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Syndrome of inappropriate antidiuretic hormone hypersecretion

 
Oncology Encyclopedia: Syndrome of Inappropriate Antidiuretic Hormone
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Key Terms: Antidiuretic hormone, Diuresis, Hormone, Hypertonic saline solution, Intracranial, Pituitary gland, SIADH, Serum.

Description

The syndrome of inappropriate antidiuretic hormone production (SIADH) is a condition in which the body develops an excess of water and a decrease in sodium (salt) concentration, as a result of improper chemical signals. Patients with SIADH may become severely ill, or may have no symptoms at all.

A syndrome is a collection of symptoms and physical signs that together follow a pattern. SIADH is one of the paraneoplastic syndromes, in which a cancer leads to widespread ill effects due to more than just the direct presence of tumor.

Normal Physiology

The body normally maintains very tight control over its total amount of water and its concentration of sodium. Many organs including the kidneys, heart, and the adrenal, thyroid, and pituitary glands participate in this regulation. One important contribution is the release of a chemical substance, or hormone, by the pituitary gland into the bloodstream. This chemical substance, called antidiuretic hormone (ADH), is also known as arginine vasopressin, or AVP.

The pituitary releases ADH into the bloodstream when receptors in various organs detect that the body has too little water or too high a concentration of salt. ADH then affects the way the kidneys control water and salt balance. ADH causes the kidneys to decrease their output of urine. The body thus saves water by undergoing antidiuresis, that is, not excreting urine.

Simultaneously, the concentration of sodium in the body serum decreases. This decrease results from a second effect of ADH on the kidneys. When the kidneys retain extra water, the existing concentration of sodium in the body decreases slightly as a result of dilution. These functions are all part of the body's extremely precise control over water and salt balance in health.

Abnormal Physiology in Siadh

Certain disease states can upset the delicate balance of water and salt in the body. If there is too much ADH in the body, or if the kidneys overreact to the ADH they receive, the body retains excess water and the serum sodium concentration becomes diluted and falls to abnormal levels. The patient with SIADH develops symptoms based on the degree of abnormality in the serum sodium concentration and the speed with which this concentration falls.

Normal serum sodium concentration is 135-145 mEq/L (milliEquivalents of sodium per liter of body fluid). When the sodium concentration is 125–135 mEq/L the patient may have mild nausea, loss of appetite, fatigue, headache, or still remain free of symptoms. As the sodium level drops below 120 mEq/L, the patient experiences greater weakness, confusion, sleepiness, vomiting, and weight gain. As the sodium concentration approaches 110 mEq/L, the patient may suffer seizures, coma, and death.

Causes

SIADH has many known causes, some of which particularly relate to cancer or its treatment. These causes include specific types of cancer, drugs used to treat cancer itself, drugs used to treat the effects of cancer, and conditions that arise as a consequence of cancer or its treatment.

Specific Types of Cancer

SIADH results from numerous different types of cancer. The malignancies known to cause SIADH include:

Certain cancers produce and secrete ADH themselves. This production occurs without regard for the needs of the body. Thus, the kidneys receive repeated signals to save water, even when the body already has a marked excess of fluid. Of all the types of cancer that produce ADH themselves, small-cell lung cancer is by far the most common. Small-cell cancer of the lung is the cause in 75% of cases of SIADH caused directly by a tumor. In some cases, the appearance of SIADH may be the first indication that a cancer exists.

Also, primary or metastatic tumors in the brain may lead to SIADH. SIADH here results from an increase in intracranial pressure (pressure within the head), or from other effects of intracranial disease on the brain. Increased intracranial pressure commonly causes various parts of the brain to work improperly.

Drugs Used to Treat Cancer Itself

A variety of drugs used in cancer treatment may lead to SIADH. The mechanism of this effect may be that the drug causes the abnormal release of ADH, or that the drug makes existing ADH work in a stronger fashion than usual. Chemotherapy drugs that cause SIADH include:

Drugs Used to Treat the Effects of Cancer

SIADH may occur as a reaction to drugs used to treat effects of cancer such as pain, depression, or seizures. SIADH also may result from general anesthesia.

Conditions That Arise As a Consequence of Cancer

SIADH may result from some of the debilitating consequences of cancer. For example, a person with cancer who is weak or unsteady will have a tendency to fall and hit the head. Skull fracture and other types of head injury may damage the brain or increase the intracranial pressure, and thus lead to SIADH.

Also, cancer patients who are weak, malnourished, receiving chemotherapy, or spending excessive time in bed have an increased risk of pneumonia and other infections. Infections including pneumonia, meningitis, and tuberculosis can cause SIADH.

Treatments

The treatment of SIADH involves relief of the urgent symptoms and correction of the underlying problem. For immediate improvement, all patients with SIADH require sharp restriction of their daily water intake. As little as two cups of liquid, about 500 ml, may be the daily limit for some patients. In cases where the sodium concentration is already dangerously low, doctors may cautiously give an intravenous infusion of fluid with a high concentration of sodium (hypertonic saline solution). However, this treatment carries some risk of damaging the brain. Physicians may also use a medicine such as furosemide (Lasix) that promotes water excretion (diuresis). Another drug, demeclocycline, blocks the action of ADH in the kidney.

The most definitive way to relieve SIADH is to address the underlying problem itself. Thus, if a tumor produces abnormal ADH, then surgery, radiation therapy, or chemotherapy may help by reducing tumor size. If SIADH results from use of a drug, then the patient must discontinue the medicine. Finally, doctors try to identify and treat any other correctable cause, such as an infection.

Prognosis

The prognosis of SIADH depends largely on its cause. Until recently, many physicians believed that the appearance of SIADH indicated a poor prognosis for cancer. However, more recent reports contradict this idea. The patient's ability to observe severe restriction of fluid intake may determine the degree of ongoing symptoms. SIADH usually improves after stopping a drug or curing an infection when that is the cause. When cancer is the direct cause of SIADH, one hopes for similar improvement of SIADH from treatments that reduce the amount of cancer in the body.

Resources

Books

DeVita, Vincent T. Jr., Samuel Hellman, and Steven A. Rosenberg, editors. Cancer: Principles and Practice of Oncology. Philadelphia: Lippincott Williams & Wilkins, 2001.

—Kenneth J. Berniker, M.D.

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Wikipedia: Syndrome of inappropriate antidiuretic hormone hypersecretion
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Home > Library > Miscellaneous > Wikipedia
Syndrome of inappropriate antidiuretic hormone
Classification and external resources
ICD-10 E22.2
ICD-9 253.6
DiseasesDB 12050
MedlinePlus 003702
eMedicine emerg/784 med/3541 ped/2190
MeSH D007177

The syndrome of inappropriate antidiuretic hormone hypersecretion (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 pituitary gland or another source. The result is hyponatremia, and sometimes fluid overload. Vasopressin has other important functions, addressed in the appropriate articles.

Contents

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 (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 edema become prominent (irritability, confusion, seizures, and coma).

Diagnosis

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). 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)
  • Low creatinine
  • Low uric acid
  • Low albumin

Causes

Some common causes of SIADH include:

Management

Management of SIADH includes:

  • Treating underlying causes when possible.
  • Fluid restriction to 800-1,000 ml/d should be obtained to increase serum sodium.
  • Intravenous saline - For very symptomatic patients (severe confusion, convulsions, or coma) hypertonic saline (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 AVP action.
    • 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."[2]
    • Tolvaptan - an antagonist of the V2 vasopressin receptor. A randomized controlled trial showed conivaptan that can raise the serum sodium by 5 mmol/L.[3]

Care must be taken when correcting hyponatremia. A rapid rise in the sodium level may cause central pontine myelinolysis.[4]

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.[5] Criteria were developed by Schwartz and Bartter in 1967,[6] and have remained essentially unchanged since then.[7] The condition is occasionally referred to by the names of the authors of the first report - Schwatz-Bartter syndrome.[8]

References

  1. ^ 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
  2. ^ "Vaprisol (conivaptan hydrochloride) Liquid [Astellas Pharma US, Inc.]". http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=3621#nlm34067-9. Retrieved 2007-06-08. 
  3. ^ 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. 
  4. ^ 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. 
  5. ^ 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. 
  6. ^ 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. 
  7. ^ 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. 
  8. ^ Schwartz-Bartter syndrome at Who Named It?
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Oncology Encyclopedia. Gale Encyclopedia of Cancer. Copyright © 2006 by The Gale Group, Inc. All rights reserved.  Read more
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