Endocrinology
A 43 year old woman presents to the Emergency Department with a 1 day history of polyuria and polydipsia. She underwent a resection of a pituitary adenoma 3 weeks ago, she otherwise has no past medical history. You suspect diabetes insipidus. Which of the following is NOT a typical feature in diabetes insipidus?
Answer:
The biochemical hallmarks of DI are:- High plasma osmolality (> 290 mOsm/kg)
- Low urine osmolality (< 300 mOsm/kg)
- High urine volume (> 3 L/24 hours)
- +/- Hypernatraemia
Diabetes Insipidus
Endocrinology / Nephrology
Last Updated: 17th January 2023
Diabetes insipidus (DI) is a metabolic disorder characterised by an absolute or relative inability to concentrate urine, resulting in the production of large quantities of dilute urine. It may result from an absolute or relative deficiency of antidiuretic hormone (ADH), which is produced by the hypothalamus and secreted via the posterior pituitary, or by resistance to its action within the renal collecting ducts. Clinically it manifests as polydipsia, polyuria, and hypotonic urine. Both types of DI may be associated with hypernatraemia, and this may present as a medical emergency.
Risk factors
- Central (due to reduced synthesis or release of ADH from the hypothalamo-pituitary axis)
- Pituitary surgery
- Craniopharyngioma
- Infiltrative pituitary stalk lesions
- Traumatic brain injury
- Subarachnoid haemorrhage
- Autoimmune disorders
- Central nervous system infections
- Congenital hypothalamo-pituitary defects
- Wolfram syndrome
- Nephrogenic (due to renal insensitivity to ADH)
- Lithium therapy
- Other drugs e.g. demeclocycline, cisplatin, colchicine, gentamicin, and rifampin
- Chronic kidney disease
- Renal sarcoidosis and amyloidosis
- Chronic hypercalcaemia or hypokalaemia
- Ureteric obstruction
Diagnosis
The approach to diagnosis requires confirming significant polyuria (as opposed to urinary frequency with normal total daily urine output), eliminating primary polydipsia (excess intake of water) as the underlying cause of polyuria, and then establishing whether the patient has central or nephrogenic DI.
Patients typically present with polyuria and polydipsia. Severe volume depletion is uncommon, as the increased thirst-stimulated drinking is usually strong enough to balance the increased renal water loss. However, in patients where free access to water is impaired (e.g. in children and older patients, cognitive or physical impairment) the patient may become dehydrated and develop hypernatraemia.
Initial laboratory tests in all patients with suspected DI are serum electrolytes (including calcium), glucose (to exclude diabetes mellitus as a cause of polyuria), urine dipstick (to help exclude diabetes mellitus and to look for evidence of renal disease), measurement of urine and serum osmolality, and confirmation of polyuria with 24-hour urine collection.
The biochemical hallmarks of DI are:
- High serum osmolality (> 290 mOsm/kg)
- Low urine osmolality (typically < 300 mOsm/kg)
- High urine volume (> 3 L/24 hours)
- +/- Hypernatraemia
The water deprivation test (WDT) is the standard, historical method of confirming a diagnosis of DI by confirming inability to concentrate urine appropriately during supervised dehydration. A second component of this test, involving ADH (desmopressin) stimulation, is used only in those patients with confirmed inability to concentrate urine appropriately on dehydration, to distinguish between central and nephrogenic DI.
Management
Treatment goals are correction and stabilisation of water deficit and electrolyte balance, together with reduction in symptoms of excessive urinary water loss and thirst.
In central DI, the long-acting, synthetic ADH analogue desmopressin (DDAVP) is the treatment of choice as replacement for endogenous ADH.
Nephrogenic DI is treated with an adequate fluid intake to match output and insensible losses; salt restriction and diuretics may help reduce polyuria.
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
