Syndrome of Inappropriate ADH Secretion

Overview

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is characterised by excess antidiuretic hormone (ADH) in the blood either from the posterior pituitary gland or from an ectopic source.

To help make sense of this chapter, it may be helpful to refer to Endocrine and Metabolic Physiology.

Antidiuretic hormone

Also known as vasopressin, antidiuretic hormone (ADH) is a hormone secreted from the posterior pituitary gland in response to increased blood osmolality. It promotes water reabsorption in the kidney’s collecting ducts through the insertion of aquaporin-2 channels. It also constricts arterioles, increasing peripheral vascular resistance and hence, arterial blood pressure.

SIADH

The increased ADH secretion causes an excess amount of water reabsorption which leads to dilution of the solutes in the blood, and a reduced osmolality. A common finding is that patients have euvolaemic hyponatraemia. At the same time, cells can swell which can lead to complications according to the site affected (e.g. the brain cells swelling leading to seizures and comas). 

Causes

• Malignant:
  • Small cell lung cancer
  • Pancreatic cancer
  • Prostate cancer
  • Lymphoma
• Neurological causes:
  • Stroke
  • Subarachnoid haemorrhage
  • Meningitis
  • Encephalitis
  • Brain abscess
  • Infection:
  • Pneumonia
  • Tuberculosis
• Drugs:
  • SSRIs
  • Tricyclic antidepressants
  • Carbamazepine
  • Sulfonylureas
  • NSAIDs

Presentation

Features may be:

• Asymptomatic
• Features of brain swelling:
  • Nausea
  • Vomiting
  • Headache
  • Seizures
  • Changes to consciousness
  • Coma

Investigations

• U&Es:
  • Shows hyponatraemia
  • Urea may be low due to dilution
• Serum osmolality:
  • Reduced
• Urine osmolality:
  • Increased (>100 mOsm/kg H2O)
• Urine sodium:
  • Increased (>30 mmol/L)

Diagnosis

Overview

SIADH can be diagnosed if there is a reduced serum osmolality, increased urine osmolality, and increased urinary sodium so long as the patient is euvolaemic, has no orthostasis, no features of dehydration or hypervolaemia, has normal thyroid and adrenal function, and there has been no recent diuretic use. 

Management

Overview

• The sodium must be corrected slowly to reduce the risk of central pontine myelinolysis
• 1st-line: fluid restriction + treat the underlying cause
• Other options are vasopressin receptor antagonists (e.g. tolvaptan)

Complications

• Features of brain swelling (mentioned above)
• Central pontine myelinolysis if hyponatraemia is corrected too quickly