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Primary Aldosteronism: an update on the management Dr Man Chi Mei Vivian Queen Mary Hospital.

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Presentation on theme: "Primary Aldosteronism: an update on the management Dr Man Chi Mei Vivian Queen Mary Hospital."— Presentation transcript:

1 Primary Aldosteronism: an update on the management Dr Man Chi Mei Vivian Queen Mary Hospital

2 Content Background information Diagnostic algorithms Localization and subtype differentiation Management

3 Case Scenario 60/M, good past health Blood test confirmed primary aldosteronism 7mm left adrenal nodule17mm right adrenal nodule

4 What should be the management? Adrenalectomy –Right adrenalectomy? –Left adrenalectomy? –Bilateral adrenalectomy? Medical therapy with aldosterone receptor antagonist

5 Background First described in 1954 Group of disorders in which aldosterone production is inappropriately high, relatively autonomous, and non- suppressible by sodium loading 1 Estimated prevalence of 11.2% in hypertensives 2 Hypokalemia not always present –52% aldosterone-producing adenoma –83.1% bilateral adrenal hyperplasia Jerome W. Conn ( ) 1 J Clin Endocrinol Metab 93: , Rossi et al. JACC vol. 48, No :

6 Types of Primary Aldosteronism TypesApproximate prevalence % Aldosterone-producing adenoma30 Bilateral idiopathic hyperaldosteronism65 Primary adrenal hyperplasia<2 Aldosterone-producing adrenocortical carcinoma 1 Aldosterone-producing ovarian tumor<1 Familial hyperaldosteronism<2 Role for adrenal venous sampling in primary aldosteronism. Young WF et al. Surgery. December 2004.

7 Diagnosis of primary aldosteronism Screening –Aldosterone/ renin ratio (ARR) –Plasma aldosterone concentration (PAC) –Elevated ARR >20ng/dl per ng/ml/h and PAC >10ng/dL Confirmation –Intravenous saline load/ oral salt load –Captopril challenge test –Fludro-cortisone suppression test

8 Lateralization and subtype differentiation Computed tomography (CT) Adrenal scintigraphy Adrenal venous sampling (AVS)

9 Computed tomography Young WF et al. The incidentally discovered adrenal mass. New England Journal of Medicine 2007; 356:

10 Adrenocortical adenoma Adrenocortical carcinoma Young WF et al. The incidentally discovered adrenal mass. New England Journal of Medicine 2007; 356:

11 Lateralization and subtype differentiation Computed tomography (CT) Adrenal scintigraphy Adrenal vein sampling (AVS)

12 Adrenal Scintigraphy Provides functional information 131I-6β-iodomethyl-19-norcholesterol (NP-59) Marker of adreno-cortical uptake Huang YE et al. Role of 131I-NP-59 Adrenal Imaging in Patients of ACTH-Independent Cushing’s Syndrome. Ann Nucl Med Sci 2001;14:75-83

13 Chen YC et al. Use of NP-59 SPECT/ CT imaging in atypical primary aldosteronism. Q J Med (2013)

14 Lateralization and subtype differentiation Computed tomography (CT) Adrenal scintigraphy Adrenal venous sampling (AVS)

15 Adrenal vein sampling First proposed in 1967 as a test to distinguish between aldosterone-producing adenoma and idiopathic hyperaldosteronism Gold standard for lateralization of disease Femoral venous access Simultaneously left and right adrenal venous sampling Blood aldosterone and cortisol level Kahn SL et al. Adrenal vein sampling. Techniques in vascular and interventional radiology 13:

16 Interpretation Confirmation of correct position of adrenal catheters: –Cortisol level from adrenal catheters being 5-10 times the value obtained from peripheral sheath Asymmetrical aldosterone: cortisol values on the affected side being 3-5 times the value obtained from the unaffected side Kahn SL et al. Adrenal vein sampling. Techniques in vascular and interventional radiology 13:

17 Right adrenal vein catheterizationLeft adrenal vein catheterization Kahn SL et al. Adrenal vein sampling. Techniques in vascular and interventional radiology 13: Lau JHG et al. Clinical Endocrinology (2010) 76;

18 Diagnostic values and accuracy 203 patients were selected for AVS from patients underwent successful adrenal vein cannulation –Success rate 95.6% Computed tomography, AVS and histopathological findings were compared Young WF et al. Role of adrenal venous sampling in primary aldosteronism. Surgery 2004; 136:

19 Discordant between CT and AVS 110 patients (56.7%) had unilateral source for aldosterone hyper-secretion Young WF et al. Role of adrenal venous sampling in primary aldosteronism. Surgery 2004; 136: Normal CT scan24 Bilateral micronodule16 Bilateral macronodule2 Unilateral micronodule7/31 contralateral gland Unilateral macronodule1/22 contralateral gland Combination of micronodule and macronodule 11/18 macronodule 4/18 micronodule

20 Discordant between CT and AVS 21.7% (42 patients) would have been incorrectly excluded as candidates for adrenalectomy 24.7% (48 patients) might have unnecessary or inappropriate adrenalectomy Young WF et al. Role of adrenal venous sampling in primary aldosteronism. Surgery 2004; 136:

21 Discordant between CT/MRI and AVS Systematic review of 38 studies, 950 patients included –37.8% discordance between CT/MRI and AVS –14.6% inappropriate adrenalectomy –19.1% inappropriate exclusion from adrenalectomy –3.9% adrenalectomy on wrong side Kempers MJE et al. Systematic Review: Diagnostic Procedures to Differentiate Unilateral From Bilateral Adrenal Abnormality in Primary Aldosteronism. Annals of Internal Medicine, 09/2009, Volume 151, Issue 5, pp

22 Computed tomography Adrenal venous sampling NP-59 adrenal scintigraphy Easily availableTechnically demanding expertise required Requirement of radio- labeled material 3-5 day test Non-invasiveInvasive complication rate ~2.5% 3 Non-invasive Good resolutionLimited spatial resolution Improved with NP-59 SPECT/CT Sensitivity 77% 1 Specificity 80% 1 Accuracy improved if discrete unilateral macronodule Sensitivity 95% 4 Specificity 100% 4 Planar scintigraphy sensitivity as low as 40% 2 Sensitivity increased to 81.8% when combined with CT 2 1.Lau JHG et al. Clinical Endocrinology (2010) 76; Yen RF et al. The Journal of Nuclear Medicine (2009) 50; 10: Young WF et al. Surgery (2004) 136; 6; Tsai YS et al. Formos J Endocrin Metab 2011; 2(2): 38-43

23 Kahn SL et al. Adrenal vein sampling. Techniques in vascular and interventional radiology 13:

24 Management Bilateral idiopathic hyperaldosteronism –Medical treatment: aldosterone receptor antagonist –Intolerance/ refractory cases: bilateral adrenalectomy Aldosterone producing adenoma Primary adrenal hyperplasia –Adrenalectomy (laparoscopic/ open) Emerging therapies: –Acetic acid injection –Radiofrequency ablation Moo TA et al. Prediction of Successful Outcome in Patients with Primary Aldosteronism. Current treatment options in oncology (2007) 8:

25 Back to our patient Adrenal to peripheral cortisol level: –Right side: 3.6 versus left side: 3.2 Lateralization index 7.4 –Right side: 42 versus left side: 5.7 Right adrenalectomy performed and Conn’s adenoma confirmed Improvement in ARR one month after operation

26 Conclusion Primary aldosteronism is frequently under- diagnosed in hypertensives Aldosterone producing adenoma and bilateral idiopathic hyperaldosteronism are two commonest causes of primary aldosteronism Lateralization is important for identification of surgically-amendable causes

27 Reference Galati SJ et al. Primary aldosteronism: emerging trends. Trends in Endocrinology and Metabolism. September 2013, Vol.24, No. 9 Role for adrenal venous sampling in primary aldosteronism. Young WF et al. Surgery. December Schwatz et al. Screening for primary aldosteronism in essential hypertension: Diagnostic accuracy of the ratio of plasma aldosterone concentration to plasma renin activity. Clinical Chemistry. 51: Young WF et al. The incidentally discovered adrenal mass. New England Journal of Medicine 2007; 356: Kahn SL et al. Adrenal vein sampling. Techniques in vascular and interventional radiology 13: Huang YE et al. Role of 131I-NP-59 Adrenal Imaging in Patients of ACTH-Independent Cushing’s Syndrome. Ann Nucl Med Sci 2001;14:75-83 Chen YC et al. Use of NP-59 SPECT/ CT imaging in atypical primary aldosteronism. Q J Med (2013)

28 Rossi GP et al. A Prospective Study of the Prevalence of Primary Aldosteronism in 1125 Hypertensive Patients. JACC vol 48, No 11, 2006 Moo TA et al. Prediction of Successful Outcome in Patients with Primary Aldosteronism. Current treatment options in oncology (2007) 8: Stowasser M et al. Update in Primary aldosteronism. J Clin Endocrinol Metab (2009) 94: Liu SYW et al. Radiofrequency ablation for benign aldosterone-producing adenoma: a scarless technique to an old disease. Annals of Surgery 256(6): Kempers MJE et al. Systematic Review: Diagnostic Procedures to Differentiate Unilateral From Bilateral Adrenal Abnormality in Primary Aldosteronism. Annals of Internal Medicine, 09/2009, Volume 151, Issue 5, pp American Association of Clinical Endocrinologists and American Association of Endocrine Surgeons Medical Guidelines for the Management of Adrenal Incidentalomas The Endocrine Society’s Clinical Guidelines. J Clin Endocrinol Metab 93: , 2008

29 Thank you Questions?

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31 Who should be screened? Moderate to severe hypertension Resistant hypertension Hypertension with a family history of early-onset disease Hypertension with an adrenal incidentaloma History of cerebrovascular accident occurring before age 40 years First-degree relative with primary aldosteronism Galati SJ et al. Primary aldosteronism: emerging trends. Trends in Endocrinology and Metabolism. September 2013, Vol.24, No. 9

32 Sequelae of primary aldosteronism Galati SJ et al. Primary aldosteronism: emerging trends. Trends in Endocrinology and Metabolism. September 2013, Vol.24, No. 9

33 ProtocolInterpretation Intravenous saline load Infusion of 2L of 0.9% normal saline over 2 hours In recumbent position PAC > 10ng/dL post-infusion is highly suggestive of PA Oral salt loadSodium intake >6g/day for 3 days with diet and sodium chloride tabs 24 hour urinary aldosterone excretion >12μg/day consistent with PA Captopril challenge test 25-50mg oral captopril after sitting or standing for 1 hour ARR >30-50 PAC remained elevated (>8.5ng/dL or greater) Renin remained suppressed Fludro-cortisone suppression test 0.1mg of fludro-cortisone every 6 hours for 4 days PAC > 6 ng/dL confirms PA Renin suppressed to <1ng/mL/h Cortisol measured 10am lower than measured 7-8am Galati SJ et al. Primary aldosteronism: emerging trends. Trends in Endocrinology and Metabolism. September 2013, Vol.24, No. 9

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35 Drug therapyDrug free Optimum ratio 95%CI12.4 (7.1 – 16.6)14.9 (14.2 – 20.9) Sensitivity 95%CI7387 Specificity 95%CI7475 Schwatz et al. Screening for primary aldosteronism in essential hypertension: Diagnostic accuracy of the ratio of plasma aldosterone concentration to plasma renin activity. Clinical Chemistry. 51:


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