Syndrome of inappropriate antidiuretic hormone overview

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Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differential Diagnosis

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

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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 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.

Syndrome of inappropriate antidiuretic hormone production (SIADH) is a condition in which the body develops an excess of water and a decrease in sodium concentration. It may be caused by central nervous system diseases, cancers, pulmonary diseases and some drugs. Signs and aymptoms vary widely. Some patients with SIADH may become severely ill, or may have no symptoms at all. Usual symptoms include nausea, vomiting, loss of appetite, fatigue, weakness,even consciousness disorders. Blood tests of hyponatremia (sodium <135 mEq/L) and low serum osmolality (<280 mOsm/kg) may prompt the diagnosis of SIADH. Treatment depends on the causes. Sharp restriction of water intake and addition of a high concentration of sodium may get immediate improvement. Prognosis of SIADH varies widely, depending on the causes.

Historical Perspective

Syndrome of SIADH 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.The condition 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, TypeD.

Pathophysiology

Clinical picture of SIADH may result fromgenetic disorders that result inantidiuresis. Amutation affecting the gene for therenal V2 receptor, which some investigators have named nephrogenic syndrome of inappropriate antidiuresis, has been found to causeclinically significanthyponatremia. Congenital nephrogenic diabetes insipidus is characterized by a resistance of the renal collecting duct to the action of the arginine vasopressin hormone responsible for the inability of thekidney to concentrateurine. The X-linked form is due to inactivating mutations of thevasopressin 2 receptor gene leading to a loss of function of the mutated receptors. Conversely, the nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is linked to a constitutive activation of the V(2)-receptor due to activatingmutations with clinical and biological features of inappropriate antidiuresis but with low or undetectable plasma arginine vasopressin hormone levels.

Causes

SIADH is caused by excess of renal water reabsorption through inappropriate antidiuretic hormone secretion, there are various causes attributed to SIADH ranging frommalignancies, drugs, central nervous system causes, infectious. Some of the most common causes are : malignancies like small cell lung cancer, drugs like selective serotonin reuptake inhibitors, and carbamazapine.

Differential diagnosis Syndrome of inappropriate antidiuretic hormone overview

SIADH consists of hyponatremia, inappropriately elevated urine osmolality, excessive urine sodium and decreased serum osmolality in a euvolemic patient without edema. These findings should occur in the absence of diuretic treatment with normal cardiac, 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

SIADH can occur at any age. It's incidence depends on various possible etiologies. Hyponatremia is the most common electrolyte abnormality in hospitalized patients. Prevalence of hyponatremia in hospitalized patients from multiple studies came to be about 2.5%-30%.SIADH was the most common clinical setting in hospitalized patients with hyponatremia. The incidence and prevalence of SIADH in particular is less thoroughly studied in the literature.

Risk Factors

The most common causes of SIADH are malignancy, pulmonary disorders, CNS disorders and medications.

Screening

There are no screening guidelines for SIADH

Natural History, Complications, and Prognosis

Natural History

The symptoms of SIADH can occur at any age. If untreated can lead to complications such as confusion,seizures, stupor and coma.

Complications

Some of the complications of treatment of SIADH are, cerebral edema, central pontine myelinolysis (if sodium level is corrected too rapidly)


Prognosis

The prognosis of Syndrome of inappropriate antidiuretic hormone (SIADH) depends largely on its cause. If the cause is drugs, SIADH usually improves after stopping a drug. If SIADH is associated with some infection, treating the infection may be important. For those SIADH with cancers, the outcomes may be poor. Patients with SIADH have different characteristics and a different prognosis according to SIADH etiology. Serum sodium concentration at short-term follow-up is predictive of long-term survival. These findings might have diagnostic and treatment-related implications.

Diagnosis

Diagnostic Criteria

History and Symptoms

The main problem in patients with SIADH is excess of water retention and low sodium levels. Symptoms depend on the levels of sodium in the blood and the rate at which the level of sodium falls. Symptoms may be non-specific like generalised fatigue, 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.

Physical Examination

The physical examination findings of SIADH depend on the level of sodium and rate of change of sodium levels.The following are the physical examination findings : Mild-moderate:Headache,lethargy,impaired memory,gait instability,falls.If severe symptoms like confusion,hallucinations,dysarthria,psychosis,seizures,hemiplegia,limb weakness,tremor,and coma may ensue.

Laboratory Findings

Lab findings helpful in diagnosing SIADH, include serum electrolytes,especially sodium,BUN,creatinine, glucose levels, and osmolality. Patients with syndrome of inappropriate antidiuretic hormone may be characterised with 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). They also have low BUN, normal creatinine,low uric acid and low albumin.

Imaging Findings

Imaging Studies, such as x-ray, CT and MRI may be help find the causes of syndrome of inappropriate antidiuretic hormone.

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 sharp restriction of their daily water intake and depending on the sodium levels, 3%hypertonic saline,loop diuretics with normal saline may be used. In emergency settings,Vasopressin-2 receptor antagonists (aquaretics, such as conivaptan or tolvaptan) are used. The most definitive way to treat SIADH is to deal with the underlying problem itself.Sometimes urea,demeclocycline and lithium are also used in the treatment of SIADH.

Surgery

If SIADH resulted from cancers; surgery, radiation therapy, or chemotherapy may be helpful.

Prevention

SIADH to some extent can be avoided by regular review and monitoring of drugs by the health care provider. Otherwise, there are no specific preventive modalities for SIADH.

References


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