Evaluation of hypertension in children and adolescents

INTRODUCTION — It has become clear that hypertension (HTN) begins in childhood and adolescence, and that it contributes to the early development of cardiovascular disease (CVD).

The evaluation of children with HTN will be reviewed here. The epidemiology, etiology, diagnosis, and treatment of childhood HTN are discussed separately. (See "Epidemiology, risk factors, and etiology of hypertension in children and adolescents" and "Definition and diagnosis of hypertension in children and adolescents" and "Nonemergent treatment of hypertension in children and adolescents".)

In addition, the evaluation for hypertensive emergency is presented elsewhere. (See "Approach to hypertensive emergencies and urgencies in children".)

DEFINITION — The following terms are used throughout this topic:

●Hypertension (HTN) – In pediatric patients, hypertension (HTN) is defined as follows (see "Definition and diagnosis of hypertension in children and adolescents"):

•In children <13 years old, the definition is based upon blood pressure (BP) percentiles for sex, age, and height, as summarized in the tables (table 1 and table 2 and table 3) [1].

•In adolescents ≥13 years old, the definition is aligned with adult guidelines (table 1).

●Primary versus secondary HTN – Childhood HTN is categorized as primary (essential) or secondary depending upon whether an underlying cause can be identified (table 4).

IMPORTANCE — There is good evidence that identifying children with HTN and successfully treating their primary HTN has an important impact on long-term cardiovascular outcomes. Pediatric data include clinical studies that demonstrate cardiovascular structural and functional changes in children with HTN, and autopsy studies that have shown an association of blood pressure (BP) with atherosclerotic changes in the aorta and coronary arteries of children and young adults. Children with primary HTN are likely to continue to have HTN as adults, and clinical trials in adults have shown that antihypertensive therapy reduces cardiovascular morbidity and mortality. In patients with secondary HTN, clinical outcomes vary depending on the underlying etiology and whether the underlying cause is amenable to treatment. (See "Nonemergent treatment of hypertension in children and adolescents", section on 'Rationale for intervention' and "Definition and diagnosis of hypertension in children and adolescents", section on 'Tracking'.)

Thus, one of the most important components of the successful management of childhood HTN is distinguishing between primary and secondary HTN, and identifying the cause of secondary hypertension, if present.

INITIAL EVALUATION

Goals — The goals of the evaluation are to:

●Distinguish between primary and secondary HTN (table 4).

●Identify any treatable conditions that may be causing or contributing to HTN (table 5). (See "Epidemiology, risk factors, and etiology of hypertension in children and adolescents", section on 'Etiology'.)

●Identify other comorbid conditions or risk factors for early cardiovascular disease (CVD), including obesity, dyslipidemia, and diabetes mellitus (table 6). (See "Overview of risk factors for development of atherosclerosis and early cardiovascular disease in childhood".)

●Identify patients for whom antihypertensive drug therapy is warranted. The presence of another CVD risk factor or disease associated with a high risk of CVD impacts the timing and choice of intervention for high BP. Indications for pharmacologic therapy are discussed separately. (See "Nonemergent treatment of hypertension in children and adolescents", section on 'Who should be treated'.)

Most children and adolescents with HTN, particularly those who are likely to have secondary HTN, should be referred to a pediatric nephrologist or other clinician experienced in childhood HTN.

History and physical examination

Assess for symptoms attributable to hypertension — Symptoms consistent with hypertensive emergencies include headache, seizures, changes in mental status, vomiting, focal neurologic complaints, visual disturbances, and cardiovascular (CV) complaints indicative of heart failure (such as chest pain, palpitations, cough, or shortness of breath). Children with hypertensive emergency require pharmacologic therapy without delay and hospitalization for evaluation and ongoing care. (See "Approach to hypertensive emergencies and urgencies in children" and "Initial management of hypertensive emergencies and urgencies in children".)

Secondary versus primary hypertension — An important focus of the history and physical examination is to differentiate secondary from primary HTN by looking for signs and symptoms that are associated with specific underlying etiologies for HTN (table 7 and table 8).

Secondary HTN should be suspected in children with any of the following findings (table 4) [1]:

●Prepubertal, particularly younger than six years of age.

●A thin child with a negative family history for HTN. (See "Epidemiology, risk factors, and etiology of hypertension in children and adolescents", section on 'Nonmodifiable risk factors' and "Epidemiology, risk factors, and etiology of hypertension in children and adolescents", section on 'Modifiable risk factors'.)

●An acute rise in blood pressure (BP) above a previously stable baseline.

●Specific ambulatory BP patterns, such as sustained diastolic HTN, nocturnal HTN, and/or blunted nocturnal dipping. (See "Ambulatory blood pressure monitoring in children".)

●Past history of the following suggests renal disease as an underlying etiology:

•Urinary tract infection, especially pyelonephritis

•Congenital kidney or urologic anomalies

•Perinatal history of neonatal umbilical arterial catheterization, oligohydramnios, or perinatal anoxia

●History of snoring, daytime sleepiness (in adolescents), or hyperactivity (in younger children) are associated with obstructive sleep apnea. (See "Evaluation of suspected obstructive sleep apnea in children", section on 'Clinical manifestations'.)

●Family history of chronic or congenital renal disease (such as polycystic kidney disease), or other genetic conditions that are associated with HTN, such as neurofibromatosis or tuberous sclerosis. (See "Neurofibromatosis type 1 (NF1): Pathogenesis, clinical features, and diagnosis" and "Renal manifestations of tuberous sclerosis complex".)

●History of drugs known to increase BP including glucocorticoids, central nervous system stimulants, decongestants with pseudoephedrine, or oral contraceptives. Recreational drugs, including anabolic steroids and stimulants (eg, cocaine and amphetamine).

●Physical finding(s) suggestive of systemic disease or a specific secondary etiology of HTN include (table 8):

•Cutaneous findings associated with tuberous sclerosis (ash leaf spots or adenoma sebaceum) or neurofibromatosis (café-au-lait spots and neurofibromas).

•Ambiguous genitalia may be suggestive of congenital adrenal hyperplasia with excess endogenous secretion of androgens and mineralocorticoids. Children with mineralocorticoid excess may develop hypokalemia. (See "Evaluation of the infant with atypical genital appearance (difference of sex development)".)

•Edema may be indicative of kidney disease or heart failure.

●Clinical findings of arthritis or rash may be suggestive of glomerulonephritis due to systemic disorders, such as immunoglobulin A vasculitis (IgAV; Henoch-Schönlein purpura [HSP]) or systemic lupus erythematosus (SLE). Abdominal pain may also be present in patients with IgAV (HSP). (See "IgA vasculitis (Henoch-Schönlein purpura): Clinical manifestations and diagnosis" and "Childhood-onset systemic lupus erythematosus (SLE): Clinical manifestations and diagnosis".)

•The presence of an abdominal bruit raises the possibility of renovascular disease, but its absence does not exclude the diagnosis.

•Coarctation of the aorta is suggested by findings of hypertension in the upper extremities, low or unobtainable blood pressure in the lower extremities, and diminished or delayed femoral pulses. (See "Clinical manifestations and diagnosis of coarctation of the aorta".)

•Symptoms suggestive of catecholamine excess in addition to elevated BP include headache, sweating, and tachycardia. Possible etiologies include pheochromocytoma, neuroblastoma, or use of sympathomimetic drugs (eg, phenylpropanolamine [an over-the-counter decongestant], cocaine, amphetamines, phencyclidine, epinephrine, phenylephrine, and terbutaline).

•Findings suggestive of hyperthyroidism include tachycardia, proptosis, or enlarged thyroid or goiter. Of note, HTN, particularly diastolic HTN, is associated with hypothyroidism. Clinical symptoms of hypothyroidism in children include weight gain, exercise intolerance, constipation, fatigue, and cold intolerance.

Assess for other CVD risk factors — The history and physical examination should assess for risk factors that contribute to high BP and early CVD [1] (table 6).

●Assess for traditional CVD risk factors (see "Overview of risk factors for development of atherosclerosis and early cardiovascular disease in childhood", section on 'Traditional ASCVD risk factors'):

•Family history – Review the family history to assess whether there is a history of premature CVD in other family members.

•Obesity – Calculate the calculating body mass index (BMI) to identify overweight/obese children (for girls: (calculator 1) (figure 1); for boys: (calculator 2) (figure 2)). (See "Definition, epidemiology, and etiology of obesity in children and adolescents".)

•Smoking or smoke exposure.

•Type 1 or 2 diabetes mellitus. (See "Complications and screening in children and adolescents with type 1 diabetes mellitus", section on 'Cardiovascular disease'.)

•Dyslipidemia. (See "Dyslipidemia in children and adolescents: Definition, screening, and diagnosis".)

●Review the medical history for other conditions associated with increased CVD risk (eg, chronic kidney disease [CKD], organ transplantation, cardiac disease, childhood cancer, Kawasaki disease, autoimmune disease, familial hypercholesterolemia, HIV infection, and adolescent depressive and bipolar disorders). (See "Overview of risk factors for development of atherosclerosis and early cardiovascular disease in childhood", section on 'Other conditions'.)

●Review the history to determine if the child has a known sleep disorder or symptoms concerning for obstructive sleep apnea (loud snoring, daytime sleepiness, or attention problems) [1-5]. (See "Evaluation of suspected obstructive sleep apnea in children".)

●Identify children with a sedentary lifestyle in whom increased physical activity may improve BP. Increased physical activity is also an important part of managing children who are overweight or obese (BMI >85^th percentile). (See "Nonemergent treatment of hypertension in children and adolescents", section on 'Exercise' and "Prevention and management of childhood obesity in the primary care setting".)

●Review the dietary history to identify dietary contributors to HTN (excess salt intake) and CVD risk (consumption of high-fat foods) and identify interventions that may decrease BP. (See "Nonemergent treatment of hypertension in children and adolescents", section on 'Diet' and "Dyslipidemia in children and adolescents: Management", section on 'Heart-healthy diet'.)

Physical findings of end-organ damage — The physical examination should assess for the following findings that suggest end-organ damage due to HTN:

●Retinal vascular changes due to HTN (image 1) (see "Ocular effects of hypertension")

●Cardiac heave or laterally displaced point of maximal impulse (PMI), which may indicate left ventricular hypertrophy (LVH)

Laboratory evaluation — Initial laboratory evaluation in all children with persistent HTN is directed at determining the etiology of HTN and identifying other CVD risk factors, especially in obese children [1].

●Testing to perform in all children and adolescents with HTN – We concur with the following initial evaluation for all children with HTN recommended by the 2017 American Academy of Pediatrics (AAP) guidelines for high BP [1]:

•Serum blood urea nitrogen (BUN), creatinine, and electrolytes

•Urinalysis

•Lipid profile (see "Dyslipidemia in children and adolescents: Definition, screening, and diagnosis", section on 'Choice of screening test')

●Additional testing for children who are obese (see "Clinical evaluation of the child or adolescent with obesity", section on 'Routine blood tests'):

•Hemoglobin A1c (screen for diabetes mellitus).

•Serum alanine transaminase (screen for fatty liver).

•In our practice, we also will obtain a fasting serum glucose if the urinalysis detects glycosuria.

These tests permit quick assessment of kidney function, potassium homeostasis, and acid-base status. In addition, they screen for common comorbid conditions associated with increased CVD risk (eg, diabetes mellitus and dyslipidemia).

The 2016 European Hypertension Society guidelines for the management of high blood pressure in children and adolescents includes a more extensive initial evaluation [6].

Kidney ultrasound — In our tertiary center, we obtain a kidney ultrasound as part of the initial evaluation for all patients referred for HTN evaluation. Other centers perform ultrasonography more selectively. The 2017 AAP high BP guidelines recommend a kidney ultrasound initially for children presenting with HTN at age <6 years and those with laboratory findings concerning for kidney disease (eg, abnormal kidney function tests or urinalysis) [1]. Ultrasonography is useful to determine the presence of both kidneys, presence of any congenital anomaly, or disparate kidney size, which may suggest scarring.

Detection of end-organ damage

Echocardiography — Left ventricular hypertrophy (LVH) is the most prominent manifestation of end-organ damage from HTN. LVH is associated with adverse cardiovascular disease (CVD) outcomes, and a significant number of children and adolescents with HTN have LVH [7-12].

Echocardiography is the recommended modality to detect LVH due to pediatric HTN. The 2017 American Association of Pediatrics (AAP) high blood pressure (BP) guidelines recommends echocardiography to assess for target-organ cardiac damage be performed at the time when pharmacologic therapy is being considered [1]. For children ≥8 to 18 years, LVH is defined as LV mass >51 g/m^2.7. For children <8 years, LVH is defined as LV mass >115 g/body surface area (BSA) for males, and LV mass >95 g/BSA for females.

The recommended interval for subsequent echocardiographic assessment is based on the results of the initial study [1]:

●For children without evidence of LV target organ damage, echocardiography is performed in 12 months for patients whose BP is not well controlled despite intervention with pharmacologic and nonpharmacologic therapy.

●For children with evidence of LV target organ damage, echocardiography is performed at six months to monitor for improvement or progression of damage. The results of the study and BP control are used to determine the scheduling of future studies.

Electrocardiography should not be performed to assess for end-organ cardiac damage, as the study is not sensitive enough to reliably identify pediatric patients with LVH [1].

Assessments that are not recommended — Studies have shown that elevated BP in childhood is associated with adverse changes in preclinical measures of atherosclerotic CVD (eg, carotid intima-media thickness, pulse wave velocity, flow-mediated dilation); however, these changes have not been directly correlated with CVD events in adulthood [1]. In addition, there are insufficient pediatric data to define threshold values for these measurements to guide clinical decision-making in children with HTN. As a result, use of these tools is generally limited to research settings and they are not recommended in routine clinical practice [1].

FURTHER EVALUATION — If the history, physical examination, and initial laboratory evaluation suggest a secondary cause of HTN (table 4 and table 5), further evaluation to determine the underlying etiology may be warranted.

Primary hypertension — Hypertensive children who fit the primary HTN profile need no further laboratory evaluation beyond the initial testing cited above (table 4) [1,6].

Data are insufficient to determine whether measurements of serum uric acid and microalbuminuria are useful in the evaluation and management of pediatric primary HTN [1]. As a result, routine assessment of uric acid and microalbuminuria is not recommended in the care of children with elevated BP.

Secondary hypertension — Further evaluation of patients with findings suggestive of secondary HTN is directed towards identifying the underlying cause. (See 'Secondary versus primary hypertension' above and "Epidemiology, risk factors, and etiology of hypertension in children and adolescents", section on 'Secondary hypertension'.)

The following diagnostic studies may be performed in hypertensive children with a high degree of suspicion that an underlying disorder is present [13].

Plasma renin and aldosterone activity — Evaluation of plasma renin and aldosterone activity (PRA) may be useful in patients in the following uncommon conditions:

●Excess mineralocorticoids (eg, aldosterone) secretion – Patients with mineralocorticoid excess usually present with hypokalemia and metabolic alkalosis and their PRA is low and often unmeasurable. (See "Pathophysiology and clinical features of primary aldosteronism".)

•Congenital adrenal hyperplasia is a common cause of excess mineralocorticoid secretion in children. Affected patients may present as a neonate with ambiguous genitalia due to the excess secretion of androgens. (See "Causes of primary adrenal insufficiency in children", section on 'Congenital adrenal hyperplasia' and "Evaluation of the infant with atypical genital appearance (difference of sex development)".)

•Aldosterone-secreting tumors, which are rare in children. Patients with primary hyperaldosteronism have low renin and high serum aldosterone with an aldosterone to renin ratio >30 (aldosterone in nanograms/dL and PRA in nanograms per mL/hour).

•Primary hypersecretion of aldosterone may result from familial hyperaldosteronism, a group of rare genetic disorders, including glucocorticoid-remediable hyperaldosteronism (GRA). GRA should be considered in a hypertensive child with a family history of early HTN (before age 21 years) and evidence of metabolic alkalosis even in the absence of hypokalemia. (See "Familial hyperaldosteronism".)

●Suppressed mineralocorticoids – Rare genetic disorders with low levels of aldosterone and renin, despite presenting with symptoms suggestive of mineralocorticoid excess, include Liddle syndrome, pseudohypoaldosteronism type 2 (also referred to as Gordon syndrome) and syndrome of apparent mineralocorticoid excess. (See "Genetic disorders of the collecting tubule sodium channel: Liddle syndrome and pseudohypoaldosteronism type 1", section on 'Liddle syndrome' and "Etiology, diagnosis, and treatment of hypoaldosteronism (type 4 RTA)", section on 'Pseudohypoaldosteronism type 2 (Gordon's syndrome)' and "Apparent mineralocorticoid excess syndromes (including chronic licorice ingestion)".)

●Renin-secreting tumor – Renin-secreting tumors are rare both in children and adults. Patients generally present with severe HTN, hypokalemia, metabolic alkalosis, and markedly elevated renin levels [14].

●Renovascular disease – The plasma renin activity may be elevated in children with renovascular HTN, but, as is true in adults, it is a relatively insensitive test. Approximately 15 percent of children with arteriographically evident renal artery stenosis have normal plasma renin activity [15,16].

●Urinary free cortisone to cortisol ratio – Patients with apparent mineralocorticoid excess syndrome have decreased 24-hour urinary free cortisone to cortisol ratio.

Plasma and urine catecholamines — Patients with HTN due to disorders with catecholamine excess such as pheochromocytoma and neuroblastoma will have elevated levels of both plasma and urine catecholamines and metabolites. In addition to HTN, affected patients may present with headache, sweating, and tachycardia. In patients with symptoms of catecholamine excess and elevated plasma and urine catecholamines, further evaluation is required. (See "Pheochromocytoma and paraganglioma in children" and "Clinical presentation, diagnosis, and staging evaluation of neuroblastoma".)

Kidney imaging — As previously discussed, we obtain a kidney ultrasound as part of the initial evaluation for all patients referred for HTN evaluation at our tertiary center. Other centers perform ultrasonography more selectively. (See 'Kidney ultrasound' above.)

In patients with a strong suspicion for renal scarring based on history (eg, recurrent febrile urinary tract infections) or with a suggestive but indeterminant finding on kidney ultrasound, a 99mTc–dimercaptosuccinic acid (DMSA) scan can be performed, since it is a more sensitive study to detect cortical loss and scarring [17].

Renovascular imaging — In our practice, renovascular imaging is considered when infants and children have known predisposing factors or findings associated with renal artery stenosis such as prior umbilical artery catheter placements, family history or findings for neurofibromatosis, an abdominal bruit, or a significant size discrepancy on renal ultrasonography. In addition, we consider renovascular imaging in younger children with HTN, who are less likely to have primary HTN, and in patients with stage 2 HTN when no other cause has been identified. (See "Epidemiology, risk factors, and etiology of hypertension in children and adolescents", section on 'Kidney disease'.)

Standard digital subtraction angiography (DSA), previously called renal angiography, is the current gold standard for evaluating renovascular disease in children [18]. Magnetic resonance angiography (MRA) and computed tomographic angiography (CTA) have also been used to screen for renovascular diseases [19], although they are not usually as reliable as DSA in detecting renovascular disease [18]. If renovascular evaluation is required, a radiological center with pediatric experience in these screening techniques should be chosen. The selection of the screening modality is dependent upon the expertise of the clinical staff and the availability of appropriate equipment and development of safe and useful protocols [20]. (See "Establishing the diagnosis of renovascular hypertension".)

We do not recommend routine duplex Doppler ultrasonography for evaluation of renovascular hypertension in otherwise healthy children because of its low sensitivity/specificity for diagnosis of renal artery stenosis [18].

For children, these procedures are not universally available or routinely performed. Considerations that must be taken into account in the use of these modalities to screen for renovascular disease in children include:

●When performing MRA, the need for conscious sedation or general anesthesia for small children and infants.

●The need to modify computed tomographic (CT) dosing to minimize unnecessary radiation exposures.

●The poorer sensitivity of Doppler ultrasonography compared with other imaging modalities in detecting renal vascular hypertension, especially in patients who have segmental artery lesions [21,22]. As a result, Doppler ultrasound should not be used to diagnose renal artery stenosis.

Sleep study evaluation — Evaluation of obstructive sleep apnea (OSA), including polysomnography is considered for children with history of snoring, daytime sleepiness (in adolescents), or hyperactivity (in younger children), especially if they are obese. (See "Evaluation of suspected obstructive sleep apnea in children", section on 'Evaluation'.)

Drug screening — If HTN is suspected due to cocaine or amphetamine use, drug testing should be initiated. (See "Cocaine: Acute intoxication", section on 'Laboratory and radiographic evaluation' and "Methamphetamine: Acute intoxication", section on 'Laboratory evaluation'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Hypertension in children".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: High blood pressure in children (The Basics)")

●Beyond the Basics topics (see "Patient education: High blood pressure in children (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Definition and importance – Hypertension (HTN) in childhood and adolescence contributes to premature cardiovascular disease (CVD). HTN is defined as follows (see 'Definition' above and 'Importance' above):

•In children <13 years old, HTN is defined based upon blood pressure (BP) percentiles for sex, age, and height, as summarized in the tables (table 1 and table 2 and table 3).

•In adolescents ≥13 years old, the definition is aligned with adult guidelines (table 1).

●Goals of evaluation – The goals of the evaluation of a child or adolescent with HTN include:

•Determine whether the patient is more likely to have primary (essential) or secondary HTN (table 4). Identify any treatable conditions that may be causing or contributing to HTN (table 5). Children with likely secondary HTN need further evaluation and management by a specialist experienced in childhood HTN. (See 'Secondary versus primary hypertension' above and 'Secondary hypertension' above.)

•Identify other comorbid conditions or risk factors for early CVD (eg, obesity, dyslipidemia, diabetes mellitus) (table 6). (See "Overview of risk factors for development of atherosclerosis and early cardiovascular disease in childhood".)

•Identify children for whom antihypertensive drug therapy is appropriate. (See "Nonemergent treatment of hypertension in children and adolescents", section on 'Who should be treated'.)

●Initial evaluation – The initial evaluation includes the following steps which help establish whether the HTN is primary or secondary (table 4) (see 'Initial evaluation' above):

•History and physical examination (table 7 and table 8) (see 'History and physical examination' above)

•Laboratory tests, including (see 'Laboratory evaluation' above):

-Serum BUN, creatinine, electrolytes

-Lipid profile

-Urinalysis

-For obese children, testing should also include hemoglobin A1c and alanine transaminase

-If drug abuse is suspected, testing should also include drug screening

•Kidney ultrasound – We obtain a kidney ultrasound in all patients referred to our center for evaluation of HTN; other centers perform ultrasound selectively in patients presenting with HTN at a young age (<6 years) or if there is laboratory evidence of kidney disease (abnormal kidney function tests or urinalysis). (See 'Kidney ultrasound' above.)

•Echocardiography – If pharmacologic antihypertensive therapy is being considered, an echocardiogram should be obtained to assess for left ventricular hypertrophy (LVH), which is the most prominent manifestation of end-organ damage from HTN. (See 'Echocardiography' above.)

●Further evaluation for underlying causes – If the history, physical examination, and initial laboratory evaluation suggest a secondary cause of HTN (table 4 and table 5), further evaluation to determine the underlying etiology may be warranted. Depending on the results of the initial evaluation, this may include renal imaging studies (eg, renal scans or arteriogram); measurement of plasma renin, aldosterone, and plasma and urine catecholamines; and/or sleep study. (See 'Secondary hypertension' above.)