What is the most likely diagnosis for a 50-year-old woman with a history of major depression, previous right mastectomy, and recent lung metastases, presenting with excessive urination and thirst, slightly elevated fasting blood sugar, and low urine osmolality?

Diabetes Insipidus (Central)

The most likely diagnosis is central diabetes insipidus (DI), given the combination of hypernatremia (150 mmol/L), inappropriately dilute urine (osmolality 110 mOsm/kg), polyuria, polydipsia, and lung metastases from breast cancer—a known cause of metastatic brain involvement affecting the hypothalamic-pituitary axis. 1

Diagnostic Reasoning

Key Laboratory Findings Point to Diabetes Insipidus

• The urine osmolality of 110 mOsm/kg is pathognomonic for diabetes insipidus when combined with elevated serum sodium (150 mmol/L) and normal-to-high serum osmolality 1
• The inappropriately dilute urine (<300 mOsm/kg) in the setting of hypernatremia indicates complete failure of urinary concentration despite adequate physiologic stimulus for ADH release 1
• This pattern is diagnostic for DI, as the kidneys are unable to concentrate urine appropriately in response to dehydration 2, 1

Why Not the Other Options?

SIADH (Option D) is definitively excluded by the laboratory findings:

• SIADH requires urine osmolality >300 mOsm/kg, but this patient has 110 mOsm/kg 3
• SIADH causes hyponatremia (low sodium), not hypernatremia 3, 4
• While lung metastases commonly cause SIADH in lung cancer patients (10-45% of cases), the electrolyte pattern here is the opposite of what SIADH produces 4

Psychogenic polydipsia (Option C) is unlikely because:

• Psychogenic polydipsia typically causes hyponatremia (low sodium), not hypernatremia 5, 6, 7
• Patients with primary polydipsia develop low serum osmolality (236-244 mOsm/kg) from excessive water intake 7
• The hypernatremia in this case indicates inadequate water intake relative to losses, not excessive intake 2
• While she has depression, the electrolyte pattern contradicts this diagnosis 5, 6

Adipsic hypernatremia (Option B) is less likely because:

• The patient reports thirst (polydipsia), which excludes adipsic (absence of thirst) hypernatremia
• Adipsic hypernatremia occurs when the thirst mechanism is impaired, but this patient is actively drinking 2

Central vs. Nephrogenic DI Distinction

Central DI is most likely given the clinical context:

• Breast cancer with lung metastases has high propensity for brain metastases affecting the hypothalamic-pituitary axis, causing central DI
• The 3-month timeline (lung metastases diagnosed 3 months ago, symptoms for 2 months) suggests progressive metastatic disease
• Central DI results from inadequate vasopressin secretion from hypothalamic-pituitary dysfunction 8

Nephrogenic DI is less likely because:

• Nephrogenic DI typically requires a medication cause (lithium, demeclocycline) or chronic kidney disease, neither mentioned here 1
• The clinical context of metastatic cancer strongly favors a central cause 3

Clinical Implications

Immediate Management Priorities

• Free access to water is essential to prevent life-threatening hypernatremic dehydration, which can develop rapidly 2, 1
• Close monitoring of fluid balance, weight, and serum sodium is critical 2
• Patients capable of self-regulating should determine fluid intake based on thirst rather than prescribed amounts 2

Diagnostic Confirmation

• Measure plasma copeptin or vasopressin levels to confirm central vs. nephrogenic DI 1
• Brain imaging (MRI) is warranted to evaluate for hypothalamic-pituitary metastases given the cancer history
• Water deprivation test may be considered but is less necessary given the clear laboratory pattern 8

Treatment Approach

• Desmopressin (DDAVP) is the treatment of choice for central DI
• Regular assessment of serum electrolytes, particularly sodium and potassium 1
• Vigilance for signs of dehydration or overhydration during treatment initiation 1

Common Pitfalls to Avoid

• Do not restrict water access in this patient—this would worsen hypernatremia and cause life-threatening dehydration 2
• Do not assume SIADH based solely on lung metastases without checking the actual sodium and urine osmolality values 3, 4
• The slightly elevated fasting glucose (6.8 mmol/L) is a red herring and does not explain the severe polyuria or low urine osmolality pattern seen here 3