What are the differential diagnoses for urinary urgency and frequency in an adult with a normal urine dip‑stick and microscopy?

Differential Diagnosis for Urinary Urgency and Frequency with Negative Urinalysis

When urinalysis is negative in a patient with urgency and frequency, overactive bladder (OAB) is the most likely diagnosis, but you must systematically exclude nocturnal polyuria, medication effects, bladder outlet obstruction, interstitial cystitis, and systemic causes before making this diagnosis of exclusion. 1

Primary Diagnostic Considerations

Overactive Bladder (Non-Neurogenic)

• OAB is characterized by urgency—a sudden, compelling desire to void that is difficult to defer—typically accompanied by frequency (>7 voids during waking hours) and often nocturia, in the absence of infection or other obvious pathology. 1
• This represents a diagnosis of exclusion after ruling out other conditions through history, physical examination, and urinalysis. 1
• Urgency is the hallmark symptom that distinguishes OAB from other causes of frequency. 1

Nocturnal Polyuria

• Nocturnal polyuria is defined as >33% of 24-hour urine output occurring during sleep (20% in younger adults), producing normal or large-volume nocturnal voids rather than the small, frequent voids typical of OAB. 1, 2
• This condition is often caused by cardiovascular disease, heart failure, chronic kidney disease, vascular disease, or sleep apnea—not bladder dysfunction. 2
• A 3-day frequency-volume chart (voiding diary) is mandatory to differentiate nocturnal polyuria from bladder-based causes before initiating treatment. 2

Medication-Induced Frequency

• Diuretics, calcium channel blockers, lithium, and NSAIDs can all cause increased urinary frequency. 1, 2
• A comprehensive medication review is essential in every patient presenting with these symptoms. 1

Bladder Outlet Obstruction

• In men, benign prostatic hyperplasia causes frequency through incomplete emptying and reduced functional bladder capacity, paradoxically mimicking OAB symptoms. 2, 3
• In women, pelvic organ prolapse can produce similar outlet obstruction. 4
• Post-void residual (PVR) measurement is indicated when patients report emptying symptoms, have a history of retention, neurologic conditions, or long-standing diabetes. 1, 4

Interstitial Cystitis/Bladder Pain Syndrome

• This condition presents with bladder pain, pressure, or discomfort associated with urinary frequency lasting more than six weeks in the absence of infection. 2
• The presence of pain distinguishes this from OAB, where urgency—not pain—is the primary symptom. 2

Polydipsia and Global Polyuria

• Excessive fluid intake or systemic causes (diabetes mellitus, diabetes insipidus) produce many voids but with normal or large volumes, not the small-volume voids of OAB. 1
• A voiding diary documenting total 24-hour urine output >3 liters suggests polyuria rather than bladder dysfunction. 5

Essential Diagnostic Steps Beyond Urinalysis

Voiding Diary (Frequency-Volume Chart)

• This is the single most important diagnostic tool to differentiate between etiologies—it quantifies voiding frequency, individual voided volumes, timing, and total 24-hour output. 1, 2
• Small voided volumes (100-150 mL) with increased frequency (>7 daytime voids) suggest reduced functional bladder capacity consistent with OAB. 5
• Normal or large voided volumes suggest polyuria or nocturnal polyuria rather than bladder dysfunction. 1

Post-Void Residual Measurement

• PVR should be measured in patients with emptying symptoms, history of retention, neurologic disease, diabetes, or prior pelvic surgery to exclude urinary retention masquerading as frequency. 1, 4
• Elevated PVR (>250-300 mL) indicates outlet obstruction or detrusor underactivity, not OAB. 4

Targeted History Elements

• Document duration and baseline symptom severity, fluid intake patterns (especially evening fluids, caffeine, alcohol), and assess whether symptoms are truly bothersome to the patient. 1
• Review for neurologic diseases, diabetes, constipation, obesity, and sleep disturbances including witnessed apneas. 1, 2, 3
• In women, assess for genitourinary syndrome of menopause, which can worsen OAB symptoms. 4

Physical Examination

• Perform abdominal examination, rectal/genitourinary examination, and assess lower extremities for edema (suggesting fluid redistribution contributing to nocturnal polyuria). 1, 2
• In women, evaluate for pelvic organ prolapse; in men, assess prostate size. 1, 4

Less Common But Important Differential Diagnoses

Bladder Cancer

• Carcinoma in situ can produce frequency and urgency symptoms through bladder irritation. 2
• Any unexplained hematuria (even microscopic) not associated with infection mandates urologic evaluation and cystoscopy. 4

Neurogenic Bladder

• Neurologic conditions (multiple sclerosis, Parkinson's disease, spinal cord injury, stroke) directly impact bladder function and require specialist evaluation. 1, 4
• Targeted neurologic history and examination should identify these patients. 4

Recurrent Urinary Tract Infections

• While the current urinalysis is negative, patients with ≥3 UTIs per year may have chronic bladder inflammation causing persistent symptoms between infections. 2, 4

Metabolic Syndrome and Sleep Apnea

• Storage LUTS show strong associations with increased abdominal fat, elevated plasma glucose, low HDL cholesterol, and obstructive sleep apnea risk. 3
• These systemic conditions should be considered and addressed in patients presenting with frequency and urgency. 3

Critical Diagnostic Pitfalls to Avoid

• Do not assume all urgency and frequency in the absence of infection is OAB—nocturnal polyuria from cardiovascular or renal disease requires completely different management (fluid restriction, treatment of heart failure, not antimuscarinics). 2
• Do not initiate antimuscarinic therapy without measuring PVR in appropriate patients—treating overflow incontinence with antimuscarinics will worsen urinary retention. 4
• Do not overlook asymptomatic bacteriuria, particularly in elderly patients—the presence of bacteria without pyuria does not require treatment and should not be confused with symptomatic UTI. 1
• The absence of pyuria on urinalysis has high negative predictive value (75%) for excluding UTI, but the presence of pyuria has poor positive predictive value (40%) for confirming infection. 6