Secondary hyperaldosteronism differential diagnosis: Difference between revisions

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{{Secondary hyperaldosteronism }}
{{Secondary hyperaldosteronism }}
[[Hypertension]] and [[hypokalemia]]
{| class="wikitable"
{| class="wikitable"
!
! rowspan="2" |
!Cause
! rowspan="2" |Cause
!
! colspan="4" |Laboratory
!
|-
!Renin activity
!Aldosterone levels
!urinary free cortisone
!Acid/base status
|-
|-
|Renin secreting tumors
|Renin secreting tumors
|
|
|↑
|↑
|
|
|
|
Line 14: Line 21:
|Apparent mineralocorticoid excess
|Apparent mineralocorticoid excess
|
|
|
|↓
|↓
|↓↓
|
|
|-
|-
|Licorice ingestion
|Licorice ingestion
|
|
|
|↓
|↓
|Moderate ↑
|
|
|-
|-
|Ectopic ACTH production
|Ectopic ACTH production
|
|
|
|↓
|↑
|Markedly ↑↑
|
|
|-
|-
|Primary hyperaldosteronism
|Primary hyperaldosteronism
|
|
|↓
|↑
|
|
|
|
|-
|-
|Familial hypoaldosteronism
|Familial hyperaldosteronism
|
|
|↓
|↑
|
|
|
|
Line 39: Line 56:
|Cushing syndrome
|Cushing syndrome
|
|
|↓
|↑
|Markedly ↑↑
|
|-
|Renal artery stenosis
|
|↑
|↑
|↓
|
|-
|[[Liddle's syndrome]]
|
|↓
|↓
|↓
|
|-
|[[Diuretic]] use
|
|Nl
|
|↓
|
|-
|[[17 alpha-hydroxylase deficiency|17 alpha hydroxylase deficiency]]
|
|↓
|↓
|↓
|
|-
|[[11β-hydroxylase deficiency|11 beta hydroxylase deficiency]]
|
|
|↓
|↓
|↓
|
|
|-
|-
|Renal artery stenosis
|Coarctation of aorta
|
|
|
|
|
|↓
|
|
|}
|}


 
Secondary hyperaldosteronism should be differentiated from other diseases causing '''[[hypertension]]''' and '''[[hypokalemia]]''' for example:<ref name="pmid24800505">{{cite journal |vauthors=Wada N, Jin S, Hui SP, Yanagisawa K, Kurosawa T, Chiba H |title=[Differential diagnosis of primary aldosteronism by measurement of hybrid steroids using mass spectrometry] |language=Japanese |journal=Rinsho Byori |volume=62 |issue=3 |pages=276–82 |year=2014 |pmid=24800505 |doi= |url=}}</ref><ref name="pmid22487411">{{cite journal |vauthors=Nielsen ML, Pareek M, Andersen I |title=[Liquorice-induced hypertension and hypokalaemia] |language=Danish |journal=Ugeskr. Laeg. |volume=174 |issue=15 |pages=1024–5 |year=2012 |pmid=22487411 |doi= |url=}}</ref><ref name="pmid21962616">{{cite journal |vauthors=Chow KM, Ma RC, Szeto CC, Li PK |title=Polycystic kidney disease presenting with hypertension and hypokalemia |journal=Am. J. Kidney Dis. |volume=59 |issue=2 |pages=270–2 |year=2012 |pmid=21962616 |doi=10.1053/j.ajkd.2011.08.020 |url=}}</ref><ref name="pmid22154539">{{cite journal |vauthors=Sarafidis PA, Georgianos PI, Germanidis G, Giavroglou C, Nikolaidis P, Lasaridis AN, Madias NE |title=Hypertension and symptomatic hypokalemia in a patient with simultaneous unilateral stenoses of intrarenal arteries and mesangioproliferative glomerulonephritis |journal=Am. J. Kidney Dis. |volume=59 |issue=3 |pages=434–8 |year=2012 |pmid=22154539 |doi=10.1053/j.ajkd.2011.11.001 |url=}}</ref><ref name="pmid17275580">{{cite journal |vauthors=Khosla N, Hogan D |title=Mineralocorticoid hypertension and hypokalemia |journal=Semin. Nephrol. |volume=26 |issue=6 |pages=434–40 |year=2006 |pmid=17275580 |doi=10.1016/j.semnephrol.2006.10.004 |url=}}</ref><ref name="pmid23953804">{{cite journal |vauthors=Weiner ID |title=Endocrine and hypertensive disorders of potassium regulation: primary aldosteronism |journal=Semin. Nephrol. |volume=33 |issue=3 |pages=265–76 |year=2013 |pmid=23953804 |pmc=3748390 |doi=10.1016/j.semnephrol.2013.04.007 |url=}}</ref><ref name="pmid25715092">{{cite journal |vauthors=Martell-Claros N, Abad-Cardiel M, Alvarez-Alvarez B, García-Donaire JA, Pérez CF |title=Primary aldosteronism and its various clinical scenarios |journal=J. Hypertens. |volume=33 |issue=6 |pages=1226–32 |year=2015 |pmid=25715092 |doi=10.1097/HJH.0000000000000546 |url=}}</ref><ref name="pmid10818057">{{cite journal |vauthors=Franse LV, Pahor M, Di Bari M, Somes GW, Cushman WC, Applegate WB |title=Hypokalemia associated with diuretic use and cardiovascular events in the Systolic Hypertension in the Elderly Program |journal=Hypertension |volume=35 |issue=5 |pages=1025–30 |year=2000 |pmid=10818057 |doi= |url=}}</ref><ref name="pmid21525970">{{cite journal |vauthors=Rossi E, Farnetti E, Nicoli D, Sazzini M, Perazzoli F, Regolisti G, Grasselli C, Santi R, Negro A, Mazzeo V, Mantero F, Luiselli D, Casali B |title=A clinical phenotype mimicking essential hypertension in a newly discovered family with Liddle's syndrome |journal=Am. J. Hypertens. |volume=24 |issue=8 |pages=930–5 |year=2011 |pmid=21525970 |doi=10.1038/ajh.2011.76 |url=}}</ref><ref name="pmid25968592">{{cite journal |vauthors=Ruecker B, Lang-Muritano M, Spanaus K, Welzel M, l'Allemand D, Phan-Hug F, Katschnig C, Konrad D, Holterhus PM, Schoenle EJ |title=The Aldosterone/Renin Ratio as a Diagnostic Tool for the Diagnosis of Primary Hypoaldosteronism in Newborns and Infants |journal=Horm Res Paediatr |volume=84 |issue=1 |pages=43–8 |year=2015 |pmid=25968592 |doi=10.1159/000381852 |url=}}</ref><ref name="pmid25908467">{{cite journal |vauthors=Ardhanari S, Kannuswamy R, Chaudhary K, Lockette W, Whaley-Connell A |title=Mineralocorticoid and apparent mineralocorticoid syndromes of secondary hypertension |journal=Adv Chronic Kidney Dis |volume=22 |issue=3 |pages=185–95 |year=2015 |pmid=25908467 |doi=10.1053/j.ackd.2015.03.002 |url=}}</ref><ref name="pmid19174076">{{cite journal |vauthors=Iglesias P, Tajada P, Martínez I, Díez JJ |title=[Salt-wasting congenital adrenal hyperplasia associated to hyperreninemic hyperaldosteronism] |language=Spanish; Castilian |journal=Med Clin (Barc) |volume=132 |issue=2 |pages=80–1 |year=2009 |pmid=19174076 |doi=10.1016/j.medcli.2008.09.002 |url=}}</ref><ref name="pmid3413779">{{cite journal |vauthors=Kikuta Y, Sanjo K, Nakajima K, Ashizawa I, Ojima M |title=Primary aldosteronism in childhood due to primary adrenal hyperplasia |journal=Tohoku J. Exp. Med. |volume=155 |issue=1 |pages=57–70 |year=1988 |pmid=3413779 |doi= |url=}}</ref><ref name="pmid21494136">{{cite journal |vauthors=Hassan-Smith Z, Stewart PM |title=Inherited forms of mineralocorticoid hypertension |journal=Curr Opin Endocrinol Diabetes Obes |volume=18 |issue=3 |pages=177–85 |year=2011 |pmid=21494136 |doi=10.1097/MED.0b013e3283469444 |url=}}</ref><ref name="pmid4299011">{{cite journal |vauthors=Bartter FC, Henkin RI, Bryan GT |title=Aldosterone hypersecretion in "non-salt-losing" congenital adrenal hyperplasia |journal=J. Clin. Invest. |volume=47 |issue=8 |pages=1742–52 |year=1968 |pmid=4299011 |pmc=297334 |doi=10.1172/JCI105864 |url=}}</ref>
 
Secondary hyperaldosteronism should be differentiated from other diseases causing '''[[hypertension]]''' and '''[[hypokalemia]]''' for example:<ref name="pmid24800505">{{cite journal |vauthors=Wada N, Jin S, Hui SP, Yanagisawa K, Kurosawa T, Chiba H |title=[Differential diagnosis of primary aldosteronism by measurement of hybrid steroids using mass spectrometry] |language=Japanese |journal=Rinsho Byori |volume=62 |issue=3 |pages=276–82 |year=2014 |pmid=24800505 |doi= |url=}}</ref><ref name="pmid24800505">{{cite journal |vauthors=Wada N, Jin S, Hui SP, Yanagisawa K, Kurosawa T, Chiba H |title=[Differential diagnosis of primary aldosteronism by measurement of hybrid steroids using mass spectrometry] |language=Japanese |journal=Rinsho Byori |volume=62 |issue=3 |pages=276–82 |year=2014 |pmid=24800505 |doi= |url=}}</ref><ref name="pmid22487411">{{cite journal |vauthors=Nielsen ML, Pareek M, Andersen I |title=[Liquorice-induced hypertension and hypokalaemia] |language=Danish |journal=Ugeskr. Laeg. |volume=174 |issue=15 |pages=1024–5 |year=2012 |pmid=22487411 |doi= |url=}}</ref><ref name="pmid21962616">{{cite journal |vauthors=Chow KM, Ma RC, Szeto CC, Li PK |title=Polycystic kidney disease presenting with hypertension and hypokalemia |journal=Am. J. Kidney Dis. |volume=59 |issue=2 |pages=270–2 |year=2012 |pmid=21962616 |doi=10.1053/j.ajkd.2011.08.020 |url=}}</ref><ref name="pmid22154539">{{cite journal |vauthors=Sarafidis PA, Georgianos PI, Germanidis G, Giavroglou C, Nikolaidis P, Lasaridis AN, Madias NE |title=Hypertension and symptomatic hypokalemia in a patient with simultaneous unilateral stenoses of intrarenal arteries and mesangioproliferative glomerulonephritis |journal=Am. J. Kidney Dis. |volume=59 |issue=3 |pages=434–8 |year=2012 |pmid=22154539 |doi=10.1053/j.ajkd.2011.11.001 |url=}}</ref><ref name="pmid17275580">{{cite journal |vauthors=Khosla N, Hogan D |title=Mineralocorticoid hypertension and hypokalemia |journal=Semin. Nephrol. |volume=26 |issue=6 |pages=434–40 |year=2006 |pmid=17275580 |doi=10.1016/j.semnephrol.2006.10.004 |url=}}</ref><ref name="pmid23953804">{{cite journal |vauthors=Weiner ID |title=Endocrine and hypertensive disorders of potassium regulation: primary aldosteronism |journal=Semin. Nephrol. |volume=33 |issue=3 |pages=265–76 |year=2013 |pmid=23953804 |pmc=3748390 |doi=10.1016/j.semnephrol.2013.04.007 |url=}}</ref><ref name="pmid25715092">{{cite journal |vauthors=Martell-Claros N, Abad-Cardiel M, Alvarez-Alvarez B, García-Donaire JA, Pérez CF |title=Primary aldosteronism and its various clinical scenarios |journal=J. Hypertens. |volume=33 |issue=6 |pages=1226–32 |year=2015 |pmid=25715092 |doi=10.1097/HJH.0000000000000546 |url=}}</ref><ref name="pmid10818057">{{cite journal |vauthors=Franse LV, Pahor M, Di Bari M, Somes GW, Cushman WC, Applegate WB |title=Hypokalemia associated with diuretic use and cardiovascular events in the Systolic Hypertension in the Elderly Program |journal=Hypertension |volume=35 |issue=5 |pages=1025–30 |year=2000 |pmid=10818057 |doi= |url=}}</ref><ref name="pmid21525970">{{cite journal |vauthors=Rossi E, Farnetti E, Nicoli D, Sazzini M, Perazzoli F, Regolisti G, Grasselli C, Santi R, Negro A, Mazzeo V, Mantero F, Luiselli D, Casali B |title=A clinical phenotype mimicking essential hypertension in a newly discovered family with Liddle's syndrome |journal=Am. J. Hypertens. |volume=24 |issue=8 |pages=930–5 |year=2011 |pmid=21525970 |doi=10.1038/ajh.2011.76 |url=}}</ref><ref name="pmid25968592">{{cite journal |vauthors=Ruecker B, Lang-Muritano M, Spanaus K, Welzel M, l'Allemand D, Phan-Hug F, Katschnig C, Konrad D, Holterhus PM, Schoenle EJ |title=The Aldosterone/Renin Ratio as a Diagnostic Tool for the Diagnosis of Primary Hypoaldosteronism in Newborns and Infants |journal=Horm Res Paediatr |volume=84 |issue=1 |pages=43–8 |year=2015 |pmid=25968592 |doi=10.1159/000381852 |url=}}</ref><ref name="pmid25908467">{{cite journal |vauthors=Ardhanari S, Kannuswamy R, Chaudhary K, Lockette W, Whaley-Connell A |title=Mineralocorticoid and apparent mineralocorticoid syndromes of secondary hypertension |journal=Adv Chronic Kidney Dis |volume=22 |issue=3 |pages=185–95 |year=2015 |pmid=25908467 |doi=10.1053/j.ackd.2015.03.002 |url=}}</ref><ref name="pmid19174076">{{cite journal |vauthors=Iglesias P, Tajada P, Martínez I, Díez JJ |title=[Salt-wasting congenital adrenal hyperplasia associated to hyperreninemic hyperaldosteronism] |language=Spanish; Castilian |journal=Med Clin (Barc) |volume=132 |issue=2 |pages=80–1 |year=2009 |pmid=19174076 |doi=10.1016/j.medcli.2008.09.002 |url=}}</ref><ref name="pmid3413779">{{cite journal |vauthors=Kikuta Y, Sanjo K, Nakajima K, Ashizawa I, Ojima M |title=Primary aldosteronism in childhood due to primary adrenal hyperplasia |journal=Tohoku J. Exp. Med. |volume=155 |issue=1 |pages=57–70 |year=1988 |pmid=3413779 |doi= |url=}}</ref><ref name="pmid21494136">{{cite journal |vauthors=Hassan-Smith Z, Stewart PM |title=Inherited forms of mineralocorticoid hypertension |journal=Curr Opin Endocrinol Diabetes Obes |volume=18 |issue=3 |pages=177–85 |year=2011 |pmid=21494136 |doi=10.1097/MED.0b013e3283469444 |url=}}</ref><ref name="pmid4299011">{{cite journal |vauthors=Bartter FC, Henkin RI, Bryan GT |title=Aldosterone hypersecretion in "non-salt-losing" congenital adrenal hyperplasia |journal=J. Clin. Invest. |volume=47 |issue=8 |pages=1742–52 |year=1968 |pmid=4299011 |pmc=297334 |doi=10.1172/JCI105864 |url=}}</ref>
*[[Primary aldosteronism]]
*[[Primary aldosteronism]]
*[[Renal artery stenosis]]
*[[Renal artery stenosis]]
*[[Cushing's syndrome]]
*[[Cushing's syndrome]]
*[[Congenital adrenal hyperplasia]] (CAH)
*[[Congenital adrenal hyperplasia]] ([[CAH]])
**[[17 alpha-hydroxylase deficiency|17 alpha hydroxylase deficiency]]
**[[17 alpha-hydroxylase deficiency|17 alpha hydroxylase deficiency]]
**[[11β-hydroxylase deficiency|11 beta hydroxylase deficiency]]
**[[11β-hydroxylase deficiency|11 beta hydroxylase deficiency]]

Revision as of 15:53, 11 September 2017

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Hypertension and hypokalemia

Cause Laboratory
Renin activity Aldosterone levels urinary free cortisone Acid/base status
Renin secreting tumors ↑ ↑
Apparent mineralocorticoid excess ↓ ↓ ↓↓
Licorice ingestion ↓ ↓ Moderate ↑
Ectopic ACTH production ↓ ↑ Markedly ↑↑
Primary hyperaldosteronism ↓ ↑
Familial hyperaldosteronism ↓ ↑
Cushing syndrome ↓ ↑ Markedly ↑↑
Renal artery stenosis ↑ ↑ ↓
Liddle's syndrome ↓ ↓ ↓
Diuretic use Nl ↓
17 alpha hydroxylase deficiency ↓ ↓ ↓
11 beta hydroxylase deficiency ↓ ↓ ↓
Coarctation of aorta ↓

Secondary hyperaldosteronism should be differentiated from other diseases causing hypertension and hypokalemia for example:[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]

 
 
 
 
 
 
 
 
Hypertension and Hypokalemia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Plasma renin activity
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Normal or High (Plasma Renin/Aldosterone ratio <10
 
 
 
 
 
 
 
 
 
 
 
Suppressed (Plasma Renin/Aldosterone ratio >20
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Renin-secreting tumors
*Diuretic use
*Renovascular hypertension
*Coarctation of aorta
*Malignant phase hypertension
 
 
 
 
 
 
 
 
 
 
 
Urinary aldosterone
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Elevated
 
Normal
 
 
Low
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Conn's syndrome (Primary aldosteronism)
 
Profound K+ depletion
 
 
• 17 alpha hydroxylase deficiency
• 11 beta hydroxylase deficiency
• Liddle's syndrome
• Licorice ingestion
• Deoxycortisone producing tumor
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Add Mineralocrticoid antagonist for 8 weeks
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BP response
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No BP response
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• Deoxycorticosterone excess( Tumor, 17 alpha hydroxylase and 11 beta hydroxylase deficiency)
• Licorice ingestion
•Glucocorticoid resistance
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Liddle's syndrome)


References

  1. ↑ Wada N, Jin S, Hui SP, Yanagisawa K, Kurosawa T, Chiba H (2014). "[Differential diagnosis of primary aldosteronism by measurement of hybrid steroids using mass spectrometry]". Rinsho Byori (in Japanese). 62 (3): 276–82. PMID 24800505.
  2. ↑ Nielsen ML, Pareek M, Andersen I (2012). "[Liquorice-induced hypertension and hypokalaemia]". Ugeskr. Laeg. (in Danish). 174 (15): 1024–5. PMID 22487411.
  3. ↑ Chow KM, Ma RC, Szeto CC, Li PK (2012). "Polycystic kidney disease presenting with hypertension and hypokalemia". Am. J. Kidney Dis. 59 (2): 270–2. doi:10.1053/j.ajkd.2011.08.020. PMID 21962616.
  4. ↑ Sarafidis PA, Georgianos PI, Germanidis G, Giavroglou C, Nikolaidis P, Lasaridis AN, Madias NE (2012). "Hypertension and symptomatic hypokalemia in a patient with simultaneous unilateral stenoses of intrarenal arteries and mesangioproliferative glomerulonephritis". Am. J. Kidney Dis. 59 (3): 434–8. doi:10.1053/j.ajkd.2011.11.001. PMID 22154539.
  5. ↑ Khosla N, Hogan D (2006). "Mineralocorticoid hypertension and hypokalemia". Semin. Nephrol. 26 (6): 434–40. doi:10.1016/j.semnephrol.2006.10.004. PMID 17275580.
  6. ↑ Weiner ID (2013). "Endocrine and hypertensive disorders of potassium regulation: primary aldosteronism". Semin. Nephrol. 33 (3): 265–76. doi:10.1016/j.semnephrol.2013.04.007. PMC 3748390. PMID 23953804.
  7. ↑ Martell-Claros N, Abad-Cardiel M, Alvarez-Alvarez B, García-Donaire JA, Pérez CF (2015). "Primary aldosteronism and its various clinical scenarios". J. Hypertens. 33 (6): 1226–32. doi:10.1097/HJH.0000000000000546. PMID 25715092.
  8. ↑ Franse LV, Pahor M, Di Bari M, Somes GW, Cushman WC, Applegate WB (2000). "Hypokalemia associated with diuretic use and cardiovascular events in the Systolic Hypertension in the Elderly Program". Hypertension. 35 (5): 1025–30. PMID 10818057.
  9. ↑ Rossi E, Farnetti E, Nicoli D, Sazzini M, Perazzoli F, Regolisti G, Grasselli C, Santi R, Negro A, Mazzeo V, Mantero F, Luiselli D, Casali B (2011). "A clinical phenotype mimicking essential hypertension in a newly discovered family with Liddle's syndrome". Am. J. Hypertens. 24 (8): 930–5. doi:10.1038/ajh.2011.76. PMID 21525970.
  10. ↑ Ruecker B, Lang-Muritano M, Spanaus K, Welzel M, l'Allemand D, Phan-Hug F, Katschnig C, Konrad D, Holterhus PM, Schoenle EJ (2015). "The Aldosterone/Renin Ratio as a Diagnostic Tool for the Diagnosis of Primary Hypoaldosteronism in Newborns and Infants". Horm Res Paediatr. 84 (1): 43–8. doi:10.1159/000381852. PMID 25968592.
  11. ↑ Ardhanari S, Kannuswamy R, Chaudhary K, Lockette W, Whaley-Connell A (2015). "Mineralocorticoid and apparent mineralocorticoid syndromes of secondary hypertension". Adv Chronic Kidney Dis. 22 (3): 185–95. doi:10.1053/j.ackd.2015.03.002. PMID 25908467.
  12. ↑ Iglesias P, Tajada P, Martínez I, Díez JJ (2009). "[Salt-wasting congenital adrenal hyperplasia associated to hyperreninemic hyperaldosteronism]". Med Clin (Barc) (in Spanish; Castilian). 132 (2): 80–1. doi:10.1016/j.medcli.2008.09.002. PMID 19174076.
  13. ↑ Kikuta Y, Sanjo K, Nakajima K, Ashizawa I, Ojima M (1988). "Primary aldosteronism in childhood due to primary adrenal hyperplasia". Tohoku J. Exp. Med. 155 (1): 57–70. PMID 3413779.
  14. ↑ Hassan-Smith Z, Stewart PM (2011). "Inherited forms of mineralocorticoid hypertension". Curr Opin Endocrinol Diabetes Obes. 18 (3): 177–85. doi:10.1097/MED.0b013e3283469444. PMID 21494136.
  15. ↑ Bartter FC, Henkin RI, Bryan GT (1968). "Aldosterone hypersecretion in "non-salt-losing" congenital adrenal hyperplasia". J. Clin. Invest. 47 (8): 1742–52. doi:10.1172/JCI105864. PMC 297334. PMID 4299011.
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