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Adh-Vasopressin-SIADH

Image: “AdhVasopressin” by Juancoronado1974. License: CC BY-SA 3.0


Overview

SIADH is characterized by hyponatremia and hypoosmolality due to the inadequate and continued secretion of the antidiuretic hormone despite normal plasma volume. The end-point is impaired water excretion, water retention, and hyponatremia. Hyponatremia occurs in SIADH because of excess water, not because of absolute sodium deficiency in the blood.

The classic Bartter-Schwartz criteria can be used to confirm SIADH diagnosis. Common symptoms include hyponatremia with hypoosmolality, no clinical evidence of volume depletion, no other causes of hyponatremia, urine that is not maximally diluted, i.e., reduced water excretion, and continued sodium excretion in the urine. Restricted fluid intake should correct hyponatremia in a child diagnosed with SIADH.

Epidemiology of SIADH in Children

Incidence and prevalence

The most common cause of hyponatremia in children is SIADH. The estimated prevalence of hyponatremia in children in the United States is between 2.5% and 30%. Hyponatremia can also be caused by administering large amounts of hypotonic intravenous fluids, so SIADH should be diagnosed with caution.

Men and boys are more likely to develop hyponatremia than girls. Women tend to develop drug-induced or exercise-induced hyponatremia. Hyponatremia and SIADH are more common in adults than in children.

Prognosis

The prognosis of SIADH depends on the etiology. Drug-induced SIADH usually has an excellent prognosis. On the other hand, SIADH due to a central nervous system infection is more likely to be associated with permanent neurological deficits and increased morbidity. Rapid correction of hyponatremia in patients with SIADH is associated with central pontine myelinolysis and permanent neurological impairment.

In addition to the central nervous system complications of SIADH, noncardiogenic pulmonary edema has also occurred in some patients. Severe hyponatremia is the most important prognostic factor for increased mortality in children with SIADH.

Etiology of SIADH in Children

Causes

SIADH can be caused by either:

  • Ectopic production of the antidiuretic hormone or
  • Antidiuretic hormone production from the normal hypothalamus

The most common causes of SIADH that are related to central nervous system disease are:

Subarachnoid-hemorraghe-SIADH

Image: “SubarachnoidP” by James Heilman, MD. License: CC BY-SA 3.0

  • Acute psychosis
  • Brain abscess
  • Cavernous sinus thrombosis
  • Cerebrovascular accident
  • Central nervous system lupus
  • Encephalitis
  • Head trauma
  • Multiple sclerosis
  • Subarachnoid hemorrhage
  • Intracranial hemorrhage
  • Epilepsy

Other causes associated with SIADH:

  • Lung carcinoma
  • Gastrointestinal cancers
  • Adrenocortical carcinoma
  • Ureter, bladder or prostate cancer
  • Ovarian cancers

The most common pulmonary causes of SIADH in children:

  • Bronchitis
  • Bronchiolitis
  • Asthma
  • Pneumonia
  • Cystic fibrosis
  • Pulmonary abscess
  • Tuberculosis
  • Sarcoidosis

SIADH can also occur as a complication of taking certain drugs, such as:

  • Antineoplastic drugs
  • Barbiturates
  • Carbamazepine
  • Anti-psychotic medication
  • Opiates
  • Antidepressants

Metformin, oxytocin, nonsteroidal anti-inflammatory drugs, and theophylline potentiate the effects of antidiuretic hormone but do not cause hormone overproduction. Therefore, such drugs are said to cause a SIADH-like picture and not true SIADH.

CNS Lungs GI Medications
  • Tumor
  • Meningitis
  • Encephalitis
  • Hemorrhage
  • Vasculitis
  • Surgical Trauma
  • Pneumonia
  • Bronchiolitis
  • Cystic Fibrosis
  • Malignancy
  • Gastroenteritis
  • TCA
  • SSRI
  • PPI
  • ACE inhibitor

Pathophysiology of SIADH

SIADH is characterized by the over-production of the antidiuretic hormone, which causes water retention. Excess water dilutes the extracellular sodium, causing hyponatremia; therefore, hyponatremia in SIADH is not caused by sodium deficiency.

The symptoms of SIADH are mainly due to the brain’s response to hyponatremia. Fortunately, in most cases, SIADH hyponatremia is mild to moderate and rarely severe. On the molecular level, the brain cells respond to hyponatremia by losing glutamate, creatinine, and potassium. The loss of these intracellular osmolytes is associated with brain cell swelling and, eventually, brain edema. Severe hyponatremia, which occurs in < 5% of patients, might cause severe brain cell swelling and fatal brain herniation.

Over-secretion of the ADH hormone leads to water retention by stimulating increased water permeability in the kidney’s renal collecting duct. This increases the glomerular filtration rate (GFR) due to volume expansion and vasodilation caused by brain natriuretic peptides (that cause excessive sodium excretion through urine). Natriuretic peptides are secreted because of ADH stimulation and increased plasma volume expansion. This blocks the reabsorption of sodium in the collecting duct, leading to SIADH.

Clinical Presentation of SIADH in Children

Most SIADH symptoms are attributed to hyponatremia, its severity, and the rate of development. Most SIADH cases are mild and are rarely asymptomatic, which why most cases of SIADH in children are diagnosed incidentally by laboratory investigations.

The most common symptoms

The most common symptoms of mild chronic hyponatremia in children are cognitive decline, ataxia, and frequent falls. It is a bit controversial whether frequent falling, i.e., repeated minor head trauma, is the cause or the consequence of SIADH. Symptoms of acute hyponatremia include anorexia, fatigue, and nausea. Muscle cramps, headaches, drowsiness, confusion, seizures, and even coma can occur in severe hyponatremia.

A mental status examination

A mental status examination in a child with SIADH might indicate confusion, disorientation, or delirium. Tremors, myoclonus, and abnormal deep tendon reflexes might also be evident. Patients with SIADH are usually normotensive.

Diagnostic Workup for SIADH in Children

Characteristic laboratory results

SIADH is characterized by hyponatremia (Na < 135 mmol/kg) and hypoosmolality (serum osmolality < 280 mOsm/kg). Urine Na concentration in SIADH is usually above 40 mEq/L and indicates normal renal sodium excretory capability.

Supporting laboratory tests

In addition to the previously-mentioned laboratory tests to confirm the SIADH diagnosis, other supporting laboratory tests are indicated to exclude other causes of hyponatremia. Serum glucose, cortisol, and thyroid-stimulating hormone levels should be checked. For instance, mineralocorticoid deficiency syndromes can cause hyponatremia.

Serum potassium levels should also be checked. Patients with hypokalemia and hyponatremia should undergo an arterial gas test for alkalosis. If metabolic alkalosis is present, the patient should be evaluated for vomiting-induced hyponatremia before confirming the SIADH diagnosis.

Radioimmunoassay for ADH is used for accurate diagnosis of SIADH.

Imaging studies

Imaging studies for SIADH are meant to exclude other causes of excessive antidiuretic hormone secretion, i.e., ectopic SIADH. A chest X-ray followed by a computed tomography scan (CT) or a magnetic resonance imaging study (MRI) of the lungs is a reasonable option in a patient suspected of having a lung nodule and is considered at high risk for lung carcinoma. Brain computed tomography scanning and magnetic resonance imaging are helpful for excluding central nervous system tumors, a potential cause of SIADH.

Chest-X-ray-of-sarcoidosis-nodules-SIADH

Image: “Chest X-ray of sarcoidosis nodules” by Mikael Häggström. License: CC0 1.0

Treatment of SIADH in Children

Treating SIADH in children includes three main interventions. First, restricting fluid intake usually solves SIADH in most patients, which is why it is part of the diagnosis. If that measure fails to correct the serum hypoosmolality, the patient should begin loop diuretics or increase their oral sodium chloride intake.

Vasopressin receptor antagonists and lithium should not be used in children with SIADH. Administering sodium to correct hyponatremia should be a last resort in patients with SIADH. If sodium administration is associated with rapid correction of hyponatremia, initiate administration of water, 5% dextrose, or desmopressin to lower the hyponatremia correction rate.

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