Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

What condition, the most common cause of euvolemic hypotonic hyponatremia, involves increased ADH secretion or action?

Syndrome of inappropriate antidiuretic hormone secretion (SIADH). Summary 1

What are the three general mechanisms causing SIADH, according to the summary?

Increased pituitary ADH secretion (e.g., due to infection, drugs), ectopic ADH production (e.g., SCLC), or enhanced ADH receptor activation (nephrogenic SIADH). Summary / Etiol 2

What is the primary electrolyte abnormality in SIADH, caused by increased renal water retention?

Hyponatremia. Summary / Clin 3

What key lab/clinical findings are needed for an SIADH diagnosis, according to the summary?

Serum hyponatremia/hypoosmolality, increased urine Na+/osmolality, clinical euvolemia, and exclusion of other causes (e.g., hypothyroidism, adrenal insufficiency). Summary / Dx 4

What are the main components of SIADH treatment mentioned in the summary?

Manage acute hyponatremia (hypertonic saline), treat underlying cause, fluid restriction, and possibly pharmacologic treatments to increase water excretion. Summary / Tx 5

Name two CNS conditions that can cause increased pituitary ADH secretion leading to SIADH.

Stroke, trauma/bleeding, infection, post-neurosurgery, or psychosis. (Any 2) Etiology 6

Name two pulmonary conditions that can cause increased pituitary ADH secretion leading to SIADH.

Pneumonia or COPD. (Also HIV, acute intermittent porphyria). Etiology 7

What anticonvulsant drugs are commonly associated with causing SIADH?

Carbamazepine and valproate. Etiology 8

What classes of antidepressant drugs are listed as causes of SIADH?

SSRIs (e.g., sertraline), MAO inhibitors, and TCAs (e.g., amitriptyline). Etiology 9

Name an antineoplastic agent class commonly associated with SIADH.

Mitotic inhibitors (e.g., vincristine) or Alkylating agents (e.g., cyclophosphamide, cisplatin). Etiology 10

What other drug classes (besides specific examples above) can cause SIADH?

Antipsychotics (e.g., haloperidol), Analgesics (e.g., NSAIDS, opioids), or illicit substances (e.g., MDMA). Etiology 11

What is the classic malignancy associated with paraneoplastic ectopic ADH production causing SIADH?

Small cell lung carcinoma (SCLC). Etiology 12

Besides SCLC, name another malignancy type associated with ectopic ADH production causing SIADH.

Head and neck cancer, extrapulmonary small cell carcinoma, or olfactory neuroblastoma. Etiology 13

What causes nephrogenic SIADH?

A mutation of the vasopressin-2 (V2) receptor gene, leading to enhanced receptor activation. Etiology 14

What channels are inserted into the distal tubule/collecting ducts due to increased ADH in SIADH?

Aquaporin-2 water channels. Pathophysiology 15

How does increased ADH in SIADH affect urine concentration and osmolality?

Water is reabsorbed from the collecting ducts, concentrating the urine and increasing urine osmolality (typically higher than serum osmolality). Pathophysiology 16

How does water retention in SIADH lead to euvolemic hyponatremia?

Initial water retention decreases serum osmolality; transient volume expansion triggers natriuresis (via ANP/BNP, suppressed aldosterone), restoring euvolemia but worsening hyponatremia. Pathophysiology 17

What potential neurological complication can occur in SIADH due to osmotic fluid shifts from severe hyponatremia?

Cerebral edema and increased intracranial pressure. Pathophysiology 18

The clinical features of SIADH are primarily due to what underlying abnormality?

Hyponatremia. Clinical Features 19

List two MILD symptoms of hyponatremia seen in SIADH.

Anorexia, nausea, vomiting, headache, or muscle cramps. (Any 2) Clinical Features 20

List two MODERATE symptoms of hyponatremia seen in SIADH.

Muscle weakness, lethargy, or confusion. (Any 2) Clinical Features 21

List two SEVERE symptoms of hyponatremia seen in SIADH.

Seizures or altered consciousness. Clinical Features 22

What is the typical volume status and blood pressure finding in patients with SIADH?

Patients are usually euvolemic and normotensive, with no edema. Clinical Features 23

What is the general diagnostic approach for SIADH?

Confirm euvolemic hypotonic hyponatremia via labs; exclude other causes (thyroid, adrenal, renal, diuretics); confirm SIADH criteria; investigate underlying etiology. Diagnosis 24

Why is SIADH considered a diagnosis of exclusion?

Other causes of euvolemic hypotonic hyponatremia (e.g., hypothyroidism, adrenal insufficiency, diuretics) must be ruled out first. Diagnosis 25

What serum sodium level defines hyponatremia in the SIADH diagnostic criteria?

Serum sodium < 135 mEq/L. Diagnosis 26

What serum osmolality level defines hypoosmolality in the SIADH diagnostic criteria?

Serum osmolality < 275 mOsm/kg. Diagnosis 27

What clinical volume status is required for an SIADH diagnosis?

Clinical euvolemia (no signs of hypovolemia or hypervolemia). Diagnosis 28

What is the minimum urine osmolality required for an SIADH diagnosis, indicating inappropriately concentrated urine?

Urine osmolality > 100 mOsm/kg. Diagnosis 29

What level of urine sodium concentration typically supports an SIADH diagnosis?

Urine sodium concentration > 20-30 mEq/L (indicating inappropriate sodium excretion). Diagnosis 30

Name two conditions that must be excluded before diagnosing SIADH.

Hypothyroidism, hypocortisolism (adrenal insufficiency), acute kidney injury (AKI), or recent diuretic use. (Any 2) Diagnosis 31

What finding regarding plasma ADH levels supports an SIADH diagnosis (though not required)?

Plasma ADH levels are inappropriately normal to elevated relative to the low serum osmolality. Diagnosis 32

What typical findings for BUN and serum uric acid may support an SIADH diagnosis?

BUN < 10 mg/dL and serum uric acid < 4 mg/dL. Diagnosis 33

What is the immediate treatment for acute, severely symptomatic hyponatremia in SIADH?

Immediate 3% hypertonic saline administration, ICU monitoring, and potentially adding a loop diuretic (e.g., furosemide). Treatment 34

What is the general management approach for non-acute, non-severe hyponatremia due to SIADH?

Fluid restriction (first-line), treat the underlying cause, and consider pharmacotherapy if restriction fails. Treatment 35

What is the maximum rate of serum sodium correction per 24 hours in chronic SIADH to prevent ODS?

10-12 mEq/L/24h is the maximum limit (use lower limit of 8 mEq/L/24h if high risk for ODS). Treatment 36

What serious neurological complication can result from over-rapid correction of chronic hyponatremia in SIADH?

Osmotic demyelination syndrome (ODS). Treatment 37

What is the first-line treatment for non-severe SIADH, and what is a typical daily target?

Restriction of all fluids is first-line (< 1000 mL/day typically recommended, ideally 500 mL less than daily urine output). Treatment 38

When is pharmacotherapy considered for increasing free water excretion in SIADH management?

When fluid restriction alone fails to adequately increase serum sodium. Treatment 39

Name one class of medications used to increase free water excretion in SIADH refractory to fluid restriction.

Vaptans (e.g., conivaptan, tolvaptan), Urea, Demeclocycline, or low-dose Loop diuretics combined with oral salt tablets. (Any 1 class/example). Treatment 40