Which monogenic form of hypertension can feature both elevated renin and aldosterone level?
Pheochromocytoma (PCC) is caused by catecholamine-producing adrenal tumors and is associated with various symptoms depending on the type and secretory pattern of the produced catecholamine(s). Hypertension can present as paroxysmal and labile hypertension, complicated by orthostatic hypotension and persistent hypertension. Hypokalemia is often seen, and renin and aldosterone levels are elevated due to volume depletion and catecholamine-mediated renin release from the juxtaglomerular cells. Familial forms of PCC are common. The majority are associated with multiple endocrine neoplasia type 2 (MEN type 2) and caused by gain-of-function mutations in the RET protooncogene. In addition to RET, more than 10 genes have been associated with familial PCC (including genes causing the phakomatoses von Hippel-Lindau disease and Neurofibromatosis type 1; Table 72.1 ). Overall, known genetic mutations may account for the pathogenesis of up to ∼60% of PCC and paragangliomas. A recent exome sequencing study from nonsyndromic adrenal PCC tissue identified de novo somatic mutations in genes associated with apoptosis-related pathways. Particularly, mutations in the “cancer” gene KMT2D (lysine [K]-specific methyltransferase 2D) were more frequent (∼14% of tissues).
The treatment of choice is surgical resection of the affected adrenal gland(s) or paraganglioma, respectively. Treatment with irreversible alpha-blockade prior to surgery is mandatory to prevent life-threatening hypertensive complications.