Diabetes Insipidus (DI)

What is the normal function of Anti Diuretic hormone (ADH)?

What is DI?

diabainein: Greek, “to pass through”
insipidus: Latin, “having no flavor”

DI is defined as excess passage of large volumes (> 3 L/day) of dilute urine (osmolality< 300mOsmol/kg)

What are the causes of excess urination (increased urine volume)?

1. Diabetes Mellitus or sugar Diabetes

2. Cranial/ Central DI – Due to deficiency of circulating arginine vasopressin (Anti- Diuretic hormone- ADH)

3. Nephrogenic DI – Due to renal resistance to ADH

4. Primary polydypsia
Polyuria due to excessive drinking

5. Gestational DI – enzyme made by the placenta destroys ADH in the mother.

What are the causes of DI?

1. Cranial – 10% of vasopressin cells sufficient to keep urine volume < 4lt/day

  1. Familial
  2. Acquired
    1. Trauma (Head injury, neurosurgery)
    2. Tumors (Craniopharyngioma, pituitary infiltration by metastasis)
    3. Infiltrations
    4. Inflammatory conditions (Sarcoidosis, Histiocytosis, Lymphocytic hypophycitis)
    5. Vascular
    6. Idiopathic

2. Nephrogenic

  1. Familia
    1. X-linked
    2. Autosomal recessive
  2. Acquired
    1. Drugs (Lithium, Demeclocycline)
    2. Metabolic (Hypercalcaemia, Hypokalaemia, Hyperglycaemia)
    3. CRF
    4. Post obstructive uropathy

3. Primary polydipsia

  1. Functional

What are the symptoms?

  • Excessive urination (>3lt/day)
  • Excessive thirst
  • Nocturia
  • The most common form of DI is that which follows trauma or surgery to the region of the pituitary and hypothalamus. It may exhibit 1 of 3 patterns-transient, permanent, or triphasic. The triphasic pattern is observed more often clinically.
    • First, a polyuric phase occurs and lasts 4-5 days. Inhibition of ADH causes the polyuric phase. An immediate increase in urine volume and a concomitant fall in urine osmolality occur.
    • Second, antidiuretic phase of 5-6 days occurs, which results from release of stored hormone. The urine osmolality rises.
    • The third phase can be permanent DI, when stores of ADH are exhausted and the cells that produce more ADH are absent or unable to produce.

What are the investigations required?

  • Confirm large quantities of urine
  • Rule out Diabetes mellitus / Renal failure
  • Check electrolytes
    • Fluid deprivation test
      • Allow fluids overnight. If psychogenic polydipsia is suspected restrict overnight fluid restriction to avoid morning overhydration
      • Patient is deprived of fluids for eight hours or until 5% loss of body weight if earlier. Weigh patient hourly
      • Plasma osmolality measured every 4 hours & urine osmolality every hour
      • Patient is given Desmopressin injection when three consecutive urine osmolality show a difference of not more than 30 mosmol/kg and urine & plasma osmolality are measured
Diagnosis After fluid deprivation After desmopressin
Cranial DI <300 >800
Nephrogenic DI <300 <300
Psychogenic >800 >800
Partial DI/ Polydipsia 300-800 <800
  • MRI
  • Serum ACE ( sarcoidosis) & other tumor markers

What are the symptoms?

  1. Vasopressin analogue which has reduced pressor activity & increased antidiuretic efficacy
    • Orally (100-1000mcg/day)
    • Intranasally (10-40mcg/day0)
    • Parenterally (0.1-2 mcg/day)
    • Monitoring of Sodium & osmolality is essential
  2. Correction of underlying renal causes
  3. In Nephrogenic DI Thiazide diuretics (Therapeutic paradox) & prostaglandin synthase inhibitors can be helpful

This article is prepared along with Dr Menaka