What could be causing my excessive thirst (polydipsia) and urination (polyuria) if I don't have diabetes?

Non-Diabetic Polydipsia and Polyuria: Diagnostic Approach

If you have excessive thirst and urination without diabetes, the most likely causes are primary polydipsia (excessive fluid intake), diabetes insipidus (central or nephrogenic), chronic kidney disease, or medication effects—and you need a systematic evaluation starting with measurement of urine osmolality and plasma sodium to differentiate these conditions. 1

Key Differential Diagnoses to Consider

The following conditions must be systematically evaluated when diabetes mellitus has been excluded:

Primary Disorders of Water Balance

• Primary polydipsia (psychogenic or habitual excessive drinking) is diagnosed by demonstrating response to water restriction, with basal plasma copeptin levels <21.4 pmol/L suggesting this diagnosis 1
• Central diabetes insipidus results from deficient vasopressin secretion and responds to exogenous vasopressin administration 2
• Nephrogenic diabetes insipidus occurs when kidneys are resistant to vasopressin, failing to concentrate urine despite adequate hormone levels 2, 3

Secondary Causes

• Chronic kidney disease impairs urine concentration ability and is a common cause of polyuria 3
• Hypercalcemia from conditions like multiple myeloma causes excessive calcium release, leading to polyuria and progressive dehydration 4
• Medication-induced polyuria from drugs that impair insulin secretion or kidney function 4
• Electrolyte disorders including hypokalemia can impair renal concentrating ability 2

Diagnostic Algorithm

Initial Assessment

• Measure 24-hour urine output: Polyuria is defined as >3 L/day in adults or >2 L/m²/day in children 3
• Check urine specific gravity/osmolality: Low urine specific gravity (<1.010) or osmolality (<300 mOsm/kg) indicates impaired concentration ability 5
• Verify plasma glucose and HbA1c: Confirm diabetes mellitus is truly excluded, as uncontrolled diabetes is the most common cause 4

Distinguishing Primary Polydipsia from Diabetes Insipidus

• Water deprivation test: This is the gold standard for differentiating causes—primary polydipsia shows appropriate urine concentration with fluid restriction, while diabetes insipidus does not 1, 2
• Plasma copeptin measurement: Basal levels <21.4 pmol/L suggest primary polydipsia or diabetes insipidus 1
• Hypertonic saline or arginine infusion test: Helps differentiate central diabetes insipidus from primary polydipsia, with primary polydipsia showing positive response to water deprivation 1
• Vasopressin challenge: Administration of exogenous vasopressin clarifies the mechanism—response indicates central diabetes insipidus, while lack of response suggests nephrogenic diabetes insipidus 2

Additional Workup Based on Initial Findings

• Serum calcium and electrolytes: Hypercalcemia can cause polyuria through excessive bone resorption or malignancy 4
• Renal function tests (creatinine, eGFR): Chronic kidney disease commonly presents with polyuria before other symptoms 4
• Medication review: Many drugs impair insulin secretion or renal concentration ability 4
• Frequency-volume charts: Help distinguish polydipsia-related frequency from other bladder disorders like overactive bladder 4

Critical Pitfalls to Avoid

• Do not assume normal glucose excludes all forms of diabetes: Check for diabetes insipidus specifically, which has nothing to do with blood sugar 1, 2
• Recognize that low urine specific gravity may be the only laboratory abnormality: More common causes like kidney disease or electrolyte disorders may not show obvious abnormalities initially 5
• Distinguish from overactive bladder: Polydipsia causes large-volume voids, while overactive bladder causes small-volume frequent voids 4
• Consider dipsogenic diabetes insipidus: A rare syndrome with abnormally low osmotic threshold for thirst, causing polydipsia at plasma osmolality below normal range 6

Treatment Considerations

For Primary Polydipsia

• Behavioral modification and fluid management education is the primary approach for physiologically self-induced polydipsia 4
• GLP-1 receptor agonists (such as dulaglutide) can reduce fluid intake by approximately 490 mL (17% reduction) in patients with primary polydipsia 1

For Central Diabetes Insipidus

• Exogenous vasopressin administration is the symptomatic treatment of choice 2

For Nephrogenic Diabetes Insipidus

• Salt restriction combined with hydrochlorothiazide/amiloride or hydrochlorothiazide/indomethacin can reduce urine output by 20-50% 2

For Secondary Causes

• Treat underlying condition: Hypercalcemia requires hydration, furosemide, bisphosphonates, steroids, and/or calcitonin 4
• Optimize kidney function: For chronic kidney disease, control blood pressure and consider ACE inhibitors or ARBs 4