Hypothyroidism symptoms in LT4-euthyroid thyroidectomized patients reflect an alteration of the serum proteome

Abstract In patients undergoing thyroidectomy one of the goals of post-surgical follow-up is the correct maintenance of thyroid hormone (TH) levels by replacement therapy with levo-thyroxine (LT4). Nevertheless, some patients complain of symptoms of hypothyroidism (memory loss, weight gain, fatigue, depression, and reduced quality of life) despite values of thyroid hormones get the physiological range. Since this recurrent issue, we aim to compare serum proteomic profiles of LT4-euthyroid thyroidectomized patients with good or reduced post-operative quality of life. Proteomic analysis highlights a different protein profile in the serum of patients with reduced quality of life compared to the other although both resulted euthyroid. Differential proteins are involved in coagulation processes, complement system activation and in lipoprotein particles remodeling, that together lead to a pro-inflammatory response. Moreover, a particular degradome of apolipoprotein A1, thrombin heavy chain and alpha 1 antitrypsin, was also detected. This study suggests that LT4 replacement therapy might restore euthyroid conditions in thyroidectomized patients but in some cases without re-establish body tissues euthyroidism and serum protein profiles strongly suggest a behavior similar to overt hypothyroidism.