Nearly 40 percent of the small adrenal tumors that cause bigproblems with high blood pressure share a genetic mutation that causes patients to retain too muchsodium, researchers report. The study of 47 human, benign adrenal gland tumors also showed amutation of the gene KCNJ5 is twice as likely to occur in women -71 versus 29 percent - as it points to potential new treatments forsome patients who don't respond to current hypertension regimens, said Dr. William E. Rainey, Scientific Director of theAdrenal Center at Georgia Health Sciences University. Addititionally, when scientists put the mutated gene into anadrenal cell, it immediately starts producing the sodium-retaininghormone aldosterone. |
"We found it turned on a whole series of genesthat cause the cell to produce aldosterone," Rainey said. Typically, KCNJ5 appears to help normalize levels of thesodium-retaining hormone aldosterone by regulating how muchpotassium is pumped in and out of aldosterone-producing cells onthe outer layer of the adrenal glands. Abnormal protein produced bythe mutated gene alters the cells' electrical status. "When this gene has a mutation, the cells lose control and juststart producing aldosterone all the time," said Rainey,corresponding author of the study in the Journal of ClinicalEndocrinology and Metabolism.
"The combination of too much salt and too much of this hormoneleads to high blood pressure and tissue damage," said Rainey. Henotes that the vast majority of the 311 million Americans consumetoo much salt, even if they never pick up a salt shaker, because ofhigh content in breads, processed and fast foods and the like. Anestimated 33 percent of Americans are hypertensive and an estimated1 in 10 have adrenal problems as the cause. A 2011 study led by Yale University and published in the journal Science showed that the tumors had a KCNJ5 mutation.
GHSU researchers,along with colleagues at University of Michigan Medical School, AnnArbor; University of Torino and University of Padova, Italy;University of Texas Southwestern Medical Center, Dallas; and KeioUniversity,Tokyo linked the gene to aldosterone production. Now the GHSU Adrenal Center is moving forward with studies todetermine why women with adrenal tumors have more of the mutatedgene - Rainey suspects it's estrogen-related. They also want toknow if any of the dozen potassium channel inhibitors already onthe market for heart and other disorders can help these patients aswell. Rainey said the gene mutation is one that occurs after birth - whenmost mutations occur - and the cause is unknown. About half thepeople who produce too much aldosterone have tumors, which tend toaffect only one of the 2-by-1-inch glands that sit like hats on topof the two kidneys and surgical removal typically fixes theirproblem.
Unexplained enlargement of both glands likely also has agenetic basis and may be medically managed, Rainey said. One of the many goals of the GHSU Adrenal Center, one of a handfulof multidisciplinary centers in the nation, is to better definegenes which can result in whole families being impacted. To date,only three genes are known to contribute to the familial form.Aldosterone excess, by whatever means, also is suspected whenpeople under age 40 become hypertensive for no other obviousreason. The adrenals are extremly efficient glands, producing threeadditional hormone groups that help maintain homeostasis includingcortisol needed for glucose/carbohydrate metabolism, weak sexsteroids that likely are the major source of androgens, or malehormones, in women; and the fight or flight hormones epinephrineand norepinephrine. In the event both glands are removed, the vitalhormones must be supplemented, Rainey said.
Patients typically come to the GHSU Adrenal Center with unexplainedhypertension that isn't responding to traditional therapy. "Theyare typically on three or four medications and their blood pressureis still not under control," said Dr. Michael A. Edwards, ClinicalDirector of the Adrenal Center and Chief of the MCG Section ofMinimally Invasive and Digestive Diseases Surgery.
Computerizedtomography done for other reasons can detect over-sized glands ortumors that may be the culprit. Additional References Citations.
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