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Diabetes Insipidus

This lecture explains the basics of diabetes insipidus, its types, causes, diagnosis, laboratory investigations, prognosis, management, case based learning and related aspects.

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Diabetes insipidus


Diabetes insipidus (DI) is a disease characterized by polyuria and polydipsia due to decrease secretion or action of antidiuretic hormone (ADH)

Types of Diabetes Insipidus

Neurogenic- also called central or pituitary, it is caused by a deficiency of the antidiuretic hormone, vasopressin.

Nephrogenic- caused by a defect in the receptor to the hormone, vasopressin, located in the kidneys.

Gestagenic- caused by a deficiency of the antidiuretic hormone, vasopressin, during pregnancy.

Dipsogenic- form of primary polydipsia, abnormal thirst and excessive intake of liquids.

Normal Physiology

Vasopressin is synthesized by the supraoptic and paraventricular nuclei of the hypothalamus

It is then transported to the posterior pituitary and stored.

Vasopressin release from posterior pituitary is primarily regulated by changes in plasma osmolality

The primary site of vasopressin action in the kidney is at the collecting duct

Vasopressin receptors are classified as V1 and V2

causes of neurogenic DI

Primary inherited forms—rare

Autosomal Dominant form

Wolfram syndrome

septo-optic dysplasia

Causes of neurogenic DI

Secondary or acquired causes—more common

tumors of the suprasellular and chiasmatic regions (craniopharyngiomas, optic gliomas, germinomas)

Head injury

Operations (near pituitary or hypothalamus)

Systemic diseases (encephalitis, histiocytosis, turberculosis, leukemia)

Autoantibodies to vasopressin-producing cells

In the newborn, DI has been reported in association with asphyxia, IVH, intravascular coagulopathy, Listeria monocytogenes sepsis, and bacterial meningitis and encephalitis.

Approx 20% of cases of DI are idiopathic

Nephrogenic diabetes (NDI)

Causes of Nephrogenic DI

Primary inherited causes

Mutations that affect the V2 receptor as well as the AQP 2 water channel

The V2 receptor gene is localized in the X chromosome

V2 receptor mutations may also appear de novo

Inherited autosomal recessive forms of nephrogenic DI also reported (mutation localized to chromosome 12)

Secondary or acquired forms

More common than primary forms

Drugs (lithium, ampho B, demeclocycline)

Can be associated with prolonged intervals of hypercalcemia or hypokalemia

Can be present in conjunction with inherited disorders of renal development (Polycystic kidney disease, renal dysplasia)

Disease processes that injure the collecting duct & surrounding tubules (sickle cell anemia, chronic pyelonephritis, urinary tract obstruction)

Gene Locus

Genetic Mutation

After testing of the AVPR2 gene, located at Xq28, almost 100% of disease-causing mutations result in individuals having NDI.

All types of mutations, such as frame shifts and splicing can be observed in the gene.

There are no other known phenotypes associated with AVPR2 gene mutations.

Protein Activity

Normally, the hormone, vasopressin links to the receptor, vasopressin-2 receptor (V2R), located in the collecting duct of the kidney. X-linked NDI is caused by a mutation on the V2R gene. The mutation inhibits the linkage of the hormone and receptor and the reabsorption of water by the kidneys.

Symptoms of Nephrogenic DI

POLYURIA, chronic passage of large volumes of urine

POLYDIPSIA, chronic, excessive thirst





failure to thrive

lack of appetite


high blood levels of sodium

Patient History

How much fluid intake per day

Voiding patterns

Dietary intake

Drug history

Clinical Manifestations



Signs and symptoms of chronic dehydration

Infants: irritability, poor feeding, growth failure, intermittent high fevers

In children who have acquired bladder control, enuresis may be the first symptom

Clinical Manifestations

Neurogenic DI

Hypothalamic tumors: growth disturbances, progressive cachexia or obesity, hyperpyrexia, sleep disturbance, sexual precocity, or emotional disorders

Lesions initially causing DI may eventually destroy the anterior pituitary and its associated endocrine axis

Laboratory investigations

Urine is usually pale and colorless

Urine analysis and urine electrolytes

Urine specific gravity varies b/w 1.001 and 1.010

Urine osmolality 50-300 mosm/kg

Serum osmolality may vary widely, depending on hydration status

Other renal function studies usually normal

Serum vasopressin measurement


Renal ultrasound

Magnetic resonance imaging.

Tumors—calcifications; enlargement of sella turcica; increased width of suture lines

“Bright spot”—differentiates between posterior pituitary and anterior pituitary; present in normal pts; absent or ectopic in pts with hypothalamic-neurohypophyseal tract lesions


Administration of desmopressin

In neurogenic DI, desmopressin will raise Urine osmolality& suppress urine out put.

In nephrogenic DI, desmopressin produces no increase in Urine osmolality and no suppression of Urinary out put.

In normal individuals, desmopressin administration can cause a vasodilatory response (flushing, fall in diastolic BP, rise in HR), believed to be mediated by extra renal V2 receptors

Water deprivation test

In patients with severe neurogenic DI, overnight water deprivation results in elevation of Serum and urine osmolality after administration of vasopressin.

In nephrogenic DI there is no effect on serum & urine osmolality after administration of desmopressin.


The cause of the underlying condition should be treated when possible

Neurogenic DI

Administration of desmopressin, usually intranasal.

Desmopressin binds almost exclusively to V2 receptors and is more resistant to degradation by body peptidases than endogenous vasopressin

Therefore, the antidiuretic effects of desmopressin last 8-10 hr, compared with 1-3 hr for endogenous vasopressin

Dose: 5-10 mcg intranasal, given in single or divided doses; < 2 y/o: 0.15-0.5 mcg/kg/24 hr

IV/SC therapy also available

Nephrogenic DI

Ensure a sufficient intake of water to replace the large urinary water losses

Stop causative medications, if applicable

Low sodium diet

Drugs that reduce polyuria

Thiazide diuretics (hydrochlorothiazide)

Prostaglandin synthesis inhibitors (indomethacin)

Potassium-sparing diuretics (amiloride)


Check serum electrolytes frequently

After episodes of dehydration, these patients usually require replacement of large quantities of water, but not sodium

Involve endocrine and nephrology services (and genetics, if indicated, for genetic counseling)


Neurogenic DI

Prognosis often determined by the underlying etiologic process

neurogenic DI may be transient or long-standing

Uncomplicated neurogenic DI can be managed effectively; permits a high quality of life for affected patients

Nephrogenic DI

Good prognosis, if careful clinical and laboratory monitoring

There are isolated reports of chronic  renal failure in patients with nephrogenic DI

Case study

A 5 yr old boy presented with polyuria and polydipsia for the last 1 month. His urine output was > 3 L per 24 hrs.

On investigations

Glucose (within range 3.3-11.1 mmol/L)

Urea           (within range 1.8-6.4 mmol/L)

Creatinine  were not deranged

urine osmolality 60 mosm/L

Case study

Water deprivation test performed.

Urine osmolality increased only to 160 mosm/L

Desmopressin 10µg intra-nasally given

Urine osmolality 610 mosm/L

Serum osmolality 295 mosm/L

Diagnosis: neurogenic DI



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