Ten-Year Longitudinal Study of Thyroid Function in Children with Down's Syndrome

Abstract

Background/Aims: The natural history of thyroid function in children with Down's syndrome is relatively unknown. We hypothesized that in these patients the occurrence of thyroid dysfunction rises during development. Methods: Thyroid function was assessed yearly in 145 children with Down's syndrome, all followed from birth up to 10 years of age. Heteroskedastic binary and ordinary logistic regression for repeated measures was used to evaluate the relationship of thyroid function with continuous time. Results: Congenital hypothyroidism was detected in 7% of cases. The probability of acquired thyroid dysfunction increased from 30% at birth to 49% at 10 years (p < 0.001). The subclinical hypothyroidism was nearly stable during the follow-up. The probability of hypothyroidism increased from 7 to 24% at 10 years (p < 0.001). Positive anti-thyroglobulin antibodies were associated with higher odds of more severe hypothyroidism (odds ratio 3.6). Positive anti-thyroid peroxidase antibodies were a better predictor of more severe hypothyroidism (odds ratio 6.1). Diffuse hypoechogenicity on thyroid ultrasound was found in 34 out of 145 children. Conclusion: The probability of thyroid dysfunction increasing during development is higher than previously reported. Such children should be carefully monitored annually to early identify thyroid dysfunction.

Demographics and co‐occurring conditions in a clinic‐based cohort with Down syndrome in the United Arab Emirates

“…During a 10‐year longitudinal study of thyroid function in children with DS, over half of the children developed some type of thyroid dysfunction (Iughetti et al, ), lending strong evidence in support of a recommended maximum post‐infancy screening interval of 1 year. Following routine screening protocols established in our clinic, analysis of our cohort revealed a total of 23.1% meeting diagnostic criteria for hypothyroidism, including 5% diagnosed congenitally, 10.9% with acquired hypothyroidism and the remaining 7.2% having subclinical hypothyroidism.…”

Trisomy 21 activates the kynurenine pathway via increased dosage of interferon receptors

“…Another key area of interest is in the management of immunerelated disorders. On one hand, people with DS show increased incidence of autoimmune disorders such as autoimmune hypothyroidism 51 , celiac disease 7 , and myriad autoimmune skin conditions 52 , indicating a hyperactive immune system. Conversely, people with DS show increased risk to specific bacterial infections, with bacterial pneumonia being a leading cause of death 53 .…”

Down syndrome—A narrative review with a focus on anatomical features

“…Thyroid dysfunction is the most common endocrine abnormality in patients with DS (Hawli et al, ; Iughetti et al, ), but prevalence estimates vary widely, ranging between 3% and 54% in adults (Hawli et al, ). The established risk factors for thyroid dysfunction in DS include old age and female sex (Rose and Brown, ).…”

“…Evidence indicates that the frequency of hypothyroidism in neonates with DS is 28 times higher than expected in the general population (Purdy et al, ). Recently, a 10‐year longitudinal study demonstrated that the probability of acquired thyroid dysfunction in DS increased from 30% at birth to 49% at 10 years of age (Iughetti et al, ). Several mechanisms have been proposed to explain the increased incidence of hypothyroidism in DS, including immaturity of the hypothalamic‐pituitary‐thyroid axis (Sharav et al, ), inappropriate thyroid stimulating hormone (TSH) secretion (Gruñeiro de Papendieck et al ), TSH insensitivity (Gibson et al, ), and reduced TSH bioactivity (Gibson et al, ).…”