Major lipoprotein(a) increase under IGF-1R inhibition in Graves' orbitopathy: A case report

Elevated plasma lipoprotein(a) [Lp(a)] is an independent cardiovascular risk factor due to its strong link with atherosclerotic cardiovascular disease. Although Lp(a) levels are mainly genetically determined and stable, conditions such as Graves' disease, which causes hyperthyroidism, can reduce Lp(a) concentration by 20% to 35%. Graves' orbitopathy (GO), a common manifestation of Graves' disease, is characterized by the interplay between thyroid-stimulating hormone (TSH) and insulin-like growth factor-1 (IGF-1) signaling. Clinical trials have shown that teprotumumab, an IGF-1 receptor inhibiting monoclonal antibody, improves GO outcomes. Since IGF-1 is known to decrease Lp(a) by 40% to 80%, its blockade by teprotumumab may disrupt Lp(a) metabolism and lead to adverse metabolic effects. Here we report the case of a 74-year-old woman with GO who experienced a significant increase in Lp(a) levels exceeding the atherogenic threshold (ie, > 125 nmol/L) following teprotumumab therapy. These variations of Lp(a) levels occur independently of thyroid homeostasis. This clinical observation underlines the importance of monitoring Lp(a) concentrations during treatment with IGF-1 inhibitors, particularly in patients at high cardiovascular risk.