Underlying Mechanism of Hypothyroidism in a Patient with ATTRv Receiving Patisiran

To the Editor We read with great interest the case report that described the development of overt hypothyroidism in a patient with hereditary transthyretin amyloidosis (ATTRv) following the administration of patisiran (1).This case raises important questions regarding the potential endocrine effects of RNA interference-based therapies and highlights the need for more comprehensive data to clarify the underlying causality.Although the authors note that hypothyroidism has rarely been reported in clinical trials and post-marketing surveillance (2), several factors in the current case warrant further investigation.The thyroid function prior to patisiran initiation was within the low-normal range, with free T4 and T3 values bordering the lower limits (1).This raises the possibility that subclinical hypothyroidism was present.However, the authors did not provide information on whether antithyroid antibodies (e.g., TPOAb and TgAb) were assessed at baseline or whether serial hormone measurements were performed leading up to treatment.These data are essential to determine whether thyroid dysfunction was preexisting, disease-related, or potentially unmasked by TTR suppression.Although the authors stated that thyroid ultrasound did not suggest Hashimoto's thyroiditis (1), detailed sonographic features such as gland size, echotexture, and vascularity were not presented.In the context of ATTRv, where tissue infiltration may be patchy or subtle, descriptive ultrasonographic findings would help support or refute amyloid involvement of the thyroid (3).Additionally, serum thyroxine-binding globulin (TBG) levels have not yet been reported.Since patisiran suppresses TTR, one of the several transport proteins for T4, TBG quantification could help differentiate true hypothyroidism from alterations in proteinbound hormone kinetics.Another concern was the biochemical course following the switch from patisiran to vutrisiran.