Trends in Endocrinology & Metabolism
Familial Forms Broaden the Horizons for Primary Aldosteronism
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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2013, Heart Lung and CirculationCitation Excerpt :Approximately 30% of FH-II patients have unilateral forms of PA (mostly aldosterone-producing adenoma, APA), the remainder being bilateral (bilateral adrenal hyperplasia, BAH). Among those with APA, some have demonstrated lack of normal responsiveness of plasma aldosterone to upright posture or angiotensin II infusion (angiotensin-unresponsive APA) and predominantly ZF cellular composition while others have retained responsiveness (angiotensin-responsive APA) and demonstrated predominantly non-ZF histology [55,75,76], with both patterns occurring in the same family [55]. The genetic basis for FH-II remains uncertain, and is almost certainly heterogeneous.
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