Primary Hyperaldosteronism: A Diagnostic Challenge

Primary Hyperaldosteronism is characterized by inappropriately high aldosterone production which leads to hypertension, and hypokalemia. Low potassium level causes false negative aldosterone levels which can be avoided by potassium replacement. However, hypokalemia may be refractory as in our case.

Case Description:

A 36-year-old gentleman was referred for secondary hypertension workup. He was on lisinopril 10 mg and amlodipine 5 mg PO daily. His preliminary tests showed mild hypokalemia, and high aldosterone level. We admitted him to correct hypokalemia before performing saline suppression. However, his potassium reached a maximum of 3.5 mmol/L despite liberal replacement. At that level, basal aldosterone and renin were collected and saline supression test was performed. The test results were compatible with primary aldosteronism. Adrenal CT showed a lipid-rich adenoma. The patient was discharged on lisinopril 10 mg and amlodipine 10 mg PO daily and potassium supplements. With follow up, serum potassium remained low, and it was corrected after adding spironolactone without potassium supplements.

The patient opted to continue on medical treatment and declined surgery.

We presented this case to elaborate that attempt to correct hypokalemia might be unsuccessful prior screening for hyperaldosteronism and the target potassium of 4.0 mmol/L may be not achievable with potassium supplements alone.

Discussion:

We admitted our patient for IV potassium replacement, however, serum potassium did not exceed 3.5 mmol/L despite liberal replacement and aldosterone proved to be high and did not suppress following saline suppression. We had a substantial interest in understanding the mechanism behind refractory hypokalemia and in eliciting a recommendation regarding prior attempt to correct hypokalemia.

Although renin is the main regulator of plasma aldosterone levels, other regulators such as potassium and ACTH are also influential. ACTH can stimulate aldosterone secretion acutely and transiently under normal conditions, but to a lesser extent than angiotensin II and potassium.

Psychological stress activate the HPA axis, leading to release of ACTH which leads to release of both cortisol and aldosterone. So, we speculated that the repetitive stress during hospitalization because of IV fluids administration, frequent blood sampling, waiting for the results and wish of early release and discharge from the hospital might induce ACTH-mediated aldosterone hypersecretion which increases urinary potassium losses and leads to refractory hypokalemia.

Another assumption, that, aldosterone release is set at a lower potassium level. Aldosterone release will stimulate more potassium urinary excretion and leads to hypokalemia again.

Treating PA by MR antagonists or unilateral adrenalectomy can help resolve hypokalemia, and lowers BP as in our case.

We conclude that persistent hypokaelemia should not preclude screening tests for hyperaldosteronism.