Endocrine
Hypertension
Clinical background
Hypertension affects up to 25% of the
population in western countries but only 2–5% will be found to have an
identifiable underlying endocrine cause that can be treated. Young people with
hypertension should be screened for secondary causes, as should those with a
strong family history of hypokalaemia. Treatment is directed towards the
underlying cause.
Hypertension may be one of the
presenting features of a number of endocrine disorders. Systolic hypertension
is typical of thyrotoxicosis, patients with acromegaly are usually hypertensive
at presentation and hypertension frequently complicates obesity and diabetes.
Two main types of hypertension are
recognized – the first is essential hypertension, which is the most prevalent
type and has no known cause but whose aetiology may involve disturbances of
endocrine function, particularly the renin–angiotensin– aldosterone system
(Fig. 37a). The other is secondary hypertension, which affects around 2–5% of
patients, and which is usually the result of endocrine disorders, for example
glucocorticoid or catecholamine excess, or hyperaldosteronism.
Clinically, high blood pressure is an
important risk factor for cardiovascular diseases such as stroke and myocardial
infarction.
Factors raising blood pressure. Blood pressure is raised (i) when the heart beats
more powerfully (positive inotropic effect); (ii) when arterioles constrict,
increasing the peripheral resistance; (iii) when fluid and salts are retained;
and (iv) through the influence of cardiovascular control centres in the brain,
or a combination of two or more of these factors.
Hormonal causes of hypertension and
treatments
Hypertension of adrenal origin
Phaeochromocytoma (see Chapter 16). Epinephrine, secreted by a
phaeochromocytoma (adrenal medullary tumour) raises blood pressure and its
effects can be countered using α- and β-blockers and the problem cured by
removing the tumour.
Hyperaldosteronism (see Chapter 20). Over-secretion of aldosterone by
an adrenal adenoma (primary hyperaldos-teronism; Conn’s syndrome).
Aldosterone promotes the retention of Na+ and water and this expands
the plasma volume and raises the blood pressure. This can be treated by
blocking aldosterone receptors with spirinolactone and cured by removing the
tumour. Aldosterone secretion can also be increased by excess renin secretion, which
increases angiotensin II production, which in turn promotes aldosterone release
(secondary hyperaldosteronism). This mechanism plays an important role
in the neurohormonal sequence in heart failure. Secondary hyperaldosteronism
can be treated by blocking angiotensin II production with ACE inhibitors, or
with angiotensin II receptor antagonists. Aldosterone receptors can also be
stimulated through over-production of cortisol or deoxycorticosterone (see
below), which bind aldosterone receptors with high affinity. Cortisol is
normally rapidly metabolized by 11β- hydroxysteroid dehydrogenase, and patients
with an hereditary deficiency or absence of this enzyme exhibit an apparent
hyperaldosteronism.
Cushing’s disease (see Chapter 17). Raised cortisol concentrations
increase angiotensinogen release from the liver. Cortisol, as described above,
also stimulates aldosterone receptors.
Excess deoxycorticosterone (DOC)
production (Fig. 37b).
Clinically, DOC ranks second after aldosterone in importance as a mineralocorticoid.
Excess DOC is diagnosed because it reduces renin and aldosterone production by
a negative feed-back on the latter two hormones. DOC is a potent
mineralocorticoid and circulates at about the same concentration as
aldosterone. However, DOC is normally inactive because most of it circulates
bound to the protein CBG and is inactivated in the liver. Urine is virtually
free of DOC. Excess DOC production can occur through overproduction of
steroids, as in primary aldosteronism, Cushing’s disease (see Chapter 17) or
when there are congenital deficiencies of certain steroid-metabolizing enzymes
such 11β-hydroxylase which also results in increased androgen production and
consequent virilization (see Chapter 19).
Congenital deficiency of adrenal
17α-hydroxylase will also promote excess
DOC production and consequent hypertension together with impaired sexual
maturation in both sexes (see Chapter 19). Deficiencies of 11β-hydroxylase and
17α- hydroxylase are treated with glucocorticoids, which is standard treatment
for all forms of congenital adrenal hyperplasia associated with Na+
retention.
Hypertension of renal origin
The renin–angiotensin–aldosterone
system is normally finely tuned through feedback mechanisms to maintain the
proper plasma osmolality and K+ and Na+ concentrations
(Fig. 37c). This balance, together with the integrated operation of the
cardiovascular system ensures the maintenance of a healthy blood pressure. This
regulatory system may involve the actions of angiotensin in the brain and/or in
circumventricular organs of the brain that do not have a blood–brain barrier,
for example the area postrema. The precise mechanism is unknown, but it is
possible that the brain ultimately regulates renin release from the
juxtaglomerular apparatus of the kidney, and a ‘resetting’ of set points for
blood pressure in the brain through the regulation of renin release may be
important in the aetiology of essential hypertension (Fig. 37c).
Hypertension of other endocrine
origin
Insulin. There is a strong association between
hypertension, insulin resistance, hyperinsulinaemia and obesity, and
hypertension may be a consequence of the latter three conditions. Indeed, many
obese patients with hypertension are also insulin-resistant. In patients with
Type 2 diabetes (see Chapter 41), glucose uptake into tissues is impaired with
consequent increased insulin release. Insulin stimulates sympathetic activity
and promotes Na+ reuptake in the kidney tubules, and these may
contribute to the hypertension produced in these patients.
Thyroid. Hyperthyroidism is associated with systolic
hypertension due to a combination of increased cardiac output and reduced
peripheral resistance.
