Neonatal Hyperthyrotropinemia Research Articles

Outcomes of newborns screened for congenital hypothyroidism in Turkey- a single center experience.

It was aimed to investigate the outcomes of babies referred to a tertiary health center in Turkey for evaluation primary congenital hypothyroidism (CH) through newborn screening. The hospital files of 328 newborns who were referred for CH from newborn screening between June 2013 and June 2020 were retrospectively reviewed. The newborns were evaluated with their clinical characteristics at admission, as well as their follow-up data and final diagnoses. Sixteen (4.9 %) newborns were diagnosed with transient neonatal hyperthyrotropinemia after follow-up. Treatment was initiated in 166 (50.6 %) of the cases with a diagnosis of CH. The median age at initiation of treatment was 17days (5-69). Treatment was initiated in 88.3 % of the cases in the first month of the life. After at least 3 years of follow-up, 30/120 (20.0 %) of the cases were diagnosed with permanent CH and 11/30 (36.7 %) of them were diagnosed with thyroid dysgenesis. All of the cases who used >37.5 µg per day levothyroxine at the age of 1 or 2 years were diagnosed with permanent CH during their follow-up. For the prediction of transient CH, the sensitivity and specificity of levothyroxine doses of≤25 µg per day at 1 year of age were calculated as 96.2 and 46.2 %, and for 2 years of age, the sensitivity and specificity were calculated as 97.8 and 65.2 %. In this cohort, 10 % of all referrals result in permanent CH. Thyroid imaging with ultrasonography and levothyroxine dose during follow-up can be guiding in predicting permanent CH.

Approach to Newborns with Elevated TSH: A Different Perspective from the International Guidelines for Iodine-Deficient Countries.

Lowering of thyroid-stimulating hormone (TSH) cutoffs in newborn screening programs has created a management dilemma by leading to more frequent detection of neonates with elevated TSH concentrations due to false-positive results, transient neonatal hyperthyrotropinemia (NHT), and milder forms of congenital hypothyroidism. Current consensus guidelines recommend starting treatment if the venous TSH level is >20 mU/l in the face of a normal free thyroxin (FT4) level, which is an arbitrary threshold for treatment decisions. In countries such as Türkiye, where transient NHT may be more common due to iodine deficiency and/or overload, putting this recommendation into daily practice may lead to unnecessary and over treatments, long-term follow-ups, and increased workload and costs. In this review, we addressed alternative approaches for infants with elevated TSH concentrations detected at newborn screening. Our management approach can be summarized as follows: Infants with mild NHT (TSH<20 mU/l) should be followed without treatment. In moderate NHT (TSH 20-30 mU/l), treatment or monitoring decisions can be made according to age, TSH trend and absolute FT4 level. Moderate cases of NHT should be treated if age at confirmatory testing is >21 days or if there is no downward trend in TSH and FT4 level is in the lower half of age-specific reference range in the first 21 days. In in-between cases of moderate NHT, thyroid ultrasound can guide treatment decision by determining mild cases of thyroid dysgenesis that require life-long treatment. Otherwise, monitoring is a reasonable option. Infants with compensated hypothyroidism (TSH>30 mU/l) and persistent hyperthyrotropinemia (>6-10 mU/l after neonatal period) should receive L-thyroxine treatment. But all treated cases of isolated TSH elevation should be closely monitored to avoid overtreatment, and re-evaluated by a trial off therapy. This alternative approach will largely eliminate unnecessary treatment of infants with transient NHT, mostly caused by iodine deficiency or excess, and will reduce workload and costs by preventing unwarranted investigation and long-term follow-up.

Patterns of Endocrine Disorders in a Neonatal Intensive Care Unit: A Single-Center Retrospective and Descriptive Study

Background: Endocrine disorders in infants in neonatal intensive care units (NICU) represent a significant clinical concern. Understanding the frequency and variety of these disorders is crucial for effective patient management. Objectives: This single-center retrospective study was conducted to examine the frequency and patterns of endocrine disorders among neonates in the NICU. Methods: We performed a retrospective review of 1 845 patient records over five years from the NICU at Çanakkale Onsekiz Mart University Health Practice and Research Hospital. The study included patients admitted between January 1, 2016, and March 31, 2021, who were diagnosed with endocrine disorders according to the international classification of diseases (ICD). Diagnostic criteria were used to identify and categorize endocrine disorders, primarily focusing on hypoglycemia, congenital hypothyroidism, hypothyroxinemia of prematurity, neonatal hyperthyrotropinemia (HTT), and disorders of calcium and magnesium metabolism. Data analysis was conducted using descriptive statistics. Results: Endocrine disorders were identified in 14.6% (CI: 13.15 - 16.38) of the neonates. The most prevalent were thyroid disorders (5.15%, CI: 4.23 - 6.25), disorders of calcium metabolism (3.68%, CI: 2.92 - 4.64), and disorders of glucose homeostasis (3.63%, CI: 2.87 - 4.58). Notably, neonatal HTT was more frequent than previously reported. The majority of endocrine issues occurred in premature infants. Hypoglycemia was the most frequent glucose homeostasis disorder, affecting 24.7% (CI: 19.9 - 30.2) of those diagnosed with endocrine issues. Among the cases with calcium metabolism disorders, hypocalcemia was predominant (79.4%, CI: 68.3 - 87.3), with the majority (89%, CI: 80.1 - 95.9) being classified as early neonatal hypocalcemia. Conclusions: Endocrine disorders, particularly those related to thyroid, calcium, and glucose homeostasis, remain prevalent issues in the NICU. Prematurity significantly contributes to these complications. The frequency and variety of endocrine disorders are likely to evolve with improvements in laboratory techniques and diagnostic methods. Future larger-scale studies could provide more comprehensive insights into these disorders.

Prevalence of congenital hypothyroidism and transient neonatal hyperthyrotropinemia in babies born to hypothyroid mothers at a tertiary care hospital

Objectives: Transient neonatal hyperthyrotropinemia (TNH) is being increasingly recognized in the developed world as a risk factor for the development of permanent hypothyroidism. It is defined as transient elevation of serum thyroid-stimulating hormone (TSH) levels between 10 and 20 mIU/L after 48 h of life with normal free thyroxine levels, returning to normal after 2 weeks of life. Factors associated with TNH as well as its consequences on growth and development are lesser known at present. Maternal hypothyroidism, both overt and subclinical, is known to have adverse neurodevelopmental outcomes in children. Maternal hypothyroidism is also one of the risk factors for developing TNH. This study aimed to measure the prevalence of congenital hypothyroidism (CH) and TNH, and evaluate neurodevelopmental outcomes in children born to hypothyroid mothers. Material and Methods: Sixty-three consecutive neonates born to mothers diagnosed as hypothyroid during pregnancy were enrolled for the study. Fifty neonates underwent evaluation for thyroid functions and development till 6 months of age, after excluding preterm and sick babies requiring intensive care. Results: None of the babies had CH. The prevalence of TNH was found to be 6.0% (n = 3/50), with TSH values normalizing by 4 weeks of age. All babies with TNH were female. Development assessment done till 6 months of life was normal for all babies. Conclusion: Our study describes the prevalence of TNH and short-term development outcomes in babies born to hypothyroid mothers. The role of TNH in the development of permanent hypothyroidism is still a debatable topic, and larger studies are needed to assess its implications on linear growth, academic performance, as well as language and intellectual development.

Iodine deficiency in pregnant women and newborns in the Saratov region: current state of the problem

Introduction. Iodine deficiency remains an urgent challenge for the Russian Federation. Pregnant women should receive prophylactic potassium iodide supplements at a dose of 200–250 mcg per day. To monitor the severity of iodine deficiency in the regions and the efficacy of prenatal iodine prophylaxis, it is prudent to use the neonatal hyperthyrotropinemia rate for newborns (thyroidstimulating hormone level is higher than 5 μIU/L) based on the results of congenital hypothyroidism screening.Objective. To assess the changes in the severity of iodine deficiency and the efficacy of iodine prophylaxis in pregnant women and newborns in the Saratov region based on the incidence of neonatal hyperthyrotropinemia over the past 25 years.Materials and methods. The incidence of neonatal hyperthyrotropinemia in newborns in the Saratov region for the period of 1996–2000 and 2015–2020 was analysed. In total, 229,625 children were examined.Results and discussion. In 1996–2000, neonatal hyperthyrotropinemia was detected in 37.4% of newborns, which was evidence of the presence of moderate iodine deficiency in the region. In 2015–2020, the incidence of neonatal hyperthyrotropinemia decreased by 5.42 times to 6.9% (p &lt; 0.0001) against the background of group iodine prophylaxis in pregnant women, but remained higher than the World Health Organization targets for iodine-rich regions (&lt;3%) suggesting the preservation of mild iodine deficiency in pregnant women and newborns in the Saratov region.Conclusions. Despite the obligatory doctor’s prescription of prenatal group iodine prophylaxis, there is still iodine insufficiency in pregnant women and newborns in the Saratov region, which requires further improvement of the regional iodine deficiency eradication action system in the risk groups. However, significant advances in the fight against iodine deficiency in the nutrition of the Russian population can only be achieved after the adoption of the federal law on universal salt iodization.

Assessment of the iodine deficiency severity in the population by serum thyrotropin levels in newborns

The problem of iodine deficiency (ID) and its adverse effects on the Ukrainian population, especially on children, pregnant and lactating women, does not lose its relevance. The aim. To assess the state of iodine status of the Northern Bukovіna population by the level of thyrotropin (TSH) in newborns during the years 2015–2020. Methods. Selective screening analysis to determine the serum level of TSH in newborns during 2015–2020 (a total of 47888 results), median ioduria and survey among pregnant women, determination of urinary iodine, ultrasonographic and hormonal profiles of 199 prepubertal children living in Northern Bukovina were performed. Results. During the analyzed period, there was a positive trend: the median ioduria in pregnant women increased from 89.8 μg/l in 2015 to 140.1 μg/l in 2020, the level of neonatal hyperthyrotropinemia above 5 μIU/l decreased to 5 % in 2020 (P &lt; 0.001), there was an upward trend in the median ioduria among prepubertal children (60.4 ± 9.3 μg/l). The frequency of goiter was different and accounted for 25.3 % among children living in the mountainous area and it was much lower among children living in the plain areas and in Chernivtsi (15.6 % and 13.1 %, respectively, P &lt; 0.05). Thyromegaly among children of the reference group occurred in 15.1 %. 12.3 % of children were characterized by TSH in the range of age standards, which were shifted towards its increase (4.23–5.00 μIU/l). Conclusions. The increase in the median ioduria and the decrease in the frequency of neonatal hyperthyrotropinemia above 5 μIU/l on the background of iodine supply has been found in the pregnant population. The indicator of neonatal hyperthyrotropinemia above 5 μIU/l can be used to assess iodine deficiency only in the population of pregnant women.

Factors associated with moderate neonatal hyperthyrotropinemia.

BackgroundMaternal iodine deficiency is related to high neonatal thyroid-stimulating hormone (TSH) values, with the threshold of 5 mIU/L recommended as an indicator of iodine nutrition status. The objective of this study was to analyse possible risk factors for increased TSH that could distort its validity as a marker of iodine status. The clinical relevance of this research question is that if the factors associated with iodine deficiency are known, iodine supplementation can be introduced in risk groups, both during pregnancy and in newborns.MethodsA case-control study was carried out in a sample of 46,622 newborns in 2002–2015 in Spain. Of these, 45,326 had a neonatal TSH value ≥5 mIU/L. The main variable was having TSH ≥5 mIU/L and the secondary variables were: sex, gestational age, day of sample extraction and maternal origin. Associated factors were analysed through a logistic regression model, calculating the odds ratio (OR).ResultsThe factors associated with this outcome were: male sex (OR = 1.34, 95% CI: 1.20–1.50, p<0.001), originating from an Asian/Oceanic country (OR = 0.80, 95% CI: 0.54–1.20, p = 0.536) or Europe (OR = 0.80, 95% CI: 0.66–0.96, p = 0.285) (including Spain, OR = 1) [p<0.001 for America (OR = 0.54, 95% CI: 0.44–0.68) and p = 0.025 for Africa (OR = 0.78, 95% CI: 0.62–0.97)] and fewer days from birth to sampling (OR = 0.80, 95% CI: 0.77–0.82, p<0.001).ConclusionsThe risk of high neonatal TSH without congenital hypothyroidism is higher in males, decreases with a greater number of days from birth to extraction, and is dependent on maternal ethnicity but not on gestational age.

Assessment of indicators of medical and biological monitoring of iodine deficiency diseases

The problem of iodine deficiency remains relevant all over the world due to the widespread prevalence and the negative impact it has on human health in all agegroups. Iodine deficiency leads to a decrease in the intellectual potential of children, the development of reproductive disorders at a young age, as well as the formation of multinodular toxic goiter as the last stage of goiter transformation, accompanied by heart rhythm disturbances in middle and old age. The article covers the issues of monitoring iodine deficiency in the regions of Russia and provides data on the situation in the world on the development of future prevention programs and current prevention programs. A detailed analysis of each criterion for the severity of iodine deficiency and the effectiveness of preventive programs was carried out. Particular attention is paid to the criterion of neonatal hyperthyrotropinemia as a promising indicator for monitoring iodine deficiency.

The role of food in prevention and correction of iodine deficiency in the endemic territory

Iodine supply remains the global problem due to the wide prevalence and a wide range of clinical manifestations in all age groups of population. However, iodine deficiency is a nutritional deficiency and the solution of this problem lies in the organization of rational nutrition of the population. The purpose of this study was to examine the food features of the population of the mild iodine-deficient region from the standpoint of adequacy of iodine sufficiency. The analysis of nutrition of the population of Tyumen Region in 2005 and 2016 was carried out according to official statistics of Tyumenstat; results of sanitary-hygienic and biomedical monitoring for the period from 1994 to 2016. A sociological study was conducted on a representative nested sample using the questionnaire method. The study involved schoolchildren (n=744) and their parents (n=677), students and full-time students (n=623). Probabilistic was sampling and nesting. Statistical sampling error does not exceed 4%. Analysis of the level of food consumption by residents of the Tyumen region over the period from 2005 to 2016 showed an increase in consumption per capita of fish and fish products (from 23.8 kg in 2005 to 33.1 kg in 2016 at recommended level of 22 kg). At the same time, a sociological study showed that only 1-4% of the population consumed iodine-rich products daily and only 53% of respondents regularly used iodized salt. The analysis of the results of biomedical monitoring over the 20-year period of the existence of preventive programs in the Tyumen region showed significant improvements in the situation in the region: median of ioduria increased significantly from 77 to 125 μg/l and the incidence of goiter in pre-pubertal children decreased from 85% in 1994 to 6.8% in 2016 (р=0,001); the incidence of neonatal hyperthyrotropinemia significantly decreased from 44.3% in 1994 to 3.9% in 2017 (р=0,001). However, most indicators did not reach the target values recommended for iodine-rich region, which indicated the insufficient effectiveness of the existing voluntary prevention system. The solution of this problem is using of iodine-enriched foods of mass consumption, such as bread and bakery products.

Iodine status of Saint Petersburg adult residents

Обоснование. В мире около двух миллиардов человек имеют недостаточное потребление йода.&#x0D; Цель. Оценить обеспеченность йодом и эффективность профилактики йодного дефицита у взрослого населения Санкт-Петербурга.&#x0D; Методы. В ретроспективной части работы проведен анализ распространенности гипертиреотропинемии новорожденных Санкт-Петербурга за период 2013–2014 гг. В одномоментное поперечное когортное исследование были включены 542 жителя Санкт-Петербурга в возрасте 18–77 лет. Все участники были разделены на три группы согласно возрасту. Беременные женщины были выделены в отдельную группу. У всех участников проведено анкетирование и проанализированы значения йодурии.&#x0D; Результаты. Количество новорожденных, имевших концентрацию тиреотропного гормона более 5 мЕД/л, составило 6,9%, отражая дефицит йода легкой степени тяжести у населения. Йодированную соль использовали в пищу только 41,1% всех обследованных и 52,2% беременных женщин. Препараты йода принимала половина беременных женщин. Медиана йодурии (МЙУ) всех участников составила 91,2 мкг/л и соответствовала дефициту йода легкой степени тяжести. Значение МЙУ у беременных женщин составило 112,4 мкг/л и соответствовало недостаточному потреблению йода.&#x0D; Заключение. Население Санкт-Петербурга проживает в регионе легкого дефицита йода. Профилактика дефицита йода, проводимая в Санкт-Петербурге в 2013–2015 гг., недостаточно эффективна. Лица репродуктивного возраста и беременные женщины имеют дефицит йода легкой степени тяжести.

AB048. Maternal and neonatal factors associated with transient neonatal hyperthyrotropinemia: Indian context

AB048. Maternal and neonatal factors associated with transient neonatal hyperthyrotropinemia: Indian context

Can One Predict Resolution of Neonatal Hyperthyrotropinemia?

To identify predictors of transience vs permanence of neonatal hyperthyrotropinemia. We hypothesized that infants with greater severity of perinatal stress are more likely to have transient thyrotropin elevations. We retrospectively studied infants diagnosed with hyperthyrotropinemia between 2002 and 2014, following them for up to 12years after diagnosis. Patients were divided into 3 groups: transient hyperthyrotropinemia (treatment was never prescribed), transient congenital hypothyroidism (treatment started but discontinued), and permanent congenital hypothyroidism (withdrawal unsuccessful or not attempted). We performed univariate and multiple logistic regression analyses, including and excluding infants with maternal thyroid disease. We included 76 infants, gestational age mean (±SD) 34.2 (±5.7) weeks, evaluated for hyperthyrotropinemia. Thirty-five (46%) were never treated, and 41 (54%) received levothyroxine. Of the treated patients, 16 successfully discontinued levothyroxine, and for 25 withdrawal either failed or was not attempted. We found that male patients were almost 5 times more likely than female patients to have transient neonatal hyperthyrotropinemia (OR 4.85; 95% CI 1.53-15.37). We documented greater maternal age (31.5±5.48years vs 26±6.76years, mean±SD, P=.02), greater rate of cesarean delivery (86.7% vs 54.2%; P=.036), and retinopathy of prematurity (37.5% vs 8%; P=.02) in the group with transient congenital hypothyroidism vs the group with permanent congenital hypothyroidism. The results show transience of neonatal thyrotropin elevations in a majority of patients and suggest a possible association of hyperthyrotropinemia with maternal and perinatal risk factors.

Use of Tc‐99 m thyroid scans in borderline congenital hypothyroidism

Mild or borderline congenital hypothyroidism [often referred to as mild neonatal hyperthyrotropinemia (MNH)] is characterized by an abnormal newborn screen (NBS), followed by mildly elevated TSH and normal FT4 on confirmatory testing. This condition is increasingly observed, but data regarding optimal management are limited. Examine the use of routine technetium thyroid scanning (TS) in the management of MNH. Retrospective study of infants with MNH between 2000 and 2011. We assessed the clinical course of infants with MNH according to TS results; as a comparator, infants with classic congenital hypothyroidism (CH) were analysed in parallel. We identified 69 infants (52% boys) with MNH and 164 (34% boys) with classic CH. TS results were divided into four subgroups: no uptake in 7% of MNH vs 24% of classic CH (P<0·01), decreased uptake/anatomical abnormalities in 39% vs 46% (p=NS), increased uptake in 35% vs 26% (p=NS) and normal uptake in 19% vs 4% (P<0·01). In MNH, neither NBS-TSH, confirmatory TSH and FT4, mean LT-4 treatment doses and number of dose escalations, nor post-treatment FT4 and TSH differed among the four subgroups. In contrast, clinical features in infants with classic CH differed among the subgroups. Among MNH infants who reached 3years of age, trial-off treatment was successful in 6 of 11 (55%) with no apparent difference in success rates among TS subgroups. The information provided by TS during evaluation of MNH does not predict clinical course; obtaining these scans in infants with MNH may not be an effective use of healthcare resources.

Transient neonatal hyperthyrotropinemia is a risk factor for developing persistent hyperthyrotropinemia in childhood with repercussion on developmental status

Transient neonatal hyperthyrotropinemia (TNH) is defined as a neonatal abnormality of thyroid function, which reverts to normal at re-examination after 2 weeks of life. The thyroid function of these infants has not been sufficiently studied in terms of the risk of developing persistent hyperthyrotropinemia (PH) in later childhood and its impact on growth and development. A prospective cohort study included all babies born in our hospital between 2001 and 2006 and screened for hypothyroidism, whose thyroid function was re-examined 6 years later. Exclusion criteria included the following conditions: preterm birth, birth weight <2500 g, Down's syndrome, descendants of mothers with immune thyroid disease, congenital malformations, cardiac, renal, hepatic, and metabolic diseases, and steroid or dopamine medication. The variables included are TSH and thyroxine at neonatal screening and 6 years later. Main outcomes are the risk of developing PH in childhood, linear growth, and development using Parents' Evaluation of Developmental Status (PEDS). Out of 5040 normal-term newborns, 301 (6.0%, 95% CI 5.3-6.6%) have TSH ≥10 mU/l (TNH). Six years later, we re-examined 65 randomly selected children with TNH and 185 controls. In the TNH cohort, we found six out of 65 children (9.2%, 95% CI 1.4-17.0%) with PH (TSH ≥6.4 mU/l), and three out of 185 (1.6%, 95% CI 0.3-4.7%) among controls, relative risk 5.7 (95% CI 1.5-22.1), P=0.0114. TSH and developmental delay were found to be significantly higher in the TNH cohort (4.7±1.3 mU/l vs 2.1±0.5 mU/l, P<0.0001 and 15/65 (23%, 95% CI 12-34.1) vs 21/185 (11.3%, 95% CI 6.5-16.2) P=0.0348). Newborns with TNH have a higher risk of developing PH in childhood, with repercussion on developmental status.

Role of thyrotropin-releasing hormone test in re-evaluation of congenital hypothyroidism

The thyrotropin-releasing hormone (TRH) test is useful for differentiating central and primary hypothyroidism, and is also valuable for diagnosing hypothyroidism. The threshold of the TRH test is usually set at 10–40 mIU/L. However, some experts are of the opinion that the TRH test has a limited role in evaluating hypothyroidism because of the clinical application of the new-generation thyroid-stimulating hormone (TSH) assay. We reviewed a case series to analyze the clinical use of the TRH test in the re-evaluation of congenital hypothyroidism. In total, data on 228 children with eutopic thyroid glands and neonatal hyperthyrotropinemia under levothyroxine replacement were collected. Basal TSH levels were measured and the TRH test was performed at the age of 3 years for re-evaluation of congenital hypothyroidism, and statistical analysis was performed. All of the patients were followed up to avoid over- or under-treatment. At the age of 3 years, 31.6% of the patients still had hypothyroidism. There was no significant difference between basal TSH level and TRH test in the diagnosis of hypothyroidism (p = 0.23). The negative predictive value of the basal TSH level was 100%, however, the positive predictive value was only 43.6%. When the TSH level was near the upper limit of the normal range (4.5–8.5 mIU/L), the TRH test result had a better correlation with hypothyroidism than the basal TSH level (p = 0.03). The threshold of the TRH test set at 60 mIU/L had the greatest area under the curve, with a negative predictive value of 95.2% and a positive predictive value of 80.2%. Neonatal hyperthyrotropinemia was a risk factor for hypothyroidism. We suggest that the TRH test should be administered in children with a basal TSH value near the upper limit of the normal range, and the threshold of the TRH test should be set at 60 mIU/L.

Evaluation of different methods of iodine prophylaxis in infants in the region of mild iodine deficiency

Aim: To evaluate of the effectiveness of different methods of iodine prophylaxis in infants. Materials and Methods: The dynamic monitoring of pregnant and lactating mothers and their infants with iodine supplementation (potassium iodine, iodized salt) and without it. Results: Lack of antenatal iodine supplementation leads to a complicated course of the perinatal period, an increase of frequency of gestational hypothyroxinemia and neonatal hyperthyrotropinemia. Infants without iodine prophylaxis have higher levels of TSH and lower content of fT4. Conclusion: The most effective method of iodine supplementation in infants is individual iodine prophylaxis with potassium iodide in pregnant and lactating mother.

Correct understanding of neonatal hyperthyrotropinemia

In recent years,with the criterion and scaling up of newborn screening work,not only the rates of neonatal congenital hypothyroidism screening increased year by year but also more and more neonatal hyperthyrotropinemia children have been found.How to correctly understand the neonatal hyperthyrotropinemia is still one of the problems in the clinical work.This article will review the causes,diagnosis,prognosis and treatment principles of hyperthyrotropinemia. Key words: Newborn; Thyroid stimulating hormone; Diagnosis; Ttreatment

Novel heterozygous thyrotropin receptor mutation presenting with neonatal hyperthyrotropinaemia, mild thyroid hypoplasia and absent uptake on radioisotope scan

Hyperthyrotropinaemia [mildly elevated thyrotropin (TSH) with normal thyroxine (T4) levels] demands a full assessment, including clinical examination, thyroid imaging and, where indicated, molecular genetic investigations. A male infant, both of whose parents were on T4 treatment, was referred at age 57 days with mild but persistent TSH elevation (12.7 mU/L) and normal free T4 (19.6 pmol/L), following notification by the screening laboratory of a capillary TSH of 10.7 mU/L (reference range, 1.7-9.1 mU/L) on day 8. Assessment showed a venous free T4 level of 15 pmol/L, venous TSH of 20.9 mU/L, serum thyroglobulin of 63 μg/L (reference range, <50 μg/L), and negative thyroglobulin and thyroid peroxidase antibodies. Thyroid ultrasound showed a eutopic, slightly small gland with heterogeneous texture; however, there was no uptake on radioisotope scan. Molecular genetic studies demonstrated a novel missense heterozygous mutation in the TSH receptor (TSHR) gene (c.1169G>T;p.Cys390Phe) in the child, mother and maternal grandmother, but not in the father. The infant was treated with T4 but this was discontinued at age 3 years when repeat testing showed a free T4 of 16.7 pmol/L (reference range, 9-23 pmol/L) and TSH of 8.5 mU/L (reference range, 0.3-5.5 mU/L). A heterozygous TSHR mutation should be considered in the context of hyperthyrotropinaemia and reduced/absent uptake on radioisotope scan. Detection of this mutation has allowed our patient to discontinue T4 treatment for the moment, with a view to staying off treatment in the long-term.

Neonatal hyperthyrotropinemia is associated with low birth weight: a twin study

Contradictory reports ascribe neonatal hyperthyrotropinemia (HT) to prematurity or small weight for gestational age. We aimed to evaluate the association between neonatal HT and birth weight (BW), recovery rate of the disorder, and possible association with perinatal stress. Based on a neonatal screening database, a retrospective twin study was designed where within-pair differences in thyroid function were evaluated while controlling for differences in gestational age and thyroid-affecting environmental confounders. Two thousand five hundred and ninety-five twin pairs that were screened both for TSH and thyroxine (T(4)) over 3 years were included. TSH and T(4) levels were evaluated along with BW, birth order, gender, and 17-hydroxyprogesterone (17OHP) that was considered as a surrogate marker for stress. Of all the twin pairs, 7.2% had neonatal HT. Among 156 pairs, HT was more prevalent in the smaller twins (64%; P<0.001), especially in the discordant pairs (76%; P=0.001). Seventy-five percent of the twins demonstrated a recovery within the first few weeks of life. 17OHP levels were similarly distributed between twins with and without HT. In a cohort of 1534 twin pairs with normal thyroid function, mean TSH levels were significantly higher in the smaller than in the larger twin in the whole group (4.1±3.2 vs 3.8±2.9 mIU/l; P<0.001) and especially among discordant twins (4.7±3.4 vs 3.8±3.0 mIU/l; P<0.001). Elevated TSH levels are associated with low BW, both in infants with HT and in normal neonates. A rapid recovery rate is expected in most cases.

SEASONAL VARIATION OF NEONATAL TRANSIENT HYPERTHYROTROPINEMIA IN TEHRAN PROVINCE, 1998–2005

Seasonal aggregation and the monthly rate of neonatal transient hyperthyrotropinemia (THT) were assessed. From November 1998 to April 2005, neonates of gestational age ≥37 wks, birth weight 2500–4000 g, birth length 45–55 cm, and 1st min Apgar score >3, who had thyrotropin (TSH) ≥20 mU/L in their cord dried-blood specimen, but without congenital hypothyroidism, were enrolled in the study. The recall rate equals the rate of THT occurrence in this study. Of 47,945 neonates, 555 had THT (recall rate: 1.2%). The aggregated seasonal recall rate (recall for further assessment to rule out congenital hypothyroidism) was significantly higher in winter (January, February, and March) than the other seasons (p < .0001). Winter had higher recall rate in each year as compared to other seasons, but the overall rate of recalls decreased in 2001 and 2002. Excluding the first 6 months (due to erratic variations), the remaining 72 months revealed a relatively sinusoidal pattern in monthly recall rates; indeed, there was an initial 11-month high recall rates (1.7%), followed by a 33-month decrease (0.7%), a 19-month increase (1.9%), and a final 9-month decrease (0.8%). The recall rate of each of these time intervals was significantly different from that of the next time interval (p < .0001). The monthly recall rates were best fitted to cubic curve estimation and then autoregressive integrated moving average (ARIMA) (0, 1, 1) models. THT occurs significantly more in winter than in other seasons, and this suggests a possible role for time-varying factor(s) contributing to its seasonal preponderance. (Author correspondence: E-mail: arash_ordookhani@yahoo.com)