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| '''''Synonyms and Keywords:''''' SIADH; syndrome of inappropriate antidiuretic hormone secretion; inappropriate ADH syndrome; Schwartz-Bartter syndrome. | | '''''Synonyms and Keywords:''''' SIADH; syndrome of inappropriate antidiuretic hormone secretion; inappropriate ADH syndrome; Schwartz-Bartter syndrome. |
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| ==Overview== | | ==[[Syndrome of inappropriate antidiuretic hormone overview|Overview]]== |
| The '''syndrome of inappropriate antidiuretic hormone''' (SIADH) is a condition commonly found in the hospital population, especially in patients being hospitalized for [[central nervous system]] (CNS) injury. This is a syndrome characterized by excessive release of [[Vasopressin|antidiuretic hormone]] (ADH or vasopressin) from the [[posterior pituitary]] gland or another source. The result is [[hyponatremia]], and sometimes fluid overload.
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| ==Historical Perspective== | | ==[[Syndrome of inappropriate antidiuretic hormone historical perspective|Historical Perspective]]== |
| The condition was first described by researchers from Boston, Massachusetts and Bethesda, Maryland (including Dr Frederic Bartter) in two patients with [[lung cancer]].<ref name="pmid13469824">{{cite journal |author=Schwarts WB, Bennett W, Curelop S, Bartter FC |title=A syndrome of renal sodium loss and hyponatremia probably resulting from inappropriate secretion of antidiuretic hormone |journal=Am. J. Med. |volume=23 |issue=4 |pages=529–42 |year=1957 |pmid=13469824 |doi=}} reproduced in {{cite journal |author=Schwartz WB, Bennett W, Curelop S, Bartter FC |title=A syndrome of renal sodium loss and hyponatremia probably resulting from inappropriate secretion of antidiuretic hormone. 1957 |journal=J. Am. Soc. Nephrol. |volume=12 |issue=12 |pages=2860–70 |year=2001 |pmid=11729259 |url=http://jasn.asnjournals.org/cgi/content/full/12/12/2860}}</ref> Criteria were developed by Schwartz and Bartter in 1967,<ref name="pmid5337379">{{cite journal |author=Bartter FC, Schwartz WB |title=The syndrome of inappropriate secretion of antidiuretic hormone |journal=Am. J. Med. |volume=42 |issue=5 |pages=790–806 |year=1967 |pmid=5337379 |doi=}}</ref> and have remained essentially unchanged since then.<ref name="pmid17981159">{{cite journal |author=Verbalis JG, Goldsmith SR, Greenberg A, Schrier RW, Sterns RH |title=Hyponatremia treatment guidelines 2007: expert panel recommendations |journal=Am. J. Med. |volume=120 |issue=11 Suppl 1 |pages=S1–21 |year=2007 |pmid=17981159 |doi=10.1016/j.amjmed.2007.09.001}}</ref> The condition is occasionally referred to by the names of the authors of the first report - Schwatz-Bartter syndrome.<ref>{{WhoNamedIt|synd|2327|Schwartz-Bartter syndrome}}</ref>
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| == Pathophysiology == | | ==[[Syndrome of inappropriate antidiuretic hormone pathophysiology|Pathophysiology]]== |
| The normal function of [[ADH]] on the [[kidney]]s is to control the amount of water reabsorbed by kidney [[nephron]]s. ADH acts in the distal portion of the [[renal tubule]] ([[Distal Convoluted Tubule]]) as well as on the [[collecting duct]] and causes the retention of water, but ''not'' solute. Hence, ADH activity effectively dilutes the blood (decreasing the concentrations of solutes such as [[sodium]]).
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| Developmentally, mammalian organisms have evolved in times of water scarcity and ADH is secreted to prevent water loss in the kidneys. When water is ingested, it is taken up into the circulation and results in a dilution of the [[Blood plasma|plasma]]. This dilution, otherwise described as a reduction in plasma [[osmolality]] is detected by [[osmoreceptor]]s in the [[hypothalamus]] of the brain and these then switch off the release of ADH. The decreasing concentration of ADH effectively inhibits the [[aquaporin]]s in the collecting ducts and [[distal convoluted tubule]]s in the [[nephron]]s of the kidney. Hence, less water is reabsorbed, thereby increasing [[urine]] output, decreasing urine osmolality, and increasing (normalization of) blood osmolality.
| | ==[[Syndrome of inappropriate antidiuretic hormone causes|Causes]]== |
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| In SIADH the release of ADH is not inhibited by a reduction in plasma osmolality when the individual ingests water and the osmolality of the plasma drops. As the main solute of plasma is sodium, this hypoosmolar state is usually detected as a low sodium level on laboratory testing. SIADH is therefore primarily a condition that results in the abnormal handling of water loading and not a problem with excessive solute loss. This is why it is usually treated with fluid (in particular water) restriction. Diuretics may also be given to decrease reabsorption of water, but care must be taken not to correct water imbalances too rapidly.
| | ==[[Syndrome of inappropriate antidiuretic hormone differential diagnosis|Differentiating Syndrome of inappropriate antidiuretic hormone from other Diseases]]== |
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| This dilutional [[hyponatremia]] and all the consequences associated with that condition: [[headache]], [[nausea]], [[vomiting]], and confusion may ensue. Severe hyponatremia may cause [[convulsion]]s or [[coma]].
| | ==[[Syndrome of inappropriate antidiuretic hormone epidemiology and demographics|Epidemiology and Demographics]]== |
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| ==Complete Differential Diagnosis of Causes of SIADH== | | ==[[Syndrome of inappropriate antidiuretic hormone risk factors|Risk Factors]]== |
| (By organ system)
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| {|style="width:70%; height:100px" border="1"
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| |style="height:100px"; style="width:25%" border="1" bgcolor="LightSteelBlue" | '''Cardiovascular'''
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| |style="height:100px"; style="width:75%" border="1" bgcolor="Beige" | No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Chemical / poisoning'''
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| |bgcolor="Beige"| [[Mesothelioma]]
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Dermatologic'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Drug Side Effect'''
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| |bgcolor="Beige"| [[Carbamazepine]], [[Chlorpropamide]], [[Cyclophosphamide]], [[Desmopressin]], [[MAO inhibitor|Mono Amine Oxidase Inhibitors]], [[Nicotine]], [[Oxytocine]], [[Phenothiazines]], [[SSRI]]s, [[Tricyclic antidepressant]]s, [[Vasopressin]], [[Vinblastine]], [[Vincristine]]
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Ear Nose Throat'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Endocrine'''
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| |bgcolor="Beige"| [[Carcinoid]]
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Environmental'''
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| |bgcolor="Beige"| [[Mesothelioma]]
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Gastroenterologic'''
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| |bgcolor="Beige"| [[Carcinoid]], Duodenal [[carcinoma]], [[Pancreatic cancer]]
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Genetic'''
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| |bgcolor="Beige"| [[Agenesis corpus collosum]], [[Amyotropic lateral sclerosis]], [[Hydrocephalus]], Midline defects, [[Multiple sclerosis]]
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Hematologic'''
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| |bgcolor="Beige"| [[Thymoma]]
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Iatrogenic'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Infectious Disease'''
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| |bgcolor="Beige"| [[AIDS]], Bacterial [[pneumonia]], [[Brain abscess]], [[Encephalitis]], [[Lung abscess]], Lung cavitation, [[Meningitis]], [[Tuberculosis]]
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Musculoskeletal / Ortho'''
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| |bgcolor="Beige"| [[Amyotropic lateral sclerosis]], [[Ewing's sarcoma]], [[Polyradiculitis]]
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Neurologic'''
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| |bgcolor="Beige"| [[Agenesis corpus collosum]], [[Amyotropic lateral sclerosis]], [[Brain abscess]], [[Carcinoid]], [[Cavernous sinus thrombosis]], [[Delirium tremens]], [[Encephalitis]], [[Hydrocephalus]], [[Meningitis]], [[Multiple sclerosis]], [[Peripheral neuropathy]], [[Polyradiculitis]], [[Stroke]]
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Nutritional / Metabolic'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Obstetric/Gynecologic'''
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| |bgcolor="Beige"| [[Ovarian cancer]]
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Oncologic'''
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| |bgcolor="Beige"| [[Bronchial adenoma]], [[Carcinoid]], Duodenal [[carcinoma]], [[Ewing's sarcoma]], [[Lung carcinoma]], [[Mesothelioma]], [[Ovarian cancer]], [[Pancreatic cancer]], [[Thymoma]]
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Opthalmologic'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Overdose / Toxicity'''
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| |bgcolor="Beige"| [[Delirium tremens]]
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Psychiatric'''
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| |bgcolor="Beige"| [[Phenothiazines]], [[Psychosis]]
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Pulmonary'''
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| |bgcolor="Beige"| [[Asthma]], Bacterial [[pneumonia]], [[Bronchial adenoma]], [[Carcinoid]], [[Lung abscess]], [[Lung carcinoma]], Lung cavitation, [[Mesothelioma]], [[Pneumothorax]], [[Tuberculosis]]
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Renal / Electrolyte'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Rheum / Immune / Allergy'''
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| |bgcolor="Beige"| [[Asthma]]
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Sexual'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Trauma'''
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| |bgcolor="Beige"| [[Pneumothorax]]
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Urologic'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Miscellaneous'''
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| |bgcolor="Beige"| Positive pressure restoration
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| |-
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| |}
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| ==Complete Differential Diagnosis of Causes of SIADH== | | ==[[Syndrome of inappropriate antidiuretic hormone screening|Screening]]== |
| (In alphabetical order)
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| *[[Agenesis corpus collosum]]
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| *[[AIDS]]
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| *[[Amyotropic lateral sclerosis]]
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| *[[Asthma]]
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| *Bacterial [[pneumonia]]
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| *[[Brain abscess]]
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| *[[Bronchial adenoma]]
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| *[[Carbamazepine]]
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| *[[Carcinoid]]
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| *[[Cavernous sinus thrombosis]]
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| *[[Chlorpropamide]]
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| *[[Cyclophosphamide]]
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| *[[Delirium tremens]]
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| *[[Desmopressin]]
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| *Duodenal [[carcinoma]]
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| *[[Encephalitis]]
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| *[[Ewing's sarcoma]]
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| *[[Hydrocephalus]]
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| *[[Lung abscess]]
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| *[[Lung carcinoma]]
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| *Lung cavitation
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| *[[Meningitis]]
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| *[[Mesothelioma]]
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| *Midline defects
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| *[[MAO inhibitor|Mono Amine Oxidase Inhibitors]]
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| *[[Multiple sclerosis]]
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| *[[Nicotine]]
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| *[[Ovarian cancer]]
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| *[[Oxytocine]]
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| *[[Pancreatic cancer]]
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| *[[Peripheral neuropathy]]
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| *[[Phenothiazines]]
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| *[[Pneumothorax]]
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| *[[Polyradiculitis]]
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| *Positive pressure restoration
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| *[[Psychosis]]
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| *[[SSRI]]
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| *[[Stroke]]
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| *[[Thymoma]]
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| *[[Tricyclic antidepressant]]s
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| *[[Tuberculosis]]
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| *[[Vasopressin]]
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| *[[Vinblastine]]
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| *[[Vincristine]]
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| == Causes == | | ==[[Syndrome of inappropriate antidiuretic hormone natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
| Some common causes of SIADH include:
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| * Head injury
| | ==Diagnosis== |
| ** [[Subarachnoid hemorrhage]]
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| * [[Cancer]]s
| | [[Syndrome of inappropriate antidiuretic hormone history and symptoms|History and Symptoms]] | [[Syndrome of inappropriate antidiuretic hormone physical examination|Physical Examination]] | [[Syndrome of inappropriate antidiuretic hormone laboratory findings|Laboratory Findings]] | [[Syndrome of inappropriate antidiuretic hormone electrocardiogram|Electrocardiogram]] | [[Syndrome of inappropriate antidiuretic hormone x ray|X Ray]] | [[Syndrome of inappropriate antidiuretic hormone CT|CT]] | [[Syndrome of inappropriate antidiuretic hormone MRI|MRI]] | [[Syndrome of inappropriate antidiuretic hormone echocardiography or ultrasound|Echocardiography or Ultrasound]] | [[Syndrome of inappropriate antidiuretic hormone other imaging findings|Other Imaging Findings]] | [[Syndrome of inappropriate antidiuretic hormone other diagnostic studies|Other Diagnostic Studies]] |
| ** [[Lung cancer]] (especially small cell lung cancer, as well as other small-cell malignancies of other organs)
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| * [[Infection]]s
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| ** [[Brain]] [[abscess]]
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| ** [[Pneumonia]]
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| ** [[Lung abscess]]
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| * [[Medication|Drug]]s
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| ** [[Chlorpropamide]]
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| ** [[Cyclophosphamide]]
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| ** [[Carbamazepine]]
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| ** [[Selective serotonin reuptake inhibitor]]s (SSRIs, a class of antidepressants)
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| ** [[Methylenedioxymethamphetamine]] (MDMA, commonly called Ecstasy. SIADH due to taking ecstasy was cited as a factor in the death of Leah Betts)
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| ==Treatment== | | ==Treatment== |
| Treatment of SIADH includes:
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| * Fluid restriction
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| * [[Intravenous]] [[saline (medicine)|saline]]
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| * Drugs
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| ** [[Demeclocycline]]
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| ** [[Conivaptan]] - an approved antagonist of both V<sub>1A</sub> and V<sub>2</sub> vasopressin receptors. Its indications are "treatment of euvolemic hyponatremia (e.g. the syndrome of inappropriate secretion of antidiuretic hormone, or in the setting of hypothyroidism, adrenal insufficiency, pulmonary disorders, etc.) in hospitalized patients."<ref name="dailymed">{{cite web |url=http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=3621#nlm34067-9 |title=Vaprisol (conivaptan hydrochloride) Liquid [Astellas Pharma US, Inc.]|format= |work=}}</ref>
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| ** [[Tolvaptan]] - an unapproved oral antagonist of the V<sub>2</sub> vasopressin receptor. A randomized controlled trial showed conivaptan that can raise the serum sodium by 5 mmol/L. <ref name="pmid17105757">{{cite journal |author=Schrier RW, Gross P, Gheorghiade M, ''et al'' |title=Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia |journal=N. Engl. J. Med. |volume=355 |issue=20 |pages=2099-112 |year=2006 |pmid=17105757 |doi=10.1056/NEJMoa065181}}</ref>
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| Care must be taken when correcting hyponatremia. A rapid rise in the sodium level may cause [[central pontine myelinolysis]].<ref name="pmid11430268">{{cite journal |author=Ashrafian H, Davey P |title=A review of the causes of central pontine myelinosis: yet another apoptotic illness? |journal=Eur. J. Neurol. |volume=8 |issue=2 |pages=103-9 |year=2001 |pmid=11430268 |doi=}}</ref>
| | [[Syndrome of inappropriate antidiuretic hormone medical therapy|Medical Therapy]] | [[Syndrome of inappropriate antidiuretic hormone surgery|Surgery]] | [[Syndrome of inappropriate antidiuretic hormone prevention|Prevention]] | [[Syndrome of inappropriate antidiuretic hormone cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Syndrome of inappropriate antidiuretic hormone future or investigational therapies|Future or Investigational Therapies]] |
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| ==Differential diagnosis== | | ==Case Studies== |
| [[Cerebral salt wasting syndrome]] also presents with hyponatremia, but is treated differently.
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| ==References==
| | [[Syndrome of inappropriate antidiuretic hormone case study one|Case #1]] |
| {{reflist|2}}
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| {{Endocrine pathology}} | | {{Endocrine pathology}} |