Hipertensiunea arteriala endocrina

Sindromul Cushing
Hiperaldosteronismul primar
Feocromocitomul
Factori de Risc pt Hipertensiune Secundara

Raspuns slab la terapie (HTA rezistenta la > 3 medic din clase )

Pierderea controlului la pacienti stabili pe medicatie anti HTA

Hipertensiune stadiul 3 (SBP>180 sau DBP>110)

Debut inainte de 20 ani sau peste 50 ani

Afectare semnificativa a organelor tinta (cord, ochi, rinichi)

Lipsa istoricului familial de hipertensiune

Elemente de HTA secundara in anamneza, ex clinic sau paraclinic

Sindromul Cushing
Sindrom clinic si biochimic determinat de excesul secretiei autonome endogene de cortizol mineralocorticoizi
si androgeni din CSR

ACTH dependent
ACTH Hipofizar
ACTH Ectopic
ACTH cu sursa necunoscuta

82%
66%
12%
4%

ACTH independent
Adenom adrenal
Carcinom adrenal
Hiperplazie macronodulara

18%
10%
7%
1%

Istoric tablou clinic

Crestere ponderala

Tegumentar: piele subtire, acnee, , hirsutism, echimoze, vergeturi, hiperpigmentare (ACTH dependent)

Obezitate centrala, facies in luna plina, adipozitate interscapulo-vertebral si mobilizarea tesutului

adipos de pe membre

Infectii recurente

Amenoree secundara, infertilitate

Scaderea fortei musculare, urca greu scarile

Depresie, labilitate psiho-afectiva

HTA, DZ, osteoporoza: secundare

Teste dinamice in Cushing
Teste screening pentru sindrom Cushing:

Cortizol urinar liber

Overnight (ON) 1-mg dexamethasone suppression test.

Confirmarea dg de sindrom Cushing

Ritm cortizol

DXM 2x2 (0.5mg la 6 ore, 2 zile)

(Normal <50nmol/l dupa 48 h)
Stabilirea formei etiopatogenice

DXM 2x8 (2 mg la 6 ore, 2 zile)

(Normal <50nmol/l dupa 48 h)

Dozare ACTH

Cateterizare de sinus pietros

Diagnostic Diferential

ACTH - nedetectabil in tumori adrenale

- foarte mare in Cushing paraneoplazic

Hypokaliemie (+alcaloza) posibil ectopic sau KK adrenal

DXM 2x8

75% adenom hipofizar (boala C) cortizolul <50% din baza

10% ectopice prezinta supresie semnificativa

Petrosal sinus sampling (+/- CRH)

V. femurala ... IPS
CRH 100 ug i.v.
Control - VCI
IPS: -5, 0, 2, 5, 10 min

Nici un TEST nu este 100% precis!

Imagistica

CT abdominal
MRI
Scintigrafie cu scintandren (Colesterol I131)

Nelson
Tratament

Tratamentul sd Cushing se adreseaza secretiei de cortizol.

Terapia primara pentru tumori adrenale este adrenalectomia.

In ACTH ectopic, controlul hipercortisolismului se obtine prin medicatie.

In boala Cushing: chirurgia hipofizei, adrenalectomie bilaterala, radioterapie hipofizara

Sd Cushing iatrogen - scaderea progresiva a dozelor

Cand chirurgia nu se poate efectua, se poate controla hipercortisolismul cu medicatie

Chimioterapie

Hiperaldosteronism primar
Hipertensiune arteriala
Hipokaliemie
Alcaloza metabolica
Poliurie
Clasificare etiopatogenica:
70%: sindrom Conn (tumora G CSR)
30%: Hiperaldosteronism primar cu hiperplazie adrenala bilaterala (Liddle)
Dg de forma etiopatogenica

Neoplasm (in cca 60% din cazuri; de obicei adenom, rar carcinom)

Hiperplazie bilaterala (in 40%)

Sdr. de exces mineralocorticoid includ deficiente enzimatice

Hiperaldosteronism autosomal dominant corectat de administrarea de glucocorticoizi

Evaluare paraclinica
Teste de rutin, biochimie i hematologie
Analiza de urin: inclusiv densitatea, albuminurie,
Potasiu seric, calciu, creatinina
Functie tiroidiana,
Colesterol, TG
EKG
radioscopie torace
Catecolamine
Ecocardiografia
Forme etiopatogenice

Adenom CSR cu productie de aldosteron (APA)

Hiperplazie bilateral idiopatic (IHA)

Hiperplazie suprarenala primara (unilateral)

Carcinom adrenocortical cu productie de Aldosteron

Hiperaldosteronism familial

Hiperaldosteronism remediabil cu glucocorticoizi (FH tip I)

Hipertensiune arterial prin deoxicorticosteron

Exces aparent de mineralocorticoizi

Tratament

Adrenalectomie laparoscopica

Terapie medicala daca trat chg este contraindicat

Spironolactona (50-200mg), corecteaza hipertensiunea

R Adv: efecte antiandrogenice care determina TDS si ginecomastie.

Laparoscopic
Left adrenal mass,
Left laparoscopic adrenalectomy
Evaluare postoperatorie

Functional: secretie tumorala (aldosteron/ renina, cortizol), ionograma

Rezerva functionala CSR: test la Synacthen

Morfologic: Imagistica adrenala

Complicatii: Ecografie cord, Oftalmologie

Feocromocitom

0.01-0.1% din populatia HTA

0.5% din cei verificati pt secretie de catecolamine

M=F

Decada de viata 3 -5

Rara, de investigat doar in suspiciune clinica:

Semne sau Simptome

HTA severa, criza HTA

HTA refractara (> 3 clase de medicamente)

HTA la < 20 sau > 50 ani

Leziune adrenala la imagistica SR (ex. incidentalom)

Regula 10

10% extra-adrenal (cca 15%)

10% apar la copii
10% familial (aprox 20%)

10% recidiveaza (> cele extra-adrenale)

10% maligne
10% descoperite intamplator

10% bilateral sau multiplu (> in F familial)

Clinica

Cinci P:

Pressure (HTA)
90%

Pain (Headache)
80%

Perspiration
71%

Palpitation
64%

Pallor
42%

Paroxysms (the sixth P!)

Triada clasica:

Pain (Headache), Perspiration, Palpitations

Lack of all 3 virtually excluded diagnosis of pheochromocytoma in a series of > 21,0000 patients
Receptori Adrenergici

Alfa-Adrenergici

1: vasoconstrictie, relaxare intestinala, contractie uterina, dilatare pupilara

2: NE presinaptic (clonidina), agregare plachetara,

vasoconstrictie, secretiei de insulina

Beta-Adrenergici

1: AV / contractilitatii, lipolizei, secretiei de renina

2: vasodilatatie,
vasodilatatie bronchodilatatie, glicogenoliza

3: lipoliza, termogeneza in tesut adipos brun

Criza

Durata 10-60 min

Frecventa: zilnic ----- la cateva luni

Spontan

Precipitata

Proceduri diagnostice, contrast I.A. (I.V. nu determina criza)

Medicatie (opiode, -blocante fara -bloc. inductia anesteziei, histamina, ACTH, glucagon,
metoclopramida)

Effort fizic, miscari care cresc presiunea intra-abdominala

Mictiune (paragangliom vezical)

Nasterea

Hipotensiune

Hipotensiune (ortostatica/paroxistica)
Mecanisme:
Contractia V LEC
Pierderea reflexelor posturale data de stimulare adrenergica prelungita
Secretie tumorala de adrenomedulina (neuropeptid vasodilatator)

Clinica

Dureri abdominale, constipatie severa (megacolon)

Dureri precordiale
Anxietate
Angina/IM cu artere coronare normale:
Catecholamin- indusa: consumul de oxigen miocardic sau vasospasm coronarian
Insuf cardiaca globala
HTA cardiomiopatie hipertrofica disfunctie diastolica
Cardiomiopatie dilatativa indusa de catecolamine disfunctie sistolica
Aritmii cardiace & defecte de conducere

Genetica
MEN2 screening
From genes to clinical picture
F, 50 y, severe HBP, Takotsubo cardiomyopathy

6 mutations (4 SDHC, 2 SDHA)

HTA paroxistica
Morfologie

Small (mg), circumscribed to large (kg) masses

Small polygonal cells arranged in vascular nests

Electron microscopy - membrane bound granules (catecholamines)

Malignancy is based on metastasis

Metabolism

Hypercalcaemia
Associated MEN2 HPT
PTHrP secretion by pheochromocytoma
Mild glucose intolerance
Lipolysis
Weight-loss
Ketosis > VLDL synthesis (TG)

Familial

MEN 2a

50% pheochromocytoma (usually bilateral), MTC, HPT

MEN 2b

50% pheochromocytoma (usually bilateral), MTC, mucosal neuroma, marfanoid habitus

Von Hippel-Landau

50% pheochromocytoma (usually bilateral), retinoblastoma, cerebellar haemangioma, nephroma,

renal/pancreas cysts

NF1 (Von Recklinghausen's)

2% pheochromocytoma (50% if NF-1 and HTN)

Caf-au-lait spots, neurofibroma, optic glioma

Familial paraganglioma
Familial pheochromocytoma & islet cell tumor
Other: Tuberous sclerosis, Sturge-Weber, ataxia-telangectgasia, Carneys Triad (Pheochromocytoma,
Gastric Leiomyoma, Pulmonary chondroma)

Metanefrine plasmatice

Nu sunt dependente postural: pot fi recoltate normal

Secretate continuu de feocromocitom

Sensibilitate 99%, specificitate 89%

Fals pozitiv: acetaminophen

Interferente de dozare

Medicatie care creste fals pozitiv nivelul metanefrinelor urinare:

Tricyclic antidepressants

Levodopa

Labetalol

Ethanol

Sotalol

Amphetamines

Buspirone

Benzodiazepines

Methyldopa

Chlorpromazine

Medicatie care scade nivelul metanefrinelor urinare :

Methyltyrosine, which inhibits tyrosine hydroxylase, the rate-limiting enzyme in catecholamine synthesis

Methylglucamine, which is present in radiocontrast media

Reserpine
Teste in urina

24h: Creatinina, catecolamine, metanefrine, normetanefrine

Rezultate Pozitive (> 2-3 ori):

24h Ucatechols > 2 ori

24h Utotal metanephrines > 1.2 ug/d (6.5 umol/d)

Teste salivare
Localizare imagistica

Ultrasonografia

CT abdomen

Feocromocitom adrenal - sensibilitate 93-100%

Feocromocitom extra-adrenal - sensibilitate 90%

MRI

> sensibilitate CT pt feocromocitom extra-adrenal

MIBG Scan

sensibilitate 77-90%, specificitate 95-100%

Ecografia
A fost inlocuita de CT si MRI; este limitata de pregatirea tractului digestiv
Valoare limitata in diferentierea leziunilor chistice de cele solide in adrenala
MRI este preferata ca modalitate de investigare.
Ecografia in Feocromocitom
CT in Feo

Cavografie / CT in Feo
IRM in feocromocitom
Localizare imagistica nucleara

MIBG
111

Indium-pentreotide
Some pheochromocytomas have somatostatin receptors

PET
18

F-fluorodeoxyglucose (FDG)

6-[18F]-fluorodopamine
Imagistica nucleara
131

I-MIBG si 123I-MIBG sunt concentrate in sistemul simpato-medular si pastrate in granule de

neurosecretie

Aproximativ 30% din patienti, au un uptake mai mic decat cel hepatic.

In feocromocitom, 131I-MIBG evidentiaza tumora ca o arie in glanda suprarenala cu captare crescuta.

123

I-MIBG permite o calitate mai buna a imaginii, poate fi evaluat prin single photon emission computed
tomography (SPECT), are expunere mai mica la radiatii si rezultate in timp mai scurt.
MIBG
MEN2 screening
Macroscopic view of a malignant pheochromocytoma, demonstrating capsular invasion, hemorrhage, necrosis,
and multinodularity
The characteristic chromogranin (left) immunoreactivity in the pheochromocytes is contrasted to the S-100
protein immunoreactivity of the supporting sustentacular supporting cells (right) in this benign
pheochromocytoma
Management: medical si anestezic

Antagonisti Alfa fenoxibenzamina* +/- metirosina*

Incepe cu 10mg /zi cu crestere progresiva sub control HTA

Corecteaza depletia volumica

Beta blocada doar dupa alfa blocada completa, cu propranolol, atenolol, labetalol

Evita eliberarea de histamina

Monitorizare invaziva arteriala IOp

Anestezie si sedare pre-op. Se evita halotanul (poate precipita aritmii)

Control volum intravascular si TA

Nitroprusiat Na i.v in perfuzie lenta, sub monitorizarea invaziva a TA

Norartrinal i.v in perfuzie lenta, sub monitorizarea invaziva a TA

*Nota: tipic, sunt necesare 10-14 zile de tratament pre-op
Clase de Terapie

Vasodilatatoare
Nitroprusiat, Nitroglicerina
Beta-blocante

eg. Labetalol

Alfa-blocante eg. Fentolamina

Blocante de Ca eg. Nicardipine

Regim de pregatire preoperatorie

Preop: + blockade

Start at least 10-14d preop

Allow sufficient time for ECFv re-expansion

Phenoxybenzamine

Special pharmacy access only (no DIN)

Drug of choice
Covalently binds -receptors (1 > 2)
Start 10 mg po bid increase q2d by 10-20 mg/d
Increase until BP cntrl and no more paroxysms
Maintenance 40-80 mg/d (some need > 200 mg/d)
Salt load: NaCl 600 mg od-tid as tolerated
Preop: + blockade
Management: rezectie chirurgicala

Midline or transverse abdominal incision

Bilateral adrenal exploration along with exploration of para-aortic and paracaval retroperitoneum
(diaphragm to pelvis)

Laparoscopic approach acceptable via a flank, retroperitoneal, or transabdominal approach

Shorter hospital LOS

Lower morbidity rate

Higher incidence of missed paragangliomas/multiple tumors

Robotic surgery

Feocromocitom malign

Recidivele apar in 5 -10 ani dupa rezectia leziunii primare

Pot fi detectate 20 ani mai tarziu.

Supravietuirea la cinci ani: 36 - 60%.

Tratament

Resectia metastazelor

Controlul TA

Radioterapia (paliativ) pentru metastaze osoase.

Terapie ablativa cu I-MIBG - raspuns partial

Chemoterapie combinata (ciclofosfamida, vincristina si dacarbazina) poate fi eficace.

Concluzii

HTA endocrina HTA secundara

CSR / MSR

Teste diagnostice functionale in dinamica

Tratament chirurgical