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Q/ Whom should you test for secondary causes of hypertension?


A/ IT'S RECOMMENDED that all children and adolescents with a new diagnosis of hypertension undergo renal ultrasound and laboratory evaluation for renal pathology (strength of recommendation [SOR]: C, consensus-based guidelines).

Specific diagnostic tests are recommended for newly diagnosed patients who have suspicious clinical findings suggestive of a secondary cause of hypertension based on the initial history (excess daytime sleepiness, palpitations, tremor, sweating); physical examination (abdominal bruit, thyromegaly, malar rash); or laboratory analysis (elevated serum creatinine, low thyroid-stimulating hormone) (SOR: C, consensus-based guidelines).

Patients with undifferentiated resistant hypertension should receive further directed evaluation for secondary causes (SOR: C, consensus-based guidelines).

Evidence summary

The evidence for selecting which patients should undergo additional testing for potentially correctable secondary causes of hypertension is based on the prevalence of these causes in different age groups, case series of reversal of hypertension with effective treatment of the underlying cause, and clinical suspicion of a secondary cause that may be reversible. We found no prospective cohort studies or randomized trials evaluating diagnostic approaches or outcomes associated with particular selection criteria for conducting additional diagnostic evaluations in search of secondary causes. Therefore, our recommendations are based primarily on expert guidelines, which we summarize here.

When caring for children and adolescents with newly diagnosed hypertension ...

Secondary hypertension is more prevalent in younger children and in children and adolescents with stage 2 hypertension (blood pressure [BP] >99th percentile for age and height plus 5 mm Hg). (1) Renoparenchymal and renovascular disease account for most cases of secondary hypertension in these children. (2)

The National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents recommends that all children and adolescents with hypertension have an additional diagnostic work-up. This is based on the observation that 70% to 85% of children <12 years and 10% to 15% of adolescents 12 to 18 years with hypertension have an underlying cause, most commonly renoparenchymal and renovascular disease. (3)

According to the National Institutes of Health (NIH), "the possibility that some underlying disorder may be the cause of the hypertension should be considered in every child or adolescent" with elevated BE but the evaluation itself should be individualized. (3)

The NIH recommends more extensive evaluation for very young children, children with stage 2 hypertension, and children or adolescents who show clinical signs suggesting hypertension-linked systemic conditions. Such evaluation should include a renal ultrasound and laboratory testing (creatinine, urinalysis, and urine culture) to look for structural or functional anomalies. (3)

What about newly diagnosed adults with suspected secondary causes?

Secondary hypertension reportedly occurs in 5% to 10% of hypertensive patients. (4,5) The only prospective study completed in a primary care setting evaluated 1020 patients at a general outpatient clinic in Yokohama, Japan. The investigators reported that 9.1% of the patients had an endocrinologic or renovascular cause contributing to their hypertension. (6) The 5 most common causes were primary aldosteronism (6%), Cushing syndrome (1%), preclinical Cushing syndrome (1%), pheochromocytoma (0.6%), and renovascular disease (0.5 %). (6)

According to the Institute for Clinical Systems Improvement (ICSI), patients at highest risk for secondary hypertension have no family history of hypertension; abrupt onset, symptomatic, or crisis hypertension; stage 2 hypertension; sudden loss of hypertensive control; and drug-resistant hypertension. (7)

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends that patients with the following characteristics undergo further directed evaluation for a secondary cause: (8)

* younger than 30 years with no family history of hypertension

* older than 55 years with new hypertension

* abdominal bruit with diastolic component

* sudden worsening of BP control

* recurrent flash pulmonary edema

* renal failure with abnormal urinary sediment or proteinuria

* acute renal failure after administration of an ACE inhibitor or ARB.

These patients should receive particular scrutiny

Patients with resistant hypertension (BP>140/90 mm Hg despite taking optimal doses of 3 antihypertensive medications, one of which is a diuretic) should receive particular scrutiny for an identifiable secondary cause, according to the ICSI. (7)

In a retrospective analysis of 141 patients with resistant hypertension referred to a university hypertension center in Chicago in 2005, 5% of patients had an identifiable secondary cause. (9) A chart review of 436 patients presenting to a tertiary hypertension clinic in Japan identified 91 with resistant hypertension. A secondary cause was identified in 9.1%. (10)

Careful history and examination should identify patients suffering from uncontrolled hypertension because of noncompliance, suboptimal antihypertensive regimen, inaccurate BP readings, antagonizing substances, and white coat hypertension. (11) The TABLE summarizes common presentations of, and workup for, secondary causes of hypertension. (12-14)


(1.) National High Blood Pressure Education Program Working Group on High Blood Pressure in children and Adolescents. The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. Rockville, ME): National Heart, Lung, and Blood Institute, US Department of Health and Human Services; May 2005. N1H Publication No. 05-5267.

(2.) Hansen ML, Gunn PW, Kaelber DC. Underdiagnosis of hypertension In children and adolescents, JAMA. 2007;296:874-879.

(3.) Brady TM, Feld LG. Pediattic approach to hypertension. Semin Nephrol. 2009;29:379-388.

(4.) Taler SJ. Secondary causes of hypertension. Prim Care Clin Office Pract 2008;35:489-500.

(5.) Cldong JR, Amnow WS, Khan IA, et al. Secondary hypertension: current diagnosis and treatment. Int J Cardiol. 2008;124:6-21.

(6.) Omura M, Salto J, Yamaguchi K, et al. Prospective study on the prevalence of secondary hypertension among hypertensive patients visiting a general outpatient clinic in Japan. Hypertens Res. 2004;27:193-202.

(7.) Luehr D, Woolley T, Burke R, et al. Institute for Clinical Systems Improvement. Hypertension Diagnosis and Treatment. Available at: Updated November 2012. Accessed January 7, 2010.

(8.) Chobanian AV, Bakris GL, Black FIR, et al. Seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension. 2003;42:1206-1252.

(9.) Garg JP, Elliott WJ, Folker A, et al; Rush University Hypertension Service. Resistant hypertension revisited: a comparison of two university-based cohorts. Am J Hypertens. 2005;185: 619-626.

(10.) Yakovlevitch M, Black HR. Resistant hypertension In a tertiary care clinic. Arch Intern Med. 1991;151:1786-1792.

(11.) O'Rorke JE, Richardson WS. What to do when hypertension is difficult to control BMJ. 2001;322:1229-1232.

(12.) Rossi GP, Seccia TM, Pessina AC. Clinical use of laboratory tests for the identification of secondary forms of arterial hypertension. Crit Rev Clin Lab Sci 2007;44:1-85.

(13.) Riley M, Bluhm B. High blond pressure in children and adolescents. Am Fam Physician. 2012;85:693-700.

(14.) Viera AJ, Neutze DM. Diagnosis of secondary hypertension: an age based approach. Am Fam Physician. 2010;82: 1471-1478.

Deborah Miller, MD, MACM

Department of Family Medicine, University of Chicago/North Shore University HealthSystem, Glenview, III

Nakia Joye Woodward, MSIS, AHIP

East Tennessee State University Quillen College of Medicine Library, Johnson City


Robert Gauer, MD

Department of Family Medicine, Womack Army Medical Center, Ft. Bragg, NC
Secondary causes of hypertension: Identifying and evaluating
suggestive findings (12-14)

History                       Physical examination    findings

Adults: Excessive daytime     Overweight/obese,       None
sleepiness, snoring,          large neck size,
morning headache,             crowded oropharynx,
witnessed apnea               adenotonsillar
Children: Poor                hypertrophy
school performance,

Headache, muscle              Resistant               Hypokalemia,
weakness, paresthesias,       hypertension,           metabolic
paralysis                     stage 2 hypertension    alkalosis,
                                                      on CT scan

Adults: African American,     Abdominal mass,         Proteinuria,
comorbid DM or                gross hematuria,        elevated
atherosclerotic disease       growth restriction      creatinine
Children: Enuresis, family
history of renal disease,
fatigue, recurrent UTI

<Age 30 yr and female         Abdominal bruit,        Elevated
or                            flash pulmonary         creatinine
>Age 50 yr and male           edema                   (particularly
                                                      after ACE-I or
                                                      ARB use for

Muscle weakness, bruising,    Truncal obesity,        Hypokalemia,
acne, edema, hirsutism,       abdominal striae,       hyperglycemia
oligomenorrhea                moon facies,

Paroxysmal hypertension,      Resistant               None
headache, palpitations,       hypertension,
tremor, flushing              tachycardia, pallor

None                          Difference in right     None
                              and left arm BP,
                              diminished femoral
                              pulses, heart murmur,
                              lower BP in legs than

Family history of thyroid     Ophthalmopathy,         Suppressed
disorder, heat intolerance,   tachycardia,            thyroid-
rash, sweating, pallor        thyromegaly,            stimulating
                              weight loss             hormone

Family history of             Friction rub, joint     Elevated white
autoimmune disease,           swelling, malar rash    blood cell
fatigue, joint pain, rash                             count

History                       etiology           Diagnostic approach

Adults: Excessive daytime     Sleep apnea        Polysomnogram
sleepiness, snoring,          syndrome
morning headache,
witnessed apnea
Children: Poor
school performance,

Headache, muscle              Primary            Plasma aldosterone
weakness, paresthesias,       aldosteronism      to-renin activity
paralysis                                        ratio; CT imaging
                                                 of adrenal glands

Adults: African American,     Renoparenchymal    24-hour urine for
comorbid DM or                disease            protein and
atherosclerotic disease                          creatinine; renal
Children: Enuresis, family                       ultrasound
history of renal disease,
fatigue, recurrent UTI

<Age 30 yr and female         Renovascular       MR or CT angiogram
or                            disease;           (normal renal
>Age 50 yr and male           fibromuscular      function); MR
                              dysplasia;         angiogram or
                              atherosclerosis    ultrasound of the
                                                 kidneys (diminished
                                                 renal function)

Muscle weakness, bruising,    Cushing disease    Urinary free
acne, edema, hirsutism,                          cortisol;
oligomenorrhea                                   dexamethasone
                                                 suppression test;
                                                 ACTH; CT/MRI of the
                                                 pituitary and/or

Paroxysmal hypertension,      Pheochromocytoma   Plasma-free
headache, palpitations,                          metanephrines;
tremor, flushing                                 CT/MRI of the

None                          Coarctation        Echocardiogram
                              of the aorta

Family history of thyroid     Hyperthyroidism    Thyroid scan
disorder, heat intolerance,
rash, sweating, pallor

Family history of             Rheumatologic      Abnormal findings on
autoimmune disease,           disorder           autoimmune
fatigue, joint pain, rash                        laboratory studies;
                                                 elevated markers of

ACE-I, angiotensin-converting enzyme inhibitor; ACTH,
adrenocorticotropic hormone; ARB, angiotensin II receptor
blocker; BP, blood pressure; CT, computed tomography; DM,
diabetes mellitus; MR, magnetic resonance; MRI, magnetic
resonance imaging; UTI, urinary tract infection.
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Article Details
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Title Annotation:CINICAL INQUIRIES: Evidence-based answers from the Family Physicians Inquiries Network
Author:Miller, Deborah; Woodward, Nakia Joye; Gauer, Robert
Publication:Journal of Family Practice
Article Type:Clinical report
Geographic Code:1USA
Date:Jan 1, 2014
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