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Secondary hypertension 

Secondary hypertension

Chapter:
Secondary hypertension
Author(s):

Morris J. Brown

and Fraz Mir

DOI:
10.1093/med/9780199204854.003.161703_update_002

Update:

Conn’s syndrome – description of somatic mutations causing adrenal adenomas. Discussion of hypothesis that low renin hypertension could be driven in some cases by small adrenal adenomas that may be detected by newer radiotracer imaging, and how these adenomas might be treated.

Updated on 29 Oct 2015. The previous version of this content can be found here.
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date: 25 March 2017

The term ‘secondary hypertension’ is used to describe patients whose blood pressure is elevated by a single, identifiable cause, with an important subdivision being into reversible and irreversible causes: clinically, it is important to exclude the former, but not necessarily to find the latter.

In the first two decades of life, the prevalence of secondary hypertension is greater than that of essential hypertension; thereafter, a patient is much more likely to have essential hypertension, but investigations for secondary hypertension should still be assiduous in the twenties and thirties because the alternative entails so many years of tablet-taking.

All patients with hypertension should have a minimum set of investigations (see Chapter 16.17.2). Common indications for further investigations are (1) any evidence of an underlying cause on history or examination; (2) proteinuria, haematuria, or elevated serum creatinine (eGFR<30; CKD 4/5); (3) hypokalaemia, even if caused by diuretics; (4) accelerated (malignant) hypertension; (5) documented recent onset or recent worsening of hypertension; (6) resistant hypertension (not controlled with three antihypertensive drugs); (7) young age—any hypertension at less than 20 years; any hypertension needing treatment at less than 35 years.

The minimum screen in younger patients should include serum electrolytes, plasma bicarbonate, renin, and metanephrines (or catecholamines) to exclude phaeochromocytoma; 24-h urinary sodium excretion should be measured either in all patients, or in those with abnormal renin levels.

Primary hyperaldosteronism (Conn’s syndrome)

Recent studies suggest that aldosterone-producing adrenal adenomas are the single commonest known cause of hypertension. Primary hyperaldosteronism causes increased sodium retention through the epithelial sodium channel (ENaC) in the distal tubule and cortical collecting duct, which leads to hypertension. It can be caused by (1) Conn’s adenoma—a small (0.5–3.5 cm) benign tumour of the adrenal gland; (2) bilateral adrenal hyperplasia—where there are macro- or micronodules in the adrenal cortex; (3) the very rare condition of glucocorticoid-remediable aldosteronism (see Chapter 16.17.4).

Diagnosis— this usually consists of three confirmatory features: suggestive clinical biochemistry; radiological imaging showing an adenoma; lateralization on selective adrenal sampling. A good blood pressure response to aldosterone antagonism with spironolactone can provide further reassurance but is not an essential, or always present, part of the diagnosis. The classic clinical picture is hypertension with plasma electrolytes showing low K+, elevated bicarbonate, and Na+ typically at the upper end of the normal range, together with suppressed plasma renin and elevated aldosterone—. . However, none of these findings is invariable, and a high index of suspicion is warranted in patients with hypertension resistant to conventional therapy. A suppressed plasma renin, despite treatment with ‘A+C+D’ drugs which normally elevate renin, is the most useful clue, whereas plasma aldosterone itself is often within the normal range but inappropriately high for the level of renin.

The imaging, like the biochemistry, is straightforward in classical patients, since the adrenals are easily imaged in most patients by either CT or MRI. However, patients with little intra-abdominal fat remain challenging, and it is important also to recognize that adrenals reported as ‘bulky’ often hide a small (<1 cm) adenoma. The key objective, once an adenoma is seen or suspected, is proving functional lateralization. This can be difficult, but is essential for predicting that removal of one adrenal will have a substantial benefit, as well as indicating which adrenal to remove. The most reliable technique in most specialist centres is adrenal vein sampling: all samples need to be assayed for aldosterone and cortisol, with the ratio compared between the two sides.

Management—medical treatment is preferred for bilateral adrenal hyperplasia, control of hypertension and hypokalaemia before surgery for adenoma, older patients with adenoma who are well controlled, or where there is any doubt about diagnosis or lateralization. Spironolactone is the treatment choice but causes gynecomastia in men. Eplerenone or amiloride are less effective alternatives, and amiloride can be used-cautiously in combination with either of the other two drugs. Elective surgery is indicated for younger patients with adenomas, and older patients intolerant of—or uncontrolled by—medical treatment.

Renovascular hypertension

This is most commonly due to intrinsic disease of the intima (acquired, atherosclerosis, etc.) or media (congenital, fibromuscular dysplasia (FMD), etc.). FMD accounts for only 10–20% of all cases, but is the commonest cause under the age of 40.

Most cases of renovascular hypertension are probably not diagnosed because of the absence of sensitive clinical or biochemical markers. The main clinical clue is the finding in 50% of cases of a bruit anteriorly or posteriorly over a renal area, but it is important to remember that such a bruit is never diagnostic. In centres where it is routinely measured in younger patients, an elevated plasma renin is the commonest trigger to investigation for FMD. The diagnosis is made radiologically, most commonly by CT or MR angiography.

In FMD, angioplasty is usually curative, with about three-quarters of patients able to discontinue antihypertensive treatment. In atheromatous disease, angioplasty is much less likely to be successful: complete cure of hypertension is rare, and often the purpose of intervention is to protect declining renal function.

Coarctation of the aorta

Coarctation causes less than 1% of all cases of hypertension. The classical clinical finding is radio–femoral pulse delay or weak lower limb pulses. Diagnosis is confirmed by two-dimensional echocardiography, or by CT or MR angiography. Treatment is by surgery, balloon dilatation, or stenting.

Phaeochromocytoma

Phaeochromocytomas are rare tumours of chromaffin tissue that account for 0.1 to 1% of cases of hypertension: 90% are benign and 90% are located in the adrenal gland (4% of adrenal incidentalomas are phaeochromocytomas). Most are sporadic, but some are associated with genetic syndromes, including von Hippel–Lindau and multiple endocrine neoplasia (MEN) type 2.

Hypertension, usually in association with one or more symptoms of headache, sweating, anxiety, and palpitations, is the most common presentation. Other rarer presentations include unexplained heart failure or paroxysmal arrhythmia.

Diagnosis—this is usually not difficult once the possibility of phaeochromocytoma has been entertained; more difficult is excluding the diagnosis in patients who have clinical and/or biochemical features of physiological catecholamine excess. Investigation must first determine whether the patient has a phaeochromocytoma, and then where the tumour is. The best screening test is to measure plasma normetanephrine (normetadrenaline) and metanephrine (metadrenaline): levels or, if unavailable, 24-h urine metanephrines: both assays in a reliable laboratory are more sensitive and specific than measurement of catecholamines or vanillylmandelic acid (VMA). Detection of elevated metadrenaline is a useful clue to the usual adrenal location of the phaeochromocytoma. A pharmacological suppression test can be performed where doubt about the diagnosis remains: physiological elevations of noradrenaline release are temporarily suppressed by administration of the ganglion-blocking drug pentolinium, or the centrally acting α‎2-agonist clonidine, but these drugs do not suppress autonomous secretion by tumour. CT or MRI scanning usually provides excellent imaging of the adrenal. Radioisotope scanning with the iodinated analogue of noradrenaline, m-iodobenzylguanidine (mIBG), beis usually helpful in localizing extra-adrenal tumours. Selective venous sampling is occasionally required.

Management surgery—is the definitive treatment that cures hypertension in most patients—; the task for the physician is to make it safe. This should be done by α‎-blockade with phenoxybenzamine, with a low dose of a β‎1-selective blocker used to prevent reflex tachycardia.

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