Polyuria And Or Polydipsia: MCCQE1 Study Guide

Introduction

Polyuria and polydipsia are common clinical presentations in Internal Medicine and Endocrinology. For the Medical Council of Canada Qualifying Examination Part I (MCCQE1), candidates must demonstrate the ability to differentiate between osmotic diuresis (e.g., Diabetes Mellitus) and water diuresis (e.g., Diabetes Insipidus or Primary Polydipsia).

Understanding the physiological mechanisms of water balance and the action of Arginine Vasopressin (AVP), also known as Antidiuretic Hormone (ADH), is central to the Medical Expert CanMEDS role.

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Definitions for MCCQE1:

Polyuria: Urine output exceeding 3 L/day (or >40-50 mL/kg/day) in adults.
Polydipsia: Excessive thirst leading to increased fluid intake.
Frequency: Voiding often, but not necessarily high volume (distinguish from polyuria).

Pathophysiology

To approach MCCQE1 questions effectively, you must distinguish between the two main mechanisms of polyuria.

Solute (Osmotic) Diuresis vs. Water Diuresis

Feature	Solute (Osmotic) Diuresis	Water Diuresis
Mechanism	Non-absorbable solutes in renal tubules hold water in the lumen.	Reduced water reabsorption due to lack of ADH or resistance to ADH.
Urine Osmolality	High or Isotonic (>300 mOsm/kg)	Low / Dilute (<250 mOsm/kg)
Common Causes	Uncontrolled Diabetes Mellitus (Glucose), Mannitol, High protein diet (Urea).	Diabetes Insipidus (Central/Nephrogenic), Primary Polydipsia.
Response to Water Deprivation	Urine remains high osmolality.	Urine remains dilute (unless Primary Polydipsia, where it concentrates slightly).

Etiology and Differential Diagnosis

For MCCQE1 preparation, organize your differential diagnosis into broad categories.

Common Causes

Most Frequent in Canadian Practice:

Diabetes Mellitus (Type 1 & 2): Osmotic diuresis due to glycosuria.
Diuretics: Thiazides, loop diuretics.
Primary Polydipsia (Psychogenic): Excessive water intake suppresses ADH. Often seen in psychiatric patients or those with hypothalamic lesions (sarcoidosis).

Clinical Approach for MCCQE1

Follow this systematic approach to investigate polyuria, aligning with Canadian clinical guidelines.

Step 1: Confirm Polyuria

History is key. Ask about the volume of urination versus frequency.

Quantify: Is it >3L/day?
Nocturia: Does the patient wake up >1 time to void? (Highly sensitive for polyuria).
Constitutional: Weight loss? (Suggests DM or malignancy).
Medications: Lithium, Diuretics, Vitamin D (Hypercalcemia).

Step 2: Initial Investigations (The “Screen”)

Rule out the most common causes (Osmotic Diuresis) first.

Serum Glucose: Rule out Diabetes Mellitus.
Electrolytes (Ca, K, Na): Rule out Hypercalcemia and Hypokalemia. Check Sodium (Hypernatremia suggests DI; Hyponatremia suggests Primary Polydipsia).
Urea & Creatinine: Assess renal function.
Urinalysis: Check for glucose, specific gravity.

Step 3: Assess Osmolalities

If glucose and electrolytes are normal, compare Serum Osmolality ( $P_{osm}$ ) and Urine Osmolality ( $U_{osm}$ ).

Diagnostic Formulas

Calculated Serum Osm = 2(Na) + Glucose + Urea

(All units in mmol/L for Canadian context)

Scenario A: $U_{osm}$ $U_{os m}$ > 600 mOsm/kg.
- The kidney can concentrate urine. Polyuria is likely due to osmotic diuresis or high solute load.
Scenario A: $U_{osm}$ $U_{os m}$ < $P_{osm}$ $P_{os m}$ (Urine is dilute).
- This confirms Water Diuresis. Proceed to Step 4.

Step 4: Water Deprivation Test

Indication: To differentiate between Primary Polydipsia, Central DI, and Nephrogenic DI.

Method: Restrict fluid intake. Monitor body weight and urine osmolality hourly.
Stop test if: Body weight drops >3-5% or Na > 145 mmol/L.
Intervention: Once urine osmolality plateaus (or patient is hypertonic), administer Desmopressin (DDAVP).

Interpreting the Water Deprivation Test

This is a high-yield concept for the MCCQE1. You must be able to interpret the response to Desmopressin.

Primary Polydipsia

Baseline: Urine dilute, Serum Na low/normal.
Deprivation: Urine concentrates (>500-600).
Post-DDAVP: Minimal change (<10%).
Mechanism: ADH axis is intact; just suppressed by water intake.

Central DI

Baseline: Urine dilute, Serum Na high/normal.
Deprivation: Urine remains dilute (<300).
Post-DDAVP: Dramatic increase in Urine Osm (>50%).
Mechanism: Kidneys respond to the exogenous ADH they were missing.

Nephrogenic DI

Baseline: Urine dilute, Serum Na high/normal.
Deprivation: Urine remains dilute (<300).
Post-DDAVP: No change or minimal increase (<10-20%).
Mechanism: Kidneys cannot respond to ADH (endogenous or exogenous).

Management

Management strategies reflect Canadian standards of care.

1. Central Diabetes Insipidus

First-line: Desmopressin (DDAVP). Available as oral, intranasal, or parenteral.
Goal: Control polyuria and thirst.
Risk: Hyponatremia if patient continues to drink excessively while on DDAVP.

2. Nephrogenic Diabetes Insipidus

Treat Underlying Cause: Correct Calcium/Potassium, stop Lithium (if psychiatrically safe).
Diet: Low sodium, low protein diet (reduces solute load).
Pharmacotherapy:
- Thiazide Diuretics (e.g., Hydrochlorothiazide): Paradoxical effect. Induces mild volume depletion $\rightarrow$ increased proximal tubule Na/Water reabsorption $\rightarrow$ less water delivery to collecting ducts.
- NSAIDs (e.g., Indomethacin): Inhibit prostaglandin synthesis (prostaglandins antagonize ADH action). Used cautiously due to renal risk.
- Amiloride: specifically for Lithium-induced NDI (blocks Li entry into distal tubule cells).

3. Primary Polydipsia

Management: Water restriction.
Warning: Do not give Desmopressin (risk of severe hyponatremia).

Canadian Guidelines & Context

Diabetes Canada Clinical Practice Guidelines (2018/2023): Emphasize the diagnosis of DM using FPG $\ge$ 7.0 mmol/L, A1C $\ge$ 6.5%, or Random PG $\ge$ 11.1 mmol/L with symptoms (polyuria/polydipsia).
Choosing Wisely Canada: Recommends against ordering imaging (MRI Pituitary) for polyuria without biochemical confirmation of Central DI.
Lithium Monitoring: In Canada, patients on chronic lithium therapy should have renal function and electrolytes monitored every 3-6 months to screen for NDI.

Key Points to Remember for MCCQE1

Hypernatremia + Dilute Urine = Diabetes Insipidus.
Hyponatremia + Dilute Urine = Primary Polydipsia.
Lithium is the most common cause of acquired Nephrogenic DI in the Canadian population.
Amiloride is the drug of choice for Lithium-induced NDI because it closes the ENaC channel, preventing Lithium uptake.
Always rule out Hypercalcemia and Hypokalemia in a patient with new-onset polyuria.
Nocturia is often the earliest symptom of renal concentrating defects.

Sample Question

Clinical Scenario

A 42-year-old male presents to his family physician complaining of excessive thirst and frequent urination for the past 3 months. He reports waking up 4-5 times per night to void. He has a history of Bipolar Disorder and has been stable on Lithium for 8 years.

Physical examination reveals dry mucous membranes. His blood pressure is 125/80 mmHg.

Laboratory investigations reveal:

Serum Sodium: 146 mmol/L (Normal: 135-145)
Serum Glucose: 5.2 mmol/L (Normal: 3.6-6.0)
Serum Calcium: 2.3 mmol/L (Normal: 2.1-2.6)
Serum Osmolality: 298 mOsm/kg (Normal: 275-295)
Urine Osmolality: 150 mOsm/kg

A water deprivation test is performed. After 6 hours, urine osmolality remains 160 mOsm/kg. Desmopressin is administered, and 1 hour later, urine osmolality is 170 mOsm/kg.

Which one of the following is the most appropriate initial management step?

A. Discontinue Lithium immediately and start Carbamazepine
B. Initiate intranasal Desmopressin
C. Prescribe Hydrochlorothiazide and advise a low-sodium diet
D. Prescribe Demeclocycline
E. Refer for MRI of the pituitary gland

Explanation

The correct answer is:

C. Prescribe Hydrochlorothiazide and advise a low-sodium diet

Detailed Explanation: This patient presents with polyuria and polydipsia. The labs show high-normal sodium and serum osmolality with inappropriately dilute urine (low urine osmolality), confirming Diabetes Insipidus (DI). The water deprivation test shows no response to fluid restriction (ruling out Primary Polydipsia) and no significant response to Desmopressin (Urine Osm increased from 160 to 170, a <10% change), confirming Nephrogenic DI.

Given the history of long-term Lithium use, this is likely Lithium-induced Nephrogenic DI.

Option C is correct: The treatment for Nephrogenic DI involves a low-sodium diet and Thiazide diuretics (like Hydrochlorothiazide). Thiazides induce mild volume depletion, increasing proximal tubular reabsorption of sodium and water, thereby reducing the volume delivered to the distal nephron. Amiloride is also often used specifically for Lithium-induced NDI.
Option A is incorrect: While stopping Lithium might be considered, it should not be done “immediately” without psychiatric consultation due to the risk of bipolar relapse. Furthermore, Lithium-induced NDI can be irreversible or take years to resolve. Management of the polyuria is the priority.
Option B is incorrect: Desmopressin treats Central DI. This patient has Nephrogenic DI and has already demonstrated a lack of response to Desmopressin.
Option D is incorrect: Demeclocycline causes Nephrogenic DI and is used to treat SIADH. It would worsen this patient’s condition.
Option E is incorrect: An MRI of the pituitary is indicated for Central DI to look for tumors or infiltrative diseases. It is not indicated for Nephrogenic DI.

References

Diabetes Canada Clinical Practice Guidelines Expert Committee. Diabetes Canada 2018 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada. Can J Diabetes. 2018;42(Suppl 1):S1-S325.
Kasper, D. L., et al. Harrison’s Principles of Internal Medicine. 20th ed. New York, NY: McGraw-Hill Education; 2018.
Bichet DG. Diagnosis and treatment of diabetes insipidus. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA. (Accessed 2023).
Medical Council of Canada. Objectives for the Qualifying Examination. Available at: mcc.ca.
Toronto Notes 2023. Endocrinology Chapter. Toronto Notes for Medical Students, Inc.