Download - Patologia Suprarenaliana Feb 2008
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Patologia Patologia suprarenalianasuprarenaliana
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Glandele suprarenale - Glandele suprarenale - anatomieanatomie
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Structura suprarenaleiStructura suprarenalei
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Sinteza hormonilor Sinteza hormonilor corticosuprarenalienicorticosuprarenalieni
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Reglarea secretiei de Reglarea secretiei de glucocorticoiziglucocorticoizi
Ritmul circadian al secretiei de ACTH si cortizol
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Efectele Efectele glucocorticoizilorglucocorticoizilor
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Sindromul Sindromul CushingCushing
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Sindromul CushingSindromul Cushing Exces cronic al hormonilor Exces cronic al hormonilor
glucocorticoiziglucocorticoizi1. 1. ACTH dependentACTH dependent• AdenomAdenom hipofizar secretant de ACTH (boala hipofizar secretant de ACTH (boala
Cushing)Cushing)• Secretie Secretie ectopicaectopica de ACTH de ACTH• Rar secretie crescuta de Rar secretie crescuta de CRHCRH2. 2. ACTH independentACTH independent• AdenomAdenom suprarenalian suprarenalian • NeoplasmNeoplasm suprarenalian suprarenalian• HiperlazieHiperlazie nodulara (macro/micro) nodulara (macro/micro)• IatrogenIatrogen
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Fiziopatologie Fiziopatologie
Boala Cushing
Sindrom Cushing
Secretie ectopica de ACTH
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Manifestari clinice in Manifestari clinice in sindromul Cushingsindromul Cushing
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Manifestari osoase ale Manifestari osoase ale excesului de excesului de
glucocorticoiziglucocorticoizi
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Particularitati cliniceParticularitati clinice Sindrom pseudo-CushingSindrom pseudo-Cushingo AlcoolismAlcoolismo ObezitateObezitateo Depresie Depresie Secretia ectopica de ACTHSecretia ectopica de ACTH – –
hiperpigmentare + scadere hiperpigmentare + scadere ponderala + modificari metabolice ponderala + modificari metabolice accentuate + alcaloza hipokaliemicaaccentuate + alcaloza hipokaliemica
Carcinom suprarenalianCarcinom suprarenalian – sindrom – sindrom intens de virilizare, posibil secretie intens de virilizare, posibil secretie simultana de mineralocorticoizisimultana de mineralocorticoizi
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InvestigatiiInvestigatii HLG – Hb, Hct la limita superioara a HLG – Hb, Hct la limita superioara a
normalului normalului
– – Limfocitopenie, eozinopenieLimfocitopenie, eozinopenie Posibil diabet zaharat sau toleranta Posibil diabet zaharat sau toleranta
alterata la glucozaalterata la glucoza DislipidemieDislipidemie Ionograma de obicei normala (exceptii)Ionograma de obicei normala (exceptii) Hipercalciurie Hipercalciurie
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Investigatii diagnosticeInvestigatii diagnostice Obiective:Obiective:1.1. Confirmarea hipercorticismuluiConfirmarea hipercorticismului
- - stergerea ritmul circadian stergerea ritmul circadian al cortizolului plasmatical cortizolului plasmatic - - cortizolul liber urinarcortizolul liber urinar (> 100µg/24 ore)(> 100µg/24 ore) - teste de supresie la - teste de supresie la doze mici de dexametazona doze mici de dexametazona (1 mg overnight sau 2 x 2)(1 mg overnight sau 2 x 2)
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Investigatii diagnosticeInvestigatii diagnostice2. Precizarea cauzei2. Precizarea cauzei- Dozarea ACTHDozarea ACTH- Teste de supresie la DXM 8mgx2Teste de supresie la DXM 8mgx2- Testul la CRHTestul la CRH- Investigatii imagistice Investigatii imagistice pentru vizualizarea
SR (TC, RMN, Scintigrama cu I-colesterol), SR (TC, RMN, Scintigrama cu I-colesterol), hipofizei (b.Cushing), plamanilor (secretie hipofizei (b.Cushing), plamanilor (secretie ectopica)ectopica)
- Cateterizarea bilaterala a sinusului pietros Cateterizarea bilaterala a sinusului pietros cu dozarea ACTHcu dozarea ACTH
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A. Hiperplazie SR bilaterala la unpacient cu B.Cushing
B. Adenom SR
C. Hiperplazie adrenala macronodulara D. Hiperplazie nodulara pigmentata
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A Carcinom suprarenalian cu metastaze hepatice (B)
A Microadenom si B macroadenom hipofizar
Scintigrama cu Iod-colesterol
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Tratamentul sindromului Tratamentul sindromului CushingCushing
ChirurgicalChirurgical
- Boala Cushing – adenomectomie - Boala Cushing – adenomectomie hipofizara transsfenoidala (de electie) hipofizara transsfenoidala (de electie) sau suprarenalectomie bilateralasau suprarenalectomie bilaterala
- Sindrom Cushing – extirparea tumorii - Sindrom Cushing – extirparea tumorii suprarenalienesuprarenaliene
- Cushing paraneoplazic – extirparea - Cushing paraneoplazic – extirparea tumoriitumorii
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Tratamentul sindromului Tratamentul sindromului CushingCushing
Radioterapie hipofizaraRadioterapie hipofizara – pentru – pentru prevenirea sd. Nelson dupa prevenirea sd. Nelson dupa suprarenalectomia bilaterala in boala suprarenalectomia bilaterala in boala CushingCushing
Tratament medicamentos:Tratament medicamentos:- Inhibitori ai sintezei de steroiziInhibitori ai sintezei de steroizi: :
ketoconazol, metyrapon, aminoglutetimidketoconazol, metyrapon, aminoglutetimid- MitotanMitotan: inhibitor enzimatic, adrenolitic, : inhibitor enzimatic, adrenolitic,
citostatic (carcinomul suprarenalian)citostatic (carcinomul suprarenalian)
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Sdr. Nelson Sdr. Nelson
2006-RMN adenom hipofizar
cu dimensiunile maxime de
25/16mm
2007 :
cortizol seric= 1,56mg/dl
ACTH>1250 pg/ml
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Sdr. Nelson Sdr. Nelson Diagnostic
1. Insuficienta corticosuprarenala primara iatrogena (postsuprarenalectomie bilaterala pentru boala Cushing)
2. Sdr Nelson
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Hipertensiunea Hipertensiunea de cauza de cauza
endocrinaendocrina
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HTA secundara - etiologieA. HTA de cauza renala 1. HTA renovasculara – Stenoza ateromatoasa a arterei renale – Displazie fibromusculara a arterei renale – Embolii si tromboze ale arterelor renale 2. HTA renoparenchimatoasa – Glomerulonefrite acute sau cronice – Pielonefrita cronica si alte nefropatii
interstitiale – Rinichi polichistic – Colagenoze, vasculite, DiabetB. HTA de cauza endocrina 1. Suprarenaliana – Feocromocitom – Hipersecretie de mineralocorticoizi – Sindromul si boala Cushing 2. Alte endocrinopatii – acromegalie, hiperparatiroidism, hipertiroidismC. HTA de cauza cardiovasculara – Coarctatie de aorta – Insuficienta aortica – BAV de grad inaltD. HTA de cauza neurologica: 1. Hipertensiune intracraniana (tumori,
encefalite) 2. PoliomielitaE. HTA medicamentoasa: ciclosporina, corticoizi, AINS (ibuprofen,
piroxicam, coxibi), estrogeni, amfetamine, bromocriptina, IMAO, steroizi anabolizanti)
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HTA secundara de cauze HTA secundara de cauze endocrineendocrine
Exces de mineralocorticoizi Exces de mineralocorticoizi FeocromocitomFeocromocitom Sindrom CushingSindrom Cushing AcromegalieAcromegalie HiperparatiroidismHiperparatiroidism Hipertiroidism (numai TA sistolica)Hipertiroidism (numai TA sistolica)
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Hiperaldosteronismul Hiperaldosteronismul primarprimar
CauzeCauze AdenomAdenom secretant de aldosteron secretant de aldosteron
(sindrom Conn)(sindrom Conn) Hiperplazie Hiperplazie adrenala primaraadrenala primara CarcinomCarcinom suprarenalian suprarenalian
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Aldosteronul – mecanism de Aldosteronul – mecanism de actiune si reglare actiune si reglare
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Excesul de mineralocorticoizi – elemente de suspiciune
Simptomatologie neuromusculara (slabiciune musculara, crampe, paralizie periodica), astenie, parestezii
HTA moderata – severa, fara edeme Poliurie, nicturie Afectarea organelor tinta – HVS disproportionata
fata de nivelul TA, reversibila HTA cu hipopotasemie, in lipsa tratamentului
diuretic
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Investigatii paracliniceInvestigatii paraclinice
HipopotasemieHipopotasemie (< 3,5 mEq/L), in (< 3,5 mEq/L), in lipsa tratamentului diuretic, aport lipsa tratamentului diuretic, aport normal-crescut de sarenormal-crescut de sare
Hiperkaliurie Hiperkaliurie Alcaloza hipercloremicaAlcaloza hipercloremica
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Investigatii hormonaleInvestigatii hormonaleScreeningScreening ARP (<1 ng/ml/h)ARP (<1 ng/ml/h) Aldosteron plasmatic (clino, aport Na normal sau crescut)>15 Aldosteron plasmatic (clino, aport Na normal sau crescut)>15
ng/mlng/ml Raport AP/ ARP > 25 (dupa 2 ore ortostatism)Raport AP/ ARP > 25 (dupa 2 ore ortostatism)
Confirmarea secretiei autonome de aldosteronConfirmarea secretiei autonome de aldosteron Incarcare de volumIncarcare de volum (2 l SF in 2-4 ore), (2 l SF in 2-4 ore), Incarcarea orala cu sareIncarcarea orala cu sare (10 g NaCl * 3 zile) (10 g NaCl * 3 zile)
Diagnostic diferential adenom – hiperplazieDiagnostic diferential adenom – hiperplazie Imagistic: TC, scintigrama cu derivati de colesterol marcati cu Imagistic: TC, scintigrama cu derivati de colesterol marcati cu
I131I131
Cateterizare venelor suprarenale cu raportarea valorilor Cateterizare venelor suprarenale cu raportarea valorilor
aldosteronului (>4, dupa corectarea in fct de cortisol)aldosteronului (>4, dupa corectarea in fct de cortisol)
Nu este inhibata secretia de aldosteron
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Diagnostic diferentialDiagnostic diferential Hiperaldosteronismul secundarHiperaldosteronismul secundar (clinica: (clinica:
ciroza, IC, HTA reno-vasculara; ARP ciroza, IC, HTA reno-vasculara; ARP crescuta)crescuta)
Alte cauze de exces de Alte cauze de exces de mineralocorticoizimineralocorticoizi
Deficit de 17 alfa hidroxilaza, 11 beta Deficit de 17 alfa hidroxilaza, 11 beta hidroxilazahidroxilaza
Excesul aparent de mineralocorticoizi Excesul aparent de mineralocorticoizi (deficit de 11 beta HSD)(deficit de 11 beta HSD)
Sindromul Liddle (mutatie activatoare a Sindromul Liddle (mutatie activatoare a canalului de Na de la nivelul TC)canalului de Na de la nivelul TC)
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Tratamentul Tratamentul hiperaldosteronismului hiperaldosteronismului
primarprimar Chirurgical: Chirurgical: Suprarenalectomie Suprarenalectomie
unilateralaunilaterala in sindromul Conn in sindromul Conn Medicamentos:Medicamentos:- SpironolactonaSpironolactona 200-400 mg/zi 200-400 mg/zi- AmiloridAmilorid 20-40mg/zi 20-40mg/zi
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Medulosuprarenala Medulosuprarenala
Tesut cromafin cu origine la nivelul Tesut cromafin cu origine la nivelul crestei neurale, similar ganglionilor crestei neurale, similar ganglionilor simpaticisimpatici
80% epinefrina, 20% noradrenalina80% epinefrina, 20% noradrenalina
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Fiziologia sistemului Fiziologia sistemului simpato-adrenalsimpato-adrenal
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Metabolizarea Metabolizarea catecoalminelorcatecoalminelor
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Feocromocitomul Feocromocitomul Tumora MSR ce Tumora MSR ce
secreta secreta catecolaminecatecolamine
10% extramedulare10% extramedulare 10% bilaterale10% bilaterale 10% maligne10% maligne 10% apar la copii10% apar la copii
Sporadic
Familial
- MEN 2a: + carcinom medular tiroidian + hiperplazie PTH
- MEN 2b: + neurinoame, pete café au lait, aspect marfanoid + hiperplazie PTH
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ClinicaClinica
Cei 5 P’:Cei 5 P’: Pressure (HTA)Pressure (HTA) 90%90% Pain (Cefalee)Pain (Cefalee) 80%80% PerspirationPerspiration 71%71% Palpitatii Palpitatii 64%64% PaloarePaloare 42%42%
Paroxisme (Paroxisme (al saselea P!al saselea P!)) Triada clasica:Triada clasica:
Cefalee, transpiratii, palpitatiiCefalee, transpiratii, palpitatii
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Criza tipicaCriza tipica
Durata Durata 10-60 min10-60 min Frecventa: zilnic - lunarFrecventa: zilnic - lunar Spontane sauSpontane sau Precipitate:Precipitate:
Proceduri diagnostice (substanta de contrast)Proceduri diagnostice (substanta de contrast) Medicamente (opioide, Medicamente (opioide, -blocante, anestezice, -blocante, anestezice,
histamina, ACTH, glucagon, metoclopramid)histamina, ACTH, glucagon, metoclopramid) Efort fizic intens, miscari ce cresc presiunea Efort fizic intens, miscari ce cresc presiunea
intraabdominala intraabdominala Mictiune (paraganglioame vezicale)Mictiune (paraganglioame vezicale)
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Indicatii pentru Indicatii pentru screeningscreening
HTA cu manifestari paroxistice HTA cu manifestari paroxistice sugestive (triada cefalee-palpitatii-sugestive (triada cefalee-palpitatii-diaforeza)diaforeza)
HTA refractaraHTA refractara HTA labilaHTA labila Raspuns presor sever sau Raspuns presor sever sau
hipotensiune inexplicabila indusa de hipotensiune inexplicabila indusa de anestezie, chirurgieanestezie, chirurgie
Masa SR descoperita intmplatorMasa SR descoperita intmplator
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Algoritm diagnostic Algoritm diagnostic
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Investigatii imagisticeInvestigatii imagistice
RMN – semnal intens in T2
CT abdominal
Ecografie abdominala
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Investigatii imagisticeInvestigatii imagistice
Scintigrama cu MIBG
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Tratament Tratament
Medicamentos preoperatorMedicamentos preoperator::
- Blocante ale canalelor de calciuBlocante ale canalelor de calciu
- Blocante alfa-adrenergice (fenoxibenzamina, Blocante alfa-adrenergice (fenoxibenzamina,
prazosin)prazosin)
- Inhibitori ai enzimei de conversieInhibitori ai enzimei de conversie
Interventie chirurgicala de excizie a Interventie chirurgicala de excizie a
tumoriitumorii
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Alte cauze endocrine de Alte cauze endocrine de HTA secundaraHTA secundara
Sindrom Cushing:Sindrom Cushing: - sinteza crescuta DOCsinteza crescuta DOC- sinteza crescuta angiotensinogensinteza crescuta angiotensinogen- stimulare R aldosteron (11 stimulare R aldosteron (11 ββ HSD HSD
depasita)depasita) AcromegalieAcromegalie ( (retentie de Na, retentie de Na,
expansiune de volumexpansiune de volum)) HiperparatiroidismHiperparatiroidism ( (secundar secundar
hipercalcemieihipercalcemiei))