[Oct. 13, 2023: Staff Writer, The Brighter Side of News]
The gene variant, uncovered in today's research, poses numerous challenges for physicians trying to diagnose patients with hypertension. (CREDIT: Creative Commons)
In a groundbreaking discovery, researchers have found that a tiny benign nodule, prevalent in 5% of hypertensive patients, is the culprit behind certain cases of high blood pressure. This nodule, as revealed, produces a hormone named aldosterone which controls the body's salt levels, leading to erratic spikes of hormone production due to a gene variant.
The gene variant, uncovered in today's research, poses numerous challenges for physicians trying to diagnose patients with hypertension. It alters a protein named CADM1, impairing cells' ability to communicate and instruct each other to halt the production of aldosterone.
Moreover, the erratic pattern of aldosterone release throughout the day further complicates the diagnosis. When the hormone production peaks, it leads to salt overload and heightened blood pressure. This fluctuation provides an explanation for why patients with the gene variant often slip under the radar unless they undertake blood tests at varying times of the day.
However, there is a ray of hope. The researchers have found that unilateral adrenalectomy - the removal of one of the two adrenal glands, could cure this form of hypertension. Patients, who previously had severe hypertension despite being treated with multiple drugs, showed no symptoms after the surgery and required no treatment through many following years.
Regrettably, less than 1% of patients with hypertension caused by aldosterone are correctly diagnosed, as aldosterone is not usually identified as a potential cause. The research team is advocating for measuring aldosterone through a 24-hour urine test rather than one-off blood measurements. This approach would significantly improve the diagnosis of undetected hypertension cases.
The patient who triggered this research was discovered when physicians noted a fluctuation in his hormone levels during his participation in a clinical trial for hard-to-treat hypertension.
In the majority of hypertension cases, the root cause remains elusive, necessitating lifelong drug treatment. The research team at Queen Mary had previously discovered that in 5-10% of hypertension patients, the condition was due to a gene mutation in the adrenal glands.
Discovery of CADM1 somatic mutations in APAs. APA of patient P1 as seen on CT scan (yellow arrowhead) and in adrenal tissue (black arrowhead). The axial CT image of patient P1’s adrenal identified a 13 × 7 mm right adrenal nodule. (CREDIT: Nature)
This mutation results in the overproduction of aldosterone, which causes excessive salt retention in the body and consequently high blood pressure. These patients exhibit resistance to conventional hypertension drugs and are at an increased risk of heart attacks and strokes.
In his statement, Professor Morris Brown, co-senior author of the study and Professor of Endocrine Hypertension at Queen Mary University of London, mentioned, “In the 900th anniversary of Barts Hospital, this story illustrates benefits from the virtuous circle of Science and Medicine.
CADM1 variants inhibit GJ communication. GJ-mediated communication as detected by a GJ-permeable dye. H295R cells were transfected with either WT or mutant CADM1-GFP vectors. (CREDIT: Nature)
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.”
The research was made possible through funding from Barts Charity and conducted by research fellows funded by the British Heart Foundation, National Institute of Health Research, Medical Research Council, and the Royal Society. Laboratories in Munich, Paris, and Michigan collaborated to find more individuals with the new variant, while teams in Osakasayama, Japan, KL, Malaysia, and Pittsburgh, USA worked together to further comprehend its effect on the human body. This extensive collaboration points towards an optimistic future in the fight against hypertension.
Research paper: Wu et al. Somatic mutations of CADM1 in aldosterone-producing adenomas and gap junction-dependent regulation of aldosterone production.
For more science news stories check out our New Discoveries section at The Brighter Side of News.
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