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Secondary Hypertension     CAUSES  |  Screening Tests  |  Hypertension Treatment    

BP Scheme for Adults (in mm Hg)

The Reference Card of the Joint National Committee (JNC VII) 2003

HYPERTENSION- Secondary                

Secondary hypertension is hypertension of known etiology.  It accounts for fewer than 5% of all cases of hypertension.

Clinical clues for secondary hypertension:

CAUSES of SECONDARY HYPERTENSION          See also   Differential Diagnosis of Hypertension  

  • Chronic renal parenchymal disease  (edema, nocturia, increased creatinine)
    - acute glomerulonephritis (GN)
    - primary glomerular disease: focal glomerulosclerosis, membranoproliferative GN, mesangioprolif. GN, membranous nephropathy
    - chronic interstitial nephritis, diabetic nephropathy, hypertensive nephrosclerosis, chronic pylonephritis,
      obstructive uropathy, polycystic kidney disease.
    -DX: BUN, Creat, UA, Renal scan or sonogram.
  • Renovascular disease or renal artery stenosis (abd. vascular bruits)   -  see  Renovascular Hypertension (Cleveland Clinic J of Med Dec. 2005: 72: 1135)
    Includes intrarenal vasculitis; 75% atherosclerosis, 25 % fibromuscular dysplasia (occurs most often in young white females between the ages of 20-40;  Rx is angioplasty), or the uncommon extrinsic compression or thrombosis of the renal artery.  
    The narrow renal artery >70-80% activates the renin angiotensin aldosterone system and leads to increased angiotensin II & aldosterone secretion which increases sodium absorption and thus hypertension.
    SX: Clinical Sx includes resistant hypertension, abd. flank bruits, acute flank pain with hematuria, abrupt onset of hypertension in < 30 yo or > 55 yo.  A precipitous drop in BP, acute deterioration in renal function in response to ACE inhibitor therapy, or both suggest possible RAS and warrant further workup.
    Diagnostic Test: Abdominal Computed tomography angiography and magnetic resonance angiography seem to be preferred in patients referred for evaluation of renovascular hypertension.
  • Acute renal failure
  • Polycystic kidney disease  (abdominal mass)
  • Pregnancy-induced Hypertension pre-eclampsia, eclampsia
  • Medications oral contraceptives, estrogens, steroid, or thyroid hormone excess, NSAID, sympathomimetics; amphetamines
  • Alcohol
  • Acute emotional & physical stress, burns, pancreatitis
  • Coarctation of the aorta  (diminished peripheral pulses)
  • Neurological disorders:
    Increased intracranial pressure (brain tumor, encephalitis, resp. acidosis); head or spinal cord injury
    Quadriplegia, sleep apnea, lead poisoing, Guillain-Barre synd., Famial dysautonomia, Acute porphyria
  • Spinal cord injury
  • Obstructive sleep apnea  (daytime somnolence, snoring, obesity)
  • Vasculitis

REF:  ACP Medicine Best Dx/Best Rx 2006  

Screening Tests for Secondary Hypertension (Sensitivity/Specificity)       

Renovascular Hypertension   

Spiral CT angiography

  • Advantages: excellent images of renal arteries; can identify dissection, accessory vessels, and fibromuscular disease
  • Disadvantages: considerable contrast load precludes use in presence of renal dysfunction; expensive

Magnetic resonance angiography - MRA (85%–100% sens./79%–98% spec.)

  • Advantages: no contrast or radiation exposure; renal dysfunction does not impair interpretation
  • Disadvantages: cost; may overstate degree of stenosis; claustrophobic patients may not tolerate test

Renal angiography: gold standard

  • Advantages: identifies accessory- and branch-vessel disease; percutaneous interventions can be performed as part of study
  • Disadvantages: cost; contrast exposure; invasive (atheroemboli)

Duplex ultrasound (80%–90% sens./90% spec.)

  • Advantages: no contrast or radiation exposure; renal dysfunction does not impair interpretation; calculation of resistive index identifies subset of patients with renal dysfunction likely to benefit from intervention (RI < 0.80)
  • Disadvantages: failure to visualize both renal arteries (15%–20% of cases); may miss accessory- or branch-vessel disease

Captopril radionuclide renal scan (75% sens./85% spec.)

  • Advantage: no contrast exposure
  • Disadvantages: renal dysfunction impairs interpretation; may miss bilateral, accessory-, or branch-vessel disease


Primary Aldosteronism   (hypokalemia  hypertension)
  • Measurement of serum sodium, potassium, plasma renin activity (PRA), and plasma aldosterone concentration (PAC)
  • 24-hr urinary aldosterone, sodium, and PRA after 3 days of a 200 mEq–sodium diet
  • Screening: ratio of PAC/PRA > 20
    • Diagnosis confirmed if UNa > 200 mEq, Ualdo > 12, and PRA < 1.0 after 3 days of high-sodium diet
    • Advantage: 30% of patients with primary aldosteronism are normokalemic at presentation; ratio is easy to obtain
    • Disadvantages: many antihypertensive drugs can influence values of PRA and PAC; sensitivity and specificity of ratio not established

Primary Aldosteronism  (Hypokalemia with hypertension)
low serum potassium, increased urine  potassium,
elevated plasma aldosterone (>10 ng/dL)
& low plasma renin level
(high plasma aldosterone/renin ratio>25-30) ;
adrenal CT or MRI scan (unilateral lesion suggests adenoma, bilateral lesions suggests bilateral adrenal hyperplasia);
bilateral adrenal vein catherization with analysis of venous aldosterone & cortisol levels.
Screening tests
include measurement of 8 a.m. plasma aldosterone and renin activity (aldosterone:renin ratios greater than 25:1 suggest inappropriate aldosterone release) in patients who have not received ACE inhibitor therapy in the month before study.
Confirmatory tests
include measurement of 24-hour urinary aldosterone excretion in patients on a high-salt diet (values greater than 14 mg in 24 hours are abnormal).
Definitive diagnosis
is by abdominal computed tomography or MRI.
Adrenal adenomas constitute 65% of the cases of primary aldosteronism.
If multiple nodules are seen or concerns of an undetected adenoma persist, adrenal vein sampling for aldosterone assay can be attempted.
In the absence of adenoma (or, in rare cases, carcinoma), idiopathic aldosteronism and bilateral hyperplasia are diagnoses of exclusion.


Pheochromocytoma  (severe hypertension with sweating, palpitations, anxiety, pallor, labile BP)
  • Plasma-free metanephrines (99% sens./89% spec.)
  • 24-hr fractionated urinary metanephrines (77% sens./93% spec.)
  • Use plasma test if degree of suspicion is high or familial syndrome is suspected

CT or MRI adrenal scan.


Cushing Syndrome   (purple striae, truncal obesity, muscle weakness)

24-hr urinary free cortisol (95%–100% sens./97%–100% spec.)

  • Diagnosis certain if 24-hr urinary free cortisol level > 3 times normal
  • Diagnosis excluded if level normal
  • Use low-dose  1mg dexamethasone suppression test if elevation < 3 times normal

If adrenal disease suspected - abdominal CT scan
If pituitary tumor suspected - brain MRI pituitary scan


Coarctation of the Aorta   (diminished peripheral  femoral pulses)
  • Chest x-ray; transesophageal echocardiogram
  • CT or MRI of the aorta
  • Diagnostic findings on chest x-ray
    • "3" sign from dilation of aorta above and below the coarctation
    • Rib notching from collateral vessels

Aortic Coarctation  
A constriction (discrete or of varying lengths) of the aorta usually located just distal to the left subclavian artery at the junction of the ligamentum arteriosum.

[Ref: Griffith's 5-Minute Clinical Consult, 2005]

  • SX:   Hypertension, Pulse disparity,  Delayed, weak, or absent pulse, Headaches, Exertional leg fatigue and pain, Prominent neck pulsations, Headache, Epistaxis, Prominent left ventricular impulse, Murmur (aortic stenosis or insufficiency, entricular septal defect, rarely mitral valve), S4 systolic ejection click, Bruit (coarctation, collaterals, patent ductus arteriosus), Cyanosis, rarely. Extensive collaterals develop from branches of the subclavian, internal mammary, superior intercostal, and axillary arteries .
  • TESTS:
    • Blood pressures - all 4 extremities; Doppler examination of pulses reveals disparity, LVH on ECG 
    • Chest x-ray may show rib notching, "3" sign, rarely cardiomegaly
    • Echocardiography for coarctation and coexisting cardiac anomalies; Transesophageal echocardiography
    • Magnetic resonance imaging (MRI) or CT scan of the aorta
    • Cardiac catheterization and angiography: post-stenotic dilation


Primary hyperparathyroidism  (hypercalcemia, constipation, muscle aches)

Clinical Presentation of Hyperparathyroidism:  

  • Stones (renal) - about 1/2 of these pts have elevated urinary calcium excretion (>250 mg/d in women, and >300 mg/d in men) < and half of these patients develop renal stones.
  • Bones (osteoporosis) - loss of cortical bone (outermost compact bone rather than the trabecular or cancellous interior bone), esp. in the distal third of the forearm. 
  • Groans (peptic ulcer, pancreatitis, constipation, fatigue, and psych overtones)                                                                                

Lab. diagnosis of Primary Hyperparathyroidism

  • Elevated PTH and serum calcium.
  • Other lab. findings:  low serum phosphorus, increased urin. calcium excretion, elevated serum 1,25-dihydroxyvitamin D, decreased tubular reabsorption of phosphorus, elevated urin. excretion of nephrogenous cAMP.


Systolic Hypertension
  • Increased cardiac output
    • Aortic valvular insufficiency
    • A-V fistula, patent ductus
    • Thyrotoxicosis
    • Hyperkinetic circulation
    • Paget's disease of bone, Beri-Beri
  • Rigidity of aorta