Diabetes Insipidus (DI)

1. Central Diabetes Insipidus (CDI): A deficiency in arginine vasopressin (AVP), also known as antidiuretic hormone (ADH), which is synthesised in the hypothalamus and secreted by the posterior pituitary gland.
2. Nephrogenic Diabetes Insipidus (NDI): A condition where the kidneys are resistant to AVP, impairing urine concentration despite sufficient hormone levels.

1. Central DI (CDI): Results from an absolute or relative deficiency of arginine vasopressin (AVP) production or secretion.
2. Nephrogenic DI (NDI): Arises due to renal insensitivity or resistance to AVP's action within the collecting ducts.
   
   

Central DI

• Idiopathic (30%): Often linked to autoimmune mechanisms with lymphocytic infiltration of the posterior pituitary or pituitary stalk. Antibodies directed against AVP-secreting cells have been identified but are not always diagnostic due to overlaps with other conditions like Langerhans cell histiocytosis and germinomas. Close monitoring with MRI is essential in idiopathic cases, especially those with pituitary stalk thickening.
• Tumor-Associated (25%): Primary intracranial tumors such as craniopharyngiomas, germinomas, and pineal tumors can lead to central DI. Craniopharyngiomas are particularly common in pediatric cases and often present pre- or postoperatively with DI and other hypothalamic manifestations.
• Postoperative (20%): Neurosurgery, particularly involving transsphenoidal approaches, frequently results in transient or permanent DI. Factors such as cerebrospinal fluid leaks during surgery significantly increase the risk of postoperative DI.
• Head Trauma (16%): Central DI is a potential complication of moderate to severe head injuries, often presenting transiently but sometimes progressing to a permanent state.
• Hereditary Central DI: Constitutes approximately 10% of cases. Autosomal dominant inheritance is common, associated with mutations in the AVP-NP2 gene, causing toxic accumulation of mutant proteins in magnocellular neurons. Autosomal recessive forms include mutations in the WFS1 gene, leading to Wolfram syndrome (DIDMOAD).
• Other Causes: Includes hypoxic encephalopathy, granulomatous diseases (e.g., sarcoidosis, histiocytosis X), vascular lesions (e.g., arteriovenous malformations, Sheehan syndrome), and certain cancers (e.g., metastases from lung cancer).
  
  

Nephrogenic DI

• Acquired Causes:
  • Medications: Lithium therapy is the leading cause, affecting up to 40% of long-term users. Other implicated drugs include demeclocycline, amphotericin B, cisplatin, and foscarnet.
  • Electrolyte Imbalances: Chronic hypercalcemia and hypokalemia impair AVP action.
  • Chronic Renal Conditions: Conditions like sickle cell disease, renal amyloidosis, or obstructive uropathy can disrupt the AVP response.
• Hereditary Causes:
  • AVPR2 Gene Mutations: X-linked recessive inheritance accounts for 90% of cases. These mutations lead to defective vasopressin receptor function.
  • AQP2 Gene Mutations: Autosomal recessive and dominant forms arise from defects in aquaporin-2 water channels in the renal collecting ducts.
    
    

Other Specific Situations

• Pregnancy: Gestational DI occurs due to increased vasopressinase activity from the placenta, unmasking subclinical AVP deficiencies.
• Drug-Induced DI: Aside from lithium, various drugs induce NDI, usually reversible upon discontinuation.
  
  

Key Mechanisms Regulating Water Balance

• AVP Synthesis and Release:
  • AVP is synthesised in magnocellular neurons of the hypothalamus, specifically in the supraoptic (SON) and paraventricular (PVN) nuclei.
  • It undergoes post-translational processing, producing AVP, neurophysin II, and copeptin. These are transported along axons to the posterior pituitary for storage and secretion.
  • Plasma osmolality, sensed by hypothalamic osmoreceptors, is the primary trigger for AVP release. Baroreceptors also regulate AVP secretion in response to blood volume or pressure changes.
• Renal Action of AVP:
  • AVP binds to V2 receptors in renal collecting duct cells, increasing water permeability by promoting the insertion of aquaporin-2 (AQP2) water channels into the apical membrane.
  • This mechanism enhances water reabsorption, concentrating the urine and maintaining plasma osmolality within a narrow range.

Pathogenesis in Central and Nephrogenic DI

1. Central DI (CDI):
   • Results from damage to the neurohypophysis, which includes the hypothalamus, pituitary stalk, and posterior pituitary.
   • Causes include trauma, neurosurgery, tumors, autoimmune diseases, or genetic mutations affecting AVP synthesis or secretion.
   • A deficiency in AVP leads to impaired renal water reabsorption, excessive urine output, and stimulation of thirst.
2. Nephrogenic DI (NDI):
   • Arises from the kidney’s inability to respond to AVP despite normal hormone levels.
   • Can be caused by genetic mutations (e.g., AVPR2 or AQP2) or acquired factors like chronic lithium use, hypercalcemia, or chronic kidney disease.
   • The absence of AVP-mediated AQP2 insertion results in dilute urine and polyuria.
     
     

Additional Pathophysiological Insights

• Adipsic DI:
  • Occurs due to damage to hypothalamic osmoreceptors, leading to deficient AVP secretion and impaired thirst response.
  • This condition is often associated with hypernatremia because thirst-dependent water intake does not compensate for urinary water losses.
• Pregnancy-Associated Changes:
  • Pregnancy alters osmoregulation, with a lower osmotic threshold for AVP release.
  • Increased placental vasopressinase activity accelerates AVP clearance, occasionally unmasking subclinical central DI.
    
    

Global Prevalence

• The estimated global prevalence of DI is approximately 1 in 25,000 individuals (0.004%).
• Central DI (CDI) is more common than nephrogenic DI (NDI), but precise data on the relative proportions are limited.
  
  

Prevalence in the United States

• DI occurs at a rate of about 3 cases per 100,000 population in the United States.
• Both CDI and NDI demonstrate similar prevalence rates between males and females, with no significant differences observed across ethnic groups.
  
  

Genetic vs. Acquired Causes

• Most cases of DI are acquired rather than hereditary.
• Hereditary forms of DI, including those caused by mutations in the AVPR2 or AQP2 genes, account for only 1–2% of all cases.
• NDI due to AQP2 gene mutations is particularly rare, with an incidence of about 1 in 20 million births.
  
  

Age of Onset

• DI may develop at any age.
• Hereditary forms often present earlier in life, while acquired forms are commonly seen in adults, often secondary to trauma, surgery, or disease.
  
  

Variations in Sex and Genetic Influences

• While both CDI and NDI show equal prevalence among sexes, NDI is more common in males when it results from X-linked recessive AVPR2 gene mutations.
• In contrast, autosomal forms of NDI due to AQP2 mutations affect males and females equally.
  
  

Clinical Relevance

• Despite its rarity, DI can significantly affect patient quality of life if left undiagnosed or mismanaged.
• Misdiagnosis or delayed diagnosis, particularly in inherited or atypical cases, can lead to poor clinical outcomes.
  
  

Common Symptoms

1. Polyuria:
   • Excessive urination, with volumes ranging from 3–20 liters per day.
   • Consistent daily urine output is a hallmark feature, distinguishing it from urinary frequency seen in other conditions.
2. Polydipsia:
   • Increased fluid intake, often due to extreme thirst.
   • Patients often prefer cold liquids, particularly water, to compensate for fluid losses.
3. Nocturia:
   • Frequent urination during nighttime, commonly disrupting sleep patterns.
     
     

Patterns of DI

• Triphasic Response (associated with CDI following trauma or surgery):
  1. Polyuric Phase (4–5 days): Characterised by abrupt increases in urine output and reduced urinary osmolality due to suppression of AVP release.
  2. Antidiuretic Phase (5–6 days): Urinary osmolality improves temporarily as stored AVP is released.
  3. Permanent DI Phase: Occurs if AVP-secreting cells are permanently damaged.
     
     

Age-Related Presentation

• Infants:
  • Manifestations include irritability, crying, growth retardation, hyperthermia, and weight loss.
  • May present with dehydration if fluid intake does not match urinary losses.
• Children:
  • Enuresis (bedwetting), fatigue, anorexia, and growth defects are common.
• Adults:
  • Symptoms vary widely based on the etiology, with possible additional signs related to the underlying cause (e.g., neurological deficits).
    
    

Specific Scenarios

1. Pregnancy:
   • DI can be unmasked due to increased AVP clearance by placental vasopressinase.
   • Typically resolves postpartum but may aggravate pre-existing subclinical DI.
2. Adipsic DI:
   • Caused by hypothalamic lesions impairing both AVP release and thirst mechanisms.
   • Results in severe dehydration and hypernatremia due to lack of compensatory fluid intake.
     
     

Historical Risk Factors

• Surgical History:
  • Pituitary or hypothalamic surgeries (e.g., transsphenoidal procedures) often precipitate CDI.
• Trauma:
  • Traumatic brain injuries can lead to transient or permanent CDI.
• Autoimmune Disorders:
  • Hashimoto’s thyroiditis and type 1 diabetes mellitus are associated with CDI.
• Medications:
  • Long-term lithium use and other drugs (demeclocycline, cisplatin, amphotericin B) can induce NDI.
• Family History:
  • X-linked mutations (AVPR2) and autosomal mutations (AQP2, AVP-neurophysin) are implicated in hereditary DI.
    
    

General Findings

• Hydration Status:
  • Most patients with access to fluids maintain normal hydration.
  • Dehydration is uncommon unless the thirst mechanism is impaired or access to water is restricted, which can lead to:
    • Dry mucous membranes
    • Poor skin turgor
    • Tachycardia
    • Postural hypotension
    • Severe cases: Shock
• Bladder and Renal Signs:
  • Bladder enlargement may occur due to chronic polyuria.
  • Hydronephrosis may be present, causing:
    • Pelvic fullness
    • Flank pain or tenderness
    • Pain radiating to the genital area

Neurological and Visual Findings

• Visual Field Defects:
  • May suggest a mass or lesion affecting the optic chiasm, such as a pituitary tumor.
• Focal Neurological Deficits:
  • Can indicate prior or coexisting intracranial pathology, such as trauma, meningitis, or tumor invasion.
    
    

Specific Findings Based on Underlying Aetiology

• Adipsic DI:
  • Characterised by signs of severe dehydration and hypernatremia without compensatory polydipsia due to an impaired thirst mechanism.
• Endocrine and Dermatological Associations:
  • Wolfram Syndrome:
    • Sensorineural deafness
    • Visual failure with optic atrophy
  • Autoimmune Diseases:
    • Skin manifestations like erythema nodosum or rashes in conditions like sarcoidosis or Langerhans cell histiocytosis
      
      

Examination in Paediatric Patients

• Infants and Children:
  • May present with symptoms indicative of chronic dehydration, including:
    • Irritability
    • Failure to thrive
    • Weight loss
    • Poor feeding
      
      

Initial Laboratory Investigations

1. Urine Osmolality:
   • Findings: Low (<300 mOsm/kg) in the context of high serum osmolality or elevated sodium.
   • Significance: Indicates impaired urinary concentration, a hallmark of DI.
2. Serum Osmolality:
   • Findings: Typically elevated (>290 mOsm/kg) in DI.
   • Significance: Elevated levels with low urine osmolality confirm a water diuresis.
3. Serum Sodium:
   • Findings: May be normal in compensated DI but elevated in cases with impaired thirst or restricted access to fluids.
   • Significance: Hypernatremia strengthens the suspicion of DI in appropriate clinical settings.
4. Serum Glucose:
   • Findings: Normal in DI.
   • Significance: Rules out diabetes mellitus as the cause of polyuria.
5. Serum Potassium and Calcium:
   • Findings: Hypokalemia or hypercalcemia may be present.
   • Significance: These abnormalities can contribute to nephrogenic DI.
6. Urine Dipstick:
   • Findings: Negative for glycosuria; may show proteinuria if renal disease is present.
   • Significance: Excludes diabetes mellitus and highlights potential renal contributions.
7. 24-Hour Urine Collection:
   • Findings: Polyuria, defined as urine output >3 liters/day.
   • Significance: Quantifies the degree of water loss.
     
     

Dynamic and Specialised Tests

1. Water Deprivation Test:
   • Method:
     • Fluid restriction for up to 8 hours or until 3% of body weight is lost.
     • Hourly monitoring of serum osmolality, urine osmolality, and urine volume.
   • Findings:
     • Failure to concentrate urine (<300 mOsm/kg) despite elevated serum osmolality (>290 mOsm/kg) confirms DI.
   • Significance: Differentiates DI from primary polydipsia.
2. Desmopressin (DDAVP) Stimulation Test:
   • Method: Administration of desmopressin followed by hourly measurements of serum and urine osmolality.
   • Findings:
     • Central DI: Urine osmolality increases significantly (>750 mOsm/kg).
     • Nephrogenic DI: Minimal or no response.
   • Significance: Helps distinguish central from nephrogenic DI.
3. Hypertonic Saline-Stimulated Copeptin Test:
   • Method: Baseline and post-hypertonic saline copeptin levels measured.
   • Findings:
     • Copeptin >21.4 pmol/L: Nephrogenic DI.
     • Copeptin >4.9 pmol/L post-stimulation: Central DI.
   • Significance: High accuracy in differentiating DI subtypes.
     
     

Imaging Studies

1. Cranial MRI:
   • Findings:
     • Absence of the posterior pituitary "bright spot."
     • Pituitary stalk thickening, sellar or para-sellar mass.
   • Significance: Identifies structural abnormalities causing central DI.
     
     

Advanced and Aetiology-Specific Tests

1. Genetic Testing:
   • Indications: Family history of DI or early onset.
   • Findings:
     • AVPR2 mutations: X-linked nephrogenic DI.
     • AQP2 mutations: Autosomal nephrogenic DI.
   • Significance: Confirms hereditary DI and guides familial risk assessment.
2. Tumor Markers:
   • Findings: Elevated alpha-fetoprotein and beta-hCG in germinomas.
   • Significance: Evaluates for malignancies in young patients with pituitary stalk lesions.
3. Autoantibody Testing:
   • Findings: Positive antithyroid peroxidase antibodies in Hashimoto's thyroiditis.
   • Significance: Supports autoimmune causes of DI.
4. Pituitary Hormone Evaluation:
   • Tests:
     • Morning cortisol and ACTH
     • TSH, T3/T4
     • IGF-1 and growth hormone
   • Significance: Identifies associated hypopituitarism in central DI.
     
     

Psychogenic Polydipsia

• Signs and Symptoms:
  • Associated with psychiatric conditions such as schizophrenia or anxiety disorders.
  • Daytime symptoms or waking with a need to drink rather than urinate are more common.
• Investigations:
  • Water Deprivation Test: A rise in urine osmolality >700 mOsm/kg during dehydration indicates normal AVP axis function, but long-standing psychogenic polydipsia may impair renal concentrating ability.
  • Hypertonic Saline-Stimulated Copeptin Test: Copeptin level ≤4.9 pmol/L suggests psychogenic polydipsia.
    
    

Diabetes Mellitus

• Signs and Symptoms:
  • Polyuria and polydipsia may mimic DI.
  • Often accompanied by weight loss, fatigue, and hyperglycemia.
• Investigations:
  • Plasma Glucose: Elevated glucose levels confirm diabetes mellitus.
  • Urine Dipstick: Presence of glycosuria supports the diagnosis.
    
    

Diuretic Use

• Signs and Symptoms:
  • Symptoms similar to DI but associated with a history of diuretic use.
• Investigations:
  • Clinical diagnosis based on patient history.
  • Urinary electrolyte excretion patterns may help confirm.

Hypercalcemia

• Signs and Symptoms:
  • Often asymptomatic but may include abdominal pain, constipation, fatigue, renal stones, and anorexia.
• Investigations:
  • Serum Calcium: Elevated levels confirm hypercalcemia.
  • Further Tests: Assess parathyroid hormone (PTH) levels if hypercalcemia is confirmed.

Hypokalemia

• Signs and Symptoms:
  • May cause nephrogenic DI-like symptoms due to impaired urinary concentrating ability.
• Investigations:
  • Serum Potassium: Low levels support the diagnosis.
  • Evaluate for underlying causes, such as gastrointestinal losses or diuretic use.
    
    

Histiocytosis (e.g., Langerhans Cell Histiocytosis)

• Signs and Symptoms:
  • Associated with central DI, systemic symptoms, and lytic bone lesions.
• Investigations:
  • MRI: Pituitary stalk thickening.
  • Biopsy: Confirms histiocytosis.
    
    

Sickle Cell Disease

• Signs and Symptoms:
  • Polyuria related to renal tubular dysfunction.
• Investigations:
  • Hemoglobin Electrophoresis: Confirms sickle cell trait or disease.
  • Urine osmolality shows impaired concentrating ability.
    
    

Medullary Cystic Disease

• Signs and Symptoms:
  • Chronic polyuria with signs of progressive renal failure.
• Investigations:
  • Renal Ultrasound: Shows medullary cysts.
  • Genetic Testing: May identify causative mutations.

Paediatric Head Trauma

• Signs and Symptoms:
  • Polyuria may follow traumatic brain injury due to central DI.
• Investigations:
  • MRI: Evaluates hypothalamic-pituitary damage.
  • Water Deprivation Test: Confirms DI if indicated.

Type 1 Diabetes Mellitus

• Signs and Symptoms:
  • Polyuria and polydipsia may mimic DI but are accompanied by hyperglycemia and weight loss.
• Investigations:
  • Serum Glucose and HbA1c: Elevated.
  • Urine Dipstick: Glycosuria.
    
    

General Principles

1. Treatment Goals:
   • Restore and maintain fluid balance.
   • Correct hypernatremia if present.
   • Alleviate polyuria, polydipsia, and nocturia.
   • Prevent long-term complications and improve quality of life.
2. Fluid Replacement:
   • Oral or Enteral Fluids: Preferred for correcting mild to moderate dehydration.
   • Intravenous Fluids: Required for severe cases or when oral intake is inadequate.
     • Hypotonic solutions such as 5% dextrose or 0.45% sodium chloride are recommended.
     • Adjust infusion rates to avoid rapid shifts in serum sodium levels, especially in chronic hypernatremia.
3. Monitoring:
   • Regular assessment of serum electrolytes and osmolality to guide therapy.
   • Frequent monitoring is crucial during fluid replacement and initiation of pharmacologic therapy to avoid hyponatremia or overcorrection.

Central Diabetes Insipidus (CDI)

1. Desmopressin (DDAVP):
   • A synthetic analog of arginine vasopressin (AVP), it is the treatment of choice for CDI.
   • Routes of Administration:
     • Intranasal, oral, subcutaneous, or intravenous.
     • Parenteral forms are preferred for acute presentations due to rapid onset of action.
   • Dosage:
     • Start with the lowest effective dose to prevent water retention and hyponatremia.
     • Nocturnal dosing may suffice for mild cases.
2. Acute Management:
   • Administer parenteral or oral DDAVP at the lowest dose.
   • Monitor urine output, serum sodium, and osmolality closely.
   • Ensure adequate fluid intake to match urine output.
3. Chronic Management:
   • Individualised dosing, often with a single nocturnal dose for mild cases.
   • Patients should periodically skip doses (e.g., one day per week) to allow excess water excretion and reduce hyponatremia risk.
     
     

Nephrogenic Diabetes Insipidus (NDI)

1. Fluid Management:
   • Encourage adequate oral fluid intake to compensate for urinary losses.
   • Monitor for signs of dehydration, especially during intercurrent illness.
2. Address Underlying Causes:
   • Discontinue offending medications (e.g., lithium, demeclocycline).
   • Correct electrolyte disturbances such as hypercalcemia or hypokalemia.
3. Dietary Modifications:
   • Implement a low-sodium diet (<500 mg/day) to reduce renal solute load.
   • A low-protein diet may also help decrease urine output.
4. Pharmacologic Therapy:
   • Thiazide Diuretics:
     • Induce mild hypovolemia, enhancing proximal tubular water reabsorption and reducing urine output.
   • Nonsteroidal Anti-Inflammatory Drugs (NSAIDs):
     • Reduce prostaglandin-mediated antagonism of AVP.
   • Combination Therapy:
     • Thiazides and NSAIDs are often synergistic in reducing polyuria.
   • High-Dose DDAVP:
     • May partially improve symptoms in cases of variable renal insensitivity to AVP.

Management of Hypernatremia

1. Acute Hypernatremia:
   • Correct serum sodium rapidly but cautiously (≤1 mmol/L per hour) to prevent cerebral edema.
2. Chronic Hypernatremia:
   • Correct serum sodium at a slower rate (≤0.5 mmol/L per hour) to reduce the risk of cerebral edema.
3. Free Water Deficit Calculation:
   • Free water deficit = TBW × [(serum Na/140) - 1]
   • TBW is estimated as 0.6 × body weight for men and children, 0.5 × body weight for women, and 0.45 × body weight for elderly women.
     
     

Paediatric Management

• Infants and Small Children:
  • Intranasal DDAVP or subcutaneous administration may be preferred due to challenges in oral dosing.
  • Monitor serum sodium frequently, especially in the early stages of treatment.
• Older Children:
  • Oral or intranasal DDAVP at doses tailored to age and weight.
  • Encourage appropriate fluid intake, and educate caregivers about symptoms of hyponatremia and hypernatremia.
    
    

General Prognosis

1. Central DI (CDI):
   • CDI is often well-controlled with desmopressin (DDAVP), a synthetic analog of AVP.
   • Postoperative or trauma-induced CDI may be transient, particularly after pituitary surgery or head trauma.
   • Lifelong monitoring is needed for associated conditions, such as anterior pituitary deficiencies, and any underlying intracranial pathology.
2. Nephrogenic DI (NDI):
   • Prognosis depends on the underlying cause:
     • Medication-Induced NDI: Discontinuing the offending agent (e.g., lithium) may lead to resolution, though long-term lithium use can cause irreversible damage.
     • Electrolyte Imbalances: NDI secondary to hypercalcemia or hypokalemia often resolves with correction of the electrolyte disturbance.
     • Congenital NDI: Inherited forms, such as those caused by AVPR2 or AQP2 mutations, are lifelong conditions that require ongoing management to prevent complications.
3. Gestational DI:
   • Typically resolves postpartum, as placental vasopressinase activity ceases after delivery.
     
     

Long-Term Complications

1. Hypernatremia and Dehydration:
   • Severe hypernatremia can lead to neurological complications, cardiovascular collapse, and, in rare cases, death.
   • At-risk populations include children, elderly patients, and individuals with restricted access to water.
2. Bladder and Renal Issues:
   • Chronic polyuria can lead to bladder dysfunction, hydronephrosis, or chronic kidney disease (CKD).
   • Regular imaging of the renal tract is recommended for patients with large-volume polyuria to detect and manage such complications early.
3. Growth and Development in Pediatric Patients:
   • A retrospective study reported that 61% of pediatric patients with congenital NDI required hospitalisation for hypernatremia and failure to thrive.
   • Long-term follow-up showed a reduction in growth delays with optimal management.
4. Mortality:
   • DI-related mortality is rare if water intake is adequate.
   • Life-threatening complications are more likely in neglected cases, such as those with undiagnosed DI or inability to access fluids.
     
     

Monitoring and Follow-Up

1. Regular Monitoring:
   • Lifelong follow-up for patients with central DI to assess for evolving intracranial pathologies and anterior pituitary hormone deficiencies.
   • Routine serum sodium and osmolality measurements to prevent complications from over- or under-treatment.
2. Imaging:
   • Periodic renal and bladder imaging is advised in patients with chronic polyuria to monitor for hydronephrosis or bladder dysfunction.
3. Management of Associated Conditions:
   • Address and monitor other comorbidities, such as electrolyte disturbances or anterior pituitary hormone deficiencies, as needed.
     
     

Short-Term Complications

1. Hypernatremia:
   • Mechanism:
     • Develops when water intake is insufficient to compensate for excessive urinary losses, especially in patients with impaired thirst or restricted access to fluids.
   • Clinical Features:
     • Mild to moderate hypernatremia: Irritability, restlessness, lethargy, muscle twitching, spasticity, hyper-reflexia.
     • Severe hypernatremia: Delirium, seizures, or coma.
   • Management:
     • Oral or intravenous fluids to correct the free water deficit.
     • Monitor serial serum sodium and osmolality to guide therapy and avoid rapid correction.
2. Thrombosis:
   • Mechanism:
     • Dehydration and hypernatremia increase the risk of thrombotic events, such as deep vein thrombosis.
   • Clinical Features:
     • Swelling, pain, or redness in the affected limb.
   • Management:
     • Address dehydration promptly and consider anticoagulation in high-risk patients.
       
       

Therapy-Related Complications

1. Iatrogenic Hyponatremia:
   • Mechanism:
     • Excessive desmopressin (DDAVP) dosing or overhydration during treatment of central DI.
   • Clinical Features:
     • Asymptomatic in most cases but can cause nausea, headache, lethargy, seizures, or coma in severe cases.
   • Management:
     • Adjust DDAVP dosage to minimise water retention.
     • Monitor serum sodium levels regularly.
       
       

Long-Term Complications

1. Bladder Dysfunction:
   • Mechanism:
     • Chronic high urinary output in nephrogenic DI can lead to bladder overdistension and dysfunction.
   • Clinical Features:
     • Urinary retention or incontinence.
   • Management:
     • Regular bladder ultrasound to assess function.
2. Renal Dysfunction:
   • Mechanism:
     • Prolonged nephrogenic DI may cause renal impairment, including chronic kidney disease (CKD).
   • Clinical Features:
     • Increased serum creatinine and reduced glomerular filtration rate.
   • Management:
     • Periodic renal function monitoring with serum creatinine and estimated GFR.
     • Correct underlying causes, such as hypercalcemia or drug-induced nephropathy.
       
       

Other Possible Complications

1. Chronic Dehydration:
   • Symptoms include tachycardia, hypotension, fatigue, weight loss, and headaches.
   • May predispose patients to kidney damage and brain dysfunction if untreated.
2. Neurological Damage:
   • Severe or prolonged hypernatremia can lead to irreversible brain injury.
     
     

Monitoring Recommendations

1. Serum Electrolytes and Osmolality:
   • Frequent checks during acute management or dose adjustments for DDAVP.
   • Periodic monitoring in stable patients.
2. Renal and Bladder Imaging:
   • Regular ultrasounds to detect hydronephrosis or bladder dysfunction in patients with chronic polyuria.
3. Thrombosis Screening:
   • Consider in dehydrated patients or those with high thrombotic risk.
     
     

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