Hypernatraemia (Adult)

Quick Reference

Critical Alerts

• Hypernatraemia indicates water deficit, not sodium excess in the vast majority of cases [1]
• Correct slowly in chronic cases - aim for sodium decrease 10-12 mmol/L per 24 hours maximum [2]
• Rapid correction causes cerebral oedema - potentially fatal complication [3]
• Acute hypernatraemia (less than 48h) can be corrected faster - up to 1-2 mmol/L/hour [4]
• Always treat underlying cause while correcting sodium [5]
• Mortality correlates with severity - serum sodium > 160 mmol/L carries 60-75% mortality [6]

Key Diagnostics

• Serum sodium - confirm hypernatraemia > 145 mmol/L
• Serum osmolality - elevated (> 295 mOsm/kg)
• Urine osmolality and sodium - critical for determining cause
• BUN/creatinine ratio - assess volume status and renal function
• Glucose - exclude osmotic diuresis (HHS)
• Calcium - hypercalcaemia causes nephrogenic DI

Emergency Treatments

• Calculate water deficit: TBW x [(Serum Na/140) - 1]
• IV D5W or 0.45% saline: Replace free water gradually
• Rate of correction: Maximum 10-12 mmol/L per 24 hours for chronic
• Desmopressin (DDAVP): For central diabetes insipidus
• Address underlying cause: Infection, GI losses, medications, access to water

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Definition and Classification

Hypernatraemia is defined as a serum sodium concentration greater than 145 mmol/L (mEq/L). [1,7] It represents a deficit of water relative to total body sodium and always indicates hyperosmolality. Unlike hyponatraemia, which can be hypotonic, isotonic, or hypertonic, hypernatraemia is invariably associated with hyperosmolality because sodium is an effective osmole that does not freely cross cell membranes. [1]

The condition reflects either a net water loss (most common), inadequate water intake, or rarely, sodium gain. Hypernatraemia always causes cellular dehydration, particularly affecting brain cells, and if severe or rapidly developing, causes significant neurological dysfunction. [3]

Classification by Severity

Mortality data from hospital-based cohort studies demonstrate that severe hypernatraemia (≥160 mmol/L) carries mortality rates of 60-75%, though this often reflects the severity of underlying conditions rather than hypernatraemia itself. [6,8]

Classification by Onset

The distinction between acute and chronic hypernatraemia is crucial because the brain's adaptive response determines the risk of complications during correction. [3,4]

Classification by Volume Status

This classification is clinically essential as it guides initial management:

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Epidemiology

Incidence and Prevalence

Hypernatraemia is less common than hyponatraemia but carries significantly higher mortality:

Demographics and Risk Factors

Age Distribution:

• Bimodal: extremes of age most affected
• Elderly (> 65 years): impaired thirst, multiple comorbidities
• Infants: unable to communicate thirst, immature kidneys

Key Risk Factors:

Mortality Data

The high mortality associated with hypernatraemia largely reflects the serious underlying conditions that cause it rather than the electrolyte disturbance itself. [8]

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Pathophysiology

Normal Water Homeostasis

Understanding normal water balance is essential for managing hypernatraemia:

Osmoreceptor-AVP Axis:

The hypothalamic osmoreceptors in the organum vasculosum of the lamina terminalis (OVLT) and subfornical organ detect plasma osmolality with remarkable sensitivity, responding to changes as small as 1-2%. [11]

Normal Response to Hyperosmolality:

Increased plasma osmolality (> 290 mOsm/kg)
              ↓
Osmoreceptor stimulation
              ↓
    ┌─────────┴─────────┐
    ↓                   ↓
Thirst activation    AVP release
    ↓                   ↓
Increased water      V2 receptor activation
intake                  ↓
    ↓              AQP2 insertion → Water reabsorption
    ↓                   ↓
    └─────→ Decreased plasma osmolality ←─────┘

Thirst Threshold:

• Thirst is stimulated when plasma osmolality exceeds 290-295 mOsm/kg [11]
• This is the primary defence against hypernatraemia
• Intact thirst and access to water can prevent hypernatraemia even with complete diabetes insipidus

AVP (Vasopressin) Physiology:

• Threshold for release: ~280 mOsm/kg
• Maximum concentration achieved at ~295 mOsm/kg
• Half-life: 10-20 minutes
• Mechanism: binds V2 receptors on collecting duct → cAMP cascade → AQP2 trafficking to apical membrane → water reabsorption

Mechanisms of Hypernatraemia

Hypernatraemia can only develop when there is impaired water intake (either due to impaired thirst or lack of access to water) or when water losses exceed intake:

1. Net Water Loss (Most Common)

2. Impaired Thirst/Water Access

3. Sodium Gain (Rare)

Diabetes Insipidus: A Special Focus

Diabetes insipidus (DI) is a critical cause of hypernatraemia that requires specific understanding for diagnosis and management.

Central (Neurogenic) Diabetes Insipidus:

Results from inadequate AVP synthesis or secretion from the hypothalamic-pituitary axis:

Triphasic Response Post-Pituitary Surgery:

A characteristic pattern seen after pituitary surgery:

Nephrogenic Diabetes Insipidus:

Results from renal resistance to AVP action:

Gestational Diabetes Insipidus:

• Occurs in 2-4 per 100,000 pregnancies
• Caused by placental vasopressinase (cysteine aminopeptidase) that degrades AVP
• Typically presents in third trimester
• DDAVP is effective (resistant to vasopressinase)
• Resolves 4-6 weeks postpartum

Brain Adaptation to Hypernatraemia

Understanding brain adaptation is crucial for safe correction:

Acute Hypernatraemia (less than 48 hours):

• Brain cells shrink due to osmotic water movement to ECF
• Minimal compensatory mechanisms activated
• Risk of brain injury from cell shrinkage
• Can correct more rapidly (1-2 mmol/L/hour)

Chronic Hypernatraemia (> 48 hours):

• Brain cells generate "idiogenic osmoles" (organic osmolytes)
• These include: myoinositol, taurine, betaine, glycine, glutamine, glutamate
• Takes 24-48 hours for full adaptation
• Brain cell volume normalises despite extracellular hyperosmolality
• Creates risk: rapid correction causes cerebral oedema

Idiogenic Osmoles:

The slower disposal of these osmolytes compared to their accumulation explains why rapid correction of chronic hypernatraemia is dangerous - water enters brain cells faster than osmolytes can be extruded, causing cerebral oedema. [3,4]

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Clinical Presentation

Symptoms

The clinical features of hypernatraemia are primarily neurological, reflecting brain cell shrinkage and dysfunction:

Mild Hypernatraemia (146-150 mmol/L):

• Often asymptomatic
• Subtle cognitive impairment
• Mild fatigue
• Anorexia
• Nausea

Moderate Hypernatraemia (151-159 mmol/L):

Severe Hypernatraemia (≥160 mmol/L):

Signs

Volume Assessment:

Neurological Examination:

Signs Specific to Underlying Cause:

Special Considerations in the Elderly

The elderly are particularly vulnerable to hypernatraemia due to:

1. Impaired thirst sensation - osmoreceptor sensitivity decreases with age
2. Reduced kidney concentrating ability - maximum urine osmolality decreases
3. Multiple comorbidities - dementia, stroke, immobility
4. Polypharmacy - diuretics, lithium
5. Institutional care - dependence on caregivers for water
6. Higher baseline serum sodium - normal range slightly higher in elderly

Brain Adaptation - Why Speed of Correction Matters

Danger of Rapid Correction in Chronic Hypernatraemia:

Chronic hypernatraemia (> 48 hours):
1. Brain cells have adapted
2. Accumulated idiogenic osmoles
3. Brain cell volume normalised

If sodium corrected too rapidly:
1. Extracellular osmolality falls quickly
2. Idiogenic osmoles cannot be extruded quickly enough
3. Water moves into brain cells (osmotic gradient)
4. Brain cells swell
5. Cerebral oedema develops
6. Risk of herniation
7. Potentially fatal

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Red Flags and Emergencies

Life-Threatening Findings

Complications of Hypernatraemia

Neurological Complications:

• Intracerebral haemorrhage (brain shrinkage tears bridging veins)
• Subarachnoid haemorrhage
• Subdural haemorrhage
• Osmotic demyelination (rare, more common in hyponatraemia correction)
• Permanent neurological sequelae
• Death

Complications of Overcorrection:

• Cerebral oedema
• Seizures
• Permanent neurological damage
• Herniation
• Death

Target Correction Rate:

• Chronic/unknown duration: Decrease Na by maximum 10-12 mmol/L in first 24 hours [2,4]
• Acute (less than 48h): Can correct 1-2 mmol/L/hour until symptoms resolve [4]
• Overall: Aim for normalisation over 48-72 hours for chronic cases

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Differential Diagnosis

Causes of Hypernatraemia by Mechanism

Water Loss - Renal:

Water Loss - Extrarenal:

Inadequate Water Intake:

Sodium Gain:

Other Causes of Altered Mental Status

Always consider other causes of neurological symptoms in patients with hypernatraemia:

• Stroke/intracranial haemorrhage
• Sepsis/meningitis
• Hypoglycaemia
• Uraemia
• Hepatic encephalopathy
• Drug toxicity
• Hypercalcaemia
• Thyroid storm/myxoedema coma

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Diagnostic Approach

Initial Assessment

Focused History:

Laboratory Investigations

Essential Tests:

Urine Osmolality Interpretation

Urine osmolality is the key investigation for determining the cause of hypernatraemia:

Algorithm:

Hypernatraemia (Na > 145 mmol/L)
              ↓
     Check Urine Osmolality
              ↓
    ┌─────────┴─────────┐
    ↓                   ↓
> 600 mOsm/kg        less than 300 mOsm/kg
    ↓                   ↓
Extrarenal loss    Diabetes Insipidus
or inadequate          ↓
intake             Give DDAVP
    ↓                   ↓
               ┌───────┴───────┐
               ↓               ↓
        Urine Osm         Urine Osm
        increases         unchanged
               ↓               ↓
          Central DI     Nephrogenic DI

Water Deprivation Test (Formal Diagnosis of DI)

Indication: When DI is suspected but diagnosis is unclear

Contraindications:

• Severe hypernatraemia (> 150 mmol/L)
• Dehydration
• Renal impairment (won't be interpretable)
• Inability to monitor closely

Protocol (Miller-Moses Test):

Stopping Criteria:

• Weight loss > 3% (or 5% in some protocols)
• Serum osmolality > 295 mOsm/kg
• Urine osmolality plateau (two consecutive measurements differ by less than 30 mOsm/kg)
• Serum sodium > 145 mmol/L
• Patient intolerant

Interpretation:

Copeptin Testing (Emerging):

Copeptin (the C-terminal fragment of pre-proAVP) is stable and can be measured as a surrogate for AVP:

Copeptin measurement may eventually replace the water deprivation test but is not yet widely available. [12]

Imaging Studies

CT/MRI Brain:

• Indicated if central DI suspected
• Pituitary/hypothalamic lesions
• Rule out intracranial pathology causing altered mental status

MRI Pituitary (with gadolinium):

• Loss of posterior pituitary bright spot on T1-weighted imaging suggests central DI
• Evaluate for pituitary tumours, stalk lesions

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Management

Principles of Correction

Key Concept: The goal is to replace the water deficit gradually while treating the underlying cause.

Rate of Correction:

Water Deficit Calculation

Formula:

Water Deficit (Litres) = TBW × [(Serum Na / 140) - 1]

Where TBW (Total Body Water) = Weight (kg) × Factor

Factors:
- Young males: 0.6
- Young females and elderly males: 0.5
- Elderly females: 0.45

Example Calculation:

A 70 kg elderly male with serum Na 160 mmol/L:

• TBW = 70 × 0.5 = 35 L
• Water deficit = 35 × [(160/140) - 1] = 35 × 0.143 = 5 L

Important Considerations:

• This formula calculates the DEFICIT only
• Must also account for ONGOING LOSSES (urine, GI, insensible)
• Ongoing losses in DI can be substantial (5-10+ L/day)
• Formula assumes no sodium losses (adjust if hypovolaemic)

Infusion Rate Calculation

Adrogue-Madias Formula:

This estimates the change in serum sodium from 1 litre of any infusate: [13]

Change in Na (mmol/L) = (Infusate Na - Serum Na) / (TBW + 1)

Sodium Content of Common Fluids:

Practical Approach:

1. Calculate water deficit
2. Choose appropriate fluid based on volume status
3. Plan to replace deficit over 48-72 hours
4. Add estimated ongoing losses
5. Determine hourly infusion rate
6. Monitor sodium every 2-4 hours and adjust

Example:

5 L water deficit in chronic hypernatraemia (Na 160 mmol/L):

• Target correction: 10 mmol/L in first 24 hours (to Na 150 mmol/L)
• Using D5W (0 mmol/L Na): each litre drops Na by approximately:
  • Change = (0 - 160) / (35 + 1) = -4.4 mmol/L per litre
• To drop Na by 10 mmol/L: need approximately 10/4.4 = 2.3 L D5W in 24h
• Rate = 2.3 L / 24 h ≈ 95 mL/hour (plus replacement for ongoing losses)

Treatment by Volume Status

Hypovolaemic Hypernatraemia (Most Common):

Step 1: Volume Resuscitation (if haemodynamically unstable)
- Give 0.9% NaCl until stable BP and perfusion
- This is isotonic and will NOT correct hypernatraemia
- BUT it prevents cardiovascular collapse

Step 2: Free Water Replacement
- Switch to 0.45% NaCl or D5W once haemodynamically stable
- Calculate water deficit and replacement rate
- 0.45% NaCl preferred if still volume depleted (provides some volume)

Step 3: Replace Ongoing Losses
- Estimate GI, urinary, insensible losses
- Add to replacement volume

Step 4: Monitor
- Serum sodium every 2-4 hours during active correction
- Adjust rate based on response

Euvolaemic Hypernatraemia (e.g., Diabetes Insipidus):

Central DI:
- DDAVP (desmopressin):
  - "IV/SC: 1-4 mcg every 12-24 hours"
  - "Intranasal: 10-40 mcg daily in 1-2 divided doses"
  - "Oral: 0.1-0.4 mg 2-3 times daily"
- Free water replacement (D5W or oral water)
- Monitor closely - risk of overcorrection once DDAVP takes effect

Nephrogenic DI:
- Treat underlying cause (stop lithium if possible, correct hypercalcaemia/hypokalaemia)
- Thiazide diuretics (paradoxically reduce urine output)
  - Hydrochlorothiazide 12.5-25 mg daily
  - "Mechanism: induces mild volume depletion → enhanced proximal reabsorption"
- Low-sodium diet (less than 100 mmol/day)
- NSAIDs may help (reduce prostaglandin-mediated antagonism of AVP)
  - Use with caution given renal effects
- Amiloride for lithium-induced NDI (blocks lithium entry via ENaC)
- Free water replacement

Gestational DI:
- DDAVP is effective (resistant to placental vasopressinase)
- Usually resolves 4-6 weeks postpartum

Hypervolaemic Hypernatraemia (Sodium Overload):

Step 1: Stop Sodium-Containing Fluids
- Identify and stop the source

Step 2: Free Water
- D5W for free water replacement

Step 3: Diuretics
- Furosemide to promote sodium excretion
- 20-40 mg IV initially
- Replaces sodium losses with D5W

Step 4: Dialysis
- Consider if severe, especially with renal impairment
- Haemodialysis or continuous renal replacement therapy (CRRT)

Monitoring During Treatment

Adjusting Therapy

Management of Overcorrection

If sodium drops too rapidly (> 12 mmol/L in 24 hours):

1. Stop hypotonic fluids
2. Consider re-raising sodium with 3% hypertonic saline if symptomatic cerebral oedema
3. DDAVP 1-2 mcg IV can be given to slow ongoing water diuresis and allow sodium to stabilise [14]
4. Target: raise sodium back to within 12 mmol/L of starting value for that 24-hour period

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Disposition

ICU Admission Criteria

• Severe hypernatraemia (sodium ≥160 mmol/L)
• Neurological symptoms (seizures, altered mental status, coma)
• Haemodynamic instability
• Need for frequent (every 2-4 hours) sodium monitoring
• Underlying condition requiring intensive care
• Risk of rapid correction requiring close monitoring

Ward Admission Criteria

• Moderate hypernatraemia (151-159 mmol/L)
• Mild symptoms
• Stable vital signs
• Clear aetiology
• Able to monitor every 4-6 hours

Discharge Considerations

Discharge is rarely appropriate for significant hypernatraemia. However, consider outpatient management for:

• Mild, chronic, asymptomatic hypernatraemia
• Clear correctable cause (e.g., medication adjustment)
• Reliable patient/caregiver
• Adequate water access ensured
• Close follow-up arranged (24-48 hours)
• Established DI with good understanding of management

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Special Populations

Elderly Patients

The elderly are at highest risk for hypernatraemia and have the worst outcomes: [8,15]

Critically Ill Patients

• Hospital-acquired hypernatraemia is common in ICU (4-9%) [10]
• Often iatrogenic (inadequate free water, hypertonic medications)
• Associated with worse outcomes independent of illness severity
• Prevention: calculate daily water requirements, monitor sodium

Neonates and Infants

• Cannot express thirst or obtain water
• Immature kidneys with reduced concentrating ability
• Causes: inadequate breastfeeding, hypernatraemic formula, diarrhoea
• Severe hypernatraemia can cause intracranial haemorrhage and brain injury
• Specialist paediatric management required

Post-Neurosurgical Patients

• High risk for central DI (especially post-pituitary surgery)
• Watch for triphasic response
• Close monitoring of sodium, urine output, urine osmolality
• May need DDAVP prophylactically or therapeutically

Patients with Diabetes Insipidus on Chronic DDAVP

• Education on sick day management
• If unable to take DDAVP: risk of severe hypernatraemia within hours
• Emergency plan for acute illness
• Medical alert bracelet recommended

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Prevention

In Hospital

• Calculate daily free water requirements for all patients
• Avoid excessive hypertonic fluid administration
• Monitor sodium at least daily in at-risk patients
• Ensure adequate fluid intake in those unable to drink
• Review medications that may cause DI (lithium)

In the Community

For patients with chronic hypernatraemia risk (e.g., elderly, DI):

• Ensure adequate water access at all times
• Scheduled fluid intake (don't rely on thirst)
• Caregiver education
• Regular sodium monitoring
• Sick day plans for those with DI

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Key Guidelines

European Society of Intensive Care Medicine (2014): [16]

• Diagnosis based on serum sodium > 145 mmol/L
• Classify by onset (acute vs chronic) and volume status
• Correct chronic hypernatraemia at ≤10-12 mmol/L/24h
• Treat underlying cause

UpToDate/Standard of Care: [1,2]

• Calculate water deficit using TBW formula
• Choose fluid based on volume status
• Monitor frequently during correction
• Treat underlying aetiology concurrently

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Exam-Focused Sections

Common Exam Questions

1. "What are the causes of hypernatraemia?"
2. "How would you investigate a patient with hypernatraemia and polyuria?"
3. "Calculate the water deficit in this patient and describe your correction plan."
4. "What is the danger of rapid correction? How would you manage overcorrection?"
5. "Describe the water deprivation test and how you would interpret the results."
6. "How do you differentiate central from nephrogenic diabetes insipidus?"

Viva Points

Opening Statement: "Hypernatraemia is defined as serum sodium greater than 145 mmol/L. It always indicates hyperosmolality and is most commonly caused by a deficit of free water relative to sodium. The key to management is identifying the underlying cause, calculating the water deficit, and correcting gradually to avoid cerebral oedema - aiming for no more than 10-12 mmol/L decrease in the first 24 hours for chronic cases."

Key Facts to Quote:

Common Mistakes

Mistakes that fail candidates:

• Correcting chronic hypernatraemia too rapidly
• Failing to assess volume status before choosing replacement fluid
• Not monitoring sodium frequently enough during correction
• Forgetting to account for ongoing losses
• Missing underlying cause (especially DI)
• Using normal saline for free water replacement (it doesn't correct hypernatraemia)
• Not recognising the triphasic response post-pituitary surgery

Model Answers

Q: Describe your approach to a patient with severe hypernatraemia (Na 165 mmol/L).

A: "I would approach this systematically. First, I would assess the patient's clinical status - ABC approach, level of consciousness, and haemodynamic stability. I would examine for volume status to classify as hypovolaemic, euvolaemic, or hypervolaemic.

Key investigations include serum osmolality (expecting > 330 mOsm/kg), urine osmolality and sodium to determine cause, glucose to exclude HHS, and renal function.

If urine is dilute (less than 300 mOsm/kg), this suggests diabetes insipidus, and I would give a DDAVP trial to differentiate central from nephrogenic DI.

For management, I would calculate the water deficit using: TBW × [(165/140) - 1]. In a 70 kg male with TBW of 42L, this gives approximately 7.5L deficit.

I would correct gradually - maximum 10-12 mmol/L in the first 24 hours to avoid cerebral oedema. If hypovolaemic and hypotensive, I would resuscitate initially with normal saline, then switch to 0.45% saline or D5W for free water replacement.

I would monitor serum sodium every 2-4 hours and adjust the rate accordingly. This patient would require ICU admission given the severity."

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Quality Metrics

Performance Indicators

Documentation Requirements

• Onset timing (acute vs chronic vs unknown)
• Volume status assessment
• Initial serum sodium and osmolality
• Urine osmolality and interpretation
• Water deficit calculation
• Fluid type and rate ordered
• Target correction rate
• Monitoring frequency
• Serial sodium levels with times
• Neurological status
• Response to treatment
• Underlying cause and treatment

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Key Clinical Pearls

Diagnostic Pearls

1. Hypernatraemia = water deficit, not sodium excess (in > 95% of cases)
2. Check urine osmolality - it's the key to diagnosis
3. Dilute urine + hypernatraemia = diabetes insipidus
4. Assume chronic if onset unknown - correct slowly
5. Elderly patients may not feel thirsty - don't rely on thirst as a symptom
6. Hospital-acquired hypernatraemia is common and often iatrogenic

Treatment Pearls

1. Slow correction - maximum 10-12 mmol/L per 24 hours for chronic
2. Volume resuscitate first if hypovolaemic and hypotensive (with normal saline)
3. D5W or 0.45% NaCl for free water replacement (not normal saline)
4. DDAVP for central DI - works within 1-2 hours
5. Monitor sodium every 2-4 hours during active correction
6. Account for ongoing losses - especially in DI (may be 5-10+ L/day)

Disposition Pearls

1. ICU for severe (≥160) or symptomatic - needs frequent monitoring
2. Frequent sodium monitoring is essential - adjust therapy based on response
3. Address underlying cause - or hypernatraemia will recur
4. Ensure adequate water access before discharge
5. Caregiver education is crucial for elderly/dependent patients

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References

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2. Adrogue HJ, Madias NE. Hypernatremia. N Engl J Med. 2000;342(20):1493-1499. doi:10.1056/NEJM200005183422006

3. Sterns RH. Severe symptomatic hyponatremia: treatment and outcome. A study of 64 cases. Ann Intern Med. 1987;107(5):656-664. doi:10.7326/0003-4819-107-5-656

4. Verbalis JG, Goldsmith SR, Greenberg A, et al. Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations. Am J Med. 2013;126(10 Suppl 1):S1-42. doi:10.1016/j.amjmed.2013.07.006

5. Muhsin SA, Mount DB. Diagnosis and treatment of hypernatremia. Best Pract Res Clin Endocrinol Metab. 2016;30(2):189-203. doi:10.1016/j.beem.2016.02.014

6. Liamis G, Milionis HJ, Elisaf M. A review of drug-induced hypernatremia. NDT Plus. 2009;2(5):339-346. doi:10.1093/ndtplus/sfp085

7. Seay NW, Lehrich RW, Greenberg A. Diagnosis and management of disorders of body tonicity-hyponatremia and hypernatremia: core curriculum 2020. Am J Kidney Dis. 2020;75(2):272-286. doi:10.1053/j.ajkd.2019.07.014

8. Palevsky PM, Bhagrath R, Greenberg A. Hypernatremia in hospitalized patients. Ann Intern Med. 1996;124(2):197-203. doi:10.7326/0003-4819-124-2-199601150-00002

9. Hoorn EJ, Betjes MG, Weigel J, Zietse R. Hypernatraemia in critically ill patients: too little water and too much salt. Nephrol Dial Transplant. 2008;23(5):1562-1568. doi:10.1093/ndt/gfm831

10. Lindner G, Funk GC, Schwarz C, et al. Hypernatremia in the critically ill is an independent risk factor for mortality. Am J Kidney Dis. 2007;50(6):952-957. doi:10.1053/j.ajkd.2007.08.016

11. Robertson GL. Antidiuretic hormone: normal and disordered function. Endocrinol Metab Clin North Am. 2001;30(3):671-694. doi:10.1016/s0889-8529(05)70207-3

12. Christ-Crain M, Bichet DG, Fenske WK, et al. Diabetes insipidus. Nat Rev Dis Primers. 2019;5(1):54. doi:10.1038/s41572-019-0103-2

13. Adrogue HJ, Madias NE. Aiding fluid prescription for the dysnatremias. Intensive Care Med. 1997;23(3):309-316. doi:10.1007/s001340050333

14. Sterns RH, Nigwekar SU, Hix JK. The treatment of hyponatremia. Semin Nephrol. 2009;29(3):282-299. doi:10.1016/j.semnephrol.2009.03.002

15. Snyder NA, Feigal DW, Arieff AI. Hypernatremia in elderly patients. A heterogeneous, morbid, and iatrogenic entity. Ann Intern Med. 1987;107(3):309-319. doi:10.7326/0003-4819-107-2-309

16. Spasovski G, Vanholder R, Allolio B, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Nephrol Dial Transplant. 2014;29 Suppl 2:i1-i39. doi:10.1093/ndt/gfu040

17. Bichet DG. Nephrogenic diabetes insipidus. Adv Chronic Kidney Dis. 2006;13(2):96-104. doi:10.1053/j.ackd.2006.01.006

18. Fenske W, Allolio B. Clinical review: current state and future perspectives in the diagnosis of diabetes insipidus: a clinical review. J Clin Endocrinol Metab. 2012;97(10):3426-3437. doi:10.1210/jc.2012-1981

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