Primary aldosteronism: hypertension with a genetic basis.
Exciting developments in knowledge of primary aldosteronism include description of new subtypes and elucidation of the genetic basis of one variety. Furthermore, relatively simple biochemical screening (aldosterone/renin ratio) has disclosed that primary aldosteronism is more common than previously thought, by diagnosing patients at an earlier, normokalaemic stage. The mutant gene discovered in the glucocorticoid-suppressible variety (FHI) codes for an aldosterone biosynythetic enzyme normally controlled by angiotensin II, and now controlled by corticotropin. The zona fasciculata is hyperplastic and makes aldosterone and "hybrid steroids" 18-oxocortisol and 18-hydroxycortisol in excess, in response to ACTH but not to angiotensin II. Adrenal tumours have not yet been described in this condition. Aldosterone-producing adenomas (Conn's syndrome) are also commonly composed of zona fasciculata-like cells, make "hybrid steroids" in excess and are very sensitive to ACTH but not to angiotensin II. We have described a new variety of aldosterone-producing adenoma which is responsive to angiotensin II (AII-responsive APA), consists of at least 20% zona glomerulosa-like cells, and does not make "hybrid steroids" in excess. We have also described a new familial variety of primary aldosteronism that includes tumours and is not glucocorticoid-suppressible (FHII). We propose that primary aldosteronism is a spectrum of genetic diseases expressed as either hyperplasia or neoplasia, and that morphological and genetic diversity explains biochemical and clinical behaviour.
University Department of Medicine, Greenslopes Hospital, Brisbane, Queensland, Australia.
R D
RD
Gordon
S A
SA
Klemm
T J
TJ
Tunny
M
M
Stowasser
D000324:Adrenocorticotropic Hormone / Q000502:physiology; D000450:Aldosterone / Q000096:biosynthesis*; D006801:Humans; D006929:Hyperaldosteronism / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D006973:Hypertension / Q000209:etiology / Q000235:genetics*
D000450:Aldosterone; D000324:Adrenocorticotropic Hormone