Primary Congenital Hypothyroidism Research Articles

Quality of life and socioeconomic and educational status in patients with congenital hypothyroidism.

The aim of this study was to investigate the influence of primary congenital hypothyroidism (CH) on quality of life, level of education and socioeconomic status (SES). Two independent study cohorts, a national and a regional, were collected from Finnish national registers and patient records. Data on social security benefits, SES, marital status, and education were collected from Statistics Finland. Health-related quality of life (HRQoL) was studied in the regional patient cohort with the standardized 15D and 16D instruments. There were no statistically significant differences in education level, marital status, or SES between CH patients (n = 40) and their matched controls at the age of 25 years. The mean 15D score was both statistically significantly and clinically importantly lower in CH patients (n = 29) than controls (0.904 vs. 0.953, p = 0.008). CH patients reported significantly lower scores across various dimensions of physical and mental HRQoL, including breathing, sleeping, speech, excretion, mental function, distress, and vitality. The mean 16D score was lower in CH patients compared to controls (0.917, vs. 0.947), but without statistical significance. SES of CH patients did not differ from matched controls. Thus, most CH patients integrate well into society, but their HRQoL is impaired. Most patients with primary congenital hypothyroidism integrate well into society. In the current study, their socioeconomic and marital status did not differ from matched controls at the age of 25 years. However, health-related quality of life measured using 15D instrument was impaired. Every fourth patient reported that congenital hypothyroidism influenced everyday life.

Optimizing the Dutch newborn screening for congenital hypothyroidism by incorporating amino acids and acylcarnitines in a machine learning-based model.

Congenital hypothyroidism (CH) is an inborn thyroid hormone (TH) deficiency mostly caused by thyroidal (primary CH) or hypothalamic/pituitary (central CH) disturbances. Most CH newborn screening (NBS) programs are thyroid-stimulating-hormone (TSH) based, thereby only detecting primary CH. The Dutch NBS is based on measuring total thyroxine (T4) from dried blood spots, aiming to detect primary and central CH at the cost of more false-positive referrals (FPRs) (positive predictive value (PPV) of 21% in 2007-2017). An artificial PPV of 26% was yielded when using a machine learning-based model on the adjusted dataset described based on the Dutch CH NBS. Recently, amino acids (AAs) and acylcarnitines (ACs) have been shown to be associated with TH concentration. We therefore aimed to investigate whether AAs and ACs measured during NBS can contribute to better performance of the CH screening in the Netherlands by using a revised machine learning-based model. Dutch NBS data between 2007 and 2017 (CH screening results, AAs and ACs) from 1079 FPRs, 515 newborns with primary (431) and central CH (84) and data from 1842 healthy controls were used. A random forest model including these data was developed. The random forest model with an artificial sensitivity of 100% yielded a PPV of 48% and AUROC of 0.99. Besides T4 and TSH, tyrosine, and succinylacetone were the main parameters contributing to the model's performance. The PPV improved significantly (26-48%) by adding several AAs and ACs to our machine learning-based model, suggesting that adding these parameters benefits the current algorithm.

FRI490 Association Between TSH Levels And Early Development Of Secondary Sexual Characteristics Among Children With Congenital Hypothyroidism

Abstract Disclosure: M.M. Nunez Stosic: None. T. Seeherunvong: None. Although hypothyroidism typically delays puberty, early pubertal development in patients with hypothyroidism and markedly elevated TSH levels has been reported. Recent studies investigated the association between thyroid function and timing of puberty among normal children. Jung et al. reported an association between serum TSH and LH levels in girls with central precocious puberty. By contrast Wilken et al. found an association between serum T4 level and onset of pubarche but not thelarche among female subjects. We investigated the association between serum TSH levels and onset of secondary sexual characteristics among patients with congenital hypothyroidism. A retrospective study was conducted including girls and boys aged ≥6 years and ≤ 18 years with confirmed primary congenital hypothyroidism who were seen in our pediatric endocrinology clinic at University of Miami, between May 2012 and May 2022. Age of onset of secondary sexual characteristics (SSC) such as body odor, acne, axillary hair, pubic hair, breast/testicular development was recorded. Early onset of SSC was defined by its presence in girls younger than 8 years and in boys younger than 9 years. Onset of SSC was considered early normal if it occurred between 8-9.5 years in girls and between 9-10.5 years in boys. A third group of patients were those with onset of SSC after 9.5 years in girls and after 10.5 years in boys. We recorded the serum TSH levels from age 6-8 years in girls and from 7-9 years in boys. We determined the average TSH levels and the proportion of the serum TSH level above normal range. IBM SPSS Statistics software version 28.0.0.0(190) was used for data analysis. Fifty-seven subjects with a history of congenital hypothyroidism, 36 girls (63.2%) and 21 boys (36.8%) were included in the study. Seventeen patients (29.8%) had early or early normal onset of SSC. The prevalence was more frequent among girls than boys, 14% and 3% respectively (p value= 0.046). Among all 57 subjects, only 9 had normal serum TSH. The mean proportion of TSH levels above normal limit was 62.4% in patients with early or normal early onset of SSC. By contrast, the mean proportion of serum TSH level above normal limit was 53.7% in those patients who had neither early nor early normal onset of SSC (p value=0.044). In summary, early and early normal onset of SSC was associated with higher TSH levels in children with congenital hypothyroidism. Further studies with a larger number of subjects will be needed to define further the specific SSC most associated with an abnormally elevated TSH. Presentation: Friday, June 16, 2023

Neonatal screening for primary and central congenital hypothyroidism: is it time to go Dutch?

Thyroid hormone (TH) is indispensable for brain development in utero and during the first two to three years of life, and the negative effects of TH deficiency on brain development are irreversible. Detection of TH deficiency early in life by neonatal screening allows early treatment, thereby preventing brain damage. Inborn shortage of TH, also named congenital hypothyroidism (CH), can be the result of defective thyroid gland development or TH synthesis (primary or thyroidal CH (CH-T)). Primary CH is characterized by low blood TH and elevated thyroid-stimulating hormone (TSH) concentrations. Less frequently, CH is due to insufficient stimulation of the thyroid gland because of disturbed hypothalamic or pituitary function (central CH). Central CH is characterised by low TH concentrations while TSH is normal, low or slightly elevated. Most newborn screening (NBS) programs for CH are primarily TSH-based thereby do not detect central CH. Only a few NBS programs worldwide aim to detect both forms of CH by different strategies. In the Netherlands, we have a unique T4-TSH-thyroxine-binding globulin (TBG) NBS algorithm for CH which enables detection of primary and central CH. Although the necessity of central CH detection by NBS is still under debate, it has been shown that most central CH patients have moderate-to-severe hypothyroidism instead of mild, and that early detection of central CH by NBS problably improves its clinical outcome and clinical care for central CH patients with multiple pituitary hormone deficiency. We are therefore convinced that detection of central CH by NBS is of utmost importance.

Comorbidity in Congenital Hypothyroidism-A Nationwide, Population-based Cohort Study.

Patients with congenital hypothyroidism (CH) are affected more often than the general population by other chronic diseases and neurological difficulties. The aim of this nationwide population-based register study was to investigate the incidence of congenital malformations, comorbidities, and the use of prescribed drugs in patients with primary CH. The study cohort and matched controls were identified from national population-based registers in Finland. All diagnoses from birth until the end of 2018 were collected from the Care Register, and subject-specific prescription drug purchases were identified from The Prescription Register from birth until the end of 2017. Diagnoses of neonatal and chronic diseases were collected for 438 full-term patients and 835 controls (median follow-up time 11.6 years; range, 0-23 years). Newborns with CH were more often found to have neonatal jaundice (11.2% and 2.0%; P < .001), hypoglycemia (8.9% and 2.8%; P < .001), metabolic acidemia (3.2% and 1.1%; P = .007), and respiratory distress (3.9% and 1.3%; P < .003) as compared to their matched controls.Congenital malformations were diagnosed in 66 of 438 (15.1%) CH patients and in 62 of 835 (7.4%) controls (P < .001). The most commonly affected extrathyroidal systems were the circulatory and musculoskeletal systems. The cumulative incidence of hearing loss and specific developmental disorders was higher among CH patients than controls. The use of antidepressant and antipsychotic drugs was similar in CH patients and their controls. CH patients have more neonatal morbidity and congenital malformations than their matched controls. The cumulative incidence of neurological disorders is higher in CH patients. However, our results do not support the existence of severe psychiatric comorbidity.

A Rare Case of Congenital Hypothyroidism

Congenital Hypothyroidism (CH) is a common preventable cause of mental retardation. The incidence of CH is 1 in 2500 to 1 in 3000 newborns. Most common causes are thyroid dysgenesis and dyshormonogenesis. Some disorder like maternal autoantibodies, maternal intake of anti thyroid medication, iodine deficiency or iodine excess can result in transient CH. Common symptoms include decreased activity and increased sleep, feeding difficulty, constipation, and prolonged jaundice. In this case report, A 3 day old baby was admitted to SNCU with chief complain of yellowish discoloration upto abdomen and respiratory distress. On examination, common signs include myxedematous facies, large fontanels, macroglossia, a distended abdomen with umbilical hernia, and hypotonia. Thyroid dysgenesis accounts for 85% of permanent, primary CH, while inborn errors of thyroid hormone biosynthesis (dyshormonogeneses) account for 10-15% of cases. Secondary or central CH may occur with isolated TSH deficiency, but more commonly it is associated with congenital hypopitiutarism. Transient CH most commonly occurs in preterm infants born.

Congenital hypothyroidism: a case report of an Egyptian child with congenital heart disease, pelvic kidney and cavernous transformation of portal vein

BackgroundA case of thyroid hormone deficiency which presented at birth. Thyroid hormones are essential for brain development and normal cognitive function. Common symptoms of congenital hypothyroidism (CH) include constipation, decreased activity, increased sleep and feeding difficulty. Common signs include dry skin, macroglossia and umbilical hernia. If congenital hypothyroidism is left untreated after birth, it can lead to permanent intellectual disability and growth failure.Case presentation.Here, we report a 10.5-year-old female with the typical features of CH. She is the sixth in order of birth of consanguineous Egyptian parents. No family history of similar condition. Our patient had primary CH caused by thyroid agenesis. She had congenital heart disease, pelvic kidney, cavernous transformation of portal vein and parenchymatous liver disease.ConclusionsCongenital hypothyroidism is associated with an elevated risk of congenital anomalies. Clinical suspicion of symptoms and signs of congenital hypothyroidism are important for early diagnosis and prevention of serious problems that are related to congenital hypothyroidism.

Thyroid function and long-term outcomes of children born to mothers with Graves' disease: A 20-year review.

Thyroid dysfunction in infants born to mothers with Graves' disease (GD) is influenced by maternal factors including thyroid status, thyroid-stimulating hormone (TSH) receptor antibody (TRAb) concentration and antithyroid drug use. Thyroid dysfunction during early life could affect growth and development later in life. The aim of this study is to evaluate thyroid function tests (TFTs), and long-term growth and development of children born to mothers with GD. A retrospective chart review of children born to mothers with GD at the Faculty of Medicine Ramathibodi Hospital, Mahidol University, between January 2000 and December 2019 was performed. Clinical data including age of children at enrolment, sex, gestational age, birthweight, maternal thyroid status, maternal TRAb level, maternal GD treatment during pregnancy, neonatal TSH screening and TFT results, and growth and development outcomes of children were collected. There were 262 children (148 males) enrolled. Twelve (4%) infants had neonatal GD. Five (2%) infants had hypothyroidism requiring levothyroxine treatment: four had secondary hypothyroidism and one patient had congenital primary hypothyroidism. Seven (3%) infants had transient TSH elevation, which fell to normal by 2 weeks of age. The remaining 238 children had normal TFT results. Three out of 12 children with neonatal GD had either delayed growth or development. A number of infants born to mothers with GD had abnormal TFTs requiring specific management, and some of them had abnormal growth and development. Careful evaluation of TFTs and long-term follow-up are mandatory for those children.

Novel Missense Variants in PAX8 and NKX2-1 Cause Congenital Hypothyroidism.

Primary congenital hypothyroidism (CH) is a common neonatal endocrine disorder characterized by elevated concentrations of thyroid stimulating hormone (TSH) and low concentrations of free thyroxine (FT4). PAX8 and NKX2-1 are important transcription factors involved in thyroid development. In this study, we detected three novel variants in PAX8 (c.149A > C and c.329G > A) and NKX2-1 (c.706A > G) by whole exome sequencing (WES) in three unrelated CH patients with variable phenotypes. The results of Western blot and immunofluorescence analysis showed that the three variants had no effect on protein expression and subcellular localization. However, the results of the electrophoretic mobility shift assay (EMSA) and dual-luciferase reporter assay suggested that the three variants in PAX8 and NKX2-1 both affected their DNA-binding ability and reduced their transactivation capacity. Moreover, a dominant-negative effect in K236E−NKX2-1 was identified by dual-luciferase reporter assay. To sum up, our findings extend our knowledge of the current mutation spectrum of PAX8 and NKX2-1 and provide important information for diagnosing, treating, and preventing CH in these families.

Prevalence of congenital hypothyroidism in North Macedonia: data from a newborn screening program conducted for twenty years.

Congenital hypothyroidism (CH) is a common endocrine disorder that can be treated if timely detected by newborn screening, optimizing the developmental outcome in affected children. In the present study, we analyze the data of the national newborn thyroid screening program in North Macedonia collected over twenty years, including the CH prevalence as well as its geographical and ethnic variations. The thyroid-stimulating hormone (TSH) was measured on a filter paper blood spot sample using the DELFIA fluoroimmunometric assay. A TSH value of 15 mIU/L whole blood was used as the cutoff point until 2010 and 10 mIU/L thereafter. Out of 377,508 screened live births, a total of 226 newborns with primary CH were detected, providing an overall prevalence of 6.0 per 10,000. Lowering the TSH cutoff led to an apparently increased prevalence of the transient CH, from 0.2 to 2.4 per 10,000 live births (p < 0.0001) with an impact on the overall prevalence of primary CH (from 4.0 to 7.1 per 10,000, p=0.0001). Taking ethnicity into account, the significantly highest primary CH prevalence of 11.3 per 10,000 live births was observed among the Roma neonates, with a predominance of permanent CH (75.5%). There were also regional differences in the prevalence of primary CH. The highest primary CH prevalence of 11.7 per 10,000 live births was observed in the Vardar region, together with the highest regional prevalence of the transient CH (3.2 per 10,000). The highest prevalence of permanent CH was observed in the Pelagonia region (6.6 per 10,000) where the largest percentage of the Roma population lives. The overall CH prevalence is high in North Macedonia, with substantial ethnic and geographical variations. Further analysis to elucidate the causes for the significant variations in the CH prevalence including environmental factors is warranted.

Guidelines for Newborn Screening of Congenital Hypothyroidism (2021 Revision)

Purpose of developing the guidelines: Newborn screening (NBS) for congenital hypothyroidism (CH) was started in 1979 in Japan, and early diagnosis and treatment improved the intelligence prognosis of CH patients. The incidence of CH was once about one in 5,000-8,000 births, but has been increased with diagnosis of subclinical CH. The disease requires continuous treatment and specialized medical facilities should conduct differential diagnosis and treatment in patients who are positive by NBS to avoid unnecessary treatment. The Guidelines for Mass Screening of Congenital Hypothyroidism (1998 version) were developed by the Mass Screening Committee of the Japanese Society for Pediatric Endocrinology in 1998. Subsequently, the guidelines were revised in 2014. Here, we have added minor revisions to the 2014 version to include the most recent findings. Target disease/conditions: Primary congenital hypothyroidism. Users of the Guidelines: Physician specialists in pediatric endocrinology, pediatric specialists, physicians referring pediatric practitioners, general physicians, laboratory technicians in charge of mass screening, and patients.

Utility of basal and peak TSH values in TRH stimulation testing for predicting the long-term therapeutic prognosis of primary congenital hypothyroidism.

In Japan, most neonates undergo screening for congenital hypothyroidism (CH). A TRH stimulation test (TRH-T) may be performed after initial treatment as a useful method for reevaluating the patient's thyroid status. However, no studies have compared basal and peak TSH values in TRH-T in patients with long-term follow-up. This was a retrospective and observational study. The inclusion criteria were as follows: (1) CH diagnosis based on positive newborn screening, (2) follow-up > 15 yr, and (3) TRH-T after LT4 discontinuation. The participants were divided into a no-treatment group (No-T group) and a treatment group (T group). The No-T and T groups included 14 and nine patients, respectively. The age at TRH-T was 5.38 yr for the No-T group and 4.25 yr for the T group, with no significant difference. The basal and peak TSH levels were significantly lower in the No-T group. The areas under the Receiver operating characteristic curve for basal and peak TSH values were 0.984 and 0.905, respectively. When the basal TSH level was under 4.594 IU/mL, the No-T group had a sensitivity of 1.00 and a specificity of 0.93. Basal TSH levels alone may be sufficient for predicting the long-term therapeutic prognosis of patients with CH.

Hypothyroidism in First-Degree Relatives of Neonates with Congenital Hypothyroidism: Is there an Association?

Recent studies have shown an increased incidence of congenital hypothyroidism (CH), especially in the middle-east region. The exact etiology is unknown; however, it has been related to several factors, the most noticeable being the high prevalence of transient CH (TCH), parental consanguinity, and the history of hypothyroidism in relatives. We sought to determine the impact of hypothyroidism in the relatives of patients with the observed trend. We included all patients with primary CH detected through the Newborn Screening (NBS) Program from 2007 to 2016. We analyzed the impact of consanguinity relationship, parental and siblings' thyroid function, second-degree relatives' thyroid function, parental educational level, age, and maternal gestational diabetes on the development of permanent CH (PCH) and TCH. A total of 1447 consecutive eligible patients were recruited during the study period. Of this number, 1171 (81%) were diagnosed with CH: 623 (53.2%) had PCH and 548 (46.8%) had TCH. Six hundred thirty-three (54.1%) participants were men, and 814 (69.5%) had a history of relatives' hypothyroidism. Our data analysis revealed a significant difference regarding the male gender, having a history of relatives' hypothyroidism, and parental hypothyroidism compared to TCH ones (P < 0.05). Patients with a history of relatives' hypothyroidism had significantly higher PCH than TCH (P < 0.0001). However, consanguineous marriage was not comparable in patients regardless of their history of relatives' hypothyroidism (P-value >0.884). Our findings indicated the role of the history of hypothyroidism in neonates' relatives in the evolution of the PCH. Meanwhile, consanguineous marriage did not impress the development of PCH and TCH.

‘Rotor free-wheeling’ in impaired F1FO-ATPase induces congenital hypermetabolism

A de novo heterozygous variant in the catalytic subunit of mitochondrial F1FO-ATPase has been recently discovered by Ganetzky et al. to be the main cause of an autosomal dominant syndrome of hypermetabolism associated with defective ATP production. We describe how the ‘rotor free-wheeling’ causes this F1FO-ATPase dysfunction in primary congenital hypothyroidism.

Genetic Factors Causing Thyroid Dyshormonogenesis as the Major Etiologies for Primary Congenital Hypothyroidism: Clinical and Genetic Characterization of 33 Patients.

Although the significance of primary congenital hypothyroidism (CH) is supported by an increasing amount of evidence, the clinical and genetic characteristics of this condition are still poorly understood. This study aimed to explore the underlying genetic etiologies in a cohort of primary CH patients. The clinical data of 33 patients with primary CH were collected and analyzed via a cross-sectional study. Genetic analysis was performed by high-throughput sequencing and Sanger verification, and the pathogenicity of the novel missense variants was predicted using a variety of comprehensive bioinformatic tools. Among the 33 patients, 22 (22/33, 66.7%) harbored pathogenic variants in the causative genes of thyroid dysgenesis or dyshormonogenesis, with DUOX2 (15/33, 45.5%) topping the list, followed by TG, TPO, DUOXA2 and PAX8. Four novel genetic variants were detected, including a pathogenic frameshift and three likely pathogenic missense variants. Positive neonatal screening for TSH, neonatal jaundice and abnormal thyroid morphology were the main positive findings among all cases. Although 31 of the total 33 CH patients exhibited normal anthropometric and social performance, the other 2 had poor prognosis in this study. This study reported 33 new CH patients bearing four novel genetic variants, which enriched the variant spectrum of CH genes. In this cohort, genetic factors causing thyroid dyshormonogenesis were the main etiologies of CH development. Most patients exhibited a favorable prognosis; however, systematic management remains a challenge in achieving improved clinical outcomes for CH patients.

Iatrogenic hyperthyroidism in primary congenital hypothyroidism: prevalence and predictive factors.

Primary congenital hypothyroidism (CH) is a preventable cause of mental retardation. Iatrogenic hyperthyroidism has occasionally been reported using the recommended LT4 dosage. Currently, information regarding iatrogenic hyperthyroidism and predictive factors for permanent hypothyroidism (P-CH) among Thai patients is lacking. The aim of this study is to determine the prevalence and factors for predicting iatrogenic hyperthyroidism at one month after LT4 initiation and for predicting P-CH in primary CH infants. This retrospective cohort study involved 87 infants with primary CH. Patients were classified by thyroid status at one month after LT4 initiation. At 3years, patients were reevaluated after LT4 cessation and assigned as P-CH or transient CH (T-CH). Differences between groups were analyzed. One month after LT4 initiation, 35.6% of patients were classified as having iatrogenic hyperthyroidism. An initial LT4 dose of 10.2μg/kg/day (sensitivity 64.5%, specificity 71.4%) was a suitable cutoff value for predicting iatrogenic hyperthyroidism, wherein 55.6 and 21.6% of patients were treated with initial doses of≥10.2 and <10.2μg/kg/day, respectively (p=0.004). Initial LT4 dose was the only predictive factor for thyroid status after initial treatment. At reevaluation, 47.4% of patients were diagnosed with P-CH. LT4 dosage at 3years of age was significantly higher in patients with P-CH (3.3 vs. 2.85μg/kg/day, p=0.02) and the only relevant factor for predicting P-CH. Iatrogenic hyperthyroidism is common among infants with primary CH when treated with the recommended LT4 dosage. LT4 dose was the only factor for predicting iatrogenic hyperthyroidism after LT4 initiation and the diagnosis of P-CH.

Genetic disorders of thyroid development, hormone biosynthesisand signalling.

Development and differentiation of the thyroid gland is directed by expression of specific transcription factors in the thyroid follicular cell which mediates hormone biosynthesis. Membrane transporters are rate‐limiting for cellular entry of thyroid hormones (TH) (T4 and T3) into some tissues, with selenocysteine‐containing, deiodinase enzymes (DIO1 and DIO2) converting T4 to the biologically active hormone T3. TH regulate expression of target genes via hormone‐inducible nuclear receptors (TRα and TRβ) to exert their physiological effects. Primary congenital hypothyroidism (CH) due to thyroid dysgenesis may be mediated by defects in thyroid transcription factors or impaired thyroid stimulating hormone receptor function. Dyshormonogenic CH is usually due to mutations in genes mediating thyroidal iodide transport, organification or iodotyrosine synthesis and recycling. Disorders of TH signalling encompass conditions due to defects in membrane TH transporters, impaired hormone metabolism due to deficiency of deiodinases and syndromes of Resistance to thyroid hormone due to pathogenic variants in either TRα or TRβ. Here, we review the genetic basis, pathogenesis and clinical features of congenital, dysgenetic or dyshormonogenic hypothyroidism and disorders of TH transport, metabolism and action.

Association of recessive c.430G>A (p.(Gly144Arg)) thyroid peroxidase variant with primary congenital hypothyroidism in cats.

BackgroundPrimary congenital hypothyroidism (CH) is a rare endocrine disorder in cats with a largely unknown genetic cause.ObjectivesDescribe the clinical presentation of CH in 11 affected cats and identify the causal genetic variant.AnimalsEleven CH‐cats from 10 unrelated families, 11 CH‐free family members, 21 unrelated CH‐free cats, and 155 unrelated nondiagnosed cats from different breeds.MethodsCase control study of CH‐cats and their siblings (2019‐2021). Diagnosis was based on low to low‐normal serum thyroxine (T4) concentrations, high thyroid‐stimulating hormone (TSH) concentrations and clinical signs compatible with CH. We identified the causal variant using Sanger sequencing, genotyping via PCR‐RFLP and variant interpretation using ACMG/AMP guidelines.ResultsAll CH‐cats (5 weeks‐8 years) had disproportionate dwarfism. A goiter was not palpable in all. Thyroid scintigraphy with radiopertechnetate showed abnormally high uptake by thyroid glands, whereas scintigraphy with radioiodine showed abnormally low uptake, compatible with a defect in iodine organification by thyroid peroxidase (TPO). All cases were homozygous for TPO variant XM_006930524.4:c.430G>A(p.(Gly144Arg)), while none of the CH‐free cats were. All sampled parents were heterozygous for this recessive variant. This variant was found in 15 cat breeds with an estimated allele frequency of 9%.Conclusions and Clinical ImportanceDisproportionate dwarfism, abnormally high TSH and abnormally low to low‐normal T4 concentrations are diagnostic for CH in cats. All cases had dyshormonogenesis demonstrated by thyroid scintigraphy. This novel TPO missense variant (not described in humans) causes CH in cats and awareness of it can assist in diagnosis and breeding.

Primary Congenital Hypothyroidism in Children Below 3 Years Old - Etiology and Treatment With Overtreatment and Undertreatment Risks, a 5-Year Single Centre Experience.

Worldwide neonatal screening for congenital hypothyroidism (CH) is a gold standard of active surveillance in newborns. Prompt diagnosis, subsequent timely treatment implementation, and proper dosage of levothyroxine (L-T4) are crucial for normal growth and development, especially of the central nervous system. However, overtreatment may have a potential negative impact on further neurodevelopment. We retrospectively analysed data of 99 newborns with CH diagnosis, referred to the Endocrinology Outpatient Clinic of the Institute of Mother and Child in Warsaw, Poland from the CH screening program from 2017 to 2021. We evaluated the diagnostic process and treatment up to the age of 3 years. We compared groups of children from the first and the second screening groups (FSG, SSG) in the neonatal screening with an evaluation of ultrasound examination (thyroid dysgenesis vs. gland in situ, GIS). The overtreatment and undertreatment risks were assessed and an analysis of the new TSH thresholds was performed. Treatment was implemented at a median of 9 days of life (3 – 27); 8 days (3 – 17) in FSG and 19 (6 – 27) in SSG. The dose of L-T4 differed between FSG and SSG at all three analysed time points (start of the therapy, 12 months, and 3 years) with significantly higher doses in FSG. The same was observed for the patients with thyroid dysgenesis vs. GIS. Screening TSH level was ≥ 28mIU/l in 91.7% of patients with thyroid dysgenesis in comparison to 74.0% of patients with GIS (p= 0.038). The optimally treated group (fT4 in the upper half of the reference range, according to the guidelines) was up to 58.0% of the children during the follow-up. The risk for overtreatment was present in 1/5 of the study group after 12 months and 1/4 after 3 years of L-T4 therapy. Analysis of new TSH thresholds showed an increased prevalence of mild hypothyroidism, GIS, and either euthyroid state or overtreatment while treating with lower L-T4 doses in comparison to the rest of the cohort. The study confirmed the general efficacy of the CH diagnostic pathway and the timely implemented L-T4 therapy. The suspected overtreatment after the first 12 months of L-T4 therapy requires consideration of the earlier diagnosis re-evaluation.

Incidence of primary congenital hypothyroidism over 24 years in Finland

BackgroundA rise in the incidence of congenital hypothyroidism (CH) has been reported worldwide. This nationwide study aimed to describe the secular trends and current incidence of CH in Finland.MethodsTwo independent study cohorts, a national and a regional, were collected from national registers and patient records. The national cohort represents all CH cases born in Finland between 1994 and 2017. Birth data, results of the screening test, and the incidence of CH were reviewed.ResultsBetween 1994 and 2017, 1,400,028 children were born in Finland. Of these children, 503 were diagnosed with primary CH (incidence 1:2783). Male-to-female sex ratio was 1:2.0. The nationwide incidence was 33 cases per 100,000 live births between 1994 and 1999, 38 cases per 100,000 live births between 2000 and 2005, 40 cases per 100,000 live births between 2006 and 2011, and 33 cases per 100,000 live births between 2012 and 2017. In the regional cohort (n = 139), the incidence of transient CH was 3.6%. The incidence of mild, moderate, and severe CH remained constant.ConclusionsIn Finland, the incidence of CH has not changed during the 24-year study period.ImpactAs opposed to recent reports worldwide, the incidence of congenital hypothyroidism has not changed between 1994 and 2017 in Finland.The proportions of mild, moderate, and severe congenital hypothyroidism did not change significantly over the study period.Lowering the TSH cut-off limit or increasing immigration did not affect the incidence rate of primary congenital hypothyroidism in Finland.