Mechanisms
Case report: the IGF-1 receptor blocker teprotumumab drove Lp(a) above the atherogenic threshold in a Graves' orbitopathy patient (J Clin Lipidol 2025)
Original title: Major lipoprotein(a) increase under IGF-1R inhibition in Graves' orbitopathy: A case report
This case report describes a 74-year-old woman with Graves' orbitopathy who developed a significant rise in Lp(a), exceeding the atherogenic threshold of 125 nmol/L, after starting teprotumumab, an IGF-1 receptor inhibiting monoclonal antibody used to treat the condition. The authors note that while Graves' disease itself typically reduces Lp(a) by 20% to 35% via hyperthyroidism, IGF-1 signalling is separately known to decrease Lp(a) by 40% to 80%, so blocking the IGF-1 receptor with teprotumumab likely disrupted this suppression independently of thyroid status, driving Lp(a) up. The case highlights a previously under-recognised metabolic side effect of IGF-1R inhibition and argues for monitoring Lp(a) during teprotumumab therapy, particularly in patients at elevated cardiovascular risk.
Original abstract
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.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.