Episodes of Overtreatment during the First Six Months in Children with Congenital Hypothyroidism and Their Relationships with Sustained Attention and Inhibitory Control at School Age

Abstract

Background/Aims: Contradictory results regarding the optimal initial dose of levothyroxine in children with congenital hypothyroidism (CH) hamper the clinical management of these children during their early infancy. We explore the relationships between the initial dose of levothyroxine and endocrine control during the first 6 months and cognition at school age. Subjects and Methods: Fifty children with CH, 14 boys (10 ± 3.1 years) and 36 girls (9.7 ± 2.6 years), at the Pediatric Endocrine Unit of the Hospital Gregorio Marañón in Madrid were studied. Neurocognitive evaluation was carried out exploring alertness and inhibitory control. The number of episodes of overtreatment during the first 6 months, the initial dose of levothyroxine, etiology and sex were the predictor variables. Results: Inhibitory control was significantly lower in children with CH than in controls. An interaction with gender and etiology was obtained. Alertness had an inverse relationship with the number of episodes of overtreatment with no interaction with gender or etiology. Conclusion: Episodes of overtreatment and not the initial dose of levothyroxine are a risk factor for deficit in alertness whereas subtle inhibitory control deficit seems to be a permanent problem with the current therapeutic approach.

ENDOCRINOLOGY AND ADOLESCENCE: Congenital hypothyroidism: a clinical update of long-term outcome in young adults

“…Such an association is also consistent with experimental studies showing the effects of chronic hypothyroidism on development (31). Overtreatment should also be avoided (32,33). These results highlight the need for careful monitoring of treatment adequacy throughout childhood and adulthood.…”

Relation between Early Over- and Undertreatment and Behavioural Problems in Preadolescent Children with Congenital Hypothyroidism

“…If the absence of over- and undertreatment would be a causative factor, a substantial proportion of all healthy newborns with normal thyroid function without over- or undertreatment in these periods would show ADHD-like or ASD-like behaviour, which is obviously not the case. Furthermore, the conclusion that overtreatment in the period 1–3 months is a causative factor for high ADA scores, and that the absence of overtreatment in the period 3–6 months is not, is in line with previous studies [3, 6]. One of these [6] suggests that at least a considerable proportion of the “difficult” patients experienced overtreatment in the period 1–3 months, because at 3 years they showed more advanced motor development than did the “easy” patients.…”

“…Thyroid abnormalities have been associated with attention deficit hyperactivity disorder (ADHD) in various studies [1-3]. This association is most clearly seen in a study on thyroid hormone resistance [1], where the majority of the patients were found to have ADHD.…”

“…In adolescents with congenital hypothyroidism (CH) the proportion of patients with ADHD was estimated at 30–40% [2]. In a group of fifty 10-year-old CH patients poor attention was seen after overtreatment in the first 6 months after birth [3]. Two other studies, however, failed to confirm poor impulse control and externalizing problems in CH patients.…”

Permanent Decompensated Congenital Hypothyroidism in Newborns with Whole-Blood Thyroid-Stimulating Hormone Concentrations between 8 and 10 mU/L: The Case for Lowering the Threshold

“…Although there are no studies to show that treating these children with levothyroxine improves outcome, treatment for subclinical hypothyroidism is frequently recommended for the vulnerable first 2 or 3 years of life when brain development is thyroid hormone dependent [3]. It has also been suggested that overtreatment with levothyroxine in this time period may adversely affect neurodevelopmental outcomes and should be avoided [9, 10]. …”