Table 11. Causes of secondary hypertension with clinical indications and diagnostic screening tests.

	Prevalence (HTN)	Prevalence (Resistant HTN)	Clinical Indications	Physical examination	Screening tests	Additional/confirmatory tests
Common causes
Primary aldosteronism	8-20%	17-23%	Resistant hypertension; hypertension with hypokalemia (spontaneous or diuretic induced); hypertension and muscle cramps or weakness; hypertension and incidentally discovered adrenal mass; hypertension and obstructive sleep apnea; hypertension and family history of early-onset hypertension or stroke.	Arrhythmias (with hypokalemia); especially atrial fibrillation.	Plasma aldosterone concentration (PAC); plasma renin activity (PRA); plasma aldosterone/renin ratio (ARR).	Oral sodium loading test, IV saline infusion test, or captopril suppression test; adrenal CT or MRI scan, adrenal vein sampling; adrenal scintigraphy.
Renal parenchymal disease	1-2%	2-10%	Urinary tract infections; obstruction, hematuria; urinary frequency and nocturia; analgesic abuse; family history of polycystic kidney disease; elevated serum creatinine; abnormal urinalysis.	Abdominal mass (polycystic kidney disease); skin pallor.	Serum creatinine, renal ultrasound, urinalysis.	Specific tests to evaluate the cause of renal disease (toxins, biopsy).
Renal artery stenosis/renovascular disease	5-34%	2.5-20%	Resistant hypertension; hypertension of abrupt onset or worsening or increasingly difficult to control; flash pulmonary edema (atherosclerotic); early-onset hypertension, especially in women (fibromuscular hyperplasia).	Abdominal systolic or diastolic bruit; bruits over other arteries (carotid or femoral artery atherosclerotic stenosis, or fibromuscular dysplasia).	Renal duplex, or CT, or MRI/MRA.	Renal angiography.
Obstructive sleep apnea	25-50%	> 30%	Resistant hypertension; snoring; unrefreshing sleep; breathing pauses during sleep; daytime sleepiness.	Obesity, Mallampati class III-IV; loss of normal nocturnal BP fall.	Berlin Questionnaire, Epworth Sleepiness Score, overnight oximetry.	Polysomnography.
Drug or alcohol induced	2-4%	NA	Sodium-containing antacids; caffeine; nicotine (smoking); alcohol; NSAIDs; oral contraceptives; cyclosporine or tacrolimus; sympathomimetics (decongestants, anorectics); cocaine, amphetamines and other illicit drugs; neuropsychiatric agents; erythropoiesis-stimulating agents; clonidine withdrawal; herbal agents (Ma Huang, ephedra).	Fine tremor, tachycardia, sweating (cocaine, ephedrine, MAO inhibitors); acute abdominal pain (cocaine).	Urinary/hair drug screen (illicit drugs).	Response to withdrawal of suspected agent.
Uncommon causes
Pheochromocytoma	0.1-0.6%	< 1%	Resistant hypertension; paroxysmal hypertension or crisis superimposed on sustained hypertension; “spells,” BP lability, headache, sweating, palpitations, pallor; positive family history of pheochromocytoma/paraganglioma; adrenal incidentaloma.	Skin stigmata of neurofibromatosis (café-au-lait spots; neurofibromas); orthostatic hypotension.	24-h urinary fractionated metanephrines or plasma metanephrines.	CT or MRI scan of the abdomen/pelvis.
Cushing’s syndrome	< 0.1%	< 1%	Rapid weight gain, especially with central distribution; proximal muscle weakness; depression; hyperglycemia.	Central obesity, “moon” face, dorsal and supraclavicular fat pads, wide (1-cm) violaceous striae, hirsutism.	Overnight 1-mg dexamethasone suppression test/24-h urinary free cortisol excretion/midnight salivary cortisol.	Low dose dexamethasone suppression test.
Hypothyroidism	< 1%	1-3%	Dry skin; cold intolerance; constipation; hoarseness; weight gain.	Delayed ankle reflex; periorbital puffiness; coarse skin; cold skin; slow movement; goiter.	Thyroid stimulating hormone; free thyroxine.	None.
Hyperthyroidism	< 1%		Warm, moist skin; heat intolerance; nervousness; tremulousness; insomnia; weight loss; diarrhea; proximal muscle weakness.	Lid lag; fine tremor of the outstretched hands; warm, moist skin.	Thyroid stimulating hormone; free thyroxine.	Radioactive iodine uptake and scan.
Aortic coarctation	0.001	< 1%	Young patients with hypertension (< 30 years of age).	BP higher in the upper extremities than in the lower extremities; absent femoral pulses; continuous murmur over the back, chest, or abdominal bruit; left thoracotomy scar (postoperative).	Echocardiogram.	Thoracic and abdominal CT angiogram or MRA.
Primary hyperparathyroidism	Rare	Rare	Hypercalcemia.	Usually none.	Serum calcium.	Serum parathyroid hormone.

Modified from Whelton PK, et al.¹⁶² and Rimoldi SF, et al.¹⁶³.

BP, blood pressure; CT, computed tomography; HTN, hypertension; IV, intravenous; MAO, monoamine oxidase; MRA, magnetic resonance angiography; NSAID, non-steroidal anti-inflammatory drug.