Introduction
The syndrome of inappropriate antidiuretic hormone secretion (SIADH) refers to a disorder in which antidiuretic hormone is continuously released from the pituitary gland or non-pituitary sources or its continued action on vasopressin receptors. The antidiuretic hormone helps the kidney to control the water balance in the body and excretion of it through the urine. Antidiuretic hormone (ADH) is made by the hypothalamus and then released by the pituitary gland at the base of the brain. SIADH is characterized by impaired water excretion resulting in hyponatremia (increase in salt content) with hypervolemia (increase in water content). It generally occurs secondary to other diseases in the body. SIADH can be hereditary, also called nephrogenic SIADH, caused due to mutation in vasopressin 2 (V2) receptors in the kidney.
What Is Anti Diuretic Hormone?
Antidiuretic hormone (ADH) is formed in the hypothalamus and released from the pituitary gland. It acts to maintain blood pressure, blood volume, and tissue water content in the body. It controls the amount of water and hence the concentration of urine excreted by the kidney. The release of antidiuretic hormone occurs when there is a decrease in blood volume or low blood pressure, which occurs during dehydration (not drinking enough water), or hemorrhage (loss of blood). This is detected by sensors called baroreceptors in the heart and large blood vessels. These stimulate the release of antidiuretic hormone. High levels of antidiuretic hormone prevent the excretion of water by the kidneys, for example, SIADH. Low levels of the antidiuretic hormone will cause the kidney to excrete excess water. Urine volume increases, leading to dehydration and a drop in blood pressure.
What Causes Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)?
Conditions leading to the syndrome of inappropriate antidiuretic hormone secretion are -
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Disturbances in the Central Nervous System - Any abnormality in the central nervous system like stroke, infection, hemorrhage, psychosis, and mental illness can enhance ADH release from the pituitary gland leading to SIADH.
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Malignancies - Small cell lung cancer is found to be the most common tumor-causing ADH production, and extrapulmonary small cell carcinomas, head neck cancers, and olfactory neuroblastoma can also cause an increase in the release of ADH hormone.
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Drugs - The most common drugs associated with SIADH are Carbamazepine, Chlorpropamide, Oxcarbazepine, Cyclophosphamide, and selective serotonin reuptake inhibitors.
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Surgery - Hypersecretion of ADH hormone is often associated with surgical procedures and mediated by pain afferent.
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Pulmonary Disease - Pulmonary diseases caused by viral, bacterial, and tuberculous infections, particularly pneumonia, can lead to SIADH by unknown mechanisms. A similar mechanism is also seen in patients with asthma, acute respiratory failure, and pneumothorax.
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Hormone Deficiency - Hypopituitarism and hypothyroidism can cause hyponatremia and SIADH.
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Hormone Administration - The excess release of the antidiuretic hormone can be induced by exogenous hormone administration by increasing the activity of vasopressin receptors.
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Human Immunodeficiency Virus (HIV) Infection - Hyponatremia is caused due to acquired immunodeficiency syndrome, early symptomatic HIV infection, or it can be due to volume depletion secondary to adrenal insufficiency.
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Hereditary SIADH - A mutation in the gene for the renal vasopressin receptor (V2) situated on the X chromosome causes hereditary SIADH.
What Are the Symptoms of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)?
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Cerebral Oedema - Decrease in sodium concentration in blood and extracellular fluid commonality causes the water to move inside the cells causing cerebral edema.
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Hyponatremia - Sodium concentration below 125 to 130 milliequivalent per liter is called hyponatremia and can cause symptoms like malaise and nausea. Severe falls in sodium concentration can also cause headaches, lethargy, and seizures. If the sodium concentration falls below 115 to 120 milliequivalents per liter, it can lead to respiratory arrest and coma.
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Chronic Hyponatremia - The patient remains asymptomatic despite a serum sodium concentration below 120 mmol per liter because of cerebral adaptation to low sodium concentration. Symptoms like nausea, vomiting, cognitive problems, fatigue, muscle cramps, confusion, gait disturbances, and dizziness can occur.
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Impaired Water Excretion - The water excretion is affected due to excess release of antidiuretic hormone. This leads to the retention of fluid inside the body.
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Hypervolaemia - It is a condition characterized by the retention of water inside the body.
Other symptoms include -
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Nausea and vomiting.
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Problems in balance can result in falls.
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Headache.
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Mental changes like strange behavior, confusion, and memory problems.
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Severe retention of water can lead to seizures or coma.
How Is Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) Diagnosed?
It is very necessary to diagnose hypothyroidism and adrenal insufficiency before confirming the patient with SIADH. Test for detection of SIADH -
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Serum osmolality and serum sodium.
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Urine sodium concentration and commonality.
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Renal function test for blood urea nitrogen and creatinine.
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Blood sugar random (BSR).
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Liver function tests.
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Fasting lipid profile.
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Thyroid profile.
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Serum cortisol.
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Serum potassium, bicarbonate, and chloride.
How Is Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) Treated?
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Sodium Levels - Patients suffering from chronic SIADH Have a combination of ADH-induced water retention and secondary solute loss. The treatment involves the correction and maintenance of corrected sodium levels and underlying abnormalities such as hypothyroidism or pulmonary or CNS infection. For patients presenting with mild to moderate symptoms, the main goal of the treatment is the restriction of water intake to less than 800 milliliters per day.
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Hyponatremia - In case of consistent low sodium levels, sodium chloride in the form of oral salt tablets or intravenous line solution can be given. Diuretics such as Furosemide can also be prescribed to decrease urine concentration and increase water excretion.
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Severe Symptoms - In order to treat severe symptoms such as seizures, confusion, and delirium, initial management of the condition with hypertonic saline infusion for the first few hours should be done. A three percent hypertonic bolus of 100 milliliters of saline is administered in the first three to four hours, and sodium levels are checked within two to three hours so that further doses can be adjusted.
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Severe Persistent SIADH - Vasopressin receptor antagonists such as Conivaptan or Tolvaptan can be given. These drugs prevent ADH-mediated water retention by antagonizing vasopressin receptors and V2 suppression to correct hyponatremia.
Conclusion :
Hyponatremia generally occurs secondary to the syndrome of inappropriate secretion of antidiuretic hormone. The diagnosis is made by confirming the presence of serum hyponatremia and natriuresis. Clinical symptoms depend upon the rate of development of hyponatremia. Symptoms include confusion, headache, vomiting, nausea, anorexia, convulsions, and coma. The treatment is decided based on the severity of the clinical symptoms.