Infantile Hypothyroidism Research Articles

The Relationship Between Maternal Hypothyroidism and the Incidence of Congenital Hypothyroidism in Infants: A Cross-Sectional Study

Background: Congenital hypothyroidism (CH) can influence neonates’ neurodevelopment. There are controversies on the cause of infantile hypothyroidism and its relationship with maternal hypothyroidism. Objectives: This study aimed to investigate the relationship between maternal hypothyroidism and the incidence of CH. Methods: This cross-sectional study was conducted on 712 newborns with hypothyroidism born in Fars province, Iran, between 2018 and 2020, identified through the national screening program for genetic, metabolic, and endocrine congenital diseases recruited by the census sampling method. The information on infants’ files was recorded in a researcher-made checklist. Descriptive data were reported by mean ± SD and No. (%). The independent t-test, chi-square test, Pearson correlation, and Spearman’s rank correlation coefficient were used to evaluate relationships between variables. Results: Of 179,448 infants screened, 712 (4 of 1,000 live births) had CH with a mean thyroid stimulating hormone (TSH) level of 22.34+24.8 mlU/L. Of these, 252 infants (35.4%) had a family history of hypothyroidism in the mother (OR = 4.951, P < 0.001). There was a significant relationship between CH and maternal hypothyroidism. Moreover, there was a significant difference in the mean TSH level between hypothyroid infants born to mothers with a history of hypothyroidism (19.10 ± 21.30 mlU/L) and those who had healthy mothers (24.23 ± 26.44 mlU/L, P = 0.027). The prevalence of CH in 2018, 2019, and 2020 were reported to be 0.34%, 0.4%, and 0.45%, respectively. Conclusions: Our results showed a significant relationship between maternal hypothyroidism and CH. Considering the importance of the prompt diagnosis of CH, especially in high-risk groups such as infants of hypothyroid mothers, it is recommended to conduct more studies to design more precise guidelines to screen infants who are at risk of CH.

Central hypothyroidism in children.

Central congenital hypothyroidism (CCH) is an underdiagnosed disorder poorly described in childhood and adolescence. Congenital defects in thyroid-stimulating hormone (TSH) synthesis, secretion or bioactivity may lead to a state of 'regulatory' hypothyroidism expressed through aberrantly low or normal TSH levels and low thyroxine (T4), a hormonal pattern undetectable by TSH-based neonatal screening programs for congenital hypothyroidism (CH) implemented in most countries worldwide. CCH is more prevalent than previously thought, reaching 1 in 16,000 neonates in countries consistently identifying CCH through T4-based CH screening strategies. Neonatal detection and early treatment of CCH would prevent the risk of developing mental retardation secondary to late diagnosis of infantile hypothyroidism. CCH is frequently associated with other pituitary defects causing life-threatening situations (like e.g. adrenocorticotropic hormone deficiency) which could benefit from the early detection of CCH, avoiding considerable morbidity and mortality. CCH is not easy to identify clinically, and therefore few children are investigated for the disorder. The current knowledge on the genetic bases of CCH is also scarce. At the hypothalamic level no gene defects causing CCH have yet been identified in humans, but pituitary (thyrotrope)-selective genes encoding the TSH-releasing hormone (TRH) receptor (TRHR), the TSH β-subunit (TSHB) and, recently, the immunoglobulin superfamily factor 1 (IGSF1) are genes involved in isolated central hypothyroidism. Moreover, central hypothyroidism is a complex condition where many regulatory signals are implicated and converge to finely modulate the activity of the hypothalamic-pituitary-thyroid axis. This review focuses on novel pathogenic mechanisms and their implications to understand human CCH and improve the identification and the therapeutic handling of this elusive disease in the pediatric age.

Unusual Case of Hypothyroidism in an Infant With Hepatic Hemangioma

Unusual Case of Hypothyroidism in an Infant With Hepatic Hemangioma

Survey of Radioiodine Therapy Safety Practices Highlights the Need for User-Friendly Recommendations

Fetuses whose mothers are treated with radioiodine after approximately 10–12 weeks of pregnancy are at high risk of developing iatrogenic hypothyroidism (1). Other than this well-documented occurrence, there is no evidence of harm to others from radiation originating from patients treated with radioiodine. Given that radioiodine is concentrated in breast milk and radioiodine has been documented to be taken up by the thyroid in nursing newborns whose mothers were given diagnostic activities of radioiodine (2), discontinuing lactation before radioiodine therapy and avoiding breastfeeding after radioiodine treatment is justified despite the lack of a case report of infantile hypothyroidism ascribed to radioiodine ingestion from breastfeeding. Aside from circumstances relating to pregnancy and lactation, the harm that a radioiodine-treated patient could inflict upon another person while following common sense instructions appears to be low. Patients, who themselves receive a much higher dose of radiation because they ingest the full radioiodine treatment, suffer relatively few side effects. For the most part these occur in tissues that actively take up the radionuclide, and the adverse effects occur in a dose-dependent manner (3). This provides some reassurance that the small amount of radiation exposure to the public from those who receive radioiodine treatment is unlikely to cause harm, even if the treated patients ignore nearly all of the radiation safety instructions they receive. On the other hand, it is known that thyroidal exposure to higher levels of radiation, especially in children, can result in harm (4) and by extrapolation with a linear no-threshold dose–response relationship, one may assume that exposure to low levels of radiation might result in some harm. Thus, this theoretical possibility of increased harm at any increase of radiation exposure beyond background radiation, combined with no evidence of benefit of radiation exposure to the public, has led to the practice of keeping radiation exposure to others As Low As Reasonably Achievable (ALARA). High levels of radiation exposure are dangerous. It has been estimated that half of the people receiving a dose to the whole body over a few minutes to a few hours of between 3500 and 5000 mSv would die within 30 days (multiple mSv by 100 to convert to mrem). Similarly, high-dose exposure (starting somewhere between 100 and 1000 mSv) over a relatively short period of time, is associated with the development of a number of malignancies. Conversely, the average yearly radiation exposure from natural sources to an individual in the United States is approximately 3 mSv. Radon gas accounts for two thirds of this exposure, while cosmic, terrestrial, and internal radiation account for the remainder. No adverse health effects have been demonstrated from these levels of natural radiation exposure. In addition, artificial sources of radiation from medical, commercial, and industrial activities contribute another 0.6 mSv, for a total average yearly radiation exposure of 3.6 mSv. Doses (in mSv) from common medical imaging procedures include the following: bitewing dental x-ray, 0.004; chest x-ray (posterior-anterior), 0.02; lateral lumbar spine x-ray, 0.3; mammography, 0.7; lung ventilation/perfusion scan, 1.5; barium swallow, 1.5; technetium-99m bone scan, 4.4; barium enema, 7; 2-deoxy2[F-18]fluoro-d-glucose positron emission tomography scan, 7; chest or abdominal computed tomography scan, 8-10; and coronary angiogram, 5–16. A personalized annual radiation dose estimate can be calculated at the website http:// www.epa.gov/radiation/understand/calculate.html. Although radiation may cause cancers at high doses and dose rates, currently there are no data that unequivocally establish the occurrence of cancer following exposure to low doses or dose rates (e.g., below about 100 mSv). People living in areas with high levels of background radiation (>10 mSv per year) such as Denver, Colorado, have shown no adverse biological effects. Keep these millisievert values in mind as you read the next paragraph. Effective May 29, 1997, and updated on July 29, 2009, the Nuclear Regulatory Commission (NRC) revised Federal Regulation 10 CFR 35.75, which permits NRC-licensed facilities to release a patient treated with radioiodine from their control if the total effective dose equivalent to any other individual from exposure to the released individual is not likely to exceed 5 mSv. Further, a licensee must provide the released individual, or the individual’s parent or guardian, with instructions (including written instructions) on actions

Pulmonary alveolar proteinosis associated with Epstein-Barr virus infection

To the Editors: We report the case of a 3-yr-old male who became unwell over a period of months. He was found to have pulmonary alveolar proteinosis (PAP), confirmed by computed tomography (CT) scan, bronchoalveolar lavage fluid and lung biopsy. Histology from the lung biopsy also revealed a high load of Epstein–Barr virus (EBV). EBV DNA was also found in the blood samples by PCR. We believe this is the first case of PAP caused by EBV reported in the literature. A 3-yr-old male, born at 34 weeks gestation, had transient infantile hypothyroidism. He had been discharged from an endocrinology clinic at 2 yrs of age, but re-presented with failure to thrive. He was the second twin of consanguineous Asian parents, who had lived in the UK for 15 yrs. They had three healthy older daughters. On examination, he was tachypnoeic and tachycardic with signs of respiratory distress. He had persistent hypoxaemia despite high-flow oxygen and was admitted to the Paediatric Intensive Care Unit (Sheffield Children’s Hospital, Sheffield, UK). Chest radiography showed bilateral air-space opacification, and he was administered i.v. cefuroxime. Within 12 h, his condition deteriorated and endotracheal mechanical ventilation was commenced. An initial diagnosis of pneumonia, possibly due to an atypical organism or tuberculosis, was made and the antibiotic spectrum was widened to include clarithromycin, cotrimoxazole, clindamycin, rifampicin, isoniazid, pyridoxine, pyrazonamide and fluconazole. A blind tracheobronchial lavage was performed by the intensive-care staff. The aspirated fluid was reported to …

Regulation or Permission?

Regulation or Permission?

Neonatal screening for congenital hypothyroidism in West Black Sea area, Turkey

The aim of this study was to investigate the incidence of congenital hypothyroidism (CH) in the West Black Sea Area, a mild-to-moderate iodine deficient area in Turkey. Neonatal screening for CH was performed using blood specimens collected onto filter paper. Thyrotropin [thyroid-stimulating hormone (TSH)] was measured by radioimmunoassay, and a value >20 microU/ml was considered as cut-off point for re-examining. Venous serum was obtained to measure TSH, thyroxin (T4), free T4 (FT4) and thyroglobulin (TG). To determine the iodine status of the study area, median urinary iodine was measured in 212 randomly selected neonates and their mothers. A total of 18606 neonates were screened from three cities (Bolu, Düzce, and Zonguldak) between 2000 and 2002. With a cut-off point of TSH value >20 microU/ml, the recall rate was found 1.6%. Eight cases of CH were diagnosed (incidence 1/2326). There were three cases of transient hypothyroidism, with an incidence of 1/6202. Twenty-six percent of the TSH values was greater than 5 microU/ml. Median urinary iodine concentrations in neonates and their mothers were 85 microg/l and 40 microg/l, respectively. The incidences of CH, transient hypothyroidism and the recall rate were higher in our study area than many countries in Europe. The study area has been affected by mild-to-moderate iodine deficiency. Neonatal screening for CH should be introduced in Turkey without delay. A national comprehensive infantile hypothyroidism and iodine prophylaxis policies should be developed.

A review of the case for neonatal thyrotropin screening in developing countries: the example of India.

Infantile hypothyroidism, either caused by iodine-deficiency disorder (IDD) or congenital hypothyroidism (CH), is the world's leading cause of preventable mental retardation. Such hypothyroidism has virtually been eliminated in the developed world by salt iodization and neonatal thyroid screening. However, most developing countries do not have neonatal thyroid screening programs. Using India as an example, we review the case for newborn screening in the developing world. A literature review on infantile hypothyroidism in India was conducted and three Indian thyroid experts were queried about their views on neonatal screening in India. Iodine nutrition improved markedly in India during the 1990s; 49% of the households are now using adequately iodized salt. The control of IDD is still insufficient in India. Nationally representative data on neonatal screening in India are not available, but two regional studies have been published. One study (n = 12,407) measured cord blood thyrotropin and the other (n = 25,244) measured filter paper thyroxine. These studies reported difficult socioeconomic and organizational barriers to the implementation of neonatal screening in India. It is time for India to make neonatal thyroid screening and mandatory iodization of salt a priority and develop a comprehensive infantile hypothyroidism policy. Prioritization of infantile hypothyroidism prevention is justified by its high frequency, sensitivity of screening in detecting both IDD and CH, adverse consequences of missing diagnosis at birth, high effectiveness of prevention, severity of disability from hypothyroidism, cost effectiveness of prevention, and lack of a clinical method of diagnosis near birth.

Results of neonatal screening for congenital hypothyrosis in the Moscow region

A total of 211418 (87.3%) neonates bom in the Moscow Region in 1991, 1995-1998 were examined for infantile hypothyroidism (111) using Delfia Finnish kits within the framework of the Federal program of mass-screening for 1H. Incidence of transitory hypothyroidism and /Н was 1:1699 and 1:5621, respectively. Mean frequency of retests was 2.98%>, 90% of them being cases of moderate hyperthyrotropinemia with the hormone level up to 50 microIU/ml. Epidemiological findings of mass screening provide evidence on moredate iodine deficiency in the Moscow region.

Neonatal screening for congenital hypothyroidism in environmentally disadvantaged regions1

A 4-year neonatal screening for infantile hypothyroidism (IH) performed in the Moscow Region in 1995—1998 under relevant Federal program has detected 29 neonates with IH. The cases distribution in the Region was sporadic with the mean frequency of 1:6286. By the incidence of retesting, 53 districts of Moscow region were grouped into 3 groups (Pl, P2, P3), differing by the functional activity of the thyroid. The incidence of retests was significantly higher in P3 region vs. P2 and P3 regions (РЗ > P2 > P3) and correlated with the incidence of transitory hypothyrosis and published data on high level of technogenic pollution of the territories, and presence of markers of ecology-related diseases. Epidemiological values of neonatal screening for congenital hypothyrosis indicate that iodine deficiency in the Moscow region can be regarded as characteristic moderately severe.

Two other cases of ANOTHER syndrome? Family report and update

We describe one daughter of a possibly distant consanguineous couple with infantile hypothyroidism, trichodysplasia, dental anomalies, dystrophic nails, skin alterations, otitis media, slight conductive hypoacusia, recurrent respiratory tract infections, and gastroenterologic problems. One of her two sisters presents dental anomalies and trichodysplasia, and had dry skin at birth. Similarity indexes are estimated for our patients in comparison with those described under the acronym ANOTHER syndrome. It is concluded that, in spite of the differences, it is possible that our two patients also present ANOTHER syndrome. The cause is unknown.

Usefulness of serum thyrotropin-binding inhibitory index measurements in infantile hypothyroidism. Relationship to serum thyrotropin concentrations.

Transplacental passage of thyrotropin (TSH)-binding inhibitory immunoglobulins may result in transient congenital hypothyroidism. We measured serum TSH-binding inhibitory index (TBII) in 11 infants with abnormal screening findings using a commercially available kit. Two of the infants, who were siblings, had markedly elevated TBII values (90% and 100%, respectively), as did their mother (89%, 100%), and had a clinical course consistent with transient antibody-mediated hypothyroidism. Four other infants had a borderline or mildly elevated TBII that was not present in maternal serum, suggesting that endogenous TSH was being measured in this assay. The TBII was measured in the sera of 18 additional children with primary hypothyroidism and in human TSH standards from 25 to 2000 mU/L. Increasing concentrations of TSH were associated with a linear increase in TBII. Measurement of TBII by this method may identify infants with transient antibody-mediated hypothyroidism, although simultaneous assessment of maternal serum is necessary.

Congenital concomitants of infantile hypothyroidism

Congenital concomitants of infantile hypothyroidism

PRELIMINARY REPORT ON PATIENTS WITH INFANTILE HYPOTHYROIDISM AFTER THE THIRD GRADE

Our first 26 hypothyroid patients to complete the third grade were tested for IQ, school achievement, and various neuropsychologic functions. Their results were compared to those of 44 age and sex matched classmates. Their rates of progress and difficulties in school were compared to those of 36 siblings. Because it has been iterated in the literature that patients with infantile hypothyroidism, even with normal IQs, have school learning problems, the correlation of IQ with school achievement test scores was analyzed for the patients analyzed for the patients and their classmates. All testing was conducted during the summer vacation. The patients repeated fewer grades by the end of 3 grades than had their siblings. The same percentage of patients and siblings required special help at school such as tutoring, use of resource room, or special education classes. No significant difference in test results or correlation of IQ and achievement scores was found comparing patients and appropriate controls. The mean and SEM for IQ of the patients and of their classmates were 109.2 ± 2.1 v 110.9 ± 1.8. The Peabody Achievement Test scores expressed as grade achieved minus grade placement were: math 1.4 ± .08 v 1.3 ± .06, reading recognition 1.5 ± .07 v 1.4 ± .06, reading comprehension 1.4 ± .07 v 1.5 ± .05, spelling 1.4 ± .07 v 1.4 ± .07, general information 1.3 ± .06 v 1.4 ± .05. The examiners were unaware of the identity of the subjects. Unless a patient or mother mentioned previous testing in the study, the reliability of the examiners in identifying the patients was no greater than chance.

CONGENITAL CONDITIONS ASSOCIATED WITH PERMANENT INFANTILE HYPOTHYROIDISM

Banforth et al have reported that among 37 patients with infantile hypothyroidism diagnosed as a result of screening, 7 had other congenital anomalies. We reviewed the records of 190 patients similarly diagnosed in N.E. in 1976 through 1981. Adequate information was available for 181 infants. We are reviewing a second cohort born in the ensuing 5 years. The incidence of congenital conditions was not significantly different from the accepted incidence of 3% in the general population. The congenital anomalies and other associated conditions (some of which were manifested only years after birth) included: mild pulmonic stenosis (n=2), atrial septal defect, imperforate anus, Pierre Robin syndrome, familial microcephaly, patent ductus arteriosus, club foot, vertex cutis aplasia, Williams syndrome, late 21-hydroxylase deficiency, Trisomy 21 (n=2), and spastic di or hemiplegia (n=3). The association of permanent and transient hypothyroidism with Down syndrome is well known. No hypothyroid patients have as yet been recognized to have Turner syndrome. The instance of cerebral palsy is interesting because of its occurrence in certain endemic cretins. Again because of the small number of hypothyroid patients the incidence cannot be distinguished from that in the general population (1:250). The patient with 21-hydroxylase deficiency has dyshormonogenesis. Her euthyroid twin also has the hydroxylase deficiency. Three of the other patients with associated congenital conditions also have dyshormonogenesis. One of the patients with pulmonic stenosis has an euthyroid twin.

Analysis of Thyrotropin‐Thyroxine Secretory Dynamics in Infantile Hyperthyrotropinemia: An Aid for Early Differential Diagnosis

AbstractFor the purpose of differentiating neonatal hyperthyrotropinemia, the interrelation between serum thyrotropin (TSH) and thyroxine (T4) was examined in 10 infants with primary hypothyroidism during 12 months of T4 replacement therapy. A significant inverse correlation was obtained between elevated TSH (Y) (above 12 μU/ml) and T4 (X) levels; Y = 324 ‐ 22 X (r = ‐0.801, p < 0.001). One patient had an abnormally high threshold of TSH‐inhibition by T4. Based on this regression line, a scattergram of TSH‐T4 correlation and changes in the time course was analyzed in 13 infants with neonatal hyperthyrotropinemia, including eight with transient hyperthyrotropinemia (t‐TSH), three with compensated hypothyroidism (c‐Hypo) and two with transient hypothyroidism (t‐Hypo). All plots from t‐TSH were distributed under the regression line and shifted downward with concomitant rise in T4 and free T4 levels. In contrast, plots from c‐Hypo and t‐Hypo showed a vertical upward shift above the line during 3–4 months of observation without treatment. These results indicate that (1) using the TSH‐T4 regression line, differentiation of c‐Hypo from t‐TSH is possible by 3 months of age, (2) the cause of t‐TSH is not an elevated threshold for TSH release, but rather the maturational delay in responsiveness of the thyroid to TSH, and (3) suppression of TSH alone should not be used as the index of adequate T4 dose in infantile hypothyroidism, because of the existence of patients with a high threshold of TSH‐inhibition by T4.

Infantile hypothyroidism in two sibs: An unusual presentation of pseudohypoparathyroidism type Ia

PATIENTS with pseudohypoparathyroidism have clinical and biochemical evidence of hypoparathyroidism, yet fail to show either a ealcemic or phosphaturic response to administered parathyroid extractk In addition to these biochemical abnormalities, many patients have Albright hereditary osteodystrophy, an unusual somatic phenotype characterized by obesity, short stature, brachydactyly, and heterotopic ossification. In many patients with PHP type 1,* impaired renal adenylate cyclase responsiveness to PTH 3 has been associated with deficient activity of the stimulatory guanine nueleotide regulatory protein of adenylate cyclase. 4, 5 Because available evidence suggests that Gs is similar in all tissues, a ubiquitous deficiency of Gs could be the basis for PTH resistance, the hallmark of PHP, and could explain the decreased responsiveness of diverse tissues (e.g., kidney, thyroid gland, gonads, and liver) to hormones that act via cAMP (e.g., PTH, TSH, gonadotropins, and glucagon). 6 Despite the generalized nature of the Gs defect in PHP type Ia , t clinical recognition of the disorder generally

Infantile hypothyroidism then and now: The results of neonatal screening

Infantile hypothyroidism then and now: The results of neonatal screening

IgA deficiency during treatment of infantile hypothyroidism with thyroxine.

Serum IgA concentrations in five children with infantile hypothyroidism fell soon after the start of treatment with thyroxine. In one child the IgA concentration fell appreciably (to less than 0.01 g/1) and remained reduced; in the four others it returned to normal. IgM and IgG concentrations were roughly normal throughout. The deficiency in IgA concentrations may have been due to stimulation by thyroxine treatment of a T cell suppressor system that, in the original hypothyroid state, was less than normally active.

Characteristics of infantile hypothyroidism discovered on neonatal screening

Clinical and laboratory data from 146 patients with infantile hypothyroidism diagnosed by neonatal screening over a five-year period are presented. In 95 patients there was adequate thyroid imaging or evidence of dyshormonogenesis; of these, 43% had ectopic thyroid tissue, 22% had goitrous hypothyroidism, and 35% had hypoplastic or aplastic glands. Stanford-Binet IQs of the patients at 3, 4, and 5 years of age were identical with those of control subjects. Patients in whom thyroid tissue was demonstrable on radioactive scanning had higher concentrations of T4 and T3, and lower concentrations of TSH and less retarded bone age, but did not differ in ultimate IQ from patients with no demonstrable thyroid tissue. No significant correlation with ultimate IQ was found for any clinical or laboratory factor except for the adequacy of treatment. Eleven children with inadequate treatment had a mean IQ significantly less than that of other patients, 87 +/- 5 (SEM) vs 105 +/- 2. Inadequate treatment was defined essentially by repeated T4 concentrations less than 8 micrograms/dl during treatment. Thus, T4 values in the lower part of the normal range are probably incompatible with maximal intellectual development, and every effort should be exerted to maintain serum T4 levels in the upper half of the normal range during the first year of life.