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Ann Pediatr Endocrinol Metab > Volume 30(4); 2025 > Article
Dermitzaki, Giapros, Deligeorgopoulou, Tsinopoulou, Kotanidou, Baltogianni, Balomenou, and Serbis: Reply to commentary on "Predictive factors of permanent versus transient congenital hypothyroidism: a pragmatic cohort study"
To the editor,
We would like to thank the authors of the recent letter to the editor for their interest in our article “Predictive factors of permanent versus transient congenital hypothyroidism: a pragmatic cohort study [1].” We appreciate their thoughtful and constructive feedback and are pleased to respond to their points.
Regarding the thyroid-stimulating hormone (TSH) cutoff value of <13.3 μIU/mL, we acknowledge that our proposed threshold is lower than those reported in most previous studies, which typically range between 30 and 75 μIU/mL. Our cohort included a substantial number of neonates identified via risk-based testing, including clinical indications such as prematurity etc. Preterm neonates may exhibit blunted TSH responses and delayed or nonstandard testing may capture post-surge TSH values that are typically lower. This likely contributed to the downward shift in TSH distribution observed in our cohort. We fully agree with the authors that this threshold may not be generalizable to all populations or clinical settings. However, we believe it may have particular relevance in real-life, mixed-risk clinical environments where transient congenital hypothyroidism (TCH) is increasingly common.
Regarding levothyroxine (LT4) dosage as a diagnostic marker, we agree that LT4 dosing thresholds may vary depending on clinical practice and population differences. In our study, a cutoff of 3.0 µg/kg/day at 12 months of age showed high specificity for distinguishing TCH from permanent congenital hypothyroidism. Other authors have proposed both higher thresholds and lower ones [2,3]. A key strength of our study is the consistent management of all patients by a single pediatric endocrinologist, ensuring uniform dose titration and follow-up. While our threshold may not be directly generalizable, it remains informative in comparable clinical settings. As the authors of the letter correctly note, larger studies with standardized protocols are essential to further refine these indicators.
Regarding the third point raised, we appreciate the authors’ emphasis on the importance of adequate follow-up after treatment discontinuation. In our study, we adopted a stricter approach compared to the 2021 European Society of Pediatric Endocrinology guidelines [4], to reduce the risk of misclassification and to increase diagnostic certainty. More specifically, patients were monitored for six months, TSH was measured at least twice, and we applied a lower TSH threshold of 8 mU/L to define recurrence. While our methodology exceeds current recommendations, we agree with the authors of the letter that rare cases of late relapse may still occur, underscoring the importance of clinical vigilance and long-term follow-up.
Finally, regarding the absence of routine thyroid imaging, we agree that thyroid scintigraphy is a valuable diagnostic tool [5]. However, due to limited access and prevailing local practice, it was not routinely performed in our cohort. While imaging can certainly enhance diagnostic precision, one of the aims of our study was to evaluate predictive markers that remain applicable in settings where advanced imaging is not readily available.
In conclusion, we are grateful for the thoughtful comments made by our colleagues. We agree that future prospective, multicenter studies are essential to refine the diagnostic approach to congenital hypothyroidism. We hope our study contributes meaningfully to this ongoing effort.

Notes

Conflicts of interest

No potential conflict of interest relevant to this article was reported.

References

1. Dermitzaki N, Giapros V, Deligeorgopoulou M, Tsinopoulou VR, Kotanidou E, Baltogianni M, et al. Predictive factors of permanent versus transient congenital hypothyroidism: a pragmatic cohort study. Ann Pediatr Endocrinol Metab 2025;30:149-56.
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2. Saba C, Guilmin-Crepon S, Zénaty D, Martinerie L, Paulsen A, Simon D, et al. Early determinants of thyroid function outcomes in children with congenital hypothyroidism and a normally located thyroid gland: a regional cohort study. Thyroid 2018;28:959-67.
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3. Higuchi S, Hasegawa Y. Levothyroxine dosages less than 2.4 μg/kg/day at 1 year and 1.3 μg/kg/day at 3 years of age may predict transient congenital hypothyroidism. Clin Pediatr Endocrinol 2019;28:127-33.
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4. Van Trotsenburg P, Stoupa A, Léger J, Rohrer T, Peters C, Fugazzola L, et al. Congenital hypothyroidism: a 2020-2021 consensus guidelines update - an ENDO-European Reference Network Initiative Endorsed by the European Society for Pediatric Endocrinology and the European Society for endocrinology. Thyroid 2021;31:387-419.
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5. Li WI, Chan TK, Ng KK, Kung BT. Predictive value of technetium-99m sodium pertechnetate thyroid scintigraphy in determining the permanence of congenital hypothyroidism. J Clin Imaging Sci 2025;15:3.
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