Evaluation and Management of the Patient with Hypertension and Hypokalemia

1. Evaluation and Management of the Patient with Hypertension and Hypokalemia Stephen L. Aronoff, MD

2. When to Expect Mineralocorticoid Excess • Hypertension • Hypokalemia • Metabolic alkalosis • Less than 50% with Primary Aldosteronism are hypokalemia

3. Differential Diagnosis of Hypokalemia and normal BP • Surreptitious vomiting • Bartter’s Syndrome • Rare primary aldosteronism

4. Other Causes of Hypertension and Hypokalemia • Renovascular Disease • Diuretic therapy • Cushing’s Syndrome • Licorice ingestion • CAH • Rare renin-secreting tumors

5. When to Screen Patient for Primary Aldosteronism • Hypokalemia • Severe, resistant or relatively acute HT • Adrenal incidentaloma • Primary aldosteronism occurs in 1-2% up to 5-10% of all hypertensives – probably an over-estimate

6. Consider screening Hypertensive patients under 30 for secondary causes • With mild to severe hypertension • No FH of hypertension • Non-obese

7. Initial Approach to Patient with HT and Hypokalemia • Plasma renin activity • Plasma aldosterone concentration

8. Plasma Renin Activity in Hypokalemia and HT • Low Primary mineralocorticoid excess • High Diuretic therapy Reno-vascular HT Malignant HT Rare – renin-secreting tumor

9. Plasma Aldosteronism/Plasma Renin Activity • Test in AM • Un-interpretable with spironolactone or eplerenone RX – stop for 6 weeks • Other K+ diuretics OK • ACEI and ARB’s may falsely elevate PRA (undetectable PRA strongly suggestive)

10. Plasma Aldosteronism/Plasma Renin Activity • Normal ratio 4 – 10 • Primary aldosteronism 30 – 50 • PRA low in many with essential HT but high PAC (>15 ng/dl) and abnormal ratio are uncommon • Cut-off for high PAC/PRA is lab dependent. Thus increased PAC is part of dx requirement

11. Other Lab Testing • 24 hour urine Potassium – usually not necessary to demonstrate K+ wasting • Unless PRA not suppressed • PAC not elevated • Clinical suspicion of surreptitious vomiting or laxative abuse • Inappropriate K+ wasting is > 30mg daily in hypokalemic patient • Urine Na+ > 50meq daily

12. Confirmation of Primary Aldosteronism • Elevated PAC/PRA • Salt load (after control of HT and correction of K+) • Dietary for 3 days 5000mg Na+ diet or 1gm NaCl tablets – 2 tid Watch out for worsening HT and hypokalemia

13. Confirmation of Primary Aldosteronism – Cont’d • 3rd day of high salt diet – collect 24 hr urine for aldosterone, sodium and creatinine • 24 hr urine Na+ should be > 200meq to show adequate Na+ loading • Urine aldosterone > 14 mcg/24 hrs consistent with primary hyperaldosteronism

14. Confirmation of Primary Aldosteronism – Cont’d • IV sodium chloride • Baseline plasma aldosterone level • 2 liters NS IV over 4 hours • Repeat plasma aldosterone level • Primary hyperaldosteronism – plasma aldosterone level does not suppress

15. Nonaldosterone Mineralocorticoid Excess • Suppressed PRA and low plasma or urine aldosterone value • Causes Some types of CAH or familial cortisol resistance Chronic licorice ingestion Severe cases of Cushing’s syndrome Deoxycorticosterone producing tumor

16. Familial Hyperaldosteronism • Type 1 – glucocorticoid-remediable aldosteronism Secondary to ACTH stimulation of aldosterone secretion • Type 2 – not ACTH dependent and not suppressible with dexamethasone Genetic defect unknown They can have APA or IPA or both

17. Differentiating Adrenal Adenoma from Hyperplasia • 30 – 60 % Adrenal adenomas • APA have higher aldosterone secretion rates • Adrenal hyperplasia less severe with less hypokalemia • PAC/PRA > 32 had 100% sensitivity and 61% specificity for APA in one study

18. Differentiating Adrenal Adenoma from Hyperplasia • Patients with APA More severe HT More profound hypokalemia - < 3.0 Higher plasma (>25 ng/dl) and urinary (>30 mcg/24 hrs) levels of aldosterone Younger - < 50

19. Differentiating Adrenal Adenoma from HyperplasiaRadiographic Tests • Hypo-dense unilateral macroadenoma (>1 cm) likely APA • Abnormality in both glands likely hyperplasia although both glands my appear normal on CT or MRI

20. Differentiating Adrenal Adenoma from HyperplasiaRadiographic Tests • Some investigators suggest low K+, nonsuppressible hyperaldosteronism, PAC/PRA ratio > 50 and a unilateral mass can go directly to surgery • But – in 3 studies of 32 pts. – 11 patients (1/3) had bilateral hyperplasia • Absence of mass does not exclude APA • Bilateral lesions do not exclude APA • CT may be accurate only 50% of time

21. Differentiating Adrenal Adenoma from HyperplasiaAdrenal Vein Sampling • Gold standard • APA - >4 fold step-up of PAC • Best performed with continuous infusion of ACTH (50 mcg per hour) • Measure cortisol in same sample to be sure samples from adrenal veins • Cortisol from right adrenal 25% higher and 10 times higher than peripheral vein

22. Differentiating Adrenal Adenoma from HyperplasiaAdrenal Vein Sampling • Most useful when no adrenal abnormality • Both adrenal glands abnormal but asymmetric • One study – 41% with normal CT and 49% with bilateral micronodules on CT had unilateral APA • In 203 pts. with primary aldosteronism – 51% with unilateral micro-nodule and 66% with unilateral macro-nodule had ipsilateral aldo hypersecretion