Adrenal Gland: V
Aldosterone
Clinical scenario
42-year-old Mr J-P T was referred to
the hypertension clinic of his local hospital as his GP had established that he
had hypertension in the order of 180–190/105–110. An ECG showed evidence of
early left ventricular hypertrophy but fundoscopy was normal. Blood tests were
taken and the results showed Na+ 144 mmol/L, K+ 2.8
mmol/L, with alkalosis and normal renal function. Repeated tests confirmed the
hypokalaemia. Estimation of plasma renin and aldosterone at 0800 h with the
patient recumbent showed elevated aldosterone concentrations and suppressed
renin activity, consistent with a diagnosis of primary hyperaldosteronism. An
abdominal MRI scan was done that revealed a 4 cm mass in the left adrenal
gland. Mr T was treated with spironolactone to control his blood pressure and
correct the hypokalaemia and after 8 weeks his blood pressure was normalized
and he underwent adrenal surgery and removal of a left sided adrenal adenoma.
Postoperatively, the spironolactone was withdrawn and his blood pressure
remained within normal limits on no therapy.
Aldosterone
Aldosterone is the physiological
mineralocorticoid of the body. In other words, it is an adrenal corticosteroid
which affects cation concentrations and movements, specifically those of sodium
(Na+) and potassium (K+).
Biosynthesis of aldosterone (Fig. 20a). Deoxycorticosterone (DOC), a weaker
mineral ocorticoid, is also secreted. Both are synthesized in the zona
glomerulosa, which lacks the enzyme 17-hydoxylase. Progesterone is hydroxylated
at C21 and C11-b, resulting in corticosterone, which is hydroxylated at C18 and
then oxidized to an aldehyde. This is shown as the last reaction product in what
is called the hemiacetal form and is the form in which it is predominantly
present. The secretion of aldosterone is controlled by the renin–angiotensin
system (Chapter 36) and, to a lesser extent, by ACTH. Essentially,
hyperkalaemia (raised blood K+), ACTH and angiotensin II can
increase aldosterone release.
Mechanism of action of aldosterone (Fig. 20b). Aldosterone stimulates the active
transport of sodium through the epithelial cell wall. In common with the other
steroid hormones, aldos- terone stimulates de novo synthesis of
proteins, which enhance sodium transport in the epithelial cell of the distal
convoluted tubule of the kidney, the site of aldosterone action in the nephron
(Fig. 20c). The aldosterone receptor is also regulated by concentrations of
aldosterone, higher concentrations of which reduce its production.
Glucocorticoids bind to the aldosterone receptor with comparable affinity;
furthermore, the same nuclear response element serves both glucocorticoid and
aldosterone receptors. Nevertheless, glucocorticoids have only minor
mineralocorticoid action because glucocorticoids are rapidly metabolized in
cells that are principal targets for aldosterone. Conversely, aldosterone binds
weakly to glucocorticoid receptors, explaining its glucocorticoid effect when
administered in high doses. The drug spironolactone competes with
aldosterone for its receptor.
There are three main theories to
account for aldosterone action: (i) the hormone increases the number of sodium
channels in the apical membrane; (ii) it increases the number of Na+K+-ATPase
molecules; (iii) it increases adenosine triphosphate (ATP) molecule number
within the cell. The hormone stimulates fatty acid synthesis and may alter
membrane phospholipid composition as part of its mechanism of action.
Recent research suggests that
aldosterone antagonists such as spironolactone may be useful for treatment of
atrial fibrillation, given that aldosterone may be important in the aetiology
of this cardiac disease.
The term pseudohypoaldosteronism encompasses
rare genetic syndromescharacterized by hypertension and hypokalaemic alkalosis.
Apparent mineralocorticoid excess (AME) is an autosomal dominant condition due
to mutations in the gene encoding 11-β hydroxysteroid dehydrogenase Type II
resulting in excessive glucocorticoid stimulation of mineralocorticoid
receptors in the kidney. Liddle’s syndrome is an autosomal dominant syndrome
associated with abnormal functioning of epithelial Na channels causing sodium
retention. AME is also mimicked by excess liquorice ingestion which blocks 11-β
