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diabetes insipidus (DI)

Classification: 1) nephrogenic diabetes insipidus 2) central diabetes insipidus 3) gestational diabetes insipidus (placental vasopressinase) [2] Pathology: - antidiuretic hormone (ADH)/vasopressin deficiency (central diabetes insipidus) or inactivity (nephrogenic diabetes insipidus) History: - head trauma, recent neurosurgery - pituitary disease, renal disease, psychiatric disease - lithium carbonate use Clinical manifestations: 1) polydipsea, cravings for water or cold liquids 2) polyuria a) urinary frequency b) nocturia, enuresis c) partial deficiency of ADH usually does not result in polyuria because the maximum urine osmolality is still high enough so that the daily solute load can be excreted in a volume of < 3 liters 2) visual field defects, amenorrhea, galactorhea, adrenal insufficiency, or hypothyroidism suggest central diabetes insipidus Laboratory: 1) urine osmolality a) low urine osmolality (< 275 mOsm/L)* b) response of urine osmolality to water deprivation test - close monitoring indicated - inability to concentrate urine in response to water deprivation - urine osmolality normally increases with water deprivation c) desmopressin stimulation test 1] when urine does NOT concentrate with water deprivation 2] an increased urine osmolality indicates central DI 3] a lack of response indicates nephrogenic DI 4] patients with primary polydipsia may show response similar to nephrogenic DI due to washout of the medullary concentration gradient 2) high serum osmolality (> 290 mOsm/L)* 3) low urine specific gravity 4) serum sodium is high or high normal* due to free water diuresis [4] - if serum sodium is normal, perform water deprivation test 5) 24 hour urine volume > 50 mL/kg/24 hr* 6) plasma arginine vasopressin (AVP, ADH) - low antigen level consistent with central diabetes insipidus - ADH level refers to antigen level not activity level - plasma copeptin# distinguishes diabetes insipidus from primary polydipsia - activity low in diabetes insipidus - not widely available [3] 7) serum glucose to rule out diabetes mellitus 8) serum calcium, serum albumin, serum PTH if hypercalcemia 9) high or high normal serum sodium with serum osmolality > urine osmolality suggests diabetes insidipus as cause of polyuria [2] * initial diagnostic tests makes diagnosis [2] # fragment of the arginine vasopressin prohormone Radiology: - CT or MRI of hypothalamus & pituitary if desmopressin stimulation test is positive - renal ultrasound if desmopressin test is negative (urine does not concentrate) Differential diagnosis: - diabetes mellitus - osmotic diuresis (normal serum glucose suggests diabetes indipidus) - psychogenic polydipsea Management: 1) general a) correct hypernatremia b) correct hypovolemia c) decrease solute load with moderate protein restriction d) decrease delivery of solute to distal tubule 1] thiazide diuretics 2] low sodium diet 2) D5W-1/2 normal saline 1st line treatment after neurosurgery or head trauma; add IV desmopressin if urinary output is excessive or electrolyte abnormalities develop 3) intranasal arginine vasopressin (desmopressin) for central DI - may be administered orally [2] 4) subcutaneous desmopressin 5) thiazide diuretics & dietary salt restriction for nephrogenic DI (not drug-induced) 6) amiloride for lithium carbonate induced nephrogenic DI

Related

nocturia polyuria urine osmolality vasopressin (antidiuretic hormone, ADH)

Specific

central diabetes insipidus; diabetes insipidus, neurohypophyseal type (CDI) nephrogenic diabetes insipidus (NDI)

General

chronic metabolic disease neuroendocrine disease

References

  1. Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 50-51
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018, 2022.
  3. Fenske W, Refardt J, Chifu I et al. A copeptin-based approach in the diagnosis of diabetes insipidus. N Engl J Med 2018 Aug 2; 379:428. PMID: 30067922 https://www.nejm.org/doi/10.1056/NEJMoa1803760 - Rosen CJ, Ingelfinger JR. A reliable diagnostic test for hypotonic polyuria. N Engl J Med 2018 Aug 2; 379:483. PMID: 30067935 https://www.nejm.org/doi/10.1056/NEJMe1808195
  4. NEJM Knowledge+ Endocrinology
  5. NEJM Knowledge+ Nephrology/Urology
  6. Diabetes Insipidus http://kidney.niddk.nih.gov/kudiseases/pubs/insipidus/index.htm