Diabetes Insipidus

Get CMEDiabetes InsipidusRecently, @EMHighAK (Alex Koyfman) asked about any “teaching points” with respect to Pediatric DKA and Cerebral Edema. In addition to referencing an oldie, but a goodie morsel on Cerebral Edema, I also mentioned that we should all be careful not to attribute all ketonuria in vomiting kids to “starvation ketosis.” That got me to thinking about other potential diabetes related urine pitfalls. What about the child with polyuria but no glucosuria? Is that reassuring and do I quickly assume that the child is just super-hydrated? Let us take a minute to recall that there is another diabetes to consider: Diabetes Insipidus.

 

Diabetes Insipidus: What’s in a name?

  • Diabetes,” etymologically, has origins in words that mean “to pass through” and was used to describe excessive passage of urine (polyuria).
  • Mellitus” has origins from words that mean honey and/or sweetness.
  • Insipidus” stems from words that meant lacking flavor or taste.
  • So to differentiate between the two, all we have to do is taste the urine. Simple.
    • This was how physicians of antiquity would evaluate the urine. (Delicious!)
    • Ok… I don’t advise this… and I’m pretty sure there are some hospital regulations that make that practice a reason to terminate your employment.
    • I am glad we have replaced human tongues with urine dipsticks for this!

 

Diabetes Insipidus: Basics

  • Diabetes Insipidus = the inability to concentrate urine
  • Can be due to:
    • Central CNS process – vasopressin deficiency 
      • Any process that impairs production and release of vasopressin can lead to diabetes insipidus.  [Dabrowski, 2016]
      • Central Diabetes Insipidus (DI) is more common than Nephrogenic DI
    • Nephrogenic process – vasopressin resistance
      • Vasopressin production is adequate.
      • Vasopressin should activate the V2 receptor in the collecting duct, inserting aquaporin 2 channels allowing free water to be reabsorbed.
      • Errors in the V2 receptor or aquaporin 2 channels will lead to diabetes insipidus.  [Dabrowski, 2016]
  • Diabetes Insipidus is rare, but can be associated with some common conditions.
    • Prevalence = 1:25,000
    • ~90% of cases are acquired, rather than inherited.
    • Some common acquired causes: [Dabrowski, 2016]
      • Intracranial tumors (ex, Craniopharyngioma, Optic Glioma)
      • Trauma (~18% of severe traumatic brain injury develop DI) [ Alharfi, 2013]
      • CNS Infections (ex, Meningococcal, Cryptococcal, Toxoplasmosis)
      • Hypoxic-Ischemic Injury
      • Postpartum Hemorrhage (Sheehan Syndrome)
      • Infiltrative (ex, Sarcoidosis, Leukemia)
      • Primary Renal Disease
      • Medications (lead to Nephrogenic DI mostly):
        • Lithium (most common culprit)
        • Antimicrobials (ex, amphotericin B)
        • Antineoplastic agents (ex, cisplatin, vinblastine)
        • Sulfonylureas
        • Colchicine
        • Ketamine (ok, only case reports of this… but just be aware) [Hatab, 2014]

 

Diabetes Insipidus: Presentation

  • Polydipsia
    • Extreme thirst, particularly with a preference for cold water. [Dabrowski, 2016; Haddad, 2016]
    • Intense water seeking behaviors.
  • Polyuria
    • Urine output > 2 L/m^2/Day
    • Urine output > 150 ml/kg/Day (neonates); 100-110 ml/kg/Day (up to 2yrs); 40-50 ml/kg/Day (older kids)
  • New onset enuresis in previously toilet-trained child? Think DM or DI.
  • Additional signs/symptoms due to intracranial processes: [Dabrowski, 2016]
    • Growth retardation
      • Infants may present in first few weeks of life with growth failure. [Ranadive, 2011]
    • Fatigue
    • Fever of unknown origin
    • Headache
    • Emesis (hmm… emesis and polyuria… sounds like DKA… but it isn’t… be vigilant)
    • Visual field cuts

 

Diabetes Insipidus: Evaluation

  • Chemistry panel for sodium, potassium, glucose, BUN, and Calcium.
    • Normal glucose? Not likely diabetes mellitus related polyuria.
    • Hypercalcemia and Hypokalemia can induced nephrogenic DI.
  • Urinalysis for urine specific gravity and urine glucose
  • Serum osmolality and Urine Osmolality [Dabrowski, 2016] 
    • Urine studies are more reliable on first morning void.
    • Radom Serum Osm > 300 mOsm/kg at the same time Random Urine Osm < 600 mOsm/kg is indicative of diabetes insipidus. [Dabrowski, 2016]
    • Water deprivation testing is used to confirm diagnosis (needs to be done as an inpatient for close monitoring). [Dabrowski, 2016]
  • Neuro imaging (Brain MRI) is often performed after diagnosis is made to evaluate the pituitary.

 

Diabetes Insipidus: Management

  • Management of children with diabetes insipidus can be very complicated and requires constant supervision and monitoring.
    • Therapies can place young children at risk of water intoxication and hyponatremia.
    • Not treating young children places them at risk of dehydration and hypernatremia.
  • Infants and young children are particularly challenging to manage. [Dabrowski, 2016]
    • Don’t have free and easy access to water.
    • < 2 months of age, normal kidneys are not able to maximally concentrate urine.
    • Breast milk has a lower solute load than standard formulas.
  • Free access to water!
    • Children with mild diabetes insipidus can be treated with only increasing fluids.
    • With more significant cases, the amount of fluid required can lead to complications (ex, hydronephrosis), so medications are required.
  • Medications
    • Synthetic vasopressin / DDAVP
      • Mainstay of treatment for Central DI
      • Will not affect Nephrogenic DI
    • Thiazide diuretics
      • Induce natriuresis and subsequent volume contraction
      • Volume contraction leads to increased water and sodium reabsorption in proximal tubule.
      • Safer alternative for infants than DDAVP.
      • Can be used for both Central and Nephrogenic DI.
    • Indomethacin or Amiloride
      • Used in combination with Thiazide Diuretic for Nephrogenic DI

 

Moral of the Morsel

  • Polyuria and Polydipsia is concerning for diabetes! Just don’t forget that it may be Insipidus and not Mellitus.
  • Remain vigilant and fight the urge to have early closure on a potential diagnosis.
  • Remember the associated acquired conditions – polyuria after closed head injury? – consider DI!

 

References

Dabrowski E1, Kadakia R2, Zimmerman D3. Diabetes insipidus in infants and children. Best Pract Res Clin Endocrinol Metab. 2016 Mar;30(2):317-28. PMID: 27156767. [PubMed] [Read by QxMD]

Haddad NG, Nabhan ZM, Eugster EA. INCIDENCE OF CENTRAL DIABETES INSIPIDUS IN CHILDREN PRESENTING WITH POLYDIPSIA AND POLYURIA. Endocr Pract. 2016 Dec;22(12):1383-1386. PMID: 27540876. [PubMed] [Read by QxMD]

Hatab SZ1, Singh A2, Felner EI3, Kamat P2. Transient central diabetes insipidus induced by ketamine infusion. Ann Pharmacother. 2014 Dec;48(12):1642-5. PMID: 25225198. [PubMed] [Read by QxMD]

Alharfi IM1, Stewart TC, Foster J, Morrison GC, Fraser DD. Central diabetes insipidus in pediatric severe traumatic brain injury. Pediatr Crit Care Med. 2013 Feb;14(2):203-9. PMID: 23314181. [PubMed] [Read by QxMD]

Ranadive SA1, Rosenthal SM. Pediatric disorders of water balance. Pediatr Clin North Am. 2011 Oct;58(5):1271-80, xi-xii. PMID: 21981960. [PubMed] [Read by QxMD]

Sean Fox

I enjoy taking care of patients and I finding it endlessly rewarding to help train others to do the same. I trained at the Combined Emergency Medicine and Pediatrics residency program at University of Maryland, where I had the tremendous fortune of learning from world renown educators and clinicians. Now I have the unbelievable honor of working with an unbelievably gifted group of practitioners at Carolinas Medical Center. I strive every day to inspire my residents as much as they inspire me.

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