Investigating hypertension in a young personBMJ 2009; 338 doi: http://dx.doi.org/10.1136/bmj.b1043 (Published 06 April 2009) Cite this as: BMJ 2009;338:b1043
- Fabian Hammer, MRC research training fellow,
- Paul M Stewart, professor of medicine
- 1Institute of Biomedical Research, Division of Medical Sciences, University of Birmingham, Birmingham, B15 2TT
- Correspondence to: P M Stewart, Professor of Medicine, Institute of Biomedical Research, Division of Medical Sciences, University of Birmingham, Birmingham B15 2TT
A 27 year old man with a six month history of mild but progressive headache visited his general practitioner and was found to have a blood pressure of 178/108 mm Hg. He had an unremarkable medical history, but his father had had high blood pressure and had died from a stroke at age 45 years. Clinical examination with a particular emphasis on the cardiovascular system including funduscopy was unremarkable, and no renal artery bruit was heard. Basic laboratory tests at his general practice were all normal (sodium 144 (normal range 135-145) mmol/l; potassium 3.8 (3.5-5.1) mmol/l; creatinine 105 (60-110) μmo/l; urea 5.4 (2.9-9.4) mmol/l), with no proteinuria.
What is the next investigation?
Arterial hypertension warrants further investigations to exclude secondary causes of hypertension in young people (aged <40 years), those with blood pressure resistant to antihypertensive treatment, and those with a family history of hypertension or stroke at age <50 years. Furthermore, a detailed social history, including alcohol intake and substance misuse (such as cocaine) might show reversible contributors of increased blood pressure.
Before further investigations the diagnosis of arterial hypertension needs to be established by blood pressure measurements on at least three occasions using a sphygmomanometer with an appropriate cuff size for arm circumference (cuffs that are too small will give false high readings). If white coat hypertension is suspected a 24 hour ambulatory blood pressure measurement is warranted.
Urea, creatinine, electrolytes, and urine analysis
All patients with diagnosed arterial hypertension must have urea and electrolytes and urine analysis performed to screen for hypokalaemia and renal disease as these basic laboratory tests are widely available and cost effective and if abnormal will give important hints on which test to perform next. Although only a third of patients with subsequently confirmed primary hyperaldosteronism exhibit frank hypokalaemia, potassium concentrations in the remaining two thirds of patients with hyperaldosteronism are usually at the lower end of the reference range and sodium concentrations at the higher end.
Renal ultrasonography, electrocardiography, chest radiography
In our patient, normal kidney function, electrolytes, and the absence of proteinuria strongly argues against renoparenchymal disease, and so renal ultrasonography is of limited benefit. Electrocardiography and chest radiography in this patient may be entirely normal, but if hypertension is longstanding they may show signs of left ventricular hypertrophy. These investigations are of limited value in establishing the underlying cause.
Measurement of plasma aldosterone and renin
Primary hyperaldosteronism is now considered to be the most prevalent form of secondary hypertension, accounting for 5-10% of all hypertensive patients.1 2 Screening for primary hyperaldosteronism is based on a high plasma aldosterone concentration and suppressed plasma renin activity, giving a high ratio of plasma aldosterone concentration to plasma renin activity. Although the exact cut-off values depend on the laboratory and assays used, a ratio of >750 (aldosterone in pmol/l and plasma renin activity in ng/ml/h) with an absolute aldosterone concentration of >400 pmol/l is highly suggestive of primary hyperaldosteronism.3
Antihypertensive drugs do not have to be stopped routinely before these measurements are conducted (except for spironolactone, eplerenone, and amiloride) but in some patients may contribute to false positive and negative results. A positive screening test warrants a hospital referral, firstly to confirm the diagnosis (usually with oral or intravenous sodium loading or a fludrocortisone suppression test) and secondly to differentiate between the two principal causes—namely, a unilateral aldosterone producing adenoma (or Conn’s adenoma) and idiopathic hyperaldosteronism, for which selective adrenal venous sampling remains the optimal test. Catheterisation of the adrenal veins (particularly the right vein) even in the most experienced hands remains technically challenging and should therefore be performed only in specialist centres.
24 hour urinary-free catecholamines or plasma-free metanephrines
Tumours that produce catecholamine, such as phaeochromocytomas and paragangliomas, are rare (found in 0.1-0.6% of hypertensive patients). However, they form an important differential diagnosis in our patient even if only mild headaches and no other classic symptoms (paroxysms of palpitations, sweating, and pallor) are present. Testing for plasma-free metanephrines is now considered to be the optimal test (sensitivity 99%, specificity 86%), but given its limited availability screening is still predominantly based on excretion of urinary catecholamines (adrenaline, noradrenaline, dopamine, metanephrine, normetanephrine, and vanillylmandelic acid) (sensitivity 86%, specificity 88%).4 False positive test results can be prevented if the patient avoids consumption of caffeine, nuts, and chocolate for 24 hours before and during urine collection.
Magnetic resonance angiography has now become the investigation of choice (sensitivity and specificity >90%) to rule out renovascular abnormalities (namely, renal artery stenosis),5 in which case hypertension develops as a result of renal hypoperfusion. In the absence of a renal artery bruit, magnetic resonance angiography should be performed only if laboratory screening tests for primary hyperaldosteronism and phaeochromocytoma are negative.
In this patient, blood tests showed a raised plasma aldosterone concentration of 712 (normal range 28-445) pmol/l and a suppressed plasma renin activity of 0.2 (0.7-5) ng/ml/h with a ratio of 3560 (normal ratio <750), therefore highly suggestive of primary hyperaldosteronism. Aldosterone concentrations remained raised at 462 pmol/l after a saline infusion study that confirmed the diagnosis of primary hyperaldosteronism. Subsequent computed tomography showed a solitary, well defined lesion of 2 cm in the right adrenal gland, which was removed by laparoscopic adrenalectomy (figure⇓). Blood pressure returned to normal.
Primary hyperaldosteronism accounts for up to 10% of all hypertensive patients and is considered to be the most prevalent form of secondary hypertension
Screening for primary hyperaldosteronism is based on the ratio of plasma aldosterone to renin
Potassium concentration is often normal in primary hyperaldosteronism, and so hypokalaemia must not be a prerequisite for screening
Antihypertensive drugs do not have to be stopped routinely before screening
Cite this as: BMJ 2009;338:b1043
This article is the first in a series of occasional articles providing an update on the best use of key diagnostic tests in the initial investigation of common or important clinical presentations. The series advisers are Steve Atkin, professor, head of department of academic endocrinology, diabetes, and metabolism, Hull York Medical School; and Eric Kilpatrick, honorary professor, department of clinical biochemistry, Hull Royal Infirmary, Hull York Medical School.
We thank Peter Guest for the figure.
Contributors: Both authors contributed to the preparation and editing of the manuscript. PMS is guarantor.
Competing interests: None declared.
Provenance and peer review: Commissioned; externally peer reviewed.
Patient consent not required (patient anonymised, dead, or hypothetical).