Primary hyperaldosteronism laboratory findings
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]
Overview
Experts recommend varying diagnostic criteria. For example:
- * plasma aldosterone to renin activity ratio (PAC/PRA) >20 with a plasma aldosterone concentration >= 15 ng/dL (414 pmol/L)
- plasma aldosterone to renin activity ratio (PAC/PRA) > 30, serum aldosterone value >6 ng/dl, and simultaneous plasma renin activity levels <1.0 ng/ml/hour after fludrocortisone suppression test or a plasma aldosterone >10 ng/dl on saline infusion test or on oral sodium loading test, the post-test 24-hour urinary aldosterone excretion <12 μg/day and a urinary sodium excretion of more than 200 mMol/day. The adrenal venous sampling test is gold standard for subtype classification of primary hyperaldosteronism.
Laboratory Findings
Plasma Aldosterone to Renin Ratio (PAC/PRA)
Protocol
- Drugs that affect the renin–angiotensin-aldosterone axis should be stopped before testing, such as beta-blockers, ACE inhibitors, ARBs (angiotensin receptor blockers), renin inhibitors, dihydropyridine calcium channel blockers, and central alpha2-agonists, for about fourteen days; and spironolactone, eplerenone, amiloride, and triamterene, and loop diuretics for about twenty eight days.
- The test should be conducted between 8 AM and 10 AM. The patient is advised to stay upright for 2 hours prior to testing, and then sit for about 10 minutes before testing.[1]
Interpretation
- Primary hyperaldosteronism (Conn's syndrome) is associated with an increased aldosterone levels (PAC) in plasma along with suppressed renin concentration (PRA) due to feedback inhibition of aldosterone on renin levels in the plasma.
- A PAC/PRA ratio >30 is a strong evidence of primary hyperaldosteronism and value >50 is considered diagnostic in the presence of resistant hypertension, hypokalemia, and metabolic alkalosis.[2][3][4][5][6][7][8]
Confirmatory Tests
After preliminary testing for primary hyperaldosteronism via PAC/PRA ratio, any one of the following tests may be performed in order to confirm the diagnosis:
1. Fludrocortisone suppression test (FST)
- This is the gold standard test for confirmation of primary hyperaldosteronism.[9][10][11]
- Patient is given a synthetic mineralocorticoid (9-alpha-fludrocortisone acetate 0.1 mg every six hours) and sodium chloride (slow-release sodium 30 mmol (1.75 g) three times daily).
- Plasma aldosterone level is measured in the morning after four days of administration.
- A value of >6 ng/dl and simultaneous PRA levels <1.0 ng/ml/hour, confirm primary hyperaldosteronism.
2. Intravenous saline load test (SLT)
- Patient is infused with two liters of NaCl 0.9% for fours hours.
- Plasma aldosterone more than 10 ng/dl is confirmatory, normally aldosterone would be suppressed to below 5 ng/dl.
3. Oral sodium loading test
- This test has a sensitivity and specificity of >90%
- Patient is fed a high sodium diet, of approximately 218 mMol/day, for three days.
- On the third day, a 24-hour urine sample is collected.
- Normal suppression is defined as post-test 24-hour urinary aldosterone excretion less than 12 μg/day and a urinary sodium excretion of more than 200 mMol/day.[12][13]
4. Captopril challenge test
- Positive test for primary hyperaldosteronism is defined as a PAC/PRA >30, measured two hours after the administration of 25 mg or 50 mg of captopril with patients in the sitting position.[14]
- Reserved for patients with reduced cardiac or renal function.
Less Common Tests
- Upright posture test
- 24-hour urinary aldosterone
- Losartan test
Subtype Classification
Once the diagnosis of primary hyperaldosteronism is confirmed, a subtype classification is required as the management may vary based on the etiology.
Tests useful in assessing subtypes are:
1. Adrenal venous sampling (AVS)
- Gold standard test for subtype classification.[15]
- It has a high sensitivity (95%) and specificity (100%) for the detection of unilateral aldosterone tumor but is highly expertise dependent.[16]
- AVS can be performed using any of the three protocols:
- (a) Unstimulated sequential or simultaneous bilateral AVS
- (b) Unstimulated sequential or simultaneous bilateral AVS followed by bolus cosyntropin-stimulated sequential or simultaneous bilateral AVS
- (c) Continuous cosyntropin infusion with sequential bilateral AVS.
- Plasma aldosterone collected from the adrenal veins is corrected to its respective plasma cortisol, measured as a ratio (PAC / cortisol ratio)
- A gradient of >4:1, points towards unilateral aldosterone secreting adenoma and <3:1 suggests bilateral adrenal hyperplasia.
2. Posture stimulation test
- May be used when AVS is equivocal.[17]
- It is based on the principle that PAC in patients with aldosterone producing adenoma (APA) there is a diurnal variation and is relatively unchanged by changes in the angiotensin II levels being under ACTH control, whereas, bilateral adrenal hyperplasia (IHA) is affected heavily by a small change in the angiotensin II, due to standing.
3. 18-Hydroxycorticosterone levels
- Less accurate than other tests.
- Hydroxylation of corticosterone leads to the formation of 18-hydroxycorticosterone.
- Historically, it was used to differentiate APA from bilateral adrenal hyperplasia.
- Supine plasma 18-hydroxycorticosterone levels > 100 ng/dl at 8 a.m. suggest aldosterone producing adenoma (APA).[18]
References
- ↑ Stowasser M, Gordon RD, Rutherford JC, Nikwan NZ, Daunt N, Slater GJ (2001). "Diagnosis and management of primary aldosteronism". J Renin Angiotensin Aldosterone Syst. 2 (3): 156–69. doi:10.3317/jraas.2001.022. PMID 11881117.
- ↑ "The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline: The Journal of Clinical Endocrinology & Metabolism: Vol 101, No 5".
- ↑ Horsley MG, Bailie GR (1988). "Effectiveness of theophylline monitoring by the use of serum assays". J Clin Pharm Ther. 13 (5): 359–64. PMID 3230101.
- ↑ Ríos MC, Izquierdo A, Sotelo M, Honnorat E, Rodríguez Cuimbra S, Catay E, Popescu BM (2011). "[Aldosterone/renin ratio in the diagnosis of primary aldosteronism]". Medicina (B Aires) (in Spanish; Castilian). 71 (6): 525–30. PMID 22167725.
- ↑ Pilz S, Kienreich K, Gaksch M, Grübler M, Verheyen N, Bersuch LA, Schmid J, Drechsler C, Ritz E, Moosbrugger A, Stepan V, Pieber TR, Meinitzer A, März W, Tomaschitz A (2014). "Aldosterone to active Renin ratio as screening test for primary aldosteronism: reproducibility and influence of orthostasis and salt loading". Horm. Metab. Res. 46 (6): 427–32. doi:10.1055/s-0034-1367033. PMID 24526370.
- ↑ "The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline: The Journal of Clinical Endocrinology & Metabolism: Vol 101, No 5".
- ↑ Doi SA, Abalkhail S, Al-Qudhaiby MM, Al-Humood K, Hafez MF, Al-Shoumer KA (2006). "Optimal use and interpretation of the aldosterone renin ratio to detect aldosterone excess in hypertension". J Hum Hypertens. 20 (7): 482–9. doi:10.1038/sj.jhh.1002024. PMID 16617310.
- ↑ Pilz S, Kienreich K, Gaksch M, Grübler M, Verheyen N, Bersuch LA, Schmid J, Drechsler C, Ritz E, Moosbrugger A, Stepan V, Pieber TR, Meinitzer A, März W, Tomaschitz A (2014). "Aldosterone to active Renin ratio as screening test for primary aldosteronism: reproducibility and influence of orthostasis and salt loading". Horm. Metab. Res. 46 (6): 427–32. doi:10.1055/s-0034-1367033. PMID 24526370.
- ↑ Djajadiningrat-Laanen SC, Galac, Boevé MH, Boroffka SA, Naan EC, IJzer J, Kooistra HS (2013). "Evaluation of the oral fludrocortisone suppression test for diagnosing primary hyperaldosteronism in cats". J. Vet. Intern. Med. 27 (6): 1493–9. PMID 24627898.
- ↑ Willenberg HS, Vonend O, Schott M, Gao X, Blondin D, Saleh A, Rump LC, Scherbaum WA (2012). "Comparison of the saline infusion test and the fludrocortisone suppression test for the diagnosis of primary aldosteronism". Horm. Metab. Res. 44 (7): 527–32. doi:10.1055/s-0032-1314786. PMID 22689209.
- ↑ Lund JO, Nielsen MD (1980). "Fludrocortisone suppression test in normal subjects, in patients with essential hypertension and in patients with various forms of aldosteronism". Acta Endocrinol. 93 (1): 100–7. PMID 6986736.
- ↑ Weigel M, Riester A, Hanslik G, Lang K, Willenberg HS, Endres S, Allolio B, Beuschlein F, Reincke M, Quinkler M (2015). "Post-saline infusion test aldosterone levels indicate severity and outcome in primary aldosteronism". Eur. J. Endocrinol. 172 (4): 443–50. doi:10.1530/EJE-14-1013. PMID 25630564.
- ↑ Nanba K, Tsuiki M, Umakoshi H, Nanba A, Hirokawa Y, Usui T, Tagami T, Shimatsu A, Suzuki T, Tanabe A, Naruse M (2015). "Shortened saline infusion test for subtype prediction in primary aldosteronism". Endocrine. 50 (3): 802–6. doi:10.1007/s12020-015-0615-9. PMID 25931414.
- ↑ Kuo CC, Balakrishnan P, Hsein YC, Wu VC, Chueh SC, Chen YM, Wu KD, Wang MJ (2015). "The value of losartan suppression test in the confirmatory diagnosis of primary aldosteronism in patients over 50 years old". J Renin Angiotensin Aldosterone Syst. 16 (3): 587–98. doi:10.1177/1470320313498632. PMC 4297265. PMID 25031295.
- ↑ Deipolyi AR, Bailin A, Wicky S, Alansari S, Oklu R (2015). "Adrenal Vein Sampling for Conn's Syndrome: Diagnosis and Clinical Outcomes". Diagnostics (Basel). 5 (2): 254–71. doi:10.3390/diagnostics5020254. PMC 4665593. PMID 26854152.
- ↑ Rossi GP, Auchus RJ, Brown M, Lenders JW, Naruse M, Plouin PF, Satoh F, Young WF (2014). "An expert consensus statement on use of adrenal vein sampling for the subtyping of primary aldosteronism". Hypertension. 63 (1): 151–60. doi:10.1161/HYPERTENSIONAHA.113.02097. PMID 24218436.
- ↑ Feltynowski T, Ignatowska-Switalska H, Wocial B, Lewandowski J, Chodakowska J, Januszewicz W (1994). "Postural stimulation test in patients with aldosterone producing adenomas". Clin. Endocrinol. (Oxf). 41 (3): 309–14. PMID 7955437.
- ↑ Mulatero P, di Cella SM, Monticone S, Schiavone D, Manzo M, Mengozzi G, Rabbia F, Terzolo M, Gomez-Sanchez EP, Gomez-Sanchez CE, Veglio F (2012). "18-hydroxycorticosterone, 18-hydroxycortisol, and 18-oxocortisol in the diagnosis of primary aldosteronism and its subtypes". J. Clin. Endocrinol. Metab. 97 (3): 881–9. doi:10.1210/jc.2011-2384. PMID 22238407.