Syndrome of inappropriate antidiuretic hormone overview: Difference between revisions
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==Pathophysiology== | ==Pathophysiology== | ||
Clinical picture of [[SIADH]] may result from[[ genetic]] disorders that result in [[Diuresis|antidiuresis]]. A[[ mutation]] affecting the gene for the[[ renal]] V2 receptor | Clinical picture of [[SIADH]] may result from[[ genetic]] disorders that result in [[Diuresis|antidiuresis]]. A [[mutation]] affecting the [[gene]] for the [[renal]] V2 receptor is implicated in the pathogenesis. [[Congenital]][[ nephrogenic diabetes insipidus]] typically has a [[resistance]] of the renal [[collecting duct]] to the action of the [[arginine vasopressin]] [[hormone]] responsible for the inability of the[[ kidney]] to [[concentrate]] [[urine]]. | ||
* In the X-linked form, inactivating [[mutations]] of the vasopressin 2 receptor gene leading to functional loss of the mutated receptors are seen | |||
==Causes== | ==Causes== | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vindhya BellamKonda, M.B.B.S [2]
Overview
The syndrome of inappropriate antidiuretic hormone (SIADH) is a condition commonly found in individuals hospitalized for central nervous system (CNS) injury. SIADH is a syndrome characterized by excessive release of antidiuretic hormone (ADH or vasopressin) from the posterior pituitary gland or any other source, resulting in hyponatremia, and sometimes fluid overload. Syndrome of inappropriate antidiuretic hormone production (SIADH) leads to excessive water retention and thus a decrease in sodium concentration. SIADH may be occur as a result of central nervous system diseases, cancers, pulmonary diseases and some drugs. Signs and symptoms of SIADH vary widely. Some patients with SIADH may become severely ill while others may have no symptoms at all. Common symptoms include nausea, vomiting, loss of appetite, fatigue, weakness and altered consciousness. Blood tests of hyponatremia (sodium <135 mEq/L) and low serum osmolality (<280 mOsm/kg) may prompt the diagnosis of SIADH. Treatment of SIADH depends on the cause. Restriction of water intake and supplementation of sodium may lead to improvement. Prognosis of SIADH varies depending on the cause.
Historical Perspective
Syndrome of inappropriate antidiuretic hormone secretion was initially described by Leaf and Mambi in the year 1951. Later it was described by researchers from Boston, Massachusetts and Bethesda, Maryland (including Dr Frederic Bartter) in two patients with lung cancer in the year 1957. SIADH is occasionally referred to as Schwartz-Bartter syndrome.
Classification
Four different types of SIADH, wereclassified defined by the pattern ofAVP secretion across a range of plasma osmolalities. Type A, Type B, Type C, Type D.
Pathophysiology
Clinical picture of SIADH may result fromgenetic disorders that result in antidiuresis. A mutation affecting the gene for the renal V2 receptor is implicated in the pathogenesis. Congenitalnephrogenic diabetes insipidus typically has a resistance of the renal collecting duct to the action of the arginine vasopressin hormone responsible for the inability of thekidney to concentrate urine.
- In the X-linked form, inactivating mutations of the vasopressin 2 receptor gene leading to functional loss of the mutated receptors are seen
Causes
SIADH is caused by excess of renal water reabsorption through inappropriate antidiuretic hormone secretion, there are various causes attributed to SIADH ranging from malignancies, drugs, central nervous system causes, infectious. Some of the most common causes of SIADH include malignancies, like small cell lung cancer and medications like selective serotonin reuptake inhibitors and carbamazepine.
Differential diagnosis
SIADH consists ofhyponatremia, inappropriately elevated urineosmolality, excessive urine sodium and decreased serumosmolality in a euvolemic patient without edema. These findings should occur in the absence of diuretic treatment with normalcardiac, renal, adrenal, hepatic and thyroid function.Hyponatremia occurs in about 30% of hospitalized patients and SIADH is the most frequent cause of hyponatremia. Differentiating hyponatremia due to SIADH from other causes of hyponatremia becomes essential to evaluate the treatment plan.
Epidemiology and Demographics
Syndrome of inappropriate antidiuretic hormone can occur at any age. The incidence of SIADH depends on various possible etiologies. Hyponatremia is the most common electrolyte abnormality in hospitalized patients. Prevalence ofSIADH in hospitalized patients from multiple studies came to be about 2500 to 30000 per 100, 000 persons. SIADH is the most common clinical setting in hospitalized patients with hyponatremia. The incidence andprevalence of SIADH in particular is less thoroughly studied in the literature.
Risk Factors
The most common risk factors of SIADH aremalignancy, pulmonary disorders, CNS disorders andmedications.
Screening
There is insufficient evidence to recommend routine screening for SIADH.
Natural History, Complications, and Prognosis
Natural History
The symptoms of SIADH can occur at any age. If untreated can lead tocomplications such as confusion, seizures, stupor and coma.
Complications
Some of the complications of treatment of SIADH are, cerebral edema andcentral pontine myelinolysis which are seen with rapid sodium correction.
Prognosis
The prognosis of Syndrome of inappropriate antidiuretic hormone (SIADH) depends primarily on its cause. If the cause is medications, SIADH usually improves after discontinuing the medication. SIADH secondary to an infection, improves with the treatment of the infection. Whereas, SIADH secondary to cancers, has poor outcome.Patients with SIADH have different signs, symptoms and prognosis depending on the etiology of SIADH. Serum sodium concentration at short-term follow-up is predictive of long-term survival. Rapid correction of serum sodium concentration can lead to various complications.
Diagnosis
History and Symptoms
The main pathology in patients with SIADH is excessivewater retention and hyponatremia. Symptoms of SIADH depend on the level of sodium in the blood and the rate at which the level of sodium falls. Symptoms may be non-specific such as generalised fatigue and weakness but if severe, symptoms such as irritability, nausea, vomiting, muscle weakness and cramps, loss of appetite, confusion, personality changes, hallucinations, seizures, stupor and coma may be seen.
Physical Examination
The physical examination findings of SIADH depend on the level of sodium and rate of change of sodium levels. The physical examination findings in case of mild to moderate SIADH include Headache, lethargy, impaired memory, gait instability, and frequent falls. In case of severe SIADH, findings such as confusion, hallucinations, dysarthria, psychosis, seizures, hemiplegia, limb weakness, tremors, and coma may ensue.
Laboratory Findings
Laboratory findings which are helpful in diagnosing SIADH include, serum electrolytes, especiallysodium, BUN, creatinine, glucose levels, and osmolality. Laboratory findings in patients withsyndrome of inappropriate antidiuretic hormone may show hyponatremia (sodium <135 mEq/L) and low serum osmolality (<280 mOsm/kg). Patients with syndrome of inappropriate antidiuretic hormone show elevated urinary sodium level (>20 mmol/L) and urine osmolality (generally >100 mOsm/L). Patients with SIADH also have low BUN, normal creatinine, hypouricemia and hypoalbuminemia.
Electrocardiogram
EKG may be helpful in the diagnosis of SIADH in rare circumstances. Some studies have reported classic Brugada like pattern (downward coving of ST-segment with T wave inversion is present in the anterior precordial leads) in patients with hyponatremia, the EKG changes normalized after the sodium levels were corrected.
Xray
Imaging Studies, such as x-ray, CT and MRI may be help find the causes of syndrome of inappropriate antidiuretic hormone.
CT scan
Imaging Studies, such as x-ray, CT and MRI may be help find the causes of syndrome of inappropriate antidiuretic hormone.
MRI
MRI is one of the important diagnostic tool to find the CNS causes of SIADH
Ultrasound
There are no ultrasound findings associated withSIADH.
Other Imaging Findings
There are no other specific imaging findings forSIADH
Other Diagnostic Studies
There are no additional diagnostic findings for SIADH.
Treatment
Medical Therapy
Treatment of syndrome of inappropriate antidiuretic hormone depends on the etiology. For immediate improvement, all patients with SIADH require strict restriction of their dailywater intake and correction of serum sodium levels. The serum sodium can can be corrected depending on the initial sodium levels of the patient. Mild cases can be managed easily with exclusive fluid restriction. Moderate cases of SIADH are treated with loop diuretics and normal saline, whereas, 3% hypertonic saline may be used in severe cases. In emergency settings, Vasopressin-2 receptor antagonists (aquaretics, such as conivaptan ortolvaptan) are used. The definitive treatment of SIADH involves treatment of the underlying condition. urea, demeclocycline and lithium are also used in the treatment of SIADH.
Surgery
The definitive treatment of SIADH involves treatment of the underlying condition. SIADH resulting from a carcinoma may require surgery, radiation therapy, or chemotherapy.
Primary prevention
Effective measures for the primary prevention of SIADH include regular monitoring of drugs by the health care provider and screening for cancers.
Secondary prevention
There are no secondary preventive measures available for SIADH.