Conn's syndrome

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Main article: Primary aldosteronism
Conn syndrome
Classification and external resources
ICD-10 E26.0
ICD-9 255.12
DiseasesDB 3073
MeSH D006929

Conn syndrome is an aldosterone-producing adenoma. 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]


Primary hyperaldosteronism has many causes, including adrenal hyperplasia and adrenal carcinoma.[2]

The syndrome is due to:


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, acidifying urine and alkalizing extracellular fluid causing a metabolic alkalosis.

Finer notes on aldosterone include the fact that it stimulates sodium-potassium ATPase in muscle cells, increasing intracellular potassium and also increases sodium reabsoption 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 high pH of the blood (few H+ ions in solution) results in a metabolic alkalosis and makes calcium less available to the tissues and causes symptoms of hypocalcemia (low calcium levels), but the total calcium levels remain normal; the decrease in calcium is only of the free fraction. This is because in an alkalotic (high pH, low H+) environment, H+ ions leave albumin to in an attempt to buffer the blood raising its H+ content and so lower its pH back to normal. The loss of H+ ions from Albumin and into the plasma leaves more sites for calcium to bind onto albumin, and it does, decreasing the free calcium (that not bound to albumin) fraction while increasing the bound calcium fraction. This leaves the total calcium (bound fraction and free fraction) within normal limits, and therefore signs and symptoms of hypocalcemia, Chvostek sign and Trousseau sign of latent tetany are present even though the plasma calcium is within normal limits.

The sodium retention leads to plasma volume expansion and elevated blood pressure. The increased blood pressure will lead to an increased glomerular filtration rate and cause a decrease in renin release from the granular cells of the juxtaglomerular apparatus in the kidney. If a patient is thought to suffer from primary hyperaldosteronism, the aldosterone:renin activity ratio is used to assess this. The decreased renin levels and in turn the reactive down-regulation of angiotensin II are thought to be unable to down-regulate the constitutively formed aldosterone, thus leading to an elevated [plasma aldosterone:plasma renin activity] ratio (lending the assay to be a clinical tool for diagnostic purposes).

Aside from hypertension, other manifesting problems include myalgias, weakness, and chronic headaches. The muscle cramps are due to neuron hyperexcitability seen in the setting of hypocalcemia, muscle weakness secondary to hypoexcitability of skeletal muscles in the setting of low blood potassium (hypokalemia), and headaches which are thought to be due to both electrolyte imbalance (hypokalemia) and hypertension.

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. The screening test of choice for diagnosis is the plasma aldosterone:plasma renin activity ratio. Renin activity, not simply plasma renin level, is assayed. Both aldosterone and renin are measured, and a ratio greater than 30 is indicative of primary hyperaldosteronism.[4][5]

Differential diagnosis[edit]

Hyperaldosteronism can be mimicked by Liddle syndrome, and by ingestion of liquorice and other foods containing glycyrrhizin. In one case report, hypertension and quadriparesis resulted from intoxication with a nonalcoholic pastis (an anise-flavored aperitif containing glycyrrhizinic acid).[6]


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. In males, one common side effect of spironolactone drug therapy is gynecomastia. Gynecomastia usually does not occur with eplerenone drug therapy. Additionally, a 2008 study conducted in Germany and Argentina proves that the endocannabinoid receptors regulate aldosterone at the level of the adrenal.[7] Anandamide inhibited 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, aldosterone would be lowered by this therapy, according to the conclusions presented in this study.


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.[8]

See also[edit]


  1. ^ Conn JW, Louis LH (1955). "Primary aldosteronism: a new clinical entity". Trans. Assoc. Am. Physicians 68: 215–31; discussion, 231–3. PMID 13299331. 
  2. ^[full citation needed]
  3. ^ Longo, Dan L et al (2012). Harrison's Principals of Internal Medicine, Vol. 2. New York: McGraw-Hill. p. 2949. ISBN 978-0-07-174887-2.
  4. ^ Tiu S, Choi C, Shek C, Ng Y, Chan F, Ng C, Kong A (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. 
  5. ^ United Bristol Healthcare NHS Trust, the major teaching trust in South West England
  6. ^ Trono D, Cereda JM, Favre L (August 1983). "Pseudo-syndrome de Conn par intoxication au pastis sans alcool" [Pseudo-Conn's syndrome due to intoxication with nonalcoholic pastis]. Schweiz Med Wochenschr (in French) 113 (31–32): 1092–5. PMID 6623028. 
  7. ^ Ziegler, C. G.; Mohn, C.; Lamounier-Zepter, V.; Rettori, V.; Bornstein, S. R.; Krug, A. W.; Ehrhart-Bornstein, M. (2009). "Expression and Function of Endocannabinoid Receptors in the Human Adrenal Cortex". Hormone and Metabolic Research 42 (2): 88–92. doi:10.1055/s-0029-1241860. PMID 19862666. 
  8. ^ Columbia Adrenal Center, Hyperaldosteronism (Conn's Syndrome)