Werner and Ingbar's The Thyroid

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.

http://www.ispae.org.in/download_docs/2014_ESPE_Consensus_Guidelines_Congenital_Hypothyroidism.pdf

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

There is growing evidence that a large number of very low birth weight infants are exhibiting neurobehavioral problems in the absence of cerebral palsy at follow-up that has extended into school age and adolescence. Many clinical factors (ie, chronic lung disease, recurrent apnea and bradycardia, transient hypothyroxemia of prematurity, hyperbilirubinemia, nutritional deficiencies, glucocorticoid exposure), as well as stressful environmental conditions, including infant-provider interaction, constant noise, and bright light, may act in combination to impact on the developing brain, even in the absence of overt hemorrhage and/or ischemia. Any potential intervention strategy designed to prevent cognitive and behavioral problems has to account for the numerous biological and clinical conditions and/or interventions, as well as postdischarge social and environmental influences.

Neurobehavioral deficits in premature graduates of intensive care--potential medical and neonatal environmental risk factors.

It is well established that the thyroid status of neonates and children has a significant long-term impact on their behaviour, locomotor ability, speech, hearing and cognition (Legrand 1986). Delay in restoring normal thyroid status in the neonate can lead to irreversible damage. Prompt thyroid supplementation following the diagnosis of neonatal hypothyroidism can restore neurodevelopment to within the normal range (Fisher 1979). Even so, there are still subtle abnormalities of language, visuo-spatial impairments and lower mean IQs later in childhood compared with euthyroid controls. This implies that brain development may, in part, be thyroid hormone sensitive not only in the neonatal period but also prior to birth (New England Congenital Collaborative 1990, Heyerdahl 1991). Development of different areas of central nervous sytem has been associated with the timing and duration of thyroid hormone deficiency, suggesting that there are critical periods during which various parts of the brain are sensitive to thyroid hormone supply (Rovet et al. 1992).

/pdf/thyroid-hormone-and-central-nervous-system-development-2mrvvmf92d.pdf

Thyroid hormone and central nervous system development.

Thyroid function in very low birth weight infants: effects on neonatal hypothyroidism screening.

OBJECTIVES
The purpose of this study was to test the hypothesis that low circulating thyroxine concentrations characteristic of very low birth weight (VLBW) neonates (< 1500 g) are the result of decreased protein binding of thyroid hormones and to elucidate the mechanism(s) responsible and possible significance thereof.

DESIGN
Cross-sectional comparison of thyroid related measurements in cord blood specimens from VLBW infants and from full term infants. Longitudinal comparison in cord and 2- and 4-week blood specimens from VLBW infants.

PATIENTS
Cord blood specimens were analysed from 47 VLBW and 45 full term infants weighing  2500 g. Repeat analyses in venous bloods from 32 of the VLBW infants were analysed at 2 weeks of age and again at 4 weeks in 23. The first cohort of patients was studied in 1994 and comprised 28 VLBW and 24 full term infants (Cohort A). The studies were repeated in 1995–96 in 19 VLBW infants and 21 full term infants (Cohort B).

MEASUREMENTS
T4, free T4 (FT4), T3, thyroxine binding globulin (TBG), and TSH were measured in cord blood and 2- and 4-week venous specimens from VLBW infants and in cord blood specimens of full term infants. Molar ratios of T4/TBG were calculated.

RESULTS
(1) Cord blood TBG, T4 and T3 concentrations of VLBW infants were each 60% of those of term infants. TBG concentrations were 397 ± 111 vs 680 ± 172 nmol/l (P < 0.0005). T4 concentrations were 76 ± 22 vs 139 ± 26 nmol/l (P < 0.0005). FT4 concentrations were in the normal adult range in both neonatal groups. T4/TBG ratios did not differ between the neonatal groups but were significantly less than that of adults (P < 0.001). (2) TSH concentrations in VLBW infants at 2 and 4 weeks were less than 50% of cord blood values. At 2 weeks, TBG concentrations of VLBW infants were unchanged from cord blood concentrations but mean T4 concentration fell by 18% and T4/TBG ratios by 21% (P < 0.005). Mean FT4 rose by 78% (P < 0.02). The changes in mean T4 and FT4 were due largely to FT4 concentrations of 37–113 pmol/l and T4 concentrations of 13–48 nmol/l in 5 infants. These infants also had lower T4/TBG ratios and were smaller and more ill than the remainder of the cohort. The changes disappeared by 4 weeks in 3 of the 4 infants tested.

CONCLUSIONS
Cord T4/TBG ratios are the same in very low birth weight and term infants and are significantly lower than in adult blood. These are more than compensated for in term infants by a 236% increase in thyroxine binding globulin concentrations. The lower thyroxine binding globulin concentrations in very low birth weight infants explain their much lower T4 concentrations. Cord FT4 concentrations of full term and very low birth weight infants are in the normal adult range. T4 concentrations are further depressed and free T4 concentrations elevated in the most ill very low birth weight infants at 2 weeks of age in a manner analogous to that of the ‘sick euthyroid syndrome’.

Thyroid function in very low birth weight infants

Screening very-low-birthweight infants for congenital hypothyroidism

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Thyroid function in very low birth weight infants

Screening very-low-birthweight infants for congenital hypothyroidism