As you would have likely guessed by looking at the picture to the left we often tend to believe what we see without giving much thought. This is frequently true in the evaluation and management of patients with primary aldosteronism (PA) where the diagnostic tests are frequently misinterpreted and findings on imaging studies such as CT and MRI of the adrenal glands often guide therapeutic decisions.
Since the initial discovery of aldosterone producing adenoma by Dr. Jerome W. Conn in 1955, PA has emerged as the most common cause of secondary hypertension and accounts for up to 10-15% of all cases of hypertension in the general population (read this article). This notable rise in the prevalence of PA has been due to the widespread use of aldosterone renin ratio (ARR) as a screening test for patients with suspected PA, and less reliance on the presence of hypokalemia (present in less than 40% patients) as a prerequisite for the diagnosis of PA. It is therefore important to remember that normokalemic hypertension is the most common presentation of PA and that the prevalence of PA increases with severity of hypertension.
Although ARR is a good screening test, cut off values are variably reported in the literature, but generally speaking, a ARR of greater than 20-40 in the presence of morning (8am-10am) plasma aldosterone concentration greater than 15ng/dL and plasma renin activity ~0.5 ng/mL/h is acceptable and testing for this does not require a washout of antihypertensive medications (except aldosterone antagonists) despite the popular belief, and is practically impossible. A positive ARR therefore, should always be followed with the suppression tests. Among the several tests that are available, oral or IV salt loading and fludrocortsone suppression test are more commonly used and are fairly comparable with moderate sensitivity and high specificity (~90%). Details about how these tests are performed can be read here.
Once the diagnosis of PA is confirmed, differentiating between the subtypes, particularly solitary adenoma vs. unilateral or bilateral adrenal hyperplasia is crucial as definitive therapies differ. This is best done by adrenal vein sampling (AVS), which although invasive and operator dependant, is the gold standard test to differentiate the subtypes. Diagnosis of APA is made when the aldosterone to cortisol ratio (A/C) from one adrenal is at least 4 times the ratio from the other adrenal gland (lateralization ratio).
However, instead of AVS, CT scan or MRI of the adrenal glands is more commonly used to differentiate subtypes of PA. CT scan of the adrenal glands is important in identifying young individuals (less than 40 years) with adrenal adenoma (≥ 1cm) or in identifying highly differentiated adrenal masses (greater than 3 cm). Beyond that, the utility of CT scan of adrenal glands to correctly identify the subtype of PA is limited (sensitivity ~77% and specificity ~75%) and the findings can often be misleading. In a large systematic review published in Annals, CT scan was concordant with AVS in only 60% of the cases for the diagnosis of PA. Reliance on CT scan instead of AVS to differentiate the subtypes would have led to inappropriate adrenelectomy in ~15% of the patients and inappropriate exclusion for unilateral adrenelectomy in 19% patients. In 5%, wrong adrenal gland would have been removed. A study of 185 patients with adrenal incidentalomas in whom only 5% were found to have solitary adenomas further supports the argument that findings on the imaging studies should be interpreted with caution.
Finally, it’s important to remember that the benefits of adrenelectomy and mineralcorticoid antagonists in correctly diagnosed patients with solitary adenoma vs. unilateral or bilateral adrenal hyperplasia respectively, extend beyond just the resolution of hypokalemia and improvement in blood pressure. Recent studies have shown a decrease in cardiovascular mortality and prevention of late renal complications such as proteinuria and chronic kidney disease.
Viresh Mohanlal, MD