Effect of initial levothyroxine dose on neurodevelopmental and growth outcomes in children with congenital hypothyroidism.

Autor:	Esposito A; Pediatric Endocrinology Unit, Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy., Vigone MC; Endocrine Unit, Department of Pediatrics, IRCCS San Raffaele Hospital, Milan, Italy., Polizzi M; Pediatric Endocrinology Unit, Department of Mother and Child, University Hospital Federico II, Naples, Italy., Wasniewska MG; Department of Human Pathology of Adulthood and Childhood, University of Messina, Messina, Italy., Cassio A; Unit of Pediatrics, University of Bologna, Bologna, Italy., Mussa A; Pediatric Clinical Genetics Unit, Department of Public Health and Pediatrics, Regina Margherita Children Hospital, Torino, Italy., Gastaldi R; Department of Pediatrics, IRCCS Istituto Giannina Gaslini, Genova, Italy., Di Mase R; Pediatric Endocrinology Unit, Department of Mother and Child, University Hospital Federico II, Naples, Italy., Vincenzi G; Endocrine Unit, Department of Pediatrics, IRCCS San Raffaele Hospital, Milan, Italy., Pozzi C; Endocrine Unit, Department of Pediatrics, IRCCS San Raffaele Hospital, Milan, Italy., Peroni E; Department of Pediatrics, Ospedale di Legnano, ASST Ovest milanese, Legnano, Italy., Bravaccio C; Pediatric Endocrinology Unit, Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy., Capalbo D; Pediatric Endocrinology Unit, Department of Mother and Child, University Hospital Federico II, Naples, Italy., Bruzzese D; Department of Public Health, University of Naples Federico II, Naples, Italy., Salerno M; Pediatric Endocrinology Unit, Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.
Jazyk:	angličtina
Zdroj:	Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2022 Sep 05; Vol. 13, pp. 923448. Date of Electronic Publication: 2022 Sep 05 (Print Publication: 2022).
DOI:	10.3389/fendo.2022.923448
Abstrakt:	Objectives: We designed a multicentre open prospective randomized trial to evaluate the risk-benefit profile of two different initial treatment schemes with levothyroxine (L-T4), 10-12.5 μg/kg/day vs 12.6-15 μg/kg/day, on growth and neurodevelopmental outcomes in children with congenital hypothyroidism (CH) detected by neonatal screening to identify the best range dose to achieve optimal neurocognitive development. Design Patients and Methods: Children detected by neonatal screening were randomly assigned to receive an initial L-T4 dose of 10-12.5 μg/kg/day (Low) or 12.6-15 μg/kg/day (High). All patients underwent periodical clinical examination with measurement of growth parameters and measurement of TSH and FT4. Neurocognitive development was evaluated at the age of 24 months using Griffiths Mental Development Scales (GMDS) and cognitive and behavioral assessment was performed at 48 months of age using Wechsler Preschool and Primary scale of Intelligence (WIPPSI-III). The study was registered with clinicaltrials.gov (NCT05371262). Results: Treatment schemes below or above 12.5 μg/kg/day were both associated with rapid normalization of TSH and thyroid hormone levels in most patients with no differences in the risk of over- and under-treatment episodes in the first months of life. Growth parameters were normal and comparable between the two groups. Developmental quotients at 24 months of age were normal in both groups (Low 100.6 ± 15.5 vs High 96.9 ± 16.6). Likewise, at 4 years of age IQ and subtest scores were comparable between patients from Low and High (Total IQ 104.2 ± 11.4 vs 101.0 ± 20.3, Verbal IQ 103.9 ± 11.5 vs 98.7 ± 15.1, Performance IQ 105.3 ± 10.4 vs 100.3 ± 19.8). 6/45 CH patients (13.3%) showed a total IQ below 85 (73.7 ± 5.9) regardless of age at diagnosis, L-T4 starting dose, time of FT4 and TSH normalization and episodes of over and undertreatment. Worse socioeconomic status and delayed bone age at diagnosis were the only predictors of an increased risk of having suboptimal IQ at 24 and IQ at 48 months. Conclusions: Our results indicate that initial treatment with L-T4, 10-12.5 μg/kg/day vs 12.6-15 μg/kg/day, are both associated with normal growth and neurodevelopmental outcomes in children with CH detected by neonatal screening. Further studies with a long-term follow-up on a larger number of patients are needed to confirm these results. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05371262?term=NCT05371262&draw=2&rank=1 identifer NCT05371262. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Esposito, Vigone, Polizzi, Wasniewska, Cassio, Mussa, Gastaldi, Di Mase, Vincenzi, Pozzi, Peroni, Bravaccio, Capalbo, Bruzzese and Salerno.)
Databáze:	MEDLINE
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