Syndrome of inappropriate antidiuretic hormone hypersecretion
The syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH) is characterized by excessive release of antidiuretic hormone (ADH or vasopressin) from the posterior pituitary gland or another source. The result is hyponatremia and sometimes fluid overload. It is usually found in patients diagnosed with pneumonia, brain tumors, head trauma, strokes, meningitis, encephalitis, or small-cell carcinoma of the lung.
Pathophysiology
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 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).
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 osmolality, is detected by osmoreceptors in the hypothalamus of 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 urine output, decreasing urine osmolality, and normalizing 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 hyponatremia and all the consequences associated with that condition: headache, nausea, vomiting, and confusion may ensue. Severe hyponatremia may cause convulsions or coma.
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, or both are found.[1] It has been suggested that this is due to abnormalities in the secretion of secretin 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."[1]
Clinical Findings
In general, increased ADH causes water retention and extracellular fluid volume expansion without edema or hypertension, owing to natriuresis (the excretion of sodium by the kidneys). 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 edema become prominent (irritability, confusion, seizures, and coma).
Diagnosis
Laboratory findings in diagnosis of SIADH include-
Other findings include-
- Urine sodium concentration >20 mEq/L (inappropriate natriuresis). Urine sodium concentration may be normal reflecting dietary intake.
- Maintained hypervolemia
- Suppression of renin-angiotensin system
- No equal concentration of atrial natriuretic peptide
- Low blood urea nitrogen (BUN)
- Normal serum creatinine
- Low uric acid
- Low albumin
- Normal Acid-Base, K+ balance
- Normal Adrenal, Thyroid function
Causes
Some common causes of SIADH include:
Management
Management of SIADH includes:
- Treating underlying causes when possible.
- Long-term fluid restriction of 1,200–1,800 mL/day[2] to increase serum sodium.
- Intravenous saline - For very symptomatic patients (severe confusion, convulsions, or coma) hypertonic saline (3-5%) 200-300 ml 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 delay in onset with extensive side effect profile, including but not limited to new onset Nephrogenic Diabetes Insipidus (70%), skin photosensitivity, and nephrotoxicity.[3]
- Urea: oral daily ingestion has shown favorable long-term results with protective effects in myelinosis and brain damage.[3] Limitations noted to be undesirable taste and is contraindicated in patients with cirrhosis to avoid initiation or potentiation of hepatic encephalopathy.
- Conivaptan - an 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.".[4] Conivaptan, however, is only available as a parenteral preparation.[3]
- Tolvaptan - an antagonist of the V2 vasopressin receptor. A randomized controlled trial showed tolvaptan is able to raise serum sodium in patients with euvolemic or hypervolemic hyponatremia with euvolemic or hypervolemic hyponatremia in 2 different tests. Combined analysis of the 2 trials showed an improvement in hyponatremia in both the short term (primary sodium change in average AUC: 3.62+/- 2.68 and 4.35 +/-2.87) and long term with long term maintenance (primary sodium change in average AUC: 6.22 +/- 4.22 and 6.20 +/- 4.92), at 4 days and 30 days, respectively. Tolvaptan’s side effect profile is minimal. Discontinuation of the Tolvaptan showed return of hyponatremia to control values at their respective time frames.[5]
-No head to head study is currently available to quantify and compare the relative efficacies of V2 vasopressin receptor antagonists with demeclocycline or other treatment options. Care must be taken when correcting hyponatremia. A rapid rise in the sodium level may cause central pontine myelinolysis.[6] Avoid correction by more than 12 mEq/L/day
Differential diagnosis
Cerebral salt wasting syndrome also presents with hyponatremia.
History
The condition was first described by researchers from Boston, Massachusetts and Bethesda, Maryland (including Dr Frederic Bartter) in two patients with lung cancer.[7] Criteria were developed by Schwartz and Bartter in 1967[8] and have remained essentially unchanged since then.[9] The condition is occasionally referred to by the names of the authors of the first report - Schwartz-Bartter syndrome.[10]
References
- ^ a b Chu JY, Lee LT, Lai CH, Vaudry H, Chan YS, Yung WH, Chow BK.(2009). Secretin as a neurohypophysial factor regulating body water homeostasis. Proceedings of the National Academy of Sciences USA, 106:15961–15966. doi:10.1073/pnas.0903695106
- ^ Schürer, L.; Wolf, S.; Lumenta, C. B. (2010). Water and Electrolyte Regulation. pp. 611. doi:10.1007/978-3-540-79565-0_40. edit
- ^ a b c Zietse, Robert; van der Lubbe N, Hoorn E (2009). "Current and Future Treatment Options in SIADH". Nephrology Dialysis Transplantation 2 [Suppl 3] (Suppl_3): iii12–iii19. doi:10.1093/ndtplus/sfp154. PMC 2762827. PMID 19881932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2762827.
- ^ "Vaprisol (conivaptan hydrochloride) Liquid [Astellas Pharma US, Inc."]. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=3621#nlm34067-9. Retrieved 2007-06-08.
- ^ Schrier RW, Gross P, Gheorghiade M, et al. (2006). "Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia". N. Engl. J. Med. 355 (20): 2099–112. doi:10.1056/NEJMoa065181. PMID 17105757.
- ^ Ashrafian H, Davey P (2001). "A review of the causes of central pontine myelinosis: yet another apoptotic illness?". Eur. J. Neurol. 8 (2): 103–9. doi:10.1046/j.1468-1331.2001.00176.x. PMID 11430268.
- ^ Schwarts WB, Bennett W, Curelop S, Bartter FC (1957). "A syndrome of renal sodium loss and hyponatremia probably resulting from inappropriate secretion of antidiuretic hormone". Am. J. Med. 23 (4): 529–42. doi:10.1016/0002-9343(57)90224-3. PMID 13469824. reproduced in Schwartz WB, Bennett W, Curelop S, Bartter FC (1 December 2001). "A syndrome of renal sodium loss and hyponatremia probably resulting from inappropriate secretion of antidiuretic hormone. 1957". J. Am. Soc. Nephrol. 12 (12): 2860–70. PMID 11729259. http://jasn.asnjournals.org/cgi/content/full/12/12/2860.
- ^ Bartter FC, Schwartz WB (1967). "The syndrome of inappropriate secretion of antidiuretic hormone". Am. J. Med. 42 (5): 790–806. doi:10.1016/0002-9343(67)90096-4. PMID 5337379.
- ^ Verbalis JG, Goldsmith SR, Greenberg A, Schrier RW, Sterns RH (2007). "Hyponatremia treatment guidelines 2007: expert panel recommendations". Am. J. Med. 120 (11 Suppl 1): S1–21. doi:10.1016/j.amjmed.2007.09.001. PMID 17981159.
- ^ Schwartz-Bartter syndrome at Who Named It?
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