Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
Basics
Description
Description
- Most common cause of hyponatremia occurring in up to 15–30% of hospitalized patients (and significantly increases patient mortality in some studies)
- A water balance problem more than one of sodium (Na) balance
- Normal regulation of water balance:
- Antidiuretic hormone (ADH):
- Integral controller of water balance
- Increases water permeability of the collecting tubules, resulting in free water reabsorption
- Synthesized by hypothalamus but secreted by posterior pituitary gland
- Water deprivation (increased plasma osmolality) stimulates secretion as sensed by:
- Osmoreceptors/atrial stretch receptors
- Carotid baroreceptors
- Aortic arch/pulmonary veins
- Antidiuretic hormone (ADH):
- Hyponatremia:
- Mild: Serum sodium <135 mEq/L
- Moderate: Serum sodium <130 mEq/L
- Severe: Serum sodium <125 mEq/L
- Excess extracellular water relative to Na
- Depletional hyponatremia:
- Sodium depletion can be caused by diet, GI losses, diuretic use, and renal or adrenal disease
- Often accompanied by extracellular fluid volume depletion
- Hyponatremia associated with clinical signs of hypovolemia
- Increased Hct, BUN, Cr
- Urinary sodium excretion <20 mEq/L
- Dilutional hyponatremia:
- Increased extracellular water in the presence of normal or increased total body sodium
- Can be caused by increased fluid intake (oral, IV), drugs, or medical conditions
- Euvolemia with edema
- Normal or decreased Hct, BUN, Cr
- Urinary sodium excretion >20 mEq/L
- Inappropriate ADH secretion is a form of dilutional hyponatremia
- Definition of SIADH:
- ADH secretion in the absence of hyperosmolality or hypovolemia leading to inappropriate elevation of arginine vasopressin (AVP) causing stimulation of aquaporins, and reabsorption of water from renal tubules
- Criteria for definition:
- Essential features:
- Plasma osmolality of <270 mOsm/kg
- Evidence of inappropriate urinary concentration (UOsm >100 mOsm/kg of water)
- Clinical euvolemia (no evidence of volume overload or depletion)
- Elevated plasma Na (>30 mmol/L) with normal salt intake
- Absence of concomitant hypoadrenalism, hypothyroidism, or renal dysfunction
- No recent diuretic use
- Supplemental features:
- Plasma uric acid <4 mg/dL
- BUN <10 mg/dL
- FENa >1%
- Failure to correct hyponatremia after an infusion of normal saline (NS) 0.9%
- Abnormal water load test (inability to excrete ≥90% of a 20 mL/kg water load in 4 hr)
- Essential features:
Etiology
Malignant DisordersEtiology
- ADH-producing tumors
- Cancer (small-cell lung, pancreatic, prostate)
- Pituitary tumors
- Thymoma
- Lymphoma
Pulmonary Disorders
- Infections (pneumonia/TB/lung abscess)
- Mechanical dysfunction (COPD/PPV)
CNS Disorders
- Mass lesions (tumor/abscess/subdural hematoma)
- Inflammation (meningitis/encephalitis)
- Demyelination (multiple sclerosis/Guillain–Barré)
- Subarachnoid hemorrhage
- Traumatic brain injury
- Acute psychosis
- CVA
Medications
- Stimulators of AVP release (nicotine, TCAs, phenothiazines)
- Altering renal function (DDAVP, oxytocin, vasopressin, prostaglandin synthesis inhibitors – NSAIDs)
- ACE inhibitors and thiazides, especially in combination
- Chlorpropamide
- Vincristine
- Anticonvulsants (carbamazepine, oxcarbazepine)
- Antidepressants (Trazadone, Mirtazapine, Venlafaxine, SSRIs)
- Antipsychotics (with higher risk associated with first generation drugs)
- Ecstasy (MDMA)
Transient
- Endurance exercise
- General anesthesia
- Pain
- Stress
Other
- Often multifactorial
- Hereditary
- HIV/AIDS
- Idiopathic
ALERT
May be underdiagnosed in psychiatric patients due to:
- Symptoms can mimic underlying psychiatric conditions
- Many psychiatric conditions (i.e., schizophrenic polydipsia, compulsive drinking behaviors, anorexia-related water loading) and medications precipitating SIADH (see Medications under Etiology)
ALERT
Cerebral salt-wasting syndrome (CSWS) can mimic SIADH
- Seen in patients with cerebral tumors or subarachnoid hemorrhage and in neurosurgical patients
- Etiology unclear
- Represents appropriate water resorption in the face of salt wasting (urine Na >30–40 mmol/L)
- Fluid restriction can help differentiate the 2:
- In SIADH: Hypouricemia will correct
- In CSWS: Hypouricemia will persist
- Treatment of CSWS may differ from that of SIADH:
- Infusion of NS
- May benefit from fludrocortisones therapy
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Citation
Schaider, Jeffrey J., et al., editors. "Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)." 5-Minute Emergency Consult, 6th ed., Lippincott Williams & Wilkins, 2020. Emergency Central, emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307273/all/Syndrome_of_Inappropriate_Antidiuretic_Hormone_Secretion__SIADH_.
Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH). In: Schaider JJJ, Barkin RMR, Hayden SRS, et al, eds. 5-Minute Emergency Consult. Lippincott Williams & Wilkins; 2020. https://emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307273/all/Syndrome_of_Inappropriate_Antidiuretic_Hormone_Secretion__SIADH_. Accessed December 9, 2024.
Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH). (2020). In Schaider, J. J., Barkin, R. M., Hayden, S. R., Wolfe, R. E., Barkin, A. Z., Shayne, P., & Rosen, P. (Eds.), 5-Minute Emergency Consult (6th ed.). Lippincott Williams & Wilkins. https://emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307273/all/Syndrome_of_Inappropriate_Antidiuretic_Hormone_Secretion__SIADH_
Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) [Internet]. In: Schaider JJJ, Barkin RMR, Hayden SRS, Wolfe RER, Barkin AZA, Shayne PP, Rosen PP, editors. 5-Minute Emergency Consult. Lippincott Williams & Wilkins; 2020. [cited 2024 December 09]. Available from: https://emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307273/all/Syndrome_of_Inappropriate_Antidiuretic_Hormone_Secretion__SIADH_.
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