In a 74‑year‑old male with a Pseudomonas aeruginosa urinary tract infection on amikacin who has hyponatremia (serum sodium 123 mmol/L), low serum osmolality, and inappropriately concentrated urine with high urine sodium, what is the diagnosis and its most likely cause?

Diagnosis: Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

This 74-year-old male has SIADH, most likely drug-induced by amikacin, as evidenced by hypotonic hyponatremia (serum osmolality 273 mOsm/kg), inappropriately concentrated urine (urine osmolality 290 mOsm/kg), and elevated urine sodium (71 mmol/L) despite low serum sodium. 1

Why This is SIADH

The laboratory findings meet all five cardinal diagnostic criteria for SIADH 2:

• Hypotonic hyponatremia: Serum sodium 123 mmol/L with serum osmolality 273 mOsm/kg (normal 275-290) 1
• Inappropriately concentrated urine: Urine osmolality 290 mOsm/kg exceeds serum osmolality, indicating failure to suppress ADH despite low serum osmolality 2, 3
• Natriuresis: Spot urine sodium 71 mmol/L (>20-40 mmol/L confirms renal sodium wasting) 1
• Euvolemic state: No clinical evidence of volume depletion (no orthostatic hypotension, dry mucous membranes) or hypervolemia (no edema, ascites, JVD) is implied by the presentation 2
• Normal renal and adrenal function: Presumed based on clinical context 2

Most Likely Cause: Amikacin-Induced SIADH

Aminoglycosides, including amikacin, are a recognized cause of drug-induced SIADH. 1, 3 The temporal relationship between amikacin therapy for Pseudomonas UTI and development of hyponatremia strongly suggests this etiology.

The four major categories of SIADH causes are 2, 3:

1. Drugs (most relevant here - amikacin)
2. Malignancy
3. CNS disorders
4. Pulmonary diseases

Pathophysiology

In SIADH, persistent or elevated plasma AVP (antidiuretic hormone) concentrations occur despite low plasma osmolality 2. This leads to:

• Impaired free water excretion: The kidneys cannot dilute urine appropriately, resulting in urine osmolality >100 mOsm/kg when it should be <100 mOsm/kg 1
• Water retention with dilutional hyponatremia: Continued fluid intake in the setting of inappropriate ADH leads to progressive hyponatremia 2
• Compensatory natriuresis: The body attempts to maintain fluid balance by excreting sodium, resulting in high urine sodium (>20-40 mmol/L) despite hyponatremia 1, 2

Clinical Significance

At sodium 123 mmol/L, this represents moderate hyponatremia (120-125 mmol/L) 4. Even without severe neurological symptoms, this level carries significant risk:

• 60-fold increase in hospital mortality (11.2% vs 0.19% in normonatremic patients) 1
• Increased fall risk: 21% in hyponatremic patients vs 5% in normonatremic patients 1
• Risk of progression to severe symptomatic hyponatremia if untreated 1

Immediate Management Recommendations

Discontinue amikacin immediately and switch to an alternative antibiotic for Pseudomonas coverage (such as cefepime or piperacillin-tazobactam). 1

Implement fluid restriction to 1 L/day as first-line therapy for euvolemic hyponatremia. 1, 5 This is the cornerstone of SIADH treatment and will prevent further sodium decline.

If fluid restriction fails after 24-48 hours, add oral sodium chloride 100 mEq three times daily. 1

Target correction rate of 4-6 mmol/L per day, never exceeding 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome. 4, 1 At age 74 with potential comorbidities, this patient may be at higher risk for complications from rapid correction.

Monitor serum sodium every 24 hours initially to ensure safe correction rates and adjust therapy accordingly. 1

Common Pitfalls to Avoid

• Do not use isotonic saline (0.9% NaCl): This will worsen hyponatremia in SIADH because the urine osmolality (290 mOsm/kg) exceeds the osmolality of normal saline (308 mOsm/kg), resulting in net free water retention 1
• Do not continue amikacin: Drug-induced SIADH will not resolve until the offending agent is discontinued 3
• Do not correct too rapidly: Exceeding 8 mmol/L correction in 24 hours risks osmotic demyelination syndrome, which manifests 2-7 days after overcorrection with dysarthria, dysphagia, and quadriparesis 4, 1
• Do not use hypertonic saline unless severe symptoms develop: Reserve 3% saline for seizures, coma, or severe neurological symptoms only 1, 5

Alternative Diagnoses to Exclude

While SIADH is most likely, briefly consider:

• Cerebral salt wasting (CSW): Would show hypovolemia (orthostatic hypotension, tachycardia, dry mucous membranes) rather than euvolemia. CSW requires volume replacement, not fluid restriction. 1
• Hypothyroidism or adrenal insufficiency: Should be excluded with TSH and cortisol if SIADH does not resolve with treatment 1, 2