11.10.08 Klemmer. Primary Aldosteronism, Resistant HTN

7/21/2019 11.10.08 Klemmer. Primary Aldosteronism, Resistant HTN

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Primary Hyperaldosteronism

and Resistant Hypertension

Philip J. Klemmer MDUNC Kidney Center

University of North Carolina

Chapel Hill NC USA


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Case '

SS8 Aldo

&aseline /.,

Post saline +.'

C8 revealed normal adrenals9 hy$rid

!ene :H5'" ne!ative

A7S Aldo Aldo - Cortisol

Ri!ht +( 0

1eft /'; ,0


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Aldosterone5Prod#cin! Adenoma Missed

$y Comp#ter5Aided 8omo!raphy


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Case '

1eft adrenalectomy 3 APA ) mm"

Post operative &P '0,-;, mm H! on

/ medications9 K4(.;

Aldo


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%hat controls aldosterone

secretion= Normal A5ll post#re> dietary Na4"

Hyper?alemia CKD" Adiponectin meta$olic syndrome"

AC8H minor"

Primary hyperaldosteronism incomplete a#tonomy"

APA A5ll,@" AC8H ,@" &AH A5ll'@"

:H5' nheritance 3 AD. AC8H via chimeric !ene"

1o* renin essential H&P A5ll


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Physiolo!ic and pathophysiolo!ic effects of

aldosterone on the ?idney and heart in

relation to dietary salt

Dluhy RG et al. N Engl J Med 2004; 351:8-10
http://content.nejm.org/content/vol351/issue1/images/large/04f1.jpeg


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Aldosterone and Ser#m Cofactor

Aldosterone

PA Normals

ARR Aldo B(

PRA

Ser#m aldo B ',

R!


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Sodi#m Cofactor

Hi!h aldo - lo* salt

Normal physiolo!ic response to2

1o* dietary sodi#m Renal salt *astin!

Hi!h aldo - hi!h salt

Hi!h $lood press#re

Heart2 fi$rosis - inflammation

Kidney2 protein#ria - fi$rosis


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Case /

&P3 ;, -


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0 E

( E

/ E

' E

E , ' ',

NFRMA1 N8AK6

HGH N8AK6

Normal

MAP mm H!"

Sodi#m

nta?e-6Hcre

tionHnorma

l"


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0 E

( E

/ E

' E

E , ' ',

NFRMA1 N8AK6

HGH N8AK6

Natri#retic handicap CKD> PA"

Normal

MAP mm H!"

Sodi#m

nta?e-6Hcre

tionHnorma

l"


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nterstiti#m nterstiti#m nterstiti#mPlasma

(., 1

Plasma

/.+ 1

Plasma

0./ 1

Cells

30.1L

Cells

25.2L

Cells28 L

10.5 L 8.4 L 12.6 L

150 mEq Na

150 mEq Na 5 mEq Na

5 mEq Na 150 mEq Na

150 mEq N

A & C

GFR = 100 GFR = 100 GFR= 30

) ?! &%

" # $0 % .05 # 3.5 &

'(" # $0 % .15 # 10.5 &

E)" # $0 % .20 # 14 &

ECV = 14L

ECV =11.2 L ECV =

16.8 L


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Aldosterone and Ser#m Cofactor

Normals

PA>


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Aldosterone5Mediated 7asc#lar

nI#ry

J*++e ," et al. ,eat a/lRe 2005; 10:31-3$


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ncreased rate of C7 events in

PA patients

FR

C7A 0./

M


20/57Copyright 2006 American Heart Association

Rossi, G. P. et al. H!e"te#sio# 2006$48%232&238

Co'a"iates&a()*ste( +E "ate i# t-e!atie#ts it- !"ima" H/N PH a#(

!"ima" al(oste"o#ism P a#( H


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Cardiovasc#lar 6vents and

Primary Aldosteronism

Rate of Cardiovasc#lar 6vents and Cardiac Str#ct#re in Primary Aldosteronism

/ay !ld*n#124

Eent/al ,6Nn#475

dd at/* 95)'

p value

(t*e 12.9 3.4 4.2 2.0-8.7 < 0.001

My*=ad/al /n+a=t/*n 4.0 0.7 7.5 1.52$.4 < 0.005>

!t/al +/?/llat/*n $.3 0.7 12.1 3.2-45.2

E=h* &", 34 24 1.7 1.1-2.5 < 0.01

E@G &", 32 14 2.9 1.8-4.7 < 0.001

M/ll/e et al. J ! )*ll )ad/*l 2005; 458:1243-1248

:isher eact test.

C 3 confidence interval9 17H 3 left ventric#lar hypertrophy


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Case Detection

Hi!her prevalence2

o#n! a!e of H&P onset

Severe refractory H&P :H of PA or C7A L0 y-o

Hypo?alemia


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Prevalence of Primary Aldosteronism

in Hypertensive Patients

M** & et al. ,yAeten/*n 2003; 422:171-

175

'0 E

'/ E

' E

+ E

< E

0 E

/ E

E

Normal Sta!e ' Sta!e / Sta!e (

'.,,'.;;

'(./

+./


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1. M** & et al. ,yAeten/*n 2003; 422:171-1752. )alh*un D! et al. ,yAeten/*n 2002; 497:892-897


in '>'/, Hypertensive Patients

/, E

/ E

', E

' E

, E

E

Sta!e ' Sta!e / Sta!e ( Sta!e 0

/

+

/

'(

PrevalenceofP

A@"

PA 3 primary aldosteronism

Accordin! to hypertension sta!e JNC 7'" classification


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1. Galley BJ et al. ! J @/dney D/ 2001; 3$:799-$05

2. )alh*un D! et al. ,yAeten/*n 2002; 40:892-897

3. E/de '@ et al. J ,yAeten/*n 2004; 22:221$-22274. (taugh B et al. J ,u ,yAeten 2003; 1$:349-352



/, E

/ E

', E

' E

, E

E

Seattle &irmin!ham Fslo Pra!#e

')@

/@';@

//@

PrevalenceofP

A@"

PA 3 primary aldosteronism


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Screenin! for PA 2 ARR

Aldosterone - PRA B ( - '

Aldosterone B', n!@ (


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Screenin! for PA 2 ARR

Mornin! testin!

F#t of $ed /hrs

Seated ' min#tes

%asho#t interferin! dr#!s 8reat H&P *ith verapamil >hydralaine> alpha $loc?ers

K4 repletion


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PA 2 Confirmation

Saline S#ppression 8est B< n!-d1"

:lorinef S#ppression 8est B


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Ran!e of S#pine PAC and '+5

FH5& in APA and &AH

Phillips J.1. et al. J Clin 6ndo Meta$ /9 +,'/"20,/


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Clinical :eat#res &AH vs. APA

8oo m#ch overlap to separate s#$types

Generaliations many eceptions"

&AH more li?ely than APA to have2 Normo?alemia

1o*er ARR

1ess severe H&P

1o*er ser#m aldosterone levels

Flder

Hi!her prevalence (2'"

Relationship $et*een &AH and 1R6H ="


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S#$types of Primary

Aldosteronism

May $e treated s#r!ically for c#re

Aldosterone5prod#cin! adenoma APA"

Primary #nilateral" adrenal hyperplasia

Aldosterone5prod#cin! adrenocorticoid

carcinoma

Sho#ld al*ays $e treated medically diopathic hyperaldosteronism &AH"

Gl#cocorticoid5remedia$le aldosteronism :H5'"

:H5/


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o#n! %: Jr. 6ndocrinolo!y /(9 '00


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Differentiation &et*een Unilateral

and &ilateral :orms of PA

Not helpf#l

Clinical feat#res

ARR> ser#m aldo Response to aldo

anta!onist

Post#ral testin!

'+ FH& C8

Definitive

A7S

Hy$rid !ene PCR:H5'"

7ery !ood

Deamethasone

s#ppression :H5'"testin!


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Adrenal 7eno#s Samplin!

A7S"



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Adrenal 7eno#s Samplin!

A7S"



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Misleadin! C8 Res#lts in PA

Gordon /'"2 '/ PA patients

lateralied on A7S had masses incontralateral $#t not ipsilateral"

adrenal

McAlister ';;+"2 ,-'+ PA patients

*ith #nilateral mass act#ally had

&AH determined $y A7S"


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diopathic Hyperaldosteronism

HA"


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R*/ G et al. J ! )*ll )ad/*l 2007; 4811:2293-2300




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PA2 University of #eensland

6perience

ARR screenin! off medications" of

all H&P patients Aldosterone s#ppression test

confirmation of PA

A7S s#$type eval#ation of allpatients


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PA2 University of #eensland

6perience

Res#lts

'O PA detection rate ; cases-yr" &AH B APA /2'"

+;0 cases total"

Fnly //@ hypo?alemic PA prevalence in referred patients '/@"


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Primary Aldosteronism

Mana!ement

PA

PA86N8QS %SH6S

M6DCA1 RO

6P16RFNFN6

CHANC6 F:

SURGCA1 CUR6

A7S

1A86RA16D

A-C

NFN1A86RA16D

A-C

1APARFSCFPC

ADR6NA16C8FM6P16RFNFN6

C8


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Adrenalectomy

Res#lts of #nilateral adrenalectomy in PApatients *ith A7S sho*in! #nilateralhypersecretion of aldosterone *ithcontralateral aldosterone s#ppressionre!ardless of C8 anatomy" Sto*asser andGordon /( H&P c#red


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Medical 8herapy of PA

&AH2 eplerenone ,5/ m!-day !ive &D"

spironolactone /, 5 ' m! - day

amiloride allo*s for lo*er spironolactone"

:H5'2 deamethasone ./,5'. m!-day


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6plerenone

SARA

MR affinity / O B spironolactone

Potency of effect ),@ of

spironolactone

&indin! affinity for andro!en and

pro!esterone receptors '5fold

lo*er than spironolactone


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Resistant Hypertension


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Resistant H&P

ncreased a!e :emale

DM

F$esity

AA

CKD

FSA

PRA L '.

Salt !l#ttony


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1. E/de '@ et al. J ,yAeten 2004; 2211:221$-22272. N/h/aa M@ et al. ! J ,yAeten 2003; 1711 t 1:925-930

Prevalence of 1o*5Renin 1evels Amon!

Patients *ith Resistant Hypertension

' E

+ E


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Characteristics of St#dy

Participants

Characteristic

ResistantHypertension

n 3 /);"

Controlsn 3 ,("

Potassi#m> m6-1 (.; .(" 0.( .


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ANP and &NP 7al#es in St#dy

Participants

Gadda @@ et al. !=h 'nten Med 2008; 17811:1159-1174


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N/h/aa M@ et al. ! J ,yAeten 2003; 1711:925-930

&P Response to Spironolactone in PA

and Non5PA Patients

S&P 3 systolic $lood press#re9 D&P 3 diastolic $lood press#re


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N/h/aa M@ et al. ! J ,yAeten 2003; 1711:925-930

&P Response to Spironolactone in

Patients *ith Resistant Hypertension


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)haAan N et al. ,yAeten/*n 200$; 494:839-845

ASCF8 Use of Spironolactone for

Resistant Hypertension
http://hyper.ahajournals.org/content/vol49/issue4/images/large/23FF2.jpeg


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Mineralocorticoid Receptor MR"

and its 1i!ands GC> aldosterone"

MR

MR

'' HSD5/

6pithelial cells

7SMC7asc#lar endotheli#m

Myocytes

&rain


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)*Ay/ght C2003 6he End*=/ne (*=/ety u/nle M. et al. J )l/n End*=/n*l Meta? 2003;88:2384-2392


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Nothin! in $iolo!y ma?es sense


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Nothin! in $iolo!y ma?es sense

ecept in li!ht of evol#tionV

8.Do$hans?y

'nt*du=t/*n t* )ultual !nth*A*l*gy: )*ue (ylla?u. )h/t*Ahe ennell all 2003


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S#mmary

%ho sho#ld $e screened for primary aldosteronism= Hypo?alemia Ris? of secondary hypertension onset yo#n! a!e> ac#te

*orsenin! of hypertension" Resistant and-or severe hypertension Adrenal mass incidentalomaV"

Aldosterone anta!onists are !enerally safe> $#thyper?alemia and-or ac#te renal ins#fficiency can occ#r Ris? in patients *ith CKD> elderly dia$etics> patients

receivin! AC65 and-or AR& or NSAD n hi!h5ris? patients> red#ced doses appropriate '/., m!

spironolactone" &iochemical monitorin! is necessary9 *ithin 0 *ee?s if renal

f#nction normal> as early as ' *ee? in hi!h5ris? patients

Documents

11.10.08 Klemmer. Primary Aldosteronism, Resistant HTN