Drugs – lithium/demeclocycline – both interfere with the binding of ADH
Chronic renal disease
Post obstructive uropathy
Dipsogenic diabetes insipidus occurs as a result of hypothalamic disease or trauma.
The hypothalamus is responsible for controlling the thirst mechanism which is a key component of maintaining normovolaemia.
In dipsogenic diabetes, the thirst mechanism damaged, resulting in the affected patient being excessively thirsty regardless of their fluid status.
The patient, therefore, consumes large volumes of fluid, which suppresses the secretion of ADH and increases urine output.
During pregnancy, the placenta produces vasopressinase which breaks down vasopressin.
Gestational diabetes insipidus is therefore thought to be caused by the overproduction of vasopressinase by the placenta causing a deficiency of functional vasopressin.
Primary polydipsia is characterised by an individual consuming large volumes of fluid and as a result producing large volumes of dilute urine.
The symptoms of primary polydipsia are therefore very similar to those of diabetes insipidus, however, a fluid deprivation test can help distinguish the diseases.
Most often primary polydipsia is due to a behavioural disorder.
Symptoms and signs
Excessive urination (>3L/24hrs)
Excessive thirst (especially for ice-cold water)
Dehydration – headache/dizziness/dry mouth
Signs of dehydration (dry mucous membranes, prolonged capillary refill time)
24-hour Urine Collection
24-hour urine collection should be performed to measure the amount of urine produced.
Diabetes insipidus typically involves the production of more than 3000ml of urine in a 24-hour period.
Plasma glucose (to help rule out diabetes mellitus)
U&Es – to assess renal function and rule out electrolyte abnormalities
Urine specific gravity
Simultaneous plasma and urine osmolality
Fluid Deprivation Test 2
The patient is deprived of fluids for up to eight hours or 5% loss of body weight, following which desmopressin is given (see the table below for the interpretation of results).
MRI imaging of the pituitary, hypothalamus and pineal gland is used to assess for cranial causes of diabetes insipidus (e.g. pituitary tumour).
Renal Tract Ultrasound
Renal tract ultrasound or intravenous pyelogram is used to assess for evidence of post-obstructive uropathy.
The fluid deprivation test can provide an initial indication as to the likely cause of diabetes insipidus (e.g. neurogenic, nephrogenic).
The table below shows the likely underlying cause based on the results of the fluid deprivation test.1,2
Urine osmolality after fluid deprivation (mOsm/kg)
Urine osmolality after desmopressin (mOsm/kg)
Partial cranial DI or nephrogenic DI or PP or diuretic abuse
If the diagnosis is neurogenic DI the urine osmolality will be low after fluid deprivation but normalise after desmopressin is given.
This is because neurogenic DI is caused by the lack of ADH production, therefore, giving a synthetic form of ADH such as desmopressin normalises levels of the hormone resulting in the normalisation of serum and urine osmolality.
If the diagnosis is nephrogenic DI then the urine osmolality will remain low throughout regardless of desmopressin.
This is because the kidneys are unable to respond to either synthetic or endogenous ADH.
If the diagnosis is primary polydipsia the urine osmolality will remain high after fluid deprivation as well as after desmopressin is given.
This is because the patient’s vasopressin axis is intact and otherwise completely normal.
Partial DI or Polydipsia
If the diagnosis is that of partial DI or polydipsia the picture may be mixed and further investigations are required.
Neurogenic DI 2
The primary issue in neurogenic DI is an endogenous deficiency of ADH.
As a result, replacement with a synthetic form of ADH such as desmopressin is usually effective.
Desmopressin can be given orally, intranasally or parenterally.
Patients require ongoing monitoring due to the risks associated with desmopressin treatment (e.g. overdose results in hyponatraemia).
Typically, patients require serum sodium osmolality measuring every 1 to 3 months.
Nephrogenic DI 2
If daily urine volume is less than 4 litres/24hrs and the patient is not severely dehydrated, definitive therapy is not always necessary.
Patients need access to drinking water and should be advised to drink enough to satisfy their thirst.
Metabolic abnormalities should be corrected if present and any medications that could be causing the problem should also be stopped (e.g. lithium, demeclocycline).
High dose desmopressin is sometimes used for mild-to-moderate cases of nephrogenic DI.
The underlying psychiatric disorder needs to be treated.
Dr Colin Tidy. Diabetes Insipidus. Patient.info. Published December 2015. Available from: [LINK]
Saifan C, Nasr R, Mehta S, et al; Diabetes insipidus: a challenging diagnosis with new drug therapies. ISRN Nephrol. 2013 Mar 242013:797620. doi: 10.5402/2013/797620. eCollection 2013.