A 21-year-old man comes to the clinic for painless vision loss in the right eye and headaches. Blood pressure is 190/100 mm Hg and pulse is 96/min. Further evaluation reveals retinal and cerebellar hemangioblastomas. The patient's father had very high blood pressure and significant hearing impairment and died of an intracranial hemorrhage at age 48. Which of the following is the most likely cause of this patient's elevated blood pressure?

Question

A 21-year-old man comes to the clinic for painless vision loss in the right eye and headaches.  Blood pressure is 190/100 mm Hg and pulse is 96/min.  Further evaluation reveals retinal and cerebellar hemangioblastomas.  The patient's father had very high blood pressure and significant hearing impairment and died of an intracranial hemorrhage at age 48.  Which of the following is the most likely cause of this patient's elevated blood pressure?

Quizplus · Accepted Answer

11ec25c8_d2cf_e6cb_bc81_b7fbb5b77d08_MD0003_00 This patient has vision loss and headaches due to retinal and CNS hemangioblastomas, which are benign but heavily vascular tumors that can lead to hemorrhage or mass effect symptoms in the brain and spinal cord. Most hemangioblastomas are sporadic; however, this patient has multiple hemangioblastomas and a family history of intracranial hemorrhage, which suggests an inherited disorder, likely von Hippel-Lindau disease (vHL). vHL is an autosomal dominant disorder associated with mutations in the VHL gene. Besides hemangioblastomas, vHL is associated with clear cell renal cell carcinoma, pancreatic neuroendocrine tumors, endolymphatic sac tumors of the middle ear (hearing loss), and pheochromocytomas. Pheochromocytomas (arising in the adrenal medulla) and paragangliomas (in the sympathetic ganglia) are neuroendocrine tumors associated with excess production of catecholamines, leading to headache, palpitations, and potentially severe hypertension. As with hemangioblastomas, most pheochromocytomas and paragangliomas are sporadic. However, a significant minority occur as a manifestation of a familial disorder. In addition to vHL, major genetic syndromes associated with catecholamine-secreting tumors include multiple endocrine neoplasia type 2 (2A and 2B) and neurofibromatosis type 1. (Choice A) Primary hyperaldosteronism (Conn syndrome) can be caused by an adrenal adenoma or bilateral adrenal hyperplasia. It typically presents with hypertension but is not associated with hemangioblastomas. (Choice C) Hypercortisolism (Cushing syndrome) can cause hypertension but typically presents with central obesity, easy bruising, proximal muscle weakness, and wide skin striae. (Choice D) Autosomal dominant polycystic kidney disease can cause hypertension due to local renal ischemia and increased renin release. It is associated with an increased risk of intracranial hemorrhage due to cerebral aneurysms (not hemangioblastomas). Although vHL may be associated with the formation of renal cysts, this is not a major contributor to hypertension. (Choice E) Glomerulonephritis (eg, acute poststreptococcal glomerulonephritis) can cause hypertension but is typically associated with gross hematuria (eg, tea-colored urine) and edema. Hemangioblastomas would not be seen and are more suggestive of vHL. Educational objective: Von Hippel-Lindau disease (vHL) is an inherited disorder caused by mutations in the VHL gene. It is associated with retinal and CNS hemangioblastomas, which are heavily vascular tumors that can lead to hemorrhage or mass effect symptoms in the brain and spinal cord. Other manifestations include clear cell renal cell carcinoma, pancreatic neuroendocrine tumors, endolymphatic sac tumors of the middle ear, and pheochromocytomas. References: Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline (http://www.ncbi.nlm.nih.gov/pubmed/24893135) Genotype-phenotype correlations in pheochromocytoma and paraganglioma (http://www.ncbi.nlm.nih.gov/pubmed/30893643)

A 21-Year-Old Man Comes to the Clinic for Painless Vision