Diabetes insipidus

Question 1

What does ADH cause to happen?

Answer 1

Causes increased expression of AQP2 channels to be inserted into the membrane allowing increased reabsorption of water.

This also happens in the DCTs.

Question 2

What are the 4 types of diabetes insipidus?

Answer 2

1) Central/ cranial DI
2) Primary polydipsia
3) Nephrogenic DI
4) Gestational DI

Question 3

1) What is the basic pathophysiology of cranial DI?
2) What is the basic pathophysiology of primary polydipsia?
3) What is the basic pathophysiology of nephrogenic DI?

Answer 3

1) Overall, a reduced amount of ADH is released, causing water loss due to fewer AQP2 being present.
2) Ingestion of large quantities of water causes decreased ADH levels in the blood. This can also happen iatrogenically if excessive volumes of IV fluids are given.
3) The kidneys have a decreased response to ADH.

Question 4

Name 5 categories of causes of cranial DI and name some conditions within these categories.

Answer 4

1) Hereditary: hereditary hypothalamic DI (inherited mutation in ADH gene).
2) Tumours: craniopharyngioma or pineal gland tumours.
3) Trauma and surgery: surgery around hypothalamic area or pituitary stalk or a basal skull fracture.
4) Immune: Autoimmune hypophysitis (inflammation of pituitary gland).
5) Infiltration: by tumours.
6) Vascular: haemorrhage.
7) Infection: meningoencephalitis.
8) Other: Hypophysectomy: pituitary removal.

Question 5

Describe the main congenital cause of nephrogenic DI.

Answer 5

Congenital nephrogenic DI = X linked mutation of ADH-2 receptor so ADH levels may be high in the blood, but the ADH has no effect.

Question 6

Name 4 acquired causes of nephrogenic DI.

Answer 6

1) PCKD
2) Renal ischaemia
3) Hypercalcaemia/ hypokalaemia
4) Medications (e.g. Lithium).

Question 7

1) Where is ADH metabolised and how is it excreted?

2) Describe the basic pathophysiology of gestational DI.

Answer 7

1) Metabolised by the liver and excreted by the kidneys.

2) Gestation causes an increase in ADH metabolism which causes decreased ADH levels and decreased activity.

Question 8

What are the 3 characteristic symptoms of diabetes insipidus?

Answer 8

1) Polyuria (>3L in 24 hours)
2) Dilute urine
3) Polydipsia

Question 9

1) Describe the urine sample of a patient with DI.

2) Why will patients with DI develop hypernatraemia?

Answer 9

1) Hypotonic and dilute.

2) Due to the resultant extreme dehydration.

Question 10

State how you would differentiate the following conditions from diabetes insipidus:

a) Diabetes mellitus
b) Intrinsic renal disease
c) Urological condition

Answer 10

a) There would be the presence of glucose in the urine and potential proteinuria.
b) Would usually be the presence of renal casts and/or haematuria.
c) Urological issues normally cause frequent urination without an increase in urine volume.

Question 11

Give 4 other characteristics of diabetes insidious which are not part of the classical triad.

Answer 11

1) Hx of other endocrine disorders
2) Nocturia
3) Signs of volume depletion
4) Signs and symptoms of hypernatraemia.
5) Skin lesions
6) Sensorineural deafness
7) Visual failure

Question 12

Name 4 signs or symptoms of hypernatraemia.

Answer 12

Irritability
Restlessness
Lethargy
Hyperreflexia
Delirium
Seizures/ coma

Question 13

Give 4 basic investigations that you might carry out in a patient with suspected diabetes insipidus.

Answer 13

24 hour urine output measure
Urine dipstick
Bloods
Serum and urine osmolarity

Question 14

Name 2 more specialised investigations that you might carry out in a patient with suspected diabetes insipidus.

Answer 14

Water deprivation test

Desmopressin stimulation test.

Question 15

1) State what you may find on a urine dipstick in a patient with DI.
2) Describe serum and urine osmolarity in patients with DI.

Answer 15

1) Possible proteinuria if there is underlying renal disease (NO glycosuria in diabetes insipidus).
2) Urine osmolarity typically low. Serum osmolarity typically elevated or high.

Question 16

Describe the results of the following blood tests in a patient with DI:

a) Sodium
b) Potassium
c) Calcium
d) Glucose
e) Urea

Answer 16

a) normal or elevated (due to dehydration)
b) normal or decreased (in nephrogenic DI)
c) normal or increased (in nephrogenic DI)
d) normal
e) normal or increased (associated with co-existent renal disease).

** In primary polydipsia, there may be dilution hyponatraemia.

Question 17

1) What is the procedure for the water deprivation test?

2) What parametres are measured hourly in the water deprivation test?

Answer 17

1) Patients are deprived of fluids for 8 hours or until at least there is a 3% loss of body weight.
2) Serum osmolarity, urine volume and urine osmolarity.

Question 18

1) What is the normal response to dehydration with a water deprivation test?
2) In DI, what happens in the water deprivation test?

Answer 18

1) A rise in urine osmolarity >700.

2) Urine remans dilute due to an inability to retain water.

Question 19

What result will be seen from the water deprivation test in a patient with diabetes insipidus?

Answer 19

Urine osmolarity will be <300 with corresponding serum osmolarity >290.

Question 20

1) What is the desmopressin stimulation test used for?
2) What is desmopressin?
3) What is the procedure for the desmopressin stimulation test?

Answer 20

1) To distinguish between cranial and nephrogenic DI after a water deprivation test.
2) An ADH (vasopressin) analogue
3) Patients are given desmopressin subcutaneously. Serum osmolarity, urine osmolarity and urine volumes are then measured hourly over 4 hours.

Question 21

1) What would results show for a patient with cranial DI?

2) What would results show for a patient with nephrogenic DI?

Answer 21

1) Patients with cranial DI respond to desmopressin with decreased urine output and increased urine osmolarity which will be >750.
2) Patients with nephrogenic DI do not respond to desmopressin so there is little or no reduction in urine output and no increase in urine osmolarity.