Primary hyperaldosteronism 2016 8 22 Clinical suspicion of

Primary hyperaldosteronism 2016. 8. 22 내과 학생컨퍼런스

Clinical suspicion of mineralocorticoid excess Patient with hypertension and • • Severe hypertension (>3 BP drugs, drug-resistant) or Hypokalemia (spontaneous or diuretic-induced) or Adrenal mass or Family history of early-onset hypertension or cerebrovascular events at < 40 years of age

Clinical suspicion of mineralocorticoid excess Patient with hypertension and • • Severe hypertension (>3 BP drugs, drug-resistant) or Hypokalemia (spontaneous or diuretic-induced) or Adrenal mass or Family history of early-onset hypertension or cerebrovascular events at < 40 years of age Screening • Measurement of aldosterone-renin ratio (ARR) on current blood pressure medication (stop spironolactone for 4 wks) and with hypokalemia corrected • Positive if ARR > 750 pmol/L: ng/ml/h (> 30 ng/dl: ng/ml/h) and aldosterone > 450 pmol/L(> 15 ng/dl)

Measurement of ARR • Testing conditions – Correct hypokalemia – Liberal salt diet – Withdraw agents who affecting the AAR • At least 4 weeks – Spironolactone, eplerenone, amiloride triamteren, Potassium wasting diuretics, Licorice • At least 2 weeks – B-blocker, Central a-2 agonist, NSAID, ACEI, ARB, renin inhibitor, Calcium channel antagonist

Effects of anti-HTN drugs on the ARR Drug Effect on Renin Effect on Aldosterone Net Effect on ARR β blockers ↓ ↑ ↑ α 1 blockers → → → α 2 sympathomimetics → → → ACE inhibitors ↑ ↓ ↓ AT 1 R blockers ↑ ↓ ↓ Calcium antagonists → → → (↑) →/(↓) Diuretics

Clinical suspicion of mineralocorticoid excess Patient with hypertension and • • Severe hypertension (>3 BP drugs, drug-resistant) or Hypokalemia (spontaneous or diuretic-induced) or Adrenal mass or Family history of early-onset hypertension or cerebrovascular events at < 40 years of age Screening • • Measurement of aldosterone-renin ratio (ARR) on current blood pressure medication with hypokalemia corrected Positive if ARR > 750 pmol/L: ng/ml/h (> 30 ng/dl: ng/ml/h) and aldosterone > 450 pmol/L(> 15 ng/dl) Confirmation of diagnosis • E. g. , saline infusion test (2 L physiologic saline over 4 h IV), oral sodium loading, fludrocortisone suppression

Confirmative Testing • The current literature does not identify a gold standard confirmatory test for PA • Saline loading test – Infusion of 2 L of normal saline over 4 h – Measurement of aldo: baseline and 4 h time points – Normal suppression: aldo < 5 ng/d. L • Captopril challenge test – 25~50 mg captopril (ACEI) p. o. – Measurement of PRA, PAC at time 0, 60, 90 min – PAC normally suppressed by captopril (>30%)

Clinical suspicion of mineralocorticoid excess Patient with hypertension and • • Severe hypertension (>3 BP drugs, drug-resistant) or Hypokalemia (spontaneous or diuretic-induced) or Adrenal mass or Family history of early-onset hypertension or cerebrovascular events at < 40 years of age Screening • • Measurement of aldosterone-renin ratio (ARR) on current blood pressure medication with hypokalemia corrected Positive if ARR > 750 pmol/L: ng/ml/h (> 30 ng/dl: ng/ml/h) and aldosterone > 450 pmol/L(> 15 ng/dl) Confirmation of diagnosis • E. g. , saline infusion test (2 L physiologic saline over 4 h IV), oral sodium loading, fludrocortisone suppression CT adrenals

Clinical suspicion of mineralocorticoid excess Patient with hypertension and • • Severe hypertension (>3 BP drugs, drug-resistant) or Hypokalemia (spontaneous or diuretic-induced) or Adrenal mass or Family history of early-onset hypertension or cerebrovascular events at < 40 years of age Screening • • Measurement of aldosterone-renin ratio (ARR) on current blood pressure medication with hypokalemia corrected Positive if ARR > 750 pmol/L: ng/ml/h (> 30 ng/dl: ng/ml/h) and aldosterone > 450 pmol/L(> 15 ng/dl) Confirmation of diagnosis • E. g. , saline infusion test (2 L physiologic saline over 4 h IV), oral sodium loading, fludrocortisone suppression CT adrenals Unilateral adrenal mass Bilateral micronodular hyperplasia Normal adrenal morphology

Clinical suspicion of mineralocorticoid excess Patient with hypertension and • • Severe hypertension (>3 BP drugs, drug-resistant) or Hypokalemia (spontaneous or diuretic-induced) or Adrenal mass or Family history of early-onset hypertension or cerebrovascular events at < 40 years of age Screening • • Measurement of aldosterone-renin ratio (ARR) on current blood pressure medication with hypokalemia corrected Positive if ARR > 750 pmol/L: ng/ml/h (> 30 ng/dl: ng/ml/h) and aldosterone > 450 pmol/L(> 15 ng/dl) Confirmation of diagnosis • E. g. , saline infusion test (2 L physiologic saline over 4 h IV), oral sodium loading, fludrocortisone suppression CT adrenals Unilateral adrenal mass Bilateral micronodular hyperplasia Age > 40 yrs Age < 40 yrs Adrenal vein sampling Unilateral adrenalectomy Drug treatment Normal adrenal morphology

Adrenal Vein Sampling • Drainage – Right adrenal vein IVC – Left adrenal vein left renal vein • Can be considered in all patients who have confirmed PA and want to pursue surgical option Clinical Practice Guideline, JCEM, 2008

Surgical Intervention • Unilateral laparoscopic adrenalectomy is the optimal treatment for patients diagnosed with APA or unilateral hyperplasia – Serum aldo and potassium levels should be measured the day after surgery – A sodium-rich diet should be recommended during the first postoperative weeks – Serum potassium levels should be monitored weekly for 4 weeks • Cure rate in patients with APA after unilateral adrenalectomy – 50 -60%

Factors Associated with Resolution of Hypertension in the Postoperative Period • Lack of a family history of hypertension • Pre operative use of no more than two antihypertensive drugs • Young age • Short duration of hypertension (<5 years) • Positive response to spironolactone • High pre operative ARR • high urinary aldosterone excretion

Pharmacological Therapy • Patients with IHA, and those with APA or unilateral hyperplasia who are not candidates for or who decline surgery • MR antagonists – Effective at controlling BP and to provide BP-independent target organ protection – Spironolactone: Primary agent – Eplerenone: Alternative • Epithelial sodium channel antagonists – Amiloride: Potassium sparing diuretic, No beneficial effects on endothelial function • Low dose glucocorticoid or additional MR antagonists for GRA • Other hypertensive agents as 3 rd or 4 th line agents for adequate BP control