An 80 year old male with atrial fibrillation, hypertension, hypokalemia is diagnosed with hyperaldosteronism with an aldosterone to renin ratio of 34.5/0.15=230 . CT scan reveals a right adrenal 1 cm presumed adenoma
1. How do you accurately diagnose primary hyperaldosteronism?
2. Do medications which the patient is taking influence the work-up?
3. Can you have primary hyperaldosteronism in the absence of hypokalemia?
4. Can the adrenal mass be incidental? Should the patient have additional testing?
-Anna Dvorak PGY-3
Commentary By: Stephen Richardson, MD Assistant Professor of Medicine, Divsion of Endocrinology
1. It is almost certain that primary hyperaldosteronism is responsible for the patient’s clinical and laboratory features of hypertension and hypokalemia with a very high aldosterone: plasma renin ratio. This test is performed in order to exclude other causes of hypertension with hypokalemia such as Cushing’s syndrome, renal artery stenosis or licorice ingestion. Patients should not be taking angiotensin blockers as they may interfere with the test results. A ratio of greater than 30:1 is suspicious for primary hyperaldosteronism, which is associated with hypokalemia in only about fifty percent of cases. Thus the lack of a low serum potassium does not exclude the diagnosis. Primary aldosteronism is under-diagnosed and should be suspected in young patients with hypertension and in those whose blood pressure is hard to control with multiple anti-hypertensive drugs.
2. Theoretically, demonstration of lack of suppression of aldosterone by salt loading is needed to confirm the diagnosis of primary hyperaldosteronism. Pragmatically, this may induce heart failure in a patient with underlying cardiac disease so the physician has to be judicious in performing the test. A 24 hour urine aldosterone is measured after three days of oral salt loading. Aldosterone values of over 18 ug are diagnostic. Another alternative is parenteral salt loading. Urine sodium levels should also be checked in order to ensure that salt loading has been adequate.
3. Imaging can sometimes be a problem in visualizing very small adenomas and in differentiating between adenomas and adrenal hyperplasia, in which case selective adrenal vein sampling may be necessary to pin point the source of excessive aldosterone production. Traditionally, selective venous sampling has been recommended to confirm the source of excess aldosterone. My personal opinion is that when a unilateral adenoma has been documented unequivocally with today’s imaging techniques (CT and or MRI) then this invasive test may be omitted (this is not the standard recommendation). Selective venous sampling should be performed only at centers with excellent and experienced radiologists.
Because of the fat content of adrenal adenomas, CT or MRI results are typically definitive in diagnosing adenomas especially if they are large. If the radiologist is unable to diagnose an adrenal mass as an adenoma then consideration should be given to the possibilities of a pheochromocytoma or malignancy, either primary or more commonly metastatic. However both processes can often be diagnosed on the basis of typical radiological features.
4. To get back to the patient, it is most likely that the adrenal adenoma seen on imaging is the source of his excess aldosterone. Laparoscopic removal would cure his hypokalemia and at least improve if not cure his hypertension. However, given his age and co-morbidities, I would skip salt loading, venous sampling and the surgery. I would treat him with the aldosterone antagonist, spironolactone, starting at a low dose and titrating up as needed to control his hypokalemia so that he no longer requires potassium replacement. This will help but may not be sufficient as a single agent to control his blood pressure if he has underlying essential hypertension. If he were younger and without concomitant co-morbidities, I would recommend laparoscopic surgery.
A recent and relevant review article was published in the NEJM: The incidentally discovered adrenal mass. W.F. Young 356: 601- 610, 2007.