The latest discovery is that a genetic mutation in some of these nodules causes massive but intermittent overproduction of the hormone.
Updated – Sun 11 Jun 23 09:14 AM
London: Researchers have discovered a genetic mutation that causes a common type of high blood pressure (hypertension) and a treatment for it.
The study was published in the journal Nature Genetics. One in 20 people with high blood pressure develops a small benign nodule that is the cause. The nodules produce aldosterone, a hormone that regulates the amount of salt in the body.
The latest discovery is that a genetic mutation in some of these nodules causes massive but intermittent overproduction of the hormone.
The gene mutations discovered cause a variety of problems that make it difficult for clinicians to diagnose some patients with high blood pressure. First, the mutation disrupts a protein called CADM1 that prevents cells in the body from “talking” to each other and signaling to stop producing aldosterone.
Doctors are particularly concerned about the variable release of aldosterone throughout the day, which can lead to excess salt and high blood pressure during peak periods. This variation explains why people with genetic mutations go undetected until they undergo blood tests at different times of the day.
The researchers also found that this form of hypertension can be cured with unilateral adrenalectomy — the removal of one of the two adrenal glands. After removal, the previously severe hypertension disappeared despite multiple medications and was observed without treatment through the subsequent years.
Aldosterone-induced hypertension is identified in less than 1% of patients because aldosterone is not routinely measured as a possible etiology. The researchers recommend measuring aldosterone with a 24-hour urine test rather than a one-off blood measurement, which would detect more people with undiagnosed hypertension.
The original patient in the study was discovered when doctors noticed fluctuating hormone levels during his participation in a clinical trial for treatment-resistant hypertension.
The cause of hypertension is unknown in most patients with hypertension and requires life-long drug treatment. Previous research by the Queen Mary group has found that 5-10% of hypertensive patients are attributable to genetic mutations in the adrenal glands that lead to hypersecretion of aldosterone.
Aldosterone causes salt to stay in the body, which raises blood pressure. Patients with high levels of aldosterone in the blood are resistant to commonly used medications for high blood pressure and are at increased risk of heart attack and stroke.
Co-senior author of the study, Professor Morris Brown, Professor of Endocrine Hypertension at Queen Mary University of London, said: “On the 900th anniversary of Barts Hospital, this story illustrates the benefits of a virtuous circle in science and medicine.
Most patients consented to our unconventional molecular analysis of their surgical samples, from which we discovered how their hypertension was caused and how to cure it in future patients. Because the aldosterone nodules in this study were very small, we are now investigating whether transient cautery of the nodules could be an alternative to surgical removal of the entire adrenal gland. “
