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Neuroendocrinologie Neuroendocrinologie

Hipotalamusul Hipotalamusul
Patologia vasopresinei Patologia vasopresinei
Diabetul insipid Diabetul insipid
Corin Badiu, 2011
NeuroEndocrinologie
Sistem nervos
$ $iist steem m
endocr endocriinn
$ $iist steem m
imun imun
citokine citokine
Proprietati Proprietati
Comune Comune
Potenti Potentiaallee dde e acti actiu unnee
$ $eecr creeti tiee
M Meedia diatori tori (Peptide) (Peptide)
RReecept ceptoor rii
$p $peciIice eciIice
Ampl Amploa oar rea ea raspunsului raspunsului
Laten Latenta ta
Du Durata rata
RReglaj eglaj
NeurosFFcrFFtion
Neurohormones Neuromodulateurs
Sistemul port hipotalamo Sistemul port hipotalamo- -hipofizar hipofizar
r. Popa and U. Fielding, Lancet, 238, 1930
ao0uuo sub talamus
Localizat inIerior de talamus, portiunea majora a dienceIalului ventral
Regleaza procese metabolice si activitati ale $'
Leaga sistemul nervos de sistemul endocrin via glanda pituitara, prin
sinteza si secretia neurohormonilor, (liberine si statine).
euronii care secreta nRH sunt conectati cu sistemul limbic, care este
implicat primar in controlul emotiilor si activitatii sexuale.
Hipotalamusul controleaza temperatura, Ioamea, setea si ritmul circadian.
Hipotalamusul este conectat cu $C, Iormatiunea reticulata, sistemul
limbic (amigdala, septum, banda diagonala Broca, bulbul olIactiv) si
cortexul cerebral).
Hipotalamus Hipotalamus
artin, Reichlin, 1987
unctii unctii
Responsiv la:
Lumina: lungimea zilei si Iotoperioada pentru a genera ritmurile circadian
si sezonier
OlIactie: stimuli, inclusiv Ieromoni (parIumuri)
$teroizi: gonadali si corticosteroizi
InIormatii vegetative periIerice : cardiovascular, stomac, tract reproductiv
$ Autonom
$timuli hormonali: leptina, ghrelin, angiotensina, insulina, hormoni
adenohipoIizari, citokine, glicemie, osmolaritate etc.
$tress
Microrganisme: prin cresterea temperaturii, resetand termostatul.
uclei hipotalamici uclei hipotalamici
edial Area
Anterior
Medial preoptic nucleus
$upraoptic nucleus
Paraventricular nucleus
Anterior nucleus
$uprachiasmatic nucleus
Tuberal
Dorsomedial nucleus
'entromedial nucleus
Arcuate nucleus
Posterior
Mammillary nuclei (part oI
mammillary bodies)
Posterior nucleus
Lateral Area
Anterior
Lateral preoptic nucleus
Lateral nucleus
Part oI supraoptic nucleus
Tuberal
Lateral nucleus
Lateral tuberal nuclei
Posterior
Lateral nucleus
Neurohormonii
Corticotropin-releasing hormone (CRH)
Dopamine
Gonadotropin-releasing hormone (GnRH)
Growth hormone releasing hormone (GHRH)
Somatostatin
Thyrotropin-releasing hormone (TRH)
Oxytocin
Antidiuretic Hormone (Vasopresina, ADH)
edian Eminence edian Eminence
Organ circumventricular Organ circumventricular
pendimal: tight J.
Tanicitele (T4FT3)
Intermediar: 'P&OT axons
xtern: capilare Ienestrate
NTRACRNE
AUTOCRNE
PARACRNE
ENDOCRNE
NEUROENDOCRNE
HORMONAL/
CHEMICAL
SISNALLINS
Controle gntique
Biosynthse
Transport axonale
Voies neurales impliques dans l Voies neurales impliques dans l homostasie osmotique homostasie osmotique
Antidiurse Osmorecpteurs
Soif Soif
Reeves et al, 1998
2Augmentation
Osmolarit du LEC
10 Diminution
Volume circulant
CNS osmorcepteurs
Barorecepteurs
Dscharge ADH
Angiotensine
Antidiurese Stimules
Soif
Apport deau Conservation d`eau
Volume circulant
G Osmolarit du LEC
ANP&BNP ANP&BNP
SO ET BALANCE d SO ET BALANCE d EAU EAU
Na apptite
Oxytocin Oxytocin- -like peptides like peptides
1 2 3 4 5 6 7 8 9
Cys-Tyr-Ile-ln-Asn-Cys-Pro-Leu-ly (H2)
Oxytocine
` ` ` ` ` ` ` le `
esotocine
` ` ` Ser ` ` ` le `
sotocine
` ` ` Ser ` ` ` Glu `
Glumitocine
` ` ` ` ` ` ` Val `
Valitocine
` ` ` Asn ` ` ` ` `
Aspargtocine
'asopressin 'asopressin- -like peptides like peptides
1 2 3 4 5 6 7 8 9
Cys-Tyr-Phe-ln-Asn-Cys-Pro-Arg-ly (H2)
Vasopressine
` ` ` ` ` ` ` Lis `
Lisine-vasopressine
` Phe ` ` ` ` ` ` `
Phenipressine
` ` Ile ` ` ` ` ` `
Vasotocine
$tructura hormonilor neurohipofizari
T
T
T
T V
T V
T V
T V
Rcepteur V1a
Neurohypophyse de rat -E
Vasopressine
Ocitocine
Uterus
Sein
Gonade
? AH
?Adipocite
?Cerveau Cerveau
Surrenales
oie
AH
uscle
lisse
Reins
Hypothalamus
Noyau paraventriculaire
Noyau supraoptique
Soif Soif
AVP AVP
Syndromes poliuro Syndromes poliuro- -polidipsiques polidipsiques
Hypothalamus Hypothalamus
Polidipsie psychog Polidipsie psychogne ne
Absence d l Absence d l AVP AVP
Vasopressinase Vasopressinase
Reins: Reins:
resistance a l resistance a l AVP AVP
insuffisance r insuffisance rnale nale
IRM normal IRM normal
Lechan RM. Neuroendocrinology of Pituitary Hormone Regulation. Endocrinology and Metabolism Clinics 16:475-501, 1987
Diabetes Insipidus. Deficiency of AJP
Damage to the hypothalamus (site oI A'P synthesis), the pituitary stalk (site oI
A'P transport) or posterior gland (site oI A'P storage) will result in a condition
known as central diabetes insipidus
Circulating levels oI A'P are low in this condition
Many oI these patients have absence oI the bright sign intensity oI the posterior
lobe oI the pituitary on MRI imaging oI the brain
CranioIaringiom
InIiltrat hipotalamic
Diabetes Insipidus
Most cases oI central diabetes insipidus are due to lesions that
involve the area oI the hypothalamus above the sella and
around the base oI the 3
rd
ventricle.
Because patients with diabetes insipidus become symptomatic
only with an 80-85 reduction oI A'P cells, lesions must be
suIIiciently large to destroy both sides oI the hypothalamus or
must be located in the pituitary stalk or posterior lobe oI the
pituitary.
Diabetes Insipidus
Clinical Features are the result of AJP deficiency
xcretion oI large volumes oI urine (polyuria)
xcretion oI a dilute urine (osm 200)
levation oI plasma osmolality (and serum a)
$timulation oI thirst (polydipsia)
AJP Levels in Patients with Central DI
As plasma osmolality
increases, A'P rises in
normal subjects but
remains low in patients
with complete or partial
A'P deIiciency
Diagnosis of Diabetes Insipidus
Determine whether the patient has an appropriate response to
dehydration, which causes both
Hyperosmolality
Hypovolemia
Both oI these stimuli should stimulate an increase in A'P
Formal water deprivation test may be needed
ater Deprivation
When the patient has lost 2-3 oI total body weight,
and two consecutive urines diIIer in osmolality by
10, a blood sample is obtained Ior serum sodium,
osmolality and plasma ADH.
ater Deprivation
Patients with complete hypothalamic diabetes
insipidus will have a urine osmolality 200 mosm at
a time that they are dehydrated and the serum sodium
and osmolality are elevated.
In patients with partial hypothalamic diabetes
insipidus, there will be some elevation oI urine
osmolality (possibly as high as 500 mosm) at the time
oI maximum concentration.
ater Deprivation
At this time either aqueous ADH or an analogue,
DDA'P desmopressin, is given subcutaneous and
another urine collected one hour later.
Patients with primary polydipsia have 10
increases in their urine osmolality with administration
oI ADH or DDA'P.
#esponse to Dehydration
Patients with complete hypothalamic diabetes insipidus at the
time oI maximum dehydration will
have a low urine osmolality 200 mosm
have elevated serum osmolality (~295)
have a low circulating A'P level
increase urine osmolality by greater than 50 iI administered
exogenous A'P
Treatment Option:
Diabetes nsipidus
DDAVP (Desamino-D-Arginine Vasopressin)-
10-20 micrograms 1-3 times/day via intranasal route for
maintenance or 1-2 micrograms post-operative.
or /SC route at 1/10th of dose.
Etiology !!!
Nursing Priorities and
anagement:
Hyposecretion of ADH
nterventions:
nclude accurate recording of fluid balance
Easy access to toilet facilities
Urine sampling for osmolality
edicine administration
Patient education: self-administration of medicines, fluid
balance charting, regular weight measurement
Advise early contact with medical staff if monitoring
demonstrates marked changes
Hipernatremia
Na
+
> 145 mEq/L
Hipodipsie primara, D (central sau nefrogen)
Diureza osmotica (DZ dezechilibrat)
Neurologic: astenie, stare confuzionala, convulsii, deficit focal.
Trat: Desmopresina 10 3g intranazal sau
0.12 mg x 3/zi slg (Minirin Melt)
aport hidric po sau 5% glucoza: 1-2 L
Hiponatremia
Neurologic:
greata,
edem cerebral,
cefalee,
obnubilare, coma
Semnele afectiunii de baza (Addison, hipopituitarism, SADH)
Scadere Na
+
hTa
Rapiditatea instalarii hNa
+
Na
+
< 120 mEq/L: risc vital
Hiponatremia - tratament
Etiologic
SADH: Restrictie hidrica Antagonist Rec V2 AVP = Vaptan
Substitutie corticoida (HHC Fludrocortizon, 2 x 0.1 mg/zi)
Substitutie tiroidiana: LT4 in doze de la 25 la 100 3g/zi, sub
protectie antiagreganta
Cresterea capitalului de Na: < 10-15 mEq / 24h
Solutii fiziologice sau saline hipertone 0.5 - 2 L/zi
Creste> 15mEq/zi Risc de mielinoza pontina (sdr de
demielinizare osmotica), mai sever in hNa
+
cronica
Reglarea yi explorarea hipofizei Reglarea yi explorarea hipofizei
Hipofiza: anatomie func(ional Hipofiza: anatomie func(ional
Tipuri celulare yi implica(ii func(ionale Tipuri celulare yi implica(ii func(ionale
Comunicarea hipotalamo Comunicarea hipotalamo -- hipofizar hipofizar
Axa de creytere: Axa de creytere: reglare yi explorare func(ional reglare yi explorare func(ional
Axa tiroidian: Axa tiroidian: reglare yi explorare func(ional reglare yi explorare func(ional
Axa suprarenal: Axa suprarenal: reglare yi explorare func(ional reglare yi explorare func(ional
Axa gonadic: Axa gonadic: reglare yi explorare func(ional reglare yi explorare func(ional
Explorarea: farmacologic / fiziologic ? Explorarea: farmacologic / fiziologic ?
Concluzii Concluzii
Cell Type Secretory Products Cell Population
$omatotroph rowth hormone 50
Lactotroph Prolactin 15
Corticotroph Adrenocorticotropic hormone 15
Thyrotroph Thyroid stimulating hormone 10
onadotroph Luteinizing hormone-
Follicle-stimulating hormone
10
Cell types in pars distalis
$ubstances Cell Types
Peptides:

Activin B, inhibin, Iollistatin F,
Aldosterone-stimulating Iactor U
Angiotensin II (angiotensinogen, angiotensin I-converting enzyme, cathepsin B, renin) C,,L, $
Atrial naturetic peptide
Corticotropin-releasing hormone-binding protein C
Dynorphin
alanin L, $,T
AWK (chromogranin B)
rowth hormone-releasing hormone U
Histidyl proline diketopiperazine U
Motilin $
euromedin B T
euromedin U C
europeptide Y T
eurotensin U
Protein 7B2 , T
$omatostatin 28 U
$ubstance P ($ubstance K) ,L,T
Thyrotropin-releasing hormone , L,$,T
'asoactive intestinal poltpeptide ,L,T
Growth factors:
Basic Iibroblast growth Iactor C,F
Chondrocyte growth Iactor U
pidermal growth Iactor ,T
Insulin-like growth Iactor I $,F
erve growth Iactor U
Pituitary cytotropic Iactor U
TransIorming growth Iactor alpha L,$,
'ascular endothelial growth Iactor F
Cytokines:
Interleukin-I beta T
Interleukin-6 F
Leukemia inhibitory Iactor C,F
Neurotransmitters:
Acetylcholine C,L
itric oxide F
C-corticotroph: F -Folliculostellate cell; -gonadotroph; L-Lactotroph;
$-somatotroph, T -thyrotroph; U-unknown.
Disorders of the Endocrine System
Excess or deficiency
mpaired synthesis
Transport and metabolism of
hormones
Resistance to hormone action
Reglarea Axei GH Reglarea Axei GH
HRH (44) $M$ (14)
H
IF1
HRP
hrelin
Insulin Tolerance Test
0.1/0.15 UI/Kgc, i.v.
Obese: 0,3 UI/Kgc
Contraindicate
Epileptic seizures
Severe heart ischemia
Oral lucose Tolerance Test
Oral glucose 75g
H peak level ~ 1 3g/L
Acromegaly:
positive & differential
diagnosis
Diabetes ellitus
IF-1 : variation with age & sex
Reglarea Axei CSR Reglarea Axei CSR
CRH / 'P
ACTH
Cortisol
Leptina
Citokine
R, CRHR, '1b, ACTH R,
Short ACTH Stimulation Test
250 3g ACTH i.v.
$creening in Cushing $yndrome
Diagnosis in Cushing $yndrome
InIerior Petrosal $inus $ampling
V. femurala ... PS
CRH 100 ug i.v.
Control - VC
PS: PS: -5, 0, 2, 5, 10 min
Reglarea Axei Tiroidiene Reglarea Axei Tiroidiene
TRH
T$H
T
4
/ T
3
Type II deiodinase
Leptina
T
R
, TRH
R
, T$H
R
TRH test
400 3g i.v. TRH
T$H is measured each
30 mins, Ior 3 h
Reglarea Axei Gonadice Reglarea Axei Gonadice
nRH
LH & F$H
Prolactina
Testosteron /2, Pg
Inhibina /activina
Pulsatile LH Pattern in Human
Pulsatility in gonadal axis
Pulsatile hormones: ix & easure
CONCLUZ
Evaluarea bazala pentru hormonii cu secre(ie
cvasiconstanta.
Evaluare dinamica pentru hormoni cu ritm, sau secretie
pulsatila.
Teste de inhibi(ie pentru sindroame de hipersecretie.
Teste de stimulare pentru deficit hormonal.
ntegrarea rezultatelor clinice, biochimice, imagistice.
Tineti cont de : hormoni, transport, metaboliozare,
receptori, interferente de reglare (feed-back nespecific).