Diagnosis

Syndrome of inappropriate antidiuretic hormone secretion

Etiology

Cause [7hx][v1y][7hx]

• Drug side effects: Acetylcholine, antidepressants (SSRI), antiepileptics (carbamazepine), antipsychotics (oxcarbazepine, chlorpropamide), chemotherapy (vincristine, cyclophosphamide, cisplatin), ACE-inhibitors, nicotine, opiates, NSAIDs, desmopressin, oxytocin, delirium tremens, ecstasy, interferons, methotrexate, ciprofloxacin, haloperidol, and high dose imatinib

• Surgery/physical stress: trauma, surgery, mechanical ventilator

• Malignancy/paraneoplasia: Lung, colorectal, pancreas, gastric, bladder, prostate, ovarian, lymphoma, leukemia, brain, breast, melanoma, thymoma

• CNS: lupus, stroke, hydrocephalus, subarachnoid hemorrhage, subdural hematoma, epilepsy, multiple sclerosis, cavernous sinus thrombosis, encephalitis, meningitis, brain abscess, psychosis, acute intermittent porphyria, delirium tremens, Guillain-Barré syndrome, head trauma, hydrocephalus

• Pulmonary disease: Asthma, Atelectasis, Acute respiratory failure, pneumonia, COPD, Emphysema, Empyema, Pneumothorax, Sarcoidosis, tuberculosis, Cystic fibrosis

• Hormone: Hypopituitarism, hypothyroidism, vasopressin, desmopressin, oxytocin

• Other: HIC, porphyria, HIV

Pathophysiology [7hx]

1. ADH (vasopressin) is produced in the hypothalamus and released in a response to hyperosmolality and circulating volume depletion

2. ADH causes water reabsorption in the tubuli:

   • Osmoregulation: maintain the plasma tonicity

   • Volume Regulation: water absorption from the kidneys

3. In SIADH, hyponatremia is a result of an excess of water and not a deficiency of Na

4. Slowly progressive hyponatremia is associated with fewer symptoms than is a rapid drop of serum-Na

5. Clinical manifestation:

   • Hyponatremia

   • Cerebral edema

   • Nausea and malaise

   • CNS: concentration, headache, lethargy, obtundation, seizure, coma

Complications [v1y]

• Headaches

• Memory problems

• Depression

• Tremors

• Muscle cramps

• Respiratory failure

• Seizure

• Hallucinations

• Coma

• Death

Epidemiology

Incidence per 100.000 [v1y][qqv][sns][wfp][ush]

Approach

• Blood tests: Serum/plasma osmolality, electrolytes (Na, K, Cl, bicarbonate), creatinine, thyroid profile, serum cortisol, fasting lipid profile, liver function tests, glucose, uric acid

• Urine osmolality

• Chest x-ray

• CT caput

Clinical presentation [ioc]

1. Plasma hypoosmolarity with similar hyponatremia

2. Plasma osmolarity higher than urinary osmolarity

3. Excessive renal excretion of sodium

4. Clinical absence of factors causing edema or volume depletion

5. Normal renal and adrenal function

Diagnostic criteria [m6a][7hx]

• Hyponatremia (Na < 135 mmol/L)

• Plasma hypo-osmolality < 280 mOsm/kg

• High urine osmolality > 100 mOsm/kg

• Elevated urinary sodium excretion > 30 mEq/L

• Euvolemic without fluid overload or dehydration

• Normal salt and water intake

• Low serum uric acid levels < 4 mg/dL

• Low blood urea nitrogen < 10 mg/dL

Treatment

1. Correction of sodium levels to > 130 mEq/L [v1y]

   • Rate of correction to avoid central pontine myelinolysis: 8 mEq/L per 24 hours or 0.5 to 1 mEq/L per hour

   • Water intake restriction < 800 mL/day

   • Sodium chloride salt tablets

   • IV hypertonic saline (3%): 100 mL bolus in the first 3 to 4 hours -> repeat?

   • Loop diuretics (furosemide 20 mg twice daily) if urine osmolality > 500 mOsm/kg

   • Vasopressin receptor antagonists: conivaptan (IV) or tolvaptan (oral)

   • Dialysis?

   • Other therapies (last resort due to nephrotoxicity): lithium or demeclocycline

2. Correction of underlying abnormalities (hypothyroidism, pneumonia, CNS infection

Differential diagnoses

Acute liver failure, Adrenal insufficiency, Cirrhosis, Diabetic ketoacidosis, Diarrhea, Drug side effects, Heart failure, Hypervolemia, Hyponatremia, Hypothyroidism, Hypovolemia, Nephrotic syndrome, Portal hypertension, Renal failure