Sindromul adreno-

genital

(CAH)
 Definitie
 Maladie genetica cu transmitere autosomal
recesiva care afecteaza sinteza steroizilor
adrenali.
 Defectul este expresia unui deficit enzimatic
adrenal.
 5 deficite enzimatice majore
 21-Hidroxilaza
 11-b-Hidroxilaza
 17-Hidroxilaza
 3-b- OH steroid hidrogenaza
 20,22 desmolasa
 .
.
 Deficit de 21-Hidroxilaza
 Cel mai frecvent >80% din cazuri.
 Incidenta 1:5000 si 1:15000 de nasteri .
 Gena localizata pe bratul scurt al
cromosomului 6.
 Purtatorii heterozigoti pot fi depistati prin
testul la ACTH.
 Deficit de 21-Hidroxilaza

 clasic ( virilizare precoce cu sau

fara pierdere de sare)

 non-clasic ( late-onset virilization)

 Deficit de 11--Hidroxilaza
 5-10% din CAH.
 Gena-brat lung cromosomul 8.
 ↑ 11-Deoxycortisol si 11-
deoxycorticosterone.
 Retinere de sare, HTA & alcaloza
hipokaliemica
 ↑ androgeni plasmatici ≡ virilizare fat de sex
feminin
 Deficit de 17--Hidroxilaza

 Gena localizata pe cromosom 10.

 Aspecte clinice similare cu cele din
deficitul de 11-hidroxilaza fara
virilizare la fete & OGE ambigue la
baieti.
 Deficit de 3--hidroxisteroid
dehidrogenaza

 Acumularede DHEA care se

transforma in T in periferie.

 Virilizare OGE la F .
Congenital Lipoid Adrenal Hyperplasia
 .
.
 Baietii cu CAH
 Nupoate fi diag. la nastere (OGE
normale).

 Criza
de pierdere de sare sau
pubertate precoce.

 HTA& hipokalemie la cei cu deficit de

11--hidroxilaza si 17--hidroxilaza.
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.
 .
.
 CAH

Cholesterol
Pituitary
Pregnenolone
Progesterone ACTH
17-OH progesterone
Adrenal cortex

21-hydroxylase

Cortisol Androgens Cortisol Androgens
 Diagnostic

 Crestere
lineara accentuata, v.o.
avansata, statura finala mica

 Pseudohermafroditism la fete

 Precocitate isosexuala la baieti

 Diagnostic

 ACTH, cortisol, aldosterone,

17-OH-P, T
 Evolutie

 50% din cei cu forma clasica

(CYP21) au sindrom de pierdere de
sare.

 La fete diag. se pune la nastere

datorita ambiguitatii genitale.
 Tratament
 Tratament permanent
 Principii:
 prevenirea inchiderii precoce
cartilaje de crestere
 normalizarea ionogramei
normalizarea cortisol
Scaderea T si 17-OH-P
 Tumorile secretante de catecolamine

Neural Crest

Sympathoadrenal Progenitor Cell Neuroblastoma

(Neuroblasts)

Chromaffin Cell Sympathetic Ganglion Cell

Intra-adrenal Extra-adrenal Ganglioneuroma

Pheochromocytoma
 Tumorile secretante de catecolamine

 Feocromocitomul

 Paragangliomul (feo extra-adrenal)

 Originar in lantul simpatic extra-adrenal /tesut cromafin

 Ganglioneurinomul
 Tumorile secretante de catecolamine
 Neuroblastomul
 Tumora maligna mai frecventa la copii
 Efect catecolic minor
 Crestere rapida cu metastaze
 Rx complex (chirurgie, XRT, chimio)

 Tumora glomus jugular

 Ram intracranian n.cr. IX si X
 Se comporta biochimic ca un paragangliom
 Catecholamines Metabolites
TH MAO, COMT
Tyrosine L-Dopa Dopamine Homovanillic acid
(HVA)
DBH

NorepinephrineCOMT Normetanephrine

PNMT MAO
COMT
Epinephrine Metaneprine
MAO
Tumor Secretion:
• Large Pheo: more metabolites
(metabolized within tumor before release) Vanillymandelic Acid
• Small Pheo: more catecholamines (VMA)
• Sporadic Pheo: Norepi > Epi
• Familial Pheo: Epi > Norepi •PNMT: Phenylethanolamine-N-
• Paraganglioma: Norepi Methyl Transferase
• Cheodectoma, glomus jugulare: Norepi •COMT : Catechol-O-Methyl
• Gangioneuroma: Norepi
• Malignant Pheo: Dopamine, HVA Ttransferase
• Neuroblastoma: Dopamine, HVA •MAO: Mono-Amine Oxidase
 .
.
 Receptori adrenergici

 Receptorii alfa
 1: vasoconstrictie, relaxare intestinala, contractie
uterina, dilatare papilara
 2: agregare plachetara, vasoconstrictie,  secretia de
insulina
 Receptorii beta
 1:  contractilitatii,  lipoliza,  secretia de renina
 2: vasodilatie, bronchodilatie,  glicogenoliza
 3:  lipoliza,  termogenezei grasime bruna
 Feocromocitomul
 0.01-0.1% din HTA

 B=F
 3 la 5 decada de viata
 Rar, investigat numai in caz de suspiciune clinica:
 Semne sau simptome
 HTA severa, criza
 HTA refractara la 3 medic.
 Leziune adrenala gasita intimplator (ex. Incidentalom)
 Feo: Semne & Simptome
 Cei 5 P :
 Pressure (HTA) 90%
 Pain (Cefalee) 80%
 Perspiration 71%
 Palpitation 64%
 Pallor 42%
 Paroxysms
 Triada clasica:
 Pain , Perspiration, Palpitations
 Lipsa celor 3 semne exclude diagnosticul de feo intr-o serie >
21,0000 pacienti
 Feo: criza
 10-60 min
 Frecventa: zilnic- lunar
 Apare spontan
 Precipitata de:
 Medicamente (opiode, histamina, ACTH, glucagon,
metoclopramid)
 Efort, presiune, lovituri
 Mictiune (paragangliom vezical)
 Feo: Hipotensiune!
 Hipotensiune (ortostatica/paroxism)
 Mecanism
 Pierderea reflexelor posturale datorita stimularii
catecolaminice prelungite
 Eliberare din tumora de adrenomedullina
(neuropeptid vasodilatator)
 Feo: Semne & Simptome
 Dureri abdominale, constipatie (megacolon)
 Dureri toracice
 Anxietate
 Angina/MI
 Insuficienta cardiaca
 Tulburari de ritm si de conducere
 Feo: Semne (metabolice)
 Hipercalcemia
 MEN2 HPT
 PTHrP
 Intoleranta moderata la glucoza
 Lipoliza
 Scadere ponderala
 Cetoza
 Feo: ‘Regula celor 10’
 10% extra-adrenale (~ 15%)
 10% apar la copii
 10% familial (~ 20%)
 10% bilateral sau multiple ( familial)
 10% recurente (extra-adrenal)
 10% maligne
 10% descoperite incidental
 Feo-familial
 MEN 2a
 50% Feo ( bilateral), MTC, HPT

 MEN 2b
 50% Feo (bilatl), MTC, neurome mucoase,

marfanoid habitus
 Von Hippel-Landau
 50% Pheo ( bilat), retinoblastom, hemangiom

cerebelos, nefrom, chist renal/ pancreatic

 NF1 (Von Recklinghausen's)
 2% Feo (50% if NF-1 and HTN)

 Café-au-lait pete, neurofibroma, gliom optic

 Paragangliom familial
 Urina 24h
 24h urine collection:
 Creatinina, catecolamine, metanefrine, VMA, +/-
dopamine
 Rezultate pozitive : cind valorile sunt duble
sau triple
 Rezultate fals positiv
 Medicamente: MAO-i, levodopa,
methyldopa, labetalol, propanolol, opiods,
amphetamines, cocaine, etanol
 Intrerupere cel putin 2 saptamini!
 Stress fizic major (hipoglicemia, AVC)
Importanta testelor biochimice
SEN SPEC
Ucatechols 83% 88%
Utotal metanephrines 76% 94%
Ucatechols+metaneph 90% 98%
UVMA 63% 94%
Plasma catecholamines 85% 80%
Plasma metanephrines 99% 89%
 Localizare
 CT abdomen
 Adrenal feo SEN 93-100%
 Extra-adrenal feo SEN 90%
 MRI
 > SEN decit CT pentru extra-adrenal feo
 Localizare: scintigrama

 MIBG Scan
 SEN 77-90% SPEC 95-100%
 Localizare

 MIBG
 111Indium-pentreotide

 PET
 18 F-fluorodeoxyglucose (FDG)
 6-[18F]-fluorodopamine
 Pregatirea preoperatorie
 Blocare  + 
 Phenoxybenzamine
 Selectiv 1-bloc (ex. Prazosin)
 Propanolol
 Metyrosine
 Blocanti canale calciu (CCB)
 Nicardipine
 Feo: criza hipertensiva
 IV phentolamine
 IV NTP
 IV esmolol
 IV labetalol –  +  blocker
HIPERALDOSTERONISM

.
 Tablou clinic clasic
 5-10% din HTA
 Hipokalemia (poate fi normala)
 Alcaloza metabolica
 Simptome nespecifice (astenie musculara, poliuria,
polidipsia)
 .
.
Collecting tubule cell
 De ce alcaloza metabolica ?
 ↑ aldosteron duce la excretia de K+ si H+
la schimb cu Na+

 Aldosteronul stimuleaza H+ ATPase in

celulele tubului colector  cresterea
reabsorbtiei of HCO3-
 HTA secundara

 <1% HTA

 5-10% ( depinde de modul de screening)

 Cind se screeneaza ?
 La hipertensivii cu :
– hipokalemia
– HTA severa, rezistenta sau relativ acuta
– incidentalom adrenal
 Metode de screening
 Aldosteron conc. / Renin activit
 Positive daca >20 ( >30)
 Aldosteron conc. >15 ng/dL
 2 eventualitati
 ↑ renina, ↑ aldosteron ( <10) – Secundar

 ↓ renina, ↑ aldosteron ( >20) – Primar

 Etiologie
 Primar (adrenal)  Secundar (extra-adrenal)
 Renin supresata  Renin
– Hyperplasia 70% – Tumori secretante de
– Adenom 25% renina
– Carcinom 5% – Ciroza
– Diuretice, hipovolemie
 Diagnostic
 Aldosteron >15 ng/dL
 Aldo / Renin >20
 Imagerie adrenala
 18-OH Corticosterone (diagnostic diferential
intre hiperplasie si adenom)
– >100 posibil adenoma
– <60 posibila hiperplasie
 Tratament
 Adenom / Carcinom  Hiperplazie
– chirurgie – Spironolactona – (max
– spironolactona pre- 200mg/zi )
operator