7. HTA Endocrina Studenti 2014

94
Corin Badiu, 2012 Hipertensiunea arteriala endocrina Hipertensiunea arteriala endocrina Sindromul Cushing Sindromul Cushing Hiperaldosteronismul primar Hiperaldosteronismul primar Feocromocitomul Feocromocitomul 

Transcript of 7. HTA Endocrina Studenti 2014

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Corin Badiu, 2012

Hipertensiunea arteriala endocrinaHipertensiunea arteriala endocrina

Sindromul Cushing Sindromul Cushing Hiperaldosteronismul primar Hiperaldosteronismul primar 

Feocromocitomul Feocromocitomul 

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Blood Pressure Classification (JNC8)

BP Classification SBP mmHg DBP mmHg

James PA et al, !"# e$idence%&ased guideline for the management of high &lood

 pressure in adults' report from the panel mem&ers appointed to the ighth Joint

National Committee (JNC 8) JA*A !"#+""(-)'-!.

Normal <120 and <80

Prehypertension 120–139 or  80

–89

HBP Stage1 140–19 or  90–99

HBP Stage 2 1!0"1#9 or 100"109

HBP Stage 3 $180 or $110

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FREQUENCY OF VARIOUS DIAGNOSES IN

HYPERTENSIVE PATIENTS 

PRIMARY CARE REFERRAL

  Essential 92-9! "9!

  C#$%ni& 'i(ne) (isease *-+! ,!

  Ren%as&.la$ (isease /02-10/! ,!

  P#e%&#$%%&)t%a /01-/02! /02!

  Al(%ste$%nis /01-/0*! /0!

  C.s#in34s s)n($%e /01-/02! /02!

  C%a$&tati%n /01-/02! 1!

  O$al &%nt$a&e5ties /02-10/! 1!

H6P in &#il($en 7 a(%les&ents8 -!%8-/ is secondar0 

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Protocol

%on&irmarea hipertensiunii

 

'denti&ica etiologia

 (&ectarea peri&erica

'denti&ica riscul cardio)ascular 

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*asurare

Metoda Descriere

'n ca+inet ,oua determinari- la minute inter)al- in“se.and”/ %on&irma )alorile crescute prin citiri la+ratul contralateral/

*onitori.aream+ulatorie

'ndicata pt e)aluarea H( de “halat"al+”/ (+senta scaderii cu 10–20 a ( in somn indicarisc % crescut/

 (uto"determinare urni.ea.a in&ormatii asupra raspunsului laterapie/ Poate auta sa im+unatateascacomplianta la terapie/

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actori de 5isc pt Hipertensiune Secundara

6 5aspuns sla+ la terapie 7H( re.istenta la $ 3 medic din clase ≠

6 Pierderea controlului la pacienti sta+ili pe medicatie anti H(

6Hipertensiune stadiul 3 7SBP$180 sau ,BP$110

6 ,e+ut inainte de 20 ani sau peste 0 ani

6  (&ectare semni&icati)a a organelor tinta 7cord- ochi- rinichi

6 ipsa istoricului &amilial de hipertensiune

6 :lemente de H( secundara in anamne.a- e; clinic sau paraclinic

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Mineralocorticoid excess

Cushing’s syn.

Pheochromocytoma

Hipertensiunea endocrina secundaraHipertensiunea endocrina secundara

suprarenalasuprarenala

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Suprarenale

lucocorticoi.i 7%orti.ol

%orte; *ineralocorticoi.i 7(ldosteron

 (ndrogeni (drenocortical

*edulla %atecolamine

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Histologie

Capsula=ona glomerulosa

=ona f asciculata

=ona r eticularis

*edulosuprarenala

ena central>

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HistologieHistologie

CGA

17 HOlaza

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 Steroidogeneza specifică

lucocorticoi.i 7C21

*edulosuprarenala

*ineralocorticoi.i 7C21

 (ndrogeni 7C19

ena central>

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 Substratul steroidogenezei

18

19

 

2 CH 2!

  CH"

 

H# 

$ B

C D

CH" CH"

CH"

CH"

CH2

CH2 CH2

CH

2%

2& 2'2221

2"

12

'

%

89

1

12

1"

1&1!

1'

1%11

!"&

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Steroidogeneza

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Steroidogeneza

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%holesterol

P40%S%%

PregnenoloneP40%1#

1#?"hydro;y"pregnenolone

P40%1#,ehydroepiandrosterone

7DH($

  3@HS, 3@HS,

ProgesteroneP40%1#

1#?"hydro;y"progesterone

  P40%21 P40%21

,eo;ycorticosterone7D#C

11",eo;ycortisol

  P40%11B1 P40%11B1

%orticosterone Cortisol

  P40%11B2

$ldosterone

)*

)+

),

)*

)+

),

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Reglarea Axei CSR Reglarea Axei CSR 

• CRH / VP

• ACTH

• Cortisol

• Leptina

•  Citokine

• GR, CRHR, V1b, ACTH R,

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,itmul Circadian

-imp

Plasma

. cortisol /

0nmol3

Stres

00A00 12A00 00A0018A000!A00100

!00

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%ortisol%ortisol

H

HH

H

H

H

ortisol

!0" # CBG$ ∆4−%&eto

'" # albu(ina

'" #liber 

T1/2 )0#120 (in

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Sindromul %ushing

*indro( lini si bio+i(i deter(inat de eesul seretiei autono(e

endo-ene de orti.ol (ineraloortioi.i si andro-eni din C*R 

6 $C-H dependent 824  AC1H  Hipofi2ar 33/

 AC1H ctopic "/ AC1H cu sursa necunoscuta #/

6 $C-H independent 184 Adenom adrenal "!/ Carcinom adrenal ./

6 Hiperpla2ie macronodulara "/

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%ushing

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'storic C ta+lou clinic

• Crestere ponderala

• Te-u(entar$ piele subtire, anee, ,+irsutis(, e+i(o.e, er-eturi,+iperpi-(entare ACTH dependent

•3be.itate entrala, 4aies 5in luna plina6,adipo.itate intersapulo#ertebral si(obili.area tesutului adipos de pe (e(bre

• 7n4etii reurente

• A(enoree seundara, in4ertilitate

• *aderea 4ortei (usulare, ura -reusarile

• 8epresie, labilitate psi+o#a4etia

• HTA, 89, osteoporo.a$ seundare

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%ushing

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%ushing

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*reenin- in Cus+in-

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este screening pentru sindrom %ushingA6 %orti.ol urinar li+er 6 )ernight 7N 1"mg de;amethasone suppression test/

Confirmarea dg de sindrom Cus5ing6 5itm corti.ol6 ,D* 2;2 70/mg la ! ore- 2 .ile

(Normal 4-!nmol5l dupa #8 h)

Staili$ea :%$ei eti%5at%3eni&e6 6D* 2;8 72 mg la ! ore- 2 .ile

(Normal 4-!nmol5l dupa #8 h)6 6o2are AC1H6 Cateteri2are de sinus pietros

este dinamice in %ushing

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este dinamice in %ushing

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8ia-nosti in Cus+in- *:ndro(e

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Diagnostic Diferential

6  (%H " nedetecta+il in tumori adrenale

6 " &oarte mare in %ushing paraneopla.ic

6 HypoEaliemie 7Falcalo.a C posi+il ectopic sau GG adrenal

6 ,D* 2;8♦ # adenom hipo&i.ar 7+oala % corti.olul <0 din +a.a

10 ectopice pre.inta supresie semni&icati)a

6 Petrosal sinus sampling 7F" %5H

6 6ici un -(S- nu este 14 precis7

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7n4erior Petrosal *inus *a(plin-

V. femurala ... IPS

CRH 100 ug i.v.

Control - VCI

IPSIPS -!" 0" #" !" 10 min

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magistica

6 % a+dominal

6 *5'

6 Scintigra&ie cu scintandren 7%olesterol '131

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Boala %ushing

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Boala %ushing

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%ushing adrenal

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Nelson

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 (natomie patologica

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 (natomie patologica

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ratament

♦ ratamentul sd %ushing se adresea.a secretiei de corti.ol/♦ erapia primara pentru tumori adrenale este adrenalectomia/♦ 'n (%H ectopic- controlul hipercortisolismului se o+tine prin

medicatie/♦

'n +oala %ushingA chirurgia hipo&i.ei- adrenalectomie +ilaterala-radioterapie hipo&i.ara♦ Sd %ushing iatrogen " scaderea progresi)a a do.elor ♦ %and chirurgia nu se poate e&ectua- se poate controla

hipercortisolismul cu medicatie

7rmarirea postoperatorie'

ratament di&erit in S5 &ata de +oala %ushing

S5A su+stitutie 3 luni- apoi teste de stimulare

Boala %ushingA ree)aluare periodica la 3 " ! "12 luni

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%himioterapie

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Hiperaldosteronism primar 

♦ Hipertensiune arteriala♦ HipoEaliemie

♦  (lcalo.a meta+olica♦ Poliurie

♦ %lasi&icare etiopatogenicaA♦   #0A  sindrom %onn 7tumora %S5♦ 30A Hiperaldosteronism primar cu

hiperpla.ie adrenala +ilaterala 7iddle

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Hipertensiunea mineralocorticoida

,enin aldosterone s:stem

5enin su+strate

 (ngiotensin '  (inacti$e)

 (ngiotensin ''

$ldosterone

'ncreased per&usion pressure

5enal sodium I

Jater retention

asoconstriction hirst

oJ renal

Blood &loJ

G',N:KJutaglomerular 

apparatus

,enin

High GF

oJ arterial

pressure

Carotid sinus

oJ sodium

intaEe

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,g de &orma etiopatogenica

6 Neoplasm 7in cca !0 din ca.uriL de o+icei adenom- rar

carcinom

6 Hiperpla.ie +ilaterala 7in 40

6 Sdr/ de e;ces mineralocorticoid includ de&iciente en.imatice

6 Hiperaldosteronism autosomal dominant corectat de

administrarea de glucocorticoi.i

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:)aluare paraclinica

este de rutin>- +iochimie iș hematologie (nali.a de urin>A inclusi) densitatea- al+uminurie-Potasiu seric- calciu- creatininaunctie tiroidiana-

%olesterol- :Gradioscopie torace%atecolamine:cocardiogra&ia

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orme etiopatogenice6

 (denom %S5 cu productie de aldosteron 7(P(6 Hiperpla.ie +ilateral> idiopatic> 7'H(

6 Hiperpla.ie suprarenala primara 7unilateral>

6 %arcinom adrenocortical cu productie de (ldosteron

6 Hiperaldosteronism &amilial

6 Hiperaldosteronism remedia+il cu glucocorticoi.i 7H tip '

6 Hipertensiune arterial> prin deo;icorticosteron

6 :;ces aparent de mineralocorticoi.i

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 (natomie patologica

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ratament

6  (drenalectomie laparoscopica

6 erapie medicala daca trat chg este contraindicat

6 Spironolactona 70"200mg- corectea.a hipertensiunea

6 5 (d)A e&ecte antiandrogenice care determina ,S si

ginecomastie/

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aparoscopic

6 e&t adrenal mass-

6 e&t laparoscopicadrenalectomy

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:)aluare postoperatorie

6 unctionalA secretie tumorala 7aldosteron renina-

corti.ol- ionograma

6 5e.er)a &unctionala %S5A test la Synacthen6 *or&ologicA 'magistica adrenala

6 %omplicatiiA :cogra&ie cord- &talmologie

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eocromocitom

6 0/01"0/1 din populatia H(6 0/ din cei )eri&icati pt secretie de catecolamine

6 * M

6 ,ecada de )iata 3 "

6 5ara- de in)estigat doar in suspiciune clinicaA6 Semne sau Simptome

6 H( se)era- cri.a H(

6 H( re&ractara 7$ 3 clase de medicamente

6 H( la < 20 sau $ 0 ani

6 e.iune adrenala la imagistica S5 7e;/ incidentalom

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5egula 10O

6 10 e;tra"adrenal 7cca 1

6 10 apar la copii

6 10 &amilial 7apro; 206 10 +ilateral sau multiplu 7$ in &amilial

6 10 recidi)ea.a 7$ cele e;tra"adrenale

6 10 maligne6 10 descoperite intamplator 

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%linica

6 %inci PA6 Pressure 7H( 90

6 Pain 7Headache 80

6 Perspiration #1

6 Palpitation !4

6 Pallor 42 Paro;ysms 7the si;th PQ

6 riada clasicaA

6 Pain 7Headache- Perspiration- Palpitations6 acE o& all 3 )irtually e;cluded diagnosis o&

pheochromocytoma in a series o& $ 21-0000 patients

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:&ecte )egetati)e:&ecte )egetati)e

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5eceptori (drenergici

6  (l&a"(drenergici∀  1; )asoconstrictie)asoconstrictie-- rela;are intestinala- contractie uterina-

dilatare pupilara

∀  2; ↓ N: presinaptic 7clonidina- agregare plachetara-

  )asoconstrictie- ↓ secretiei de insulina

6 Beta"(drenergici

∀  

1; ↑ ( contractilitatii- ↑ lipoli.ei- ↑ secretiei de renina∀ 2; )asodilatatie)asodilatatie- +ronchodilatatie- ↑ glicogenoli.a

∀ "; ↑ lipoli.a- ↑ termogene.a in tesut adipos +run

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%ri.a

6 ,urata 10"!0 min

6 rec)entaA .ilnic """"" la cate)a luni

6 Spontan

6 Precipitata6 Proceduri diagnostice- contrast '/(/ 7'// nu determina cri.a

6 *edicatie 7opiode- β"+locante &ara α"+loc/ inductia

aneste.iei- histamina- (%H- glucagon- metoclopramida

6 :&&ort &i.ic- miscari care cresc presiunea intra"a+dominala

6 *ictiune 7paragangliom )e.ical

6 Nasterea

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Hipotensiune

6 Hipotensiune 7ortostaticaparo;istica

6 *ecanismeA6 %ontractia :%

6 Pierderea re&le;elor posturale data de stimulare

adrenergica prelungita

6 Secretie tumorala de adrenomedulina7neuropeptid )asodilatator

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6 ,ureri a+dominale- constipatie se)era 7megacolon

6 ,ureri precordiale6  (n;ietate

6  (ngina'* cu artere coronare normaleA

%atecholamin" indusaA ↑ consumul de o;igen miocardic sau)asospasm coronarian

6 'nsu& cardiaca glo+ala6 H( cardiomiopatie hipertro&ica dis&unctie diastolica

6 %ardiomiopatie dilatati)a indusa de catecolamine dis&unctiesistolica

6  (ritmii cardiace I de&ecte de conducere

%linica

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enetica

Sindrom Anomaliegenetica

Anomalie fenotipica

*:N 2(- 2B 10 R11/2

75:

*%- HP5- :-

neuroame mucoase-ganglioneurom

Neuro"ectodermaleN"1

1#R11 7N"1

3p2"2! 7H

Neuro&i+romato.a

 (ngioame retiniene- GG

renal- Hemang SNS,H B

S,H %-,

1p3!

1R21- 11R23

P- : malign

7n sfert din feocromocitoame% determinare genetica

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*:N2 screening

S 9adian, C Badiu et al, Acta ndocrinologica (Buc), $ol :::, no ", p " % , !!. 

rom genes to clinical picture

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rom genes to clinical picture- 0 y- se)ere HBP- aEotsu+o cardiomyopathy

6 ! mutations 74 S,H%- 2 S,H(

Ma$iana D%$es&.; Si%na Ve$<ea; C%$in 6a(i. Acta ndocrinologica (Buc), $ol ;, no #, p-#, !!<

Preop

Postop

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yrosine ",opa ,opamine

Norepinephrine

:pinephrine

Catecolamine

Normetanephrine

*etaneprine

PN*

,BH

%*

%*

*eta&oliti 

Homo)anillic acid

7H(

*(- %*

anillymandelic (cid7*(

*(

*(

H

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yrosine ",opa ,opamine

Norepinephrine

:pinephrine

Catecolamine

Normetanephrine

*etaneprine

PN*

,BH

%*

%*

*eta&oliti 

Homo)anillic acid

7H(

*(- %*

anillymandelic (cid7*(

*(

*(

Secretia tumoralaA6 eo mareA $ meta+oliti

  7meta+oli.are in tumora inainte de secretie

6 eo micA more catecholamines

6 eo Sporadic A N: $ :6 eo amilialA : $ N:6 ParagangliomA N:6 %hemodectom- glomus ugularA N:6 anglioneuromA N:6 eo malignA ,opamina- H(

6 Neuro+lastomA ,opamina- H(

H

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H( paro;istica

*esserli et al- (m %ardiol 200#L99A132C1329

9epetate cri2e de angor, cu documentarea => a 8 episoade de ?:*A

1S9 stg (feocromocitom), ",- cm

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*or&ologie

6 Small 7mg- circumscri+ed to large 7Eg masses

6 Small polygonal cells arranged in )ascular nests

6 :lectron microscopy " mem+rane +ound granules

7catecholamines

6 *alignancy is +ased on metastasis

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*eta+olism

6 Hypercalcaemia6  (ssociated *:N2 HP

6 PHrP secretion +y pheochromocytoma6 *ild glucose intolerance

6 ipolysis

6 Teight"loss6 Getosis $ , synthesis 7

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amilial

6 *:N 2a6 0 pheochromocytoma 7usually +ilateral- *%- HP

6 *:N 2+6 0 pheochromocytoma 7usually +ilateral- *%- mucosal

neuroma- mar&anoid ha+itus6 on Hippel"andau

6 0 pheochromocytoma 7usually +ilateral- retino+lastoma-cere+ellar haemangioma- nephroma- renalpancreas cysts

6 N1 7on 5ecElinghausenUs6 2 pheochromocytoma 70 i& N"1 and HN6 %a&V"au"lait spots- neuro&i+roma- optic glioma

6 amilial paraganglioma6 amilial pheochromocytoma I islet cell tumor 6 therA u+erous sclerosis- Sturge"Te+er- ata;ia"telangectgasia- %arneyWs

riad 7Pheochromocytoma- astric eiomyoma- Pulmonary chondroma

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*etane&rine plasmatice

6 Nu sunt dependente posturalA pot &i recoltate normal

6Secretate continuu de &eocromocitom

6 Sensi+ilitate 99- speci&icitate 89

6 als po.iti)A acetaminophen

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'nter&erente de do.are

6 *edicatie care creste &als po.iti) ni)elul metane&rinelorurinareA ricyclic antidepressants e)odopa a+etalol :thanol Sotalol  (mphetamines Buspirone Ben.odia.epines *ethyldopa %hlorproma.ine

6 *edicatie care scade ni)elul metane&rinelor urinare A *ethyltyrosine- Jhich inhi+its tyrosine hydro;ylase- the rate"

limiting en.yme in catecholamine synthesis *ethylglucamine- Jhich is present in radiocontrast media 5eserpine

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este in urina

6 24hA %reatinina- catecolamine- metane&rine- normetane&rine

6 5e.ultate Po.iti)e 7$ 2"3 oriA6 24h Xcatechols $ 2 ori

6 24h Xtotal metanephrines $ 1/2 ugd 7!/ umold

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este sali)are

  (/ */ Ste&anescu et al, (cta :ndocrinologica 7Buc- )ol/ ''- no/ 4- p/ 431"442- 2011

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ocali.are imagistica

6 Xltrasonogra&ia

6 % a+domen6 eocromocitom adrenal " sensi+ilitate 93"100

6 eocromocitom e;tra"adrenal " sensi+ilitate 90

6 *5'6 $ sensi+ilitate % pt &eocromocitom e;tra"adrenal

6 *'B Scan6 sensi+ilitate ##"90- speci&icitate 9"100

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:cogra&ia

6  ( &ost inlocuita de % si *5'L este limitata depregatirea tractului digesti)

6 aloare limitata in di&erentierea le.iunilor chistice decele solide in adrenala

6 *5' este pre&erata ca modalitate de in)estigare/

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:cogra&ia in eocromocitom

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% in eo

e.iuni adrenale $1 cm- e;tra"adrenale $2 cm- sensi+ilitate 9- speci&icitate #0

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%a)ogra&ie % in eo

 6M6<1'81"& pgm- *NM231# pgm- 6M62& ore<2898 mcg- *N24 oreM9 mcg

Cromogranina $<'"8 ngm

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'5* in &eocromocitom

 T1 weighted  T2 weighted

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6 *'B

6 111'ndium"pentreotide6 Some pheochromocytomas ha)e somatostatin

receptors

6 P:6 18"&luorodeo;yglucose 7,

6 !"Y18Z"&luorodopamine

ocali.are imagistica nucleara

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'magistica nucleara

6 131'"*'B si 123'"*'B sunt concentrate in sistemul simpato"medular si pastrate in granule de neurosecretie

6  (pro;imati) 30 din patienti- au un uptaEe mai mic decat cel

hepatic/

6 'n &eocromocitom- 131'"*'B e)identia.a tumora ca o arie inglanda suprarenala cu captare crescuta/

6 123'"*'B permite o calitate mai +una a imaginii- poate &ie)aluat prin single photon emission computed tomography7SP:%- are e;punere mai mica la radiatii si re.ultate in timpmai scurt/

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*'B

:n feocromocitom, "":%*:B> e$identia2a tumora ca oarie in glanda suprarenala cu captare crescuta

*etastatic Pheo

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6 12=212; '131" *'B scanA tracer pathological uptaEe on+oth lungs- Jithout a+dominal or cer)ical uptaEe

6 1%=1=21"; '131" *'B therapy 10 m %i

6 %=212 present; asymptomatic- normotensi)e patient

*etastatic Pheo

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*:N2 screening

S/ 5adian- %/ Badiu et al- (cta :ndocrinologica 7Buc- )ol/ '''- no/ 1- p/ 13 " 22- 200#

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Macroscopic view of a malignant pheochromocytoma,

demonstrating capsular invasion, hemorrhage, necrosis,

and multinodularity

 The characteristic small nests pattern was seen in allh h t h th b i li t A

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pheochromocytomas, whether benign or malignant. Agranular, basophilic cytoplasm was usually

identied surrounding slightly irregular nuclei (right)

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 ( large nest is seen u;taposed to small nests/ (n area o& central

comedonecrosis is also appreciated/

 The characteristic chromogranin (left) immunoreactiity

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in the pheochromocytes is contrasted to the S!1""protein immunoreactiity of the supporting sustentacularsupporting cells (right) in this benign pheochromocytoma

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;ana-e(ent$ (edial si aneste.i 

• Anta-onisti Al4a < 4enoiben.a(ina= >/# (etirosina=♦ 7nepe u 10(- /.i u restere pro-resia sub ontrol HTA

• Coretea.a depletia olu(ia

• Beta bloada doar dupa al4a bloada o(pleta, u propranolol, atenolol,labetalol

• ?ita eliberarea de +ista(ina

• ;onitori.are ina.ia arteriala 73p

• Aneste.ie si sedare pre#op@ *e eita +alotanul poate preipita arit(ii

• Control olu( intraasular si TA

•  itroprusiat a i@ in per4u.ie lenta, sub (onitori.area ina.ia a TA•  orartrinal i@ in per4u.ie lenta, sub (onitori.area ina.ia a TA

=ota$ tipi, sunt neesare 10#1 .ile de trata(ent pre#op

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%lase de erapie

6 asodilatatoare♦ Nitroprusiat- Nitroglicerina

6 Beta"+locante eg/ a+etalol6  (l&a"+locante eg/ entolamina

6 Blocante de %a eg/ Nicardipine

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5egim de pregatire preoperatorie

∀α F β +locada com+inata

eno;i+en.amina

6 Selecti)e α1"+locEer 7e;/ Pra.osin6 Propranolol

6 *etiro.ina

6 Blocante de %alciu 7%%B6 Nicardipina

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PreopA > +locEade

6 Start at least 10"14d preop6  (lloJ su&&icient time &or :%) re"e;pansion

6 Pheno;y+en.amine6 Special pharmacy access only 7no ,'N

6 ,rug o& choice

6 %o)alently +inds α"receptors 7α1 $ α2

6 Start 10 mg po +id  increase R2d +y 10"20 mgd

6 'ncrease until BP cntrl and no more paro;ysms

6 *aintenance 40"80 mgd 7some need $ 200 mgd

6 Salt loadA Na%l !00 mg od"tid as tolerated

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PreopA > +locEade

∀ +locEade

6 Xsed to control re&le; tachycardia and prophyla;is

against arrhythmia during surgery

6 Start only a&ter e&&ecti)e α"+locEade 7may ppt

HN

6 '& suspect %Hdilated %*K start loJ dose

6 Propanolol most studied in pheo prep Start 10 mg po +id  increase to cntrl H5

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;ana-e(ent$ re.etie +irur-iala

• ;idline or transerse abdo(inal inision

• Bilateral adrenal eploration alon- it+ eploration o4 para#aorti and paraaal retroperitoneu( diap+ra-(to pelis

• Laparosopi approa+ aeptable ia a 4lank,retroperitoneal, or transabdo(inal approa+♦ *+orter +ospital L3*

♦ Loer (orbidit: rate

♦ Hi-+er inidene o4 (issed para-an-lio(as/(ultipletu(ors

♦ Roboti sur-er:

D i li

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Deoro(oito( (ali-n

• Reidiele apar in ' #10 ani dupa re.etia le.iunii pri(are

• Pot 4i detetate 20 ani (ai tar.iu@

• *upraietuirea la ini ani$ %E # E0"@

• Trata(ent♦ Resetia (etasta.elor

♦ Controlul TA

Radioterapia paliati pentru (etasta.e osoase@♦ Terapie ablatia u 7#;7BG # raspuns partial

♦ C+e(oterapie o(binata ilo4os4a(ida, inristina si

daarba.ina poate 4i e4iae@ 

C l ii

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Conlu.ii

• HTA endorina < HTA seundara

• C*R / ;*R 

• Teste dia-nostie 4untionale in dina(ia

• Trata(ent +irur-ial