Primary Aldosteronism
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1 Primary Aldosteronism Odelia Cooper, MD Assistant Professor of Medicine Division of Endocrinology, Diabetes, and Metabolism Cedars-Sinai Medical Center HYPERTENSION CENTER
2 Barriers to diagnosing primary aldosteronism Too many drugs interfere with tests Dangers of washout and switching BP meds Hard to interpret results ARR? PRA? PAC? Cutoffs? Confirmatory tests-which is safest, easiest, and cheapest? Adrenal venous sampling is risky Can t we just treat with eplerenone? Kline GA. Clinical Endocrinology (2015) 82,
3 Goals of talk: Dissolve the barriers BP medications do not need to be held for screening. Aldosterone must be elevated and PRA must be suppressed. The Aldosterone-Renin Ratio (ARR) is not a screening criterion. Oral salt loading for confirmation safe, easy, effective Adrenal venous sampling (AVS) is absolutely necessary for localization. Imaging is not sufficient. Surgery is safe, gives chance to cure
4 Primary Aldosteronism Inappropriate aldosterone Reflex plasma renin activity HTN Hypokalemia (<37%) Galati SJ Trends in Endocrinology and Metabolism. 2013, Vol. 24, No. 9
5 Causes of primary aldosteronism Surgically curable Aldosterone producing adenoma (30-50%) Primary unilateral adrenal hyperplasia Multinodular unilateral adrenocortical hyperplasia Ovarian aldosterone secreting tumor Aldosterone producing carcinoma Not surgically curable Bilateral adrenal hyperplasia (up to 50%) Familial hyperaldosteronism Type I: Glucocorticoid remediable hyperaldosteronism Type II Type III Rossi GP. Curr Hypertens Rep (2010) 12:
6 Genetics of APAs: K + channel somatic mutations Choi M. Science :331 Wang T. European Journal of Endocrinology
7 Primary aldo is prevalent! Study Population Biochemical PA Confirmed APA Rossi referred 11% 4.8% Douma referred 11% NA Mosso primary care 6.1% 0 Loh referred 4.6% 1.7% Mulatero referred 7% 1.6% Nishizaka referred 24% AA 20% Caucasians NA HTN severity: Rossi GP. J Am Coll Cardiol 2006;48:2293 Douma S. Lancet 2008; 371: 1921 Mosso L. Hypertension. 2003;2: Loh KC. J Clin Endocrinol Metab. 2000;85:2854 Mulatero P. J Clin Endocrinol Metab. 2004;89:1045 Nishizaka MK. Am J Hypertens 2005;18: 805
8 Step 1: Suspect? Step 2: Screen? Step 3: Suppress? Step 4: Site? Step 5: Surgery? Courtesy of Dr. Ron Victor
9 Case 54 year old man with hypertension for 30 years evaluated for marked acceleration x 1 year Stable on nifedipine monotherapy until 2012 when BP increased to 220/125 mmhg Family history of HTN BP 141/82 mmhg on: Clonidine 0.1 mg tid Diltiazem CD 180 mg twice daily Hydralazine 50 mg tid Isosorbide dinitrate 30 mg daily Spirinolactone 25 mg daily Valsartan-HCTZ 320/12.5 mg daily Na 139 K 3.3 Cr 1.14 ECG shows LVH Hypertension Center
10 Suspect Primary Aldo Hypertension BP >160/100 (Stage 2) Resistant HTN (> 140/90 on 3 medications) Personal or family history of early onset HTN, CVA Marked LVH With hypokalemia Whenever suspecting secondary HTN First degree relative of known PA patient Adrenal Incidentaloma Funder JW, Young WF. Hypertension J Clin Endocrinol Center Metab 93: , 2008
11 Step 1: Suspect Step 2: Screen Step 3: Suppress Step 4: Site? Step 5: Surgery?
12 SCREEN: PRA <1 AND Aldo 15 Most BP meds are OK on 1 st screen. If equivocal, repeat after holding: ACEIs, ARBs, diuretics, aldo blockers x 4 weeks Hypertension Center
13 Who has Primary Aldo? Case Serum aldosterone (ng/dl) PRA (ng/ml/hr) ARR Potassium (meq/l) Interpretation Stop, not PA Probably PA, go to confirmatory testing Probably PA, go to confirmatory testing Probably PA, stop diuretic and rescreen Forget the aldo/renin ratio (ARR)! Auchus R. 2011; Rev Endocr Metab Disord
14 Screening results in our patient Date Serum K Oral KCl meq daily Aldosterone ng/dl PRA ng/ml/hr 4/15/ PRA suppressed AND Aldosterone elevated, but only when serum K is replete Proceed to confirmatory testing Hypertension Center
15 Step 1: Suspect Step 2: Screen Step 3: Suppress Step 4: Site? Step 5: Surgery?
16 Can you suppress Aldo? Oral Salt Suppression Test 1 tablespoon salt daily X 3 days >250 meq Na + per 24 hour urine = adequate salt load >12 ng aldosterone per 24 hour urine = positive test Auchus R. 2011; Rev Endocr Metab Disord
17 Optimal conditions for suppression testing Control HTN with non-interfering medications CCB (amlodipine) Central sympatholytics (guanfacine) Alpha blocker (doxazosin) Keep K > 4.0 K is an aldo secretagogue Hypertension Center Auchus R. 2011; Rev Endocr Metab Disord
18 Oral salt loading test in this patient Date Serum K Urine Na (mmol/24h) Urine aldo (mcg/24h) 1/30/ Adequate salt load > 250 Non-suppressible hyperaldo (+) test Hypertension Center
19 Step 1: Suspect Step 2: Screen Step 3: Suppress Step 4: Site? Step 5: Surgery?
20 SITE Localization Surgical candidates only Requires adrenal vein sampling (AVS) CT abdomen (adrenal venogram) Exclude adrenocortical carcinoma Adrenal vein anatomy Exceptions Unacceptable surgical risk Suspected adrenocortical carcinoma Proven FH-I or with FH-III. Suspected subclinical Cushings Hypertension Center
21 AVS anatomy Casemebasi A,. Clinical Anatomy 27: (2014)
22 CT cannot localize aldo! CT correct CT wrong! Young WF, Young et WF. al. Surgery 2004;136:
23 Interpretation of AVS Cosyntropin infusion during AVS to stimulate cortisol secretion Confirm the catheter is in the adrenal vein [Cortisol] adrenal vein : [Cortisol) IVC ratio > 3:1 Lateralization Aldo/cortisol ratio one side : Aldo/cortisol ratio other side > 4:1 Funder JW, Young WF. J Clin Endocrinol Metab 93: , 2008 Rossi GP. Hypertension. Expert Consensus Statement on Use of Adrenal Vein Sampling for the Subtyping Of Primary Aldosteronism. 2014;63:
24 Patient s CT scan: no adenoma seen Right Left
25 Patient s adrenal vein sampling Vein Aldosterone Cortisol A:C ratio Aldosterone ratio (Dominant A:C 2 Nondominant A:C) 1 > 3: 1 R adrenal vein L adrenal vein IVC > 4: 1 = Right APA
26 Step 1: Suspect Step 2: Screen Step 3: Suppress Step 4: Site? Step 5: Surgery? Courtesy of Dr. Ron Victor
27 Why treat Aldo? Anxiety, depression OSA LVH Cardiac fibrosis Atrial fibrillation Coronary disease Stroke VT/SCD Hypokalemia Diabetes Metabolic syndrome Ox stress Endothelial dysfunct. Fibrosis Remodeling Hyperparathyroidism CKD Renal fibrosis
28 Surgery or Medicine? Laparoscopic adrenalectomy Surgical candidates Documented unilateral APA or hyperplasia BP and K improve 30-60% cure for HTN younger patients No family history of HTN Few postop complications 5-7% morbidity <1% mortality Mineralocorticoid antagonist Nonsurgical candidates: bilateral disease patient preference Spironolactone Reduces BP by 25% Side effects Eplerenone Selective MR antagonist Less side effects Amilioride/triamterene Na channel antagonist in distal tubule Some benefit, no endothelial effects Funder JW, Young WF. J Clin Endocrinol Metab 93: , 2008
29 Rossi GP. Hypertension. 2013;62:62-69 Surgery or Meds?
30 Case: After adrenalectomy 6 mm right adenoma Diltiazem, amlodipine, telmisartan therapy Aldosterone: PRA: 0.67
31 Diagnosing primary aldosteronism: barriers dissolved! Too many drugs interfere with tests ok to screen on drugs Dangers of interfering BP med washout short term only with confirmatory stage Hard to interpret results ARR? PRA? PAC? PRA < 1 AND aldo 15 Kline GA. Clinical Endocrinology (2015) 82,
32 Diagnosing primary aldosteronism: barriers dissolved! Adrenal venous sampling is hard and risky surgical patients at experienced center Can t we just treat with eplerenone? Surgery cures hypokalemia and improves or cures hypertension. Kline GA. Clinical Endocrinology (2015) 82,
33 Team approach is vital! Rader Hypertension Center Team Aldo Cooper Victor Friedman Phillips An ASH Comprehensive Hypertension Center
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