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Quando il surrene è causa di
ipertensione
Alberto Morganti
Centro di Fisiologia Clinica e Ipertensione ,
Ospedale Policlinico, Milano
Giornate Mediche Fiorentine
Firenze 7-9 Novembre 2014
1925 Mo
CLINICAL CASE: MEDICAL HISTORY
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•
•
Female, black, 21 years old.
No relevant medical history.
In April 2011 occasional diagnosis of severe systo-diastolic
hypertension , asymptomatic. Treatment is started with
hydrochlorotiazide 12.5 mg/d and lercanidipine 10 mg/d.
In June 2011 the patient is seen in the Emergency Department
of San Giuseppe Hospital for dizziness and paresthesias.
PA 190/120 mmHg, HR 100 bpm.
No significant abnormalities except for a systolic 2/6 murmur
on the apex at cardiac examination.
ECG: signs of left ventricular hypertrophy and overload, QTc
prolongation.
CLINICAL CASE: BASELINE WORK-UP
The patient is admitted in the Hypertension Unit for diagnostic
work-up:
•Routine laboratory data: Cr 0.68 mg/dl, Az 59 mg/dl, Na 141
mEq/l, K 2.5 mEq/l, Cl 103 mEq/l, Gl 105 mg/dl, Cholesterol 213
mg/dl, HDL 48 mg/dl, LDL 143 mg/dl, TG 60 mg/dl, Uric acid
3.1 mg/dl,Ca 10.5mg/dl Hb 13.0 g/dl, WBC 3590/mm3, PLT
189000/mm3.
•Urinalysis: pH 7.0, sw 1017, no proteins, glucose or blood.
Microalbuminuria 10 mg/24 hs.
•Echocardiography: concentric left ventricular hypertrophy (IVS
13 mm, PW 13 mm, LVM 120 g/m2).
•Abdominal ultrasonography and EchocolorDoppler ultrasound of
the carotid and renal arteries: normal.
Indici Clinici di Sospetto Iperaldosteronismo Primitivo (IA)
Anamnestici
- Storia di ipertensione lieve-moderata resistente ai comuni farmaci
antipertensivi
- Gravi ipopotassiemie in corso di trattamento con diuretici
Obiettivi / soggettivi
- Astenia-fascicolazioni-parestesie
- Paralisi
- Poliuria
- Polidipsia
Laboratoristici
- Ipopotassiemia
- Ipomagnesiemia
- pH urinario alcalino (alcalosi metabolica)
- Alterazioni della ripolarizzazione (onda U) e aritmie all’ECG
306
Prevalence of Primary Hyperaldosteronism in Italy
PAPI Study
1308 Mo
Patients recruited
1121
Primary hyperaldosteronism
118 (10.5%)
Aldosteronoma
49 (41%)
Adrenal hyperplasia
(mono / bilateral)
69 (59%)
Rossi GP et al., JACC 2006
Aldosterone and Cardiovascular Damage
Inflammation and
Vascular Damage
Prothrombotic
Effects
Fibrosis and Ventricular
Remodeling
Pathological
Effects of
Aldosterone
Potentiation of
Catecholamines
and Angiotensin II
Reduction in
BRS and HRV
Potassium and
Magnesium Loss
Sodium
Retention
Pro-hypertensive
Effects on the Brain
Endothelial
Dysfunction
Impaired
Ventricular
Vascular
Arrhythmias Compliance
Cardiovascular Disease
Stroke
Ischaemia
Hypertension
Struthers AD Cardiovasc Res 2004
Mulatero P Cardiovasc Hematol Ag 2006
Heart Failure
End-Stage
Renal Disease
Cardiovascular Events in Patients with
Primary Aldosteronism vs Essential Hypertensives
p=0.001
%
p=0.005
p=0.0001
PA
PA
14
12
10
8
6
4
2
0
PA
EHT
Stroke
3 years follow-up
EHT
Myocardial
Infarction
EHT
Atrial
Fibrillation
Milliez P et al. J Am Coll Cardiol 2005
Renin-angiotensin-aldosterone-system
Aldosterone
increase
+ Na
Renin suppresion
BP elevation
-K
Flow chart for screening hyperaldosteronism
Aldosterone/Renin-ratio (ARR)
Normal ARR
Elevated ARR
Primary hypertension
Florinef \Saline suppression test
Not suppressed
Suppressed
CT + Adrenal vein sample
Primary hypertension
Adenoma
Hyperplasia
Surgery
Medical treatment
Number of Diagnosed Cases of PA per Year
Before and After Using ARR for Screening
90
80
Before ARR
70
After ARR
60
50
40
30
20
10
0
Torino
1310 Mo
Rochester
Brisbane
Singapore
Santiago
Mulatero P et al., J Clin Endocrinol Metab 2004; 89: 1045-1050
Educational Workshop EuroMedLab Milano 2013
ARR cut-off - JCEM Guidelines and units
•
Variability between different assays
•
Additional source of confusion:
- Aldosterone in ng/dL, pg/mL or pmol/L
- Renin activity in ng/mL*h or pmol/L*min
- Renin concentration in mU/L or ng/L
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
11 21.05.2013
ENDOKRINOLOGISCHES LABOR
MEDIZINISCHE KLINIK UND POLIKLINIK IV
CLINICAL CASE: ENDOCRINOLOGIC WORK UP
Cortisol 3.86 µg/dl
(nv 6.70-22.60)
ACTH 4.44 pg/ml
(nv 5-80)
UFC 30 µg/24 hs
(nv 28-213)
Renin supine <0.5 mU/l
(nv 2.8-39.9)
Aldosterone supine 187 ng/dl
(nv 0.75-15)
ARR 374
(nv<3.7)
Renin standing <0.5 mU/l
(nv 4.40-46.10)
Aldosterone standing 190 ng/dl
(nv 3.5-30)
TSH 1.39 μUI/ml
(nv 0.34-5.6)
S-DHEA 66 µg/dl
(nv 35-430)
U-Catecholamines 25 µg/24 hs
(nv <120 µg)
U-Metanephrines
60 µg/24 hs (nv <400 µg)
U-Normetanephrines 163 µg/24 hs
(nv <800 µg)
Saline infusion 2L NaCl 0,9%
32
24
ALD
ng/dl
16
8
0
0h
2h
4h
Saline infusion 2L NaCl 0,9%
32
24
ALD
ng/dl
16
8
0
0h
2h
4h
CLINICAL CASE: ENDOCRINOLOGIC WORK UP
Aldosterone Suppression test
Time
0’
60’
120’
180’
240’
Renin
<0.5
<0.5
<0.5
<0.5
<0.5
180
180
168
170
Aldosterone 175
Primary Aldosteronism
The Role of Adrenal Venous Sampling (AVS)
At centers with experience with AVS, the complication rate is 2.5% or less
Complications may include:
-Symptomatic groin hematoma
-Adrenal hemorrhage
-Dissection of an adrenal vein
-Adrenal venous thrombosis
-Adrenal infarction
Mayo Clinics Recommendations
Precautions to be taken to optimize AVS results
Perform the procedure in the morning
Correct hypokalemia prior to AVS
Adjust anti-HT treatment with alpha-blocker or calcium
antagonists
Withdraw RAS and MR antagonists (4 weeks)
Visualize right adrenal vein with CT
Minimize stress prior to and during AVS
Simultaneous sampling from the adrenal veins (because of pulsatile
secretion of aldosterone)
Inject the least possible amount of dye into adrenal vein
2902 Mo
CLINICAL CASE: CONFIRMATION OF LATERALIZATION
Adrenal vein sampling
Aldosterone
Cortisol
Aldo/Cortisol
Right adrenal vein
187
91.5
2.04
Left adrenal vein
52
30.6
1.7
Vena cava
56
14.8
0.3
CLINICAL CASE: IMAGING


Adrenal CT scan: right adrenal mass, 27 x 15 x 27 mm,
hypodense (10 HU), with light enhancement after iodine
contrast medium.
Iodocholesterol Adrenal scintigraphy after
dexamethasone suppression: rigth adrenal hyper-uptake
of the tracer.
Clinical characteristics associated with greater chances of
cure of hypertension following adrenalectomy
Young age
Short duration of HT (5-10 yrs)
Fewer anti-HT medications
Higher pre-operative blood pressure
Pre-operative normal renal function
BMI < 25 kg/m2
Female gender
Lack of family history of HT
No evidence of CV organ damage
2905 Mo
Estimated costs of medical and surgical therapy
Cost (Canadian $)
2735 Mo
Adrenalectomy
8463
Adrenalectomy plus ongoing
antihypertensive medication
19960
Estimated cost of medical therapy alone
39080
Estimated cost savings for adrenalectomy
per patient
31132
Sywak M et al., Br J Surg 2002; 89: 1587-1593
Anti-aldosterone medications
Aldosterone receptor
antagonist (ARA)
Non-steroids
Aldosterone biosynthesis
inhibitor (ASI)
2744 Mo
Denomination
Development
Spironolactone
Early 1960s
Canrenone
1980s
Eplerenone
2000s
Some DHP CCBs
(nimodipine, felodipine,
nitrendipine)
2000s
BR-4628, FAD 286,
LCI 1699
2010s
Incidence of Combined CV End-point in Patients with PA and EH
Treated with Adrenalectomy or Aldosterone Antagonists
Patients (%)
Patients (%)
30
30
25
25
20
20
15
15
10
10
Essential hypertension
5
0
Primary aldosteronism
0
1
2
3
4
5
6
7
8
Follow-up (y)
2336 Mo
9
10 11 12
Adrenalectomy
5
0
Spironolactone
0
1
2
3
4
5
6
7
8
9
10 11 12
Follow-up (y)
Catena C et al., Arch Intern Med 2008; 168: 80-85
CLINICAL CASE: TREATMENT
DIAGNOSIS: Primary hyperaldosteronism
due to aldosterone producing adenoma
Antihypertensive
therapy was initiated with
potassium canrenoate 100 mg, nifedipine GITS 60
mg and doxazosin 4 mg.
After 4 weeks blood pressure and kalemia were
normalised:
• PA 125/80 mmHg.
• Na 138 mEq/l, K 4.1 mEq/l.
CLINICAL CASE: TREATMENT
In
February 2012 elective laparoscopic right
adrenalectomy was perfomed.
Hystologic diagnosis: adrenal adenoma.
After 5 weeks blood pressure, kalemia and
renin/aldosterone profile were normalised without
any therapy:
• PA 110/75 mmHg.
• Na 137 mEq/l, K 4.5 mEq/l.
• Renin supine 14.9 mU/l, Aldosterone supine 3
ng/dl, ARR 0.2
Conclusions
The prevalence of Primary Aldosteronism (PA) among patients
with hypertension is about 10%, being due in similar percentages
to aldosteronoma and to adrenal hyperplasia.
Because of the deleterious actions of excess aldosterone, PA is
associated with high prevalence of CV disorders.
Resistance to conventional anti-hypertensive agents and
hypokaliemia are clinical features strongly suggestive of PA.
Aldosterone / renin ratio (ARR), aldosterone suppressive test and
adrenal veins sampling (AVS) are the three screening tests required
for the diagnosis of PA and for subtype classification.
Adrenalectomy is indicated for treatment of aldosteronoma but
antialdosterone agents are suitable alternatives.
In patients with aldosteronoma, adrenalectomy is more costeffective than medical treatment.
2902 Mo