A recently discovered gene variant found in benign nodules in 5% of people with hypertension causes excess production of the hormone aldosterone, which causes high blood pressure. This condition can be cured by the unilateral removal of the adrenal glands. The study highlights the need for a 24-hour urinalysis to measure aldosterone levels to improve the diagnosis and treatment of hypertension.
Doctors at Queen Mary University of London and the Barts Hospital have identified a gene variant that causes a common type of hypertension (high blood pressure) and a way to treat it, according to a new study published in the journal. Nature genetics shows
The cause is a tiny benign nodule that occurs in one in twenty people with hypertension. The nodule produces the hormone aldosterone, which controls how much salt is in the body. The new discovery is a gene variant in some of these nodules that causes massive but intermittent overproduction of the hormone.
The gene variant discovered today causes several problems, making it difficult for doctors to diagnose some patients with hypertension. First, this variant affects a protein called CADM1, preventing the body’s cells from “talking” to each other and telling them it’s time to stop producing aldosterone. The diurnal fluctuation of aldosterone release is also a problem for physicians, leading to salt overload and hypertension at peak times. This variation explains why patients with the gene variant may escape diagnosis unless they have blood tests at different times of the day.
Aldosterone is a type of mineralocorticoid hormone produced by the adrenal cortex, the outer layer of the adrenal glands. It plays a critical role in maintaining the body’s water and salt balance by promoting sodium retention and potassium excretion in the kidneys. However, excess aldosterone can cause hypertension, or high blood pressure, and fluid buildup in the body’s tissues.
Researchers have also discovered that this form of hypertension can be treated unilaterally with adrenalectomy, the removal of one of the two adrenal glands. After removal, the previously severe hypertension resolved despite multiple drug therapies and was treatment-free during many subsequent years of follow-up.
Less than 1% of people with aldosterone-induced hypertension are diagnosed because aldosterone is not routinely measured as a possible cause. The researchers recommend that aldosterone be measured with a 24-hour urine test rather than with a one-time blood test, as this will detect more people with undiagnosed hypertension.
The original patient in this study was discovered when doctors noticed fluctuations in his hormone levels while he was participating in a clinical trial for the treatment of severe hypertension.
For most people with hypertension, the cause is unknown, and the condition requires lifelong medication. Previous research from Queen Mary’s group found that 5–10% of people with hypertension are caused by an adrenal gene mutation that produces too much aldosterone. Aldosterone promotes salt retention in the body, which increases blood pressure. Patients with too much aldosterone in their blood are resistant to treatment with commonly used antihypertensive drugs and are at increased risk of heart attacks and strokes.
Professor Morris Brown, one of the senior authors of the study and Professor of Endocrine Hypertension,
Queen Mary University of London said:
“On the 900th anniversary of Barts Hospital, this story illustrates the benefits of the beneficial circle of science and medicine. Most patients consent to us performing an unusual molecular analysis of their surgical specimens to learn how their hypertension was caused and how to treat it in future patients. Because aldosterone nodules were so small in this study, we are now investigating whether short-term nodule cauterization is an alternative to total adrenalectomy.
The Queen Mary research was funded by the Barts Charity and carried out by researchers funded by the British Heart Foundation, the National Institute for Health Research, the Medical Research Council and the Royal Society. The team collaborated with laboratories in Munich, Paris, and Michigan to find more people with the new variant, and in Osaka, Japan, KL, Malaysia, and Pittsburgh, USA, to better understand its effects on the body.