Endocrine · Year 2 · from Endocrine

Case 2: Hereditary Pheochromocytoma - Von Hippel-Lindau Syndrome

Patient Demographics

  • Age: 28 years
  • Sex: Female
  • Occupation: Graduate student

Chief Complaint

"I was told I might have a tumor because of my genetic condition."

History of Present Illness

A 28-year-old woman with known Von Hippel-Lindau (VHL) syndrome presents for routine annual screening. Her VHL diagnosis was made at age 18 after genetic testing prompted by her father's history of renal cell carcinoma and cerebellar hemangioblastoma. She has been followed with annual surveillance. Previous screenings revealed a small retinal hemangioblastoma treated with laser photocoagulation at age 22. She reports recent intermittent headaches over the past 2 months, occasional palpitations, and episodes of sweating, particularly during exercise. She attributed these symptoms to stress from her dissertation work. No weight loss or tremor.

Physical Examination

  • Vital Signs: BP 155/95 mmHg (elevated for age), HR 92 bpm
  • General: Healthy-appearing young woman
  • HEENT: Fundoscopic exam shows prior laser scars, no active lesions
  • Cardiovascular: Regular tachycardia, no murmurs
  • Abdomen: Soft, no palpable masses
  • Neurologic: Normal cerebellar function

Workup

  • Biochemical Screening:
  • Plasma free metanephrines:
  • Metanephrine: 0.3 nmol/L (normal)
  • Normetanephrine: 2.8 nmol/L (elevated - characteristic of VHL-associated pheochromocytoma)
  • Plasma epinephrine: Normal
  • Plasma norepinephrine: Elevated
  • Imaging:
  • CT abdomen: Bilateral adrenal masses - 2.2 cm right, 1.5 cm left
  • MRI: Both masses T2 hyperintense
  • 68Ga-DOTATATE PET/CT: Avid uptake in both adrenal masses, no metastatic disease
  • MRI brain/spine: No new hemangioblastomas
  • Renal protocol CT: No renal masses
  • Genetic Confirmation: VHL gene mutation (previously confirmed)

Diagnosis

Bilateral pheochromocytoma in the setting of Von Hippel-Lindau syndrome

Treatment

SURGICAL APPROACH (Cortical-sparing to preserve adrenal function):

  1. Preoperative alpha-blockade followed by beta-blockade (standard protocol)
  2. Bilateral cortical-sparing adrenalectomy (partial adrenalectomy)
  • Preserves zona fasciculata to maintain cortisol production
  • Reduces risk of lifelong adrenal insufficiency
  • Accepted approach for bilateral hereditary pheochromocytomas
  1. If complete bilateral adrenalectomy required: Lifelong glucocorticoid and mineralocorticoid replacement

VHL SYNDROME SURVEILLANCE (Lifelong):

  1. Annual plasma free metanephrines (pheochromocytoma recurrence)
  2. Annual ophthalmologic examination (retinal hemangioblastoma)
  3. Annual MRI brain and spine (CNS hemangioblastoma)
  4. Annual abdominal imaging (renal cell carcinoma, pancreatic lesions)
  5. Annual audiometry (endolymphatic sac tumor)

FAMILY IMPLICATIONS:

  1. Cascade genetic testing for first-degree relatives
  2. At-risk relatives: Begin surveillance at age 5-10 years
  3. Genetic counseling regarding inheritance (autosomal dominant, 50% transmission risk)

Clinical Pearl

VHL syndrome is caused by mutations in the VHL tumor suppressor gene and includes pheochromocytoma (20% penetrance), CNS and retinal hemangioblastomas, clear cell renal cell carcinoma, and pancreatic neuroendocrine tumors. VHL-associated pheochromocytomas characteristically secrete predominantly norepinephrine (not epinephrine) because of lower PNMT expression. They are frequently bilateral (50-80%) and virtually always benign. The recognition that 30-40% of all pheochromocytomas are hereditary has made genetic testing standard of care for all patients. Identifying germline mutations enables surveillance for associated tumors and cascade testing of family members. Cortical-sparing surgery aims to preserve adrenal function in bilateral cases, though recurrence risk necessitates continued surveillance.

Clinical Image

Histologic appearance of pheochromocytoma showing chromaffin cells arranged in characteristic nests (Zellballen pattern), typical of both sporadic and syndromic tumors.

Image Source: Wikimedia Commons - "Pheochromocytoma histology" License: CC BY-SA 3.0 URL: https://commons.wikimedia.org/wiki/File:Pheochromocytoma_-_very_high_mag_-_cropped.jpg

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