A tumour was detected in the right adrenal gland of a woman in her 30s with hypertension and low potassium levels by CT (Figure on the left). A 11C-metomidate PET-CT scan revealed that the tumour in the right adrenal gland was producing an excessive amount of aldosterone (Figure on the right; red area indicates high aldosterone levels). The woman underwent surgery to remove this adrenal gland, after which her hypertension and low potassium condition were cured.
by Dr Khor Ing Wei
Senior Manager, Dean’s Office
Hypertension is a serious and underestimated silent killer in Singapore and around the world, with one in four adults aged 25 years and above diagnosed with the illness here1.
Left untreated, hypertension is a leading risk factor for heart disease, kidney problems and stroke.
The Global Burden of Disease 2017 report found that hypertension accounted for about 48% of deaths from cardiovascular disease in Singapore. Recent studies indicate that as many as 33% of Singaporean adults diagnosed and treated for hypertension continue to have uncontrolled blood pressure (BP) readings despite treatment with medications (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg)2.
Most patients with hypertension have to take lifelong medication to control their condition. However, approximately 5% of patients have a treatable underlying condition called primary aldosteronism (PA). Appropriate treatment of this condition may lead to improved blood pressure and, possibly, a complete cure of hypertension in some patients.
Now, a novel imaging technique can identify the source of the hormonal excess in patients with PA, according to Professor Roger Foo from the Department of Medicine at the NUS Yong Loo Lin School of Medicine and Senior Consultant Cardiologist at the National University Heart Centre, Singapore; and Adjunct Assistant Professor Troy Puar, Consultant Endocrinologist at Changi General Hospital (CGH). They believe that these findings are pertinent to Singapore and also relevant to patients worldwide.
What is PA and how is it detected and treated?
Hypertension can be explained by either excess salt in the body, or excess vasoconstriction (tightening of blood vessels): two ends of the hypertension disease spectrum. Ideally, knowing where the patient lies on this spectrum will enable a more successful choice of treatment that targets the underlying problem. Hormone measurement helps to tell where the patient is located along the spectrum.
This understanding has also led to the recognition that more patients than previously suspected have salt excess because of a hormonal problem.3 This condition, PA, occurs when the adrenal glands (small glands above the kidneys) produce too much of the hormone aldosterone, resulting in hypertension. In half of these patients, only one adrenal gland is affected. This condition is termed unilateral PA.
… having an alternative,non-invasive method to detect unilateral PA will identify more patients who can be helped by surgery, leading to better health outcomes and improved quality of life for these patients.
Keyhole (laparoscopic) surgery to remove the abnormal adrenal gland cures PA in these patients4. After surgery, aldosterone levels return to normal. Most patients see an improvement in their blood pressure or are able to either stop their antihypertensive medications altogether. The other half of patients with PA have excessive aldosterone production in both adrenal glands (bilateral adrenocortical hyperplasia). These patients are usually managed with medications, such as mineralocorticoid receptor antagonists, rather than surgery.
PA may be suspected in patients with difficult-to-control hypertension or those with low potassium levels. If suspected, the patients should then be referred to a specialist for evaluation, who will confirm the condition.
Currently, if hormone levels are high, patients with unilateral PA are identified through further testing using an invasive procedure called adrenal vein sampling (AVS). Even though CGH has improved their sampling success to 100% in more than 60 patients with PA over the last 5 years, AVS remains an invasive, technically difficult and expensive procedure. In many centres, failure to successfully sample the adrenal veins can lead to inconclusive results in as many as 50% of patients. Thus, having an alternative, non-invasive method to detect unilateral PA will identify more patients who can be helped by surgery, leading to better health outcomes and improved quality of life for these patients.
Scan to non-invasively detect curable hypertension in patients with PA
Working with the Clinical Imaging Research Centre (CIRC) at the NUS Yong Loo Lin School of Medicine, Prof Foo and Adjunct Assistant Prof Puar used a sensitive functional imaging scan to pick up these abnormal adrenal glands. This scan, called 11C-metomidate PET/CT, is able to identify small (<1 cm) growths in the adrenal gland, and show if the gland is producing too much aldosterone (see Figures above). The PET/CT scan can be done in less than an hour, without the need for hospitalisation.
Local studies have found that about 5% of all patients with hypertension have PA and may benefit from further assessment. Prof Foo and Adj Asst Prof Puar hope that, one day, many more of such patients could be evaluated for unilateral PA using the 11C-metomidate PET/CT scan and receive the appropriate treatment. They emphasise that the procedure is currently being evaluated in a relatively small clinical trial involving 25 patients, and requires a larger patient cohort validation before being ready for clinical use. A limiting factor is the scarcity of centres that are able to provide this sophisticated imaging. CIRC is one of only three centres in the world equipped to perform the new scan and is on track to being the first to demonstrate the effectiveness of the scan in a large cohort of patients. However, as the method is validated in more patients, the number of centres performing the imaging technique is likely to increase.
This scan, called 11C-metomidate PET/CT, is able to identify small (<1 cm) growths in the adrenal gland, and show if the gland is producing too much aldosterone. The PET/ CT scan can be done in less than an hour, without the need for hospitalisation.
The research study is being supported through a grant from the National Medical Research Council.
REFERENCES
1 Ministry of Health Singapore. National Health Survey 2010. Singapore: Ministry of Health Singapore; 2011.
2 Ministry of Health Singapore. Hypertension: MOH Clinical Practice Guidelines, 1/2017. Singapore: Ministry of Health Singapore; 2017.
3 Loh KC, Koay ES, Khaw MC, Emmanuel SC, Young WF Jr. Prevalence of primary aldosteronism among Asian hypertensive patients in Singapore. J Clin Endocrinol Metab. 2000;85:2854-2859.
4 Deinum J, Prejbisz A, Lenders JWM, van der Wilt GJ. Adrenal vein sampling is the preferred method to select patients with primary aldosteronism for adrenalectomy: Con side of the argument. Hypertension. 2018;71:10-14.