Evaluation of permanent and transient congenital hypothyroidism in cases referred from National Neonatal Screening Program

Aim: The incidence of congenital hypothyroidism (CH) has increased world-wide. Lowering cut-off in screening programs has led to an increase in the rate of transient CH. We aimed to evaluate the rates of permanent and transient CH in cases referred from the screening program and to investigate the clinical and laboratory factors which predict transient CH.

Methods: In 109 cases referred from the neonatal screening program to our hospital, from September 2015 to April 2018, 52 primarily diagnosed CH cases were prospectively evaluated. Regularly followed up, 44 CH cases were included in the study at the end of 3 years.

Results: 38.2 ± 1.31 weeks (w) and mean birthweight 3021.3 ± 389.6 gram (g) in the transient CH group; both were significantly lower compared to permanent CH cases with 39.06 ± 1.33 w and 3375.3 ± 425.3 g (P = 0.025, P = 0.007) respectively. Transient CH rate was found to be 50% (all hypoplastic) in the dysgenesis group and 73.3% in groups with normal and hyperplasic thyroid gland. While fT₄ , thyroid-stimulating hormone, and thyroglobulin levels at diagnosis do not predict transient/permanent CH, levothyroxine (LT-4) dosage was significantly lower in the transient CH group in all years. The optimal cut-off value with highest sensitivity and specificity for LT-4 dosage as a predictive marker to differentiate transient CH from permanent CH was 2.27 μg/kg/day (P = 0.004; sensitivity: 71%, specificity: 83%) at 1st year, 1.85 μg /kg/day (P = 0.013; sensitivity: 66%, specificity: 72%) at 2nd year and 1.69 μg /kg/day at 3rd year (P < 0.0001; sensitivity: 90%, specificity: 83%).

Conclusion: Transient CH is more frequent than expected. Our results suggest that LT-4 requirement may be a good marker for predicting transient CH, while thyroid hormone levels at the time of diagnosis do not significantly predict permanent and transient CH. Therefore, infants with CH requiring LT-4 doses <2.27 μg/kg/day at 1st year, <1.85 μg /kg/day at 2nd year may be re-evaluated earlier to discriminate transient CH rather than at 3 years of age.