How is primary hyperaldosteronism diagnosed in pregnancy given the normal increase in aldosterone levels?

Diagnosing Primary Hyperaldosteronism in Pregnancy

Diagnosis of primary hyperaldosteronism in pregnancy relies on demonstrating repeatedly suppressed plasma renin levels in the context of hypertension, as confirmatory testing is contraindicated and both aldosterone and renin are physiologically elevated during normal pregnancy. 1, 2

Why Standard Diagnostic Approaches Don't Work

• Aldosterone and renin are both physiologically increased during normal pregnancy, making the standard aldosterone-to-renin ratio (ARR) unreliable for screening 1, 2
• Confirmatory tests (saline suppression, oral salt loading, fludrocortisone suppression) are contraindicated during pregnancy due to potential maternal and fetal risks 1, 2
• The antagonistic effect of progesterone on aldosterone further complicates interpretation of biochemical testing 3

Diagnostic Approach During Pregnancy

The key diagnostic finding is repeatedly suppressed or low plasma renin activity in a pregnant woman with hypertension, particularly if resistant to treatment or accompanied by hypokalemia 1, 2, 4

Clinical Clues to Suspect Primary Aldosteronism

• Resistant hypertension requiring multiple antihypertensive medications, especially in early pregnancy 1, 5
• Hypokalemia, though this is absent in many cases and should not be relied upon as a screening trigger 1, 3
• Hypertension that worsens or fails to improve despite the expected progesterone-mediated amelioration that occurs in normal pregnancy 1

Laboratory Testing Strategy

• Measure plasma renin activity (PRA) and plasma aldosterone concentration (PAC) simultaneously in the morning after the patient has been upright for 2 hours 6
• Repeatedly suppressed PRA (typically <0.5-1.0 ng/mL/h) with elevated aldosterone suggests primary aldosteronism, though absolute aldosterone values must be interpreted cautiously given physiologic pregnancy-related increases 1, 2, 4
• A nomogram based on gestational age-specific aldosterone and renin values has been developed to help identify cases, as normal pregnancy shows predictable increases in both hormones 4

Imaging Considerations

• MRI (without gadolinium) is the preferred imaging modality if unilateral disease is suspected and surgical intervention is being considered 1, 2
• Adrenal venous sampling is contraindicated during pregnancy due to radiation exposure and procedural risks 1
• Imaging should only be pursued if it will change management, typically when second-trimester adrenalectomy is being considered for unilateral disease 1, 5

Critical Pitfalls to Avoid

• Do not rely on hypokalemia as a screening criterion - many pregnant women with primary aldosteronism remain normokalemic 1, 3
• Do not use standard ARR cutoffs (such as ARR >30) that apply to non-pregnant patients, as both hormones are physiologically elevated 1, 2
• Do not attempt confirmatory testing with saline suppression or oral salt loading during pregnancy 1, 2
• Do not use spironolactone due to anti-androgenic effects that can cause undervirilization of male fetuses (FDA pregnancy category C) 1, 2

Management Implications

• Ideally, screen and treat women with resistant hypertension for primary aldosteronism before conception, as cure rates and pregnancy outcomes are superior when unilateral disease is surgically treated prior to pregnancy 4
• If eplerenone is needed for resistant hypertension or persistent hypokalemia, it appears safe and effective based on limited data (FDA pregnancy category B) 1, 2
• Laparoscopic adrenalectomy during the second trimester can be considered for unilateral disease when medical therapy fails to control hypertension or complications develop 1, 2, 5
• Complications occur in approximately 62% of pregnant women with non-familial primary aldosteronism, underscoring the importance of early diagnosis and aggressive management 4