What is the diagnosis for a 46-year-old perimenopausal female with iron deficiency (ferritin 14, iron saturation 8), impaired renal function (creatinine 1.01), hyperlipidemia (LDL 173), elevated aldosterone (30) and aldosterone-to-renin ratio (32.3), mild hyperglycemia (A1c 5.8), hypothyroidism (TSH 67), and elevated ACTH (16)?

Elevated Aldosterone-to-Renin Ratio: Primary Aldosteronism Workup Required

This patient has a significantly elevated aldosterone-to-renin ratio (ARR) of 32.3 with suppressed plasma renin activity (0.93), strongly suggesting primary aldosteronism as the underlying diagnosis, which requires confirmatory testing and subtype differentiation to guide definitive treatment. 1, 2

Understanding the Aldosterone-Renin Relationship

The ARR of 32.3 exceeds the diagnostic threshold of 30, indicating autonomous aldosterone secretion independent of renin stimulation. 2 While the aldosterone level of 30 ng/dL is elevated and the renin is suppressed at 0.93, this pattern is characteristic of primary aldosteronism (PA), which affects approximately 6% of hypertensive patients in primary care settings. 2

A critical caveat: In patients with severe hypertension and secondary kidney damage (your creatinine of 1.01 suggests early renal impairment), renin can "escape" from complete suppression despite true primary aldosteronism. 3 This means the renin may not be as suppressed as expected, but the disproportionately elevated aldosterone relative to renin still indicates PA. 3

Immediate Next Steps for Diagnosis

Confirmatory Testing Required

You must proceed with confirmatory testing to rule out false positives before making treatment decisions. 2, 4 The options include:

• Captopril challenge test: Aldosterone remains elevated despite ACE inhibition 2
• Oral sodium loading test: 24-hour urine aldosterone remains >12 mcg after 3 days of high sodium intake 2
• Intravenous saline suppression test: Plasma aldosterone >10 ng/dL after 2L saline infusion 2
• Fludrocortisone suppression test: Most definitive but requires hospitalization 2

Subtype Differentiation After Confirmation

Once PA is confirmed, you must distinguish unilateral from bilateral disease: 2, 4

• Adrenal CT scan: Initial imaging to identify adenomas or hyperplasia 2, 4
• Adrenal vein sampling (AVS): Gold standard for lateralization, essential before considering surgery 2, 4

Treatment Implications Based on Subtype

Unilateral aldosterone-producing adenoma: Surgical adrenalectomy is curative and the optimal treatment. 2, 4

Bilateral idiopathic hyperplasia: Medical management with mineralocorticoid receptor antagonists (spironolactone 25-100mg daily or eplerenone 50-100mg daily). 2, 4

Critical Management Considerations

Medication Effects on Testing

Important pitfall: Many antihypertensive medications interfere with ARR testing. 5 The least interfering drugs are:

• Calcium channel blockers (preferred) 5
• Alpha-blockers 5
• Hydralazine 5

Beta-blockers, ACE inhibitors, and ARBs can be continued if necessary, but results must be interpreted cautiously. 5 Ideally, mineralocorticoid receptor antagonists should be stopped 4-6 weeks before testing, though this may not be feasible with severe hypertension. 5

Concurrent Issues Requiring Attention

Severe hypothyroidism (TSH 67): This requires immediate thyroid hormone replacement, as hypothyroidism can worsen hypertension and cardiovascular risk. 6

Iron deficiency (ferritin 14, saturation 8%): At age 46 with perimenopausal hormone patterns (elevated FSH 5.3, LH 13.5), menstrual blood loss is the likely cause, but gastrointestinal sources must be excluded. 1, 7 Start oral iron supplementation 60-120mg elemental iron daily and recheck in 4 weeks. 1, 7

Hyperlipidemia (LDL 173): This is a risk-enhancing factor for cardiovascular disease and warrants statin therapy, particularly given the increased cardiovascular risk associated with PA. 6

Prediabetes (A1c 5.8): Requires lifestyle modification counseling for diet and exercise. 6

Cardiovascular Risk Context

PA carries significantly higher cardiovascular morbidity than essential hypertension, independent of blood pressure levels. 4 Patients with PA have increased rates of myocardial infarction, stroke, atrial fibrillation, and heart failure compared to matched controls with essential hypertension. 4 This underscores the urgency of accurate diagnosis and appropriate treatment—surgical cure when possible, or targeted medical therapy when surgery is not indicated. 2, 4

Practical Algorithm

1. Confirm PA diagnosis with one of the confirmatory tests listed above 2
2. If confirmed positive, obtain adrenal CT scan 2, 4
3. Proceed to adrenal vein sampling for lateralization (unless clear unilateral adenoma >1cm with normal contralateral adrenal) 2, 4
4. If unilateral disease: Refer for adrenalectomy 2, 4
5. If bilateral disease: Initiate spironolactone or eplerenone 2, 4
6. Monitor for hyperkalemia and worsening renal function when starting mineralocorticoid antagonists, especially given baseline creatinine of 1.01 3