We read with great interest Dermitzaki et al. [1], article titled "Predictive factors of permanent versus transient congenital hypothyroidism (CH): a pragmatic cohort study." The authors provide helpful evidence to differentiate between temporary CH (TCH) and permanent CH (PCH) using markers like initial thyroid-stimulating hormone levels and levothyroxine (LT4) dosage trends. This study tackles a relevant clinical issue, given rising TCH rates due to increased screening and better outcomes for premature infants. The study's internal validity is increased by the retrospective design and management by a single endocrinologist. However, we have some clinical considerations about this article.

Firstly, the recommended diagnostic TSH cutoff of <13.3 μIU/mL for TCH prediction in this study is significantly lower than thresholds found in previous research, which roughly range from 38 to 75 μIU/mL [2]. Lowering the cutoff increases detection of mild or transient cases. The authors suggest that this lower figure reflects the inclusion of neonates diagnosed via non-routine screening, which biases the sample. Additionally, variations in screening protocols, like timing of sampling and inclusion criteria, can have a significant influence on initial TSH values. The study’s TSH cutoff reflects its unique referral population and cannot be a universal predictor of TCH. Therefore, caution is needed while applying this cutoff universally because it may not apply to different populations or clinical settings, which limits its generalizability.

Secondly, while LT4 dosage offers a practical approach to assess disease persistence, starting dose and dosage adjustment can highly fluctuate across clinicians and institutions. For instance, the cutoff of more than 3.0 μg/kg/day at 12 months in the current study is in contrast to a larger threshold (>4.7 μg/kg/day) identified in a multicenter Japanese cohort [3]. Many clinics treat mild CH more aggressively, while others tolerate borderline cases. These variations suggest that LT4 dosing trends may not reproduce across different clinical settings. Thus, relying on the LT4 dose as a diagnostic marker of TCH or PCH without taking into account these differences may limit reproducibility.

Furthermore, classifying CH as transient on the basis of normal TSH levels 6 months after discontinuation of LT4 at age 3 may be premature. A large observational study found that many children between ages 2–3 initially classified as having TCH relapsed after discontinuation [4]. This indicates the risk of misclassification and suggests longer follow-up.

Lastly, no patients had thyroid scintigraphy done, and only 30 out of 92 babies got thyroid ultrasonography. Scintigraphy is a definitive tool for distinguishing PCH from TCH. It provides accurate anatomical and functional data that are critical for prognosis [5]. The lack of imaging weakens the claim that all TCH cases truly had a normal gland and would not have relapsed. When paired with laboratory and clinical data, more thorough imaging would improve accuracy.

In conclusion, Dermitzaki et al. [1] provides important information for more customized treatment of CH. Future studies should focus on longer follow-up, routine imaging, and refined TSH thresholds to enhance diagnostic accuracy and reduce the risk of misclassification.