Familial Forms Broaden the Horizons for Primary Aldosteronism

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Abstract

The identification of familial forms of primary aldosteronism (PAL) has led to its detection in relatives of affected patients not suspected previously of having PAL. Many are normokalemic and some are even normotensive. This broadens the spectrum of PAL, permitting the study of its evolution and of intervention with specific therapy when hypertension develops. The genetic basis of one form involves steroid biosynthetic enzymes and the other form predisposes to hyperplasia and benign neoplasia.

Section snippets

Historical

Conn's clinical investigation of a 34-year-old female with hypertension and hypokalemia, which led to the removal of her right adrenal containing a 4-cm aldosterone-producing adenoma with cure of these features (Conn, 1955), is a superb example of careful deductive reasoning (Conn, 1968) based on then little-understood physiological processes. During the period 1955–66, Conn and his co-workers showed first that suppressed levels of plasma renin activity (PRA) differentiated primary from

Familial Hyperaldosteronism Type 1 (FH-I)

In 1966, Sutherland et al. encountered a father and son with severe hypertension and hypokalemia. By careful, methodical investigation, they demonstrated that the excessive aldosterone production could be controlled by suppression of ACTH with dexamethasone. This condition, transmitted as an autosomal dominant trait, became known as glucocorticoid-suppressible hyperaldosteronism (GSH), but was rarely recognized for 26 years. During this time, Ulick and Chu (1982)described the overproduction of

Familial Hyperaldosteronism Type II (FH-II)

When we establish a diagnosis of PAL by fludrocortisone suppression testing (Gordon, 1995) we test for FH-I, originally using dexamethasone, but more recently (last 300 patients) using Southern blotting or long-PCR. We have, as a result, diagnosed six new cases of FH-I (a further 23 identified by family screening), suggesting that this is a rare condition. However, we have encountered additional familial instances of PAL that are not caused by FH-I (Table 2).

For example, in 1987 we removed a

Acknowledgements

The work described in this review was supported by the National Heart Foundation of Australia, The National Health and Medical Research Council of Australia and the Australian Department of Veterans' Affairs. Dr David Cohn (Queensland Medical Laboratories, Brisbane) kindly prepared the photomicrographs.

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