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NeuroendocrinologieNeuroendocrinologie
HipotalamusulHipotalamusul
Patologia vasopresineiPatologia vasopresinei
Diabetul insipidDiabetul insipidInsuficienta hipofizaraInsuficienta hipofizara
Corin Badiu, 2015
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NeuroEndocrinologie
Sistem nervos
SSiiststeemm
endocrendocriinn
SSiiststeemm
imunimun
citok
ine
citok
ine
neurohorm
oni
neurohorm
oni
citokinecitokine
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ProprietatiProprietati
ComuneComune
PotentiPotentiaalleeddee actiactiuunnee SSeecrcreetitiee
MMeediadiatoritori(Peptide)(Peptide)
RReeceptceptoorrii
Sp
Speciiceeciice
!mpl!mploaoarreaearaspunsuluiraspunsului "aten"atentata
#u#uratarata
RRe$la%e$la%
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Neuroseecreetie
Neurohormoni Neuromodulatori
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Sistemul port hipotalamo-hipofizarSistemul port hipotalamo-hipofizar
&r' Popa and ' ieldin$, "ancet, 2*+, 1*0
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-./.3 4 su talamus
"ocali6at inerior de talamus, portiunea ma%ora a diencealului 7entral
Re$lea6a procese metaolice si acti7itati ale S89
"ea$a sistemul ner7os de sistemul endocrin 7ia $landa pituitara, prin sinte6a sisecretia neurohormonilor, (lierine si statine)'
8euronii care secreta &nR: sunt conectati cu sistemul limic, care este implicatprimar in controlul emotiilor si acti7itatii se;uale'
:ipotalamusul controlea6a temperatura, oamea, setea si ritmul circadian' :ipotalamusul este conectat cu S8C, ormatiunea reticulata, sistemul limic
(ami$dala, septum, anda dia$onala Broca, ulul olacti7) si corte;ul cereral)'
HipotalamusHipotalamus
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FunctiiFunctii
Responsi7 la< "umina< lun$imea 6ilei si otoperioada pentru a $enera ritmurile circadian
si se6onier =lactie< stimuli, inclusi7 eromoni (parumuri) Steroi6i< $onadali si corticosteroi6i >normatii 7e$etati7e perierice < cardio7ascular, stomac, tract reproducti7
? S8 !utonom? Stimuli hormonali< leptina, $hrelin, an$iotensina, insulina, hormoni
adenohipoi6ari, citokine, $licemie, osmolaritate etc' Stress Micror$anisme< prin cresterea temperaturii, resetand termostatul'
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8uclei hipotalamici8uclei hipotalamici
Medial %rea %nterior Medial preoptic nucleus
Supraoptic nucleus
Para7entricular nucleus!nterior nucleusSuprachiasmatic nucleus
&uberal #orsomedial nucleus
9entromedial nucleus!rcuate nucleus
Posterior Mammillar@ nuclei (part o
mammillar@ odies)Posterior nucleus
'ateral %rea
%nterior
"ateral preoptic nucleus"ateral nucleus
Part o supraoptic nucleus&uberal
"ateral nucleus"ateral tueral nucleiPosterior
"ateral nucleus
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Neurohormonii
(orticotropin-releasing hormone )(H* Dopamina +onadotropin-releasing hormone )+nH*
+roth hormone releasing hormone )+HH* Somatostatin &hrotropin-releasing hormone )&H* ./tocin
%ntidiuretic Hormone )0asopresina, %DH*
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Median EminenceMedian Eminence
.rgan circumventricular.rgan circumventricular
Apendimal< ti$ht 'anicitele (D*)
>ntermediar< 9PE= a;ons
A;tern< capilare enestrate
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IN&%(INE
%1&.(INE
P%%(INE
END.(INE
NE1.END.(INE
Semnalizare
chimica /
Hormonala
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(ontrol genetic
2iosinteza
&ransport a/onal
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Slide Source:www.obesityonline.org
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Slide Source:www.obesityonline.org
Neuroendocrinologia aportului alimentarNeuroendocrinologia aportului alimentarTrunchiul cerebral - tinta pentru semnale de satietate perifericeTrunchiul cerebral - tinta pentru semnale de satietate periferice
Modified from Marx, Science2003 February 7 2!!" #$%-#$!& 'in Ne(s)
*eptin+nsulin
.hrelin
.+ tract
/pinalneres
1ag
4ypothalamus56
NT/5
Area Postrema:
part of dorsal vagal complex
chemoreceptive (no BBB)
site of neural integration
bi-directional projections to the
G tract (via vagal afferentsand efferents)
bi-directional projections to the
h!pothalamus" am!gdala and
other regions
5mylin8 peptide intestinale
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Slide Source:www.obesityonline.org
6eglarea aportului alimentar6eglarea aportului alimentar
reierreier 3actori e/terniAmotii
ipul de alimente
Comportament alimentar
actori de mediu
8PF
!&RP
$alanin
=re;inG!
d@norphin
Stimulea6aStimulea6aGMS:
CR:HC8
&"PG>
C!R
8A
5G:
>nhia>nhia
Semnale centraleSemnale centrale
&luco6a
CCI, &"PG1,!poG!G>9
!erente 7a$ale>nsulina
&hrelina
"eptina
Corti6ol
/emnale periferice/emnale periferice 9rgane periferice9rgane periferice
J
J
ract &>
esutadipos
%port dealimente
Suprarenale
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Slide Source:www.obesityonline.org
5fectiuni pulmonare5fectiuni pulmonare
Apneea obstructivaApneea obstructiva
de somnde somn#indrom de hipoventilatie#indrom de hipoventilatie
4epatopatia steato:ica4epatopatia steato:ica
non-alcoolicanon-alcoolica
steato$asteato$a
steatohepatitasteatohepatitaciro$aciro$a
;oala coronariana;oala coronariana
%iabet%iabet
%islipidemie%islipidemie
&ipertensiune arteriala&ipertensiune arteriala
5nomalii ginecologice5nomalii ginecologice
'ulburari de 'ulburari de
infertilitateinfertilitate#indromul ovarelor polichistice#indromul ovarelor polichistice
9steoartrita9steoartrita
5fectiuni cutanate5fectiuni cutanate
*itia:a biliara*itia:a biliara
ancerancer
san" uter" col" colon" esofag"san" uter" col" colon" esofag"
pancreas" rinichi" prostatapancreas" rinichi" prostata
FlebitaFlebita
#ta$a venoasa#ta$a venoasa
.uta.uta
omplicatiile medicale ale obe:itatii4ipertensiune4ipertensiune
intracraniana idiopaticaintracraniana idiopatica
5151
ataractaataracta
ancreatitaancreatita
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Slide Source:www.obesityonline.org
Tulburarile alimentatieiTulburarile alimentatiei
Anorexia nervosa 'eama intensa de castig ponderal
magine corporeala distorsionata
*efu$ul de a mentine greutatea corporala
minima recomandata
Amenoree secundara
+, din femeile tinere sunt afectate
., - femei
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Slide Source:www.obesityonline.org
Tulburarile alimentatieiTulburarile alimentatiei
Bulimia nervosa /pisoade repetate de apetit exagerat urmate
de inducerea varsaturilor
Acest comportament apare de 0-1 ori 2 sapt" 1luni
#imptomele pot apare independent de
anorexie
+-0, din tinerele femei sunt afectate
., -femei
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(ai neurale implicate in homeostazia osmotica(ai neurale implicate in homeostazia osmotica
%ntidiureza .smoreceptori
SeteSete
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eeves et al, !""#
0olum circulant
.smolaritate 'E(
Setea si balanta apeiSetea si balanta apei
45(restere
.smolaritatea 'E(
!65 Scadere
0olum circulant
.smoreceptori(NS 2aroreceptori
Descarca %DH %ngiotensina II
%ntidiureza
Stimuli
Sete
%port de apa(onservarea apei
%NP72NP %NP72NP
%petit de Na
N i i i iN i i ti t i
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Neuroimagistica seteiNeuroimagistica setei
8ece subiecti au efectuat PE&-(& si o
evaluare psihologica a setei )Denton et al9,
PN%S, ":, ;
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=;@tocinGlike peptides=;@tocinGlike peptides1 2 * D 5 K L +
C@sG@rG>leG&lnG!snGC@sGProG"euG&l@ (8:2)
./tocine
> > > > > > > Ile >
Mesotocine> > > Ser > > > Ile >
Isotocine
> > > Ser > > > +lu >
+lumitocine
> > > > > > > 0al >0alitocine
> > > %sn > > > > >
%spargtocine
9asopressinGlike peptides9asopressinGlike peptides
1 2 * D 5 K L +
C@sG@rGPheG&lnG!snGC@sGProG!r$G&l@ (8:2)
0asopressine
> > > > > > > 'is >'isine-vasopressine
> Phe > > > > > > >
Phenipressine
> > >le > > > > > >
0asotocine
Structura hormonilor neurohipofizari
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&M I
&M III
&M II
&M I0
&M 0
&M 0I
&M 0II
eceptor 0!a
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Noau paraventriculaire
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Noau supraopti?ue
Neurohpophse de rat -ME
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Neurohpophse de rat -ME
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0asopresina ./itocina
1ter
Sin
+onade
@ %H
@%dipocite
(reier
Suprarenale
3icat
%H
Muschi neted
inichi
Hipotalamus
(reier
Sindroame poliuro-polidipsiceSindroame poliuro-polidipsice
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SeteSete
%0P%0P
Sindroame poliuro-polidipsiceSindroame poliuro-polidipsice
HipotalamusHipotalamus
Polidipsie psihogenaPolidipsie psihogena
%bsenta %0P%bsenta %0P
0asopresinaza0asopresinaza
inichiAinichiArezistenta la %0Prezistenta la %0P
insuficienta renalainsuficienta renala
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>RM normal>RM normal
3echan *4 5euroendocrinolog! of Pituitar! &ormone *egulation4 /ndocrinolog! and etabolism linics +6:78.-.9+" +8
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#iaet insipid< #eicitul de !9P#iaet insipid< #eicitul de !9P #eteriorarea hipotalamusului (siteGul de sinte6a !9P), ti%ei pituitare
(transportul !9P) sau a retrohipoi6ei (siteGul de stocare !9P), 7a duce la ooala cunoscut su numele de diaet insipid central'
Mul i dintre ace ti pacien i nu au hipersemnal in 1 in loul posterior al hipoi6ei pe ima$istica RM8 a creierului'
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Diabet Insipid
(aracteristici clinice sunt rezultatul deficientei de %0P
A;cre ia unor 7olume mari de urin (poliurie)
A;cre ia de urin diluat (=SM N200 m=smH")
Cresterea osmolaritatii plasmei ( i 8aJ
seric) Stimularea setei (polidipsie)
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Cranioarin$iom
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>niltrat hipotalamicSarcoido6a
:istiocito6aMetasta6a
umora de ti%a&erminom!$enti pato$eni
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Diabet Insipid
Cele mai multe ca6uri de diaet insipid central sunt datorate
unor le6iuni care implica 6ona hipotalamusului i On %urul a6ei7entriculului trei'
#eoarece pacien ii cu diaet insipid de7in simptomatic i numaila o reducere de +0G+5 din celulele !9P, le6iunea treuie sie suicient de mare'
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Nivelurile AVP la pacien ii cu DI Central
Pe msur ce cre te osmolalitateaplasmatic, !9P se ridic la
suiec ii normali, dar rmQnesc6ut la pacien ii cu deicit de!9P complet sau par ial'
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Diagnosticul Diabetului Insipid
#etermina i dac pacientul are un rspuns adec7at la deshidratare, care
pro7oac atQt? :iperosmolalitate? :ipo7olemie
!mele ar treui s stimule6e o cre tere a !9P
estul de pri7are de ap permite dia$nosticul CQnd pacientul a pierdut 2G* din $reutatea totala a corpului i
dou urini consecuti7e dier On osmolalitate cu N10, esteo inut o proa de san$e pentru sodiu si osmolalitate
plasmatica (rar se do6ea6a !#:)'
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Raspunsul la Deshidratare
Pacien ii cu diaet insipid complet hipotalamic, in momentulde deshidratare ma;im 7or a7ean7a6i7 (!d hip, CR, meta)
2' >niltrati7 (:ist, Sarc, :emocr')
*' >narct (apople;ie !:, Sheehan)
D' >atro$en (=p, R;t)
5' >necUioas (BC, mico6e)
K' >mpact traumatic (sect' ti%a)
L' >munolo$ic (hipoi6ita)+' >6olat (Iallman sau pluritropa)
' >diopatic
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M hi i
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Metasta6e hipoi6are
:i l i hi i
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:ipopla6ia hipoi6ar
Sh h
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Sheehan
S:4nd, *4102 n$Hd", D4 * $, cortisol412 $
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eglarea %/ei +Heglarea %/ei +H
&:R: (DD) SMS (1D)
&:
>&1
&:RP
&hrelin
>nsulin olerance est
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>nsulin olerance est
0'1H0'15 >HI$c, i'7'
=ese< 0,* >HI$c
Contraindicate
Epileptic seizures
Severe heart ischemia
=ral &lucose olerance est
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=ral &lucose olerance est
=ral $lucose L5$
&: peak le7el 1 $H"
%cromegalApositive 7 differential
diagnosis
Diabetes Mellitus
>& 1 < 7ariation ith a$e E se;
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>&G1 < 7ariation ith a$e E se;
l % i + di l % i + di
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eglarea %/ei +onadiceeglarea %/ei +onadice
&nR:
": E S:
Prolactina
estosteron HA2, P$
>nhiina Hacti7ina
( t l l i t i 'H i 3SH d Ft + h
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:@pothalamic:@poph@sealPortal S@stem
&onadotrophs
&nR: este elierat in sistemulport hipotalamoG hipoi6ar,pornind din eminenamedianF ile$Qnd 7ascular adenoGhipoi6a'
Alierarea este pulsatil tonic,iniUial nocturn, apoi Vi diurn,ulterior apare o descrcare ma%or,
preGo7ulatorie'Alierarea tonic pro7ine din MB!,cea preGo7ulatorie din !:P=
(ontrolul sintezei 'H i 3SH de cFtre +nh
Pulsatile ": Pattern in :uman
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Pulsatile ": Pattern in :uman
Pulsatilit in gonadal a/is
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Pulsatile hormonesA Mi/ 7 Measure
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androgeni
testosteron
precursor - colesterol
&1 &1
&1&1
&1
&E
&ipofi$a
3& D#&
germ line cells
Sertoli cellsLeydig cells
plasma
acetate
StaStadiile dezvoltariidiile dezvoltariipubertpubertareare
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#tage +: Prepubertal" no pubic hair groFth
#tage 0: 'estes groF scrotal sHin
becomes redder and coarser
sparse and fine hair develops at
base of penis
#tage 1: Penis lengthens Fith smallincrease in diameter scrotal sHin
reddens" thicHens and crinHles"
pubic hair thicHer and coarser
#tage 7: Penis and testes continue to
groF pubic hair coarser" darHerand more curl!
#tage .: Penis at adult si$e pubic hair
covers s!mph!sis pubis and
extends to inner thighs
Stage !
Stage 4
Stage > deiodinase
"eptina
R, R: R, S: R
est la R:
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est la R:
D00 $ i'7' R:S: se msoar laiecare *0 min, * h
eglarea %/ei (Seglarea %/ei (S
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eglarea %/ei (Seglarea %/ei (S
CR: H 9P
!C:
Cortisol
"eptina
Citokine
&R, CR:R, 91, !C: R,
Procesarea proteolitica a proopiomelanocortinei (PE)
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-#& A'& -3ipotropin
-#& 3P -3ipotropin -/ndorphin
-#& et-enHephalin
Procesarea proteolitica a proopiomelanocortinei (PE)
#ecretia A'& este episodica" pulsatila si determina un nivel adecvat
d ti l
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de corti$ol
>nsulin olerance est
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0'1H0'15 >HI$c, i'7'
=e6i< 0,* >HI$c
Contraindicate
(omitialitate2oalF cardiacF ischemicF
&estul scurt de Stimulare cu %(&H
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&estul scurt de Stimulare cu%(&H
250 $ !C: i'7'
(ortisol )g5*
PrecauUii On e7aluarea hipopituitarismuluiPrecauUii On e7aluarea hipopituitarismului
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PrecauUii On e7aluarea hipopituitarismuluiPrecauUii On e7aluarea hipopituitarismului
=e6itate (&:, corti6ol On >) #iaet 6aharat (7alori &:, >&1N)
>nsu' Renala cronica (&:, PR", S:, S:, ":, C")
!nore;ia ner7oasa Vi caVe;ie (&:T A2HN, cort) :ipercorticism endo sau e;o$en (S:, S:, ":N)
#epresie (corti6ol, S:N)
8euroradiolo$ie
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8euroradiolo$ie
Radio$raia de sa turceasc
8euroradiolo$ie
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8euroradiolo$ie
omo$raia computeri6at
:ipopituitarism si Mortalitatea
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Prematura
Cerero7asculara, Cardio7asculara, Respiratorie
Cresc actorii de risc cardio7ascular? anomalii in proilul lipidic (adip' 7iscerala), Imetaolism? disunctie endoteliala
:ipopituitarism complet H partial sustituit? Sustitutie i6iolo$icaW CeW CandW Cu ce riscuriW
ratamentul cau6ei cu eect pe mortalitate? Chirur$ie, Radioterapie pt' tumori hipoi6areH de re$ selara
ratament etiolo$ic
7/25/2019 3_curs-hipotalamus-si-hipopituitarism-2015.ppt
89/91
ratament etiolo$ic
Proila;ie (Sheehan)
Chimioterapie speciica (BRC, Ca, SMSa)
Chirur$ie
Radioterapie (X, poate induce hPit)
ratament sustituti7
7/25/2019 3_curs-hipotalamus-si-hipopituitarism-2015.ppt
90/91
ratament sustituti7
Principii
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