Overview
Diabetes Insipidus (DI)
1. Topic Overview (Clinical Overview)
Summary
Diabetes Insipidus (DI) is a disorder of water balance characterised by the excretion of large volumes of dilute urine (Polyuria – >3L/day) and compensatory thirst (Polydipsia). It occurs due to either insufficient secretion of Antidiuretic Hormone (ADH / Vasopressin) from the posterior pituitary (Cranial / Central DI) or renal resistance to ADH (Nephrogenic DI). If the patient cannot access water (e.g., unconscious patient, infants, elderly), severe hypernatraemia develops rapidly. Diagnosis involves demonstrating dilute urine (Low Urine Osmolality) in the presence of concentrated plasma (High Plasma Osmolality), confirmed by the Water Deprivation Test. Treatment of Cranial DI is Desmopressin (DDAVP); Nephrogenic DI is treated with thiazide diuretics, low sodium diet, and addressing the underlying cause.
Key Facts
- Definition: Polyuria (>3L/day) + Polydipsia due to ADH deficiency or resistance.
- Types: Cranial (Central) DI – ADH deficiency. Nephrogenic DI – ADH resistance.
- Biochemistry: High Plasma Osmolality (>295 mOsm/kg), Low Urine Osmolality (<300 mOsm/kg), Often Hypernatraemia.
- Diagnosis: Water Deprivation Test.
- Treatment (Cranial): Desmopressin (DDAVP).
- Treatment (Nephrogenic): Thiazides, Low salt diet, Treat cause.
Clinical Pearls
"The Urine is Inappropriate for the Plasma": Dilute urine when plasma is concentrated = DI.
"Water Deprivation Test with Desmopressin": Cranial DI responds to desmopressin (urine concentrates). Nephrogenic DI does NOT.
"Post-Pituitary Surgery – Watch for DI": Common cause of Cranial DI. May show "Triphasic Response" (Initial DI -> SIADH -> Permanent DI).
"Lithium is a Classic Cause of Nephrogenic DI": Lithium (Bipolar treatment) causes tubular resistance to ADH.
Why This Matters Clinically
DI can cause life-threatening hypernatraemia if patients cannot access water. Post-neurosurgical DI requires vigilant monitoring.
2. Epidemiology
Incidence
- Incidence: Rare (~1 in 25,000).
- Cranial DI: More common than Nephrogenic.
- Age: Any age. Nephrogenic DI – Can present in infancy (Hereditary forms).
Causes
Cranial (Central) Diabetes Insipidus
| Cause | Notes |
|---|---|
| Idiopathic | ~30%. Autoimmune damage to posterior pituitary. |
| Pituitary Surgery / Trauma | Common post-trans-sphenoidal surgery. |
| Tumours | Craniopharyngioma, Pituitary adenoma (Stalk effect), Metastases. |
| Infiltrative | Sarcoidosis, Langerhans Cell Histiocytosis. |
| Infections | Meningitis, Encephalitis. |
| Vascular | Sheehan's Syndrome (Pituitary apoplexy). |
| Congenital | AVP gene mutations (Rare). |
Nephrogenic Diabetes Insipidus
| Cause | Notes |
|---|---|
| Drugs | Lithium (Most common acquired). Demeclocycline. Amphotericin B. |
| Metabolic | Hypercalcaemia. Hypokalaemia. |
| Chronic Kidney Disease | |
| Post-Obstructive Uropathy | |
| Congenital | AVPR2 receptor mutations (X-linked). Aquaporin-2 mutations. |
| Pregnancy | Vasopressinase from placenta (Gestational DI). |
3. Pathophysiology
ADH (Vasopressin) Physiology
| Step | Detail |
|---|---|
| Synthesis | ADH synthesised in Hypothalamus (Supraoptic, Paraventricular nuclei). |
| Secretion | Released from Posterior Pituitary in response to Increased Plasma Osmolality or Decreased Blood Volume. |
| Action | Binds V2 receptors on collecting duct -> Aquaporin-2 insertion -> Water reabsorption. |
| Result | Concentrated urine. Water conserved. |
In Cranial DI
- ADH secretion is insufficient.
- Collecting duct cannot reabsorb water.
- Dilute urine excreted.
In Nephrogenic DI
- ADH secretion is normal or high.
- Kidney is resistant to ADH (Receptor or post-receptor defect).
- Dilute urine excreted despite high ADH.
4. Clinical Presentation
Symptoms
| Symptom | Notes |
|---|---|
| Polyuria | >L/day. Can be up to 15-20L/day in severe cases. |
| Polydipsia | Intense thirst. Compensatory. Preference for cold water. |
| Nocturia | Multiple times at night. |
| Dehydration Signs | If water access limited. |
| Weight Loss (If severe polyuria) | |
| Fatigue |
If Water Access Restricted
| Finding | Notes |
|---|---|
| Hypernatraemia | Plasma Na >45 mmol/L. Can be severe. |
| Altered Consciousness | Confusion, Lethargy. |
| Hypovolaemic Shock | Severe cases. |
Post-Pituitary Surgery "Triphasic Response"
| Phase | Timing | Mechanism |
|---|---|---|
| Phase 1: Initial DI | Days 1-5 | Hypothalamic dysfunction. ADH deficiency. |
| Phase 2: SIADH | Days ~5-10 | Uncontrolled ADH release from damaged neurons. |
| Phase 3: Permanent DI | After Day 10 | Neuronal death. Permanent ADH deficiency. |
Not all patients follow triphasic pattern. Many only have transient DI.
5. Investigations
Baseline
| Investigation | Expected in DI |
|---|---|
| Plasma Osmolality | Raised (>95 mOsm/kg) or Upper Normal. |
| Urine Osmolality | Inappropriately Low (<300 mOsm/kg). Should be >00 if concentrating. |
| Plasma Sodium | Normal to High (Hypernatraemia if dehydrated). |
| Urine Specific Gravity | Low (<1.005). |
Water Deprivation Test (Diagnostic)
Protocol (Simplified)
- Fasting from Water (8 hours, or shorter if polyuria severe).
- Monitor: Weight, Plasma Osmolality, Urine Osmolality, Urine Volume.
- Stop if: Weight loss >3%, Plasma Osmolality >300 mOsm/kg, or Patient dehydrated.
- Administer Desmopressin (IM or SC).
- Measure Urine Osmolality after Desmopressin.
Interpretation
| Finding | Diagnosis |
|---|---|
| Urine Concentrates After Dehydration | Normal (No DI). |
| Urine Remains Dilute After Dehydration, Concentrates After Desmopressin | Cranial DI. |
| Urine Remains Dilute After Dehydration AND After Desmopressin | Nephrogenic DI. |
| Urine Partially Concentrates After Desmopressin | Partial Cranial DI. |
Additional Investigations
| Investigation | Purpose |
|---|---|
| MRI Pituitary | Cranial DI – Look for cause (Tumour, Infiltration, Absent Bright Spot). |
| Calcium, Potassium | Nephrogenic DI causes. |
| Lithium Level | If on Lithium. |
| Genetic Testing | Congenital forms. |
6. Management
Principles
- Ensure Adequate Fluid Intake (Critical).
- Treat Underlying Cause (If identified).
- Specific Treatment (Desmopressin for Cranial DI, Thiazides for Nephrogenic).
- Monitor Sodium Closely (Avoid hypo- and hypernatraemia).
Cranial Diabetes Insipidus
Desmopressin (DDAVP)
| Route | Dose | Notes |
|---|---|---|
| Intranasal Spray | 10-40 mcg OD-BD | Common. Titrate to response. |
| Oral Tablets | 100-400 mcg OD-TDS | |
| Sublingual Melt | 60-240 mcg OD-TDS | |
| IM/SC Injection | 1-4 mcg OD-BD | Acute situations. |
Monitoring: Serum Sodium. Avoid Water Intoxication (Hyponatraemia from excessive DDAVP + water intake).
Nephrogenic Diabetes Insipidus
| Intervention | Detail |
|---|---|
| Treat Underlying Cause | Stop Lithium if possible. Correct Hypercalcaemia. Correct Hypokalaemia. |
| Thiazide Diuretics | Hydrochlorothiazide 25-50mg OD. Paradoxically reduces urine output. (Mild volume depletion -> Enhances proximal Na/Water reabsorption). |
| Low Sodium Diet | Reduces solute load. |
| NSAIDs (Indomethacin) | May help. Reduce renal prostaglandin synthesis. |
| Amiloride | Useful in Lithium-induced (Blocks Lithium entry into collecting duct). |
Acute Management (Hypernatraemia / Dehydration)
| Intervention | Detail |
|---|---|
| IV Fluids | Replace free water deficit. Use 5% Dextrose or 0.45% Saline. Correct Na slowly (<10-12 mmol/L/day). |
| Desmopressin | If Cranial DI confirmed. |
| Monitor Na Frequently | Every 4-6 hours initially. |
7. Complications
| Complication | Notes |
|---|---|
| Hypernatraemia | If water not replaced. Neurological sequelae. |
| Hyponatraemia | Over-treatment with DDAVP + excess water intake. |
| Dehydration | Volume depletion if access to water limited. |
| Bladder Dysfunction | From chronic polyuria. |
| Impaired Quality of Life | Nocturia. Constant thirst. |
8. Prognosis & Outcomes
| Scenario | Prognosis |
|---|---|
| Cranial DI with Treatment | Excellent. Normal life expectancy with DDAVP. |
| Nephrogenic DI | Depends on cause. Congenital forms require lifelong management. |
| Post-Surgical DI | Often transient. ~10-30% permanent. |
9. Differential Diagnosis: Polyuria
| Condition | Features |
|---|---|
| Diabetes Mellitus | Hyperglycaemia. Glycosuria. |
| Primary Polydipsia (Psychogenic Polydipsia) | Compulsive water drinking. Plasma Osm Low/Normal. Urine concentrates with water deprivation. |
| Chronic Kidney Disease | Renal impairment. Isosthenuria. |
| Hypercalcaemia | Nephrogenic DI picture. Check Calcium. |
| Hypokalaemia | Nephrogenic DI picture. Check Potassium. |
10. Evidence & Guidelines
Key Guidelines
| Guideline | Organisation | Notes |
|---|---|---|
| Endocrine Society Guidelines | Endocrine Society | Clinical approach to DI. |
| European Expert Consensus | Various | Water Deprivation Test protocols. |
11. Exam Scenarios
Scenario 1:
- Stem: A 30-year-old woman presents 3 days after trans-sphenoidal pituitary surgery with polyuria (5L urine/day) and plasma Na 148 mmol/L. What is the most likely diagnosis?
- Answer: Cranial Diabetes Insipidus (Post-operative).
Scenario 2:
- Stem: A patient on Lithium for bipolar disorder develops polyuria. What is the diagnosis and mechanism?
- Answer: Nephrogenic DI. Lithium inhibits aquaporin-2 channels in the collecting duct, causing resistance to ADH.
Scenario 3:
- Stem: Describe the Water Deprivation Test.
- Answer: Patient is deprived of water while monitoring plasma and urine osmolality. If urine remains dilute and then concentrates after desmopressin, it is Cranial DI. If urine stays dilute after desmopressin, it is Nephrogenic DI.
12. Triage: When to Refer
| Scenario | Urgency | Action |
|---|---|---|
| Suspected DI (Polyuria + Polydipsia) | Routine | Endocrinology. Water Deprivation Test. |
| Severe Hypernatraemia (Na >55) | Emergency | Medical Admission. IV Fluids. Monitor Na. |
| Post-Pituitary Surgery | Inpatient Monitoring | Watch for Triphasic Response. |
14. Patient/Layperson Explanation
What is Diabetes Insipidus?
Diabetes Insipidus (DI) is a condition where you pass very large amounts of dilute urine and feel very thirsty. It is caused by a problem with a hormone called ADH that normally tells your kidneys to hold on to water.
What causes it?
- Cranial DI: The brain doesn't make enough of the hormone (ADH).
- Nephrogenic DI: The kidneys don't respond to the hormone (e.g., caused by Lithium).
How is it treated?
- Cranial DI: A medicine called Desmopressin (DDAVP) replaces the missing hormone.
- Nephrogenic DI: Reducing salt, taking a water pill (Thiazide), or stopping the offending drug.
Key Counselling Points
- Always Drink When Thirsty: "Free access to water is essential."
- Take DDAVP as Prescribed: "Do not take extra doses – this can cause low sodium."
- Medical Alert: "Wear a medical alert bracelet. Tell doctors about your condition if unwell."
15. Quality Markers: Audit Standards
| Standard | Target |
|---|---|
| Paired Plasma + Urine Osmolality in suspected DI | 100% |
| Water Deprivation Test for diagnostic confirmation | >0% |
| MRI Pituitary in Cranial DI | 100% |
| Sodium monitoring on Desmopressin | 100% |
16. Historical Context
- "Diabetes Insipidus": Term introduced in 1794 (Insipidus = "tasteless", vs Mellitus = "sweet" – urine was not sweet).
- ADH/Vasopressin Discovery: 1950s. Vincent du Vigneaud (Nobel Prize, 1955) synthesised Vasopressin.
- Desmopressin: Synthetic analogue of Vasopressin developed for clinical use.
17. References
- Christ-Crain M, et al. Diabetes insipidus. Nat Rev Dis Primers. 2019. PMID: 31488843
- Endocrine Society Guidelines: endocrine.org
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. If you have symptoms of DI, please consult a healthcare professional.