Introduction
The World Health Organization (WHO) goal to reduce mortality due to chronic
non-communicable diseases (CNCD) by 2% per year requires a huge effort from
countries.
1-4
This challenge for health professionals asks for a
global political action on control of social measures, with cost-effective
population interventions to reduce CNCD and their risk factors (RF). Health
professionals should demand from their government the implementation of acceptable
cost measures, such as tobacco cessation counseling, guidance on healthy feeding
practices and need for regular physical exercise, systemic arterial hypertension
(SAH) control, and promotion of teaching and updating activities in programs
directed to those issues. Those measures would contribute with around 70% of the
goal of 2% per year reduction in CNCD.
2,5
Dyslipidemia, SAH
and obesity are highly prevalent multifactorial diseases in Portuguese language
countries (PLC).
5,6
Systemic arterial hypertension is the major RF for
complications, such as stroke, acute myocardial infarction and chronic kidney
disease, corresponding in importance to dyslipidemia and obesity for the development
of atherosclerotic diseases.
5,6
In addition to their significant
epidemiological impact, the non-pharmacological treatment of those cardiovascular
RF
plays a relevant economic role in the expenditures of the Ministries of Health,
Social Security and Economy, because those affections are major causes directly or
indirectly involved with absenteeism in the workplace. There is evidence that
preventive actions are more promising in the primary health care setting.
The number of adults with SAH increased from 594 million in 1975 to 1.13 billion in
2015, being 597 million men and 529 million women. That increase might be due to
both population aging and increase in number.
6
When analyzing the trends in blood pressure (BP) levels of
19.1 million adults from several population studies in the past four decades
(1975-2015), the elevated levels shifted from high-socioeconomic-level countries to
low-intermediate-socioeconomic-level countries of South Asia and Sub-Saharan Africa.
However, BP levels remain high in Eastern and Central Europe and Latin
America.
6
Several trends were identified when analyzing the proportional mortality and
percentage change in the mortality rates due to hypertensive diseases and their
outcomes, ischemic heart diseases (IHD) and stroke, in the PLC from 1990 to 2015
(Table 1). The highest proportional
mortality rates due to hypertensive diseases were observed in Brazil, Mozambique and
Angola. Portugal had the highest human development index (HDI) in 2015 and the
highest mortality due to stroke.
7-9
The reduced access, around 50-65%,
to essential pharmacological treatment in low-and
low-intermediate-socioeconomic-level countries might have contributed to those
results. In addition, in 40% of those countries there is less than 1 physician per
1000 in habitants, and a small number of hospital beds for the care of the
uncontrolled-SAH-related outcomes.
7
Thus, joint actions to implement primary prevention measures can reduce the outcomes
related to hypertensive disease, especially IHD and stroke. It is mandatory to
ensure the implementation of guidelines for the management of SAH via a continuous
process, involving educational actions, lifestyle changes and guaranteed access to
pharmacological treatment.
Table 1
Proportional mortality and annual percentage of change in mortality rates in
both sexes, all ages, from 1990 to 2015, due to hypertensive disease,
ischemic heart disease and stroke, in addition to human development index
(HDI) and population in 2015
Countries
Hypertensive disease
Ischemic heart disease
Stroke
HDI 2015
Population 2015*
Proportional mortality (annual % change
in mortality rates)
Brazil
1.77 (+1.79)
14.44 (+0.44)
10.61 (+0.12)
0.754*
205,002,000
Mozambique
1.46 (+0.27)
3.84 (+1.25)
5.37 (+0.52)
0.418*
25,727,911
Angola
1.28 (-0.97)
4.65 (-0.96)
5.35 (-1.09)
0.533*
25,789,024
Portugal
1.08 (+1.20)
12.71 (-1.32)
14.96 (-2.32)
0.843*
10,374,822
Guinea-Bissau
0.53 (-0.43)
4.87 (+0.25)
5.07 (+0.22)
0.424*
1,844,000
East Timor
1.33 (+0.38)
11.84 (+1.16)
10.02 (+0.57)
0.605*
1,212,107
Macao
NA
NA
NA
0.566#
642,900
Cape Verde
0.75 (-0.62)
11.74 (+1.34)
13.74 (-0.18)
0.648*
524,833
Saint Thomas and Prince
0.44 (-0.55)
8.18 (-0.41)
10.22 (-0.18)
0.574*
190,000
*
last year available - 2015,
#
last year available - 2014, NA: not available. Source:
7-9
Diagnosis and classification
The risk resulting from high BP levels increases with age, and every 2-mmHg
elevation is associated with a 7% and a 10% increase in the risk of death due to
IHD and stroke, respectively.
2
At the medical office, BP can be assessed by use of either the automated or
auscultatory method, being elevated when systolic BP (SBP) ≥ 140 mm Hg
and/or diastolic BP (DBP) ≥ 90 mm Hg, at least on two occasions.
The diagnosis of SAH is based on the measurement at the doctor's office of two or
more high BP values on at least two occasions. The classification of BP
according to measurements taken at the medical office, for individuals older
than 18 years, is shown in Table 2.
Ambulatory BP monitoring for 24 hours (ABPM) or home BP monitoring (HBPM) can
help in the diagnosis of white-coat hypertension (WCH) and masked hypertension
(MH). The WCH relates to the difference between BP measured at the office (high)
and that measured with ABPM or HBPM (normal). In MH, the situation is the
opposite (Figure 1). In view of the
suspicion of WCH and MH, ABPM is mandatory, and may be replaced by HBPM in
communities where ABPM is not available. Figure
1 shows the flowchart for the diagnosis of SAH.
Table 2
Blood pressure classification according to measurements taken at the
office for individuals older than 18 years
Classification
SBP (mm Hg)
DBP (mm Hg)
Normal
≤ 120
≤ 80
Prehypertension
121 – 139
81 – 89
Stage 1 hypertension
140 – 159
90 – 99
Stage 2 hypertension
160 – 179
100 – 109
Stage 3 hypertension
≥ 180
≥ 110
When SBP and DBP are in different categories, the highest should be
used to classify BP.
Systolic hypertension is considered isolated if SBP ≥ 140 mm
Hg and DBP < 90 mm Hg, and it should be classified into stages 1,
2 and 3. SBP: systolic blood pressure; DBP: diastolic blood
pressure. Source: 7th Brazilian guideline for arterial hypertension
management, 2016.
1
Figure 1
Flowchart for the diagnosis of arterial hypertension. BP: blood
pressure; ABPM: ambulatory BP monitoring; HBPM: home BP monitoring;
SBP: systolic BP; DBP: diastolic BP.
The ABPM enables the identification of circadian BP changes, especially those
related to sleep. In ABPM, BP is considered increased when BP in 24 hours
≥ 130/80 mmHg, ranging from wakefulness ≥ 135/85 mm Hg to sleep
≥ 120/70 mmHg. For HBPM, BP is considered elevated when ≥ 135/85
mmHg.
1
Recommended technique for measuring blood pressure
Initially the patients should be informed about the procedure, and the steps on
Table 3 should be followed.
3,10,11
Blood
pressure should be measured by all health professionals on every clinical
assessment and at least once a year.
Table 3
Recommended technique for measuring office blood pressure by using the
auscultatory method
•
BP should be measured with a validated, calibrated
and accurate sphygmomanometer, with cuff size adequate to arm
circumference (according to the manufacturer's recommendation):
usually cuff width close to 40% and cuff length covering 80-100%
of arm circumference.
•
The cuff should be placed snugly, 2-3 cm above the
cubital fossa, with its compressive part centralized on the
brachial artery, and the arm supported at heart level.
•
The patient should rest at a calm environment for 5
minutes, sitting in a chair with back supported, legs uncrossed
and feet on the floor. The patient should be relaxed, having
neither exercised in the previous 30 minutes, nor consumed
tobacco, alcohol or energetic foods (including coffee) in the
previous 1 hour.
•
In addition, BP will be measured after 2 minutes in
the supine position with the arm supported, especially for
diabetics and the elderly, and when orthostatic hypotension is
suspected. It is worth noting that measuring BP in the sitting
position will be useful for therapeutic decision-making, while
that in the orthostatic position, for treatment changes in case
of orthostatic hypotension.
•
The cuff should be inflated rapidly up to 30 mm Hg
above the level the radial pulse can no longer be palpated, and
then deflated at approximately 2 mm Hg/beat. SBP will be
determined by auscultation of the first sound (Korotkoff phase
I), and DBP, by disappearance of the sounds (Korotkoff phase V).
If the heart beats persist until level zero, determine DBP on
the muffling of sounds (Korotkoff phase IV).
•
The first reading should be discarded, and two
sequential readings in both members should be taken, the highest
one being recorded. If arrhythmia is present, more measurements
should be taken to determine mean BP.
•
Record the BP reading obtained for the patient.
Reassess BP levels at least monthly until control is achieved,
and then every 3 months.
BP: blood pressure; SBP: systolic blood pressure; DBP: diastolic
blood pressure.
Clinical assessment and risk stratification
Complementary assessment is aimed at detecting target-organ damage (TOD), aiding
cardiovascular risk stratification and identifying signs of secondary SAH. Table 4
shows the recommended complementary
tests (routine and for specific populations).
Table 4
Recommended complementary tests (routine and for specific
populations)
Routine tests for all hypertensive
patients
Urinalysis
Fasting glycemia and HbA1c
eGFR
Total cholesterol, HDL-C and serum
triglycerides
Conventional ECG
Serum levels of creatinine, potassium and uric
acid
Recommended tests to search for
TOD in specific populations
Chest X ray
Clinical suspicion of cardiac and/or pulmonary
impairment. Aortic dilatation or aneurysm (if echocardiogram is
not available). Suspicion of aorta coarctation.
Echocardiogram
Evidence of LVH on ECG or patients with clinically
suspected HF. LVH = LV mass corrected for BS ≥ 116
g/m2 (men) or 96 g/m2 (women)
Albuminuria
Diabetic hypertensive patients, with metabolic
syndrome or at least two RF. Normal values < 30 mg/24h.
Carotid US
Carotid murmur, CbVD signs, atherosclerotic disease
in other sites. IMT values > 0.9 mm and/or atherosclerotic
plaques.
Renal US or Doppler
Patients with abdominal masses or abdominal
murmurs.
Exercise test
Suspicion or family history of CAD, DM.
Brain MRI
Patients with cognitive disorders and dementia.
Detection of silent infarctions and micro hemorrhages.
HbA1c: glycated hemoglobin; eGFR: estimated glomerular filtration
rate; TOD: target-organ damage; ECG: electrocardiogram; LVH: left
ventricular hypertrophy; HF: heart failure; LV: left ventricular;
BS: body surface; RF: risk factors; US: ultrasonography; CbVD:
cerebrovascular disease; IMT: intima-media thickness; CAD: coronary
artery disease; DM: diabetes mellitus; MRI: magnetic resonance
imaging.
Target-organ damage should be investigated with the complementary tests
shown in Table 4, in addition to
the following exams:
Left ventricular hypertrophy, assessed on electrocardiogram: Sokolow-Lyon
index [S in V1 + R in V5 or V6 (whichever is larger)] > 35 mm; RaVL
> 1.1 mV; Cornell index [S in V3 + R in aVL > 28 mm (men), and S
in V3 + R in aVL > 20 mm (women)]; or on echocardiogram: left
ventricular mass index ≥ 116 g/m2 (men), and ≥
96 g/m2 (women);
Atherosclerotic disease in other sites and chronic kidney disease ≥ stage
3 [estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73
m2] (Table 5).
Table 5
Stratification based on risk factors, target-organ damage and
cardiovascular or kidney disease
SBP 130-139 or DBP 85-89
Stage 1 SAH SBP 140-159 or DBP 90-99
Stage 2 SAH SBP 160-179 or DBP 100-109
Stage 3 SAH SBP ≥ 180 or DBP ≥
110
No risk factor
No additional risk
Low risk
Intermediate risk
High risk
1-2 risk factors
Low risk
Intermediate risk
High risk
High risk
≥ 3 risk factors
Intermediate risk
High risk
High risk
High risk
Presence of TOD, CVD, CKD or DM
High risk
High risk
High risk
High risk
BP: blood pressure; SBP: systolic blood pressure; DBP: diastolic
blood pressure; SAH: systemic arterial hypertension; TOD:
target-organ damage; CVD: cardiovascular disease; CKD: chronic
kidney disease; DM: diabetes mellitus. Source: 7th Brazilian
guideline for arterial hypertension management, 2016.
1
Risk stratification should consider the classical RF, relating them to BP levels
as shown in Table 5.
The following risk factors are considered:
male sex and age (men > 55 years and women > 65 years);
smoking habit, dyslipidemia (triglycerides > 150 mg/dL; LDL-C > 100
mg/dL; HDL-C < 40 mg/dL), obesity (body mass index ≥ 30
kg/m2), abdominal obesity (abdominal circumference >
102 cm for men, and > 88 cm for women), diabetes mellitus, abnormal
oral glucose tolerance test or fasting glycemia of 102-125 mg/dL, and
family history of premature cardiovascular disease (men < 55 years,
and women < 65 years).
Treatment
Blood pressure reduction is followed by a significant cardiovascular risk
reduction, which is higher in individuals at high cardiovascular risk, with a
relative residual risk reduction in the other individuals.
2,11
Non-pharmacological therapy with changes in lifestyle
(CLS) should be initially implemented for all stages of SAH and for individuals
with BP of 135-139/85-89 mmHg (Table 6).
For stage 1 hypertensives at low or intermediate cardiovascular risk, management
can start with CLS, and 3 to 6 months can be waited before deciding to start
pharmacological treatment. For the other stages, antihypertensive agents should
be initiated as soon as the diagnosis is established.
Table 6
Recommendations for the non-pharmacological treatment of arterial
hypertension
Measure
Recommendations
Body weight control
Maintain BMI < 25 kg/m2
up to 65 years of age;
Maintain BMI < 27 kg/m2 after 65 years
of age;
Maintain AC < 88 cm for women and < 102 cm for
men.
Dietary pattern
Adopt a diet rich in fruits and
vegetables, with a reduced amount of saturated fat.
The DASH (Dietary Approach to Stop Hypertension)
diet, with 2100 kcal/day as originally proposed, is the most
used:
Fruits (portions/day)
4-5
Vegetables (portions/day)
4-5
Milk and dairy products < 1% fat (portions/day)
2-3
Lean meat, fish and poultry (g/day)
< 180
Oils and fats (portions/day)
2-3
Seeds and nuts (portions/week)
4-5
Added sugars (portions/week)
< 5
Salt (portion/day)
~ 6 g (3000 mg of sodium)
Whole grains (portions/day)
6-8
Moderate alcohol consumption
Limit daily alcohol consumption to 1
dose for women and low-weight individuals, and 2 doses for
men.
Physical activity
For all hypertensives –
population recommendation – physical activity
practice
Moderate, continuous (1 x 30 min) or cumulative (2 x
15 min or 3 x 10 min) physical activity (similar to walking): at
least 30 min/day, 5 to 7 days/week.
Aerobic training
At least 3 times/week (ideally 5 times/week),
minimum of 30 min (ideally 40 to 50 min); Several
modalities: walking, running, dancing, swimming;
Moderate intensity defined as: higher intensity that still
allows talking (no breathlessness), and sensation of mild to
moderate tiredness; Maintain training heart rate (THR)
between the lower and upper THR calculated as follows:
Lower THR = (maximum HR – resting HR) x 0.5 + resting HR*; upper
THR = (maximum HR – resting HR) x 0.7+ resting HR*
Ideally, the HR used to calculate the intensity of the aerobic
training should be determined on a maximum exercise test, with
patients on their usual medication. *Maximum
HR: obtained either on a maximum exercise test
with regular medications, or by calculating maximum HR estimated
according to age (220 - age; not to be used for individuals with
heart disease or hypertensives on beta-blockers or
nondihydropyridine calcium channel blockers). Resting
HR: measured after a 5-minute rest, lying
down.
Resistance training
2 - 3 times/week, 8 - 10 exercises for the large
muscle groups, prioritizing unilateral execution, when
possible; 1 - 3 sets with 10 - 15 repetitions up to
moderate fatigue (reducing the movement velocity and avoiding
apnea, exhaling during contraction and inhaling when returning
to the initial position); Long passive pauses: 90 - 120
s.
BMI: body mass index; AC: abdominal circumference. Source: Adapted
from the 7th Brazilian guideline for arterial hypertension
management, 2016.
1
A BP target lower than 130/80 mm Hg is recommended for patients at high
cardiovascular risk, including those with diabetes mellitus, and lower than
140/90 mm Hg for stage 3 hypertensives. For patients with coronary artery
disease, BP should not be lower than 120/70 mm Hg because of the risk of
coronary hypoperfusion, myocardial damage and cardiovascular events. For elderly
hypertensives ≥ 80 years, BP levels should be lower than 145/85 mm Hg.
Special attention should be paid to patients with dark skin phenotype who will
benefit more from the use of calcium-channel blockers.
12-14
Figure 2 shows the pharmacological approach
to SAH.
Figure 2
Flowchart for the treatment of arterial hypertension. (adapted from
Malachias et al
1
)
CV: cardiovascular; BP: blood pressure; ACEI:
angiotensin-converting-enzyme inhibitor; ARB: angiotensin-receptor
blocker; CCB: calcium-channel blocker.
When angiotensin-converting enzyme inhibitors (ACEI) are not tolerated, they
should be replaced with low-cost angiotensin-receptor blockers (ARB).
Beta-blockers should be considered for young individuals intolerant to ACEI and
ARB, lactating women, individuals with increased adrenergic tone, and those with
IHD or heart failure (HF). In case of intolerance to calcium-channel blockers
(CCB) because of edema, or HF or suspected HF, diuretics can be used: thiazide
diuretics (chlorthalidone - 12.5-25 mg 1X day; indapamide - 1.5-2.5 mg 1X day).
Individuals with dark skin phenotype should have ARBs rather than ACEIs for
pharmacological combinations.
2,11-14
Approximately two thirds of the patients will need combinations of at least two
drugs to control BP. The advantage of the association is the synergism of
different mechanisms of action, with dose reduction and consequent decrease in
adverse effects, in addition to higher therapeutic adherence.
There is no preference for a therapeutic class of drug to treat a hypertensive
patient with a previous stroke, but a BP lower than 130/80 mm Hg should be
targeted.
Table 7 depicts the clinical situations
with indication for or contraindication to specific drugs. For chronic kidney
disease, ACEI and ARB reduce albuminuria, and thiazide diuretics are used for
stages 1 to 3, while loop diuretics, for stages 4 and 5.
2,11-14
Table 7
Clinical situations with indication for or contraindication to specific
drugs
Drugs with specific indication
Clinical situation
Initial therapy indicated
Heart failure
ACEI/ARB, diuretics and BB
AMI, angina pectoris, percutaneous or surgical
myocardial revascularization
ACEI/ARB, BB, ASA, statins
Diabetes mellitus
Thiazide diuretics, ACEI/CCB, BB
Chronic renal failure
ACEI/ARB, loop diuretics
Metabolic syndrome
CCB, ACEI/ARB
Aortic aneurysm
BB
Peripheral arterial disease
ACEI, CCB
Pregnancy
Methyldopa, CCB
Contraindicated
drugs
Clinical situation
Contraindicated therapy
Asthma and chronic bronchitis
Non-cardioselective BB
Pregnancy
ACEI, ARB
AV block
BB, nondihydropyridine CCB
Gout
Diuretics
Bilateral stenosis of the renal artery
ACEI, ARB
ACEI: angiotensin-converting-enzyme inhibitor; ARB:
angiotensin-receptor blocker; CCB: calcium-channel blocker; BB:
beta-blockers; AMI: acute myocardial infarction; ASA:
acetylsalicylic acid; AV: atrioventricular.
*
ACEI and ARB should not be associated, because of the ONTARGET study.
Adapted from
2,4
Arterial hypertension in pregnancy
Pregnant women with uncomplicated chronic hypertension should have BP levels
lower than 150/100 mmHg, but DBP should not be < 80 mmHg.
1,2,11-14
The use of ACEI and ARB is
contraindicated during pregnancy, and atenolol and prazosin should be avoided.
Methyldopa, beta-blockers (except atenolol), hydralazine and CCBs (nifedipine,
amlodipine and verapamil) can be safely used.
2,11-14
In chronic gestational hypertension with TOD, BP levels should be maintained
under 140/90 mmHg, and the pregnant woman should be referred to a specialist for
proper care during delivery and to avoid teratogenicity. Delivery should not be
hastened if BP < 160/110 mmHg (with or without anti-hypertensive drugs) up to
the 37th week. The fetal growth and amount of amniotic fluid should
be monitored with ultrasonography between the 28th and
30th weeks and between the 32nd and 34th
weeks, and with umbilical artery Doppler. During delivery, BP levels should be
monitored continuously.
1,2,12-14
During the
puerperium period, BP levels should be maintained under 140/90 mmHg, preferably
with the following drugs, whose use is safe during lactation:
hydrochlorothiazide, spironolactone, alpha-methyldopa, propranolol, hydralazine,
minoxidil, verapamil, nifedipine, nimodipine, nitrendipine, benazepril,
captopril and enalapril.
1,2,12-15
Preeclampsia (PE) is defined by the presence of SAH after the 20th
gestational week, associated with significant proteinuria or presence of
headache, blurred vision, abdominal pain, low platelet count (<
100,000/mm3), elevation of liver enzymes (twice the baseline
level), kidney impairment (creatinine > 1.1 mg/dL or twice the baseline
level), pulmonary edema, visual or cerebral disorders and scotomas. Eclampsia
occurs when grand mal seizure associates with PE. The use of magnesium sulfate
is recommended to prevent and treat eclampsia, at an attack dose of 4-6 g IV for
10-20 minutes, followed by infusion of 1-3 g/h, usually for 24 hours after the
seizure. In case of relapse, 2-4 g IV can be administered. The use of
corticosteroids, IV anti-hypertensives (hydralazine, labetalol) and blood volume
expansion are recommended. Patients should be admitted to the intensive care
unit.
1,2,11-15
Table 8 lists the reasons for not
achieving proper BP control. It is worth noting the importance of ruling
pseudoresistance out (WCH).
Table 8
Possible reasons of not achieving proper blood pressure control
•
Inadequate adherence to medications, diet, physical
activity practice, and consumption of salt, tobacco and
alcohol.
•
Associated conditions: overweight and obesity,
obstructive sleep apnea, chronic pain, blood volume overload,
chronic kidney disease, thyroid disease.
•
Drug interaction: nonsteroidal anti-inflammatory
drugs, corticosteroids, anabolic steroids, sympathomimetic
drugs, decongestants, amphetamine, erythropoietin, cyclosporine,
tacrolimus, licorice, monoamine oxidase inhibitors, serotonin
and norepinephrine reuptake inhibitors.
•
Suboptimal therapeutic regimen, low doses of drugs,
inappropriate combinations of anti-hypertensive drugs, renal
sodium retention (pseudotolerance).
•
Secondary hypertension: renovascular disease,
primary hyperaldosteronism, pheochromocytoma.
Source: Leung et al.
11
Secondary arterial hypertension
The prevalence of secondary SAH in the hypertensive population is around 3-5%.
The most common cause of secondary SAH is renal parenchymal disease, responsible
for 2-5% of the SAH cases. The adrenal causes of SAH and pheochromocytoma occur
in less than 1% of all cases of SAH. However, 80% of the patients with Cushing's
syndrome have SAH. Physicians must keep a high level of clinical suspicion when
managing hypertensives of difficult control. Table 9 lists the clinical findings of
the major etiologies of
secondary SAH, associating them with the complementary tests that should be used
to establish the diagnosis.
Table 9
Causes of secondary SAH, signs and complementary diagnostic tests
Clinical findings
Diagnostic suspicion
Additional studies
Snoring, daytime sleepiness, MS
OSAHS
Berlin questionnaire, polysomnography or home
respiratory polygraphy with at least 5 episodes of apnea and/or
hypopnea per sleep hour
RAH and/or hypopotassemia (not necessary) and/or
adrenal nodule
Primary hyperaldosteronism (adrenal hyperplasia
or adenoma)
Measurements of aldosterone (> 15 ng/dL) and
plasma renin activity/concentration; aldosterone/renin > 30.
Confirmatory tests (furosemide and captopril). Imaging tests:
thin-sliced CT or MRI
Edema, anorexia, fatigue, high creatinine and urea,
urine sediment changes
Kidney parenchymal disease
Urinalysis, eGFR calculation, renal US, search
for albuminuria/proteinuria
Abdominal murmur, sudden APE, renal function
changes due to drugs that block the RAAS
Renovascular disease
Renal Doppler US and/or renogram, angiography via
MRI or CT, renal arteriography
Absent or decreased femoral pulses, decreased blood
pressure in the lower limbs, chest X ray changes
Coarctation of the aorta
Echocardiogram and/or chest angiography via
CT
Weight gain, decreased libido, fatigue, hirsutism,
amenorrhea, 'moon face', 'buffalo hump', purple striae, central
obesity, hypopotassemia
Cushing's syndrome (hyperplasia, adenoma and
excessive production of ACTH)
Salivary cortisol, 24-h urine free cortisol and
suppression test: morning cortisol (8h) and 8 hours after
administration of dexamethasone (1 mg) at 12PM. MRI
Paroxysmal AH with headache, sweating and
palpitations
Pheochromocytoma
Free plasma metanephrines, plasma catecholamines
and urine metanephrines. CT and MRI
Fatigue, weight gain, hair loss, DAH, muscle
weakness
Hypothyroidism (20%)
TSH and free T4
Intolerance to heat, weight loss, palpitations,
exophthalmos, hyperthermia, hyperreflexia, tremors,
tachycardia
Hyperthyroidism
TSH and free T4
Renal lithiasis, osteoporosis, depression,
lethargy, muscle weakness or spasms, thirst, polyuria
Hyperparathyroidism (hyperplasia or adenoma)
Plasma calcium and PTH
Headache, fatigue, visual disorders, enlarged
hands, feet and tongue
Acromegaly
IGF-1 and GH levels at baseline and during oral
glucose tolerance test
MS: metabolic syndrome; OSAHS: obstructive sleep apnea-hypopnea
syndrome; RAH: resistant arterial hypertension; CT: computed
tomography; MRI: magnetic resonance imaging; eGFR: estimated
glomerular filtration rate; US: ultrasonography; APE: acute
pulmonary edema; RAAS: renin-angiotensin-aldosterone system; ACTH:
adrenocorticotropin; AH: arterial hypertension; DAH: diastolic
arterial hypertension; TSH: thyroid stimulating hormone; PTH:
parathormone; IGF-1: insulin-like growth factor type 1; GH: growth
hormone. Source: Malachias et al.
1
Similarly to CNCD, lifelong adherence to the SAH treatment is poor. In the first
year, 40% of the patients quit regular treatment, which prevent them from
profiting from a reduction in both TOD and cardiovascular events, such as
myocardial infarction and stroke. The following factors are related to
non-adherence to treatment: adverse effects, number of daily doses and drug
tolerance. Fixed drug combinations increase adherence by enabling better
individual adequacy, reducing the likelihood of irregular use of daily doses.
The involvement of patients and families, as well as a multidisciplinary
approach enhance adherence to treatment. The use of interactive apps that
increase the participation of patients in BP control is suggested to encourage
their persistence and regular medication use.
16