Diabetes insipidus

The inability to produce concentrated urine due to either antidiuretic hormone deficiency or resistance, which leads to extreme thirst and polyuria. The diagnosis may be confirmed using a water deprivation test.

Baseline investigations - all patients

Fluid diary

Where possible arrange for the patient to perform a 48-hour input/output diary to bring to their initial assessment as a diagnosis may sometimes be obvious.

Full blood count

Useful indicator of general health and underlying disease. 

Normocytic normochromic anaemia and eosinophilia may be seen with glucocorticoid deficiency.

Urea and electrolytes

Typical findings at presentation with DI are hypernatraemia and elevated urea. If hypokalaeamia is present, this must be corrected and the tests repeated before a diagnosis is confirmed, as this and hypercalcaemia may contribute to nephrogenic DI.

Hyperkalaemia and hyponatraemia may also occur in glucocorticoid deficiency.

Paired urine and plasma osmolalities

This test is highly informative in a fasting patient, as a normal or high urinary osmolality is very unlikely in DI. Typical findings in untreated DI would be an elevated plasma sodium and osmolality with an inappropriately low urine osmolality.

Liver function test

Useful indicator of general health and underlying disease, for example malignancy.

Bone profile

Hypercalcaemia of any cause must be corrected and tests repeated before a diagnosis of DI is confirmed, as this and hypokalaemia may contribute to nephrogenic DI.

This is also a useful indicator of general health and underlying disease including malignancy.

Hypercalcaemia may occur with glucocorticoid deficiency.

Fasting glucose and HbA1c

Patients with diabetes mellitus will also complain of thirst and polyuria at presentation.

Baseline pituitary function


Prolactin

A patient with apparent DI must be screened for pituitary dysfunction though isolated DI is unusual with intrinsic pituitary pathology.


9am cortisol

A waking cortisol is a useful screen for pituitary function, and if low should prompt formal dynamic testing with of ACTH reserve with an insulin stress test or glucagon test.

Ensure patients have stopped sex steroid therapy, for example HRT or the combined oral contraceptive pill for six weeks prior to test.

Estrogen replacement therapy leads to elevation of cortisol binding globulin, and hence serum cortisol, and so is difficult to interpret.


Thyroid stimulating hormone, free thyroxine

It is essential to assess levels of both thyroxine and TSH in patients with potential pituitary pathology, since a normal TSH level is frequently associated with loss of thyroid function in this patient group.

Levels of both TSH and thyroxine are typically at the lower end of the normal range in hypopituitary patients.


Growth hormone, insulin like growth factor I

Very low IGF-I levels alone are not diagnostic for GH deficiency but are a useful screen mandating a formal GH provocation test, for example insulin stress test or glucagon test.


Luteinising hormone, follicle stimulating hormone

In the presence of pituitary disease both luteinising hormone and follicle stimulating hormone are typically low or not elevated in post-menopausal women.


Estrodiol, testosterone, sex hormone binding globulin

These should be assessed early morning and in the early follicular phase and off the contraceptive pill in women. 

Sex hormone binding globulin is necessary to calculate free androgen index in some cases, for example where the decision to start testosterone replacement is not clear cut.

Further investigations - selected cases only

Water deprivation test

Water deprivation testing should be performed after the baseline investigations if clinical suspicion of diabetes insipidus remains.

Erythrocyte sedimentation rate

Patients presenting with diabetes insipidus should be evaluated for possible peripituitary pathology, for example immune or granulomatous disease.

Auto-antibody screen

Patients presenting with diabetes insipidus should be evaluated for possible peripituitary pathology, for example immune or granulomatous disease.

Angiotensin converting hormone

Patients presenting with diabetes insipidus should be evaluated for possible peripituitary pathology, for example sarcoidosis.

Alfa feto protein, human choriotropic hormone

Patients presenting with diabetes insipidus should be evaluated for possible peripituitary masses, for example germ cell tumours.

Other tumour markers may be tested if metastatic disease is suspected, for example the prostate specific antigen.

MRI pituitary

This should be performed in all cases with confirmed central DI, or documented abnormality of pituitary function and urgently if there is visual field loss or optic disc pallor.

PET CT

This may be considered after oncology and multidisciplinary team review, if a germ cell tumour is suspected.

Chest radiograph

All patients presenting with a new DI or pituitary mass should have a CXR performed as an assessment of general health and as a simple screen for underlying malignancy, inflammatory or granulomatous disease.

Electrocardiogram

This is essential in patients with electrolyte imbalance, and is usefully performed at presentation as it is required prior to performing an insulin stress test, or considering general anaesthesia.

Visual perimetry and acuity

Formal visual field testing is mandatory if there is clinical or MRI suspicion of chiasmal impingement.

Insulin stress test

This should be performed if GH or ACTH deficiency is suspected but not yet confirmed subject to the usual safety exclusion criteria.

Arginine-GHRH or Glucagon test

If GH or ACTH deficiency is suspected but not yet confirmed and the patient is unable to tolerate an insulin stress test, alternative dynamic function testing will be required.