Primary aldosteronism including CONN adenoma

Introduction to primary aldosteronism and Conn adenoma
Primary aldosteronism is in approximately 30% caused by an adenoma in one of the adrenals – denoted Conn adenoma – or is in 70% a consequence of uni- or bilateral hyperplasia. An overview of diagnosis and treatment follows.

Background to primary aldosteronism
Autonomous overproduction of aldosterone from the adrenal cortex leads to primary aldosteronism. The excess aldosterone in plasma leads to retention of sodium, which generally is compensated why high values are rarely seen. Exess excretion of potassium in the urine also occurs, and hypokalemiamay develop, but many patients are normokalemic. As a secondary consequence to this, the renin/angiotensin-system is suppressed, seen as low levels of renin in serum. Screening has found that primary aldosteronism is more common thatn previously anticipated, up to 7-15% of patients with essential hypertension may suffer from primary aldosteronism. This would mean that most patients are undiagnosed, and only in Sweden numbers of 100-200 000 individuals today suffer from unknown primary aldosteronism.

The histopathological diagnosis is in 30% of cases an adenoma (Conn adenoma), primary unilateralhyperplasia in 1 % and bilateral hyperplasia in the remaining. The Conn adenomas are usually but not exclusively unsensitive to angiotensin. The bilateral hyperplasia are usually dependant on angiotensin. Some adenomas may express a mixed production of steroids, which clinically manifests as primary aldosteronism. In 1-2% hereditary disorders exists, divided into Familial hyperaldosteronism type I, II and III. FHI is characterized by that glucocorticoids may inhibit the aldosterone production due to a gene translocation where the prmoter to the glucocortiocoid producing enzyme (CYP11B1) is translocated to be situated before the reading frame of CYP 11B2 – the gene encoding for aldosterone stynthetase.

Recently a breakthrough regarding knowledge about genetic disturbances in sporadic primary aldosteronism caused by an adenoma have occurred, where mutations in genes encoding for several potassium channels are identified. Some of these genes, e.g.KCNJ5, ATP1A1 and ATP2B3, may be used in the future for diagnostic and treatment purposes.

Diagnostics of primary aldosteronism
Aldosteron/renin ratio: Primary aldosteronism should be suspected in all cases with severe hypertension with or without hypokalemia, and especially in patiens with adrenal incidentaloma and hypertension. In early stages may the aldosterone level still be normal, but the renin level suppressed, which is the reason to use the aldosteron/renin-ratio as diagnostic tool. Aldosterone and renin should ideally be measured on patients not taking any medication, which may need in-hospital evaluation.

Confirmatory testing may be needed in doubtful cases, and there are several methods to be used, such as NaCl-infusion test, postural test, Florinef test etc.

Selective adrenal venous sampling is the definite diagnostic method, although difficult to perform and has low sensitivity at many centers. This is definitely a method that should be centralized to gather experience. Metomidate-PETis used to demonstrate adrenocortical origin of an adrenal tumor, but higher signal is also present in primary aldosteronism than in non-fucntional adenomas, especially after pre-PET dexametasone suppression.

Treatment of primary aldosteronism
In case of adenoma or assymetrical hyperplasia where it has been demonstrated that there exists an unilateral dominance in the hormone production laparoscopic or retroperitoneoscopicadrenalectomy should be performed. In many cases is the retroperitoneoscopic route advantageous since a tendency towards lesser postoperative pain and easier operation if the patient has been operated before in the abdomen.

In non-lateralized primary aldosteronism as in most cases of bilateral hyperplasia, mineralcorticoid receptor antagonists should be given (spironolactone or epleronone). In case of FHI (see above), glucocorticoids are given.

Postoperative treatment of surgically treated primary aldosteronism
Operated patients usually have an excellent outcome, and can normally give up their potassium medication within 3-7 days. Antihypertensive medication may in mild cases be taken off, but usually a reduction in number of medications are seen.