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Early levothyroxine dose may identify patients with transient congenital hypothyroidism
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A lower dose of levothyroxine treatment at age 6 months in infants with a normally located thyroid gland and a lower likelihood of having a first-degree family history of congenital hypothyroidism were associated with transient congenital hypothyroidism vs. permanent disease, according to data published in Thyroid.
“According to current guidelines, children with congenital hypothyroidism and a eutopic gland should undergo a reevaluation of thyroid function at or before the age of 3 years to distinguish between cases of transient and permanent congenital hypothyroidism,” Juliane Léger, MD, head of the Reference Centre for Endocrine Growth and Development Diseases and cochair of the Pediatric Endocrinology Department at the Robert Debré University Hospital in Paris, told Endocrine Today. “[These findings] highlight the need to evaluate the levothyroxine dose requirement in patients as young as 6 months old, particularly for those with no familial history of congenital hypothyroidism for early identification of ... patients for whom treatment should be stopped.”
Léger and colleagues conducted an observational cohort study of all patients who had been treated for congenital hypothyroidism with a normally located gland in northern Paris during 2002 to 2012. Systematic neonatal screening revealed 240 patients with congenital hypothyroidism, including 110 with thyroid dysgenesis and 130 (54%) with a normally located thyroid gland. After exclusion of patients who did not receive levothyroxine treatment and those lost to follow-up and death, 92 infants treated for congenital hypothyroidism with a normally located gland remained. Patients were aged a median of 19 days when treatment was initiated, with median thyroid-stimulating hormone concentrations of 69 mIU/L and median free thyroxine concentrations of 12.8 pmol/L. The median initial levothyroxine dose was 8.4 mcg/kg per day. Treatment was discontinued in patients with transient congenital hypothyroidism at a median age of 1.5 years (range, 0.6–3.2 years).
Logistic regression analysis showed patients with transient congenital hypothyroidism were less likely to have a familial form of congenital hypothyroidism and had lower doses of levothyroxine at age 6 months compared with those with permanent congenital hypothyroidism (P < .03). Patients with transient congenital hypothyroidism were more likely to have smaller increases in serum TSH concentrations at diagnosis and were more likely to start levothyroxine treatment later during the first month of life compared with patients with permanent congenital hypothyroidism. They also had lower doses of levothyroxine initially and at 6 months and 12 months old. Patients with transient congenital hypothyroidism were also less likely than those with permanent congenital hypothyroidism to be the offspring of consanguineous parents and to have positive perchlorate test results.
Researchers found that sex, being small for gestational age, neonatal problems, associated malformation, iodine overload, congenital hypothyroidism severity based on serum TSH and free T4 levels or bone maturation delay at diagnosis, and thyroid gland morphology were not associated with disease course.
Receiver operating characteristic curve analysis revealed the optimal cutoff values for levothyroxine dose to individually predict transient congenital hypothyroidism were 3.2 mcg/kg per day at age 6 months and 2.5 mcg/kg per day at age 12 months (sensitivity, 71%; specificity, 79% and 78%, respectively).
The researchers called for further prospective studies to confirm the levothyroxine dose requirement with these cutoffs during routine monitoring or reevaluation of thyroid function in patients with no history of familial congenital hypothyroidism.
“Parents should be made aware, when they are informed of their child’s diagnosis during the neonatal period, that subsequent reinvestigation will be necessary to determine whether the congenital hypothyroidism is persistent during childhood,” Léger said. “The early identification of patients with transient, as opposed to permanent, congenital hypothyroidism has a number of important implications, relating to levels of parental anxiety, expense and potential chronic overtreatment, which has been shown to be associated with poorer neurodevelopmental outcomes.” – by Tina DiMarcantonio Brown
For more information:
Juliane Léger, MD, can be reached at Endocrinologie Diabétologie Pédiatrique & INSERM U 1141, Centre de Référence Maladies Endocriniennes de la Croissance et du Développement, Université Paris 7 Diderot, AP-HP, Hôpital Universitaire Robert Debré, 75019 Paris, France; email: juliane.leger@aphp.fr.
Disclosure: The authors report no relevant financial disclosures.
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