Introduction
Background
Conn syndrome is characterized by increased aldosterone secretion from the adrenal glands, suppressed plasma renin activity (PRA), hypertension, and hypokalemia. It was first described in 1955 by J. W. Conn in a patient who had an aldosterone-producing adenoma (ie, Conn syndrome), as shown in the image below and in Image 1. Later, many other cases of adrenal hyperplasia with increased aldosterone secretion were described, and now the term primary hyperaldosteronism is used to describe Conn syndrome and other etiologies of primary hypersecretion of aldosterone (eg, adrenal hyperplasia). Currently, primary hyperaldosteronism, especially Conn syndrome, seems to be the most common form of secondary hypertension.
Magnetic resonance imaging (MRI) scan in a patient with Conn syndrome showing a left adrenal adenoma.
Pathophysiology
Primary hyperaldosteronism is caused by increased aldosterone excretion from the adrenals, which results primarily from 2 major subtypes: (1) unilateral aldosterone-producing adenoma (APA) or Conn syndrome (50-60% of cases) and (2) idiopathic hyperaldosteronism (IHA) or bilateral adrenal hyperplasia (40-50% of cases).
A rare subtype is renin-responsive adenoma, which morphologically and in response to adrenalectomy appears as APA, but it responds to physiologic maneuvers, as do hyperplastic glands of IHA. Another rare subtype is primary adrenal hyperplasia, in which a hyperplastic adrenal morphologically resembles that in IHA but mimics the APA response to physiologic maneuvers and unilateral adrenalectomy. The last rare subtype is glucocorticoid-remediable aldosteronism (GRA), which is autosomal dominant in inheritance and is associated with variable degrees of hyperaldosteronism that are suppressible with exogenous glucocorticoids. Rarely, aldosterone can be secreted by adrenocortical carcinomas and ovarian tumors.
Frequency
United States
Prevalence estimates for primary hyperaldosteronism, specifically Conn syndrome, are, respectively, 0.05-2% and 0.03-1.2% of the population with hypertension.
Mortality/Morbidity
The morbidity and mortality associated with primary hyperaldosteronism, especially Conn syndrome, are primarily related to hypertension and hypokalemia.1,2
- Hypertension, especially if left untreated for many years, can lead to many complications, including heart disease (eg, coronary artery disease, congestive heart failure), stroke, and intracerebral hemorrhage (with very high blood pressure).
- Hypokalemia, especially if severe, causes cardiac arrhythmias, which can be fatal.
Sex
Primary hyperaldosteronism is twice as common in women as in men.
Age
Peak incidence occurs in the third to sixth decades of life.
Clinical
History
- Few symptoms are specific, and mostly they result from hypokalemia and alkalosis. Aldosterone, by inducing renal distal tubular reabsorption of sodium, enhances secretion of potassium and hydrogen ions, causing hypernatremia, hypokalemia, and alkalosis.
- 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.
- As mentioned previously, long-standing hypertension may lead to cardiac and neurologic problems, with all the associated symptoms.
Physical
No specific physical findings are evident.
- Patients with congestive heart failure, stroke, or cerebral hemorrhage from hypertension have physical examination findings related to these conditions.
Causes
Primary aldosteronism can be divided into many subtypes.
- The most common subtype is Conn syndrome, an APA that is usually small (<3 cm), unilateral, and renin-unresponsive. This means that aldosterone secretion is not affected by changes in posture. Rarely, the adenoma is renin-responsive (ie, aldosterone levels increase with standing). Conn syndrome occurs in 50-60% of cases.
- The remaining 40-50% of cases are due to bilateral adrenal hyperplasia or IHA, in which aldosterone increases in response to postural studies. Rarely, patients are hyperplastic (ie, primary adrenal hyperplasia), and the response of aldosterone to standing is similar to renin-unresponsive APA.
- Rarely, adrenocortical carcinomas secrete aldosterone. Usually, the tumors are large (>4 cm).
- Aldosterone can be ectopically secreted by adrenal embryologic rest neoplasms within the kidney and ovary.
- Primary hyperaldosteronism can be inherited in an autosomal dominant fashion in patients with GRA, in whom activation of aldosterone secretion is induced by corticotropin and is suppressible with glucocorticoids. The involved gene is on chromosome 8.
More on Conn Syndrome |
 Overview: Conn Syndrome |
| Differential Diagnoses & Workup: Conn Syndrome |
| Treatment & Medication: Conn Syndrome |
| Follow-up: Conn Syndrome |
| Multimedia: Conn Syndrome |
| References |
| Further Reading |
| Next Page » |
References
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. Apr 2009;94(4):1125-30. [Medline].
Bernini G, Galetta F, Franzoni F, et al. Arterial stiffness, intima-media thickness and carotid artery fibrosis in patients with primary aldosteronism. J Hypertens. Dec 2008;26(12):2399-405. [Medline].
Bravo EL. Primary aldosteronism: new approaches to diagnosis and management. Cleve Clin J Med. Sep-Oct 1993;60(5):379-86. [Medline].
Funder JW, Carey RM, Fardella C, et al. Case detection, diagnosis, and treatment of patients with primary aldosteronism: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. Sep 2008;93(9):3266-81. [Medline].
Doppman JL, Gill JR Jr. Hyperaldosteronism: sampling the adrenal veins. Radiology. Feb 1996;198(2):309-12. [Medline].
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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. Sep 2008;26(9):1816-23. [Medline].
Al Fehaily M, Duh QY. Clinical manifestation of aldosteronoma. Surg Clin North Am. Jun 2004;84(3):887-905. [Medline].
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Gill JR. Primary aldosteronism: Strategies for diagnosis and treatment. The Endocrinologist. 1991;1:365-9.
Hirohara D, Nomura K, Okamoto T, et al. Performance of the basal aldosterone to renin ratio and of the renin stimulation test by furosemide and upright posture in screening for aldosterone-producing adenoma in low renin hypertensives. J Clin Endocrinol Metab. Sep 2001;86(9):4292-8. [Medline].
Jabbour SA, De Papp AE. Pitfalls in the diagnosis and management of primary hyperaldosteronism. The Endocrinologist. 1999;9:395-8.
Montori VM, Schwartz GL, Chapman AB, et al. Validity of the aldosterone-renin ratio used to screen for primary aldosteronism. Mayo Clin Proc. Sep 2001;76(9):877-82. [Medline].
Mulatero P, Stowasser M, Loh KC, Fardella CE, Gordon RD, Mosso L. Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents. J Clin Endocrinol Metab. Mar 2004;89(3):1045-50. [Medline].
Rose BD, Kaplan NM. Approach to the patient with hypertension and hypokalemia. UpToDate [CD-ROM and online]. 1997;1-8.
Seiler L, Rump LC, Schulte-Monting J, et al. Diagnosis of primary aldosteronism: value of different screening parameters and influence of antihypertensive medication. Eur J Endocrinol. Mar 2004;150(3):329-37. [Medline].
Vallotton MB. Primary aldosteronism. Endocrine Investigation. 1996;45:47-60.
Weinberger MH, Fineberg NS. The diagnosis of primary aldosteronism and separation of two major subtypes. Arch Intern Med. Sep 27 1993;153(18):2125-9. [Medline].
Young WF Jr. Clinical practice. The incidentally discovered adrenal mass. N Engl J Med. Feb 8 2007;356(6):601-10.
Young WF Jr. Pheochromocytoma and primary aldosteronism: diagnostic approaches. Endocrinol Metab Clin North Am. Dec 1997;26(4):801-27. [Medline].
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Further Reading
Related eMedicine topics:
Adrenal Adenoma [Endocrinology]
Adrenal Adenoma [Radiology]
Adrenal Glands
Adrenal Surgery
Hyperaldosteronism [Pediatrics: General Medicine]
Hyperaldosteronism [Radiology]
Hyperaldosteronism, Primary
Hypertensive Heart Disease
Hypokalemia [Emergency Medicine]
Hypokalemia [Nephrology]
Hypokalemia [Pediatrics: Cardiac Disease and Critical Care Medicine]
Clinical guidelines:
Case detection, diagnosis, and treatment of patients with primary aldosteronism: an Endocrine Society clinical practice guideline. The Endocrine Society - Disease Specific Society. 2008 Sep. 26 pages. NGC:006766
Clinical trials:
Diagnostic Properties of Aldosterone-Renin Ratio in Primary Aldosteronism Among Hypertensives.
Kallikrein-Kinin (KKS) and Renin-Angiotensin-Aldosterone System (RAAS) in Primary Aldosteronism
Metabolic Syndrome and Insulin Resistance in Primary Aldosteronism
Proof-of-Concept for the Aldosterone Synthase Inhibitor LCI699 in Patients With Primary Hyperaldosteronism
The Therapeutic Effect of Bromocriptin in Patients With Primary Aldosteronism
Keywords
Conn syndrome, Conn's syndrome, adrenal, adrenal gland, adrenal glands, hyperaldosteronism, aldosteronism, adenoma, spironolactone, renin, primary hyperaldosteronism, adrenalectomy, hypertension, hypokalemia, adrenal hyperplasia, unilateral aldosterone-producing adenoma, bilateral adrenal hyperplasia, idiopathic hyperaldosteronism, increased aldosterone secretion, primary hypersecretion of aldosterone, secondary hypertension, renin-responsive adenoma, primary adrenal hyperplasia, glucocorticoid-remediable aldosteronism
