Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is characterized by excessive unsuppressible release of
antidiuretic hormone
Human vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the AVP gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It then travel ...
(ADH) either from the
posterior pituitary
The posterior pituitary (or neurohypophysis) is the posterior lobe of the pituitary gland which is part of the endocrine system. The posterior pituitary is not glandular as is the anterior pituitary. Instead, it is largely a collection of axonal ...
gland, or an abnormal non-pituitary source.
Unsuppressed ADH causes an unrelenting increase in solute-free water being returned by the tubules of the kidney to the
venous
Veins are blood vessels in humans and most other animals that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are the pulmonary and umbilical veins, both of which carry oxygenated b ...
circulation.
The causes of SIADH are grouped into six categories: 1)
central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
diseases that directly stimulate the
hypothalamus
The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...
, the site of control of ADH secretion; 2) various cancers that synthesize and secrete
ectopic ADH; 3) various lung diseases; 4) numerous drugs that chemically stimulate the hypothalamus; 5) inherited mutations; and 6) miscellaneous largely transient conditions.
[
ADH is derived from a ]preprohormone
A preprohormone is the precursor protein to one or more prohormones, which are in turn precursors to peptide hormones. In general, the protein consists of the amino acid chain that is created by the hormone-secreting cell, before any changes have ...
precursor that is synthesized in cells in the hypothalamus
The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...
and stored in vesicles in the posterior pituitary. ''Appropriate'' ADH secretion is regulated by osmoreceptors
An osmoreceptor is a sensory receptor primarily found in the hypothalamus of most homeothermic organisms that detects changes in osmotic pressure. Osmoreceptors can be found in several structures, including two of the circumventricular organs – t ...
on the hypothalamic
The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamus i ...
cells that synthesize and store ADH: plasma hypertonicity
In chemical biology, tonicity is a measure of the effective osmotic pressure gradient; the water potential of two solutions separated by a partially-permeable cell membrane. Tonicity depends on the relative concentration of selective membrane- ...
activates these receptors, ADH is released into the blood stream, the kidney increases solute-free water return to the circulation, and the hypertonicity is alleviated. ''Inappropriate'' (increased) ADH secretion causes an ''unrelenting increase'' in solute-free water ("free water") absorption by the kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...
s, with two consequences. First, in the extracellular fluid
In cell biology, extracellular fluid (ECF) denotes all body fluid outside the cells of any multicellular organism. Total body water in healthy adults is about 60% (range 45 to 75%) of total body weight; women and the obese typically have a lower ...
(ECF) space, there is a dilution
Dilution may refer to:
* Reducing the concentration of a chemical
* Serial dilution, a common way of going about this reduction of concentration
* Homeopathic dilution
* Dilution (equation), an equation to calculate the rate a gas dilutes
*Tradema ...
of blood solutes
In chemistry, a solution is a special type of homogeneous mixture composed of two or more substances. In such a mixture, a solute is a substance dissolved in another substance, known as a solvent. If the attractive forces between the solvent ...
, causing hypoosmolality
Molality is a measure of the number of moles of solute in a solution corresponding to 1 kg or 1000 g of solvent. This contrasts with the definition of molarity which is based on a specified volume of solution.
A commonly used unit for molali ...
, including a low sodium
Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable iso ...
concentration - hyponatremia
Hyponatremia or hyponatraemia is a low concentration of sodium in the blood. It is generally defined as a sodium concentration of less than 135 mmol/L (135 mEq/L), with severe hyponatremia being below 120 mEq/L. Symptoms can be abs ...
. Then virtually simultaneously, in the intracellular space
Intracellular space is the interior space of the plasma membrane. It contains about two-thirds of TBW. Cellular rupture may occur if the intracellular space becomes dehydrated, or if the opposite happens, where it becomes too bloated. Thus it ...
, cells swell, i.e. intracellular volume increases. Swelling of brain cell
Brain cells make up the functional tissue of the brain. The rest of the brain tissue is structural or connective called the stroma which includes blood vessels. The two main types of cells in the brain are neurons, also known as nerve cells, an ...
s causes various neurological
Neurology (from el, νεῦρον (neûron), "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the brain, the spinal ...
abnormalities which in severe or acute cases can result in convulsions
A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is sometimes used as a s ...
, coma
A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...
, and death
Death is the irreversible cessation of all biological functions that sustain an organism. For organisms with a brain, death can also be defined as the irreversible cessation of functioning of the whole brain, including brainstem, and brain ...
.
Potential treatments of SIADH include restriction of fluid intake, correction of an identifiable reversible underlying cause, and/or medication which promotes solute-free water excretion by the kidney. The presence of cerebral edema
Cerebral edema is excess accumulation of fluid (edema) in the intracellular or extracellular spaces of the brain. This typically causes impaired nerve function, increased pressure within the skull, and can eventually lead to direct compressio ...
may necessitate intravenous isotonic or hypertonic saline administration.[ SIADH was originally described in 1957 in two people with ]small-cell carcinoma
Small-cell carcinoma is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix, prostate, and gastrointestinal tract. Compared to non-small cell ca ...
of the lung.[ reproduced as a Milestone in Nephrology with author commentary in ]
Signs and symptoms
Gastro-intestinal
* Anorexia
Anorexia nervosa, often referred to simply as anorexia, is an eating disorder characterized by low weight, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. ''Anorexia'' is a term of Gre ...
* Nausea
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
Musculoskeletal
* Muscle aches
* Generalized muscle weakness
Neuro-muscular
* Myoclonus
Myoclonus is a brief, involuntary, irregular (lacking rhythm) twitching of a muscle or a group of muscles, different from clonus, which is rhythmic or regular. Myoclonus (myo "muscle", clonic "jerk") describes a medical sign and, generally, is ...
* Decreased reflexes
* Ataxia
Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...
* Pathological reflexes
In biology, a reflex, or reflex action, is an involuntary, unplanned sequence or action and nearly instantaneous response to a Stimulus (physiology), stimulus.
Reflexes are found with varying levels of complexity in organisms with a nervous s ...
* Tremor
A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, fa ...
* Asterixis
Respiratory
* Cheyne-Stokes respiration
Neurological
* Dysarthria
Dysarthria is a speech sound disorder resulting from neurological injury of the motor component of the motor–speech system and is characterized by poor articulation of phonemes. In other words, it is a condition in which problems effectively ...
* Lethargy
Lethargy is a state of tiredness, sleepiness, weariness, fatigue, sluggishness or lack of energy. It can be accompanied by depression, decreased motivation, or apathy. Lethargy can be a normal response to inadequate sleep, overexertion, overwo ...
* Confusion
In medicine, confusion is the quality or state of being bewildered or unclear. The term "acute mental confusion"
* Delirium
Delirium (also known as acute confusional state) is an organically caused decline from a previous baseline of mental function that develops over a short period of time, typically hours to days. Delirium is a syndrome encompassing disturbances in ...
* Seizures
An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or neural oscillation, synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much o ...
* Coma
A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...
(from brain swelling)
* Death
Death is the irreversible cessation of all biological functions that sustain an organism. For organisms with a brain, death can also be defined as the irreversible cessation of functioning of the whole brain, including brainstem, and brain ...
Causes
Causes of SIADH include conditions that dysregulate ADH secretion in the central nervous system, tumors that secrete ADH, drugs that increase ADH secretion, and many others. A list of common causes is below:[ ]
Pathophysiology
Normally there are homeostatic
In biology, homeostasis (British also homoeostasis) (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physical, and chemical conditions maintained by living systems. This is the condition of optimal functioning for the organism and i ...
processes in the body which maintain the concentration of body solutes
In chemistry, a solution is a special type of homogeneous mixture composed of two or more substances. In such a mixture, a solute is a substance dissolved in another substance, known as a solvent. If the attractive forces between the solvent ...
within a narrow range, both inside and outside cells. The process occurs as follows: in some hypothalamic cells there are osmoreceptors
An osmoreceptor is a sensory receptor primarily found in the hypothalamus of most homeothermic organisms that detects changes in osmotic pressure. Osmoreceptors can be found in several structures, including two of the circumventricular organs – t ...
which respond to hyperosmolality in body fluids by signalling the posterior pituitary gland to secrete ADH. This keeps serum sodium
Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable iso ...
concentration - a proxy for solute concentration - at normal levels, prevents hypernatremia
Hypernatremia, also spelled hypernatraemia, is a high concentration of sodium in the blood. Early symptoms may include a strong feeling of thirst, weakness, nausea, and loss of appetite. Severe symptoms include confusion, muscle twitching, and b ...
and turns off the osmoreceptors. Specifically, when the serum sodium rises above 142 mEq/L, ADH secretion is maximal (and thirst is stimulated as well); when it is below 135 mEq/L, there is no secretion. ADH activates V2 receptors on the basolateral membrane of principal cells in the renal collecting duct, initiating a cyclic AMP-dependent process that culminates in increased production of water channels (aquaporin 2), and their insertion into the cells’ luminal membranes.
''Excessive'' ADH causes an ''inappropriate'' increase in the reabsorption in the kidneys of solute-free water ("free water"): excess water moves from the distal convoluted tubule
The distal convoluted tubule (DCT) is a portion of kidney nephron between the loop of Henle and the collecting tubule.
Physiology
It is partly responsible for the regulation of potassium, sodium, calcium, and pH.
On its apical surface (lumen ...
s ( DCT)s and collecting tubule
The collecting duct system of the kidney consists of a series of tubules and ducts that physically connect nephrons to a minor calyx or directly to the renal pelvis. The collecting duct system is the last part of nephron and participates in elect ...
s of the nephron
The nephron is the minute or microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a renal tubule. The renal corpuscle consists of a tuft of capillaries called a glomerulus and a cup-shaped structure ca ...
s - via activation of aquaporins
Aquaporins, also called water channels, are channel proteins from a larger family of major intrinsic proteins that form pores in the membrane of biological cells, mainly facilitating transport of water between cells. The cell membranes of a v ...
, the site of the ADH receptors - back into the circulation. This has two consequences. First, in the extracellular fluid
In cell biology, extracellular fluid (ECF) denotes all body fluid outside the cells of any multicellular organism. Total body water in healthy adults is about 60% (range 45 to 75%) of total body weight; women and the obese typically have a lower ...
(ECF) space, there is a dilution
Dilution may refer to:
* Reducing the concentration of a chemical
* Serial dilution, a common way of going about this reduction of concentration
* Homeopathic dilution
* Dilution (equation), an equation to calculate the rate a gas dilutes
*Tradema ...
of blood solutes
In chemistry, a solution is a special type of homogeneous mixture composed of two or more substances. In such a mixture, a solute is a substance dissolved in another substance, known as a solvent. If the attractive forces between the solvent ...
, causing hypoosmolality
Molality is a measure of the number of moles of solute in a solution corresponding to 1 kg or 1000 g of solvent. This contrasts with the definition of molarity which is based on a specified volume of solution.
A commonly used unit for molali ...
, including a low sodium
Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable iso ...
concentration - hyponatremia
Hyponatremia or hyponatraemia is a low concentration of sodium in the blood. It is generally defined as a sodium concentration of less than 135 mmol/L (135 mEq/L), with severe hyponatremia being below 120 mEq/L. Symptoms can be abs ...
. here is no expansion of the ECF volume because as it attempts to expand, aldosterone is suppressed and atrial natriuretic peptide (ANP) is stimulated: both of these hormones cause isotonic ECF fluid to be excreted by the kidneys sufficient to keep ECF volume at a normal level.] Also, virtually simultaneously to these ECF events, the intracellular space
Intracellular space is the interior space of the plasma membrane. It contains about two-thirds of TBW. Cellular rupture may occur if the intracellular space becomes dehydrated, or if the opposite happens, where it becomes too bloated. Thus it ...
(ICF) volume expands. This is because the osmolality of the ECF is (transiently) less than that of the ICF; and since water is readily permeable to cell membranes, solute-free water moves from the ECF to the ICF compartment by osmosis
Osmosis (, ) is the spontaneous net movement or diffusion of solvent molecules through a selectively-permeable membrane from a region of high water potential (region of lower solute concentration) to a region of low water potential (region of ...
: ''all'' cells swell. Swelling of brain cell
Brain cells make up the functional tissue of the brain. The rest of the brain tissue is structural or connective called the stroma which includes blood vessels. The two main types of cells in the brain are neurons, also known as nerve cells, an ...
s - cerebral edema
Cerebral edema is excess accumulation of fluid (edema) in the intracellular or extracellular spaces of the brain. This typically causes impaired nerve function, increased pressure within the skull, and can eventually lead to direct compressio ...
- causes various neurological
Neurology (from el, νεῦρον (neûron), "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the brain, the spinal ...
abnormalities which in acute and/or severe cases can result in convulsions
A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is sometimes used as a s ...
, coma
A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...
, and death
Death is the irreversible cessation of all biological functions that sustain an organism. For organisms with a brain, death can also be defined as the irreversible cessation of functioning of the whole brain, including brainstem, and brain ...
.
The normal function of ADH on the kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...
s is to control the amount of water reabsorbed by kidney nephron
The nephron is the minute or microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a renal tubule. The renal corpuscle consists of a tuft of capillaries called a glomerulus and a cup-shaped structure ca ...
s. ADH acts in the distal portion of the renal tubule (Distal Convoluted Tubule
The distal convoluted tubule (DCT) is a portion of kidney nephron between the loop of Henle and the collecting tubule.
Physiology
It is partly responsible for the regulation of potassium, sodium, calcium, and pH.
On its apical surface (lumen ...
) as well as on the collecting duct
The collecting duct system of the kidney consists of a series of tubules and ducts that physically connect nephrons to a minor calyx or directly to the renal pelvis. The collecting duct system is the last part of nephron and participates in elect ...
and causes the retention of water, but ''not'' solute. Hence, ADH activity effectively dilutes the blood (decreasing the concentrations of solutes such as sodium
Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable iso ...
), causing hyponatremia
Hyponatremia or hyponatraemia is a low concentration of sodium in the blood. It is generally defined as a sodium concentration of less than 135 mmol/L (135 mEq/L), with severe hyponatremia being below 120 mEq/L. Symptoms can be abs ...
; this is compounded by the fact that the body responds to water retention by decreasing aldosterone
Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays a c ...
, thus allowing even more sodium wasting. For this reason, a high urinary sodium excretion will be seen.
The abnormalities underlying type D syndrome of inappropriate antidiuretic hormone hypersecretion concern individuals where vasopressin release and response are normal but where abnormal renal expression and translocation of aquaporin 2
Aquaporin-2 (AQP-2) is found in the apical cell membranes of the kidney's collecting duct principal cells and in intracellular vesicles located throughout the cell. It is encoded by the gene.
Regulation
It is the only aquaporin regulated b ...
, or both are found.
It has been suggested that this is due to abnormalities in the secretion of secretin
Secretin is a hormone that regulates water homeostasis throughout the body and influences the environment of the duodenum by regulating secretions in the stomach, pancreas, and liver. It is a peptide hormone produced in the S cells of the duode ...
in the brain and that "Secretin as a neurosecretory hormone from the posterior pituitary, therefore, could be the long-sought vasopressin independent mechanism to solve the riddle that has puzzled clinicians and physiologists for decades." There are no abnormalities in total body sodium metabolism. Hyponatremia and inappropriately concentrated urine (UOsm >100 mOsm/L) are seen
Diagnosis
Diagnosis is based on clinical and laboratory findings of low serum osmolality and low serum sodium.
Urinalysis reveals a highly concentrated urine with a high fractional excretion of sodium (high sodium urine content compared to the serum sodium).
A suspected diagnosis is based on a serum sodium under 138. A confirmed diagnosis has seven elements: 1) a decreased effective serum osmolality - <275 mOsm/kg of water; 2) urinary sodium concentration high - over 40 mEq/L with adequate dietary salt intake; 3) no recent diuretic usage; 4) no signs of ECF volume depletion or excess; 5) no signs of decreased arterial blood volume - cirrhosis, nephrosis, or congestive heart failure; 6) normal adrenal and thyroid function; and 7) no evidence of hyperglycemia (diabetes mellitus), hypertriglyceridemia, or hyperproteinia (myeloma).
There are nine supplemental features: 1) a low BUN; 2) a low uric acid; 3) a normal creatinine; 4) failure to correct hyponatremia with IV normal saline; 5) successful correction of hyponatremia with fluid restriction; 6) a fractional sodium excretion >1%; 7) a fractional urea excretion >55%; 8) an abnormal water load test; and 9) an elevated plasma AVP.[
]
Differential diagnosis
Antidiuretic hormone
Human vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the AVP gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It then travel ...
(ADH) is released from the posterior pituitary for a number of physiologic reasons. The majority of people with hyponatremia, other than those with excessive water intake (polydipsia
Polydipsia is excessive thirst or excess drinking.Porth, C. M. (1990). ''Pathophysiology: Concepts of altered health states''. Philadelphia: J.B. Lippincott Company. The word derives from the Greek () "very thirsty", which is derived from (, "mu ...
) or renal salt wasting, will have elevated ADH as the cause of their hyponatremia. However, not every person with hyponatremia and elevated ADH has SIADH. One approach to a diagnosis is to divide ADH release into appropriate (not SIADH) or inappropriate (SIADH).
Appropriate ADH release can be a result of hypovolemia, a so-called non-osmotic trigger of ADH release. This may be true hypovolemia, as a result of dehydration with fluid losses replaced by free water. It can also be perceived hypovolemia, as in the conditions of congestive heart failure
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...
(CHF) and cirrhosis
Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue repai ...
in which the kidneys perceive a lack of intravascular volume. The hyponatremia caused by appropriate ADH release (from the kidneys' perspective) in both CHF and cirrhosis have been shown to be an independent poor prognostic indicator of mortality.
Appropriate ADH release can also be a result of non-osmotic triggers. Symptoms such as nausea/vomiting and pain are significant causes of ADH release. The combination of osmotic and non-osmotic triggers of ADH release can adequately explain the hyponatremia in the majority of people who are hospitalized with acute illness and are found to have mild to moderate hyponatremia. SIADH is less common than appropriate release of ADH. While it should be considered in a differential, other causes should be considered as well.
Cerebral salt wasting syndrome
Cerebral salt-wasting syndrome (CSWS), also written cerebral salt wasting syndrome, is a rare endocrine condition featuring a low blood sodium concentration and dehydration in response to injury (trauma) or the presence of tumors in or surroundi ...
(CSWS) also presents with hyponatremia
Hyponatremia or hyponatraemia is a low concentration of sodium in the blood. It is generally defined as a sodium concentration of less than 135 mmol/L (135 mEq/L), with severe hyponatremia being below 120 mEq/L. Symptoms can be abs ...
, there are signs of dehydration
In physiology, dehydration is a lack of total body water, with an accompanying disruption of metabolic processes. It occurs when free water loss exceeds free water intake, usually due to exercise, disease, or high environmental temperature. Mil ...
for which reason the management is diametrically opposed to SIADH. Importantly CSWS can be associated with subarachnoid hemorrhage
Subarachnoid hemorrhage (SAH) is bleeding into the subarachnoid space—the area between the arachnoid membrane and the pia mater surrounding the brain. Symptoms may include a severe headache of rapid onset, vomiting, decreased level of consci ...
(SAH) which may require fluid supplementation rather than restriction to prevent brain damage.
Most cases of hyponatremia in children are caused by appropriate secretion of antidiuretic hormone
Human vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the AVP gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It then travel ...
rather than SIADH or another cause.
Treatment
How to manage SIADH depends on whether symptoms are present, the severity of the hyponatremia, and the duration. Management of SIADH includes:[
* Removing the underlying cause when possible.
* Mild and asymptomatic hyponatremia is treated with adequate solute intake (including salt and protein) and fluid restriction starting at 500 ml per day of water with adjustments based on serum sodium levels. Long-term fluid restriction of 1,200–1,800 mL/day may maintain the person in a symptom free state.
* Moderate and symptomatic hyponatremia is treated by raising the serum sodium level by 0.5 to 1 mmol per liter per hour for a total of 8 mmol per liter during the first day with the use of furosemide and replacing sodium and potassium losses with 0.9% saline.
* For people with severe symptoms (severe confusion, convulsions, or coma) hypertonic saline (3%) 1–2 ml/kg IV in 3–4 h should be given.
* Drugs
** Demeclocycline can be used in chronic situations when fluid restrictions are difficult to maintain; demeclocycline is the most potent inhibitor of Vasopressin (ADH/AVP) action. However, demeclocycline has a 2–3 day delay in onset with extensive side effect profile, including skin photosensitivity, and nephrotoxicity.]
** Urea: oral daily ingestion has shown favorable long-term results with protective effects in myelinosis and brain damage. Limitations noted to be undesirable taste and is contraindicated in people with cirrhosis to avoid initiation or potentiation of hepatic encephalopathy
Hepatic encephalopathy (HE) is an altered level of consciousness as a result of liver failure. Its onset may be gradual or sudden. Other symptoms may include movement problems, changes in mood, or changes in personality. In the advanced stages ...
.
** Conivaptan
Conivaptan, sold under the brand name Vaprisol, is a non-peptide inhibitor of the receptor for anti-diuretic hormone, also called vasopressin. It was approved in 2004 for hyponatremia (low blood sodium levels). The compound was discovered by As ...
– an antagonist of both V1A and V2 vasopressin receptors.
** Tolvaptan
Tolvaptan, sold under the brand name Samsca among others, is an aquaretic drug that functions as a selective, competitive vasopressin receptor 2 (V2) antagonist used to treat hyponatremia (low blood sodium levels) associated with congestive hea ...
– an antagonist of the V2 vasopressin receptor.
Raising the serum sodium concentration too rapidly may cause central pontine myelinolysis
Central pontine myelinolysis is a neurological condition involving severe damage to the myelin sheath of nerve cells in the ''pons'' (an area of the brainstem). It is predominately iatrogenic (treatment-induced), and is characterized by acute par ...
. Avoid correction by more than 12 mEq/L/day. Initial treatment with hypertonic saline may abruptly lead to a rapid dilute diuresis and fall in ADH.
Epidemiology
The incidence of SIADH rises with increasing age. Residents of nursing homes are at highest risk.
History
The condition was first described at separate institutions by William Schwartz and Frederic Bartter
Frederic Crosby Bartter (September 10, 1914 – May 5, 1983) was an American endocrinologist best known for his work on hormones affecting the kidney and his discovery of syndrome of inappropriate antidiuretic hormone reproduced in and Bartter ...
in two people with lung cancer
Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissue (biology), tissues of the lung. Lung carcinomas derive from tran ...
.[ Criteria were developed by Schwartz and Bartter in 1967 and have remained unchanged since then.]
Society and culture
The condition is occasionally referred to by the names of the authors of the first report: ''Schwartz-Bartter syndrome''. Because not all people with this syndrome have elevated levels of vasopressin, the term "syndrome of inappropriate antidiuresis" (SIAD) has been proposed as a more accurate description of this condition.
References
External links
{{DEFAULTSORT:Syndrome Of Inappropriate Antidiuretic Hormone Hypersecretion
Pituitary disorders
Syndromes
Oncological emergencies
Articles containing video clips