A 34-year-old woman is referred to A&E from an inpatient psychiatric unit with a 3-d history of polyuria. She also reports being excessively thirsty despite drinking lots of water. Four weeks ago, she was diagnosed with epilepsy and bipolar disorder and was commenced on lithium and carbamazepine with good effect. Routine bloods performed by the psychiatry team are unremarkable, except for a sodium of 146.

Which of the following is the next best investigation?

Options:
explanation: The recreational drug Ecstasy (3,4-methylenedioxy-methamphetamine) directly triggers ADH release, producing a syndrome of inappropriate antidiuretic hormone secretion. The drug also stimulates thirst, which can worsen the hyponatraemia by drinking. There is no suggestion of recreational drug use in the clinical history and the symptoms indicate the more likely diagnosis of AVP resistance (nephrogenic diabetes insipidus) secondary to lithium therapy. Sodium is also raised in this case.
name: Urine toxicology screen
label: d
answer: no
explanation: This patient has presented with polyuria and polydipsia in the context of recent initiation of lithium therapy. The patient should be investigated for AVP resistance (nephrogenic diabetes insipidus), with the first investigation being paired serum and urine osmolalities. There would be a lack of response to desmopressin administration after water deprivation, due to resistance to desmopressin in the renal collecting ducts. In AVP deficiency (central diabetes insipidus), there is a deficiency of ADH; therefore, there should be a marked response to desmopressin administration, with over a 50% increase in urine osmolality. The desmopressin challenge may be useful further down the line during a water deprivation test line but not in the first instance.
name: Desmopressin challenge
label: e
answer: no
explanation: This patient has presented with polyuria and polydipsia in the context of recent initiation of lithium therapy. The patient should be investigated for AVP resistance (nephrogenic diabetes insipidus) and in the first instance a paired serum and urine osmolality should be used. Water deprivation is a confirmatory test done further down the line since it is more time-consuming. During the water deprivation test, patients with AVP deficiency or resistance will develop an increasing osmolality of their serum as they become dehydrated. However, the urine remains dilute since they are unable to concentrate their urine in response to dehydration. A desmopressin challenge can be provided to distinguish between deficiency or resistance during this test. A response to desmopressin (ie. concentration of urine) would indicate a central cause. In AVP resistance there is little to no response to a desmopressin challenge.
name: Water deprivation test
label: c
answer: no
explanation: This patient has been recently started on lithium, which is associated with AVP-resistance (nephrogenic diabetes insipidus). In AVP-R, the collecting ducts are insensitive to the effects of antidiuretic hormone (ADH) and aquaporins cannot be mounted. This results in an inability to concentrate urine and excessive free water loss. Patients typically present with polydipsia and polyuria and are at risk of dehydration if they do not maintain a good volume of oral fluid intake. The serum sodium may be raised or at the upper limit of normal due to dehydration. The best investigation for AVP deficiency or resistance in the first instance is paired urine and sodium osmolalities. Serum osmolality should be greater than 300 mOsm/kg and urine osmolality less than 750 mOsm/kg in this condition.
name: Urine and serum osmolality
label: a
answer: yes
explanation: This patient is presenting with polyuria and polydipsia, after recent commencement on lithium therapy for bipolar disorder. A diagnosis of AVP resistance (nephrogenic diabetes insipidus should be suspected). Diabetes insipidus is split into AVP deficiency (cranial DI) and AVP resistance. AVP deficiency is a deficiency of ADH, which is released from the posterior pituitary gland, whereas in AVP resistance, ADH is present but there is a failure of response in the renal collecting ducts. An MRI head would be indicated to evaluate for a central cause. In this case, given the initiation of lithium therapy and the absence of any neurological history or signs, AVP resistance is more likely. In any case, the diagnosis is still best initially made using paired serum and urine osmolalities.
name: MRI head with contrast
label: b
answer: no

Correct answer: a


Learning point: Lithium can cause nephrogenic diabetes insipidus, a condition where the kidneys become resistant to antidiuretic hormone (ADH), leading to the production of large volumes of dilute urine, decreased urine osmolality, and an elevated serum osmolality due to the body’s inability to concentrate urine properly.