Primary Aldosteronism Clinical Presentation
- Author: Gabriel I Uwaifo, MD; Chief Editor: Romesh Khardori, MD, PhD, FACP more...
The clinical presentation of primary aldosteronism is not distinctive, and the correct diagnosis requires a high index of suspicion on the part of the physician. The common clinical scenarios in which the possibility of primary aldosteronism should be considered include the following:
Patients with spontaneous or unprovoked hypokalemia, especially if the patient is also hypertensive 
Patients who develop severe and/or persistent hypokalemia in the setting of low to moderate doses of potassium-wasting diuretics
Patients with treatment-refractory/-resistant hypertension (HTN)
Patients with severe hypokalemia report fatigue, muscle weakness, cramping, headaches, and palpitations. They can also have polydipsia and polyuria from hypokalemia-induced nephrogenic diabetes insipidus. Long-standing HTN may lead to cardiac, retinal, renal, and neurologic problems, with all the associated symptoms and signs.
In a study comparing the cardiac effects of primary versus secondary aldosteronism, Cesari et al determined that while both types of aldosteronism were frequently characterized by left ventricular hypertrophy and diastolic dysfunction, only primary aldosteronism was associated with evident subclinical systolic dysfunction. Moreover, patients with primary aldosteronism had lower heart rates and higher blood pressure and vascular resistance values than did those with the secondary condition, while plasma renin activity was lower in primary than in secondary aldosteronism (0.56 vs 15.00 ng/mL/h, respectively).
Familial primary aldosteronism
The 2 major familial varieties of primary aldosteronism are glucocorticoid-remediable aldosteronism (GRA; type 1 familial primary aldosteronism) and a non–glucocorticoid-remediable type (type 2 familial primary aldosteronism).
The recognition of GRA is particularly important because of its implications for patients who are hypertensive and whose family members are apparently unaffected. HTN, strokes, and other significant cardiovascular events are described in young persons with this syndrome.
Although the syndrome is uncommon, heightened levels of suspicion are essential for the diagnosis. Fewer than 200 well-validated cases exist in the literature. All patients with GRA should be treated medically with glucocorticoids and without surgery.
Although uncommon, GRA may be more prevalent than was previously presumed. A significant subgroup of patients with the milder normokalemic variety of this syndrome is probably incorrectly presumed to have essential HTN.
A family history of HTN (particularly with a young age of onset), HTN in children, low-renin HTN, and presumed IAH are the typical situations in which this diagnosis should be considered.
The third type of familial PA, due to mutations in the KCNJ5 potassium channel-coding gene, is considered to be exceedingly rare, but can also lead to HTN and hypokalemia at a very early age.
Patients with primary aldosteronism do not present with distinctive clinical findings, and a high index of suspicion based on the patient's history is vital in making the diagnosis. The findings could include the following:
Hypertension (HTN) - This condition almost invariably occurs, although a few rare cases of primary aldosteronism unassociated with HTN have been described in the literature.
Ileus from hypokalemia
Findings related to complications of HTN - These include cardiac failure, hemiparesis due to stroke, carotid bruits, abdominal bruits, proteinuria, renal insufficiency, hypertensive encephalopathy (confusion, headache, seizures, changes in the level of consciousness), and hypertensive retinal changes
It is important to note that primary aldosteronism in and of itself is typically not associated with edema, despite the volume-expanded state associated with it. The lack of edema results from spontaneous natriuresis and diuresis (called the "aldosterone escape") that occurs in patients with primary aldosteronism and that appears to be mediated by atrial natriuretic peptide (ANP).[14, 15] Of note, this effect is probably based on the activation of the apical ATP/UTP/P2Y2 receptor system (at the connecting tubule/collecting duct level), leading to increased presentation of sodium, which, in turn, induces closure of the epithelial sodium channel (ENaC), with resultant decrease in sodium reabsorption (ie, enhanced natriuresis). Hence, the finding of significant edema in patients who are presumed to have aldosteronism suggests either that a wrong diagnosis has been made or that associated complications, such as renal or cardiac failure, are present.
Rossi GP, Ragazzo F, Seccia TM, Maniero C, Barisa M, Calò LA, et al. Hyperparathyroidism can be useful in the identification of primary aldosteronism due to aldosterone-producing adenoma. Hypertension. 2012 Aug. 60(2):431-6. [Medline].
Dluhy RG, Lifton RP. Glucocorticoid-remediable aldosteronism. Endocrinol Metab Clin North Am. 1994 Jun. 23(2):285-97. [Medline].
Funder JW. The genetic basis of primary aldosteronism. Curr Hypertens Rep. 2012 Apr. 14(2):120-4. [Medline].
Young DB. Quantitative analysis of aldosterone's role in potassium regulation. Am J Physiol. 1988 Nov. 255(5 Pt 2):F811-22. [Medline].
Stowasser M, Klemm SA, Tunny TJ, et al. Plasma aldosterone response to ACTH in subtypes of primary aldosteronism. Clin Exp Pharmacol Physiol. 1995 Jun-Jul. 22(6-7):460-2. [Medline].
Litchfield WR, New MI, Coolidge C, et al. Evaluation of the dexamethasone suppression test for the diagnosis of glucocorticoid-remediable aldosteronism. J Clin Endocrinol Metab. 1997 Nov. 82(11):3570-3. [Medline]. [Full Text].
Mulatero P, Stowasser M, Loh KC, Fardella CE, Gordon RD, Mosso L, et al. Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents. J Clin Endocrinol Metab. 2004 Mar. 89(3):1045-50. [Medline].
Born-Frontsberg E, Reincke M, Rump LC, et al. Cardiovascular and cerebrovascular comorbidities of hypokalemic and normokalemic primary aldosteronism: results of the German Conn's Registry. J Clin Endocrinol Metab. 2009 Apr. 94(4):1125-30. [Medline].
Bernini G, Galetta F, Franzoni F, Bardini M, Taurino C, Bernardini M, et al. Arterial stiffness, intima-media thickness and carotid artery fibrosis in patients with primary aldosteronism. J Hypertens. 2008 Dec. 26(12):2399-405. [Medline].
Apostolopoulou K, Künzel HE, Gerum S, Merkle K, Schulz S, Fischer E, et al. Gender differences in anxiety and depressive symptoms in patients with primary hyperaldosteronism: A cross-sectional study. World J Biol Psychiatry. 2012 May 8. [Medline].
Cruz DN, Perazella MA. Hypertension and hypokalemia: unusual syndromes. Conn Med. 1997 Feb. 61(2):67-75. [Medline].
Cesari M, Letizia C, Angeli P, Sciomer S, Rosi S, Rossi GP. Cardiac Remodeling in Patients With Primary and Secondary Aldosteronism: A Tissue Doppler Study. Circ Cardiovasc Imaging. 2016 Jun. 9 (6):[Medline].
Hall JE, Granger JP, Smith MJ Jr. Role of renal hemodynamics and arterial pressure in aldosterone "escape". Hypertension. 1984. 6:1183.
Yokota N, Bruneau BG, Kuroski de Bold ML, et al. Atrial natriuretic factor significantly contributes to the mineralocorticoid escape phenomenon. Evidence for a guanylate cyclase-mediated pathway. J Clin Invest. 1994 Nov. 94(5):1938-46. [Medline]. [Full Text].
Schiffrin EL, Chrétien M, Seidah NG, et al. Response of human aldosteronoma cells in culture to the N-terminal glycopeptide of pro-opiomelanocortin and gamma 3-MSH. Horm Metab Res. 1983 Apr. 15(4):181-4. [Medline].
[Guideline] Funder JW, Carey RM, Fardella C, Gomez-Sanchez CE, Mantero F, Stowasser M, et al. Case detection, diagnosis, and treatment of patients with primary aldosteronism: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2008 Sep. 93(9):3266-81. [Medline].
Quamme GA. Control of magnesium transport in the thick ascending limb. Am J Physiol. 1989 Feb. 256(2 Pt 2):F197-210. [Medline].
Seiler L, Rump LC, Schulte-Mönting J, Slawik M, Borm K, Pavenstädt H, et al. Diagnosis of primary aldosteronism: value of different screening parameters and influence of antihypertensive medication. Eur J Endocrinol. 2004 Mar. 150(3):329-37. [Medline].
Tzanela M, Effremidis G, Vassiliadi D, et al. The aldosterone to renin ratio in the evaluation of patients with incidentally detected adrenal masses. Endocrine. 2007 Oct. 32(2):136-42. [Medline].
Diederich S, Mai K, Bahr V, et al. The simultaneous measurement of plasma-aldosterone- and -renin-concentration allows rapid classification of all disorders of the renin-aldosterone system. Exp Clin Endocrinol Diabetes. 2007 Jul. 115(7):433-8. [Medline].
Wu VC, Chang HW, Liu KL, et al. Primary aldosteronism: diagnostic accuracy of the losartan and captopril tests. Am J Hypertens. 2009 Aug. 22(8):821-7. [Medline].
Burton TJ, Mackenzie IS, Balan K, Koo B, Bird N, Soloviev DV, et al. Evaluation of the sensitivity and specificity of (11)C-metomidate positron emission tomography (PET)-CT for lateralizing aldosterone secretion by Conn's adenomas. J Clin Endocrinol Metab. 2012 Jan. 97(1):100-9. [Medline].
Otsuka F, Otsuka-Misunaga F, Koyama S, et al. Hormonal characteristics of primary aldosteronism due to unilateral adrenal hyperplasia. J Endocrinol Invest. 1998 Sep. 21(8):531-6. [Medline].
Stowasser M, Bachmann AW, Tunny TJ. Production of 18-oxo-cortisol in subtypes of primary aldosteronism. Clin Exp Pharmacol Physiol. 1996 Jun-Jul. 23(6-7):591-3. [Medline].
Hamlet SM, Gordon RD, Gomez-Sanchez CE, et al. Adrenal transitional zone steroids, 18-oxo and 18-hydroxycortisol, useful in the diagnosis of primary aldosteronism, are ACTH-dependent. Clin Exp Pharmacol Physiol. 1988 Apr. 15(4):317-22. [Medline].
McAlister FA, Lewanczuk RZ. Primary hyperaldosteronism and adrenal incidentaloma: an argument for physiologic testing before adrenalectomy. Can J Surg. 1998 Aug. 41(4):299-305. [Medline].
Georgiades CS, Hong K, Geschwind JF, et al. Adjunctive use of C-arm CT may eliminate technical failure in adrenal vein sampling. J Vasc Interv Radiol. 2007 Sep. 18(9):1102-5. [Medline].
Young WF, Stanson AW, Grant CS, et al. Primary aldosteronism: adrenal venous sampling. Surgery. 1996 Dec. 120(6):913-9; discussion 919-20. [Medline].
Webb R, Mathur A, Chang R, Baid S, Nilubol N, Libutti SK, et al. What is the Best Criterion for the Interpretation of Adrenal Vein Sample Results in Patients with Primary Hyperaldosteronism?. Ann Surg Oncol. 2011 Nov 3. [Medline].
Young WF, Stanson AW, Thompson GB, et al. Role for adrenal venous sampling in primary aldosteronism. Surgery. 2004 Dec. 136(6):1227-35. [Medline].
Naruse M, Naruse K, Yoshimoto T, et al. Dopaminergic regulation of aldosterone secretion: its pathophysiologic significance in subsets of primary aldosteronism. Hypertens Res. 1995 Jun. 18 Suppl 1:S59-64. [Medline].
Carey RM. Primary aldosteronism. Horm Res. 2009 Jan. 71 Suppl 1:8-12. [Medline].
Hood SJ, Taylor KP, Ashby MJ, et al. The spironolactone, amiloride, losartan, and thiazide (SALT) double-blind crossover trial in patients with low-renin hypertension and elevated aldosterone-renin ratio. Circulation. 2007 Jul 17. 116(3):268-75. [Medline]. [Full Text].
Ronconi V, Turchi F, Appolloni G, di Tizio V, Boscaro M, Giacchetti G. Aldosterone, Mineralocorticoid Receptor and the Metabolic Syndrome: Role of the Mineralocorticoid Receptor Antagonists. Curr Vasc Pharmacol. 2011 Oct 21. [Medline].
Minowada S, Fujimura T, Takahashi N, et al. Computed tomography-guided percutaneous acetic acid injection therapy for functioning adrenocortical adenoma. J Clin Endocrinol Metab. 2003 Dec. 88(12):5814-7. [Medline]. [Full Text].
Sukor N, Gordon RD, Ku YK, et al. Role of unilateral adrenalectomy in bilateral primary aldosteronism: a 22-year single center experience. J Clin Endocrinol Metab. 2009 Jul. 94(7):2437-45. [Medline].
Celen O, O'Brien MJ, Melby JC, et al. Factors influencing outcome of surgery for primary aldosteronism. Arch Surg. 1996 Jun. 131(6):646-50. [Medline].
Waldmann J, Maurer L, Holler J, Kann PH, Ramaswamy A, Bartsch DK, et al. Outcome of surgery for primary hyperaldosteronism. World J Surg. 2011 Nov. 35(11):2422-7. [Medline].
Letavernier E, Peyrard S, Amar L, et al. Blood pressure outcome of adrenalectomy in patients with primary hyperaldosteronism with or without unilateral adenoma. J Hypertens. 2008 Sep. 26(9):1816-23. [Medline].
Milsom SR, Espiner EA, Nicholls MG, et al. The blood pressure response to unilateral adrenalectomy in primary aldosteronism. Q J Med. 1986 Dec. 61(236):1141-51. [Medline].
Giacchetti G, Turchi F, Boscaro M, Ronconi V. Management of primary aldosteronism: its complications and their outcomes after treatment. Curr Vasc Pharmacol. 2009 Apr. 7(2):244-49. [Medline].
Baguet JP, Steichen O, Mounier-Vehier C, Gosse P. SFE/SFHTA/AFCE consensus on primary aldosteronism, part 1: Epidemiology of PA, who should be screened for sporadic PA?. Ann Endocrinol (Paris). 2016 Apr 15. 86 (20):1002-8. [Medline]. [Full Text].
Steichen O, Amar L, Chaffanjon P, Kraimps JL, Menegaux F, Zinzindohoue F. SFE/SFHTA/AFCE consensus on primary aldosteronism, part 6: Adrenal surgery. Ann Endocrinol (Paris). 2016 Jun 10. [Medline]. [Full Text].
Pechère-Bertschi A, Herpin D, Lefebvre H. SFE/SFHTA/AFCE consensus on primary aldosteronism, part 7: Medical treatment of primary aldosteronism. Ann Endocrinol (Paris). 2016 Jun 14. [Medline]. [Full Text].