- Syndrome of inappropriate antidiuretic hormone
Name = Syndrome of inappropriate antidiuretic hormone |
DiseasesDB = 12050
ICD10 = ICD10|E|22|2|e|20
ICD9 = ICD9|253.6
MedlinePlus = 003702
eMedicineSubj = emerg
eMedicineTopic = 784
eMedicine_mult = eMedicine2|med|3541 eMedicine2|ped|2190
MeshID = D007177
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 antidiuretic hormone (ADH or vasopressin) from the posterior pituitarygland or another source. The result is hyponatremia, and sometimes fluid overload. It should be noted that vasopressin has other important functions, addressed in the appropriate articles.
The normal function of ADH on the
kidneys is to control the amount of water reabsorbed by kidney nephrons. ADH acts in the distal portion of the renal tubule ( Distal Convoluted Tubule) as well as on the collecting ductand causes the retention of water, but "not" solute. Hence, ADH activity effectively dilutes the blood (decreasing the concentrations of solutes such as sodium).
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 plasma. This dilution, otherwise described as a reduction in plasma
osmolalityis detected by osmoreceptors in the hypothalamusof the brain and these then switch off the release of ADH. The decreasing concentration of ADH effectively inhibits the aquaporins in the collecting ducts and distal convoluted tubules in the nephrons of the kidney. Hence, less water is reabsorbed, thereby increasing urineoutput, decreasing urine osmolality, and increasing (normalization of) blood osmolality.
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.
This causes dilutional
hyponatremiaand all the consequences associated with that condition: headache, nausea, vomiting, and confusion may ensue. Severe hyponatremia may cause convulsions or coma.
In general, increased ADH causes water retention and extracellular fluid volume expansion "without"
edemaor hypertension, owing to natriuresis (retention of water and passing of sodium in urine). The water retention and sodium loss both cause hyponatremia, which is a key feature in SIADH. Hyponatremia and concentrated urine (UOsm >300 mOsm) are seen, as well as "no signs of" edema or dehydration. When hyponatremia is severe (sodium <120 mOsm), or acute in onset, symptoms of cerebral edemabecome prominent (irritability, confusion, seizures, and coma).
Laboratory findings in diagnosis of SIADH include-
* Hyponatremia <130 mEq/L, and POsm <270 mOsm/kg. Other findings include-
* Urine sodium concentration >20 mEqlL (inappropriate natriuresis)
* Maintained hypervolemia
* Suppression of renin-angiotensin system
* No equal concentration of atrial natriuretic peptide
blood urea nitrogen(BUN)
Some common causes of SIADH include:
* Head injury
Lung cancer(especially small cell lung cancer, as well as other small-cell malignancies of other organs)
Selective serotonin reuptake inhibitors (SSRIs, a class of antidepressants)
Methylenedioxymethamphetamine(MDMA, commonly called Ecstasy. SIADH due to taking ecstasy was cited as a factor in the death of Leah Betts)
Management of SIADH includes:
* Treating underlying causes when possible.
* Fluid restriction to 800-1,000 ml/d should be obtained to increase serum sodium.
Intravenoussaline - For very symptomatic patients (severe confusion, convulsions, or coma) hypertonic saline (5%) 200-300 ml IV in 3-4 h should be given.
Demeclocyclinecan be used in chronic situations when fluid restrictions are difficult to maintain; demeclocycline is the most potent inhibitor of AVP action.
Conivaptan- an approved antagonist of both V1A and V2 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."cite web |url=http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=3621#nlm34067-9 |title=Vaprisol (conivaptan hydrochloride) Liquid [Astellas Pharma US, Inc.] |accessdate=2007-06-08 |format= |work=]
Tolvaptan- an unapproved oral antagonist of the V2 vasopressin receptor. A randomized controlled trial showed conivaptan that can raise the serum sodium by 5 mmol/L. 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]
Care must be taken when correcting hyponatremia. A rapid rise in the sodium level may cause
central pontine myelinolysis.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=10.1046/j.1468-1331.2001.00176.x]
Cerebral salt wasting syndromealso presents with hyponatremia, but is treated differently.
The condition was first described by researchers from
Boston, Massachusettsand Bethesda, Maryland(including Dr Frederic Bartter) in two patients with lung cancer.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] Criteria were developed by Schwartz and Bartter in 1967,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=10.1016/0002-9343(67)90096-4] and have remained essentially unchanged since then.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] The condition is occasionally referred to by the names of the authors of the first report - Schwatz-Bartter syndrome. [WhoNamedIt|synd|2327|Schwartz-Bartter syndrome]
Wikimedia Foundation. 2010.