ANSWER 58
This woman has mild hypercalcaemia but this is not high enough to explain her extreme
thirst and polyuria. It is more likely that she has polyuria due to neurogenic diabetes
insipidus as a result of secondary metastases in her hypothalamus. The hypercalcaemia
and raised alkaline phosphatase are suggestive of bony metastases secondary to her breast
carcinoma. The recent-onset headache, worsened by coughing and lying down and associ-
ated with vomiting is characteristic of raised intracranial pressure, which is confirmed by the
presence of papilloedema. In some tumours around the pituitary there may be compression
of the optic nerve causing visual field abnormalities. Neurogenic diabetes insipidus is due to
inadequate arginine vasopressin (AVP, antidiuretic hormone) secretion. About 30 per cent of
cases of neurogenic diabetes insipidus are idiopathic. The remaining causes are neoplastic,
infectious, inflammatory (granulomas), traumatic (neurosurgery, deceleration injury) or vas-
cular (cerebral haemorrhage, infarction). Patients with central diabetes insipidus typically
describe an abrupt onset of polyuria and polydipsia. This is because urinary concentration
can be maintained fairly well until the number of AVP-secreting neurones in the hypothal-
amus decreases to 10–15 per cent of the normal number, after which AVP levels decrease to
a range where urine output increases dramatically.
- Solute diuresis, e.g. diabetes mellitus.
- Renal diseases which impair urinary concentrating mechanisms, e.g. chronic renal
failure. - Drinking abnormalities: psychogenic polydipsia.
- Renal resistance to the action of AVP.
- Nephrogenic diabetes insipidus (due to inherited defects either in the AVP V 2
receptor or the aquaporin-2 receptor) - Hypokalaemia
- Hypercalcaemia
- Drugs, e.g. lithium, demeclocycline.
! Major causes of polyuria and polydipsia
A water-deprivation test should be performed in this patient, measuring the plasma sodium,
urine volume and urine osmolality until the sodium rises above 146 mmol/L, or the urine
osmolality reaches a plateau and the patient has lost at least 2 per cent of body weight. At
this point AVP is measured, and the response to subcutaneous desmopressin is measured.
An increase in urine osmolality#50 per cent indicates central diabetes insipidus and! 10
per cent nephrogenic diabetes insipidus. The hypothalamus should be imaged by magnetic
resonance imaging (MRI) scanning and bone X-rays and bone scans performed to identify
metastases (Fig. 58.1). The MRI scan (T 1 -weighted coronal image) through the pituitary in
Fig. 58.1 shows thickening of the pituitary stalk due to metastatic disease (short arrow) and
partial replacement of the normal bone marrow of the clivus by metastatic tumour (long
arrow). Treatment of the neurogenic diabetes insipidus involves regular intranasal DDAVP
(L-deamino-8-D-arginine vasopressin). She should be referred to an oncologist for treatment
of her metastatic carcinoma.