Issue: March 2011
March 01, 2011
2 min read

Hypertension may be caused by mutation in adrenal gland

Issue: March 2011
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Hypertension in those who have aldosterone-producing adrenal adenomas may be traced to genetic mutations in the potassium channel KCNJ5, data suggest.

Approximately 5% of patients with elevated blood pressure have benign endocrine tumors in their adrenal gland. The tumors produce abnormally high levels of aldosterone, which in turn causes BP to rise.

“Endocrine tumors such as aldosterone-producing adrenal adenomas, a cause of severe hypertension, feature constitutive hormone production and unrestrained cell proliferation; the mechanisms linking these events are unknown,” researchers at Uppsala University Hospital in Sweden and Yale School of Medicine in Hartford, Conn., wrote in a study.

To investigate this association, the researchers identified 22 patients with aldosterone-producing adrenal adenomas and conducted exome sequencing of genes in both tumor and normal tissue. All patients presented with hypertension and varying degrees of hypokalemia.

Their investigation revealed that eight of 22 patients had mutations of the KCNJ5 gene. One mutation, G151R, was found in two tumors, and another mutation, L186R, was discovered in six tumors. The researchers said these variants elevate aldosterone production and, therefore, can cause tumor growth. They may also contribute to hypertension by raising levels of potassium and water in the blood.

A third mutation, T158A, was identified in a father and his two daughters — all of whom had severe hypertension and massive adrenal hyperplasia. The detection of these variants indicates that the KCNJ5 mutations may be a cause of a Mendelian form of primary aldosteronism with bilateral adrenal hyperplasia, the researchers said.

“The discovery may help to improve diagnostics in connection with primary aldosteronism and cases of severe BP elevation,” study researcher Peyman Björklund, MD, PhD, of the department of surgical sciences at Uppsala University, said in a press release. “The mutated potassium channel also represents a potential target molecule for treatment of the tumors in question.”

In an accompanying editorial, John W. Funder, MD, PhD, said although the study is important, the results should be interpreted carefully, noting that the patients had severe aldosterone-producing adrenal adenomas, with only three tumors less than 20 mm in diameter. Additionally, all had hypokalemia and exceptionally high plasma aldosterone concentrations. Although not affecting the findings’ validity, these limitations may overestimate prevalence of these mutations in all types of severe aldosterone-producing adrenal adenomas.

“There remains a major disconnect between the prevalence of primary aldosteronism and the low levels of diagnosis and management, medical or surgical. This is in part due to cost, and in larger part to clinical ignorance and indifference. Choi et al have made great strides toward elucidating the etiology of the condition, and their findings should stimulate a much more focused approach to the condition,” Funder said.

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