Validity of Six Month L-Thyroxine Dose for Differentiation of Transient or Permanent Congenital Hypothyroidism

Abstract

Objective: The tendency to reduce thyroid stimulating hormone (TSH) referral cut-off values in congenital hypothyroidism (CH) neonatal screening programs has resulted in an increase in the incidence of CH, but also the referral of infants with mild transient elevation of TSH. Therefore, there is a need to develop markers for differentiation of transient elevated TSH and permanent CH as early as safely possible to avoid unnecessary treatment. The aim was to evaluate sixth-month L-thyroxine (LT4) dose as a predictive marker for differentiation of transient elevated TSH and permanent CH. Methods: Data of patients who had been followed after referral from the neonatal screening programme between the year 2010 and 2019 in a tertiary pediatric endocrine centre were examined retrospectively. Results: There were 226 cases referred, of whom 186 (82.3%) had eutopic thyroid gland, and 40 (17.7%) had dysgenetic gland. In patients with a dysgentic gland there was a non-significant tendency to have lower diagnostic free thyroxine concentration but significantly higher TSH compared with those with eutopic gland (p=0.44 and p=0.023, respectively). Patients with thyroid dysgenesis required higher initial and six month LT4 doses compared with those with eutopic glands (p=0.001). Receiver operator curve analysis showed the optimum cut-off value for LT4 at six months for transient vs. permanent CH was 2 μg/kg/day (sensitivity 77% and specificity 55%), regardless of etiology. Similarly, in patients with eutopic glands the optimum cut-off value for LT4 dose at six months for permanent vs. transient patients was 2 μg/kg/day (sensitivity 72% and specificity 54%). Conclusion: Results suggest that LT4 requirement at six months of therapy may be a good marker for predicting transient TSH elevation in patients with eutopic thyroid gland, thus facilitating the decision to halt LT4 therapy.

Predictors of transient congenital primary hypothyroidism: data from the German registry for congenital hypothyroidism (AQUAPE “HypoDok”)

“…L-T 4 treatment dosages at various time points during the first 3 years have been reported to discriminate TCH from PCH [2,[7][8][9][10]16]. Based on these parameters, the decision to withdraw L-T 4 treatment in infancy in order to re-evaluate endogenous thyroid function may be made.…”

“…L-T 4 treatment is then paused for 4 to 6 weeks in order to assess endogenous thyroid function. Earlier withdrawal is discussed when transient elevations of neonatal TSH concentrations are likely and there is impending overtreatment [7][8][9][10]. Paediatric endocrinologists tend to conduct therapy in the first 2 years of life in order to avoid defects in the myelinisation of the central nervous system and to assure normal neurodevelopmental outcomes.…”

Etiological Evaluation of Congenital Hypothyroidism Cases

“…Geçici konjenital hipotiroidinin etiyolojisi multifaktöriyeldir. Geçici hipotiroidi olgularında tedavinin daha erken sonlandırılabileceği durumlar olsa da, klasik olarak bu hastalarda tedavinin 3 yaşına kadar tedavi ettirilmesi ve 3 yaşında değerlendirme yapılması önerilmektedir (5,7,8) .…”

Predictors of Transient Congenital Primary Hypothyroidism: Data from the German Registry for Congenital Hypothyroidism (AQUAPE "HypoDok")

“…Thus, these cases will not to be reported to "HypoDok", if temporary treatment is expected. L-T4 treatment dosages at various time points during the first three years have been reported to discriminate TCH from PCH (2,7,8,9,10,16). Based on these parameters, the decision to withdraw L-T4 treatment in infancy in order to re-evaluate endogenous thyroid function may be made.…”

“…L-T4 treatment is then paused for 4 to 6 weeks in order to assess endogenous thyroid function. Earlier withdrawal is discussed when transient elevations of neonatal TSH concentrations are likely and there is impending overtreatment (7,8,9,10). Paediatric endocrinologists tend to conduct therapy in the first 2 years of life in order to avoid defects in the myelinisation of the central nervous system and to assure normal neurodevelopmental outcomes.…”