Case 39: Diagnosis & Conclusions

Case 39 Index

Diagnosis: Primary hyperaldosteronism, due to adrenal adenoma

Case Summary:

Great work! This young man has primary hyperaldosteronism as the result of an adrenal adenoma causing his hypertension. Let’s first take a moment to dive into the preliminary work-up of secondary hypertension!

Initial history and physical exam may suggest primary/essential hypertension given his family history and obesity.  However, he is under 30 years old, and his blood pressure elevation is quite extreme (>180/110 mmHg). This, along with other clinical clues in his preliminary work-up, should prompt consideration of secondary hypertension.

What is the differential diagnosis for secondary hypertension (Click!)?
Renal artery stenosis
Primary hyperaldosteronism
Underlying/primary kidney disease
Sleep apnea
Cushing’s syndrome
Medication-induced (oral contraceptives, chemotherapies)
Aortic coarctation
Primary hyperparathyroidism

The clinical work-up of this patient confirms severe hypertension. His age, absence of systemic atherosclerotic disease, and absence of a bruit or atrophic kidney seem to suggest against renovascular hypertension. Preliminary evaluation reveals normal kidney function without proteinuria or hematuria, but we do find hypokalemia and metabolic alkalosis. This is a major clue of primary mineralocorticoid excess.

Testing for primary aldosteronism should be performed in patients with hypertension and hypokalemia OR hypokalemia that develops with diuretic therapy (not all patients will be hypokalemic at presentation). Patients with resistant hypertension, sleep apnea, family history of primary aldosteronism, or an adrenal incidentaloma should also undergo testing.

Measurement of plasma aldosterone concentration and plasma renin activity (or plasma renin concentration) is the appropriate initial test. Of note, our patient was on no medications prior to testing. In general, a mineralocorticoid receptor antagonist (spironolactone, eplerenone), angiotensin-converting enzyme (ACE) inhibitor, angiotensin receptor blocker (ARB), or direct renin inhibitor could interfere with testing. 

Results suggestive of primary aldosteronism
Plasma renin activity (PRA)
<1 ng/ml/hr (suppressed)
Plasma aldosterone concentration (PAC)
≥10 ng/dL (elevated)
Plasma aldosterone concentration/Plasma renin activity (PAC/PRA) ratio
>20 ng/dL per ng/mL/hr

Here’s an infographic summarizing some of suggestions above:

This patient has a PAC of 25 ng/dL (normal < 10ng/dL) and PRA of 0.5 ng/mL/hour (suppressed, < 1ng/mL/hour). Given his hypertension and spontaneous hypokalemia, primary hyperaldosteronism is the most likely diagnosis. If confirmation is needed, a sodium loading test can be performed (high salt diet over several days, or a Saline Infusion); high aldosterone levels despite sodium loading is consistent with hyperaldosteronism.

Once primary aldosteronism is confirmed, the differential diagnosis includes an aldosterone-producing adenoma (rarely carcinoma) or bilateral adrenal hyperplasia. Although more rare, there are also ectopic aldosterone-secreting tumors as well as several inherited disorders that can lead to hyperaldosteronism.

Adrenal CT imaging should be performed to look for a unilateral adrenal adenoma, particularly if the patient would be a good surgical candidate, as adrenalectomy is the treatment of choice. Even positive adrenal CT imaging findings can be deceptive, however, so the gold standard is adrenal vein sampling. Aldosterone concentration is measured bilaterally at the adrenal veins and at the IVC (and normalized/corrected to cortisol levels) to confirm excess unilateral aldosterone excretion. This test, however, is invasive, technically challenging, and difficult to interpret.

For patients awaiting unilateral adrenalectomy, poor surgical candidates, or patients with bilateral adrenal hyperplasia, mineralocorticoid receptor antagonists (spironolactone, eplerenone) are the medical management of choice. 

Take a look at a few additional resources for a more detailed look at primary aldosteronism:

  1. Vilela, LAP, Almeida, MQ. Diagnosis and management of primary aldosteronism. Arch Endocrinol Metab 2017; 61: 305–312.

  2. A helpful article from Renal Fellow Network from February 2011, Evaluation of primary aldosteronism: seeing is not believing


Case 39 Index
Case 39 Introduction
Case 39 Physical Exam
Case 39 Diagnostic Testing
Case 39 More Diagnostic Testing