History Of Congenital Hypothyroidism Research Articles

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

Mitotically Active Follicular Nodule in Early Childhood: A Case Report with A Novel Mutation in the Thyroglobulin Gene.

Dyshormonogenesis is the failure of thyroid hormone production due to a defect in thyroid hormonogenesis. Loss-of-function mutations in the thyroglobulin(TG) gene are a cause of dyshormonogenesis, leading to gland stimulation by thyroid-stimulating hormone (TSH), resulting in goiter. We report a mitotically active follicular nodule in an 11-year-old female with a novel mutation in the TG gene. The patient had been under follow-up due to congenital hypothyroidism since the neonatal period, and she had normal TSH levels. Genetic test revealed a novel compound heterogeneous mutation [c.2149C>T (p.R717*) (P.Arg717Ter) / c.5361_5362delCCinsG (p.H1787Qfs*3) (p.His1787GlnfsTer3)] in TG gene. She underwent total thyroidectomy for a thyroid nodule that was reported as Bethesda IV on FNAB and noted as suspicious for noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Pathological examination revealed a 16 mm well-demarcated follicular nodule with a solid/insular pattern. Mitotic activity and Ki67 proliferation index were unusually high (10 mitoses/2mm2 and 10% respectively). Marked cellular pleomorphism and nuclear atypia are well-known diagnostic pitfalls in patients with dyshormonogenetic goiter. However, high mitotic activity is a feature that is less emphasized in dyshormonogenetic goiter and may raise suspicion of poorly differentiated carcinoma when observed together with a solid pattern. The absence of signs of invasion, history of congenital hypothyroidism, and awareness of the presence of mutations compatible with dyshormonogenetic goiter can prevent the overinterpretation of such lesions. The risk of cancer development in the dyshormonogenetic thyroid gland is possible in childhood. The close follow-up is life-saving and prevents morbidities and mortalities.

Assessment of intelligence quotient score in children at the age of six with suspected congenital hypothyroidism: A retrospective cohort study.

Background: The clinical suspicion of Congenital Hypothyroidism (CH) is identified by abnormal results in the first test of Thyroid Stimulating Hormone (TSH) (5-9.9 mIU/L), and normal results in re-test (TSH<4 mIU/L). The CH has a contribution to physical and mental health. This study aimed to determine the Intelligence Quotient (IQ) score in children with suspected congenital hypothyroidism. Methods: This research is a retrospective cohort study conducted in Mashhad, Iran. The IQ scores of 1976 children at the age of 6 were considered as an outcome variable. The history of CH screening for each newborn was assessed, then all suspected CH newborns that diagnosed healthy in re-test were considered as an exposed group, the effects of this situation on IQ score was assessed using logistic regression. All analysis was performed in STATA. Results: The averages of IQ score (p<0.001), weight (p=0.024), and height (p<0.001) in the exposed group were lower than the unexposed group. The exposed group was related to those whose parental education was less or equal to 12 years (p<0.001). Similarly, the history of CH and maternal education for ≤12 years were detected as risk factors for having an IQ score of <90 in children. Conclusion: Aside from the link between parental education and clinical suspicion of CH in neonates, our findings underline the possible strong effect of CH status and maternal education for ≤12 years on reducing IQ scores in the next years of child life.

Severe hypercholesterolemia in a 2-year-old

Routine and selective cholesterol screening of children is an effective tool to help identify those with familial hypercholesterolemia. In children found to have elevated levels of cholesterol, secondary causes should be excluded, including hypothyroidism. Thyroid hormone has multiple effects on the regulation of lipid synthesis, absorption, and metabolism. In this case report, we described a 2-year-old with a history of congenital hypothyroidism who was found to have severe hypercholesterolemia. A detailed medical history and appropriate screening tests are important in determining the underlying cause of elevated low-density lipoprotein cholesterol to help inform clinical decision-making.

S112. Relationship of mismatch negativity with the IQ and executive functions in school children with a history of congenital hypothyroidism. Study of cases

Introduction Congenital hypothyroidism (CH) is related to alterations in cognitive growth and development. Even with timely treatment, motor and/ or cognitive sequelae occur. Children with HC have low IQ compared to children with low biological risk; cases with atirosis (AT) have greater deficits than children with sublingual nodules (NSL). Analyzing complex cognitive processes through executive functions and mismatch negativity (MMN) will allow us to explore more deeply the alterations of the central nervous system in this syndrome. Objective- To analyze the relationship between executive functions and the mismatch negativity in school children with HC. Methods Case study, prospective and transversal. 9 children of 12 years, 4 girls (3 AT and 1 NSL) and 5 children (4 NSL and 1 AT), with initiation of hormone replacement therapy in the first 60 days of extrauterine life, attended the intervention program until the 6 years old. For the recording of auditory MMN with oddball paradigm, stimuli of 1000 Hz (80%) and 1500 Hz (20%). For the evaluation of executive functions, the neuropsychological battery ENI and the scale of intelligence Weschler for CI were used. Results In children with AT, verbal fluency, planning and organization were identified as having very low performance, children with NSL presented limit cognitive flexibility. In the IC assessment, two children with AT were borderline and 7 within the normal average. In MMN in the 9 cases there was frontal response latency with between 150 and 287 ms; 8 cases presented a central response with latencies between 157 and 315 ms. The amplitudes were variable between −.012 to −5.71 μ v. Conclusion The MMN shows late response in the discrimination of stimuli in cases with HC with a low performance EF profile and low CI.

Sigmoid Volvulus In Myxedema Megacolon

ABSTRACT Objective: To report a case of myxedema megacolon complicated with sigmoid volvulus that was successfully managed with surgery and intensive thyroid hormone replacement therapy (THRT). Methods: The clinical presentation, laboratory and imaging results, treatment of the myxedema megacolon episode, and post-surgical evolution with THRT are presented. Results: We present the case of a 17-year-old woman with history of congenital hypothyroidism, chronic constipation, and irregular treatment with levothyroxine, who was admitted to the emergency room following 7 days of abdominal pain, nausea, and vomiting. She presented with marked abdominal distention and without bowel sounds. An abdominal computerized tomography scan showed a severe colon enlargement. Thyroid-stimulating hormone (TSH) was 222 μIU/mL, total thyroxine was <1 μg/dL, and total triiodothyronine was <40 ng/dL. Exploratory laparotomy was performed. Sigmoid volvulus was found and sigmoidectomy was performed. No evidence of colonic obstructi...

Biochemical, radiological, and genetic characterization of congenital hypothyroidism in Abu Dhabi, United Arab Emirates.

Congenital hypothyroidism (CH) is caused by thyroid gland (TG) dysgenesis or inadequate thyroid hormone biosynthesis in a structurally normal gland. Different etiologies are known to be associated with various clinical, biochemical and imaging markers and a subset of cases have an underlying genetic basis. Despite the presence of neonatal screening programs in the UAE, there is a lack of data on the disease etiology in the area. We aim to study the etiology of CH in our center and examine its relationship with the clinical, biochemical, genetic and radiological features. Patients with CH who were followed in our center between 2011 and 2014 are enrolled in the study. Data collected included gender, gestational age, history of CH in a first-degree relative, initial thyroid stimulating hormone (TSH) and thyroxine (T4) levels, imaging findings, associated disease/malformation and treatment details. Selected patients with associated systemic disease or familial CH underwent genetic testing. Sixty-five patients were enrolled. Ten patients underwent genetic study: seven patients with associated congenital disease/malformation, one with a sibling and two with cousins with CH. Forty-nine subjects had technetium99 and/or ultrasound scans. Dyshormonogenesis was diagnosed in two-thirds of the patients. Three patients of 10 tested had likely causative genetic mutations; two homozygous thyroid peroxidase (TPO) and one heterozygous thyroid stimulating hormone receptor (TSHR) missense mutations. Dyshormonogenesis is the commonest etiology in CH in the studied group. It is expected that genetic mutations are more prevalent in our region due to the nature of the CH etiology and the rate of high consanguinity rate.

Ophthalmic Manifestations in Children With Congenital Hypothyroidism.

To evaluate the frequencies of ophthalmic abnormalities in children with congenital hypothyroidism. A total of 121 patients with a history of congenital hypothyroidism, aged 1 to 216 months, were included in the study. The initial ophthalmological examinations and demographic data of patients who were examined between April 2013 and April 2015 were retrospectively reviewed. Accompanying systemic abnormalities were also noted. Ophthalmic pathology was determined in 40.4% (49 of 121) of patients with congenital hypothyroidism, of which 79.5% (39 of 49) had significant refractive errors and 32.6% (16 of 49) had strabismus. Systemic abnormalities were observed in 74.3% (90 of 121) of the children, among which 47.1% (57 of 121) were congenital heart defects and 38.0% (46 of 121) were neurologic abnormalities. A high prevalence of Down syndrome (17.3%; 21 of 121) and atopic dermatitis (8.2%; 10 of 121) was detected among patients with congenital hypothyroidism. In addition to many associated systemic abnormalities, ophthalmic pathologies may also occur in children with congenital hypothyroidism. Thus, routine ophthalmological examination is recommended for these children, starting from the time of initial diagnosis.

Dyshormonogenetic goiter‐like changes in a child with congenital hypothyroidism and a euthyroid adult

Dyshormonogenetic goiter is a rare entity that presents in patients who typically have a history of congenital hypothyroidism, and generally arises from a genetic mutation compromising the production of functional thyroxine or thyroglobulin. Clinically, physical manifestations of goiter can result if left untreated. Histologically, the thyroid lesions usually show prominent bridging fibrosis, multiple thyroid nodules with different architectures, microfollicular arrangement, scant colloid, and enlarged vesicular or hyperchromatic nuclei. Cytologically, the features of the lesion are not distinguishable from follicular lesion and follicular neoplasm. We describe two patients exhibiting similar histological and cytological features resembling dyshormonogenetic goiter with cytologic misinterpretation as follicular neoplasm. One was a child with an established history of congenital hypothyroidism. The other was an adult euthyroid patient who presented with an associated parathyroid adenoma. These findings further affirm that cytologically and histologically, morphologic features associated with dyshormonogenetic goiter can also be found in patients without a history of congenital hypothyroidism.

Genetics, clinical management and natural history of congenital hypothyroidism

Congenital hypothyroidism has an incidence of 1:3000–4000 newborns. In the past, it was a common cause of mental retardation, although newborn screening has improved the prognosis. Several transcription factors are crucial to the early organogenesis of the thyroid, including TITF1, FOXE1, PAX8 and HHEX. Nevertheless, a small minority of humans with congenital hypothyroidism carry mutations in these genes. Long-term follow-up studies show that with appropriate therapy, the mental and physical development of congenital hypothyroidism patients is in the normal range, although somewhat delayed when compared with appropriate controls. Critical issues of treatment include early diagnosis and rapid correction of hypothyroidism by ensuring rapid initiation of treatment and rapid normalization of thyroid-stimulating hormone levels, especially in cases of severe congenital hypothyroidism. There has been recent question of the need to treat premature infants with hypothyroxinemia but no elevation of the thyroid-stimulating hormone concentration. Numerous controlled studies of the short- and long-term effects of thyroid hormone supplementation have not shown a consistent benefit in this group of patients. Future research will investigate further the genetic underpinnings of the condition. There is a worldwide need to prevent congenital hypothyroidism by ensuring adequate dietary iodine and to develop infrastructure to diagnose and treat congenital hypothyroidism in developing countries.

Alterations of neonatal thyroid function.

Recent progress has been made in understanding the pathogenesis of neonatal thyroid disorders. Autosomal recessive inheritance of mutations of the thyroid peroxidase and thyroglobulin genes has been described in some patients with congenital hypothyroidism (CH) and a family history of CH. Autosomal recessive inheritance of mutations of the thyrotrophin (TSH) receptor gene has also been reported in patients with CH and thyroid hypoplasia, and autosomal dominant mutations of the PAX8 gene have been described in patients with different forms of thyroid dysgenesis. These discoveries are important for patients with CH diagnosed by neonatal screening, as these patients will have normal fertility. The molecular genetic analysis of mutations of the TSH gene in patients with familial and sporadic cases of isolated central CH, who are missed by TSH screening programmes, now enables rapid diagnosis and appropriate therapy in the neonate. In newborn infants with severe non-autoimmune hyperthyroidism, autosomal dominant gain-of-function mutations in the TSH receptor gene have been demonstrated. In these patients, molecular genetic studies are extremely helpful in therapeutic decision making, as early thyroid ablation is the only effective treatment that avoids the sequelae of long-term hyperthyroidism. Molecular genetic studies are therefore useful in the diagnostic work-up of neonatal thyroid alterations.

Congenital hypothyroidism and IQ increase: A quarter century follow-up

Ten patients with a history of congenital hypothyroidism were recalled for IQ evaluation 16 to 26 years after an original IQ test at age 5 to 6. From childhood through adulthood, the IQ (Wechsler) increased (mean full scale IQ increase = 21; range = -5 to 43 points). Serial testing in three instances showed the timing of the increase to be sudden and unpredictable. Life achievements, mental health, and sexual adjustment were concordant with the IQ attained. The data suggest that in hypothyroidism intellectual growth may not occur in equal annual increments; with effective hormonal replacement and educational experience it may be subject to spurts of growth, with a resultant improved prognosis.