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
17mm right adrenal nodule
7mm left 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 loading1
Estimated prevalence of 11.2% in hypertensives2
Hypokalemia not always present
52% aldosterone-producing adenoma
83.1% bilateral adrenal hyperplasia
Jerome W. Conn ( )
Dr Jerome W. Conn: American endocrinologist
Presented his index patient in the Clinical research meeting in 1954
1 J Clin Endocrinol Metab 93: , 2008
2 Rossi et al. JACC vol. 48, No :

6. Types of Primary Aldosteronism
Approximate prevalence %
Aldosterone-producing adenoma 30
Bilateral idiopathic hyperaldosteronism 65
Primary adrenal hyperplasia
<2
Aldosterone-producing adrenocortical carcinoma 1
Aldosterone-producing ovarian tumor
<1
Familial hyperaldosteronism
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
Screening test
SI unit pmol/L x 27.7, pmol/L/min x 12.8 = 550pmol/L per ng/ml/h
No standard cutoff value
Higher cut-off results in higher false negative values
can be influenced by most antihypertensive drug therapy
Diagnostic test
Collaboration with endocrinologists
No consensus on the optimal 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 carcinoma Adrenocortical adenoma
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
Resolution problem
Previous study suggested that the detection rate was related to adenoma size. It failed to detect adenoma size <1cm
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. Left adrenal vein catheterization
Right 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
194 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
Normal CT scan 24
Bilateral micronodule 16
Bilateral macronodule 2
Unilateral micronodule
7/31 contralateral gland
Unilateral macronodule
1/22 contralateral gland
Combination of micronodule and macronodule
11/18 macronodule
4/18 micronodule
Young WF et al. Role of adrenal venous sampling in primary aldosteronism. Surgery 2004; 136:

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. Adrenal venous sampling NP-59 adrenal scintigraphy
Computed tomography
Adrenal venous sampling
NP-59 adrenal scintigraphy
Easily available
Technically demanding
expertise required
Requirement of radio-labeled material
3-5 day test
Non-invasive
Invasive
complication rate ~2.5%3
Good resolution
Limited 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 CT2
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
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 2004.
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?

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. Protocol Interpretation 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 load
Sodium 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

35. Drug therapy Drug free Optimum ratio 95%CI 12.4 (7.1 – 16.6)
14.9 (14.2 – 20.9)
Sensitivity 95%CI 73 87
Specificity 95%CI 74 75
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: