Endocrinology Internal Medicine

Diabetes Insipidus (DI)

Diabetes Insipidus
Checking urine osmolality is important when diagnosing diabetes insipidus.

Introduction – Diabetes Insipidus

Central diabetes insipidus (DI) occurs as a result of a lack of vasopressin/ADH production, whereby the patient secretes excessive amounts of dilute urine (polyuria) and secondary to this becomes thirsty and increases fluid intake (polydipsia).

The vasopressin deficiency can be subtle, partial or complete.

Urine output can vary between 3 and 15 l/day.

The condition is usually subacute with initially pronounced polyuria 5-8 l, which after a week stabilizes over the clock and becomes individually constant.


  1. Diseases of the hypothalamus
    – Craniopharyngioma
    – Pituitary tumors with substantial hypothalamic involvement
    – Metastases
    – Histiocytosis
    – Sarcoidosis
    – Tuberculosis
    – Meningioma
    – Glioma
  2. Iatrogenic after surgery
    – 10-20% transient DI
    – 5% chronic DI
  3. Autoimmune, due to antibodies that inhibit ADH synthesis
  4. Familial vasopressin synthesis defect, autosomal dominant and recessive variants
  5. Vasopressinase overactivity from the placenta – provides increased clearance of vasopressin
  6. Idiopathic DI

Differential Diagnoses – Diabetes Insipidus

(Other polyurias with polydipsia)

Nephrogenic diabetes insipidus

  • Diabetes mellitus – osmotic diuresis
  • Pyelonephritis, polycystic kidney disease, medullary cysts
  • Hypokalemia – inhibits the renal concentration ability
  • Hypercalcemia – inhibits the renal concentration ability
  • Pharmaceuticals, especially lithium, methoxyflurane anesthesia, aminoglycosides, cisplatin, amphotericin B, demeclocycline, fluorine, colchicine, sodium foscarnet, cidofovir
  • Vasopressin receptor 2 mutation
  • Inhibitory vasopressin receptor antibodies
  • Sickle cell anemia
  • Protein malnutrition

Primary / psychogenic polydipsia

Diagnostics – Diabetes Insipidus

  1. Verify polyuria by collecting 1-2 days of urine – measure volume + creatinine.
  2. Careful medical history, especially regarding pharmaceuticals, hypothalamic and pituitary function, mental disorders, and related polyuria.
  3. Exclude nephrogenic DI via analysis of creatinine, urea, K, Na, Ca, Albumin and fasting blood glucose.
  4. Analyze Plasma-osmolality and U-osmolality.
    If U-osm < P-osm this indicates neurogenic or nephrogenic DI. In both of these conditions, P-osm is elevated or within the upper normal range. In both conditions, the patients end up becoming dehydrated, because the resulting thirst, for unknown reasons, does not fully compensate for the loss of fluid. Thus, P-osm ends up being elevated.

    If both U-osm and P-osm are low, this indicates primary/psychogenic polydipsia. In this condition, the primary cause is that the patient drinks too much liquids, the kidneys do not have time to excrete the excess water and the patient becomes over-hydrated, with low P-osm.

    Fluid deprivation tests are available in several different types: Baseline P-vasopressin is low in neurogenic DI and does not rise adequately during the fluid deprivation test. In primary/psychogenic polydipsia, baseline vasopressin is also low but rises adequately after thirst. Unfortunately, fluid deprivation tests, even when performed well on a patient, are often inconclusive. You can then give the patient vasopressin analogue per os, desmopressin (Minirin), and wait for the effect clinically during the day. ADH / vasopressin assays are difficult to perform and interpret. Determination of copeptin is simpler and more reliable. It is currently being evaluated as an alternative to the ADH / vasopressin analysis.
  5. With MRT/MRI, the need for a fluid deprivation test has decreased. If MRI shows a clear structural lesion in the hypothalamic-infundibular stalk or the pituitary gland and the patient has polyuria, low U-osm polydipsia <280 mosm/kg, a fluid deprivation test does not be performed. If MRI cannot detect the typical glowing signal that corresponds to the posterior pituitary, “bright spot”, it strongly supports that the patient has central DI, and further investigation does not need to be done.

Treatment – Diabetes Insipidus

Neurogenic DI is treated with the active vasopressin analog, desmopressin (Minirin) 60 µg or 120 µg. The usual substitution dose is 120-600 µg daily. The vasopressin analog can also be given as a spray, nose drops or injection.

Hard work increases the need for Minirin and vice versa.

Older people are at increased risk of Minirin-overdose with hyponatremia as a result.

Patients with DI and concurrent endogenously or iatrogenically impaired thirst sensation are more difficult to treat. Together with the patient, routines for fluid intake are created. Before finding the right dose, allow the patient to check osmolality and sodium at frequent intervals (2-3 weeks).

Further Reading