London [UK]: Researchers discovered a gene mutation that causes a common type of hypertension (high blood pressure) and a treatment for it.
This study was published in the journal, ‘Nature Genetics.’ A little benign nodule, occurring in one out of every twenty persons with hypertension, is the cause. The nodule generates aldosterone, a hormone that regulates how much salt is in the body.
The latest finding is a gene mutation in some of these nodules that causes a massive, although intermittent, overproduction of the hormone.
The gene mutation found causes various issues, making it difficult for clinicians to diagnose some hypertensive patients. To begin, the variation disrupts a protein called CADM1, which prevents cells in the body from ‘talking’ to one another and signalling that it is time to cease producing aldosterone.
Doctors are particularly concerned about the variable release of aldosterone throughout the day, which produces salt overload and hypertension at its peak. This variation explains why people with the gene mutation can go undetected until they receive blood testing at different times of the day.
The researchers also discovered that this form of hypertension could be cured by unilateral adrenalectomy – removing one of the two adrenal glands. Following removal, previously severe hypertension despite treatment with multiple drugs disappeared, with no treatment required through many subsequent years of observation.
Fewer than 1% of people with hypertension caused by aldosterone are identified because aldosterone is not routinely measured as a possible cause. The researchers are recommending that aldosterone is measured through a 24-hour urine test rather than one-off blood measurements, which will discover more people living with hypertension but going undiagnosed.
The initial patient in this study was detected when doctors noticed a fluctuation in his hormone levels during his participation in a clinical trial of treatments for difficult hypertension.
In most people with hypertension, the cause is unknown, and the condition requires life-long treatment with drugs. Previous research by the group at Queen Mary discovered that in 5-10% of people with hypertension, the cause is a gene mutation in the adrenal glands, which results in excessive amounts of aldosterone being produced.
Aldosterone causes salt to be retained in the body, driving up blood pressure. Patients with excessive aldosterone levels in the blood are resistant to treatment with the commonly used drugs for hypertension and are at increased risk of heart attacks and strokes.
Professor Morris Brown, co-senior author of the study and Professor of Endocrine Hypertension at Queen Mary University of London, said, ‘On the 900th anniversary of Barts Hospital, this story illustrates benefits from the virtuous circle of Science and Medicine.
Most patients consent to our undertaking non-routine molecular analyses of their surgical samples, from which we discover how their hypertension was caused, and how to cure it in future patients.
Because the aldosterone nodules in this study were so small, we are now investigating whether momentary cauterisation of the nodule is an alternative to surgical removal of the whole adrenal gland.’