'New blood pressure scan' of limited use

Researchers have developed a test “that could spot a curable cause of high blood pressure in thousands of people”, the Daily Mirror has reported. According to the newspaper, up to 5% of high blood pressure cases could be due to Conn’s syndrome, where benign tumours on the adrenal glands affect the body’s hormone levels. The adrenal glands are located above the kidneys. When correctly identified, these tumours can be removed, returning a person’s blood pressure to normal levels.

The study behind this news examined two techniques for diagnosing Conn’s syndrome. It compared the use of body scans against an existing, difficult technique of taking blood samples from deep within the body. Researchers found that the non-invasive scans could correctly identify 76% of patients with a tumour causing Conn’s syndrome, and could accurately rule out the problem in 87% of patients with increased adrenal hormones due to another cause.

The results suggest a new and useful tool for diagnosing Conn’s syndrome. However, the condition is thought to cause only a very small proportion of high blood pressure cases, which some medical sources suggest is less than 1%. This diagnostic technique is not relevant to the vast majority of people with high blood pressure, who have what is known as essential hypertension, which is high blood pressure without a known cause.

Where did the story come from?

The study was carried out by researchers from the University of Cambridge and Addenbrooke’s Hospital in Cambridge, and was supported by the British Heart Foundation, the National Institute of Health Research and the West Anglia Comprehensive Local Research Network. It was published in the Journal of Clinical Endocrinology & Metabolism.

Many news sources wrongly claimed that a new high blood pressure test has been developed. The research involved a diagnostic test that could identify a relatively rare condition called Conn’s syndrome, which may cause a very small proportion of high blood pressure cases. The diagnostic scanning technique described in the study is intended to confirm Conn’s syndrome only after blood tests for levels of the hormone aldosterone have suggested that a person may have the syndrome.

In short, the specialist diagnostic techniques described in this research are not required for, or of benefit to, the vast majority of people with high blood pressure.

What kind of research was this?

The research examined the use of a non-invasive scanning technique for diagnosing Conn’s syndrome and compared it with the invasive test currently used to identify the condition. In Conn’s syndrome, the body produces excess levels of the hormone aldosterone due to the presence of a benign tumour on the adrenal gland (known as an adenoma). This causes the kidneys to retain salt and water, which then raises blood pressure.

Although Conn’s syndrome is the most common cause of excess aldosterone production, other conditions can cause excessive aldosterone to be produced. These included enlargement of both adrenal glands, known as bilateral adrenal hyperplasia. After blood tests have shown that a person has excess aldosterone levels, further tests can be performed to confirm the cause of the excess production. While scans can be used to diagnose the cause, diagnosis currently often involves an invasive technique called adrenal vein sampling (AVS). This involves directly sampling blood from the veins around both adrenal glands. The technique is generally preferred to scans, which may miss smaller adenomas or detect benign tumours that do not produce excessive aldosterone.

If Conn’s syndrome can be correctly identified, it can be cured by surgically removing the adrenal gland containing the adenoma. However, few patients undergo such surgery given the difficulty in pinpointing an adenoma as a cause. This research looked at how effectively a type of imaging scan could detect the presence of adrenal adenomas, the tumour that causes Conn’s syndrome.

Diagnostic tests have two main measures, known as sensitivity and specificity:

• Sensitivity is the ability of the test to correctly identify people with a condition. For example, if a test could correctly identify eight cases of a disease among 10 people with that disease, the test would have a sensitivity of 80%. The higher the sensitivity, the better. The two cases missed by the test would be called “false negatives”.
• Specificity determines how often the test will correctly indicate that someone does not have the condition. If 10 people without a disease were tested and the results suggested nine of them did not have the condition, then the test would have a specificity of 90%. The one person wrongly identified as having the condition is known as a “false positive”. The higher the specificity, the better.

What did the research involve?

The researchers recruited two groups of patients:

• 25 patients with excessive aldosterone caused by Conn’s syndrome, to estimate sensitivity
• 15 control subjects with excessive aldosterone due to other causes, to estimate specificity

Some of the controls had “non-functioning” adenomas, which do not produce aldosterone and, therefore, do not cause symptoms. All patients had undergone AVS, the standard diagnostic blood test.

The new test, called C-metomidate Positron Emission Tomography-CT (or PET-CT), involves injecting patients with a chemical (C-metomidate) that collects in the benign tumours, but not in the surrounding healthy tissue. A PET-CT scan is then used to detect the injected chemical, identifying the tumour.

To assess sensitivity (the proportion of patients with the condition who had a positive test result, or the true positives), patients with Conn’s syndrome were injected with the chemical and underwent PET-CT imaging for 45 minutes. An identical test was used in the control patients to assess specificity (the proportion of patients without the condition who had a negative test result, or the true negatives).

What were the basic results?

When testing the sensitivity and specificity of the C-metomidate PET-CT test, the researchers found that:

• 19 of the 25 patients with Conn’s syndrome were correctly identified, and six patients who had the disease were incorrectly diagnosed as not having it (sensitivity of 76%).
• 13 of the 15 patients with excessive aldosterone due to other causes had a negative test, and two patients who did not have the disease were incorrectly diagnosed as having it (specificity of 87%)

How did the researchers interpret the results?

The researchers concluded that using C-metomidate PET-CT scans could improve the ease and accuracy of determining whether a diagnosis of elevated aldosterone levels was caused by Conn’s syndrome.

Conclusion

This assessment of a new diagnostic test may provide a non-invasive alternative for diagnosing an adenoma as the cause of excessive levels of the hormone aldosterone. This is likely to increase the successful treatment of the condition as more patients are able to undergo the surgical removal of the affected adrenal gland.

Currently, diagnosis of Conn’s syndrome occurs in two stages. The first involves detecting elevated levels of the hormone aldosterone (using hospital blood tests), and the second involves determining the size and location of the benign tumour, usually through other forms of imaging scan. This new test would be part of the second stage, and patients would only be eligible for it if excessive levels of aldosterone had already been confirmed through blood tests.

While this less invasive test may increase the identification and surgical treatment of Conn’s syndrome, it is only relevant to the small proportion of people with high blood pressure caused by high levels of aldosterone. The vast majority of people with high blood pressure have essential hypertension, which is high blood pressure without a known or identified cause.

Also, while the research tells us about the identification of Conn’s syndrome, there were no undiagnosed patients in this study as everyone with Conn’s syndrome had been diagnosed before the research began. This means we cannot directly tell how the technique might affect the diagnosis of suspected cases of Conn’s syndrome. That said, studies of this type are necessary in early-stage research to determine how a new diagnostic test compares to a current standard. Further studies in people with Conn’s syndrome, but with unknown diagnostic status, will be needed.