Case history #2
A 28-year-old woman presents with a 2-year history of hypertension, associated with nocturia (4-5 times per night), polyuria, palpitations, limb paraesthesias, lethargy, and generalised muscle weakness. There is no other past medical history. Physical examination is unremarkable apart from a BP of 160/100 mmHg, global hyporeflexia, and weak muscles. Plasma potassium is 2.2 mmol/L (2.2 mEq/L), bicarbonate is 34 mmol/L (34 mEq/L), and serum creatinine is normal.
Other presentations
Hypertension in primary aldosteronism (PA) may be mild or severe and is rarely malignant.[18]Murphy BF, Whitworth JA, Kincaid-Smith PA. Malignant hypertension due to an aldosterone-producing adrenal adenoma. Clin Exp Hypertens A. 1985;7(7):939-50.
http://www.ncbi.nlm.nih.gov/pubmed/3899416?tool=bestpractice.com
BP levels vary widely among patients with either aldosterone-producing adenoma or bilateral adrenal hyperplasia, and cannot be used to distinguish these subtypes.[19]Vetter H, Siebenschein R, Studer A, et al. Primary aldosteronism: inability to differentiate unilateral from bilateral adrenal lesions by various routine clinical and laboratory data and by peripheral plasma aldosterone. Acta Endocrinol (Copenh). 1978 Dec;89(4):710-25.
http://www.ncbi.nlm.nih.gov/pubmed/213920?tool=bestpractice.com
In familial hyperaldosteronism type I (FH-I), hypertension is often delayed, especially in females, but can be of early onset and severe enough to cause early death, usually from haemorrhagic stroke.[20]Stowasser M, Gartside MG, Gordon RD. A PCR-based method of screening individuals of all ages, from neonates to the elderly, for familial hyperaldosteronism type I. Aust N Z J Med. 1997 Dec;27(6):685-90.
http://www.ncbi.nlm.nih.gov/pubmed/9483237?tool=bestpractice.com
[21]Rich GM, Ulick S, Cook S, et al. Glucocorticoid-remediable aldosteronism in a large kindred: clinical spectrum and diagnosis using a characteristic biochemical phenotype. Ann Intern Med. 1992 May 15;116(10):813-20.
http://www.ncbi.nlm.nih.gov/pubmed/1567095?tool=bestpractice.com
Family screening in FH-I and families with PA of uncertain genetic aetiology has revealed highly diverse phenotypes with some patients normotensive, consistent with PA evolving through a pre-clinical phase.[4]Gordon RD, Stowasser M, Klemm SA, et al. Primary aldosteronism - some genetic, morphological, and biochemical aspects of subtypes. Steroids. 1995 Jan;60(1):35-41.
http://www.ncbi.nlm.nih.gov/pubmed/7792813?tool=bestpractice.com
[13]Gordon RD, Stowasser M. Familial forms broaden the horizons for primary aldosteronism. Trends Endocrinol Metab. 1998 Aug;9(6):220-7.
http://www.ncbi.nlm.nih.gov/pubmed/18406272?tool=bestpractice.com
[21]Rich GM, Ulick S, Cook S, et al. Glucocorticoid-remediable aldosteronism in a large kindred: clinical spectrum and diagnosis using a characteristic biochemical phenotype. Ann Intern Med. 1992 May 15;116(10):813-20.
http://www.ncbi.nlm.nih.gov/pubmed/1567095?tool=bestpractice.com
[22]Stowasser M, Gordon RD. Familial hyperaldosteronism. J Steroid Biochem Mol Biol. 2001 Sep;78(3):215-29.
http://www.ncbi.nlm.nih.gov/pubmed/11595502?tool=bestpractice.com
[23]Stowasser M, Gordon RD. Primary aldosteronism: from genesis to genetics. Trends Endocrinol Metab. 2003 Sep;14(7):310-7. [Erratum in: Trends Endocrinol Metab. 2003 Nov;14(9):397.]
http://www.ncbi.nlm.nih.gov/pubmed/12946873?tool=bestpractice.com
[24]Stowasser M, Huggard PJ, Rossetti TR, et al. Biochemical evidence of aldosterone overproduction and abnormal regulation in normotensive individuals with familial hyperaldosteronism type I. J Clin End Metab. 1999 Nov;84(11):4031-6.
http://www.ncbi.nlm.nih.gov/pubmed/10566645?tool=bestpractice.com
[25]Stowasser M. New perspectives in the role of aldosterone excess in cardiovascular disease. Clin Exp Pharmacol Physiol. 2001 Oct;28(10):783-91.
http://www.ncbi.nlm.nih.gov/pubmed/11553016?tool=bestpractice.com
Less than one quarter of patients diagnosed with PA and less than half of those with aldosterone-producing adenoma are hypokalaemic.[26]Gordon RD, Rutherford JC, Stowasser M. Primary aldosteronism: are we diagnosing and operating on too few patients? World J Surg. 2001 Jul;25(7):941-7.
http://www.ncbi.nlm.nih.gov/pubmed/11572036?tool=bestpractice.com
[27]Stowasser M, Gordon RD. Primary aldosteronism - careful investigation is essential and rewarding. Mol Cell Endocrinol. 2004 Mar 31;217(1-2):33-9.
http://www.ncbi.nlm.nih.gov/pubmed/15134798?tool=bestpractice.com
In these patients, PA is indistinguishable from essential hypertension unless renin and aldosterone are measured. When hypokalaemia does occur, it may be associated with nocturia, polyuria, muscle weakness, cramps, paraesthesias, and/or palpitations. Nocturia is frequent even in the absence of hypokalaemia. Other common symptoms among either normokalaemic or hyperaemic patients include headaches, lethargy, mood alterations (including irritability, anxiety, or depression), and impaired mental concentration. During pregnancy, hypertension and symptoms may improve. This is thought to be due to the anti-mineralocorticoid effects of high circulating levels of placental progesterone, which antagonise aldosterone action at the mineralocorticoid receptor.