presumably of thyroidal origin.

Objective And Design: Lowered neonatal plasma thyroxine (T(4)) and mildly elevated thyrotropin concentrations together with developmental benefits from neonatally started T(4) treatment in a randomized clinical trial demonstrated Down syndrome (DS) neonates to be mildly hypothyroid, at least during their first weeks of life. To prove that this hypothyroid state persists beyond this period in all, and to elucidate its etiology, we evaluated the course of the thyroid function determinants in all DS infants participating in this 24-month trial.

Main Outcome: Mean plasma thyrotropin concentrations and thyrotropin frequency distributions of 97 placebo-treated infants were persistently shifted to substantially higher concentrations, while free T(4) frequency distributions were in the lower two thirds of the reference interval.

Clinical effectiveness and cost-effectiveness of the use of the thyroxine/thyroxine-binding globulin ratio to detect congenital hypothyroidism of thyroidal and central origin in a neonatal screening program.

Context: Since the introduction of screening for congenital hypothyroidism (CH) in 1974, the optimal laboratory strategy has been the subject of debate.

Objective: To assess the clinical effectiveness and cost-effectiveness of various types of thyroxine (T(4))-based strategies to screen for CH.

Design, Setting, And Participants: In the Netherlands, since January 1, 1995, a primary T(4) determination with supplemental thyroid-stimulating hormone (TSH) and T(4)-binding globulin (TBG) measurements has been used.

Neonatal detection of congenital hypothyroidism of central origin.

Due to the high frequency of concurrent pituitary hormone deficiencies, congenital hypothyroidism (CH) of central origin (CH-C) is a life-threatening disorder. Yet only a minority of these patients are detected by neonatal CH screening programs worldwide. We conducted a prospective multicenter study involving a 2-yr cohort of neonatally diagnosed CH-C patients to determine whether a T(4)-TSH-based neonatal CH screening protocol extended with T(4) binding globulin determinations improves early detection of CH-C and to assess the extent of pituitary hormone deficiency among the identified CH-C patients.

The effect of thyroxine treatment started in the neonatal period on development and growth of two-year-old Down syndrome children: a randomized clinical trial.

Context: Young Down syndrome children appear to have a mild form of congenital hypothyroidism that is rarely detected by neonatal screening and usually left untreated.

Objective: To investigate the effects of thyroxine treatment on development and growth of young Down syndrome children.

Design, Setting, And Participants: Single-center, randomized, double-blind, 24-month trial (enrollment June 1999 to August 2001) with nationwide recruitment, comparing thyroxine administration with placebo in 196 Down syndrome neonates.

Genes differentially expressed in thyroid carcinoma identified by comparison of SAGE expression profiles.

To identify transcripts that distinguish malignant from benign thyroid disease serial analysis of gene expression (SAGE) profiles of papillary thyroid carcinoma and of normal thyroid are compared. Of the 21,000 tags analyzed, 204 tags are differentially expressed with statistical significance in the tumor. Thyroid tumor specificity of these transcripts is determined in silico using the tissue preferential expression (TPE) algorithm.

Central congenital hypothyroidism due to gestational hyperthyroidism: detection where prevention failed.

Much worldwide attention is given to the adverse effects of maternal Graves' disease on the fetal and neonatal thyroid and its function. However, reports concerning the adverse effects of maternal Graves' disease on the pituitary function, illustrated by the development of central congenital hypothyroidism (CCH) in the offspring of these mothers, are scarce. We studied thyroid hormone determinants of 18 children with CCH born to mothers with Graves' disease.

A randomized, masked study of triiodothyronine plus thyroxine administration in preterm infants less than 28 weeks of gestational age: hormonal and clinical effects.

A randomized, placebo-controlled, masked study was conducted of the responses of thyroid parameters, cortisol, and the cardiovascular system to a single dose of triiodothyronine (T(3)) 24 h after birth, followed by a daily dose of thyroxine (T(4)) during 6 wk to infants <28 wk gestational age. Thirty-one infants were assigned to three groups: 1) group A: T(3) 24 h after birth plus daily T(4) during 6 wk; 2) group B: placebo T(3) and T(4) during 6 wk; and 3) group C: placebo T(3) and placebo T(4). T(4), free T(4), T(3), free T(3), reverse T(3), thyroid-stimulating hormone, and cortisol were measured in cord blood and on days 1, 3, 7, 14, 21, 42, and 56.

Primary congenital hypothyroidism: defects in iodine pathways.

The thyroid gland is the only source of thyroid hormone production. Thyroid hormone is essential for growth and development, and is of special importance for the development of the central nervous system. It was for that reason that neonatal screening on congenital hypothyroidism was introduced and is now performed in many countries.

No damaging effect of chemotherapy in addition to radiotherapy on the thyroid axis in young adult survivors of childhood cancer.

Late effects of treatment for childhood cancer on the thyroid axis are ascribed predominantly to radiotherapy. Whether chemotherapy has an additional detrimental effect is still unclear. Our aim was to evaluate this effect in young adult survivors of a broad spectrum of childhood cancers.

Improved radiation protection of the thyroid gland with thyroxine, methimazole, and potassium iodide during diagnostic and therapeutic use of radiolabeled metaiodobenzylguanidine in children with neuroblastoma.

Background: During radiolabeled metaiodobenzylguanidine (MIBG) administration in children with neuroblastoma, the thyroid is protected from (123/131)I uptake by potassium iodide. Despite this protection, up to 64% of patients develop thyroid dysfunction. The authors introduce a new method of radiation protection for the thyroid gland.

Dynamics of the plasma concentrations of TSH, FT4 and T3 following thyroxine supplementation in congenital hypothyroidism.

Objective: The dynamics of the plasma concentrations of various diagnostic determinants of thyroid function were analysed in children with congenital hypothyroidism (CH) after the start of T4 supplementation. The description of the biochemical dynamics of TSH and free T4 (FT4) during the first period of thyroxine treatment is important to depict the practical outlines of the initial dosage of T4 and dosage adjustments for newborns with variable forms of CH.

Design: A retrospective analysis was performed of frequent plasma TSH, total T4 (T4), FT4 and total T3 (T3) measurements in 30 CH neonates during the first weeks of treatment, treated with initial daily T4 dosages ranging from 4.

Free thyroxine levels during the first weeks of life and neurodevelopmental outcome until the age of 5 years in very preterm infants.

Background: We have conducted a randomized trial with thyroxine (T4) in 200 infants <30 weeks' gestation. T4 treatment was associated with better 5-year outcome in infants <29 weeks' gestation, but with worse outcome in infants of 29 weeks. These effects could be related to low, respectively high free thyroxine (FT4) levels

Methods: For each infant, the average FT4 of 5 scheduled measurements was calculated between day 3 and day 28.

Inactivating mutations in the gene for thyroid oxidase 2 (THOX2) and congenital hypothyroidism.

Background: Several genetic defects are associated with permanent congenital hypothyroidism. Immunologic, environmental, and iatrogenic (but not genetic) factors are known to induce transient congenital hypothyroidism, which spontaneously resolves within the first months of life. We hypothesized that molecular defects in the thyroid oxidase system, which is composed of at least two proteins, might be involved in the pathogenesis of permanent or transient congenital hypothyroidism in babies with defects in iodide organification, for which the oxidase system is required.

The quantity of thyroid hormone in human milk is too low to influence plasma thyroid hormone levels in the very preterm infant.

Background: Thyroid hormone is crucial for brain development during foetal and neonatal life. In very preterm infants, transient low levels of plasma T4 and T3 are commonly found, a phenomenon referred to as transient hypothyroxinaemia of prematurity. We investigated whether breast milk is a substantial resource of thyroid hormone for very preterm neonates and can alleviate transient hypothyroxinaemia.

High incidence of thyroid dysfunction despite prophylaxis with potassium iodide during (131)I-meta-iodobenzylguanidine treatment in children with neuroblastoma.

Background: Treatment modalities like targeted radiotherapy with (131)I-meta-iodobenzylguanidine ((131)I-MIBG) improve survival rates after neuroblastoma (NB). Radiation to the thyroid gland can lead to hypothyroidism and even malignancy. Because hypothyroidism after (131)I-MIBG treatment was reported, the current KI prophylaxis against thyroidal radiation damage was evaluated.