Hypothyroidism In Down Syndrome Research Articles

Hypothyroidism in Patients with Down Syndrome: Prevalence and Association with Congenital Heart Defects.

This population-based study aimed to assess the prevalence of congenital hypothyroidism (CH) and overt hypothyroidism (OH) and their association with congenital heart defects (CHDs) in patients with Down syndrome (DS). The population included all live births residing in Tuscany (Italy) diagnosed with DS recorded in the Registry of Congenital Defects and in the Registry of Rare Diseases of Tuscany in the years 2003-2017. The prevalence of CH and OH in DS patients was calculated by sex and by period. The association of CH and OH with CHDs in DS patients was assessed using multivariate logistic regression. The cohort included 228 subjects. The prevalence of CH and OH was 11.4% (95%CI: 7.4-16.7%) and 12.7% (95%CI: 8.5-12.3%), respectively, with no significant difference by sex. A significant increase in the prevalence of CH (p < 0.0001) was found in the years 2010-2017 compared to the previous period, and among preterm infants (p = 0.009). The presence of CH was associated with a higher prevalence of CHDs (adjusted OR = 2.24, p = 0.082). A significant association between ventricular septal defects (VSDs) and the occurrence of OH (adjusted OR = 3.07, p = 0.025) was also observed. This study confirmed the higher prevalence of both CH and OH in DS compared to the general population. Furthermore, the risk of association between DS and CHDs was higher in the presence of CH, while VSDs are associated with OH, providing relevant insights into the epidemiology of hypothyroidism in DS and associated anomalies.

Social and clinical factors associated with the early diagnosis of hypothyroidism in Down syndrome

Objective: To establish the social and clinical factors associated with the early diagnosis of hypothyroidism in patients with Down syndrome in a highly complex hospital in Colombia. Methodology: An observational, cross-sectional and analytic study was conducted in patients with hypothyroidism and Down syndrome aged three years old or younger, attended between the years 2017 - 2018. We had as secondary source the information of the clinical histories and as primary source a telephone survey carried out to the caregiver of the patient, we evaluated demographic, social and clinical variables. Results: 144 clinical histories were evaluated, of which 78 were able to comply with the variables; 32 patients presented hypothyroidism and with them the investigation was carried out. The early diagnosis of hypothyroidism, understood as that before 6 months of age, was 59. 4%. Clinical hypothyroidism was 71. 1% with connection to the subclinical, 87. 5% had thyroid stimulating hormone (TSH) levels lower than 15 mU/L neonatal and 3% of the population had congenital hypothyroidism. 50% of cases were diagnosed with hypothyroidism in the first three months of life. The height at birth in relation to the early diagnosis of hypothyroidism presented an RP: 14, IC 95%: 1.06-186. Conclusions: Early diagnosis of hypothyroidism has an association by the size of the patients at birth. Continuous monitoring of thyroid function in the first months and years of life of patients with Down syndrome, independent of neonatal TSH values, should be performed.

Prospective evaluation of autoimmune and non-autoimmune subclinical hypothyroidism in Down syndrome children.

To evaluate the prevalence and natural course of autoimmune and non-autoimmune subclinical hypothyroidism (SH) in Down syndrome (DS) children and adolescents. Prospective multicenter study. For the study, 101 DS patients with SH (TSH 5-10 mIU/L; FT4 12-22 pmol/L), aged 2-17 years at SH diagnosis were enrolled. Annual monitoring of TSH, FT4, BMI, height, and L-thyroxine dose was recorded for 5 years. Thyroid autoimmunity was tested at diagnosis and at the end of follow-up. Thirty-seven out of 101 patients displayed autoantibody positivity (group A); the remaining 64 were classified as non-autoimmune SH (group B). Group A was characterized by higher median age at SH diagnosis and by more frequent family history of thyroid disease (6.6 vs 4.7 years, P = 0.001; 32.4% vs 7.8%, P = 0.001 respectively), whereas congenital heart defects were more common in group B (65.6% vs 43.2%, P = 0.028). Gender, median BMI (SDS), height (SDS), FT4, and TSH were similar in both groups. At the end of follow-up: 35.1% of group A patients developed overt hypothyroidism (OH) vs 17.2% of group B (P = 0.041); 31.25% of group B vs 10.8% of group A became biochemically euthyroid (P = 0.02); and 37.8% of group A vs 51.5% of group B still had SH condition (P = 0.183). Logistic regression suggested autoimmunity (OR = 3.2) and baseline TSH values (OR = 1.13) as predictive factors of the evolution from SH to OH. In DS children, non-autoimmune SH showed higher prevalence and earlier onset. The risk of thyroid function deterioration over time seems to be influenced by thyroid autoimmunity and higher baseline TSH values.

Ovarian cysts, vaginal bleeding and hypothyroidism in a 4-year-old female with Down Syndrome: A case of Van Wyk-Grumbach Syndrome

Abstract Van Wyk-Grumbach Syndrome (VWGS) is a constellation of symptoms including precocious puberty without adrenarche, delayed bone age, ovarian cysts, and hypothyroidism. We report here a four-year-old Down Syndrome patient who presented for evaluation of abdominal distension, vaginal bleeding, and bilateral ovarian cysts. Her work-up and management demonstrates the importance of screening for hypothyroidism in Down Syndrome, as well as considering the diagnosis of VWGS when evaluating a patient with precocious puberty and an apparent intra-abdominal surgical process. Given the presence of ovarian masses, a surgical emergency such as ovarian torsion or rupture must be ruled out. Even when the diagnosis of VWGS is confirmed, practitioners must be vigilant to consider surgical intervention in the presence of uncontrolled vaginal bleeding, hemodynamic instability, or failure of regression of ovarian cysts with exogenous thyroid hormone replacement.

Characterization of Thyroid Abnormalities in a Large Cohort of Children with Down Syndrome

Background/Aims: Thyroid disease is a common comorbidity in individuals with Down syndrome (DS), but historical studies have multiple limitations. We assessed thyroid abnormalities in a large cohort of children with DS. Methods: Retrospective records review from a single institution. Calculated prevalence of common thyroid abnormalities and associations with common comorbidities. Results: Among 508 patients, 120 (24%) had a thyroid-related diagnosis, the majority having elevated thyrotropin treated with levothyroxine. A Kaplan-Meier estimate projects that 50% have thyroid disorder by adulthood, with 20% of hypothyroidism diagnosed before the age of 6 months. When tested, approximately 50% had positive antithyroid antibodies, though this rate was 100% in overt hypothyroidism. There was no association between congenital or acquired hypothyroidism and common comorbidities. Conclusion: Thyroid disease in DS is more common and occurs earlier than in the general population, and is often transient. Thyroid disease is unrelated to gender, obesity, or other comorbidities. Apart from overt hypothyroidism, much of hypothyroidism in DS appears unrelated to autoimmunity; we recommend checking of antithyroid antibodies only in select cases. An additional screen for thyroid disease between the newborn screen and the 6-month well-child visit will detect early cases of hypothyroidism who passed their newborn screen.

Capillary blood screening for hypothyroidism in Down syndrome?

Children and adolescents with Down syndrome carry a lifelong increased risk of acquired hypothyroidism, particularly from autoimmune disease. Their hypothyroidism can be difficult to detect clinically, as symptoms such as short stature, constipation, dry skin, and lethargy occur commonly in these children. Thus, multiple societies have endorsed various thyroid hormone screening guidelines, based upon venipuncture. Screening programs are almost always debated and need to take into account disease prevalence, test sensitivity and specificity, cost of screening, and test acceptability, among other factors. In this issue of The Journal, McGowan et al consider whether the Scottish capillary thyroid stimulating hormone (TSH) screening program might contain data to establish a threshold value below which low venous free T4 and elevated venous TSH are unlikely, so that capillary blood screening could serve as a first-stage screening for children in lieu of venipuncture. Using a limited cohort of 99 children with Down syndrome identified over 10 years by capillary TSH ≥ 4 mU/L, they determine that a cutoff TSH value of 6 mU/L was 73.5% sensitive and 80.8% specific in predicting venous TSH >10 mU/L. Correlation between capillary TSH and venous free T4 was low. The authors propose an algorithm for management based upon capillary TSH. For any child with capillary TSH > 6 mU/L, they recommend clinical assessment and immediate venipuncture. For those children <5 years of age with capillary TSH in the 4-5.9 mU/L range they also suggest immediate venipuncture. In those children aged 5 years and older with a result in the 4-5.9 mU/L range, they suggest repeat capillary screening six months later because decompensated hypothyroidism was so rare in these patients, only 1 of 38. Whether their less invasive and likely less expensive approach should be adopted more globally will require additional study. Article page 1013▶ Screening for Hypothyroidism in Down Syndrome Using the Capillary Thyroid Stimulating Hormone MethodThe Journal of PediatricsVol. 166Issue 4PreviewTo analyze data from the Scottish capillary thyroid stimulating hormone (TSH) screening program for hypothyroidism in Down syndrome to identify a threshold for capillary TSH elevation below which low venous free thyroxine (fT4) (<9 pmol/L) and/or frank venous TSH elevation (>10 mU/L) range is unlikely. Full-Text PDF

Screening for Hypothyroidism in Down Syndrome Using the Capillary Thyroid Stimulating Hormone Method

To analyze data from the Scottish capillary thyroid stimulating hormone (TSH) screening program for hypothyroidism in Down syndrome to identify a threshold for capillary TSH elevation below which low venous free thyroxine (fT4) (<9 pmol/L) and/or frank venous TSH elevation (>10 mU/L) range is unlikely. Review of proformas prospectively submitted on all children with Down syndrome referred via the screening program between 2003 and 2013. Ninety-nine patients with Down syndrome (50 females, 49 males) were identified, 76 school-age (≥ 5 years) and 23 preschool (<5 years), mean (range) age at referral 9.4 (0.9-18.1) years. Pearson correlation between capillary TSH and venous TSH was 0.814; between capillary TSH and venous fT4 -0.522 (P = .01). Receiver operator curve analysis showed that capillary TSH values of 4 and 6 mU/L were 95.9% and 73.5% sensitive, 5.8% and 80.8% specific, respectively, in predicting venous TSH >10 mU/L. Fifty-three children had capillary TSH values of 4-5.9 mU/L of whom only one, a boy of 15.8 years, had subnormal venous fT4 (<9 pmol/L), and venous TSH >10 mU/L was found in 13 (4 preschool). Venous fT4 is normal in almost all patients with Down syndrome with capillary TSH 4-6 mU/L. We propose an algorithm incorporating rescreening by finger prick after 6 months, rather than venepuncture, in school-aged children with borderline capillary TSH elevation. Further data are needed before this approach can be recommended for preschool children.

Thinking outside the skin: Look at the thyroid for true diagnosis

Keratoderma is a group of disorders characterized by abnormal thickening of skin. Acquired palmar keratoderma has many underlying causes. The association of thyroid disease and palmar keratoderma rarely reported. Hypothyroidism, although very rare association, must be suspected in patients with acquired PPK, particularly when it occurs in setting of systemic symptoms or predisposing conditions.We report first case of acquired plantar keratoderma associated with undiagnosed hypothyroidism in Down syndrome.

Cardiac Spectrum, Cytogenetic Analysis and Thyroid Profile of 418 Children with Down Syndrome from South India: A Cross-sectional Study

To describe the spectrum of congenital heart disease in children with Down syndrome and their cytogenetic profile (and that of parents of those with translocation), and thyroid profile. A cross sectional study was conducted in 418 consecutive patients with Down syndrome attending the Department of Pediatric Genetics from a tertiary care centre in Kerala with a comprehensive Pediatric Cardiac Program, from November 2005 through April 2012. All children were offered cytogenetic analysis and were subjected to echocardiography. Parental karyotyping was offered for children with translocation type of Down syndrome. The thyroid profiles of all children were checked at the first visit and once every 6mo during follow up. Congenital heart disease was present in 256 (63.4%) of 404 children with Down syndrome. Ventricular septal defect (72; 28.1%) was the commonest, followed by atrio-ventricular septal defect (70; 27.3%) and patent ductus arteriosus (43; 16.8%). Surgical correction was accomplished in 104 (40.6%) with excellent intermediate-term outcomes. Three hundred eighty seven of 418 children (92.6%) underwent cytogenetic tests. The abnormalities included non-disjunction (340, 87.8%), translocation (33, 8.5%) and mosaicism (12, 3.1%). Hypothyroidism was detected in 57 children (13.6%). The prevalence of congenital heart disease in children with Down syndrome in Kerala is the highest reported (63.4%). Ventricular septal defect is the most common heart disease in the present study. The results highlight the changing attitudes of families towards the surgical correction of congenital heart disease in children with Down syndrome. Prevalence of hypothyroidism in Down syndrome in Kerala is 13.6%.

Antithyroid antibodies and thyroid dysfunction in Saudi children with Down syndrome.

Fifty children (ages seven months to nine years) with Down syndrome compared with age and sex matched controls were tested for antithyroid antibodies. Seven (14%) of the Down group were found to be seropositive; six (12%) for antimicrosomal antibodies; three for both antimicrosomal and antithyroglobulin; none was positive for antithyroglobulin alone. All the control group were seronegative and had no clinical evidence of thyroid disease. Three (6%) of the Down group had hypothyroidism, two due to autoimmune thyroiditis and one had thyroid dysgenesis; one of the previous two had insulin dependent diabetes mellitus. One child had Graves disease. Thyroid dysfunction was not previously suspected in the two symptomatic children. In view of our findings, recommendations are made to regularly screen these children for autoantibodies and evidence of thyroid dysfunction.

Pericardial effusion as a sign of acquired hypothyroidism in children with Down syndrome

In three children with Down syndrome and acquired hypothyroidism echocardiography was performed before and after the start of L-thyroxine treatment. Initial studies revealed pericardial effusions which resolved during treatment suggesting that they were caused by hypothyroidism. The incidence of hypothyroidism in Down syndrome is high, but the diagnosis is often missed for lack of specific clinical criteria. The finding of pericardial effusion by echocardiography may be essential in discovering thyroid dysfunction. The cases illustrate that regular thyroid function tests are important in Down syndrome.