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Diabetes Insipidus

Diabetes insipidus (DI) is a condition in which the kidneys are unable to concentrate urine. There are 2 subforms of DI: central DI (CDI) and nephrogenic DI (NDI). In CDI, the amount of antidiuretic hormone (ADH) produced by the hypothalamus or released from the pituitary gland is decreased. In nephrogenic DI, the kidneys fail to respond to circulating ADH. Both conditions result in the kidneys being unable to concentrate urine, leading to polyuria, nocturia, and polydipsia. Central and NDI are differentiated based on measured ADH levels and response to a water deprivation test. Central DI is treated with desmopressin, while nephrogenic DI is treated with diuretics and dietary salt restriction.

Last updated: January 24, 2024 804 views

Diabetes insipidus (DI) is a condition in which the kidneys are unable to concentrate urine. There are 2 subforms of DI: central DI (CDI) and nephrogenic DI (NDI). It is more common in men than women

  • Central DI, the most common form of diabetes insipidus, is caused by insufficient levels of circulating antidiuretic hormone (ADH). In CDI, the amount of antidiuretic hormone (ADH) produced by the hypothalamus or released from the pituitary gland is decreased.

المشكلة هنا في نقصان التصنيع أو مشكلة في افراز الهرمون من الغدة النخامية

  • Nephrogenic DI (rare) is characterized by defective ADH receptors in the distal tubules and collecting ducts. In nephrogenic DI, the kidneys fail to respond to circulating ADH.

هنا يكون تصنيع وإفراز هرمون ADH طبيعي، لكن يوجد خلل في الكلية ولا تستجيب لتأثير الهرمون

 

Either ↓ ADH (central DI) or defective renal ADH receptors (nephrogenic DI) → impaired ability of the kidneys to concentrate urine (hypotonic collecting ducts) → dilute urine (low urine osmolarity)

Diabetes insipidus causes
Central Nephrogenic
  • Idiopathic
  • Hereditary (very rare)
  • Brain tumors (especially craniopharyngioma) and cerebral metastasis (most common: lung cancer and leukemia/lymphoma)
  • Neurosurgery: usually after the removal of large adenomas
  • Traumatic brain injury; , pituitary bleeding, subarachnoid hemorrhage
  • Pituitary ischemia (e.g., Sheehan syndrome, ischemic stroke)
  • Infection (e.g., meningitis)
  • Sarcoid histocytosis
  • Radiotherapy
  • Hypertension
  • Hereditary (mutation in ADH receptor): very rare
  • Adverse effect of medications (lithium, demeclocycline)
  • Hypokalemia, hypercalcemia
  • Renal disease (e.g., autosomal dominant polycystic kidney disease, renal amyloidosis)
  • Pregnancy (Due to transient ADH resistance in the 2nd half of pregnancy; called gestational diabetes insipidus)

  • Polyuria (Defined as > 3 L urine output/day) with dilute urine تبول كثير ويكون البول مخفف
  • Polydipsia (excessive thirst) عطش
  • Nocturia تبول ليلي→ (leading to daytime sleepiness)
  • Neurologic symptoms may occur secondary to hypernatremia.
    • Irritability
    • Coma, if severe
Note  
In the absence of nocturia, diabetes insipidus is very unlikely. ملاحظة

  • High serum sodium (usually > 150 mEq/L) and low urine sodium
  • High plasma osmolality and low urine osmolality
  • Urine specific gravity < 1.006

  • Water deprivation test
    • Can distinguish between central and nephrogenic DI and also definitively exclude primary polydipsia
    • Desmopressin is given to distinguish between central and nephrogenic DI.
      • If urine osmolarity increases → CDI (= lack of central ADH secretion is compensated through desmopressin)
      • If urine osmolarity stays low → NDI (= defect in kidneys prevents the ADH-mimicking effect of desmopressin)

للتبسيط، نقوم بقياس الــ Plasma and urine osmolality بعد إعطاء المريض desmopressin. إذا زاد تركيز البول فهذا يدل على Central DI أما إذا لم يزد أو تغير بسيط جدا، فهذا يدل على Nephrogenic DI

  • Additional testing:
    • Head computed tomography (CT) or magnetic resonance imaging (MRI) (if CDI is suspected)
    • Review of current medications (lithium salts, foscarnet, clozapine)

Treat the underlying condition, ensure sufficient fluid intake, and initiate a low-sodium, low-protein diet.

  • Central diabetes insipidus:
    • Desmopressin (synthetic vasopressin) à Administration: intranasal, subcutaneous, or oral
    • Alternative medication: chlorpropamide
  • Nephrogenic diabetes insipidus
    • Discontinuation of the causative agent (e.g., lithium, demeclocycline) in medication-induced NDI
    • Thiazide diuretics
    • NSAIDs (e.g., indomethacin)
    • Amiloride: Indicated in patients with lithium-induced NDI; amiloride blocks lithium entry through the sodium channel.

Central and Nephrogenic DI مُلخص
  Central DI Nephrogenic DI
Cause
  • ADH deficiency (CNS pathology)
  • ADH resistance (renal disease)
Etiology
  • Idiopathic
  • Trauma
  • Pituitary surgery
  • Ischemic encephalopathy
  • Chronic lithium use
  • Hypercalcemia
  • Hereditary (AVPR2 & aquaporin 2 mutations)
Results
of water
deprivation
  • Low urine osmolality
  • Low urine osmolality
Response to
desmopressin
  • Increased urine osmolality
  • No change
ADH = antidiuretic hormone; AVPR2 = vasopressor V2; DI = diabetes insipidus.