Secondary Hypertension

Hypertension caused by an identifiable and often treatable condition; about 5 to 10% of all hypertension, more in young patients and in resistant disease.

• Causes: chronic kidney disease and glomerular disease, renal artery stenosis, primary aldosteronism (about 5 to 10% of hypertensives and up to 20% of resistant cases), phaeochromocytoma and paraganglioma (less than 1%), Cushing syndrome, thyroid disease, hyperparathyroidism, obstructive sleep apnoea, aortic coarctation, and drugs (NSAIDs, oral contraceptives, corticosteroids, decongestants, ciclosporin, erythropoietin, liquorice, cocaine, amphetamines, venlafaxine).

• Suspect it with: onset before age 30 to 40 (or after 60), sudden worsening, resistant hypertension (not at target on three drugs including a diuretic at full dose), malignant hypertension, spontaneous or diuretic induced hypokalaemia, adrenal incidentaloma, abdominal bruit, creatinine rise greater than 30% after an ACE inhibitor, snoring with daytime sleepiness, radio femoral delay.
• Features by cause: episodic headache, sweating and palpitations (phaeochromocytoma); muscle weakness and polyuria (aldosteronism); central obesity, striae and proximal weakness (Cushing); tremor and weight loss (hyperthyroidism); upper limb hypertension with weak leg pulses (coarctation).
• Differential diagnosis: primary hypertension, white coat hypertension, non-adherence, pain, anxiety, inaccurate cuff size.
• Complications: left ventricular hypertrophy, heart failure, stroke, chronic kidney disease, retinopathy, and cause specific harm (arrhythmia and fracture with hyperparathyroidism, hypertensive crisis with phaeochromocytoma).

• Confirm with ambulatory or home BP monitoring; check adherence and drug history.
• Basic tests: urea, creatinine, electrolytes, urinalysis and protein quantification, glucose, calcium, thyroid stimulating hormone, ECG, echocardiography, renal ultrasound.
• Primary aldosteronism: morning plasma aldosterone to renin ratio, after correcting potassium and, where safe, stopping spironolactone and eplerenone for 4 weeks. Confirm with saline suppression, then CT and adrenal vein sampling in candidates for surgery.
• Phaeochromocytoma: plasma free metanephrines or 24-hour urinary fractionated metanephrines; CT or MRI of adrenals and abdomen if positive; genetic counselling.
• Cushing syndrome: overnight 1 mg dexamethasone suppression test (morning cortisol greater than 50 nmol/L, or 1.8 micrograms/dL, is abnormal), late night salivary cortisol, 24-hour urinary free cortisol.
• Renovascular disease: duplex ultrasound, CT or MR angiography.
• Sleep apnoea: overnight oximetry or polysomnography.
• Coarctation: echocardiography, CT or MR angiography.

• Target BP less than 130/80 mmHg in most adults.
• Primary aldosteronism: spironolactone 25 to 100 mg daily (or eplerenone 25 to 50 mg twice daily), monitoring potassium and creatinine at 1 and 4 weeks. Unilateral adenoma: laparoscopic adrenalectomy.
• Phaeochromocytoma: alpha blockade first, phenoxybenzamine 10 mg twice daily increased every 2 to 3 days by 10 to 20 mg to 1 mg/kg/day, or doxazosin 2 to 16 mg daily, with liberal salt and fluid intake. Add a beta blocker (propranolol 20 to 40 mg three times daily) only after alpha blockade, never first. Operate after 7 to 14 days of blockade.
• Renovascular hypertension: ACE inhibitor or ARB with monitoring of creatinine (accept a rise up to 30%; stop if creatinine rises further, particularly with bilateral stenosis); angioplasty for fibromuscular dysplasia; revascularisation in atherosclerotic disease only for flash pulmonary oedema, refractory hypertension or progressive renal loss.
• Chronic kidney disease: salt restriction to less than 5 g/day, ramipril 2.5 to 10 mg daily, chlorthalidone 12.5 to 25 mg daily (or furosemide 40 to 120 mg daily when eGFR is less than 30), amlodipine 5 to 10 mg daily.
• Cushing syndrome: surgery of the pituitary or adrenal source; control BP with spironolactone and an ACE inhibitor meanwhile.
• Sleep apnoea: continuous positive airway pressure, weight loss.
• Coarctation: balloon dilatation with stenting, or surgical repair.
• Drug induced: stop or substitute the offending drug.
• Resistant hypertension of any cause: ensure a thiazide like diuretic, a calcium channel blocker, and an ACE inhibitor or ARB at full dose, then add spironolactone 25 to 50 mg daily, then bisoprolol or doxazosin.
• Pregnancy: methyldopa 250 to 500 mg 8-hourly (maximum 3 g/day), nifedipine retard 10 to 20 mg twice daily, labetalol 100 to 400 mg two to three times daily (maximum 2.4 g/day); avoid ACE inhibitors, ARBs and spironolactone.
• Red flags: BP greater than 180/120 mmHg with end organ damage, flash pulmonary oedema, paroxysmal crises, severe hypokalaemia, young age.
• Follow up: monthly until target, then every 3 to 6 months; annual renal function, potassium, and urinary albumin.