Diabetes Insipidus Clinical Overview
I. The "On-Call" Snapshot
Clinical Significance in Malaysia: Essential to recognise in post-neurosurgery patients, those with head trauma, or as a cause of severe hypernatraemia in the wards. Mismanagement leads to dangerous electrolyte imbalance and dehydration.
High-Yield Definition: A condition characterised by the passage of large volumes (>3 L/24 hours for an adult) of dilute urine (urine osmolality <300 mOsmol/kg) due to either deficient secretion of antidiuretic hormone (ADH) or renal resistance to its effects. (Source: UpToDate)
Clinical One-Liner: The patient is a "human tap" – constantly drinking and urinating, but their blood sugar is normal and their sodium is high.
II. Etiology & Risk Factors
Etiology:
Central DI (CDI): Deficient ADH secretion. Can be idiopathic, post-traumatic (accidental/surgical), or due to tumours (craniopharyngioma, pituitary adenoma), infiltrative disease (sarcoidosis, histiocytosis), or hypoxic encephalopathy.
Nephrogenic DI (NDI): Renal insensitivity to ADH. Can be congenital (X-linked V2 receptor mutation) or acquired from drugs (lithium is a classic cause), hypercalcaemia, hypokalaemia, or chronic kidney disease.
Gestational DI: Increased metabolism of ADH by placental vasopressinase during pregnancy.
Dipsogenic DI (Primary Polydipsia): A disorder of thirst, leading to excessive water intake which suppresses ADH and causes polyuria. Not a true DI.
Risk Factors:
Neurosurgery (transsphenoidal) or significant head trauma
Pituitary or hypothalamic tumours
Family history of DI
Medications: Lithium, demeclocycline
Metabolic disturbances: Chronic hypercalcaemia, chronic hypokalaemia
III. Quick Pathophysiology
ADH (vasopressin) acts on V2 receptors in the renal collecting ducts, inserting aquaporin-2 water channels. This allows free water reabsorption, concentrating the urine.
In Central DI: No ADH means no signal to insert water channels. The kidney cannot reabsorb water. Result: massive water loss (polyuria) and rising plasma osmolality/sodium (hypernatraemia).
In Nephrogenic DI: ADH is present, but the kidney's receptors or channels are faulty. The signal is sent but not received. Result is the same: polyuria and hypernatraemia.
IV. Classification
The primary classification is based on etiology, as this dictates management entirely:
Central Diabetes Insipidus (CDI): The most common form. Can be complete or partial.
Nephrogenic Diabetes Insipidus (NDI): Can be complete or partial.
Gestational Diabetes Insipidus
Dipsogenic DI / Primary Polydipsia (an important differential)
V. Clinical Assessment
Red Flags & Immediate Actions
Altered Mental Status / Seizures: Suggests severe hypernatraemia (>160 mmol/L) causing cerebral cell shrinkage.
Action: Secure ABCs, inform senior immediately. Requires careful IV fluid correction in a high-dependency setting to avoid cerebral oedema.
Hypotension / Signs of Shock: Indicates severe volume depletion.
Action: IV access x2, start rapid infusion of Normal Saline or Hartmann's solution. Escalate to your Registrar/Specialist.
Urine output > 400ml/hr for 2 consecutive hours: Massive ongoing water loss.
Action: Urgent electrolyte check, inform senior, prepare for fluid replacement and potential desmopressin.
History
Key Diagnostic Clues:
Abrupt onset of intense thirst (polydipsia) and massive urination (polyuria).
Pathognomonic: Craving for ice-cold water.
Nocturia is almost always present and severe.
Symptom Breakdown:
Common (>50%): Polyuria, Polydipsia, Nocturia, Dehydration.
Less Common (10-50%): Fatigue, irritability, headache (especially if due to a CNS lesion).
Pertinent Negatives:
Absence of polyphagia (rules against DM).
No history of psychiatric illness (makes primary polydipsia less likely, but doesn't exclude it).
Urine is clear like water, not frothy (nephrotic syndrome) or tea-coloured (hepatitis/rhabdomyolysis).
Physical Examination (OSCE Approach)
General Inspection: Patient may look tired, distressed, constantly reaching for water.
Vitals: Postural hypotension and tachycardia are key signs of volume depletion. Fever is not typical.
Disease-Specific Examination:
Hydration Status (Crucial):
Look: Dry mucous membranes, sunken eyes.
Feel: Reduced skin turgor.
Measure: Check JVP (will be low), assess for postural drop in BP.
Neurological Examination:
Assess GCS.
Check visual fields (bitemporal hemianopia suggests a large pituitary mass compressing the optic chiasm).
Examine cranial nerves.
Differentiating Disease Stage:
Mild: Compensated by oral intake. Normal vitals, mild thirst.
Moderate/Severe: Unable to keep up with water loss. Tachycardia, postural hypotension, dry mucous membranes, rising sodium.
Late / Severe: Altered mental status, shock. This happens when the patient cannot access water or their thirst mechanism is impaired.
Clinical Pearl: When you clerk a post-neurosurgery patient, the first thing you look at is their fluid balance chart. The classic DI pattern is a sudden spike in urine output on day 1 or 2 post-op.
VI. Diagnostic Workflow
Differential Diagnosis
Diabetes Mellitus:
Points For: Polyuria, polydipsia.
Points Against: Normal blood glucose, absence of ketones, no polyphagia.
How to Differentiate: Bedside RPG.
Primary Polydipsia:
Points For: Polyuria, polydipsia, dilute urine.
Points Against: Serum sodium is often low-normal or low (due to water overload). History may reveal psychiatric conditions (schizophrenia, OCD).
How to Differentiate: Water deprivation test.
Osmotic Diuresis (Non-DM):
Points For: Polyuria.
Points Against: History of mannitol infusion, high protein tube feeds, or resolving AKI. Urine osmolality is high (>300 mOsm/kg), not low.
How to Differentiate: Check urine osmolality and solute.
Investigations Plan
Bedside / Initial (First 15 Mins):
RPG/CBG: To immediately rule out DM.
Urine Dipstick: Look for low specific gravity (<1.005).
Strict Input/Output Charting: Quantify the polyuria.
First-Line Labs:
Paired Serum & Urine Osmolality and Electrolytes: This is the cornerstone. In DI, you expect:
Serum: High osmolality (>295 mOsmol/kg), high sodium (>145 mmol/L).
Urine: Inappropriately low osmolality (<300 mOsmol/kg).
Confirmatory / Gold Standard:
Water Deprivation Test (followed by Desmopressin administration): Done in a controlled setting.
Patient is deprived of fluids. Urine and serum osmolality are measured hourly.
Normal/Primary Polydipsia: Urine osmolality will rise and concentrate (>600 mOsm/kg).
DI (Central or Nephrogenic): Urine remains dilute despite rising serum osmolality.
Desmopressin (DDAVP) is then given.
Central DI: The kidney is fine, just needed the signal. Urine osmolality rises sharply (>50% increase). Diagnosis confirmed.
Nephrogenic DI: The kidney is resistant. Urine osmolality shows minimal or no increase (<50%). Diagnosis confirmed.
MRI Brain (Pituitary/Hypothalamus): Indicated for all patients with new-onset Central DI to rule out an underlying tumour or infiltrative disease. The absence of the posterior pituitary "bright spot" on T1-weighted images is characteristic of CDI.
VII. Staging & Severity Assessment
Severity is a clinical and biochemical spectrum, not a formal staging system. It's determined by:
Volume of polyuria: >5L/day is significant, >10L/day is severe.
Degree of hypernatraemia: Mild (146-150), Moderate (151-159), Severe (≥160).
Response in Water Deprivation Test: Differentiates partial from complete DI. In partial DI, there is some ability to concentrate urine, but it's sub-optimal.
VIII. Management Plan
A. Principle of Management
Correct dehydration and hypernatraemia safely.
Reduce urine output to improve quality of life.
Treat the underlying cause.
B. Immediate Stabilisation (The ABCDE Plan)
Applies only to haemodynamically unstable or obtunded patients.
A/B: Ensure patent airway, give oxygen if needed.
C: IV access. Correct hypovolemia with isotonic fluids (0.9% NaCl or Hartmann's) until haemodynamically stable.
D: Monitor GCS. If severe hypernatraemia, avoid rapid correction of sodium (>10 mmol/L in 24h) to prevent cerebral oedema. Calculate free water deficit and replace slowly, typically with D5W or 0.45% NaCl.
E: Send urgent electrolytes, osmolalities. Insert urinary catheter for accurate monitoring.
C. Definitive Treatment (The Ward Round Plan)
Central DI (CDI):
First-Line: Desmopressin (DDAVP), a synthetic analogue of ADH.
Dosing (highly variable, titrate to effect):
Intranasal spray: 10-40 mcg daily, often split BD.
Oral tablets: 50-200 mcg TDS. Less predictable absorption.
IV/IM/SC (for acute setting): 1-4 mcg every 12-24 hours.
Goal: Normalise urine output (to ~1.5-2.5L/day) and thirst, while avoiding hyponatraemia from over-treatment.
Nephrogenic DI (NDI):
First-Line:
Treat underlying cause: Stop lithium, correct calcium/potassium.
Low Sodium, Low Protein Diet: Reduces solute load for excretion.
Thiazide Diuretic (e.g., Hydrochlorothiazide): Paradoxically reduces polyuria by causing mild volume depletion, which increases proximal tubule reabsorption of water and salt, so less water reaches the collecting ducts.
Second-Line:
NSAIDs (e.g., Indomethacin): Reduce renal prostaglandin production, which increases ADH sensitivity.
Amiloride: Specifically for lithium-induced NDI as it blocks lithium entry into collecting duct cells.
IX. Complications
Immediate/Short-Term:
Severe Dehydration & Hypovolemic Shock: From massive fluid loss. Action: Rapid isotonic fluid resuscitation.
Severe Hypernatraemia: Can cause seizures, coma, death. Action: Careful, slow correction with hypotonic fluids.
Long-Term:
Hydronephrosis and Bladder Dilation: From chronic polyuria stressing the urinary tract. Action: Monitor renal function and ensure adequate treatment to control urine volume.
Complications from over-treatment with DDAVP: Hyponatraemia, fluid overload. Action: Patient education is key. Advise them to skip a dose if they feel fluid overloaded and to monitor for signs like headache or nausea.
X. Prognosis
Prognosis is generally excellent for idiopathic CDI or post-traumatic DI if the diagnosis is made and treatment is consistent. Patients can lead normal lives.
The prognosis is dictated by the underlying cause (e.g., a malignant brain tumour has a poor prognosis).
Top Prognostic Factors:
Underlying etiology.
Patient adherence to treatment.
Access to water (if thirst mechanism is intact).
XI. How to Present to Your Senior
Use the SBAR format. Be sharp and concise.
S (Situation): "Dr, I'm calling about Mr. Tan in Bed 5, a 45-year-old man, Day 2 post-transsphenoidal surgery."
B (Background): "His urine output has acutely increased to 6L over the past 24 hours. He is complaining of intense thirst. His GCS is full."
A (Assessment): "Vitals are stable but his serum sodium has risen from 142 to 153. Paired urine osmolality is low at 150 mOsm/kg while serum osmolality is high at 310 mOsm/kg. My impression is post-operative Central Diabetes Insipidus."
R (Recommendation): "I think we should start him on IV Desmopressin 1 mcg and monitor his urine output and electrolytes closely. I would also like to calculate his free water deficit for replacement. Is that okay?"
XII. Summary & Further Reading
Top 3 Takeaways:
Think DI in any patient with massive polyuria, especially in a neurosurgical or head trauma context.
The first step is to rule out DM. The next is to send paired serum/urine osmolality.
The water deprivation test followed by desmopressin challenge is the definitive diagnostic test to differentiate central, nephrogenic, and dipsogenic causes.
Key Resources:
UpToDate: Search for "Central Diabetes Insipidus" and "Nephrogenic Diabetes Insipidus".
Amboss: Search "Diabetes Insipidus".
Key Review Article: Fenske, W., & Allolio, B. (2012). Clinical review: Current state and future directions in the diagnosis of diabetes insipidus: a clinical review. The Journal of Clinical Endocrinology & Metabolism, 97(10), 3426–3437. (This is a foundational review, still highly relevant).
