scholarly journals Approach to the Diagnosis and Treatment of Neonatal Hypothyroidism

2011 ◽  
Vol 96 (10) ◽  
pp. 2959-2967 ◽  
Author(s):  
Stephen H. LaFranchi
Keyword(s):  
Newborn Screening ◽  
Congenital Hypothyroidism ◽  
Neurodevelopmental Outcome ◽  
Diagnosis And Treatment ◽  
Thyroid Function Tests ◽  
Free T4 ◽  
Neonatal Hypothyroidism ◽  
Serum Free ◽  
Screening Programs ◽  
Diagnostic Studies

Abstract Congenital hypothyroidism, occurring in 1:3000 newborns, is one of the most common preventable causes of mental retardation. Neurodevelopmental outcome is inversely related to the age of diagnosis and treatment. Infants detected through newborn screening programs and started on l-T4 in the first few weeks of life have a normal or near-normal neurodevelopmental outcome. The recommended starting dose of l-T4 (10–15 μg/kg · d) is higher on a weight basis than the dose for children and adults. Tailoring the starting l-T4 dose to the severity of the hypothyroidism will normalize serum T4 and TSH as rapidly as possible. It is important to obtain confirmatory serum thyroid function tests before treatment is started. Further diagnostic studies, such as radionuclide uptake and scan and ultrasonography, may be performed to determine the underlying cause of hypothyroidism. Because results from these tests generally do not alter the initial treatment decision, however, these diagnostic studies are rarely indicated. The developing brain has a critical dependence on thyroid hormone for the first 2–3 yr of life; thus, monitoring occurs at more frequent intervals than in older children and adults. Serum free T4 and TSH should be checked at intervals frequent enough to ensure timely adjustment of l-T4 dosing and to keep serum free T4 and TSH levels in target ranges. Given the success of early detection and treatment of neonates with congenital hypothyroidism, a public health mandate should be to develop similar programs for the 75% of babies worldwide who are born in areas without newborn screening programs.

Detecting Congenital Central Hypothyroidism by Newborn Screening: Difficulty in Distinguishing from Congenital Thyroxine-Binding Globulin Deficiency

2017 ◽  
Vol 88 (5) ◽  
pp. 331-338 ◽  
Author(s):  
Kara J. Connelly ◽  
Melinda J. Pierce ◽  
Cheryl Hanna ◽  
Stephen H. LaFranchi
Keyword(s):  
Newborn Screening ◽  
Thyroid Function ◽  
Thyroid Stimulating Hormone ◽  
Pituitary Hormone ◽  
Thyroid Function Tests ◽  
Free T4 ◽  
Central Hypothyroidism ◽  
Serum Free ◽  
Thyroxine Binding Globulin ◽  
Healthy Infants

Background/Aims: Congenital central hypothyroidism (CH-C) can be detected on newborn screening (NBS) by programs using thyroxine (T4)-reflex thyroid-stimulating hormone (TSH) test approach. CH-C must be distinguished from T4-binding globulin (TBG) deficiency. We sought to determine whether thyroid function tests reliably separate CH-C from TBG deficiency. Methods: We analyzed NBS and serum free and total T4, T3 resin uptake (T3RU) or TBG, and TSH for infants in the Northwest Regional NBS Program (NWRSP) between the years 2008 and 2015 with either CH-C or TBG deficiency. Results: We discovered a significant overlap in T3RU and TBG levels amongst 21 cases of CH-C and 250 cases of TBG deficiency. Mean serum TBG levels were lower in CH-C cases (20.3 µg/mL, range 14.2–33.3) than what is reported in healthy infants (28.6 µg/mL, range 19.1–44.6). Serum free T4 was lower in CH-C cases than TBG deficiency but did not always differentiate between the two conditions. Conclusion: CH-C benefits from detection on NBS but must be distinguished from TBG deficiency. The diagnosis of CH-C rests solely on subnormal serum free T4, but is supported by the demonstration of other pituitary hormone deficiencies. As an overlap exists, serum TBG (or T3RU) levels do not play a role in the diagnosis of CH-C.

scholarly journals Newborn Screening for Congenital Hypothyroidism in Japan

2021 ◽  
Vol 7 (3) ◽  
pp. 34
Author(s):  
Kanshi Minamitani
Keyword(s):  
Birth Weight ◽  
Low Birth Weight ◽  
Newborn Screening ◽  
Congenital Hypothyroidism ◽  
Failure To Thrive ◽  
Thyroid Stimulating Hormone ◽  
Low Birth Weight Infants ◽  
Term Infants ◽  
Screening Programs ◽  
Screening Strategies

Congenital hypothyroidism (CH) is the most common preventable cause of intellectual impairment or failure to thrive by early identification and treatment. In Japan, newborn screening programs for CH were introduced in 1979, and the clinical guidelines for newborn screening of CH were developed in 1998, revised in 2014, and are currently undergoing further revision. Newborn screening strategies are designed to detect the elevated levels of thyroid stimulating hormone (TSH) in most areas of Japan, although TSH and free thyroxine (FT4) are often measured simultaneously in some areas. Since 1987, in order not to observe the delayed rise in TSH, additional rescreening of premature neonates and low birth weight infants (<2000 g) at four weeks of life or when their body weight reaches 2500 g has been recommended, despite a normal initial newborn screening. Recently, the actual incidence of CH has doubled to approximately 1:2500 in Japan as in other countries. This increasing incidence is speculated to be mainly due to an increase in the number of mildly affected patients detected by the generalized lowering of TSH screening cutoffs and an increase in the number of preterm or low birth weight neonates at a higher risk of having CH than term infants.

Current and future perspective of newborn screening: an Indian scenario

2016 ◽  
Vol 29 (1) ◽  
Author(s):  
Gurjit Kaur ◽  
Kiran Thakur ◽  
Sandeep Kataria ◽  
Teg Rabab Singh ◽  
Bir Singh Chavan ◽  
...  
Keyword(s):  
Health Care ◽  
Congenital Adrenal Hyperplasia ◽  
Newborn Screening ◽  
Health Care System ◽  
Congenital Hypothyroidism ◽  
G6pd Deficiency ◽  
Metabolic Disorders ◽  
Adrenal Hyperplasia ◽  
Screening Programs ◽  
Care System

AbstractNewborn screening comprises a paramount public health program seeking timely detection, diagnosis, and intervention for genetic disorders that may otherwise produce serious clinical consequences. Today newborn screening is part of the health care system of developed countries, whereas in India, newborn screening is still in the toddler stage.We searched PubMed with the keywords newborn screening for metabolic disorders, newborn screening in India, and congenital disorder in neonates, and selected publications that seem appropriate.In India, in spite of the high birth rate and high frequency of metabolic disorders, newborn screening programs are not part of the health care system. At Union Territory, Chandigarh in 2007, newborn screening was initiated and is currently ongoing for three disorders, that is, congenital hypothyroidism, congenital adrenal hyperplasia, and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Prevalence of these disorders is found to be 1:1400 for congenital hypothyroidism, 1:6334 for congenital adrenal hyperplasia, and 1:80 for G6PD deficiency.Mandatory newborn screening for congenital hypothyroidism should be implemented in India, and other disorders can be added in the screening panel on the basis of region-wise prevalence. The objective of this review is to provide insight toward present scenario of newborn screening in India along with recommendations to combat the hurdles in the pathway of mandatory newborn screening.

Newborn Screening for Congenital Hypothyroidism: Recommended Guidelines

PEDIATRICS ◽  
1993 ◽  
Vol 91 (6) ◽  
pp. 1203-1209
Author(s):  
Keyword(s):  
Thyroid Hormone ◽  
Newborn Screening ◽  
Congenital Hypothyroidism ◽  
Placental Transfer ◽  
Fetal Brain ◽  
Iodothyronine Deiodinase ◽  
Screening Programs ◽  
Organ Systems ◽  
Fetal Hypothyroidism ◽  
Maternal Thyroid

Congenital hypothyroidism (CH) represents one of the most common preventable causes of mental retardation. The fetal hypothalamic-pituitary-thyroid axis begins to function by midgestation and is mature in the term infant at delivery. If fetal hypothyroidism develops, untoward effects may be demonstrated in certain organ systems, including the central nervous system and skeleton. However, most infants with CH appear normal at birth. Recent data suggest that the hypothyroid fetus is protected to a certain extent by placental transfer of maternal thyroid hormone; serum thyroxine (T4) levels in the cord blood of athyroid fetuses approximate one third of maternal levels.1 In addition, studies in animal models of hypothyroidism demonstrate increased levels of brain iodothyronine deiodinase, the enzyme which converts T4 to triiodothyronine (T3). In the hypothyroid fetus, this increased enzyme acting on T4 of maternal origin is sufficient to produce near normal fetal brain T3 concentrations.2 Thus, it appears that early detection and treatment of congenital hypothyroidism should have the potential to completely reverse the effects of fetal hypothyroidism in all but the most severe cases, for example, athyreotic infants born to mothers with thyroid problems resulting in inadequate placental transfer of maternal thyroid hormone. Since the development of pilot screening programs for CH in Quebec and Pittsburgh in 1974,3 newborn screening for CH has become routine in essentially all developed countries of the world and is under development in Eastern Europe, South America, Asia, and Africa. In North America it is estimated that more than 5 million newborns are screened, with approximately 1400 infants with congenital hypothyroidism detected annually.

scholarly journals Universal Implementation of Newborn Screening in India

2020 ◽  
Vol 6 (2) ◽  
pp. 24 ◽  
Author(s):  
Thomas Mookken
Keyword(s):  
Newborn Screening ◽  
Congenital Hypothyroidism ◽  
Universal Screening ◽  
Screening Program ◽  
Developed Countries ◽  
Screening Programs ◽  
Successful Program ◽  
Personal Experiences ◽  
High Incidence ◽  
Glucose 6 Phosphate Dehydrogenase

Newborn screening is a successful program in many developed countries. In India, the benefits of dried blood spot screening have been recognized and that screening is slowly gaining traction. There are significant issues standing in the way of universal implementation of a newborn screening program in India: awareness, cost, advocacy, public policy, and politics. Three regional screening programs, Chandigarh, Goa, and Kerala could serve as models for other programs in India. The data for this commentary were based on personal experiences from managing public newborn screening programs, searches on PubMed and Google, and personal interactions with experts in the field. The overwhelming recommendation is to universally screen for congenital hypothyroidism in India, because it is easy and inexpensive to treat, with excellent outcomes. It would also be beneficial to consider screening universally for glucose-6-phosphate dehydrogenase deficiency due to its high incidence and ease of treatment. Finally, sickle cell disease should be screened in those areas in India where it is prevalent due to the costs associated with universal screening. Achieving universal screening is a challenge, and it is very difficult to predict when every baby born in India will be screened for at least congenital hypothyroidism.

scholarly journals Diverse Genotypes and Phenotypes of Three Novel Thyroid Hormone Receptor-α Mutations

2016 ◽  
Vol 101 (8) ◽  
pp. 2945-2954 ◽  
Author(s):  
Korcan Demir ◽  
Anja L. M. van Gucht ◽  
Muammer Büyükinan ◽  
Gönül Çatlı ◽  
Yavuz Ayhan ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Motor Development ◽  
Thyroid Hormone Receptor ◽  
Clinical Phenotype ◽  
Case Series ◽  
Detailed Knowledge ◽  
Thyroid Function Tests ◽  
Free T4 ◽  
Serum Free ◽  
Free T3

Context: Recently several patients with resistance to thyroid hormone (RTH)-α due to T3 receptor-α (TRα) mutations were identified. The phenotype of these patients consists of varying degrees of growth impairment, delayed bone, mental and motor development, constipation, macrocephaly, and near-normal thyroid function tests. Objective: The objective of the study was to describe the clinical phenotype of three new families with RTHα and thereby gain more detailed knowledge on this novel syndrome. Design, Setting, and Participants: RTHα was suspected in three index patients from different families. Detailed clinical and biochemical assessment and imaging and genetic analyses were performed in the patients and their relatives. In addition, functional consequences of TRα mutations were investigated in vitro. Results: We studied 22 individuals from three families and identified 10 patients with heterozygous TRα mutations: C380fs387X, R384H, and A263S, respectively. The frame-shift mutation completely inactivated TRα, whereas the missense mutations produced milder defects. These mutations were associated with decreasing severity of the clinical phenotype: the patient in family 1 showed severe defects in growth, mental, and motor development, whereas the seven patients in family 3 had only mild clinical features. The most frequent abnormalities were anemia, constipation, and a delay in at least one of the developmental milestones. Serum free T3 ranged from high-normal to high and serum free T4 and rT3 from normal to low. TSH levels were normal in all patients. Conclusions: This large case series underlines the variation in the clinical phenotype of RTHα patients. RTHα should be suspected in subjects when even mild clinical and laboratory features of hypothyroidism are present along with high/high-normal free T3, low/normal free T4, and normal TSH.

Simultaneous radioimmunoassay of thyrotropin and thyroxine in human serum.

1977 ◽  
Vol 23 (9) ◽  
pp. 1644-1647 ◽  
Author(s):  
M K Bluett ◽  
E O Reiter ◽  
G E Duckett ◽  
A W Root
Keyword(s):  
Human Serum ◽  
Congenital Hypothyroidism ◽  
Diagnosis And Treatment ◽  
Rapid Evaluation ◽  
Dual Isotope ◽  
Screening Programs ◽  
Double Antibody ◽  
Specimen Collection ◽  
Analytical Recovery

Abstract The importance of early diagnois and treatment of congenital hypothyroidism has been well established, and several screening programs have been undertaken to detect neonates with this disorder by measurement of concentrations of thyrotropin or thyroxine in the serum. However, measurement of either hormone alone may fail to identify all affected patients. Accordingly, we have established a simultaneous double-antibody, dual-isotope radioimmunoassay for both. Sensitivity, slope, analytical recovery, and precision characteristics of the simultaneous assay do not differ from those of each assay performed separately. Values for the two analyses in the single and simultaneous assays correlate well (r = 0.951 for thyroxine, 0.983 for thyrotropin). This assay system permits determination of both hormones within 72 h after specimen collection and thus should allow more rapid evaluation, diagnosis, and treatment of infants with congenital hypothyroidism.

scholarly journals Pilot Neonatal Screening Program for Central Congenital Hypothyroidism: Evidence of Significant Detection

2017 ◽  
Vol 88 (3-4) ◽  
pp. 274-280 ◽  
Author(s):  
Débora Braslavsky ◽  
Maria Virginia Méndez ◽  
Laura Prieto ◽  
Ana Keselman ◽  
Rosa Enacan ◽  
...  
Keyword(s):  
Congenital Hypothyroidism ◽  
Neonatal Screening ◽  
Screening Program ◽  
Recall Rate ◽  
Free T4 ◽  
Screening Programs ◽  
Screening Study ◽  
Term Newborns ◽  
Neonatal Screening Program ◽  
Congenital Hypopituitarism

Background/Aim: Congenital hypothyroidism (CH) is a heterogeneous entity. Neonatal screening programs based on thyrotropin (TSH) determination allow primary CH diagnosis but miss central CH (CCH). CCH causes morbidity, alerts to other pituitary deficiencies, and is more prevalent than previously thought. We aimed at developing a pilot neonatal screening program for CCH detection. Patients and Methods: A prospective 2-year pilot neonatal screening study based on simultaneous dried blood specimen TSH and thyroxine (T4) measurements was implemented in term newborns aged 2–7 days. Those with T4 ≤4.5 µg/dL (–2.3 SDS) and TSH <10 mIU/L were recalled (suspicious of CCH) and underwent clinical and biochemical assessment performed by expert pediatric endocrinologists. Results: A total of 67,719 newborns were screened. Primary CH was confirmed in 24 (1: 2,821). Forty-four newborns with potential CCH were recalled (recall rate 0.07%) at a mean age of 12.6 ± 4.8 days. In this group, permanent CCH was confirmed in 3 (1: 22,573), starting L-T4 treatment at a mean age of 12.3 ± 6.6 days; 14 boys showed T4-binding globulin deficiency (1: 4,837); 24 had transient hypothyroxinemia (21 non-thyroidal illness and 3 healthy); and 3 died before the confirmation stage. According to initial free T4 measurements, CCH patients had moderate hypothyroidism. Conclusions: Adding T4 to TSH measurements enabled the identification of CCH as a prevalent condition and contributed to improving the care of newborns with congenital hypopituitarism and recognizing other thyroidal disorders.

scholarly journals Recent advances in central congenital hypothyroidism

2015 ◽  
Vol 227 (3) ◽  
pp. R51-R71 ◽  
Author(s):  
Nadia Schoenmakers ◽  
Kyriaki S Alatzoglou ◽  
V Krishna Chatterjee ◽  
Mehul T Dattani
Keyword(s):  
Congenital Hypothyroidism ◽  
Pituitary Hormone ◽  
Central Hypothyroidism ◽  
Neonatal Hypothyroidism ◽  
Neurodevelopmental Delay ◽  
Screening Programs ◽  
Pituitary Development ◽  
Pituitary Thyroid Axis ◽  
Life Threatening ◽  
Tsh Deficiency

Central congenital hypothyroidism (CCH) may occur in isolation, or more frequently in combination with additional pituitary hormone deficits with or without associated extrapituitary abnormalities. Although uncommon, it may be more prevalent than previously thought, affecting up to 1:16 000 neonates in the Netherlands. Since TSH is not elevated, CCH will evade diagnosis in primary, TSH-based, CH screening programs and delayed detection may result in neurodevelopmental delay due to untreated neonatal hypothyroidism. Alternatively, coexisting growth hormones or ACTH deficiency may pose additional risks, such as life threatening hypoglycaemia. Genetic ascertainment is possible in a minority of cases and reveals mutations in genes controlling the TSH biosynthetic pathway (TSHB, TRHR,IGSF1) in isolated TSH deficiency, or early (HESX1, LHX3, LHX4, SOX3, OTX2) or late (PROP1, POU1F1) pituitary transcription factors in combined hormone deficits. Since TSH cannot be used as an indicator of euthyroidism, adequacy of treatment can be difficult to monitor due to a paucity of alternative biomarkers. This review will summarize the normal physiology of pituitary development and the hypothalamic–pituitary–thyroid axis, then describe known genetic causes of isolated central hypothyroidism and combined pituitary hormone deficits associated with TSH deficiency. Difficulties in diagnosis and management of these conditions will then be discussed.

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