Hiperaldosteronismul

primar
 MINERALOCORTICOIZI – actiuni
Echlibrul hidro-electrolitic
• Reabsorbtia activa de Na prin cresterea expresiei
• canalului epitelial de Na sensibil la amiloride in ductul colector
• cotransportorului de Na-Cl sensibil la tiazide in TCD
+ Gl. salivare, ileo­n,
• Reabsorbtia H2O colon, gl.
•  excretia de K - blocarea reabsorbtiei sudoripare
•  excretia de Mg
•  excretia H+

Cardio-vascular
• creste tonusul vascular bazal si reactivitatea vasculara la vasoconstrictori:
epinefrina, norepinefrina, angiotensina II si vasopresina
• inhiba vasodilatatia prin scaderea oxidului nitric
• stimuleaza fibroza perivasculara si interstitiala intracardiaca (ATS, insuf cardiaca)
SNC
• regleaza aportul de sare, setea si are efect presor
RENINA

• Enzima produsa de
aparatul juxtaglomerular
+ zona glomerulata (CSR)
actionind paracrin

• Factori care
cresc sinteza de renina:
–  Na (macula densa)
– Hipotensiunea (<85 mm Hg in aparatul juxtaglomerular)
– SNS -  stimularea (raspuns la ortostatism)
– Prostaglandinele, NO
Inhiba renina: angiotensina II, vasopresina, fact natriuretic atrial, cresterea livrarii Cl in
ap juxtaglomerular
Renina scindeaza angiotensinogenul eliberind Ang I
Enzima de conversie converteste Ang I in Ang II
 Reabsorbtie Na
ALDOSTERONUL : Eliminare a K+
Eliminare de Mg ++, H+
Cel epiteliale
• Rinichi
– canalele epitelia Na amilorid sensibile ductul colector
– pompa Na -K -ATPase

– cotransporter Na+/Cl- sensibil la tiazide (NCC)

TCD

– canalelor ROMK in TCD, Ductul colector

hiperpotasemii fara depletie volemica

• Alte sedii - glandele salivare,

colonul distal

Mf, adipocite,cardiomiocite, SNC

(nu au 11 HSD2 )
MINERALOCORTICOIZI – actiuni

Cardio-vascular
• creste tonusul vascular bazal si reactivitatea vasculara la
vasoconstrictori: epinefrina, norepinefrina, angiotensina II si
vasopresina
• inhiba vasodilatatia prin scaderea oxidului nitric
• stimuleaza fibroza perivasculara si interstitiala intracardiaca (ATS,
insuf cardiaca)
SNC
• ANG II si ALD regleaza aportul de sare, setea si are efect presor
Aldosteronul

Stimulat de
 angiotensina II (acut si cronic) RAng tip 1
 potasiu
 ACTH - control f redus, doar acut
+ serotonina, vasopresina, endotelina, estrogeni (via GPER-1), urotensin, PTH,
leptina
Inhibat de
 fact natriuretic atrial
Dopamina, somatostatin
 HIPERALDOSTERONISMUL
PRIMAR
= hiperproductie de aldosteron (relativ autonoma fata de reglatorii
secretiei - angiotensina II, K seric - si nesupresibila la incarcarea cu
Na) + HTA + activitatea supresata a reninei plasmatice (PRA)

Hiperplazie glomerulara bilaterala

Adenom Conn
Carcinom adreno-glomerular
Hiperaldosteronism primar familial glucocorticoid
frenabil
 HIPERALDOSTERONISMUL
SECUNDAR

Stimularea in esces a sistemului RAAld

• Stenoza arterei renale
• Insuf cardiaca stg sau CPC Renina 
• Ciroza cu ascita
• Tumori producatoare de renina din ap
juxtaglomerular
 Hiperaldosteronism primar
- fiziopatologie -

Hipersecretie
de aldosteron

 reabsorbtia de Na  excretia de K  excretia de H

Hipervolemie Hipokaliemie Alcaloza metabolica

HTA Poliurie

Inhibarea sistemului
Fenomene musculare
renina-angiotensina
 feocromocitom
Frecventa hiperALD in renovascular 5%
HTA moderat/severa 4% renal
1%

hipercortizolism
2%

hiperaldosteronism
primar
19%

HTA esentiala
69%

B Strauch et al, J Hum Hypertension, 2003

Hiperaldosteronismul primar

Cea mai frecventa

cauza de HTA
secundara
4.6-13% din toate HTA
20% din HTA rezistente

Yang et al 2017 John

Wiley & Sons, Ltd.
• 1672 unselected patients with hypertension, the prevalence of PA was 5.9%
– 3.9% HTN stage 1
– 11.8% HTN stage 3
 Clasificare
hiperaldosteronism
Adenom glomerular solitar (APA)
primar
Hiperplazie idiopatica bilaterala (IHA)
Hiperplazie unilaterala adrenala primara
Carcinom glomerular
Hiperaldosteronism familial (FH)
- Hiperplazie glucocorticoid supresibila (FH tip I)
- FH tip II (APA sau IHA) si III

alte forme de exces Sindrom adrenogenital - deficit de 11-hidroxilaza

mineralocorticoid
primar
Secretie tumorala a altor
mineralocorticoizi
Act mineralocorticoida Sindromul Liddle
crescuta
Deficit de
11-OH dehidrogenaza
Exces glucocorticoizi
- deficit de 17-hidroxilaza
- tumori suprarenaliene
- tumori ovariene
Autoactivarea ENaC
- congenital
- dobândit (liquoritia)
Forme clinice
Hiperplazie glomerulara bilaterala
– 60%
– Sensibila la ANGII

Adenom Conn
– 40%
– Nu răspunde la ANG II

– talie mica:  < 2 cm

Carcinom adreno-glomerular
– voluminos > 3 cm
– hK ++, abundenta precursorilor
CLASIC

Sdr NEUROMUSCULAR + HTA +

astenie musculara prin
hipokaliemie
accese paretice
Sdr POLIURO-
paroxistice
POLIDIPSIC
hiperexcitabilitate neuro-
musculara prin alcaloza si
hipmagnezemie

HIPERALDOSTERONISM
clinic

1. SINDROMUL CARDIOVASCULAR
• hipertensiunea arteriala
– constanta, sistolo-diastolica, moderata (200/100 mmHg)
– in general bine tolerata
– FO stadiul I-II

• modificari ECG
– HVS
– subdenivelare ST, aplatizare uT, uU
– tulburari de ritm (EsV), FbA
clinic
2. SINDROMUL NEUROMUSCULAR
• astenie musculara (miasteniform)
– predominant diurna
– jena la deglutitie, ptoza palpebrala…
• accese paretice paroxistice
– brusc, revenire spontana
– predominant la membrele inferioare, evolutie ascendenta, 0 ROT
• hiperexcitabilitate neuro-musculara
– crampe, spasme musculare, acroparestezii
– Chvostek / Trousseau (+)
– rar, tetanie generalizata ( femei)

3. SINDROMUL RENO-URINAR
– polidipsie (restrictia hidrica rau tolerata)
– poliurie cu nicturie (nemodificata de ADH)
Dg hiperaldosteronismului

I. Screening

II. Teste de confirmare

III. Determinarea subtipului de hiperaldosteronism
Screening Funder et al 2016, Mulatero 2020

• Pacienti cu HTA si hipopotasemie spontana sau indusa

de diuretice (K< 3.5)
• HTA (140/90mmHg) rezistenta la 3 antihipertensive
(inclusive un diuretic) sau controlata ≥ 4 antihipertensive
• HTA sevara (TAs>150 si Tad>100) la 3 determinari separate
• Incidentalom SR ± HTA
• HTA si sleep-apnee
• HTA la o persoana tinara
• HTA si istoric familial de HTA/ AVC la o varsta tanara (<40 ani)
• rudele de gradul I cu HTA la pacientii cu hiperaldosteronism
primar
Biologie – teste bazale

ALDOSTERONUL

Sanguin
N: 2.52 – 39.2 ng/dL la 2 h de ortostatism, 15 min poz sezanda
In hiperaldosteronism > 15ng/dl
Metode
LC-MS/MS ideal

Urinar
N < 17 µg/24 h

La pacientii cu renina supresata, in absenta hipopotasemiei, cu un aport

Na normal (Na urinar > 200mEq/l), valoarea ALD urinar > 15 ug /zi
confirma hiperaldosteronismul
Biologie – teste bazale

RENINA
Activitatea reninei plasmatice (PRA) – exprimata in cantitatea de
angiotensina I generata pe unitatea de timp

Renina activa sau directa (DRC)

inhibata in hiperaldosteronism primar

Exceptie
• dieta hiposodata
• + HTA renovasculara
• anumite medicamente care cresc renina

ALDOSTERON/ RENINA (ARR) crescut

Valori “normale” ale ALD trebuie privite ca “inadecvat de normale ”

in fata unei renine supresate
Drug Renin Aldosterone ARR
MRA, amiloride ↑↑ ↑ ↓ (FN)
Ø Carectarea hipoK
Thiazides/thiazide-like and ↑↑ ↑ ↓ (FN) Ø regim normosodat
loop diuretics Ø eliminarea agenţilor
ACE-inhibitors ↑ ↓ ↓ (FN)
care afectează
ARBs ↑ ↓ ↓ (FN)
Direct renin inhibitors ↓ or ↑* ↓ ↑ (FP) or semnificativ raportul
aldosteron/renina
↓ (FN)
β-blockers ↓↓ ↓ ↑ (FP)
Central α2-agonists ↓↓ ↓ ↑ (FP)

(clonidine; α-methyldopa)
α1-antagonists ↔ ↔ ↔ (U)
CCBs (DHPs) ↔ or ↑ ↔ or ↓ ↔ (U); ↓ (FN)
CCBs (non DHPs) ↔ ↔ ↔ (U)
Hydralazine ↔ ↔ ↔ (U)
NSAIDs ↓↓ ↓ ↑ (FP)
SGLT2-i [82] ↑ ↔ ↓ (FN)
SSRI [83] ↑↑ ↑ ↓ (FN)
Oral contraceptives [11,84] ↓ or ↑↑# ↑ ↑ (FP) or

↓ (FN)
Central I1-agonists ↔ ↔ ↔ (U)

(Moxonidine)
Low Na+ diet ↑↑ ↑ ↓ (FN)
High Na+ diet ↓↓ ↓ ↑ (FP)
Rezultate fals pozitive

H Sexuali

• Utilizarea de estrogeni creste (-) renina

substratul reninei - angiotensinogenul
(contraceptive , HRT)  ALD si
renina
• In faza luteala creste progesteronul,

antagonist al Rmin, creste natriureza

De preferat
dozarea ARP sau
dozare in faza foliculara a ciclului
 Rezultate fals pozitive

Renina - secretata de la nivelul ap juxta glomerular sub control

beta adrenergic

• Beta blocantele
• Antihipertensivele centrale
inhiba renina
(clonidina, alpha metil-Dopa)

• AINS
determina retentie de apa si Na si inhiba PG renale

determina retentie de K stimularea ALD

fals
pozitive
Rezultate fals negative
Diureticele
• depletizatoare de K (inclusiv tiazidicele) si economizatoare de
(+) renina
K determina contractia volumului circulant si vasoconstrictie
betaadrenergica

(-) ALD
• diureticele depletizatoare de K - hipoK

Antagonistii canalelor de Ca
dihidropiridinici
prin stimulare simpatica reflexa cresc renina
efect natriuretic
stimulare directa Ca dependenta
sintetezei intracelulare de ALD
blocarea directa Ca dependenta
Verapamilul-efecte minime
Rezultate fals negative

Inhibitorii ECA si inhibitorii de receptor

ANG II
• stimuleaza renina

• Inhiba sinteza ALD prin reducerea ANGII la nivelul

zonei glomerulare in formele de particulare de
hiperaldosteronism primar cu raspuns la ANGII
 Dieta
Dieta normosodata
• hiposodata stimuleaza renina cu rezultate fals
negative
• hipersodata inhiba renina cu rezultate fals pozitive

Hipopotasemia
• Inhiba ALD cu rezultate fals negative

Stowasser & Gordon R Physiol Rev 2016, Endocrine Society Clinical Practice Guideline 2016, Vilela & Almeida
Arch Endocrinol Metab. 2017
Precautii
• regim normosodat (Na urinar 100-150 mmol/l)
• corectarea hipokaliemiei

• conditii de recoltare:
• dimineata dupa 2 ore ortostatism apoi 5-15 min pozitie sezanda
• probe tinute la temperature camerei
• la persoanele > 65 renina poate avea valori mai mici ( rezulatete fals + )

2 ore 5-15’
Recoltare
 Intreruperea
• Spironolactonei, Eplerenonei, Amilorid 4-6 sapt
• +/- intrerupearea antihipertensivelor ce pot influenta
ARR pt 2-4 sapt
• (atentie la utilizarea CO, HRT sau perioada menstrual (f
luteala) daca se foloseste DRC (rezulatte fals positive)
+ Verapamil, Doxazosin, Prazosin
hiperALD primar renina este
totdeauna supresata
Stowasser & Gordon R Physiol Rev 2016, Endocrine Society Clinical Practice Guideline 2016, Vilela & Almeida
Arch Endocrinol Metab. 2017
 Preparate cu efecte minime
asupra ALD

Moxonidine 200-400 mcg/day

Stowasser & Gordon R Physiol Rev 2016, Endocrine Society Clinical Practice Guideline 2016, Vilela & Almeida
Arch Endocrinol Metab. 2017 , Yang 2017 John Wiley & Sons, Ltd.
Biologie – teste bazale
Fara strangerea pumnului
Eliberarea torniquetului imediat dupa
IONOGRAMA punctia venoasa
Se asteapta 10 s
a. sanguina Preferabil cu siringa
Centrifugare si separarea plasmei in
• Hipokaliemia 30 min de la colectie

• Na  moderat sau N
• Alcaloza metabolica
• hipoMg
• hipoCl
 dieta normosodata
Hipokaliemia un regim hiposodat ar
masca depletia de potasiu
intreruperea medicatiei
• < 3,5 mEq/L spironolactona (3
saptamâni)
• Doar in 20% din cazuri alte diuretice (1 saptamâna)
inainte).

hipokaliemia la pacienti cu
hiperaldosteronism
– inainte (alb)
– si dupa (negru)
introducerea screeningului
A/R

Mulatero JCEM, 2004,

 Biologie – teste dinamice
1. incarcarea cu sare (! hipertensiune severa)

dieta cu 6 g NaCl/zi, 3 zile

excretie urinara Na > 200 mmol/zi
K seric ≈ 4mmol/l
– Ald urinar ziua ¾ >12 /24 h in hiperladosteonism primar

perfuzie de 2 l NaCl 0.9% in 4 h cu determinarea Ald, DRC, cortizol

– poz culcata/ sezanda 1 ora inainte si in timpul testului
– +/- 30 min in poz sezanda _ recoltare
– aldosteron
• subiecti normali (<5ng/dl/ = 140 pmol/L)
• ?/ hiperplazie (5-10ng/dl)
• non-frenat – adenom (>10ng/dl = 280pmol/L )
• cutoff of 6.8 ng/ dL (190 pmol/L) cel mai bun echilibru specificitate/ senzitivitate
Stowasser & Gordon R Physiol Rev 2016, Endocrine Society Clinical Practice Guideline 2016, Vilela & Almeida
Arch Endocrinol Metab. 2017
Biologie – teste dinamice
2. Test fludrocortizon
– administrare de Fludrocortizon 0.1 mg x 4/zi, 4 zile cu
aport suficient de K (K ≈ 4mmol/l) si NaCl
– determina normal scaderea Ald ;
– Ald >6 ng/dl – sugestiv pentru hiperaldosteronism
3. Test la captopril
– Pacient in pozitie sezanda 1h ora inaintea testului si
pe parcusul testului
– 25- 50 mg captopril
– determinarea Ald la 1 si 2 h
– Ald > 30% - subiecti normali, hiperplazie
– nemodificat – adenom

Endocrine Society Clinical Practice Guideline 2016, Vilela & Almeida Arch Endocrinol Metab. 2017
Confirmatory test Description End point Cut-off for PA Other requirements Remarks
diagnosis
Saline Recumb 4h infusion of 2L of 0.9% Post-infusion PAC > 10 ng/dL PA highly Antihypertensive Contraindicated in patients
infusion ent NaCl likely treatment adjustment with severe uncontrolled HT,
test renal insufficiency, cardiac
Recumbent position 1h 5-10 ng/dL PA Potassium arrhythmia,
  before and during test intermediate likely supplementation
heart failure, severe
< 5 ng/dL PA unlikely uncorrected hypokalemia.
Seated 4h infusion of 2L of 0.9% Post-infusion PAC >6 ng/dL (Australia) Antihypertensive
NaCl treatment adjustment Seated SIT is preferred.
> 16 ng/dL (Taiwan)
Seated position 30 min Potassium
before and during test PA confirmed supplementation
  Plasma cortisol lower at
the end lower than at
baseline
Captopril challenge 25–50 mg of captopril PAC and PRA 2h after PAC > 11 ng/dl and PRA Antihypertensive It avoids potential fluid
test captopril remaining suppressed treatment adjustment overload in patients at risk
orally after sitting for at least Or ARR > 20 ng/dL / (renal insufficiency, heart
1 h. ng/ml/h: PA confirmed Potassium failure).
supplementation
Potential angioedema.
Oral sodium loading Sodium intake >200 mmol Urinary aldosterone >12 or 14 ug/24h – PA Antihypertensive Contraindicated in patients
test (6g/24h) for 3 consecutive excretion 24h from highly likely treatment adjustment with severe uncontrolled
days morning of day 3 to hypertension, renal
morning of day 4 <10 ug/24h – PA Potassium insufficiency, cardiac
unlikely supplementation arrhythmia, heart failure,
severe uncorrected
hypokaliemia.
24h-urine collection
inconvenient for patients and
aldosterone measurement by
HPLC-MS advisable
Fludrocortisone Every 6h for 4 days: On day 4, PAC and PAC >6 ng/dL Antihypertensive Requires hospital admission,
suppression test PRA are treatment adjustment blood test several times daily
- oral fludrocortisone 0.1 mg PRA <1 ng/ml/h
measured at 10 a.m. Plasma cortisol at 10
- slow-release KCl (seated posture) a.m. is lower than 7 a.m.
supplements measurement
 
Three times daily with meals:
- slow-release NaCl
supplements (30 mmol);
Sufficient
IMAGISTICA
Scanner (CT) suprarenalian 
• > 5mm
• 2 - 8 % : incidentaloame SR

Cateterismul venelor suprarenaliene  

• dozaj aldo, cortizol dupa Synacthène
– invaziv (!necroza, hemoragie)
• gradient de secretie in adenom

(11)C-Metomidate PET-CT
CT adrenal Pacient < 35 ani
hipoK spontana
• Nu detecteaza 50% din masa adrenala
adenoamele secretante de unilaterala
ALD de obicei mici, (< 1cm) (caractere adenom)

Incidentaloame SR
• Evidentiaza 3% din populatia gen < 50 ani
– noduli adrenali non-functionali 10% din pop gen > 50 ani

– leziuni aparent unilaterala in

hiperplazia bilaterala
• Esentiala in detectia leziunilor mari >4 cm cu
potential malign
Acuratetea dg 53%
Young et al Surgery. 2004,
Nwariaku et al Arch Surg. 2006 37% dg eronat
Cateterismul venelor SR

– dozare
• Aldosteron & cortizol in venele
adrenale si periferic
• Cortizol
– Indicator al localizarii cateterului
– Evaluarea dilutiei sg. adrenal in
SR stg (vena frenica inf se
uneste cu vena SR stg

Raport > 4 aldosteron (dr fata de stg sau invers)

corectat pt. cortizol este indicator al unui adenom care
produce aldosteron
 Hiperaldosteronismul primar
-diagnostic
• Clinic
HIPERALDOSTERONISM =
HTA +
Sdr NEUROMUSCULAR +
Sdr POLIURO-POLIDIPSIC
• Biologic
HIPERALDOSTERONISM PRIMAR =
ALDOSTERON crescut/limita sup
RENINA (ARP sau DRC) inhibata, non-stimulabila
(ortostatism)
• Imagistic
– Adenom / hiperplazie (CT)
Pacientii cu HTA si hiperaldosteronism Weiner Pag

NIH-PA Author Manuscript

 Risc de
IMA ~2.5X
AVC ~3–4X
Aritmie cardiaca ~5X trebuie reduse
b. arteriala perifericanu
~3 doar
X HTA si hipoK
ci
In caz de tratament chirurgical/
NIH-PA Author Manuscript

 ALD cu
medicamentos specific
Figure 2.
Risk of cardiovascular events in patients with unrecognized primary aldosteronism.

Fata de pacientii cu dezinhibarea reninei Incidence of previous cardiovascular events was determined at time of diagnosis of primar

risc identic cu HTAes

aldosteronism in 54 consecutive patients, and compared with 323 patients matched for age
sex, body mass index and estimated duration of hypertension 51. Incidence of previous
HTAes myocardial infarction or reversible ischemia, cerebrovascular accident (CVA) or transient
ischemic attack (TIA), sustained cardiac arrhythmia and peripheral arterial disease (PAD)
was assessed, and in each case was significantly greater (P<0.05) than in patients with
 sdr metabolic si tulburari ale metabolismului glucidic essential hypertension.

 alterari ale metabolismului osos (interactiune sist RAA-PTH)

Weiner D Semin Nephrol. 2013, Kline et al CMAJ 2017m Milliez et al , Journal of the American College of
NIH

Cardiology 2005, Seccia Hypertension 2017

 TRATAMENT
Obiectivele tratamentului
• Blocarea actiunii sistemice a
mineralocorticoicilor
– Eradicarea sursei de hipermineralocorticism
(chirugical)
– Inhibarea sintezei (in studiu)
– Blocarea receptorului (Spironolactona, Eplerenona)

• Normalizarea balantei electrolitice

 Regim hiposodat

severitatea hipokaliemiei (mai putin sodiu de reabsorbit

in tubii colectori, mai mica pierderea de K)

ALD crescut asociat cu aport crescut de sare determina

deteriorarea organelor tinta
– masa VS
– gradul proteinuriei
excretia de Na/24
– severitatea sleep-apneei

Stowasser M, Gordon RD Physiol Rev 2016 , Lenders 2016Vilela & Almeida

Arch Endocrinol Metab. 2017
TRATAMENT
Chirurgical
Adenom
• adenomectomie / suprarenalectomie unilaterala

• laparoscopic

Hiperplazie
• ± suprarenalectomie sub-totala
Monitorizare pre si
postoperatorie
• Tratament preoperator cu spironolactona pt desupresia
reninei si normalizarea K
• Intreruperea preoperatorie a Spironolactonei 2-3 zile (T1/2
lung)
• Postoperator risc de hipoaldosteronism
hiporeninemic
– Inhibitia indelungata a SR controlaterale  risc hiperK
– Monitorizare postop a K de x 2 /zi 2 zi apoi zilnic
 Indicatii
TRATAMENT MEDICAMENTOS  Hiperplazie
 Adenom inoperabil
 Inainte de chirurgie

Antagonisti specifici
Spironolactona – doza unica
• Efecte adverse
»F – perturbarea ciclului menstrual (agonist pentru R
progesteron)
»B– ginecomastie,  libidoului TDS (antagonist pt R androgenic)
–Hiperkaliemie
–Agravarea insuficientei renale preexistene
• Doze
–100-400 mg/z, 2-4 spt inainte de chirurgie
–12.5 -300 mg/z tratament de lunga durata
Canrenone (metabolit activ i) sau K canrenoate
Deinumet et al Pharmacology and Therapeutics 2015, Vilela & Almeida Arch Endocrinol Metab. 2017
TRATAMENT MEDICAMENTOS Indicatii
 Hiperplazie
 Adenom inoperabil
 Inainte de chirurgie

Antagonisti specifici
Eplerenona (Inspra)
– Actiune mai specifica pentru Raldosteron dar afinitate mai redusa
• 15% din afinitatea de legare de R androgenic
• < 1% din capactatea de legare de R progesteronic
25-50 mg x 2/zi

Antagonisti nespecifici
Amilorid
– inhibitor al transp tubular distal cu actiune direct pe canalul de sodiu
10-40 mg/zi
– mai putin potent HTA/ hipoK mai putin severe
– maiM,putine
Stowasser Gordonefecte adverse
RD Physiol Rev 2016 asociere la spironolactona (ef sec)
Vilela & Almeida Arch Endocrinol Metab. 2017 ,
TRATAMENT MEDICAMENTOS

Antihipertensive
IEC
? Sist renina –ang supresat in hiperald
Blocarea sistemului renina-angiotensina tisular
Renina nesupresata in caz de trat adecvat cu antag ALD
Blocantii receptorului de angiotensina (ARB)

Blocanti de Ca
celulele din ZG dependente de Ca intracel

Deinumet et al Pharmacology and Therapeutics 2015, Stowasser M, Gordon RD Physiol Rev 2016 Vilela &
Almeida Arch Endocrinol Metab. 2017, Dick et al Clin Chem Lab Med. 2017
 ALEGEREA TRATAMENTULUI
LEZUNE TRATAMENT EVOLUTIE POSTOPERATORIE
DE ELECTIE

Adenom Chirurgie Normalizarea TA

glomerular spironolactona • 70% in primul an
• alti 53% in 5 ani
Hiperplazie spironolactona • normalizare imediata a hipokaliemiei
bilaterala • normalizarea TA in 4-8 saptamini

Carcinom chirurgie, Supravietuire limitata

glomerular cisplatina
Hiperplazie dexametazona Normalizarea TA in citeva saptamini
glucocorticoid
supresibila
In loc de concluzii
Screeningul pacientilor cu HTA rezistenta la
tratament/ hipoK pentru hiperaldosteronism

Incidentaloame SR asociate cu HTA

Dozarea ALD, renina in ROMANIA

Cateterism vene adrenale ?
 Clasificare
hiperaldosteronism
Adenom glomerular solitar (APA)
primar
Hiperplazie idiopatica bilaterala (IHA)
Hiperplazie unilaterala adrenala primara
Carcinom glomerular
Hiperaldosteronism familial (FH)
- Hiperplazie glucocorticoid supresibila (FH tip I)
- FH tip II (APA sau IHA) si III

alte forme de exces Sindrom adrenogenital - deficit de 11-hidroxilaza

mineralocorticoid
primar
Secretie tumorala a altor
mineralocorticoizi
Act mineralocorticoida Sindromul Liddle
crescuta
Deficit de
11-OH dehidrogenaza
Exces glucocorticoizi
- deficit de 17-hidroxilaza
- tumori suprarenaliene
- tumori ovariene
Autoactivarea ENaC
- congenital
- dobândit (liquoritia)
 colesterol  
20-22  

5-pregnenolon 17 17-OH 17 Dehidro- 17 Androstendiol  

OH pregnenolon DH epiandrosteron HSD
3HSD 3HSD 3HSD 3HSD  

Progesteron 17 17-OH 17 Androstendion 17 Testosteron  

OH progesteron DH HSD
21OH 21OH arom arom  

deoxi- deoxicortisol Estrona 17 Estriadiol  

corticosteron HSD
11OH 11OH  
11HSD
Corticosteron Cortizol Cortizon
18OH
 
18OH
corticosteron  

18oxid  
Aldosteron
Hiperaldosteronism glucocorticoid sensibil
crossover inegal intre CYP11B1 (11α-hydroxylaza) si CYP11B2 (aldosteron sintetaza)
gena hibrid ce codeaza aldosteron sintetaza dar localizata in z fasciculata si
dependenta de ACTH (nu de angiotensina II)
Hiperaldosteronismul familial de tip I
glucocorticoid supresibil
crossover inegal intre CYP11B1
(ce codeaza 11α-hydroxylaza) si
CYP11B2 (ce codeaza aldosteron
sintetaza)

gena hibrid ce codeaza aldosteron sintetaza dar localizata in z

fasciculata si dependenta de ACTH (nu de angiotensina II)
ALD supresibil dupa testul DXM 2x2
Clinic fenotipul variaza de la normotensive la HTA hipoK rezistenta
la treatment
evenimente cerebrovasculare la varsta tanara
Vilela & Almeida Arch Endocrinol Metab. 2017
Hiperaldosteronismul familial
Hiperaldosteronismul familial de tip II
• mutatii ale geneiCLCN2 gene (codifica un canal de Cl din mb cel granuloasei ce se deschide la potentiale
membranare hiperpolarizate). Deschiderea canalului determina depolarizare mb cu activarea aldosterone
sintetazei. Mutatia activanta determina cresterea sintezei de ALD.
• dg cand cel putin 2 membrii ai familiei, rude de grd I, au hiperaldosteronism primar

• chromosome 7p22

Hiperaldosteronismul familial de tip III

• mutatie in gena KCNJ5 ce codeaza canalul de K Kir3.4
• se produce depolarizarea permanentă a membranei celulare prin cu creșterea Ca intracelular si stimularea
sintezei de aldosteron și proliferarea celulelor glomeruloasei.
• HTA severa din copilarie cu hiperaldosteronism primar, hipokaliemie si hiperplazie macronodulara bilaterala

Hiperaldosteronismul familial de tip IV

• Mutatii ale genei CACNA1H (codifica pore-forming α1 subunit of the T-type voltage-dependent calcium channel
CaV3.2, din cel adrenala)
PASNA (primary aldosteronism with seizures and neurologic abnormalities) syndrome
• F rar, hyperaldosteronism cu afectare neurologica importanta ( mutatie de novo, activanta a CACNA1D =
α1D subunit of a L-type voltage-gated calcium channel Cav1.3)

Vilela & Almeida Arch Endocrinol Metab. 2017, Mulatero et al.2020

 Clasificare
hiperaldosteronism
Adenom glomerular solitar (APA)
primar
Hiperplazie idiopatica bilaterala (IHA)
Hiperplazie unilaterala adrenala primara
Carcinom glomerular
Hiperaldosteronism familial (FH)
- Hiperplazie glucocorticoid supresibila (FH tip I)
- FH tip II (APA sau IHA) si III

alte forme de exces Sindrom adrenogenital - deficit de 11-hidroxilaza

mineralocorticoid
primar
Secretie tumorala a altor
mineralocorticoizi
Act mineralocorticoida Sindromul Liddle
crescuta
Deficit de
11-OH dehidrogenaza
Exces glucocorticoizi
- deficit de 17-hidroxilaza
- tumori suprarenaliene
- tumori ovariene
Autoactivarea ENaC
- congenital
- dobândit (liquoritia)
 Adenomul secretant de ALD (APA)

50% din APA au o mutatie somatica activatoare a celor 4 gene susceptibile de

depolarizarea mb cel glomeruloasei cu activarea sintezei de ALD :
• KCNJ5, encoding GIRK4, the G-protein–activated inward rectifier potassium
channel 4
• ATP1A1, encoding Na+/K+-ATPase 1
• ATP2B3 , encoding Ca2+-ATPase 3
• CACNA1D, encoding Cav1
The proportion of APAs with somatic mutations increases up to 90% when
genotyping is performed using immunohistochemistry-guided next generation
sequencing techniques. Genotype appears to influence adrenal steroid production
with specific peripheral venous steroid profiling performed by mass spectrometry
correctly classifying >90% of APAs according to genotype.
Hiperaldosteronismul familial de tip I
glucocorticoid supresibil

• crossover inegal intre CYP11B1 (ce codeaza 11α-

hydroxylaza) si CYP11B2 (ce codeaza aldosteron sintetaza)
• Gena hibrid ce codeaza aldosteron sintetaza dar localizata in
z fasciculata si dependenta de ACTH (nu de angiotensina II)
• ALD supresibil dupa testul DXM 2x2

Tratament cu
Dexametazona
0.125– 0.25 mg/zi

Vilela & Almeida Arch Endocrinol Metab. 2017

Forme clinice
Hiperplazie glomerulara bilaterala
– 60%
– Sensibila la ANGII
Adenom Conn
– 40%
– Nu răspunde la ANG II

– talie mica:  < 2 cm

Carcinom adreno-glomerular
– voluminos > 3 cm
– hK ++, abundenta precursorilor