Best Practice & Research Clinical Endocrinology & Metabolism
8Treatment of primary aldosteronism
Section snippets
The need to treat
For a long time primary aldosteronism (PA) was regarded as a benign and rare secondary form of hypertension. However, data has emerged showing that aldosterone (in combination with sodium) has a detrimental effect on the cardiovascular system. In addition, it is now accepted that PA is the most common cause for secondary hypertension, affecting up to 10% of the hypertensive population,1, 2, 3, 4, 5, 6, 7, 8*, 9 although some authors still dispute these data.10, 11 Nevertheless, it is important
General treatment aspects
In general, sodium restriction (<2 g/day NaCl) for patients with all forms of mineralocorticoid hypertension is useful to minimize potassium loss and to lower blood pressure.27, 28
The treatment aim in patients with PA should be the normalization of blood pressure (<140/90 mmHg) but also the inhibition of the proinflammatory and profibrotic effects of aldosterone and salt and thereby the reduction of the increased morbidity and mortality.
Treatment of aldosterone-producing adenoma (APA)
Patients with documented unilateral PA (i.e. APA or unilateral adrenal hyperplasia (UAH)) should be treated with unilateral laparoscopic adrenalectomy.29 However, if the patient is unable or unwilling to undergo surgery, it is recommended that the patient receives medical treatment with a MR antagonist.
Laparoscopic adrenalectomy is associated with fewer complications and a shorter hospital stay compared with open adrenalectomy. Due to the low morbidity (5–7%) and mortality (<1%) laparoscopic
Treatment of bilateral adrenal hyperplasia
There are no randomized placebo-controlled trials that have evaluated the relative efficacy of drugs in the treatment of adrenal hyperplasia. Data showed that in a total of 99 surgically treated patients with bilateral adrenal hyperplasia, the hypertension cure rate was only 19% after unilateral or bilateral adrenalectomy.45, 46, 47, 48, 49 A recent retrospective study of 40 patients with bilateral adrenal hyperplasia confirmed by AVS underwent unilateral adrenalectomy. After a median follow-up
Treatment of adrenal cortical carcinoma
Adrenocortical carcinoma (ACC) is a rare and heterogeneous malignancy with incompletely understood pathogenesis and poor prognosis. Patients present with hormone excess (e.g. virilization, Cushing's syndrome, hypertension) and/or a local mass effect. The rare aldosterone-producing ACCs present with hypertension and pronounced hypokalemia (mean serum potassium 2.3 ± 0.08 mmol/liter).78 Hypersecretion of hormonal steroids in ACC frequently contributes to the disease burden and can severely affect
Treatment of macronodular hyperplasia
Unilateral macronodular hyperplasia should be handled as an APA, whereas bilateral macronodular should be treated in a similar fashion to bilateral adrenal hyperplasia. However no large studies have been published on this entity of PA.
Treatment of GRA
The pathogenesis of the autosomal dominant glucocorticoid-remediable hyperaldosteronism (GRA) is due to formation of a chimeric gene caused by an unequal crossing over between the aldosterone-synthase gene (CYP11B2) and the 11ß-hydroxylase gene (CYP11B1).82, 83 This process causes an aldosterone-synthase gene, which is not regulated by an angiotensin-II driven promoter, but by an ACTH-dependent promoter. Therefore GRA can be treated medically with a glucocorticoid to partially suppress
Future treatment options
As mentioned above new non-steroidal mineralocorticoid receptor antagonists are being developed and will be available soon.77 Another hope for the future are aldosterone-synthase inhibitors that are currently undergoing phase II clinical trials.86 Recently, the new aldosterone synthase inhibitor LCI699 was used for the first time in patients with primary hyperaldosteronism.97 14 patients with primary hyperaldosteronism received LCI699 for 4 weeks resulting in normalization of plasma potassium
Cardiovascular benefits of treatment
Aldosterone excess is linked to endothelial dysfunction independent of blood pressure and to microvascular inflammation and fibrosis in the myocardium, the kidney and blood vessels.87, 88, 89 Accordingly, mineralocorticoid receptor antagonistic therapy as evaluated in the RALES,90 EPHESUS,62 and 4E trials91 conclusively demonstrated a major therapeutic benefit in the heart.
Some smaller retrospective studies are available in patients with PA investigating the effect of adrenalectomy or
Conflict of interest
None.
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