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Localizarea hipofizei
B: Empty sella: Partea anterioara a eii turceti este ocupata progresiv de un diverticul al
spaiului subarahnoidian, coninnd LCR
TUMORILE HIPOFIZARE
Benigne (adenoame), rar maligne (numai in prezenta metastazelor)
Prevalenta: 10%-25% la autopsie
Incidenta: adenoame clinic manifeste: 1-2/100.000/an
Patogenie:
activarea oncogenelor:
- mutatie Gs alpha la 40% din tumorile GH-secretante
- PTTG: over-expressed in tumorile hipof
- mutatie Ras in tumori agresive(carcinoame)
- mutatie PRKAR1A in Carney syndrome
inactivarea unor gene supresor tumoral : MENI, AIP
alterari in expresia unor receptori si factori de crestere : FGF-2 &
ptd-FGFR4, EGF-R & ERBB2, NGF& p75NGFR activin, inhibin, follistatin, IL6,
LIF
ACROMEGALIA/ GIGANTISMUL
ADENOAME HIPOF. GH-SECRETANTE
(SOMATOTROPINOAME)
Semne
Faciale: trasaturi ingrosate, bose frontale, nas marit, prognatism, piele grasa,
largirea spatiilor interdentale
Ingrosarea vocii
Marirea limbii
Edeme ale tes. moi: sindrom tunel carpian
Modif. musculoscheletale: cresterea nr. la picior, cresterea mainilor,
osteoartrita, miopatie generalizata
Gusa si alte organomegalii (ingrosarea muc. bronsiolelor, hipertrofie
ventriculara)
COMPLICATII
1. HIPERTENSIUNE ARTERIALA (40%)
2. DIABET ZAHARAT(20%)/ TOLERANTA ALTERATA
LA GLUCOZA (40%)
3. APNEE DE SOMN OBSTRUCTIVA
4. BOALA CORONARIANA ISCHEMICA
/CEREBROVASCULARA
5. INSUFICIENTA CARDIACA CONGESTIVA
6. POLIPI COLONICI SI and CARCINOM COLONIC
7. COMPLICATII DATE DE MASA TUMORALA
INVESTIGATII
Test toleranta orala la glucoza
Lipsa de supresie a GH < 1ng/ml = acromegalie
or IGF
Radiografia de sa turceasca
1-clinoide anterioare;
2-planseu selar;
3-sinus sfenoid
4-lama patrulatera;
5.clinoide
posterioare;
6. stanca temporala;
7. clivus.
TRATAMENT
1.Chirurgia trans-sfenoidala a tumorii :
vindecare: 40-90% microadenoame;10-50% in macroadenoame
recurenta 6% la 5 ani
2. Radioterapie
Radiochirurgie Gamma-knife
3. Tratament medicamentos:
Medical therapy in
acromegaly
Somatostatin analogs
GH Receptor Antagonist
Pegvisomant
GH binding on GHR
GH
GH
Site 1
Binding
Pre-formed
GHR Dimer
Cell Surface
GH
GH
Site 2
Binding
Signal
Transduction
Generation of
IGF-l
GHRA
Site
2: 2:
Site
1 Amino
Acid
Substitution
1 Amino
Acid
Substitution
Site 1:
8 Amino Acid
Substitutions
Pre-formed
GHR Dimer
Cell Surface
GHRA
Site 2
Binding
Site 1
Binding
Site 2
Binding
Peak serum levels: 33-77
h
Reduced immunogenicity
Internalization not impaired
No
Signal
Transduction
No
Generation
of IGF-l
Improper or Nonfunctional
GHR Dimerization
Adapted from Kopchick JJ. Presented at: Global Endocrine Summit: Focus on Acromegaly; November 7-8, 2003; Barcelona, Spain.
Safe GH (%)
Tumor size
reduction
2365 (Macro)
Yes
Outcome dependent on
expertise of surgeon,
pretreatment GH, tumor
position
90
6080
Yes
1020
1043
May be seen
in PRL
cosecreting
tumors
2255 (sc)
45 (sc)
Uncertain
6070 (LA)
5060 (LA)
6090 (Micro)
Conventional radiotherapy
Dopamine agonists
SMS analog
Comments
Aggressive acromegaly
TZ, male, 32 yr
+ Left eye hemianopia
+ Central
hypogonadism
normal PRL
30
60
120
Glycaemia (mg/dl)
108
179
191
161
GH (ng/ml)
78
77
87
84
677
Aggressive acromegaly
post 2nd surgery (craniotomy)
3.4 /
2.2
cm
Before
After
3.0 /
1.4
cm
Aggressive acromegaly
surgery (SS + FS), SSA (lanreotide), gamma knife, SSA
(octreotide 30 mg/month), pegvisomant
100
80
60
40
77
677
885
855
774
793
62.2
60
36.9
35.3
29.3
20
0
Time
Nadir GH (ng/ml)
IGF1 (ng/ml)
1000
900
800
700
600
500
400
300
200
100
0
IGF1
Nadir GH in OGTT
After
PROLACTINOMUL
(TUMORA LACTOTROFA)
Cautati galactoreea!
CAUZE DE HIPERPROLACTINEMIE
1.
2.
3.
4.
5.
6.
TRATAMENT
Obiective: MicroPRL: restabilirea functiei gonadale
MacroPRL: - reducerea dimensiunii tumorii
- prevenirea expansiunii tumorii
- restabilirea functiei gonadale
Medicamentos: Agonisti dopamina
Bromocriptina 7,5 mg 15 mg/day
Cabergolina 0,5 3 mg /week
Chirurgical:
rezistenta/intoleranta la agonisti dopaminergici
MacroPRL cu fistula LCR (prolactinom invaziv )
BOALA CUSHING
(ADENOM HIPOFIZAR CORTICOTROF)
Tablou clinic
Facies: rotund, pletoric, acnee, hirsutism, rarirea pilozitatii scalpului
Crestere ponderala: obezitate tronculara cartof pe scobitori), ceafa
de bizon , depozite adipoase supraclaviculare
Piele: subtire si fragila, vergeturi purpurice pe abdomen, sani, coapse,
axile, vanatai instalate rapid, uneori hiperpigmentatie datorita excesului
de ACTH
Scaderea fortei musculaturii proximale (- genuflexiuni)
Tulburari de dispozitie, labilitate, depresie, insomnie, psihoza
Dereglari menstruale / Libidou scazut, disfunctie erectila
Oprirea cresterii la copil
COMPLICATII
1. HIPERTENSIUNE (>50%)
2. DIABET ZAHARAT(30%)/ TOLERANTA
ALTERATA LA GLUCOZA (40%)
3. OSTEOPENIE/OSTEOPOROZA
4. BOALA VASCULARA
5. COAGULOPATII
6. SINDROM METABOLIC
5. SUSCEPTIBILITATE LA INFECTII
INVESTIGATII
1. Cortisol liber urinar /24h crescut
2. Pierderea ritmului circadian
Ora 23- 24 cortizol >50nmol/l (sau de 5ug/dl)
3. Teste de supresie la Dexametazona
Overnight 1mg;
DXM 2mg x 2 zile
DXM 8mg x 2 zile
4. ACTH
5. Cateterism de sinus pietros inferior
masoara ACTH si cortisol dupa CRH (100mcg i.v.)
raport central:periferic >2 inainte de CRH
raport central:periferic >3 dupa CRH
6. K seric <3.2 mmol/l caract in sd Cushing ectopic
7. Imagistica hipofizara: MRI (80% microadenoame)
Sindromul Nelson
hiperpigmentare +
tumora hipofizara in
dimensionala +
ACTH foarte crescut
evolutie
TIROTROPINOAME
Rare, 1% din adenoamele hipof; 90% macroadenoame
produc TSH / TSH+GH /TSH+PRL
Dg: - hipertiroidism cu TSH crescut sau normal
- alpha subunits :TSH >1
- test la TRH : raspunsul TSH absent dupa TRH;
(diferentiaza tumorile TSH- secretante de rezistenta la hh. tiroidieni)
- MRI:
macroadenom hipofizar
Managementul NFPA
1. Chirurgie
2. Radioterapie
3. Medical: substitutia hipotiroidismului
CRANIOFARINGIOAMELE
Tumori cu originea in resturile epiteliale ale pungii Rathke.
Benigne, local infiltrative
Localizare: suprasellara/ intrasellara sau ambele
Este cea mai frecventa tumora cerebrala la copil
Histologie: - epiteliu adamantinos cu formare de chisturi si calcificari
- hCG prezent in fluidul chistic.
Tablou Clinic :
- Presiune intracraniana crescuta la copii
- tulburari de vedere
- diabet insipid
- hipopituitarism
- obesitate
MRI: masa tumorala cu chisturi si calcificari
Tratament: chirurgie, urmata de radioterapie , mai ales daca resturile tum sunt
vizibile sau evolutive postop