Presenting Complaint:

• Excessive thirst (polydipsia)

Symptoms:

• Site: Generalised thirst – “My whole body feels dry”
• Onset: Gradual over 3–4 weeks, worsening – “I’m constantly thirsty now” 
• Character: Persistent, unrelenting thirst – “My mouth always feels dry”
• Associated symptoms: Polyuria, nocturia, mild fatigue, occasional headaches – “I pee a lot especially at night, feel tired and sometimes have a headache”
• Exacerbating/alleviating factors: Improves temporarily with drinking water, worse after taking his morning medication – “It is usually worse after I take my meds, but gets better for a bit after I drink some water”
• Severity: Severe – “It’s affecting my sleep and work”

Systemic Symptoms (answer only if specifically asked for):

• Urinary: Profusely dilute urine, increased frequency (at least once hourly), no obvious blood, no retention, no dysuria 
• Bowels: Bowel movements today, no constipation or diarrhoea, normal coloured stools noted previously, no PR bleeding noticed
• Head: No headache, no focal neurology changes noticed
• Eyes: No changes in vision or visual acuity, no scleral icterus
• Ears: No hearing loss noticed
• Weight: Lost around 1.5 kg unintentionally, normal appetite
• Fatigue: Mild fatigue, stable mood overall
• Fever: No fever
• Vomiting and nausea: No vomiting episodes or nausea
• Hydration: Reports dry mouth

Past Medical History:

• Bipolar affective disorder (diagnosed age 24)

Past Surgical History:

• None

Drug History:

• Lithium carbonate (on treatment for 3 years), dose recently increased 6 weeks ago during medication review
• Sertraline
• Occasional ibuprofen for headaches

Allergies:

• NKDA

Family History:

• Brother with type 1 diabetes

Social History:

• BMI: 24
• Smoker: None
• Alcohol: Two to three pints of beer socially per week
• Occupation: IT support worker
• Diet: Normal
• Lives with partner

Ideas, Concerns, and Expectations:

• Thinks he may have diabetes
• Worried something is wrong with his kidneys
• Wants an explanation for the constant thirst

Observations:

• Respiratory rate: 16
• Oxygen sats: 99% RA
• Pulse: 88 
• Blood pressure: 128/78
• Temperature: 36.9

NEWS: 0

Physical Examination:

General Inspection:

• Appears mildly dehydrated (dry mucous membranes)
• Alert, oriented
• No acute distress

Hands:

• No clubbing or tremor
• Capillary refill time < 2 seconds
• Peripheries cool
• Regular pulse and rhythm 
• No palmar erythema or Dupuytren’s contracture

Face:

• Dry mucous membranes
• No scleral icterus present

Neck:

• JVP not raised
• No thyroid enlargement
• No scars or palpable lymphadenopathy

Abdomen:

• No scars visible
• Abdomen soft and non-tender on palpation of lower abdomen without guarding
• No suprapubic tenderness or distension

Cardiovascular:

• Heart sounds normal, no murmur 

Respiratory:

• Normal chest expansion
• Clear breath sounds 

Neurological:

• No focal motor or sensory deficits
• Normal gait
• Normal cognition
• Normal examination of the cranial nerves 
• Normal visual fields, no changes in visual acuity
• No changes in gross hearing

Other:

• No peripheral or sacral oedema

Laboratory tests:

• Na 151 mmol/L (Normal Na range: 135–145 mmol/L)
• K 4.2 mmol/L (Normal K range: 3.5–5.0 mmol/L)
• Urea 7.9 mmol/L (Normal urea range: 2.5–7.8 mmol/L)
• Creatinine 84 µmol/L (Normal creatinine range: 64–104 µmol/L)
• Serum osmolality 310 mOsm/kg (Normal serum osmolality: 275–295 mOsm/kg)
• Urine osmolality 90 mOsm/kg (Normal random urine osmolality 300-900 mOsm/kg) 
• HbA1c < 36 mmol/mol (Normal HbA1c range < 42 mmol/mol) 
• Urine dipstick: glucose negative, ketones negative, protein negative, blood negative, leukocytes negative, nitrites negative, specific gravity low (≤ 1.005), pH 6.5

Examiner questions:

1. What is your main differential diagnosis and why is this more likely than other differentials?

Answer: Nephrogenic diabetes insipidus – secondary to lithium use 

• High serum sodium with low urine osmolality is suggestive of DI due to an inability to concentrate urine while volume-depleted, and lithium exposure is a well-known cause. Lithium disrupts aquaporin-2 (AQP2) channels in the collecting ducts and thereby impairs renal tubular response to ADH, leading to large volumes of dilute urine and polydipsia 
• Central diabetes insipidus is a key differential to consider; however, the use of lithium makes nephrogenic DI more likely
• Primary polydipsia is less likely here; you would expect to see low serum osmolality rather than high
• Diabetes mellitus is excluded by normal HbA1c and absence of glycosuria

2. How would you confirm the diagnosis of nephrogenic diabetes insipidus?

Possible answer:

• Water deprivation test – within a specialist unit, patients are deprived of fluid for 8 hours and carefully monitored for developing dehydration. Serum osmolality, urine volume, and urine osmolality are measured hourly. In DI, this would fail to concentrate urine (osmolality remains inappropriately low at <300 mOsm/kg), while serum osmolality would be raised (>290 mOsm/kg). 
• Desmopressin challenge – this test differentiates Cranial DI and Nephrogenic DI. Cranial DI, also known as arginine vasopressin deficiency (AVP-D), is characterised by a failure to produce ADH/AVP, whereas Nephrogenic DI, also known as arginine vasopressin resistance (AVP-R), is defined by insensitivity to ADH/AVP. During this investigation, patients are administered the synthetic ADH analogue, desmopressin (DDAVP), and response is measured by changes in urine output and osmolality. In Cranial DI, patients are responsive to desmopressin and subsequently reduce urine output and increase osmolality (>750 mOsm/kg), whereas in Nephrogenic DI patients are resistant to desmopressin and there is minimal or no reduction in urine output, or rise in urine osmolality 
• Serial lithium levels
• Renal ultrasound – to assess baseline renal structure

3. Describe the management of this condition

Possible answer:

• Initial A-E assessment, including ECG, full set of bloods including FBC, U&Es, LFTs, Lactate, CRP, Glucose, Lithium level
• Restore fluid balance (oral or IV fluids depending on severity) and correct any electrolyte abnormalities. Use caution in the correction of chronic hypernatraemia due to the risk of cerebral oedema
• Desmopressin is generally ineffective due to renal resistance, however in patients with variable acquired nephron insensitivity, high-dose desmopressin can be partially effective
• ECG to assess for arrhythmias (DI has associations with hypokalaemia and hypercalcaemia; arrhythmias caused by lithium toxicity)
• Review lithium therapy urgently. Reduce dose or consider switching to an alternative mood stabiliser (liaise with psychiatry). Unfortunately, cessation of lithium frequently does not resolve the AVP-R
• Low-sodium diet and thiazides
• Optimise renal function and avoid NSAIDs where possible (risk renal impairment), and seek nephrology input if required
• Arrange monitoring of lithium levels, renal function and psychiatric review for mood stabiliser optimisation

4. Name some possible complications of untreated diabetes insipidus

Possible answer:

• Severe dehydration
• Hypernatraemia
• Confusion, seizures
• Renal impairment
• Hypotension and shock