Endocrine Abstracts

Background: We previously published data for short-term outcomes in patients with SIADH-related hyponatraemia unresponsive to fluid restriction and treated with tolvaptan. In light of concerns over longer-term side-effects we have revisited the topic and extended both group size and follow-up period to determine longer-term safety and treatment implications.

Aims/methods: We report ongoing treatment outcomes (case-note review) for 25 patients (age 71±5 years, 60% females) consecutively treated with tolvaptan as an in-patient for confirmed SIADH with persistent Na <125 mmol/l despite removal of reversible causes and 48 h fluid restriction, and include longer-term outcome data (re-treatment/readmissions/mortality) for 2 years follow-up.

Results: Concordance with locally agreed criteria for tolvaptan use remains high:

Short-term outcomes remain good, 92% achieve target of treatment (Na >125 mmol/l with clinical improvement) after a mean of 3.4±2.6 days treatment, 8% partial response (rise >5 mmol/l but not achieving 125 with initial therapy). No patient experienced a Na rise >12 mEq/24 h, hypernatraemia, drug-associated liver injury or CNS-myelinosis.

Longer-term outcomes were less good, mortality rates in this population was 40% within 3 months and 56% over the follow-up period. Underlying causes for SIADH were found to be malignancy-related in 60% (of whom 90% were undiagnosed at presentation). Mortality in those with malignancy was 46% at 3 months and 75% over the follow-up period. 24% of patients required re-treatment for recurrent hyponatraemia after tolvaptan discontinuation (100% of whom had relapsed within a week and had underlying malignancy).

Conclusions: Tolvaptan use remains safe and effective in-patient short-term therapy option in the group we have identified and these data merit investigation for its wider use.

Sodium level 1 week after discontinuation is a good indicator of re-treatment/longer-term therapy needs, nearly all of whom have malignancy. Thus, the criteria we have set locally to indicate tolvaptan use also identifies a group who should receive urgent investigation for underlying malignancy.