Primary hyperaldosteronism laboratory findings: Difference between revisions
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==Overview== | ==Overview== | ||
Laboratory findings consistent with the diagnosis of primary hyperaldosteronism include plasma aldosterone to renin activity ratio (PAC/PRA) of >30<ref name="urlThe 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">{{cite web |url=http://press.endocrine.org/doi/10.1210/jc.2015-4061 |title=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 |format= |work= |accessdate=}}</ref>, serum aldosterone value of > 6 ng / dl and simultaneous | Laboratory findings consistent with the diagnosis of primary hyperaldosteronism include [[Blood plasma|plasma]] [[aldosterone]] to [[renin]] activity ratio (PAC/PRA) of >30<ref name="urlThe 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">{{cite web |url=http://press.endocrine.org/doi/10.1210/jc.2015-4061 |title=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 |format= |work= |accessdate=}}</ref>, serum [[aldosterone]] value of > 6 ng / dl and simultaneous [[Blood plasma|plasma]] [[renin]] activity levels < than 1.0 ng / ml / hour after [[fludrocortisone]] supression test, or a [[Blood plasma|plasma]] [[aldosterone]] more than 10 ng / dl on [[Saline (medicine)|saline]] [[infusion]] test or on [[oral]] [[sodium]] loading test, the post-test 24-hour [[urinary]] [[aldosterone]] excretion less than 12 μg / day and a [[urinary]] [[sodium]] excretion of more than 200 mmol / day. The adrenal venous sampling test is [[Gold standard (test)|gold standard]] for subtype classification of primary hyperaldosteronism. | ||
==Laboratory Findings== | ==Laboratory Findings== | ||
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==== Protocol ==== | ==== 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. | * Drugs that affect the [[Renin angiotensin aldosterone system|renin–angiotensin-aldosterone axis]] should be stopped before testing, such as: [[Beta blockers|beta-blockers]], [[ACE inhibitor|ACE inhibitors]], [[ARBs]] ([[Angiotensin II receptor antagonist|angiotensin receptor blockers]]), [[Renin inhibitor|renin inhibitors]], [[Calcium channel blockers|dihydropyridine calcium channel blockers]], and central [[Alpha2-adrenergic agonists|alpha2-agonists]], for about fourteen days, and [[spironolactone]], [[eplerenone]], [[amiloride]], and [[triamterene]], and [[Loop diuretic|loop diuretics]] for about twenty eight days. | ||
* The test should be conducted between 8 a.m. and 10 a. m. The patient is advised to stay upright for 2 hours prior to testing, and then sit for about 10 minutes before testing.<ref name="pmid11881117">{{cite journal |vauthors=Stowasser M, Gordon RD, Rutherford JC, Nikwan NZ, Daunt N, Slater GJ |title=Diagnosis and management of primary aldosteronism |journal=J Renin Angiotensin Aldosterone Syst |volume=2 |issue=3 |pages=156–69 |year=2001 |pmid=11881117 |doi=10.3317/jraas.2001.022 |url= |issn=}}</ref> | * The test should be conducted between 8 a.m. and 10 a. m. The patient is advised to stay upright for 2 hours prior to testing, and then sit for about 10 minutes before testing.<ref name="pmid11881117">{{cite journal |vauthors=Stowasser M, Gordon RD, Rutherford JC, Nikwan NZ, Daunt N, Slater GJ |title=Diagnosis and management of primary aldosteronism |journal=J Renin Angiotensin Aldosterone Syst |volume=2 |issue=3 |pages=156–69 |year=2001 |pmid=11881117 |doi=10.3317/jraas.2001.022 |url= |issn=}}</ref> | ||
==== Interpretation ==== | ==== 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. | * 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 of >30 is a strong evidence of primary hyperladosteronism and value >50 is considered diagnostic in the presence of resistant hypertension, hypokalemia and metabolic alkalosis.<ref name="urlThe 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">{{cite web |url=http://press.endocrine.org/doi/10.1210/jc.2015-4061 |title=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 |format= |work= |accessdate=}}</ref><ref name="pmid3230101">{{cite journal |vauthors=Horsley MG, Bailie GR |title=Effectiveness of theophylline monitoring by the use of serum assays |journal=J Clin Pharm Ther |volume=13 |issue=5 |pages=359–64 |year=1988 |pmid=3230101 |doi= |url= |issn=}}</ref><ref name="pmid22167725">{{cite journal |vauthors=Ríos MC, Izquierdo A, Sotelo M, Honnorat E, Rodríguez Cuimbra S, Catay E, Popescu BM |title=[Aldosterone/renin ratio in the diagnosis of primary aldosteronism] |language=Spanish; Castilian |journal=Medicina (B Aires) |volume=71 |issue=6 |pages=525–30 |year=2011 |pmid=22167725 |doi= |url= |issn=}}</ref><ref name="pmid24526370">{{cite journal |vauthors=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 |title=Aldosterone to active Renin ratio as screening test for primary aldosteronism: reproducibility and influence of orthostasis and salt loading |journal=Horm. Metab. Res. |volume=46 |issue=6 |pages=427–32 |year=2014 |pmid=24526370 |doi=10.1055/s-0034-1367033 |url= |issn=}}</ref><ref name="urlThe Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline: The Journal of Clinical Endocrinology & Metabolism: Vol 101, No 52">{{cite web |url=http://press.endocrine.org/doi/10.1210/jc.2015-4061 |title=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 |format= |work= |accessdate=}}</ref><ref name="pmid16617310">{{cite journal |vauthors=Doi SA, Abalkhail S, Al-Qudhaiby MM, Al-Humood K, Hafez MF, Al-Shoumer KA |title=Optimal use and interpretation of the aldosterone renin ratio to detect aldosterone excess in hypertension |journal=J Hum Hypertens |volume=20 |issue=7 |pages=482–9 |year=2006 |pmid=16617310 |doi=10.1038/sj.jhh.1002024 |url= |issn=}}</ref><ref name="pmid245263702">{{cite journal |vauthors=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 |title=Aldosterone to active Renin ratio as screening test for primary aldosteronism: reproducibility and influence of orthostasis and salt loading |journal=Horm. Metab. Res. |volume=46 |issue=6 |pages=427–32 |year=2014 |pmid=24526370 |doi=10.1055/s-0034-1367033 |url= |issn=}}</ref> | * A PAC/PRA ratio of >30 is a strong evidence of primary hyperladosteronism and value >50 is considered diagnostic in the presence of resistant [[hypertension]], [[hypokalemia]] and [[metabolic alkalosis]].<ref name="urlThe 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">{{cite web |url=http://press.endocrine.org/doi/10.1210/jc.2015-4061 |title=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 |format= |work= |accessdate=}}</ref><ref name="pmid3230101">{{cite journal |vauthors=Horsley MG, Bailie GR |title=Effectiveness of theophylline monitoring by the use of serum assays |journal=J Clin Pharm Ther |volume=13 |issue=5 |pages=359–64 |year=1988 |pmid=3230101 |doi= |url= |issn=}}</ref><ref name="pmid22167725">{{cite journal |vauthors=Ríos MC, Izquierdo A, Sotelo M, Honnorat E, Rodríguez Cuimbra S, Catay E, Popescu BM |title=[Aldosterone/renin ratio in the diagnosis of primary aldosteronism] |language=Spanish; Castilian |journal=Medicina (B Aires) |volume=71 |issue=6 |pages=525–30 |year=2011 |pmid=22167725 |doi= |url= |issn=}}</ref><ref name="pmid24526370">{{cite journal |vauthors=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 |title=Aldosterone to active Renin ratio as screening test for primary aldosteronism: reproducibility and influence of orthostasis and salt loading |journal=Horm. Metab. Res. |volume=46 |issue=6 |pages=427–32 |year=2014 |pmid=24526370 |doi=10.1055/s-0034-1367033 |url= |issn=}}</ref><ref name="urlThe Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline: The Journal of Clinical Endocrinology & Metabolism: Vol 101, No 52">{{cite web |url=http://press.endocrine.org/doi/10.1210/jc.2015-4061 |title=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 |format= |work= |accessdate=}}</ref><ref name="pmid16617310">{{cite journal |vauthors=Doi SA, Abalkhail S, Al-Qudhaiby MM, Al-Humood K, Hafez MF, Al-Shoumer KA |title=Optimal use and interpretation of the aldosterone renin ratio to detect aldosterone excess in hypertension |journal=J Hum Hypertens |volume=20 |issue=7 |pages=482–9 |year=2006 |pmid=16617310 |doi=10.1038/sj.jhh.1002024 |url= |issn=}}</ref><ref name="pmid245263702">{{cite journal |vauthors=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 |title=Aldosterone to active Renin ratio as screening test for primary aldosteronism: reproducibility and influence of orthostasis and salt loading |journal=Horm. Metab. Res. |volume=46 |issue=6 |pages=427–32 |year=2014 |pmid=24526370 |doi=10.1055/s-0034-1367033 |url= |issn=}}</ref> | ||
=== Confirmatory Tests === | === Confirmatory Tests === | ||
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'''''1. Fludrocortisone suppression test (FST)''''' | '''''1. Fludrocortisone suppression test (FST)''''' | ||
* This is the gold standard test for confirmation of primary hyperaldosteronism.<ref name="pmid24627898">{{cite journal |vauthors=Djajadiningrat-Laanen SC, Galac, Boevé MH, Boroffka SA, Naan EC, IJzer J, Kooistra HS |title=Evaluation of the oral fludrocortisone suppression test for diagnosing primary hyperaldosteronism in cats |journal=J. Vet. Intern. Med. |volume=27 |issue=6 |pages=1493–9 |year=2013 |pmid=24627898 |doi= |url=}}</ref><ref name="pmid22689209">{{cite journal |vauthors=Willenberg HS, Vonend O, Schott M, Gao X, Blondin D, Saleh A, Rump LC, Scherbaum WA |title=Comparison of the saline infusion test and the fludrocortisone suppression test for the diagnosis of primary aldosteronism |journal=Horm. Metab. Res. |volume=44 |issue=7 |pages=527–32 |year=2012 |pmid=22689209 |doi=10.1055/s-0032-1314786 |url=}}</ref><ref name="pmid6986736">{{cite journal |vauthors=Lund JO, Nielsen MD |title=Fludrocortisone suppression test in normal subjects, in patients with essential hypertension and in patients with various forms of aldosteronism |journal=Acta Endocrinol. |volume=93 |issue=1 |pages=100–7 |year=1980 |pmid=6986736 |doi= |url=}}</ref> | * This is the [[Gold standard (test)|gold standard]] test for confirmation of primary hyperaldosteronism.<ref name="pmid24627898">{{cite journal |vauthors=Djajadiningrat-Laanen SC, Galac, Boevé MH, Boroffka SA, Naan EC, IJzer J, Kooistra HS |title=Evaluation of the oral fludrocortisone suppression test for diagnosing primary hyperaldosteronism in cats |journal=J. Vet. Intern. Med. |volume=27 |issue=6 |pages=1493–9 |year=2013 |pmid=24627898 |doi= |url=}}</ref><ref name="pmid22689209">{{cite journal |vauthors=Willenberg HS, Vonend O, Schott M, Gao X, Blondin D, Saleh A, Rump LC, Scherbaum WA |title=Comparison of the saline infusion test and the fludrocortisone suppression test for the diagnosis of primary aldosteronism |journal=Horm. Metab. Res. |volume=44 |issue=7 |pages=527–32 |year=2012 |pmid=22689209 |doi=10.1055/s-0032-1314786 |url=}}</ref><ref name="pmid6986736">{{cite journal |vauthors=Lund JO, Nielsen MD |title=Fludrocortisone suppression test in normal subjects, in patients with essential hypertension and in patients with various forms of aldosteronism |journal=Acta Endocrinol. |volume=93 |issue=1 |pages=100–7 |year=1980 |pmid=6986736 |doi= |url=}}</ref> | ||
* 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]. | * 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 a.m. after four days of administration. | * [[Blood plasma|Plasma]] [[aldosterone]] level is measured in the a.m. after four days of administration. | ||
* A value of > 6 ng / dl and simultaneous PRA levels < than 1.0 ng / ml / hour, confirm primary hyperaldosteronism. | * A value of > 6 ng / dl and simultaneous PRA levels < than 1.0 ng / ml / hour, confirm primary hyperaldosteronism. | ||
'''''2. Intravenous saline load test (SLT)''''' | '''''2. Intravenous saline load test (SLT)''''' | ||
* Patient is infused with two liters of NaCl 0.9% for fours hours. | * Patient is infused with two liters of [[Sodium chloride|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. | * [[Blood plasma|Plasma]] [[aldosterone]] more than 10 ng / dl is confirmatory, normally [[aldosterone]] would be suppressed to below 5 ng / dl. | ||
'''''3. Oral sodium loading test''''' | '''''3. Oral sodium loading test''''' | ||
* This test has a sensitivity and specificity of >90% | * This test has a [[Sensitivity (tests)|sensitivity]] and [[Specificity (tests)|specificity]] of >90% | ||
* Patient is fed a high sodium diet, of approximately 218 mmol / day, for three days. | * 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. | * 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.<ref name="pmid25630564">{{cite journal |vauthors=Weigel M, Riester A, Hanslik G, Lang K, Willenberg HS, Endres S, Allolio B, Beuschlein F, Reincke M, Quinkler M |title=Post-saline infusion test aldosterone levels indicate severity and outcome in primary aldosteronism |journal=Eur. J. Endocrinol. |volume=172 |issue=4 |pages=443–50 |year=2015 |pmid=25630564 |doi=10.1530/EJE-14-1013 |url=}}</ref><ref name="pmid25931414">{{cite journal |vauthors=Nanba K, Tsuiki M, Umakoshi H, Nanba A, Hirokawa Y, Usui T, Tagami T, Shimatsu A, Suzuki T, Tanabe A, Naruse M |title=Shortened saline infusion test for subtype prediction in primary aldosteronism |journal=Endocrine |volume=50 |issue=3 |pages=802–6 |year=2015 |pmid=25931414 |doi=10.1007/s12020-015-0615-9 |url=}}</ref> | * 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.<ref name="pmid25630564">{{cite journal |vauthors=Weigel M, Riester A, Hanslik G, Lang K, Willenberg HS, Endres S, Allolio B, Beuschlein F, Reincke M, Quinkler M |title=Post-saline infusion test aldosterone levels indicate severity and outcome in primary aldosteronism |journal=Eur. J. Endocrinol. |volume=172 |issue=4 |pages=443–50 |year=2015 |pmid=25630564 |doi=10.1530/EJE-14-1013 |url=}}</ref><ref name="pmid25931414">{{cite journal |vauthors=Nanba K, Tsuiki M, Umakoshi H, Nanba A, Hirokawa Y, Usui T, Tagami T, Shimatsu A, Suzuki T, Tanabe A, Naruse M |title=Shortened saline infusion test for subtype prediction in primary aldosteronism |journal=Endocrine |volume=50 |issue=3 |pages=802–6 |year=2015 |pmid=25931414 |doi=10.1007/s12020-015-0615-9 |url=}}</ref> | ||
'''''4. Captopril challenge test''''' | '''''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.<ref name="pmid25031295">{{cite journal |vauthors=Kuo CC, Balakrishnan P, Hsein YC, Wu VC, Chueh SC, Chen YM, Wu KD, Wang MJ |title=The value of losartan suppression test in the confirmatory diagnosis of primary aldosteronism in patients over 50 years old |journal=J Renin Angiotensin Aldosterone Syst |volume=16 |issue=3 |pages=587–98 |year=2015 |pmid=25031295 |pmc=4297265 |doi=10.1177/1470320313498632 |url=}}</ref> | * 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.<ref name="pmid25031295">{{cite journal |vauthors=Kuo CC, Balakrishnan P, Hsein YC, Wu VC, Chueh SC, Chen YM, Wu KD, Wang MJ |title=The value of losartan suppression test in the confirmatory diagnosis of primary aldosteronism in patients over 50 years old |journal=J Renin Angiotensin Aldosterone Syst |volume=16 |issue=3 |pages=587–98 |year=2015 |pmid=25031295 |pmc=4297265 |doi=10.1177/1470320313498632 |url=}}</ref> | ||
* Reserved for patients with reduced cardiac or renal function. | * Reserved for patients with reduced [[cardiac]] or [[renal]] function. | ||
=== Less Common Tests === | === Less Common Tests === | ||
* | * Upright posture test | ||
* 24-hour urinary aldosterone | * 24-hour urinary aldosterone | ||
* Losartan test | * [[Losartan]] test | ||
=== '''Subtype Classification''' === | === '''Subtype Classification''' === | ||
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'''''1. Computed Tomography (CT)''''' | '''''1. Computed Tomography (CT)''''' | ||
* A high-resolution CT (HRCT) scan with contrast, has a high sensitivity (78%) and specificity (75%) for detection of adrenal masses (inluding aldosterone producing adenomas-APAs) | * A [[high-resolution CT]] (HRCT) scan with contrast, has a high [[Sensitivity (tests)|sensitivity]] (78%) and [[Specificity (tests)|specificity]] (75%) for detection of adrenal masses (inluding [[aldosterone]] producing adenomas-APAs) | ||
* CT scan is best when used for adrenal adenomas > 2cm but accuracy decreases if the mass is < 1cm. | * [[Computed tomography|CT scan]] is best when used for [[Adrenal adenoma|adrenal adenomas]] > 2cm but accuracy decreases if the mass is < 1cm. | ||
* A unilateral lesion exceeding 4 cm suggests possible carcinoma | * A unilateral lesion exceeding 4 cm suggests possible [[carcinoma]] | ||
* Moreover, it cannot distinguish between a functional APA and a non-secreting adrenal adenoma (incidentaloma). | * Moreover, it cannot distinguish between a functional APA and a non-secreting [[adrenal adenoma]] ([[incidentaloma]]). | ||
'''''2. Magnetic Resonance Imaging (MRI)''''' | '''''2. Magnetic Resonance Imaging (MRI)''''' | ||
* Sensitivity of 70 to 100% in detecting APA, depending on the size of the lesion, being greatest for lesions > 2 cm. | * [[Sensitivity (tests)|Sensitivity]] of 70 to 100% in detecting APA, depending on the size of the lesion, being greatest for lesions > 2 cm. | ||
* Limitations are similar to that of CT scan. | * Limitations are similar to that of [[Computed tomography|CT scan]]. | ||
'''''3. Adrenal venous sampling (AVS)''''' | '''''3. Adrenal venous sampling (AVS)''''' | ||
* Gold standard test for subtype classification.<ref name="pmid26854152">{{cite journal |vauthors=Deipolyi AR, Bailin A, Wicky S, Alansari S, Oklu R |title=Adrenal Vein Sampling for Conn's Syndrome: Diagnosis and Clinical Outcomes |journal=Diagnostics (Basel) |volume=5 |issue=2 |pages=254–71 |year=2015 |pmid=26854152 |pmc=4665593 |doi=10.3390/diagnostics5020254 |url=}}</ref> | * Gold standard test for subtype classification.<ref name="pmid26854152">{{cite journal |vauthors=Deipolyi AR, Bailin A, Wicky S, Alansari S, Oklu R |title=Adrenal Vein Sampling for Conn's Syndrome: Diagnosis and Clinical Outcomes |journal=Diagnostics (Basel) |volume=5 |issue=2 |pages=254–71 |year=2015 |pmid=26854152 |pmc=4665593 |doi=10.3390/diagnostics5020254 |url=}}</ref> | ||
* It has a high sensitivity (95%) and specificity (100%) for the detection of unilateral aldosterone excess but is highly expertise dependent.<ref name="pmid24218436">{{cite journal |vauthors=Rossi GP, Auchus RJ, Brown M, Lenders JW, Naruse M, Plouin PF, Satoh F, Young WF |title=An expert consensus statement on use of adrenal vein sampling for the subtyping of primary aldosteronism |journal=Hypertension |volume=63 |issue=1 |pages=151–60 |year=2014 |pmid=24218436 |doi=10.1161/HYPERTENSIONAHA.113.02097 |url=}}</ref> | * It has a high [[Sensitivity (tests)|sensitivity]] (95%) and [[Specificity (tests)|specificity]] (100%) for the detection of unilateral [[aldosterone]] excess but is highly expertise dependent.<ref name="pmid24218436">{{cite journal |vauthors=Rossi GP, Auchus RJ, Brown M, Lenders JW, Naruse M, Plouin PF, Satoh F, Young WF |title=An expert consensus statement on use of adrenal vein sampling for the subtyping of primary aldosteronism |journal=Hypertension |volume=63 |issue=1 |pages=151–60 |year=2014 |pmid=24218436 |doi=10.1161/HYPERTENSIONAHA.113.02097 |url=}}</ref> | ||
* AVS can be performed using any of the three protocols: | * AVS can be performed using any of the three protocols: | ||
** (a) Unstimulated sequential or simultaneous bilateral AVS | ** (a) Unstimulated sequential or simultaneous bilateral AVS | ||
** (b) Unstimulated sequential or simultaneous bilateral AVS followed by bolus cosyntropin-stimulated 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. | ** (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) | * [[Blood plasma|Plasma]] [[aldosterone]] collected from the adrenal [[veins]] is corrected to its respective [[Cortisol level|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. | * A gradient of > 4:1, points towards unilateral [[aldosterone]] secreting [[adenoma]] and < 3 : 1 suggests bilateral [[Adrenal gland|adrenal]] [[hyperplasia]]. | ||
'''''4. Posture stimulation test''''' | '''''4. Posture stimulation test''''' | ||
* May be used when AVS is equivocal.<ref name="pmid7955437">{{cite journal |vauthors=Feltynowski T, Ignatowska-Switalska H, Wocial B, Lewandowski J, Chodakowska J, Januszewicz W |title=Postural stimulation test in patients with aldosterone producing adenomas |journal=Clin. Endocrinol. (Oxf) |volume=41 |issue=3 |pages=309–14 |year=1994 |pmid=7955437 |doi= |url=}}</ref> | * May be used when AVS is equivocal.<ref name="pmid7955437">{{cite journal |vauthors=Feltynowski T, Ignatowska-Switalska H, Wocial B, Lewandowski J, Chodakowska J, Januszewicz W |title=Postural stimulation test in patients with aldosterone producing adenomas |journal=Clin. Endocrinol. (Oxf) |volume=41 |issue=3 |pages=309–14 |year=1994 |pmid=7955437 |doi= |url=}}</ref> | ||
* It is based on the principal 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. | * It is based on the principal that PAC in patients with [[aldosterone]] producing [[adenoma]] (APA) there is a [[Diurnal|diurnal variation]] and is relatively unchanged by changes in the [[angiotensin II]] levels being under [[Adrenocorticotropic hormone|ACTH control]], whereas, bilateral [[Adrenal gland|adrenal]] [[hyperplasia]] (IHA) is affected heavily by a small change in the [[angiotensin II]], due to standing. | ||
'''''5. Iodocholesterol scintigraphy (NP-59 scan)''''' | '''''5. Iodocholesterol scintigraphy (NP-59 scan)''''' | ||
* 6 beta- 131I iodomethyl-19-norcholesterol (NP-59), was introduced in 1977 for the diagnosis for primary aldosteronism. | * 6 beta- 131I iodomethyl-19-norcholesterol (NP-59), was introduced in 1977 for the diagnosis for primary aldosteronism. | ||
* The NP-59 scan is performed with dexamethasone suppression. | * The NP-59 scan is performed with [[Dexamethasone suppression test|dexamethasone suppression]]. | ||
* It is not very useful in identifying micro adenomas of the adrenals (<1.5cm).<ref name="pmid24235884">{{cite journal |vauthors=Chen YC, Chiu JS, Wang YF |title=NP-59 SPECT/CT imaging in stage 1 hypertensive and atypical primary aldosteronism: a 5-year retrospective analysis of clinicolaboratory and imaging features |journal=ScientificWorldJournal |volume=2013 |issue= |pages=317934 |year=2013 |pmid=24235884 |pmc=3818974 |doi=10.1155/2013/317934 |url=}}</ref> | * It is not very useful in identifying micro [[adenomas]] of the [[Adrenal gland|adrenals]] (<1.5cm).<ref name="pmid24235884">{{cite journal |vauthors=Chen YC, Chiu JS, Wang YF |title=NP-59 SPECT/CT imaging in stage 1 hypertensive and atypical primary aldosteronism: a 5-year retrospective analysis of clinicolaboratory and imaging features |journal=ScientificWorldJournal |volume=2013 |issue= |pages=317934 |year=2013 |pmid=24235884 |pmc=3818974 |doi=10.1155/2013/317934 |url=}}</ref> | ||
'''''6. 18-Hydroxycorticosterone levels''''' | '''''6. 18-Hydroxycorticosterone levels''''' | ||
* Less accurate than other tests. | * Less accurate than other tests. | ||
* Hydroxylation of corticosterone leads to the formation of 18-hydroxycorticosterone. | * [[Hydroxylation]] of [[corticosterone]] leads to the formation of 18-hydroxycorticosterone. | ||
* Historically, it was used to differentiate APA from bilateral adrenal hyperplasia. | * Historically, it was used to differentiate APA from bilateral [[Adrenal gland|adrenal]] [[hyperplasia]]. | ||
* Supine plasma 18-hydroxycorticosterone levels > 100 ng/dl at 8 a.m., suggest aldosterone producing adenoma (APA).<ref name="pmid22238407">{{cite journal |vauthors=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 |title=18-hydroxycorticosterone, 18-hydroxycortisol, and 18-oxocortisol in the diagnosis of primary aldosteronism and its subtypes |journal=J. Clin. Endocrinol. Metab. |volume=97 |issue=3 |pages=881–9 |year=2012 |pmid=22238407 |doi=10.1210/jc.2011-2384 |url=}}</ref> | * Supine plasma 18-hydroxycorticosterone levels > 100 ng/dl at 8 a.m., suggest [[aldosterone]] producing [[adenoma]] (APA).<ref name="pmid22238407">{{cite journal |vauthors=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 |title=18-hydroxycorticosterone, 18-hydroxycortisol, and 18-oxocortisol in the diagnosis of primary aldosteronism and its subtypes |journal=J. Clin. Endocrinol. Metab. |volume=97 |issue=3 |pages=881–9 |year=2012 |pmid=22238407 |doi=10.1210/jc.2011-2384 |url=}}</ref> | ||
==References== | ==References== | ||
Revision as of 14:24, 24 July 2017
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Primary hyperaldosteronism Microchapters |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Laboratory findings consistent with the diagnosis of primary hyperaldosteronism include plasma aldosterone to renin activity ratio (PAC/PRA) of >30[1], serum aldosterone value of > 6 ng / dl and simultaneous plasma renin activity levels < than 1.0 ng / ml / hour after fludrocortisone supression test, or a plasma aldosterone more than 10 ng / dl on saline infusion test or on oral sodium loading test, the post-test 24-hour urinary aldosterone excretion less than 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 a.m. and 10 a. m. The patient is advised to stay upright for 2 hours prior to testing, and then sit for about 10 minutes before testing.[2]
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 of >30 is a strong evidence of primary hyperladosteronism and value >50 is considered diagnostic in the presence of resistant hypertension, hypokalemia and metabolic alkalosis.[1][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 a.m. after four days of administration.
- A value of > 6 ng / dl and simultaneous PRA levels < than 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. Computed Tomography (CT)
- A high-resolution CT (HRCT) scan with contrast, has a high sensitivity (78%) and specificity (75%) for detection of adrenal masses (inluding aldosterone producing adenomas-APAs)
- CT scan is best when used for adrenal adenomas > 2cm but accuracy decreases if the mass is < 1cm.
- A unilateral lesion exceeding 4 cm suggests possible carcinoma
- Moreover, it cannot distinguish between a functional APA and a non-secreting adrenal adenoma (incidentaloma).
2. Magnetic Resonance Imaging (MRI)
- Sensitivity of 70 to 100% in detecting APA, depending on the size of the lesion, being greatest for lesions > 2 cm.
- Limitations are similar to that of CT scan.
3. 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 excess 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.
4. Posture stimulation test
- May be used when AVS is equivocal.[17]
- It is based on the principal 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.
5. Iodocholesterol scintigraphy (NP-59 scan)
- 6 beta- 131I iodomethyl-19-norcholesterol (NP-59), was introduced in 1977 for the diagnosis for primary aldosteronism.
- The NP-59 scan is performed with dexamethasone suppression.
- It is not very useful in identifying micro adenomas of the adrenals (<1.5cm).[18]
6. 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).[19]
References
- ↑ 1.0 1.1 "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".
- ↑ 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.
- ↑ 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.
- ↑ Chen YC, Chiu JS, Wang YF (2013). "NP-59 SPECT/CT imaging in stage 1 hypertensive and atypical primary aldosteronism: a 5-year retrospective analysis of clinicolaboratory and imaging features". ScientificWorldJournal. 2013: 317934. doi:10.1155/2013/317934. PMC 3818974. PMID 24235884.
- ↑ 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.