SUN-067 - Preoperative Belzutifan for Recalcitrant Hypertensive Emergency in Secretory Noradrenergic Paraganglioma

Background: Pheochromocytomas and paragangliomas (PPGL) can cause catecholamine-induced hypertensive crises. Although α- and β-adrenergic receptor antagonism is generally effective, some patients exhibit treatment-refractory episodic hypertension. Belzutifan is a novel hypoxia-inducible factor 2α (HIF-2α) inhibitor recently approved for treatment of unresectable or metastatic PPGL. Belzutifan may lower catecholamine production and improve cardiovascular stability in patients with HIF-2α mutation-associated paragangliomas. We report the efficacious use of Belzutifan as a preoperative medication for hyper-adrenergic paraganglioma with refractory cardiovascular parameters.

Clinical

Case: A 49-year-old female presented to a nearby facility with chest pain and elevated systolic blood pressures (SBP) up to 270 mmHg. CT angiogram of the chest revealed a posterior mediastinal soft tissue mass (5.5 x 3.1 x 4.3 cm). Over 12 days, treatment with multiple medications (losartan 50mg daily, prazosin 1mg BID, nifedipine 90mg daily, spironolactone 75mg daily, and carvedilol 6.25mg BID) failed to prevent intermittent hypertensive episodes (SBP>190 mmHg). Testing revealed elevated plasma normetanephrine (15 nmol/L, normal < 0.90) and normal metanephrine levels. A diagnostic biopsy confirmed a paraganglioma (synaptophysin+, S100+).

Wanting to transfer her care to an academic center, the patient presented one week later to our emergency room with a BP of 191/99 mmHg and elevated troponin to 181 ng/L (normal < 4). A Ga68 DOTATATE PET/CT scan identified the posterior mediastinal mass without evidence of additional disease. Over the next 18 days, despite aggressive pharmacologic therapy (phenoxybenzamine 40mg QID, valsartan 160mg BID, hydralazine 75mg daily, carvedilol 12.5mg BID, and spironolactone 50mg daily), labile blood pressure prevented surgical intervention.

A trial of Belzutifan 120mg daily was initiated. Within 48 hours, SBP improved to 120-130 mmHg, hydralazine and valsartan were discontinued, and phenoxybenzamine (20mg BID) and carvedilol (6.25mg BID) were reduced. After 30 days of Belzutifan, repeat plasma normetanephrine levels improved (6.2 nmol/L). The patient underwent uncomplicated resection of the mediastinal paraganglioma. Pathology demonstrated paraganglioma with retained SDHB staining; germline testing was negative. Plasma normetanephrines normalized (0.61 nmol/L) and Belzutifan was discontinued.

Conclusions: Belzutifan provided acute blood pressure control for paraganglioma related cardiovascular lability with hypertensive crises, allowing for definitive surgical treatment. To our knowledge, this is the first reported use of Belzutifan as a preoperative agent. Whether Belzutifan is uniquely beneficial as an anti-hypertensive in the setting of HIF-2α mutation-associated PPGL, or has broader utility remains undetermined.

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