Primary aldosteronism

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Primary hyperaldosteronism
Classification and external resources
ICD-10 E26.0
ICD-9 255.1
DiseasesDB 3073
MedlinePlus 000330
eMedicine med/432
MeSH D006929

Primary aldosteronism, also known as primary hyperaldosteronism, is characterized by the overproduction of the mineralocorticoid hormone aldosterone by the adrenal glands,[1] when not a result of excessive renin secretion. Aldosterone causes increase in sodium and water retention and potassium excretion in the kidneys, leading to arterial hypertension (high blood pressure). An increase in the production of mineralocorticoid from the adrenal gland is evident. It is amongst the most common causes of secondary hypertension,[2] renal disease being the most common.

Primary hyperaldosteronism has many causes, including adrenal hyperplasia and adrenal carcinoma.[3] When it occurs due to a solitary aldosterone-secreting adrenal adenoma (a type of benign tumor), it is known as Conn's syndrome.[4] In practice, however, the terms are often used interchangeably, regardless of the underlying physiology.


The syndrome is due to:[5]

  • Adrenal (Conn’s) adenoma (Conn's Syndrome) (66%)
  • Bilateral idiopathic (micronodular) adrenal hyperplasia (30%)
  • Primary (unilateral) adrenal hyperplasia—2% of cases
  • Aldosterone-producing adrenocortical carcinoma—<1% of cases
  • Familial Hyperaldosteronism (FH)
  • Glucocorticoid-remediable aldosteronism (FH type I)—<1% of cases
  • FH type II (APA or IHA)—<2% of cases
  • Ectopic aldosterone-producing adenoma or carcinoma—< 0.1% of cases

One recent study indicates that the prevalence of aldosteronism due to bilateral idiopathic adrenal hyperplasia (IAH) may be higher than had previously been believed, existing to some degree for as many as 75% of aldosteronism cases.[6] If true, this means that bilateral adrenal hyperplasias may actually be present to some degree for about 60% of cases, with single-sided adrenal adenomas dropping to only 40% of cases. The claims of this one study remain to be replicated, however, by other researchers.


40% of patients with an adrenal aldosterone producing adenoma have somatic gain-of-function mutations in a single gene (KCNJ5).[7] This gene is mutated in inherited cases albeit less frequently. These mutations tend to occur in young women with the adenoma in the cortisol secreting zona fasciculata. Adenomas without this mutation tend to occur in older men with resistant hypertension.

Signs, symptoms and findings[edit]

Aldosterone has effects on most or all cells of the body but, clinically, the most important actions are on cells of the late distal tubule and medullary collecting duct. In the principal cells aldosterone increases activity of basolateral membrane sodium-potassium ATPase and apical epithelial sodium channels, ENaC, as well as potassium channels, ROMK. These actions increase sodium reabsorption and potassium secretion. Since more sodium is reabsorbed than potassium secreted, it also makes the lumen more electrically negative, causing chloride to follow sodium. Water then follows sodium and chloride by osmosis. In Conn syndrome these actions cause increased extracellular sodium and fluid volume and reduced extracellular potassium. Aldosterone also acts on intercalated cells to stimulate an apical proton ATPase, causing proton secretion that acidifies urine and alkalizes extracellular fluid.

Finer notes on aldosterone include the fact that it stimulates sodium-potassium ATPase in muscle cells, increasing intracellular potassium and also increases sodium reabsorption all along the intestine and nephron, possibly due to widespread stimulation of sodium-potassium ATPase. Finally, epithelial cells of sweat gland ducts and distal colon surface respond exactly the same as the principal cells of the nephron. These responses are important in climate adaptation and as a cause of constipation with elevated aldosterone.

The sodium retention leads to plasma volume expansion and elevated blood pressure. The increased blood pressure will lead to increased glomerular filtration rate and cause a decrease in renin release from the granular cells of the juxtaglomerular apparatus in the kidney. If there is a primary hyperaldosteronism the decreased renin (and subsequent decreased angiotensin II) will not lead to a decrease in aldosterone levels (a very helpful clinical tool in diagnosis of primary hyperaldosteronism).

Aside from high blood pressure, manifestations of muscle cramps (due to hyperexcitability of neurons secondary to hypocalcemia), muscle weakness (due to hypoexcitability of skeletal muscles secondary to hypokalemia), and headaches (due to hypokalemia or high blood pressure) may be seen.

Secondary hyperaldosteronism is often related to decreased cardiac output which is associated with elevated renin levels.


Measuring aldosterone alone is not considered adequate to diagnose primary hyperaldosteronism. Rather, both renin and aldosterone are measured, and a resultant aldosterone-to-renin ratio is used for case detection.[8][9] A high aldosterone-to-renin ratio suggests the presence of primary hyperaldosteronism. The diagnosis is made by performing a saline suppression test, ambulatory salt loading test, or fludrocortisone suppression test.[10]

If primary hyperaldosteronism is confirmed biochemically, CT scanning or other cross-sectional imaging can confirm the presence of an adrenal abnormality, possibly an adrenal cortical adenoma (aldosteronoma), adrenal carcinoma, bilateral adrenal hyperplasia, or other less common changes. Imaging findings may ultimately lead to other necessary diagnostic studies, such as adrenal venous sampling, to clarify the etiology. It is not uncommon for adults to have bilateral sources of aldosterone hypersecretion in the presence of a nonfunctioning adrenal cortical adenoma, making adrenal venous sampling mandatory in cases where surgery is being considered.[11]

The diagnosis is best accomplished by an appropriately-trained subspecialist, though primary care providers are critical in recognizing clinical features of primary aldosteronism and obtaining the first blood tests for case detection.

Primary hyperaldosteronism can be mimicked by Liddle syndrome, and by ingestion of licorice and other foods containing glycyrrhizin. In one case report, hypertension and quadriparesis resulted from intoxication with a non-alcoholic pastis (an anise-flavored aperitif containing glycyrrhizinic acid).[12]


The treatment for hyperaldosteronism depends on the underlying cause. In patients with a single benign tumor (adenoma), surgical removal (adrenalectomy) may be curative. This is usually performed laparoscopically, through several very small incisions. For patients with hyperplasia of both glands, successful treatment is often achieved with spironolactone or eplerenone, drugs that block the effect of aldosterone. With its antiandrogen effect, spironolactone drug therapy may have a range of effects in males, including sometimes gynecomastia. These symptoms usually do not occur with eplerenone drug therapy.[13]

A 2008 study conducted in Germany and Argentina proves that the endocannabinoid receptors regulate aldosterone at the level of the adrenal.[14] Anandamide inhibited both basal release and stimulated release of the adrenocortical steroids corticosterone and aldosterone. Since cannabinoid receptors are affected by the active ingredient in marijuana, THC, the same way as anandamide,[15] this therapy could prove useful to those who cannot tolerate the side effects of spironolactone or eplerenone, and do not respond to surgery.

In the absence of proper treatment, individuals with hyperaldosteronism often suffer from poorly controlled high blood pressure, which may be associated with increased rates of stroke, heart disease, and kidney failure. With appropriate treatment, the prognosis is excellent.[16]


Conn's syndrome is named after Jerome W. Conn (1907–1994), the American endocrinologist who first described the condition at the University of Michigan in 1955.[1]


  1. ^ a b Conn JW, Louis LH; Louis (1955). "Primary aldosteronism: a new clinical entity". Trans. Assoc. Am. Physicians 68: 215–31; discussion, 231–3. PMID 13299331. 
  2. ^ [1][dead link]
  3. ^
  4. ^ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease. St. Louis, Mo: Elsevier Saunders. p. 1210. ISBN 0-7216-0187-1. 
  5. ^ Williams textbook of endocrinology. (11th ed.). Philadelphia: Saunders/Elsevier. 2008. ISBN 978-1-4160-2911-3.  |first1= missing |last1= in Authors list (help)
  6. ^ [2][dead link]
  7. ^ Brown, MJ (Sep 30, 2012). "Platt versus Pickering: what molecular insight to primary hyperaldosteronism tells us about hypertension". JRSM cardiovascular disease 1 (6): cvd.2012.012020. doi:10.1258/cvd.2012.012020. PMC 3738367. PMID 24175075. 
  8. ^ Tiu S, Choi C, Shek C, Ng Y, Chan F, Ng C, Kong A; Choi; Shek; Ng; Chan; Ng; Kong (2005). "The use of aldosterone-renin ratio as a diagnostic test for primary hyperaldosteronism and its test characteristics under different conditions of blood sampling". J Clin Endocrinol Metab 90 (1): 72–8. doi:10.1210/jc.2004-1149. PMID 15483077. 
  9. ^ United Bristol Healthcare NHS Trust, the major teaching trust in South West England
  10. ^ "Case Detection, Diagnosis, and Treatment of Patients with Primary Aldosteronism". Retrieved 5 December 2014. 
  11. ^ "Case Detection, Diagnosis, and Treatment of Patients with Primary Aldosteronism". Retrieved 5 December 2014. 
  12. ^ Trono D, Cereda JM, Favre L (August 1983). "[Pseudo-Conn's syndrome due to intoxication with nonalcoholic pastis]". Schweiz Med Wochenschr (in French) 113 (31–32): 1092–5. PMID 6623028. 
  13. ^
  14. ^ Expression and Function of Endocannabinoid Receptors in the Human Adrenal Cortex
  15. ^ Anandamide
  16. ^ Columbia Adrenal Center, Hyperaldosteronism (Conn's Syndrome)