Conns Syndrome
Encyclopedia
Conn's syndrome is an Aldosterone-Producing Adenoma (APA). 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.
has many causes, including adrenal hyperplasia
and adrenal carcinoma
.
The syndrome is due to:
and hypokalemia
. Once the potassium has been significantly reduced by aldosterone, a sodium/hydrogen pump in the nephron
becomes more active leading to increased excretion of hydrogen ions and further exacerbating the hypernatremia
. The hydrogen ions that are exchanged for sodium are generated by carbonic anhydrase
in the renal tubule epithelium causing increased production of bicarbonate
. The increased bicarbonate and the excreted hydrogen combine to generate a metabolic alkalosis
.
The high pH
of the blood makes calcium
less available to the tissues and causes symptoms of hypocalcemia (low calcium levels).
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 a patient is thought to suffer from primary hyperaldosteronism, the Aldo:renin activity ratio is used to assess this. The thought behind this is that decreased renin levels and in turn the reactive down-regulation of angiotensin II are unable to down-regulate the constitutively formed aldosterone, thus leading to an elevated [plasma Aldo: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
being due to neuron hyperexcitability seen in the setting of hypocalcemia, muscle weakness
secondary to hypoexcitability of skeletal muscles in the setting of hypokalemia, and headache
s which are thought to be due to both electrolyte imbalance (hypokalemia) and HTN.
Secondary hyperaldosteronism is often related to decreased cardiac output
which is associated with elevated renin levels.
and aldosterone are measured and a ratio of >30 is indicative of primary hyperaldosteronism.
. In one case report, hypertension and quadriparesis resulted from intoxication with a non-alcoholic pastis
(an anise
-flavored aperitif
containing glycyrrhizinic acid).
or eplerenone
, drugs that block the effect of aldosterone. In males, one common side effect of spironolactone drug therapy sometimes seen is gynecomastia
. Gynecomastia usually does not occur with eplerenone drug therapy.
Jerome W. Conn
Jerome W. Conn was an American endocrinologist best known for his description of Conn syndrome or primary hyperaldosteronism.-Biography:...
(1907–1994), the American
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
endocrinologist who first described the condition at the University of Michigan in 1955.
Causes
Primary hyperaldosteronismHyperaldosteronism
Hyperaldosteronism, also aldosteronism, is a medical condition where too much aldosterone is produced by the adrenal glands, which can lead to lowered levels of potassium in the blood.-Types:...
has many causes, including adrenal hyperplasia
Hyperplasia
Hyperplasia means increase in number of cells/proliferation of cells. It may result in the gross enlargement of an organ and the term is sometimes mixed with benign neoplasia/ benign tumor....
and adrenal carcinoma
Carcinoma
Carcinoma is the medical term for the most common type of cancer occurring in humans. Put simply, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that generally arises from cells originating in the endodermal or ectodermal germ layer during...
.
The syndrome is due to:
- bilateral idiopathic adrenal hyperplasia 70 %
- unilateral idiopathic adrenal hyperplasia 20 %
- aldosteroneAldosteroneAldosterone is a hormone that increases the reabsorption of sodium ions and water and the release of potassium in the collecting ducts and distal convoluted tubule of the kidneys' functional unit, the nephron. This increases blood volume and, therefore, increases blood pressure. Drugs that...
-secreting adrenal adenomaAdrenal adenomaA adrenal adenoma is a benign tumor of the glandular type in the adrenal gland. While some adrenal adenomas do not secrete hormones at all , some secrete cortisol , aldosterone , or androgens ....
(benign tumor, < 5%) - rare forms, including disorders of the renin-angiotensin systemRenin-angiotensin systemThe renin-angiotensin system or the renin-angiotensin-aldosterone system is a hormone system that regulates blood pressure and water balance....
Pathogenesis
Aldosterone enhances exchange of sodium for potassium in the kidney so increased aldosteronism will lead to hypernatremiaHypernatremia
Hypernatremia or hypernatraemia is an electrolyte disturbance that is defined by an elevated sodium level in the blood. Hypernatremia is generally not caused by an excess of sodium, but rather by a relative deficit of free water in the body...
and hypokalemia
Hypokalemia
Hypokalemia or hypokalaemia , also hypopotassemia or hypopotassaemia , refers to the condition in which the concentration of potassium in the blood is low...
. Once the potassium has been significantly reduced by aldosterone, a sodium/hydrogen pump in the nephron
Nephron
The renal tubule is the portion of the nephron containing the tubular fluid filtered through the glomerulus. After passing through the renal tubule, the filtrate continues to the collecting duct system, which is not part of the nephron....
becomes more active leading to increased excretion of hydrogen ions and further exacerbating the hypernatremia
Hypernatremia
Hypernatremia or hypernatraemia is an electrolyte disturbance that is defined by an elevated sodium level in the blood. Hypernatremia is generally not caused by an excess of sodium, but rather by a relative deficit of free water in the body...
. The hydrogen ions that are exchanged for sodium are generated by carbonic anhydrase
Carbonic anhydrase
The carbonic anhydrases form a family of enzymes that catalyze the rapid interconversion of carbon dioxide and water to bicarbonate and protons , a reversible reaction that occurs rather slowly in the absence of a catalyst...
in the renal tubule epithelium causing increased production of bicarbonate
Bicarbonate
In inorganic chemistry, bicarbonate is an intermediate form in the deprotonation of carbonic acid...
. The increased bicarbonate and the excreted hydrogen combine to generate a metabolic alkalosis
Metabolic alkalosis
Metabolic alkalosis is a metabolic condition in which the pH of tissue is elevated beyond the normal range . This is the result of decreased hydrogen ion concentration, leading to increased bicarbonate, or alternatively a direct result of increased bicarbonate concentrations.-Terminology:*Alkalosis...
.
The high pH
PH
In chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...
of the blood makes calcium
Calcium in biology
Calcium plays a pivotal role in the physiology and biochemistry of organisms and the cell. It plays an important role in signal transduction pathways, where it acts as a second messenger, in neurotransmitter release from neurons, contraction of all muscle cell types, and fertilization...
less available to the tissues and causes symptoms of hypocalcemia (low calcium levels).
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
Renin
Renin , also known as an angiotensinogenase, is an enzyme that participates in the body's renin-angiotensin system -- also known as the Renin-Angiotensin-Aldosterone Axis -- that mediates extracellular volume , and arterial vasoconstriction...
release from the granular cells of the juxtaglomerular apparatus
Juxtaglomerular apparatus
The juxtaglomerular apparatus is a microscopic structure in the kidney, which regulates the function of each nephron. The juxtaglomerular apparatus is named for its proximity to the glomerulus: it is found between the vascular pole of the renal corpuscle and the returning distal convoluted tubule...
in the kidney. If a patient is thought to suffer from primary hyperaldosteronism, the Aldo:renin activity ratio is used to assess this. The thought behind this is that decreased renin levels and in turn the reactive down-regulation of angiotensin II are unable to down-regulate the constitutively formed aldosterone, thus leading to an elevated [plasma Aldo: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
Myalgia
Myalgia means "muscle pain" and is a symptom of many diseases and disorders. The most common causes are the overuse or over-stretching of a muscle or group of muscles. Myalgia without a traumatic history is often due to viral infections...
being due to neuron hyperexcitability seen in the setting of hypocalcemia, muscle weakness
Muscle weakness
Muscle weakness or myasthenia is a lack of muscle strength. The causes are many and can be divided into conditions that have true or perceived muscle weakness...
secondary to hypoexcitability of skeletal muscles in the setting of hypokalemia, and headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
s which are thought to be due to both electrolyte imbalance (hypokalemia) and HTN.
Secondary hyperaldosteronism is often related to decreased cardiac output
Cardiac output
Cardiac output is the volume of blood being pumped by the heart, in particular by a left or right ventricle in the time interval of one minute. CO may be measured in many ways, for example dm3/min...
which is associated with elevated renin levels.
Diagnosis
Measuring aldosterone alone is not considered adequate to diagnose primary hyperaldosteronism. The screening test of choice for diagnosis is Plasma Aldosterone: Plasma renin activity ratio. Note that renin activity and NOT simply plasma renin is being assayed. Both reninRenin
Renin , also known as an angiotensinogenase, is an enzyme that participates in the body's renin-angiotensin system -- also known as the Renin-Angiotensin-Aldosterone Axis -- that mediates extracellular volume , and arterial vasoconstriction...
and aldosterone are measured and a ratio of >30 is indicative of primary hyperaldosteronism.
Dif. Diagnosis
Hyperaldosteronism can be mimicked by Liddle syndrome, and by ingestion of licorice and other foods containing glycyrrhizinGlycyrrhizin
Glycyrrhizin is the main sweet-tasting compound from liquorice root. It is 30–50 times as sweet as sucrose . Pure glycyrrhizin is odorless....
. In one case report, hypertension and quadriparesis resulted from intoxication with a non-alcoholic pastis
Pastis
Pastis is an anise-flavored liqueur and apéritif from France, typically containing 40–45% alcohol by volume, although alcohol-free varieties exist.-Origins:...
(an anise
Anise
Anise , Pimpinella anisum, also called aniseed, is a flowering plant in the family Apiaceae native to the eastern Mediterranean region and Southwest Asia. Its flavor resembles that of liquorice, fennel, and tarragon.- Biology :...
-flavored aperitif
Aperitif
Apéritifs and digestifs are alcoholic drinks that are normally served with meals.-Apéritifs:An apéritif is usually served before a meal to stimulate the appetite. This contrasts with digestifs, which are served after a meal for the purpose of aiding digestion...
containing glycyrrhizinic acid).
Therapy
In patients with a single benign tumor (adenoma), surgical removal (adrenalectomy) is curative. This is usually performed laparoscopically, through several very small incisions. For patients with hyperplasia of both glands, successful treatment is often achieved with spironolactoneSpironolactone
Spironolactone , commonly referred to as simply spiro, is a diuretic and is used as an antiandrogen.It is a synthetic 17-lactone drug that is a renal competitive aldosterone antagonist in a class of pharmaceuticals called...
or eplerenone
Eplerenone
Eplerenone is an aldosterone antagonist used as an adjunct in the management of chronic heart failure. It is similar to the diuretic spironolactone, though it may be more specific for the mineralocorticoid receptor and is specifically marketed for reducing cardiovascular risk in patients...
, drugs that block the effect of aldosterone. In males, one common side effect of spironolactone drug therapy sometimes seen is gynecomastia
Gynecomastia
Gynecomastia or Gynaecomastia, , is the abnormal development of large mammary glands in males resulting in breast enlargement. The term comes from the Greek γυνή gyné meaning "woman" and μαστός mastós meaning "breast"...
. Gynecomastia usually does not occur with eplerenone drug therapy.