Bilateral papillopathy as a presenting sign of pheochromocytoma associated with von Hippel–Lindau disease
An otherwise healthy 7-year-old girl was evaluated for 1 month of bilateral vision loss. She reported no history of headaches, eye pain, neurological deficits, or other associated symptoms. Her past medical history and family history were negative for eye disease, renal cell carcinoma, or neurologic syndromes. She was on no medications and had no allergies.\nThe patient was in no distress, and her screening vital signs were normal with a blood pressure of 110/70 mmHg and a heart rate of 95 bpm. Best-corrected visual acuity was 20/50 in the right eye and 20/60 in the left eye, with a normal pupillary examination and intact color vision. Ocular motility and intraocular pressures were normal. Automated visual field testing (Humphrey 30-2 threshold, Swedish Interactive Threshold Algorithm-standard strategy; Carl Zeiss Meditec, Dublin CA, USA) demonstrated bilateral enlarged blind spots and cecocentral scotomas (). Fundoscopy showed diffuse bilateral optic nerve head edema with extensive circumferential peripapillary and macular exudation. The optic nerve heads had no spontaneous venous pulsations (). The neurologic examination was unremarkable.\nThe brain magnetic resonance imaging (MRI) with and without contrast revealed multiple high T2 and fluid-attenuated inversion–recovery (FLAIR) signal lesions found diffusely in the cortical and subcortical white matter region of the frontal and parietal lobes (). One lesion in the left frontal posterior frontal lobe had higher T1 signaling, and a computed tomography (CT) scan confirmed calcifications of this single lesion ( and ). A lumbar puncture revealed an opening pressure of 150 mm water with normal cerebrospinal fluid cytology and analysis: red blood cells =1; white blood cell =0; protein =20 mg/dL; glucose =71 mg/dL; immunoglobulin G =1.76 mg/dL; no oligoclonal bands; and no growth in cultures.\nThree days later on follow-up examination, the patient was found to have paroxysmal tachycardia with a heart rate of 180 bpm and blood pressure of 120/75 mmHg. Repeat blood pressure measurements showed episodic elevation in blood pressure reaching as high as 240/160 mmHg. The patient was treated medically for hypertension. In an extensive workup, an abdominal CT scan showed a 3.5×3.0×3.0 cm enhancing noncalcified mass in the right adrenal gland ().\nLaboratory analysis of the patient’s 24-hour urine collection showed elevated vanillylmandelic acid of 15.1 mg (normal <2.3 mg) and random total metanephrines of 22,295 μg/g of creatinine (normal 202–750 ug/g). A scintigraphic distribution of iodine-131-meta-iodobenzylguanidine (I-131 MIBG), an adrenal medullary imaging agent, showed increased radioactive I-MIBG uptake by the right adrenal mass but the absence of pathologic radioactivity elsewhere, and the patient underwent laparoscopic resection of the mass. The pathological specimen showed whorled nests of chromaffin tumor cells () embedded in a fibrovascular stroma. These histopathological findings were consistent with pheochromocytoma.\nPostoperatively, the episodic hypertensive episodes resolved and vanillylmandelic acid/metanephrines normalized. After 5 months, the patient’s visual acuity improved to 20/30 in both eyes. Fundoscopically, the optic disc edema and exudates improved, and the postoperative MRI showed a subsequent decrease in white matter lesions ().\nThe patient was lost to follow-up for many years and returned at the age of 18 when she developed shortness of breath over 4 days. She was found to have multiple pulmonary lesions bilaterally; a biopsy showed metastatic pheochromocytoma. Blood pressure at that time was well-controlled on atenolol; however, serum metanephrines were elevated. She underwent serial thoracotomies for resection of the lesions, and she then started on chemotherapy with sunitinib for 12 months. Multiple follow-up metaiodobenzylguanidine (MIBG) scans and urine collections have been negative for metastatic pheochromocytoma. Subsequent genetic testing identified a 3p25-26 (c.482 G>A) chromosomal mutation consistent with a mutation of the VHL gene. RET proto-oncogene sequencing detected no mutation in exons 10, 11, 13, 14, 15, and 16.\nThe patient’s family history was negative for neuroendocrine disorders, including multiple endocrine neoplasia 2A and 2B, VHL disease, von Recklinghausen disease, tuberous sclerosis, and Sturge–Weber syndrome. Recommendations were made to have family members tested; however, the patient declined as the family lived out of the country. Ophthalmic evaluation at this time showed multiple peripheral vascular dilations and small retinal capillary hemangioblastomas (). Repeat imaging and follow-up over a year showed her to be stable without evidence of brain or spinal cord hemangioblastomas, or abdominal pathology, which is concerning for renal cell carcinoma.