Syndrome of inappropriate antidiuretic hormone production (SIADH)
Syndrome of inappropriate antidiuretic hormone production (SIADH) is a condition characterized by excessive release of antidiuretic hormone (ADH), leading to fluid retention and diluted sodium levels in the blood. Originally identified in 1957, SIADH is particularly associated with certain cancers, especially small-cell lung cancer, and can also be triggered by medications, such as chemotherapy and antidepressants. The syndrome causes euvolemic hyponatremia, a condition where sodium levels fall below normal (135-145 mEq/L) without significant fluid loss. Common symptoms include weakness, confusion, nausea, and in severe cases, seizures or unresponsiveness.
Diagnosis involves blood tests revealing low sodium levels alongside increased urine sodium and osmolarity, without signs of dehydration. Treatment focuses on managing sodium levels cautiously to prevent complications, such as central pontine myelinolysis. Approaches may include fluid restrictions, dietary changes, and medications to enhance sodium retention or increase urine output. The prognosis of SIADH largely depends on its underlying cause and the speed of sodium normalization. Managing the condition effectively is crucial for improving patient outcomes.
On this Page
Subject Terms
Syndrome of inappropriate antidiuretic hormone production (SIADH)
ALSO KNOWN AS: Syndrome of inappropriate antidiuresis (SIAD)
RELATED CONDITIONS: Dehydration, water intoxication (hyponatremia), electrolyte abnormalities
DEFINITION: Syndrome of inappropriate antidiuretic hormone (SIADH) was first described by Frederic C. Bartter and William B. Schwartz in 1957 when their patient, diagnosed with oat cell carcinoma, was experiencing symptoms related to a low sodium level. Sodium is an electrolyte important for the function of many cells within the body. SIADH occurs when there is an excessive release of antidiuretic hormones (ADH, or vasopressin), which causes an increase in fluid retention by the kidneys.
Risk factors: Patients who have small-cell lung cancer are at high risk for developing SIADH. Other cancers that may place the patient at high risk for developing this syndrome are pancreatic cancer, head and neck cancers, colon adenocarcinoma, olfactory neuroblastoma, lymphoma, and leukemia. Chemotherapy drugs, pain medications, tricyclic antidepressants, general anesthesia, and other drugs used to treat cancer side effects can also cause SIADH.
Etiology and the disease process: Antidiuretic hormone (ADH) is normally produced in the hypothalamus and stored in the posterior pituitary, both located in the brain. ADH is released by the pituitary gland but also can be released from a few cancer tumors. It works with the kidneys to regulate the amount of fluid that either remains in the body or is released in the urine. An increase in ADH can cause the kidney to retain fluid, which in turn causes fluid volume overload and dilutes the sodium as well as other electrolytes in the body.
Incidence: SIADH is the most common cause of euvolemic hyponatremia, which affects between 12 and 42 percent of patients in hospitals. It occurs more frequently in females and older patients.
Symptoms: Symptoms are related more to the sudden changes in the sodium level than to the sodium level itself. Early signs and symptoms of SIADH include weakness and lethargy, confusion, irritability, altered mental status, nausea, vomiting, increased thirst, abdominal cramping, decreased urine output, and weight gain. Unresponsiveness, muscle cramping, and seizures are symptoms of progressively greater sodium deficiency. Normal blood sodium levels are 135 to 145 milliequivalents of solute per liter of solvent (mEq/l). Symptoms usually start when the blood's sodium level decreases to 120 to 125 mEq/l.
Screening and diagnosis: Initial blood tests should be taken to evaluate sodium levels. The blood test of a patient with SIADH will commonly reveal low serum (blood) sodium levels. Urine levels will show an increase in sodium levels and osmolarity. Patients will typically show no edema or volume depletion (dehydration). The patient will have normal renal, adrenal, and cardiac function. The decrease in sodium levels can be a slow, gradual process or may have rapid onset.
Additional blood tests include a complete blood count, electrolytes, urea, creatinine clearance, glucose, and serum (blood) osmolarity. Urine can also be tested for electrolytes.
Tests that may also be considered are thyroid-stimulating hormone (TSH) levels, cortisol level, and liver function tests (LFTs). A chest X-ray and a computed tomography (CT) scan of the head may also be completed to assist with diagnosis.
Treatment and therapy: SIADH will need to be corrected slowly. Sodium levels that rise too quickly can cause central pontine myelinolysis (CPM), a type of nerve damage caused by the destruction of the layer covering the nerve cells in the brain stem. Symptoms of CPM are mental status changes, weak muscles, and cranial nerve abnormalities. There is no known cure.
Medical personnel will assess patients with SIADH for any signs of swelling, increase in thirst, intake and output, urine concentration, daily weights, and current consumption.
Asymptomatic cases are treated by treating the underlying cause. Symptomatic patients will be initially treated with fluid restrictions that allow for one half to one liter of fluid every twenty-four hours. Patients may also be placed on a high-protein, high-salt diet. Loop diuretics, such as furosemide (Lasix), may help the body excrete more urine while retaining the sodium. Demeclocycline, a form of tetracycline antibiotic, may also be used to increase urine output. Demeclocycline is a pill that stops the kidneys from responding to the increased ADH, allowing the body to excrete large amounts of urine. For more severe cases, hypertonic saline (3 percent saline) is given intravenously to increase sodium levels within the serum. Furosemide can also be given with the hypertonic saline to help balance the fluid levels. Vaptans, antagonists to the renal V2 vasopressin receptor, are considered breakthrough treatments for SIADH, and urea have emerged as a safe and inexpensive treatment.
Prognosis, prevention, and outcomes: Outcomes for SIADH are related to the underlying disease. Prompt treatment of the underlying condition may improve the patient's outcomes. The more rapid the increase in sodium levels, the higher the risk of mortality. Patients may have to limit fluid intake for an extended period to ensure that the SIADH does not return if the underlying condition does not improve.
Bibliography
Gross, Peter. "Clinical Management of SIADH." Therapeutic Advances in Endocrinology and Metabolism, vol. 3, no. 2, 2012, pp. 61-73, doi.org/10.1177/2042018812437561. Accessed 3 July 2024.
Itano, Joanne, et al. Core Curriculum for Oncology Nursing. 5th ed., St. Louis: Elsevier, 2016.
Johnson, Bonny Libbey., and Jody Gross. Handbook of Oncology Nursing. 3rd ed., Boston.: Jones, 1998.
Langhorne, Martha, Janet Fulton, and Shirley E. Otto. Oncology Nursing. 5th ed., St. Louis: Elsevier, 2007.
Lenhard, R. E., R. T. Osteen, and T. Gansler. Clinical Oncology. 3rd ed., Atlanta: American Cancer Soc., 2001.
Pomares-Gomez, Francisco, et al. "Clinical Efficacy of Urea Treatment in Syndrome of Inappropriate Antidiuretic Hormone Secretion." Scientific Reports, vol. 12, no. 1, 2022, pp. 1-7, doi.org/10.1038/s41598-022-14387-4. Accessed 3 July 2024.
“SIADH (Syndrome of Inappropriate Antidiuretic Hormone Secretion).” Cleveland Clinic, 3 Aug. 2022, my.clevelandclinic.org/health/diseases/23976-siadh-syndrome-of-inappropriate-antidiuretic-hormone-secretion. Accessed 3 July 2024.
“Syndrome of Inappropriate Antidiuretic Hormone.” Canadian Cancer Society, cancer.ca/en/treatments/side-effects/syndrome-of-inappropriate-antidiuretic-hormone. Accessed 3 July 2024.
Yarbro, Connie Henke, Debra Wujcik, and Barbara Holmes Gobel. Cancer Nursing: Principles and Practice. 7th ed., Sudbury, Mass.: Jones, 2011.
Yarbro, Connie Henke, Debra Wujcik, and Barbara Holmes Gobel. Cancer Symptom Management. 4th ed., Burlington: Jones, 2014.
Yasir, Muhammad. “Syndrome of Inappropriate Antidiuretic Hormone Secretion - StatPearls.” NCBI, 6 Mar. 2023, www.ncbi.nlm.nih.gov/books/NBK507777. Accessed 3 July 2024.
Zhang, Xu, and Ying Li. "Prevalence of Hyponatremia among Older Inpatients in a General Hospital." European Geriatric Medicine, vol. 11, no. 4, 2020, pp. 685-692, doi.org/10.1007/s41999-020-00320-3. Accessed 3 July 2024.