What are the causes of Syndrome of Inappropriate Antidiuretic Hormone (SIADH) secretion?

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Last updated: March 17, 2025View editorial policy

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From the Guidelines

Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) is primarily caused by malignancies, central nervous system disorders, pulmonary diseases, and certain medications, leading to excessive release of antidiuretic hormone (ADH) and resulting in water retention and hyponatremia. The causes of SIADH can be categorized into several main groups, including:

  • Malignancies, such as small cell lung cancer, head and neck cancers, and lymphomas
  • Central nervous system disorders, including stroke, hemorrhage, trauma, infections, and tumors
  • Pulmonary diseases, such as pneumonia, tuberculosis, asthma, and COPD
  • Medications, including SSRIs, carbamazepine, cyclophosphamide, opioids, and certain chemotherapeutic agents
  • Post-surgical states Other causes include HIV infection, acute intermittent porphyria, and idiopathic SIADH where no underlying cause is identified 1. The excessive ADH causes increased water reabsorption in the kidneys' collecting ducts, resulting in dilutional hyponatremia with concentrated urine despite low serum osmolality. Some medications, such as phenytoin, carbamazepine, valproic acid, zonisamide, sulfasalazine, gold, penicillamine, hydroxychloroquine, and nonsteroidal anti-inflammatory drugs (NSAIDs), can also induce SIADH, and a thorough history of medication use is needed for patients with SIADH 1. Treatment depends on addressing the underlying cause while managing the hyponatremia through fluid restriction, salt supplementation, or in severe cases, using vasopressin receptor antagonists like tolvaptan.

From the Research

Causes of Syndrome of Inappropriate Antidiuretic Hormone (SIADH) Secretion

The causes of SIADH secretion can be categorized into several groups, including:

  • Malignant tumors: SIADH can be caused by various types of cancer, such as small cell lung cancer 2, 3, squamous cell carcinoma of the pharynx 4, and other malignancies 3, 5.
  • Central nervous system disorders: Traumatic brain injury can lead to chronic SIADH 6, and other conditions such as meningo-encephalitis can also cause SIADH.
  • Intrathoracic disorders: Infections, positive pressure ventilation, and conditions with decreased left atrial pressure can cause SIADH 3.
  • Pharmaceutical agents: Certain drugs, including vincristine, vinblastine, cisplatin, cyclophosphamide, and melphalan, can induce SIADH 3, 5.
  • Other conditions: SIADH can also be caused by stress from surgery, pain, and nausea 5.

Specific Tumors Associated with SIADH

Some specific tumors that have been reported to cause SIADH include:

  • Small cell lung cancer: This type of cancer is commonly associated with SIADH, with an incidence of 11%-15% 2, 3.
  • Squamous cell carcinoma of the pharynx: A rare case of SIADH secondary to well-differentiated squamous cell carcinoma of the naso-oropharynx has been reported 4.
  • Other malignancies: SIADH has been reported in various other types of cancer, including head and neck cancer, non-small-cell lung cancer, and hematologic malignancies 3, 5.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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