A Rare Case of Incidental Bilateral Pheochromocytoma and Paraganglioma in a Patient With Tuberous Sclerosis

Introduction:
Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors that occur in 2-8 per million people. Clinical presentation is variable, with a peak incidence in 3rd to 4th decade of life. Majority of PPGL are sporadic, however up to 24–32% of cases have a hereditary germline mutation. We report a rare case of a patient with tuberous sclerosis syndrome who was diagnosed with synchronous PPGL.

Case Description:
A 49-year-old female was referred for bilateral adrenal and retroperitoneal masses noted incidentally on computed tomography (CT) performed for kidney transplant evaluation. Her medical history was significant for tuberous sclerosis syndrome with brain, kidney, and skin involvement, hypertension (not requiring treatment), bilateral renal masses requiring bilateral nephrectomies, and a prior failed kidney transplant with end-stage renal disease (ESRD). She denied chest pain, palpitations, headaches, or a history of hypertensive crisis. CT with adrenal protocol showed a 3.2 x 2.9 cm retroperitoneal mass with a unenhanced attenuation value of 35.6 Hounsfield units (HU), a 6.0 x 3.3 cm centrally cystic right adrenal mass (unenhanced attenuation value of 40.7 HU, absolute washout of 72%), and a 4.6 x 3.3 cm left adrenal mass (unenhanced attenuation value of 35.3 HU, absolute washout of 73%). Meta-iodobenzylguanidine (MIBG) and 68Ga-Dotatate positron emission tomography/CT scan confirmed lesions to be of neuroendocrine origin. Labs showed an elevated plasma normetanephrine (20.20 nmol/L) and Chromogranin A [CgA] (1,518 ng/ml). After medical optimization, bilateral adrenalectomy and excision of bilateral retroperitoneal masses were performed. Pathology confirmed pheochromocytoma in both adrenal glands and paraganglioma of retroperitoneal masses. Post-operatively, she received steroid replacement for primary adrenal insufficiency. Normetanephrine level decreased (1.21 nmol/L) as did CgA (592 ng/ml), but remained above the normal range in the setting of ESRD.

Discussion:
Routine imaging has increased incidental diagnosis of PPGL tumors. Diagnostic workup includes measurement of urinary or plasma metanephrines and catecholamines. However, this can be difficult to interpret with ESRD due to impaired catecholamine excretion in urine, or compromise of plasma measurements from the increased sympathetic outflow. CT, magnetic resonance imaging and other imaging studies specific to neuroendocrine tumors are performed to confirm and detect metastatic disease. Patients with young age, syndromic lesions, bilateral PPGL, or unilateral disease with a positive family history should have genetic testing. Definitive treatment is surgical after dual blockade with alpha and beta blockers. Long-term prognosis after surgery is good but up to 50% may remain hypertensive.