Chronic Care Programme
Treatment guidelines
Diabetes Insipidus
Chronic condition
Consultations protocols
Preferred treating provider
Notes
 preferred as indicated by option
 referral protocols apply
Provider
General Practitioner
Physician
Neurologist
Paediatrician
Maximum consultations per annum:
 Initial consultation
 Follow-up consultation
Tariff codes
Option/plan
GMHPP
Gold Options
G1000, G500 and
G200.
Blue Options
B300 and B200.
GMISHPP
One Level
New And Ecisting patients
1
3
0183; 0142; 0187; 0108
Investigations protocols
Type
Serum urea
Serum Creatinine
Serum potassium
Serum sodium
Blood glucose
Osmolality (serum or urine)
Provider
Pathologist
Pathologist
Pathologist
Pathologist
Pathologist, GP or
Specialist (see list)
Pathologist
Maximum investigations per annum
Tariff code
4151
4032
4113
4114
4057
4050
4093
4
4
4
4
1
1
E23.2.
ICD 10 coding
General
Diabetes insipidus (DI) is a condition characterized by excretion of large amounts of severely
diluted urine, which cannot be reduced when fluid intake is reduced. It denotes inability of the
kidney to concentrate urine. DI is caused by a deficiency of antidiuretic hormone (ADH), also
known as vasopressin, due to the destruction of the back or "posterior" part of the pituitary gland
where vasopressin is normally released from, or by an insensitivity of the kidneys to that
hormone. It can also be induced iatrogenically by various drugs.
Signs and symptoms
Excessive urination and extreme thirst (especially for cold water and sometimes ice or ice water)
are typical for DI. Symptoms of diabetes insipidus are quite similar to those of untreated diabetes
mellitus, with the distinction that the urine is not sweet as it does not contain glucose and there is
no hyperglycemia (elevated blood glucose). Blurred vision is a rarity. Signs of dehydration may
also appear in some individuals since the body cannot conserve much (if any) of the water it takes
in.
The extreme urination continues throughout the day and the night. In children, DI can interfere
with appetite, eating, weight gain, and growth as well. They may present with fever, vomiting, or
diarrhea. Adults with untreated DI may remain healthy for decades as long as enough water is
drunk to offset the urinary losses. However, there is a continuous risk of dehydration.
Diagnosis
In order to distinguish DI from other causes of excess urination, blood glucose levels, bicarbonate
levels, and calcium levels need to be tested. Measurement of blood electrolytes can reveal a high
sodium level (hypernatremia as dehydration develops). Urinalysis demonstrates a dilute urine
with a low specific gravity. Urine osmolality and electrolyte levels are typically low.
A fluid deprivation test helps determine whether DI is caused by:
1. excessive intake of fluid
2. a defect in ADH production
3. a defect in the kidneys' response to ADH
This test measures changes in body weight, urine output, and urine composition when fluids are
withheld and as dehydration occurs. The body's normal response to dehydration is to concentrate
urine and conserve water, so urine becomes more concentrated and urination becomes less
frequent. Those with DI continue to urinate large amounts of dilute urine in spite of not drinking
any fluids. Sometimes measuring blood levels of ADH during this test is also necessary.
To distinguish between the main forms, desmopressin stimulation is also used; desmopressin can
be taken by injection, a nasal spray, or a tablet. While taking desmopressin, a patient should drink
fluids or water only when thirsty and not at other times, as this can lead to sudden fluid
accumulation in central nervous system. If desmopressin reduces urine output and increases
osmolarity, the pituitary production of ADH is deficient, and the kidney responds normally. If the
DI is due to renal pathology, desmopressin does not change either urine output or osmolarity.
If central DI is suspected, testing of other hormones of the pituitary, as well as magnetic
resonance imaging (MRI), is necessary to discover if a disease process (such as a prolactinoma, or
histiocytosis, syphilis, tuberculosis or other tumor or granuloma) is affecting pituitary function.
Thankfully most people with this form either have experienced past head trauma or simply have
stopped ADH production for no apparent reason.
Habit drinking (in its severest form termed psychogenic polydipsia) is the most common imitator
of diabetes insipidus at all ages. While many adult cases in the medical literature are associated
with mental disorders, most patients with habit polydipsia have no other detectable disease. The
distinction is made during the water deprivation test, as some degree of urinary concentration
above isosmolar is usually obtained before the patient becomes dehydrated.
Pathophysiology
Electrolyte and volume homeostasis is a complex mechanism that balances the body's
requirements for blood pressure and the main electrolytes sodium and potassium. In general,
electrolyte regulation precedes volume regulation. When the volume is severely depleted,
however, the body will retain water at the expense of deranging electrolyte levels.
The regulation of urine production occurs in the hypothalamus, which produces antidiuretic
hormone (ADH or vasopressin) in the supraoptic and paraventricular nuclei. After synthesis, the
hormone is transported in neurosecretory granules down the axon of the hypothalamic neuron to
the posterior lobe of the pituitary gland where it is stored for later release. In addition, the
hypothalamus regulates the sensation of thirst in the ventromedial nucleus by sensing increases in
serum osmolarity and relaying this information to the cortex.
The main effector organ for fluid homeostasis is the kidney. ADH acts by increasing water
permeability in the collecting ducts and distal convoluted tubule, specifically it acts on proteins
called aquaporins which open to allow water into the collecting duct cells. This increase in
permeability allows for reabsorption of water into the bloodstream, thus concentrating the urine.
There are several forms of DI:

Central diabetes insipidus is due to damage to the hypothalamus or pituitary due to a
tumor, stroke, neurosurgery or some rather rare causes (which include hemochromatosis,
sarcoidosis, histiocytosis, diseases that can form masses in the vicinity like a tuberculoma
or syphilis and some genetic disorders). If the hypothalamus is damaged, the feeling of
thirst may be completely absent.

Nephrogenic diabetes insipidus is due to the inability of the kidney to respond normally to
ADH. There are hereditary causes (90% are due to mutations of the ADH V2 receptor,
and 10% mutations of the aquaporin 2 water channel), but these are rare (incidence is
around 4 per million live births). Most are male, because V2 receptor mutations are xlinked recessive defects. More common are acquired forms of NDI, which occur as a sideeffect to some medications (such as lithium citrate and amphotericin B), as well as in
polycystic kidney disease (PKD) and sickle-cell disease, and electrolyte disturbances such
as hypokalaemia and hypercalcaemia. In some cases, no cause is found.

Dipsogenic DI is due to a defect or damage to the thirst mechanism, which is located in
the hypothalamus. This defect results in an abnormal increase in thirst and fluid intake that
suppresses ADH secretion and increases urine output. Desmopressin is ineffective, and
can lead to fluid overload as the thirst remains.

Gestational DI only occurs during pregnancy. While all pregnant women produce
vasopressinase in the placenta, which breaks down ADH, this can assume extreme forms
in GDI. Most cases of gestational DI can be treated with desmopressin. In rare cases,
however, an abnormality in the thirst mechanism causes gestational DI, and desmopressin
should not be used.
Treatment
Central DI and gestational DI respond to desmopressin. Also gestational DI tends to abate on its
own 4 to 6 weeks following labour, though some women may develop it again in subsequent
pregnancies. In dipsogenic DI, desmopressin is not usually an option.
Desmopressin will be ineffective in nephrogenic DI. Instead, the diuretic hydrochlorothiazide
(HCT or HCTZ) or indomethacin can improve NDI; HCT is sometimes combined with amiloride
to prevent hypokalemia. Again, adequate hydration is important for patients with DI, as they may
become dehydrated easily.
Medicine formularies
Plan or option
[Link to appropriate formulary]
GMHPP
Gold Options
G1000, G500 and
G200
Blue Options
B300 and B200
GMISHPP
Blue Option B100
[Core]
n/a
Epidemiology
Incidence
18.3% following transsphenoidal microsurgery (1)
Prevalence
· Vasopressin deficiency may occur at any age, including infancy and childhood.
· Nephrogenic diabetes insipidus (DI) is usually manifest in infancy.
· Nephrogenic DI is encountered in males with rare exception, reflecting its X-linked recessive
mode of inheritance
Prognosis
Uncomplicated diabetes insipidus is controllable with adequate intake of water and most patients
can lead normal lives
References
1. Berl T. Psychosis and water balance. N Engl J Med 1988;318:441. (An editorial summarizing
disturbances of regulation of osmolality in psychotic persons.)
2. Bichet DG. Nephrogenic diabetes insipidus. Am J Med 1998;105:431. (Discussion of basic
science aspects of vasopressin including genetics, cellular action, receptor function, and clinical
correlations.)
3. Boton R, Gaviria M, Batlle DC. Prevalence, pathologies, and treatment of renal dysfunction
associated with chronic lithium therapy. Am J Kidney Dis 1987;10:329. (The most prevalent
effect of lithium on the kidney is impairment of concentrating ability; overt polyuria was present
in 19% of cases. Amiloride was helpful in treating nephrogenic diabetes insipidus.)
4. Goldman MB, Luchins DJ, Robertson GL. Mechanisms of altered water metabolism in
psychotic patients with polydipsia and hyponatremia. N Engl J Med 1988;318:397. (Defects in
regulation of osmolality and secretion of antidiuretic hormone were found.)
5. Maghnie M, Cosi G, Genovese E, et al. Central diabetes insipidus in children and young adults.
N Engl J Med 2000;343:998. (Children and young adults with acquired central diabetes insipidus
are prone to the development of anterior pituitary hormonal deficiency, especially that of growth
hormone.)
6. Pivonello R, DeBellis A, Faggiano A, et al. Central diabetes insipidus and autoimmunity;
relationship between the occurrence of antibodies to arginine vasopressin-secreting cells and
clinical, immunological and radiological features in a large cohort of patients with central
diabetes insipidus of known and unknown etiology. J Clin Endocrinol Metab 2003;88:1629.
(Evidence for an autoimmune mechanism.)P.717
7. Robertson GL. Diabetes insipidus. Endocrinol Metab Clin North Am 1995;24:549.
(Authoritative review.)
8. Vokes TJ, Robertson GL. Disorders of antidiuretic hormone. Endocrinol Metab Clin North Am
1988;17:281. (Authoritative review, with a good section on inadequate production.)
9. Robertson GL. Differential diagnosis of polyuria. Annu Rev Med 1988;39:425.
(Comprehensive treatment of causes and workup.)
10. Halperin M, Skorecki KL. Interpretation of the urine electrolytes and osmolality in the
regulation of body fluid tonicity. Am J Nephrol 1986;6:241. (Written for the subspecialist, but
there are some very useful sections for the generalist reader.)
11. Zeerbe RL, Robertson GL. A comparison of plasma vasopressin measurements with a
standard indirect test in the differential diagnosis of polyuria. N Engl J Med 1981;305:1539. (Use
of the assay improves the workup for polyuria.)
12. Batlle DC, VonRiotte AB, Gaviria M, et al. Amelioration of polyuria by amiloride in patients
receiving long-term lithium therapy. N Engl J Med 1985;312:408. (Amiloride mitigated lithiuminduced polyuria by blunting the inhibitory effect of lithium on water transport in the renal
collecting tubule.)
13. Tetiker T, Sert M, Kocak M. Efficacy of indapamide in central diabetes insipidus. Arch Intern
Med 1999;159:2085. (Example of the efficacy of a thiazide-like diuretic; there was a 40%
reduction in urinary volume.)
Editors: Goroll, Allan H.; Mulley, Albert G.
Title: Primary Care Medicine, 5th Edition
Copyright ©2007 Lippincott Williams & Wilkins
14. The public domain document "Diabetes Insipidus", NIH Publication No. 01-4620, December
2000