Early differentiation between transient congenital hypothyroidism (TCH) and permanent congenital hypothyroidism (PCH) is crucial for optimizing the duration of treatment. This retrospective cohort study aimed to evaluate whether levothyroxine (LT4) dose requirements over time can predict TCH and guide earlier discontinuation of treatment. We retrospectively analyzed 105 infants with congenital hypothyroidism and normal thyroid glands confirmed by imaging at a single tertiary care center (Inha University Hospital) between January 2013 and December 2022. Patients were classified into TCH (n=70) or PCH (n=35) based on thyroid function after LT4 withdrawal at 3 years of age. LT4 dose/kg at 6, 12, and 24 months, along with clinical and biochemical parameters, were compared between the 2 groups. Receiver operating characteristic (ROC) curve analysis was used to assess the predictive performance of LT4 dose thresholds. The LT4 dose was significantly lower in the TCH group at 6 (3.16±0.83 μg/kg vs. 3.75±0.99 μg/kg, P=0.005), 12 (2.51±0.82 μg/kg vs. 3.37±1.17 μg/kg, P<0.001), and 24 months (2.02±0.61 μg/kg vs. 3.09±1.19 μg/kg, P<0.001). ROC curve analysis showed an area under the curve (AUC) of 0.649, 0.746, and 0.794 at 6, 12, and 24 months, respectively. A logistic regression model incorporating LT4 dose, birth weight, and thyroid-stimulating hormone (TSH) levels improved prediction accuracy (AUC: 0.740, 0.782, 0.833 at 6, 12, and 24 months, respectively). LT4 dose requirements at 6, 12, and 24 months serve as useful indicators for differentiating TCH from PCH. A combined predictive model incorporating LT4 dose, birth weight, and TSH levels may improve diagnostic accuracy, supporting earlier discontinuation of treatment.

Distinguishing between transient congenital hypothyroidism (TCH) and permanent congenital hypothyroidism (PCH) remains clinically challenging and is typically deferred until the age of 2-3 years, to minimise the potential risk of adverse neurodevelopmental effects due to treatment cessation. However, evidence suggests that earlier discrimination may be feasible, thus avoiding unnecessary, potentially harmful, prolonged levothyroxine (LT4) treatment. This narrative review aims to provide an overview of the current literature regarding potential predictive markers for distinguishing PCH from TCH. A comprehensive search of the PubMed and Google Scholar databases was independently performed by two authors to identify studies that evaluated the utility of several predictive factors. A total of 27 studies were included. The most commonly proposed predictors were thyroid imaging findings, thyroid-stimulating hormone (TSH) levels at diagnosis, LT4 doses at various time points during the treatment period, absolute daily LT4 dose, and episodes of TSH elevation above the reference interval during treatment. Despite these advances, no single marker or combination of markers has yet proven definitive in reliably differentiating PCH from TCH. Further research is needed to establish predictive models that could facilitate the early identification of TCH and the timely and safe treatment withdrawal.

Before the introduction of newborn screening, congenital hypothyroidism was the leading cause of intellectual disability in infants and children. Patients with permanent congenital hypothyroidism require lifelong levothyroxine supplementation to prevent intellectual disability and growth failure. With progressively lower thyrotropin (TSH) cutoffs in newborn screening programs, more transient congenital hypothyroidism cases-requiring only temporary treatment-have also been identified. To avoid unnecessary medication use and reduce the burden on healthcare systems, early differentiation is essential. We retrospectively enrolled congenital hypothyroidism patients born between 2004 and 2018 and followed at MacKay Children's Hospital and classified them as permanent congenital hypothyroidism or transient congenital hypothyroidism based on levothyroxine dependence. Basic demographic data, including gender, gestational age, birth weight, newborn screening TSH levels, body height and weight, serum free T4, TSH levels, levothyroxine doses at every clinical visit, and age of TSH normalization were collected and compared between permanent and transient congenital hypothyroidism groups. A total of 152 infants were enrolled in this study, with 73 (48%) classified as permanent congenital hypothyroidism. Term births were more common in permanent than transient congenital hypothyroidism (80% vs. 48%, p < 0.01). TSH normalization took longer in permanent congenital hypothyroidism (75 vs. 45 days, p < 0.01). Serum TSH and levothyroxine doses remained higher in permanent congenital hypothyroidism at 6 months, and at 1, 2, and 3 years. The levothyroxine dose that provided the best discrimination between permanent and transient congenital hypothyroidism was 2.5 𝛍g/kg/d at age 2 years (sensitivity: 73%, specificity: 90%), and 1.8 𝛍g/kg/d at age 3 years (sensitivity: 82%, specificity: 91%). Nearly half of the patients required lifelong levothyroxine supplements under the current newborn screening program. Permanent congenital hypothyroidism patients were more likely term-born, showed delayed TSH normalization, had higher TSH levels, and required higher levothyroxine doses during follow-up. The best cut-off level to discriminate permanent from transient congenital hypothyroidism was 2.5 and 1.8 µg/kg/day at the age of 2 and 3 years, respectively.

Transient congenital hypothyroidism (CH) caused by maternal thyrotropin receptor-blocking antibody (TBAb) has been uncommonly reported. Goiter is a significant indicator of fetal thyroid dysfunction that may facilitate early identification, but some cases present without this manifestation. This report describes a case of CH attributed to maternal elevated levels of thyroid-stimulating hormone receptor antibody (TRAb) with normal thyroid size, and further provides a systematic review of neonatal thyroid size classification in other CH cases from the literature. The mother had a history of hypothyroidism related to Hashimoto's thyroiditis and elevated TRAb levels. Maternal TRAb level exceeded 40 IU/L in the first trimester. The circumference of fetal thyroid gland maintained within the normal range throughout pregnancy. However, the secondary ossification centers were not visible at 37 weeks of gestation. CH was confirmed through thyroid function testing on postnatal day 9. Neonatal TRAb levels became undetectable by 3 months after birth, and levothyroxine (LT4) treatment was discontinued at 7 months of age. The young child demonstrated appropriate intellectual development during 18 months of follow-up. We conducted an analysis of 17 TRAb-related CH cases from PubMed, Web of Science and Embase. Most maternal TRAbs (13/17) were detected postpartum, and TBAb levels were measured in nine women with values ranging from 1.13 to 9.94 times of the upper limit of the reference range (ULRR). Neonatal TBAb levels ranged from 1.1 to 8.15 times ULRR. Twelve cases (70.6%) exhibited normal thyroid size, three (17.6%) presented with small thyroids, and two cases (11.8%) displayed goiter. The majority of TBAb-induced CH cases present with normal thyroid size. In the absence of goiter, monitoring additional signs of hypothyroidism and early evaluation of neonatal thyroid function remain essential. The online version contains supplementary material available at 10.1186/s12884-025-08437-8.

Transient congenital hypothyroidism (TCH) refers to temporary deficiency of thyroid hormone identified after birth which later recovers to improved thyroxine production. Its prevalence in the Philippines has not been reported in a large-scale study. Its diagnosis remains difficult due to its numerous possible etiologies. Identifying the predictive factors of TCH may aid in earlier diagnosis and decreased risk of overtreatment. This study aimed to determine the predictive factors for TCH in children with congenital hypothyroidism (CH) detected by newborn screening (NBS) in the Philippines from January 2010 to December 2017. In this multicenter retrospective cohort study involving 15 NBS continuity clinics in the Philippines, medical records were reviewed, and clinical and laboratory factors were compared between children with TCH and those with permanent congenital hypothyroidism (PCH). Of the 2,913 children diagnosed with CH in the Philippines from 2010 to 2017, 1,163 (39.92%) were excluded from the study due to an unrecalled or lost to follow-up status, or a concomitant diagnosis of Down Syndrome. Among the 1,750 patients included in analysis, 6.97% were diagnosed with TCH, 60.80% were female, mean gestational age at birth was 38 weeks, and mean birth weight was 2,841 grams. Confirmatory thyrotropin (TSH) was lower and confirmatory free thyroxine (FT4) was higher in the TCH group compared to those with PCH (TSH 32.80 vs 86.65 µIU/mL [p <0.0001]; FT4 9.90 vs 7.37 pmol/L [p 0.001]). The TCH group required lower L-thyroxine doses compared to the PCH group at treatment initiation and at 1, 2, and 3 years of age (initial 6.98 vs 12.08 µg/ kg/day [p <0.0001]; at 1 year 1.89 vs 4.11 µg/kg/day [p <0.0001]; at 2 years 1.21 vs 3.72 µg/kg/day [p <0.0001]; at 3 years 0.83 vs 3.45 µg/kg/day [p <0.0001]). Among those with TCH, mean serum TSH decreased significantly after treatment with L-thyroxine (32.80 vs. 6.55 µIU/ mL, p 0.0001). Other factors associated with TCH were results of thyroid ultrasonography (p 0.007), gestational age at birth (p 0.02), and maternal history of thyroid illness (p <0.0001). Of all the patients with confirmed congenital hypothyroidism via the newborn screening, 6.97% were diagnosed with transient CH. Factors associated with TCH are confirmatory TSH and FT4, L-thyroxine dose requirements, thyroid ultrasound findings, gestational age at birth, and a maternal history of thyroid illness.