The Journal of Steroid Biochemistry and Molecular Biology
General reviewFamilial hyperaldosteronism
Section snippets
Introduction: the evolution of primary aldosteronism
Professor Jerome W. Conn, Head of the Endocrinology Division, Department of Medicine, University of Michigan, first described the syndrome of primary aldosteronism (PAL) in 1954 [1], the same year that the chemical structure of aldosterone was identified [2]. Conn's first patient was a 34-year-old hypertensive female who, for the 7 years preceding her presentation to his clinic, had suffered polydipsia, polyuria, nocturia, attacks of muscle weakness and episodic tetany due to severe hypokalemic
Familial hyperaldosteronism type I
In Sutherland's original family with FH-I [15], a 41-year-old Canadian man and his 16-year-old son exhibited hypertension, hypokalemia, increased aldosterone secretion rate and suppressed plasma renin activity (PRA), all of which normalized during the administration of dexamethasone 2 mg/day. Hypertension had been detected at an early age in both individuals (19 and 13-years old, respectively) and three of the father's 11 siblings had died prematurely (two in their 40s and one in his 60s) from
Original reports
In 1991, prior to the availability of genetic testing for FH-I, we were able to report the occurrence in three families of a familial variety of PAL that was not responsive to glucocorticoids; this was associated with either APA (four patients from two families) or BAH (two patients from one family) [43]. This represented the first description of the familial occurrence of APA, confirmed by pathological examination of removed adrenal tissue and cure (three patients) or marked improvement (one
Conclusions
The study of familial varieties has expanded the clinical, biochemical and genetic spectrum of PAL. Like FH-I, FH-II is associated with hyperaldosteronism and probable autosomal dominant inheritance. Unlike FH-I, hyperaldosteronism in FH-II is not glucocorticoid-remediable and FH-II is not associated with the hybrid gene mutation. In contrast to FH-I, FH-II is unlikely to be caused by a single genetic mutation, but by a variety of mutations, each predisposing to adrenal cortical hyperplasia and
Acknowledgements
The authors gratefully acknowledge the National Heart Foundation of Australia, National Health and Medical Research Council of Australia and the Commonwealth Department of Veterans’ Affairs for their support of studies conducted by the Greenslopes and Princess Alexandra Hospital Hypertension Units, which were described in this review.
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2020, Best Practice and Research: Clinical Endocrinology and MetabolismCitation Excerpt :These patients presented also high levels of 18-hydroxycortisol and 18-oxocortisol, their secretion being again under the control of ACTH and suppressible by glucocorticoids. FH-I is more often associated with bilateral adrenal hyperplasia rather than adrenocortical adenoma [32,33]. In 1992, the molecular basis of this autosomal dominant form of PA was elucidated by Lifton and coll [34,35].