Liddle's syndrome: Difference between revisions

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This syndrome is caused by dysregulation of an epithelial [[Na+ channel]] ([[ENaC]]) due to a genetic mutation at the 16p12-p13 locus.  The mutation changes a domain in the channel so it is no longer degraded correctly by the [[Ubiquitin]] [[Proteasome]] system.  Specifically the PY motif in the protein is deleted or altered so the E3 ligase (Nedd4) no longer recognizes the channel.
This syndrome is caused by dysregulation of an epithelial [[Na+ channel]] ([[ENaC]]) due to a genetic mutation at the 16p12-p13 locus.  The mutation changes a domain in the channel so it is no longer degraded correctly by the [[Ubiquitin]] [[Proteasome]] system.  Specifically the PY motif in the protein is deleted or altered so the E3 ligase (Nedd4) no longer recognizes the channel.


==Differentiating Liddle's Syndrome from Conn's Syndrome==
==Differentiating Liddle's Syndrome from other diseases==
Aldosterone levels are high in hyperaldosteronism ([[Conn's syndrome]]), whereas they are low to normal in Liddle's syndrome.
Liddle's syndrome 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>
*[[Renal artery stenosis]]
*[[Cushing's syndrome]]
*[[Congenital adrenal hyperplasia]] (CAH)
**[[17 alpha-hydroxylase deficiency|17 alpha hydroxylase deficiency]]
**[[11β-hydroxylase deficiency|11 beta hydroxylase deficiency]]
*[[Primary hyperaldosteronism]]
*[[Diuretic]] use
*[[Licorice]] ingestion
*[[Renin]]-secreting [[Tumor|tumors]]
{{familytree/start}}{{familytree | | | | | | | | | A01 | | | | | |A01=Hypertension and Hypokalemia}}
{{familytree | | | | | | | | | |!| | | | | | | | }}
{{familytree | | | | | | | | | B01 | | | | | |B01=Plasma renin activity}}
{{familytree | | |,|-|-|-|-|-|-|^|-|-|-|-|-|-|.| }}
{{familytree | | C01 | | | | | | | | | | | |C02|C01=Normal or High (Plasma Renin/Aldosterone ratio <10|C02=Suppressed (Plasma Renin/Aldosterone ratio >20}}
{{familytree | | |!| | | | | | | | | | | | | |!| }}
{{familytree | | D01 | | | | | | | | | | | |D02|D01=*Renin-secreting tumors<br>*Diuretic use<br>*Renovascular hypertension<br>*Coarctation of aorta<br>*Malignant phase hypertension|D02=Urinary aldosterone}}
{{familytree | | | | | | | | | | | | |,|-|-|-|+|-|-|-|-|.|}}
{{familytree | | | | | | | | | | | | E01 | | E02 | | | E03 |E01=Elevated|E02=Normal|E03=Low|}}
{{familytree | | | | | | | | | | | | |!| | | |!| | | | |!| | }}
{{familytree | | | | | | | | | | | | F01 | | F02 | | | F03 |F01=Conn's syndrome (Primary aldosteronism)|F02=Profound K+ depletion|F03=• 17 alpha hydroxylase deficiency<br>• 11 beta hydroxylase deficiency<br>• Liddle's syndrome<br>• Licorice ingestion<br>• Deoxycortisone producing tumor|}}
{{familytree | | | | | | | | | | | | | | | | | | | | | |!| | | | }}
{{familytree | | | | | | | | | | | | | | | | | | | | |G01|G01=Add Mineralocrticoid antagonist for 8 weeks}}
{{familytree | | | | | | |,|-|-|-|-|-|-|-|-|-|-|-|-|-|-|^|-|-|-|-|-|-|-|-|-|-|-|-|-|-|.}}
{{familytree | | | | | |H01| | | | | | | | | | | | | | | | | | | | | | | | | | | |H02|H01=BP response|H02=No BP response}}
{{familytree | | | | | | |!| | | | | | | | | | | | | | | | | | | | | | | | | | | | | |!| }}
{{familytree | | | | | |I01| | | | | | | | | | | | | | | | | | | | | | | | | | | |I02|I01=• Deoxycorticosterone excess( Tumor, 17 alpha hydroxylase and 11 beta hydroxylase deficiency)<br>• Licorice ingestion<br>•Glucocorticoid resistance|I02=Liddle's syndrome)|}}
{{familytree/end}}
 
{| style="border: 0px; font-size: 90%; margin: 3px; width: 600px" align="center"
 
|+
! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Differential Diagnoses}}
! colspan="10" align="center" style="background:#4479BA; color: #FFFFFF; width: 400px;" + | Clinical features
! align="center" style="background:#4479BA; color: #FFFFFF;" + |
! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|History Findings}}
! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Laboratory Findings}}
|-
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Headache and hypertension
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Nausea and vomiting
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Palpitations
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Shortness of breath
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Diminished pulses
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Fatigue
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Constipation
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Visual abnormalities
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Pruritis
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Polyuria
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Ambiguous genitalia
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |[[Renin-Secreting tumors]]
| style="padding: 5px 5px; background: #F5F5F5;" | ✔
(Due to hypertension)
| style="padding: 5px 5px; background: #F5F5F5;" |<nowiki>✔</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" |✔
| style="padding: 5px 5px; background: #F5F5F5;" |<nowiki>✔</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" |
* Drug-resistant hypertension
* Chronic headaches
| style="padding: 5px 5px; background: #F5F5F5;" |
* Normal [[renal function tests]]
* Normal [[liver function tests]]
* [[Metabolic alkalosis]] (pH > 7.45)
* [[Hypokalemia]]
* [[Plasma]] [[renin]]-[[aldosterone]] ratio <10
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |[[Coarctation of aorta]]
| style="padding: 5px 5px; background: #F5F5F5;" | ✔
| style="padding: 5px 5px; background: #F5F5F5;" |<nowiki>✔</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" |✔
| style="padding: 5px 5px; background: #F5F5F5;" |<nowiki>✔</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" |<nowiki>✔</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" |<nowiki>✔</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" | -
| style="padding: 5px 5px; background: #F5F5F5;" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" |
*Young patients ([[neonates]]) may have history of:
** [[Failure to thrive]]
** Poor feeding
** Lethargy
** [[Turner syndrome|Turner's syndrome]]
** Familial predisposition
** [[Ventricular septal defects]]
*Adults may have a history of:
** [[Claudication]]
** [[Epistaxis]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* [[Bicuspid aortic valves]]
* Notching of [[ribs]]
* [[Metabolic alkalosis]] (pH > 7.45)
* [[Hyperkalemia]]
* [[Plasma]] [[renin]]-[[aldosterone]] ratio <10
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[11β-hydroxylase deficiency|11-beta hydroxylase deficiency]]
| style="padding: 5px 5px; background: #F5F5F5;" | ✔ ([[Hypertensive crisis]] due to increased [[11-deoxycorticosterone]]-11-DOC)
| style="padding: 5px 5px; background: #F5F5F5;" |<nowiki>✔</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" |<nowiki>✔</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" | -
| style="padding: 5px 5px; background: #F5F5F5;" | -
| style="padding: 5px 5px; background: #F5F5F5;" |<nowiki>✔</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" | -
| style="padding: 5px 5px; background: #F5F5F5;" | -
| style="padding: 5px 5px; background: #F5F5F5;" | -
| style="padding: 5px 5px; background: #F5F5F5;" | -
| style="padding: 5px 5px; background: #F5F5F5;" |✔
| style="padding: 5px 5px; background: #F5F5F5;" |
* Females:
** [[Clitoral body|Clitoral]] enlargement
** [[Labioscrotal folds|Labioscrotal]] fusion
* Males:
** [[Penis|Penile]] enlargement
* (If not diagnosed at birth, may present as premature [[adrenarche]], developing body odor with [[Axillary hair|axillary]] and [[pubic hair]] development)
| style="padding: 5px 5px; background: #F5F5F5;" |
* Hypokalemia
* Increased 11-DOC levels
* Increased androgens
* Low [[urinary]] [[aldosterone]] level
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[17 alpha-hydroxylase deficiency|17-alpha hydroxylase deficiency]]
| style="padding: 5px 5px; background: #F5F5F5;" | ✔
| style="padding: 5px 5px; background: #F5F5F5;" |✔
| style="padding: 5px 5px; background: #F5F5F5;" |✔
| style="padding: 5px 5px; background: #F5F5F5;" | -
| style="padding: 5px 5px; background: #F5F5F5;" | -
| style="padding: 5px 5px; background: #F5F5F5;" | -
| style="padding: 5px 5px; background: #F5F5F5;" | -
| style="padding: 5px 5px; background: #F5F5F5;" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" | -
| style="padding: 5px 5px; background: #F5F5F5;" | -
| style="padding: 5px 5px; background: #F5F5F5;" |✔
| style="padding: 5px 5px; background: #F5F5F5;" |
* [[Phenotypically]] females at birth
* Lack of [[pubertal]] development in females
* Incompletely developed external [[genitalia]] in males
| style="padding: 5px 5px; background: #F5F5F5;" |
* Increased [[serum]] [[mineralocorticoids]]
* Decreased [[androgen]] levels
* [[Hypokalemia]]
* Low [[urinary]] [[aldosterone]] level
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |'''[[Uremia]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |✔
| style="padding: 5px 5px; background: #F5F5F5;" |✔
| style="padding: 5px 5px; background: #F5F5F5;" |✔
| style="padding: 5px 5px; background: #F5F5F5;" | -
| style="padding: 5px 5px; background: #F5F5F5;" |✔
| style="padding: 5px 5px; background: #F5F5F5;" |✔
| style="padding: 5px 5px; background: #F5F5F5;" | -
| style="padding: 5px 5px; background: #F5F5F5;" |✔
| style="padding: 5px 5px; background: #F5F5F5;" | -
| style="padding: 5px 5px; background: #F5F5F5;" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" |
* Patients have [[chronic kidney disease]] and maybe on [[dialysis]]
* Features of uremic neuropathy:
** [[Autonomic nervous system|Autonomic]] features with postural [[hypotension]],
** Impaired [[sweating]]
** [[Diarrhea]]
** Impotence
** [[Paraesthesia]]
** Delayed [[Deep tendon reflex|deep tendon reflexes]]
** [[Muscle wasting]]
* [[Encephalopathy]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Increased [[blood urea nitrogen]] ([[Blood urea nitrogen|BUN]]) and [[creatinine]] ([[Cr]])
* [[Hyperkalemia]]
* Decreased [[serum]] [[Vitamin D3|vitamin 1,25 dihydroxy vitamin D3]] level
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |[[Liddle's syndrome|'''Liddle's syndrome''']]
| style="padding: 5px 5px; background: #F5F5F5;" |✔
| style="padding: 5px 5px; background: #F5F5F5;" |✔
| style="padding: 5px 5px; background: #F5F5F5;" |✔
| style="padding: 5px 5px; background: #F5F5F5;" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" |✔
| style="padding: 5px 5px; background: #F5F5F5;" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" |
* [[Family history]] of Liddle's syndrome ([[autosomal dominant inheritance]])
* [[Nephropathy]]
* [[Arrythmias]]
* [[SCNN1B]] or [[SCNN1G]] [[gene mutation]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* [[Hyporeninemic hypoaldosteronism]]
* [[Hypertension]]
* [[Hypokalemia]]
* Enhanced [[erythrocyte]] [[sodium]] influx 
* Low [[urinary]] [[aldosterone]]
|}


==Epidemiology and Demographics==
==Epidemiology and Demographics==

Revision as of 17:38, 16 October 2017

Liddle's syndrome
OMIM 177200
DiseasesDB 7471

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Liddle's Syndrome is an autosomal dominant disorder that mimics hyperaldosteronism.[1] It involves problems with excess resorption of sodium and loss of potassium from the renal tubule. Hypertension begins at a very early age, often in infancy.

Pathophysiology

This syndrome is caused by dysregulation of an epithelial Na+ channel (ENaC) due to a genetic mutation at the 16p12-p13 locus. The mutation changes a domain in the channel so it is no longer degraded correctly by the Ubiquitin Proteasome system. Specifically the PY motif in the protein is deleted or altered so the E3 ligase (Nedd4) no longer recognizes the channel.

Differentiating Liddle's Syndrome from other diseases

Liddle's syndrome should be differentiated from other diseases causing hypertension and hypokalemia for example:[2][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]

 
 
 
 
 
 
 
 
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)
Differential Diagnoses Clinical features History Findings Laboratory Findings
Headache and hypertension Nausea and vomiting Palpitations Shortness of breath Diminished pulses Fatigue Constipation Visual abnormalities Pruritis Polyuria Ambiguous genitalia
Renin-Secreting tumors

(Due to hypertension)

- - - - - - -
  • Drug-resistant hypertension
  • Chronic headaches
Coarctation of aorta - - - - -
11-beta hydroxylase deficiency ✔ (Hypertensive crisis due to increased 11-deoxycorticosterone-11-DOC) - - - - - -
17-alpha hydroxylase deficiency - - - - - - -
Uremia - - - -
Liddle's syndrome - - - - - - -

Epidemiology and Demographics

This syndrome is rare and may only be considered by the treating physician after the child's hypertension is found to be recalcitrant to antihypertensive agents.

Diagnosis

Symptoms

Children and aliens with Liddle's syndrome are frequently asymptomatic.

Physical Examination

Vitals

The first indication of the disease is often the incidental finding of hypertension during a routine physical exam.

Laboratory Studies

Evaluation of the pediatric hypertensive patient usually involves analysis of blood electrolytes and an aldosterone level, as well as other tests. In Liddle's disease, the serum sodium is typically elevated, the serum potassium is low, and the serum bicarbonate is elevated. These findings are also found in hyperaldosteronism, another rare cause of pediatric hypertension. Primary hyperaldosteronism (also known as Conn's syndrome), is due to an aldosterone-secreting adrenal tumor or adrenal hyperplasia.

Treatment

The treatment is with a low-salt diet and a potassium-sparing diuretic that directly blocks the sodium channel, such as amiloride or triamterene. Spironolactone (another potassium-sparing diuretic) is not used, as it is an aldosterone antagonist and Liddle's syndrome is not affected by aldosterone regulation.

References

  1. http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=177200
  2. 2.0 2.1 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.
  3. Nielsen ML, Pareek M, Andersen I (2012). "[Liquorice-induced hypertension and hypokalaemia]". Ugeskr. Laeg. (in Danish). 174 (15): 1024–5. PMID 22487411.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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.


de:Liddle-Syndrom it:Sindrome di Liddle fi:Liddlen syndrooma

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