At a Glance

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is characterized by hyponateremia and hypo-osmolality in the setting of an inappropriately concentrated urine specimen. The condition (as the name suggests) is produced by excessive action of vasopressin, thereby reducing the ability of the kidneys to excrete free water. This results in excessive dilution of the plasma component; hence, the hypo-osmolality. The condition is not associated with edema and signs of overhydration. Clinically, the patient is usually euvolemic, and renal function in terms of creatinine excretion is normal. Natriuresis (excessive renal excretion of sodium) is common and is likely a consequence of natriuretic peptides.

Causes of SIADH include:

Malignancy, including solid tumors and lymphomas

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Pulmonary conditions (i.e., pneumonia, tuberculosis (TB), vasculitis, and positive pressure ventilation)

Drugs (e.g., selective serotonin reuptake inhibitors, tricyclics, phenothiazines, carbamazepine, cyclophosphamide)

Desmopressin: Synthetic vasopressin is used in the therapy of von Willebrand disease and mild hemophilia.

Intracranial Disorders (e.g., meningitis, encephalitis, abscess, vasculitis, hemorrhage (subdural or subarachnoid))

Acute porphyria

Multiple sclerosis

Guillain-Barre syndrome

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

The criteria for SIADH include:

Hyponatremia (Na <134 mmol/L) and/or plasma hypo-osmolality (<280 mosmols/kg H2O)

Inappropriately concentrated urine with urine osmolality exceeding 100 mosmols/kg H2O

Natriuresis (urine sodium >40 mmols/L with normal diet)

Clinical euvolemic (not edematous)

No evidence of hypothyroidism or adrenal disorder

(Table 1)

Table 1.
Sodium ≤ 135 mmol/
Osmolality ≤ 280 mosmols/kg Osmolality > 100 mosmols/kg This is a supplementary test.
Supplementary: [Na+] > 40 mmol/ Normally >80% of a water load* is excreted over a 4-hour period. In SIADH, this is <80%.
Uric Acid < 4 mg/dL * 20 mls per kg body weight
BUN < 10 mg/dL

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

Medications, including antipsychotics, antidepressants, and certain antiepileptic drugs, may produce SIADH or may exacerbate the condition.

What Lab Results Are Absolutely Confirmatory?

There is no single test that is absolutely confirmatory. All the criteria (and perhaps the supplementary tests) should be taken into account. For example, a single measurement of vasopressin may be difficult to interpret and hyponatremia and hypo-osmolality can be produced by primary polydipsia.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Supplementary tests for SIADH include:

Plasma uric acid less than 4 mg/dL, BUN less than 10 mg/dL (reflecting hemodilution with normal GFR), fractional excretion of Na greater than 1%, and fractional excretion of urea greater than 55%

Abnormal water load test: This is performed by (oral) administration of water at 20 ml of water per kg of bodyweight over 30 minutes. Then urine samples are collected at 30-minute intervals for 4 hours. Urine volume is expressed as a percentage of water intake. Normally, more than 80% of the water load is excreted over 4 hours, and urine osmolality falls to less than 100 mosmols/kg H2O.

Analysis of plasma arginine vasopressin is complex in this group of patients. Four patterns have been recognized:

  • Type A is the most common form of SIADH. Plasma vasopressin is inappropriately elevated for the serum osmolality and is apparently independent of any osmotic regulation. There is no linear relationship between vasopressin and plasma osmolality. Type A is common in lung cancer.

  • Type B is also common. Here, there is a linear relationship between vasopressin and plasma osmolality, and a rise in plasma osmolality stimulates vasopressin secretion. What is abnormal is that the osmotic threshold is reset so that vasopressin is released at much lower plasma osmolalities than normal.

  • Type C is rare. Plasma arginine vasopressin (AVP) concentrations are inappropriately high only at low plasma osmolalities. Vasopressin concentrations and responses to plasma osmolality are entirely normal within the reference range for plasma osmolality. However, when the plasma is hypo-osmolar, typically less than 278mOsm/kg H2O, vasopressin is over-secreted in a fixed pattern, leading to an inappropriately elevated concentration.

  • Type D is also rare. Vasopressin is appropriately low in the setting of hypo-osmolality. Regulation of vasopressin secretion by plasma osmolality appears normal. If the plasma osmolality is raised into the physiologic range by hypertonic saline infusion, plasma vasopressin responds normally and rises. Type D may be a consequence of a nephrogenic form of SIADH in which water transport in the distal nephron/collecting tubules is constitutively activated.

In types A, B, and C, the plasma vasopressin is inappropriately elevated for the low plasma osmolality. In type D, however, the plasma vasopressin is appropriately suppressed.