Endocrinology of Blood Pressure Control Medical Assignment Help

The control of blood pressure (BP) is complex involving neural, cardiac, hormonal and many other mechanisms. BP is dependent upon cardiac output and peripheral resistance. Although cardiac output can be increased in endocrine disease (e.g. thyrotoxicosis), the main role of hormonal mechanisms is control of peripheral resistance  and of circulating blood volume. The oral contraceptive pill is a common endocrine cause of hypertension. When to investigate for secondary


Endocrine causes account for less than 5% of all hypertension (Table 16.39). It is impracticable and unnecessary to screen all hypertensive patients for secondary causes. The highest chances of detecting such causes are in:
• Subjects under 35 years old, especially those without a family history of hypertension
• Those with accelerated (mali nant) hypertension
• Those with indications of renal disease (proteinuria, unequal renal sizes)
• Those with hypokalaemia before diuretic therapy
• Those resistant to conventional antihypertensive therapy
• Those with unusual symptoms (e.g. sweating attacks or weakness)
Excessive renin, and thus angiotension II, production
Renal artery stenosis
Other local renal disease
Renin-secreting tumours
Excessive production of catecholamines
Excessive GH production
Excessive aldosterone production
Adrenal adenoma (Conn’s syndrome)
Idiopathic adrenal hyperplasia
Dexamethasone-suppressible hyperaldosteronism
Excessive production of other mineralocorticoids
Cushing’s syndrome (massive excess of cortisol, a weak mineralocorticoid)
Congenital adrenal hyperplasia (in some cases)
Tumours producing other mineralocorticoids, e.g. corticosterone
Exogenous ‘mineralocorticoids’
Liquorice ingestion
Abuse of mineralocorticoid preparations

The renin-angiotensin-aldosteroneaxis

Biochemistry and actions

The renin-angiotensin-aldosterone system is illustrated Angiotensinogen, an a2-globulin of hepatic origin, circulates in plasma. The enzyme, renin, is secreted by thekidney in response to decreased renal perfusion pressure  or flow; it cleaves the decapeptide angiotensin I from angiotensinogen. Angiotensin I is inactive but is further cleaved by converting enzyme (present in lung and vascular endothelium) into the active peptide, angiotensin II, which has two major actions:
1 It causes powerful vasoconstriction (within seconds).
2 It stimulates the adrenal zona glomerulosa to increase aldosterone production. Aldosterone causes sodium retention and urinary potassium loss (hours to days).
The vasoconstrictor action of angiotensin II is short term, while the sodium retention induced by aldosterone increases total body sodium and BP in the longer term. As BP increases and sodium is retained, the stimuli to renin secretion are reduced. Dietary sodium excess will tend to suppress renin secretion, whereas sodium deprivation or urinary sodium loss will increase it.

The renin-angiotensin-aldosterone system. ACE, angiotensin converting enzyme.

The renin-angiotensin-aldosterone system. ACE,
angiotensin converting enzyme.

Atrial natriuretic factors/peptides (ANP)

These peptides are secreted from atrial granules. They produce marked effects on the kidney, increasing sodium and water excretion and glomerular filtration rate and lowering BP, plasma renin activity and plasma aldosterone. They appear to playa significant role in cardiovascular and fluid homeostasis but there is no evidence of primary defects in their secretion causing disease. Analogues that break down ANP as well as inhibiting the aminopeptidases are under development and might prove of value in producing a sodium diuresis.


Many forms of unilateral and bilateral renal diseases are associated with hypertension. The classic example is renal artery stenosis: the major hypertensive effects of this and other situations such as renin-secreting tumours are directly or indirectly due to angiotensin II.
Renin inhibitors have  been produced and are under clinical trial. They appear to produce much the same effects as angiotensin-converting enzyme inhibitors and hold promise as antihypertensive agents, though none are yet available for clinical use.

Renal artery stenosis


Primary hyperaldosteronism


This rare condition « 1% of all hypertension) is causedby excess aldosterone production leading to sodium retention, potas sium loss and the combination of hypokalaemia and hypertension.


Adrenal adenomas (Conn’s syndrome) account for 60% of cases; 30% are due to bilateral adrenal hyperplasia, which may be secondary to excess of a pituitary aldosterone- stimulating factor that is as yet unidentified.


The usual presentation is with hypertension and hypokalaemia «3.5 mmol litre””), although 20% of patients have initial potassium levels of 3.5-4.2 mmollitre-I. The few symptoms are non-specific; muscle weakness, nocturia and tetany are rarely seen. The hypertension may be severe and associated with renal and retinal damage. Adenomas, often very small, are commoner in young females, while bilateral hyperplasia rarely occurs before age 40 years and is commoner in males.


The characteristic features are:
HYPOKALAEMIA. A high-salt diet should be given for several days before testing and diuretics must be stopped 3 weeks before investigation; plasma samples must be separated quickly. Bethanidine or prazosin may be used for temporary control of blood pressure as they do not alter renin or aldosterone secretion.
URINARY POTASSIUM LOSS. Levels over 30 mmol daily during hypokalaemia are inappropriate.
ELEVATED PLASMA ALDOSTERONE LEVELS that are not suppressed with saline infusion (300 mmol over 4 hours) or fludrocortisone administration.
SUPPRESSED PLASMA RENIN ACTIvITy-l3-blockers and other drugs may interfere with renin activity. Once a diagnosis of aldosteronism is established, differentiation of adenoma from hyperplasia involves adrenal CT or MRI (not infallible as tumours may be very small), complex biochemical testing, adrenal scintillation scanning (now rarely needed) and venous catheterization.


An adenoma should be surgically removed; BP falls in 70% of patients. Those with hyperplasia should be treated with the aldosterone antagonist spironolactone (100- 400 mg daily); side-effects include nausea, rashes and gynaecomastia. Amiloride (10-40 mg daily) is a less effective alternative, used especially as spironolactone in long term use has been linked with tumour development in animals. Calcium channel blockers are also effective.

Secondary hyperaldosteronism

This situation arises when there is excess renin (and hence angiotensin II) stimulation of the zona glornerulosa. Common causes are accelerated hypertension and renal artery stenosis, when the patient will be hypertensive. Causes associated with normotension include congestive cardiac failure and cirrhosis, where excess aldosterone production contributes to sodium retention. Spironolactone is of value in both situations. Angiotensin-
converting enzyme (ACE) inhibitors, e.g. captopril, enalapril or lisinopril, are effective in heart failure, both symptomatically and in increasing life expectancy.


Except as part of primary hypoadrenalism (Addison’s disease, see p.813), this is very uncommon. Causes include hyporeninaemic hypoaldosteronism, aldosterone biosynthetic defects and drugs (e.g. ACE inhibitors, heparin).


The major catecholamines, noradrenaline and adrenaline, are produced in the adrenal medulla although most noradrenaline is derived from sympathetic neuronal release. While noradrenaline and adrenaline undoubtedly produce hypertension when infused, they probably play little part in BP regulation in normal humans.


Phaeochromocytomas, tumours of the sympathetic nervous system, are very rare (less than 1 in 1000 cases of hypertension); 90% arise in the adrenal, while 10% occur elsewhere in the sympathetic chain; 25% are multiple and 10% are malignant, though this cannot be determined on simple histological examination. Some are associated with MEN syndromes (see below). Most tumours release both noradrenaline and adrenaline but large turn ours produce almost entirely noradrenaline.


The clinical features are those of catecholamine excess and are frequently, but not necessarily, intermittent. The diagnosis should particularly be considered when cardiovascular instability has been demonstrated and in severe hypertension in pregnancy.


The possibility needs to be considered quite frequently in patients with hypertension. Specific tests are:
MEASUREMENT OF URINARY METABOLITES (preferably metanephrines rather than vanillylmandelic acid (VMA) – Fig. 16.29) is a useful screening test;
normal levels on three 24-hour collections of metanephrines virtually exclude the diagnosis. Many drugs and dietary vanilla interfere with these tests.
IF HIGH METANEPHRINES OR VMAs ARE FOUND, plasma catecholamines are estimated.
URINARY CATECHOLAMINES are measured in some centres.
CT SCANS, initially of the abdomen, are helpful to localize the tumours which are often large. MR I usually shows the lesion clearly.
SCANNING WITH [131I] METAIODOBENZYLGUANIDINE  produces specific uptake in sites of sympathetic activity with about 90% success. It is particularly useful in extra-adrenal turn ours.


Tumours should be removed if this is possible. Medical preoperative and perioperative treatment is vital and includes complete a- and f3-blockade with phenoxybenzamine (20-80 mg daily initially in divided doses), then propranolol (120-240 mg daily), plus transfusion of whole blood to re-expand the contracted plasma volume. The a-blockade must precede the f3-blockade. Labetolol is not recommended. Surgery in the unprepared patient is fraught with dangers of both hypertension and hypotension; expert anaesthetic help is vital and sodium nitroprusside should be available in case sudden severe hypertension develops.
When operation is not possible, combined a- and f3- blockade can be used long term. Patients should be kept under clinical and biochemical review after tumour resection as about 10% recur or
develop a fur ther tumour.

Posted by: brianna




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