Early Detection Of Congenital Hypothyroidism Research Articles

Newborn Screening for the Early Detection of Congenital Hypothyroidism: A Countrywide Comprehensive Program of Bangladesh Atomic Energy Commission

Newborn Screening for the Early Detection of Congenital Hypothyroidism: A Countrywide Comprehensive Program of Bangladesh Atomic Energy Commission

Screening T4 and TSH in Early Detection of Congenital Hypothyroidism in Newborns: What’s the Dilemma?

Untreated congenital hypothyroidism (CH) leads to intellectual disability. Newborn screening (NBS) for CH should be done on all infants. Prompt diagnosis by NBS leads to early and adequate treatment outcomes in very normal neurocognitive outcomes in adulthood. Newborn screening (NBS) for congenital hypothyroidism (CH) is one of the major achievements in preventive medicine. Most neonates born with CH have a normal appearance and no detectable physical signs. Blood spot thyroid stimulating hormone (TSH), thyroxine (T4), or both can be used for CH screening. The latter is more sensitive but not cost-effective, so screening by TSH or T4 is used in various programs worldwide. TSH screening is more specific in the diagnosis of CH. T4 screening is more sensitive in detecting newborns with rare hypothalamic-pituitary-hypothyroidism, but it’s less specific with a high frequency of false positives especially in low birth weight and premature infants. NBS alone is not sufficient to prevent adverse outcomes from CH in a pediatric population. In addition to NBS, the management of CH requires timely confirmation of the diagnosis and accurate interpretation of thyroid function testing, effective treatment, and consistent follow-up. Doctors need to consider hypothyroidism in the face of clinical symptoms, even if NBS thyroid test results are normal. When clinical symptoms and signs of hypothyroidism appear (such as large posterior fontanelles, large tongue, umbilical hernia, prolonged jaundice, constipation, lethargy, and/or hypothermia), measurement of serum thyroid hormone and free thyroxine is indicated, regardless of NBS results. So all these babies should be treated as having CH during the first 3 years of life, taking into account the risk of mental retardation. Re-evaluation after 3 years is required in such patients.

An observational study on the prevalence of congenital hypothyroidism and factors affecting TSH levels in premature babies at tertiary care rural centre

Background: Premature babies, particularly those with very low birth weight (VLBW), are at a higher risk of developing congenital hypothyroidism. The inadequate development of the hypothalamic-pituitary axis in preterm infants contributes to the higher prevalence of this condition in this population. However, the optimal screening and treatment protocols for congenital hypothyroidism in preterm newborns remain unclear. Methods: This was a hospital-based observational study conducted over a period of 18 months. The study included 150 preterm babies born at the Sri Adichunchanagiri hospital and research centre. Non-probability sampling was used to select the study subjects. Data on demographic and clinical factors were collected from mothers and newborns. Blood samples were collected at day 3 of life to estimate thyroid-stimulating hormone levels. Correlations between TSH levels and various parameters were analyzed using statistical methods. Results: The study found that the prevalence of congenital hypothyroidism in preterm newborns was 2%. The mean TSH level at day 3 was 7.56 mIU/L, and 9.3% of cases had TSH levels above 20 mIU/l. Significant associations were found between high TSH levels and primiparity, vaginal delivery, and maternal gestational diabetes mellitus. There was an inverse correlation between TSH levels and gestational age, birth weight, and Apgar scores at 1 and 5 minutes. Conclusions: The study revealed a prevalence of congenital hypothyroidism of 2% in preterm newborns. Risk factors such as primiparity, vaginal delivery, and maternal GDM were associated with high TSH levels. These findings highlight the importance of screening and early detection of congenital hypothyroidism in premature babies to improve outcomes.

Molecular genetic screening of full-term small for gestational age

ObjectiveTo examine the clinical application of genomic screening in newborns small for gestational age (SGA), hoping to provide an efficient technique for early discovery of neonatal diseases, which is necessary to elevate survival rates and the quality of life in infants.MethodsTotally 93 full-term SGA newborns were assessed. Dried blood spot (DBS) samples were obtained at 72 h after birth, and tandem mass spectrometry (TMS) and Angel Care genomic screening (GS, using Targeted next generation sequencing) were carried out.ResultsAll 93 subjects were examined by Angel Care GS and TMS. No children showing inborn errors of metabolism (IEM) were detected by TMS, while 2 pediatric cases (2.15%, 2/93) were confirmed as thyroid dyshormonogenesis 6 (TDH6) by Angel Care GS. Additionally, 45 pediatric cases (48.4%) had one or more variants conferring a carrier status for recessive childhood-onset disorders, with 31 genes and 42 variants associated with 26 diseases. The top three gene-related diseases with carrier status were autosomal recessive deafness (DFNB), abnormal thyroid hormone and Krabbe disease.ConclusionsSGA is tightly associated with genetic variation. Molecular Genetic Screening allows early detection of congenital hypothyroidism and may be a potent genomic sequencing technique for screening newborns.

Assessment of thyroid function in the preterm and/or very low birth weight newborn

The screening program or early detection of congenital hypothyroidism is one of the greatest advances achieved in Pediatrics. Thyroid hormones are essential for brain development and maturation, which continue into the neonatal stage. Alterations in thyroid function in premature and underweight children in the first months of life causes irreversible damage to the central nervous system and is one of the most frequent and avoidable causes of mental retardation. Diagnosis in the neonatal period is difficult, so it requires an analytical study to be able to carry out the appropriate treatment.The relevance of this problem justifies its communication to all areas of pediatrics. The main objective is to avoid brain damage in these patients. Other aspects to optimize the adequate development of these children with all the necessary periodic controls and to achieve the inclusion of the diagnosis of thyroid alterations during the stay in neonatal units and in the first months of life, need to implement the resources of the health centers and continue advancing according to current knowledge.In this document, we will focus on the screening of preterm newborns VLBW (<32 weeks of gestation) and/or very low weight for gestational age (1500–1000 g VLBW or <1000 g) and the function evaluation protocol thyroid in premature babies.We update the diagnostic procedures, the essential and complementary tests required, the etiology and the differential diagnoses in this pathology.

A study to estimate similarities or dissimilarities of thyroid parameters of cord blood and new-born venous blood amongst new-borns

Background: Hypothyroidism may be congenital or may be acquired which might or may not have a delayed onset. Incomplete thyroid development and decreased thyroid hormone biosynthesis is a result of congenital hypothyroidism. Screening is usually missed in areas where testing is not done and being the reason for new cases of hypothyroid cases. The aim was to assess/evaluate whether cord blood can be used as a primary screening method for congenital hypothyroidism.Methods: The study was taken up in the department of pediatrics of a tertiary teaching hospital. A total of 200 babies were taken for the study during the whole study period. The cord blood at the time of delivery and 48 hour serum blood was collected and sent to the lab for thyroid profile estimation.Results: The study consisted of 109 males and 91 female infants. Among the 200 subjects, 156 were term babies and 44 preterm. The mean birth weight was 2.44 kgs. The mean cord TSH was 6.89±4.56, the mean T3 level was 81.03±38.84 and mean T4 level among the subjects was 11.17±3.33. The capillary venous blood was collected after 48 hours for thyroid profiling. The mean TSH was 5.15±3.13, mean T3 level was 111.53±36.49 and mean T4 level was 14.65±6.07. On comparison of cord blood and venous blood association was noted between them.Conclusions: From the present study findings it can be suggested cord blood can be used as a marker for early detection of congenital hypothyroidism.

Evaluación de la función tiroidea en el recién nacido pretérmino o de muy bajo peso

The screening program or early detection of congenital hypothyroidism is one of the greatest advances achieved in Pediatrics. Thyroid hormones are essential for brain development and maturation, which continue into the neonatal stage. Alterations in thyroid function in premature and underweight children in the first months of life causes irreversible damage to the central nervous system and is one of the most frequent and avoidable causes of mental retardation. Diagnosis in the neonatal period is difficult, so it requires an analytical study to be able to carry out the appropriate treatment.The relevance of this problem justifies its communication to all areas of pediatrics. The main objective is to avoid brain damage in these patients. Other aspects to optimize the adequate development of these children with all the necessary periodic controls and to achieve the inclusion of the diagnosis of thyroid alterations during the stay in neonatal units and in the first months of life, need to implement the resources of the health centers and continue advancing according to current knowledge.In this document, we will focus on the screening of preterm newborns VLBW (<32 weeks of gestation) and/or very low weight for gestational age (1500-1000g VLBW or <1000g) and the function evaluation protocol thyroid in premature babies.We update the diagnostic procedures, the essential and complementary tests required, the etiology and the differential diagnoses in this pathology.

MON-474 Coexistence of Thyroid Dysgenesis and Premature Ovarian Failure: A Case Report

Background. Congenital hypothyroidism (CH) secondary to thyroid dysgenesis is rare. It may present with ascites and short stature. Primary ovarian failure (POF) is most commonly associated with autoimmune thyroid diseases1. However, there is no report of the association of POF with congenital hypothyroidism. Clinical case. A 30 year old female presented with increasing abdominal girth, short stature and arrest of menstruation at 27 years old. Newborn screening was not done. Developmental milestones were at par. She had a low timber voice and was slow to respond. Her skin was rough and dry. Her hair was sparse, and she had thin eyebrows. Her tongue was not enlarged. Her abdomen was globular with a positive fluid wave test and shifting dullness. Initial tests indicated a hypothyroid state: elevated TSH (50.40 IU/mL, N=0.35-4.94 IU/mL), low FT4 (0 pmol/L, N=12-22 pmol/L). Ultrasound of the thyroid suggests thyroid dysgenesis (small right thyroid gland measuring 1.4 x 0.2 x 0.4 cm and an absent left thyroid gland). Karyotyping was 46, XX and insulin growth factor 1 was normal. Unexpectedly, further tests were consistent with a concomitant primary ovarian failure: low estradiol (5 pg/mL, N=12.4-233 pg/mL), high FSH (112.7 mIU/mL, N=3.5-12.5 mIU/mL) and LH (61.9 mIU/mL, N = 2.4-12.6 mIU/mL). Chest radiography showed left pleural effusion. Abdominal CT scan showed marked ascites with normal reproductive organs. Anti-TPO antibodies were normal (4.87 IU/mL, N=0-25 IU/mL). The patient was treated with Levothyroxine 50 mcg daily then gradually increased to 100 mcg daily. She was given Spironolactone 50 mg daily and paracentesis was also done to address ascites. The patient had improvement of symptoms after a month of treatment. However, the etiology of POF remains to be further elucidated. Conclusion. This case report emphasizes the importance of the early detection of congenital hypothyroidism through newborn screening. Severe hypothyroidism is rarely seen due to the wide availability of the TSH assay and its diagnosis should instigate further work-up for its etiology. Concomitant premature ovarian failure in the absence of an autoimmune thyroid disorder should prompt further investigation for another etiology since premature ovarian failure is not commonly associated with congenital hypothyroidism. Reference: (1) Ayesha, Jha V, Goswami D. Premature Ovarian Failure: An Association with Autoimmune Diseases. J Clin Diagn Res. 2016;10(10):QC10-QC12.

Evaluation and management of the child with hypothyroidism.

Thyroid hormones are critical for early neurocognitive development as well as growth and development throughout childhood. Prompt recognition and treatment of hypothyroidism is, therefore, of utmost importance to optimize physical and neurodevelopmental outcomes. A PubMed search was completed in Clinical Queries using the key terms "hypothyroidism". Hypothyroidism may be present at birth (congenital hypothyroidism) or develop later in life (acquired hypothyroidism). Thyroid dysgenesis and dyshormonogenesis account for approximately 85% and 15% of permanent cases of congenital primary hypothyroidism, respectively. More than 95% of infants with congenital hypothyroidism have few, if any, clinical manifestations of hypothyroidism. Newborn screening programs allow early detection of congenital hypothyroidism. In developed countries, Hashimoto thyroiditis is the most common cause of goiter and acquired hypothyroidism in children and adolescents. Globally, iodine deficiency associated with goiter is the most common cause of hypothyroidism. Central hypothyroidism is uncommon and may be associated with other congenital syndromes and deficiencies of other pituitary hormones. Familiarity of the clinical features would allow prompt diagnosis and institution of treatment. To optimize neurocognitive outcome in infants with congenital hypothyroidism, treatment with levothyroxine should be started as soon as possible, preferably within the first 2weeks of life. Children with acquired hypothyroidism should also be treated early to ensure normal growth and development as well as cognitive outcome. The target is to keep serum TSH < 5mIU/L and to maintain serum free T4 or total T4 within the upper half of the age-specific reference range, with elimination of all symptoms and signs of hypothyroidism.

Transient hypothyroidism in the newborn: to treat or not to treat.

Transient congenital hypothyroidism (CH) refers to a temporary deficiency of thyroid hormone identified after birth, with low thyroxine (T4) and elevated thyrotropin (TSH), which later recovers to improved thyroxine production, typically in first few months of infancy. Approximately 17% to 40% of children diagnosed with CH by newborn screening (NBS) programs were later determined to have transient hypothyroidism. Causes of transient CH are prematurity, iodine deficiency, maternal thyrotropin receptor blocking antibodies, maternal intake of anti-thyroid drugs, maternal or neonatal iodine exposure, loss of function mutations and hepatic hemangiomas. The classic clinical symptoms and signs of CH are usually absent immediately after birth in vast majority of infants due to temporary protection from maternal thyroxine. NBS has been largely successful in preventing intellectual disability by early detection of CH by performing thyroid function tests in infants with abnormal screening results. In this review we present the evidence for decision making regarding treatment vs. withholding treatment in infants with transient CH and present a rational approach to identifying transient CH based on American Academy of Pediatrics (AAP) recommendation.

Profile of umbilical cord blood TSH ,T4 and influence of perinatal factors on thyroid functions in Newborns

Background: Congenital Hypothyroidism, if not treated well in time, may be disastrous for growth and development of child ,therefore early detection of congenital hypothyroidism is important, either by TSH or T4, or both by newborn screening . Influence of several perinatal factors have to be considered while interpreting values of thyroid functions in newborns. The present study is to determine Umbilical cord blood TSH and T4 profile in Newborns and to study influence of Perinatal factors on Umbilical cord blood TSH and T4 . Methods: Umbilical cord blood samples were collected for assessment of TSH and T4 in 830 newborns. The influence of Perinatal factors such as gestational age ,weight, sex, mode of delivery, Ecclampsia, Ante partum haemorrhage , Birth Asphyxia ,Premature rupture of membranes and maternal HIV status on the newborns TSH ,T4 were analyzed . Results: Mean TSH and T4 levels between Pre term and Term and between Term and Post term was statistically significant .Whereas, only T4 level between Preterm and Post term ,was statistically significant . Mean TSH levels, when compared in babies with & without severe birth asphyxia was also statistically significant . Other perinatal factors did not affect cord TSH and T4 levels ,as it was not statistically significant . Conclusion: Perinatal factors have influence over values of Cord blood TSH and T4 levels and a caution in their interpretation should be considered . Key words: TSH (Thyroid stimulating hormone), CH (Congenital Hypothyroidism), APH (Ante Partum Hemorrhage).

Congenital Hypothyroidism Diagnosed At 9 Years Old

Congenital hypothyroidism is a common endocrine disorder of newborn. It is an important cause of global developmental delay. The early diagnosis and treatment is crucial. In this paper we are describing case of congenital hypothyroidism in Saudi Arabia presenting as 9-year-old Bormann boy who was born at home with no neonatal screening and family ignorance. He was discovered incidentally with chest infection, despite of that screening for congenital hypothyroidism has been available in since 1989. This case shows the importance of conducting newborn screening for early detection of congenital hypothyroidism in newborn, which is still being neglected in some developing countries. It also shows the importance of early starting adequate replacement therapy to prevent irreversible sequels.

Intervalos de referencia para tirotropina sérica durante los primeros 14 días de vida

Early detection of congenital hypothyroidism (CH) prevents impaired cognitive and motor development at problems. To increase the screening program specificity, we defined reference intervals for serum TSH in newborns between 2 and 14 days of life. Newborn infants from our neonatal screening program between 2001 and 2007. Serum TSH was determined by electrochemiluminescence. There were excluded neonates who died before the first month of life or with less than 1500 grams at birth, samples with TSH <0,01 µU/ml., processed after 14 days of life and from other medical centers. Statistical tools: Student t-tests, measures of centrality and dispersion, and logarithmic transformations. Studied population: 6772 newborn infants out of 7869, 50.49% were males. The male/ female ratio was similar during the 14 days. The mean age at testing was 5.85 days (± 2.58), and the mean of TSH value was 4.42 µU/ml (± 4.17). Inverse relationship was found between age and TSH (mean TSH at days 2 and 14 was 5.82 µU/ ml and 2.58 respectively). We found statistical evidence on an inverse relationship between TSH and age in newborn infants with 14 days of age. Reference intervals for TSH contribute to a better assessment of thyroid status in neonates and to define an appropriate conduct for individual therapy.

Associations between brominated flame retardants in human milk and thyroid-stimulating hormone (TSH) in neonates

Background Brominated flame retardants (BFRs) have been in widespread use in a vast array of consumer products since the 1970s. The metabolites of some BFRs show a structural similarity to thyroid hormones and experimental animal studies have confirmed that they may interfere with thyroid hormone homeostasis. A major concern has been whether intrauterine exposure to BFRs may disturb thyroid homeostasis since the fetal brain is particularly susceptible to alterations in thyroid hormones. However, few reports on newborns have been published to date. Objectives To evaluate the association between BFRs and neonatal thyroid-stimulating hormone (TSH). Methods We studied six polybrominated diphenyl ethers (PBDEs) measured in milk samples from 239 women who were part of the “Norwegian Human Milk Study” (HUMIS), 2003–2006. Hexabromocyclododecane (HBCD) and BDE-209 were measured in a subset of the women (193 and 46 milk samples, respectively). The milk was sampled at a median of 33 days after delivery. TSH was measured in babies three days after delivery as part of the routine national screening program for early detection of congenital hypothyroidism. Additional information was obtained through the Medical Birth Registry and questionnaires to the mothers. Results The PBDE concentrations in human milk in Norway were comparable to concentrations reported from other European countries and Asia, but not the US and Canada where levels are approximately one order of higher magnitude. We observed no statistically significant associations between BDE-47, 99, 153, 154, 209 and HBCD in human milk and TSH in models adjusted for possible confounders and other environmental toxicants including polychlorinated biphenyls (PCBs). Conclusions We did not observe an association between TSH and exposure to HBCD and PBDEs within the exposure levels observed.

Hypothyroidism

Thyroid function is essential to growth and to all aspects of development. Hypothyroidism is not preventable, however, early detection and immediate treatment can prevent deleterious and irreversible effects on the growing child. Newborn screening is mandated in all fifty states and it is critical to the early detection of congenital hypothyroidism and the institution of treatment in the first weeks of life. Awareness of acquired hypothyroidism in school-aged children and adolescents is important to the detection of this often subtle condition that usually first presents as deceleration of growth. Lymphocytic thyroiditis is the most common cause of acquired thyroid deficiency in children and adolescents. Hypothyroidism may also develop years after radiation treatment for cancer directed at the area of the thyroid gland or the cranium. Replacement therapy with thyroxine is generally well tolerated. The use of lithium carbonate and other medications, as well as conditions of starvation and chronic malnutrition may be associated with disturbed thyroid function. Persons with the rare disorder of generalized resistance to thyroid hormone are at significant risk for attention deficit hyperactivity disorder. However, the reverse is not the case.

Cardiac Function of Neonates with Congenital Hypothyroidism Before Treatment

Because of previous reports of myocardial dysfunction in adults and children with hypothyroidism, 12 newborns with congenital hypothyroidism were studied using standard electrocardiographic and echocardiographic techniques. The infants were between the ages of 7 and 28 days at the time of study. Five infants were athyrotic, and of these two had delayed skeletal maturation. Electrocardiogram revealed normal heart rates and QRS voltages in all children, while five had abnormal dome-shaped T-waves and absent ST-segments (Mosque sign). Echocardiograms were normal in all patients indicating no myocardial dysfunction or pericardial effusion. This study suggests that myocardial dysfunction is not present in the immediate newborn period of infants with congenital hypothyroidism. It is reasonable to conclude that early detection of congenital hypothyroidism by mass screening may prevent the cardiac affects of hypothyroidism as well as the other known sequelae.

Circulating thyrotrophin as an index of thyroid function.

Thyroid function testing has provided the major endocrine workload in laboratories for many years. This workload has been considerably augmented by the introduction in some laboratories over the last 5 years of regional screening programmes for the early detection of congenital hypothyroidism. The pressure on laboratories to provide efficient thyroid function testing has been partly responsible for the enormous technological developments that have been introduced recently through the efforts of research laboratories and commercial manufacturers. Sadly, however, there have been occasions where diagnostic accuracy has been sacrificed in favour of technical convenience, for example, in the use of certain free hormone assays.' In this article we shall review recent advances in the measurement of thyrotrophin (TSH) and try to assess the potential of the new generation of TSH assays in improving the diagnostic accuracy of thyroid function testing.

Early detection of congenital hypothyroidism by TSH radioimmunoassay using filter paper blood samples (author's transl)

It has been reported that mental retardation due to congenital hypothyroidism can be prevented by early detection and early adequate replacement therapy. We have developed a radioimmunoassay for TSH using the dried blood spot and have started screening for newborn congenital hypothyroidism using a part of sample of the inborn metabolic error screening. (1) The dried blood spot TSH of 61,000 newborn infants was assayed in the first half of our screening and that of 74,505 newborn infants was assayed in the latter half of our screening. As a result, although we were not able to detect any cases in the first screening, we were able to detect 9 cases of congenital hypothyroidism in the latter screening. From the results obtained through our investigation of the thyroid function of these 9 infants, we confirmed that mild hypothyroidism can be better detected by the screening of TSH. (2) As to the program of the screening, we chose from the latter half of our screening all the samples in which TSH concentrations contained above 3 percent of each assay and were remeasured on the next assay. (3) As we confirmed that the sensitivity of measurement was increased at very low concentrations, when the volume of antibodies, radioisotopes and eluates used for each assay were decreased, we measured TSH successfully using two 3 mm discs. (4) As we can perform very simple screening by the 3 mm disc method, we are changing the screening method from that with 10 mm disc to one with two 3 mm discs. We intend to extend our screening, and will make every effort to prevent mental retardation due to congenital hypothyroidism.

Early detection of congenital hypothyroidism.

Early detection of congenital hypothyroidism.