Rapid Cardiovascular Response to Belzutifan in HIF2A-Mediated Paraganglioma

This correspondence reports the rapid cardiovascular effects of belzutifan, a hypoxia inducible factor 2α (HIF 2α) inhibitor, in two patients with HIF2A mediated paraganglioma (PPGL). Patient 1, an 18 year old woman with Pacak-Zhuang syndrome, experienced severe blood pressure fluctuations and catecholamine excess. Within hours of belzutifan administration (80 mg daily), her plasma norepinephrine and normetanephrine levels normalized, resolving hypertension and tachycardia. Patient 2, a 34 year old woman with a similar HIF2A mutation, also showed rapid catecholamine reduction despite lacking hypertension. Mechanistic studies suggest belzutifan inhibits catecholamine synthesis by reducing tyrosine hydroxylase phosphorylation and may also block catecholamine release via adenosine A2A receptor suppression. These findings highlight belzutifan’s potential as a rapid, effective treatment for catecholamine-induced crises in PPGL, offering advantages over traditional alpha/beta-blockers and metyrosine.

This correspondence reports the rapid cardiovascular effects of belzutifan, a hypoxia inducible factor 2α (HIF 2α) inhibitor, in two patients with HIF2A mediated paraganglioma (PPGL). Patient 1, an 18 year old woman with Pacak-Zhuang syndrome, experienced severe blood pressure fluctuations and catecholamine excess. Within hours of belzutifan administration (80 mg daily), her plasma norepinephrine and normetanephrine levels normalized, resolving hypertension and tachycardia. Patient 2, a 34 year old woman with a similar HIF2A mutation, also showed rapid catecholamine reduction despite lacking hypertension. Mechanistic studies suggest belzutifan inhibits catecholamine synthesis by reducing tyrosine hydroxylase phosphorylation and may also block catecholamine release via adenosine A2A receptor suppression. These findings highlight belzutifan’s potential as a rapid, effective treatment for catecholamine-induced crises in PPGL, offering advantages over traditional alpha/beta-blockers and metyrosine.