Endocrine Abstracts

Background: Chronic SIAD with its disabling impact is challenging to manage in elderly patients as fluid restriction or demeclocycline often has a limited success. Tolvaptan is a novel selective antagonist of vasopressin receptor (V2R) which is safely used in patients with SIAD and other conditions with hypervolemia. We report a case of longest Tolvaptan use with significant challenges amongst our case series which we had previously published

Method: A Case Report of SIAD managed with long term Tolvaptan therapy with significant cytochrome P450 drug interactions. A 78-year-old male presented with recurrent falls and reduced mobility in April 2017. He had multiple falls prior and was being investigated for cavitating lung lesion in Right Upper lobe. He was found to have severe euvolemic hyponatremia (serum sodium of 104 nmol/l) with a paired serum (228 mOsm/kg) and Urine Osmolalities (419 mOsm/kg), a normal Cortisol of 666 nmol/l and a normal Thyroid function test. His prior baseline sodium was around 130 mmol/l. SIAD was confirmed which failed to respond to fluid restriction (19 days) and demeclocycline (10days). A clinical diagnosis of Aspergillosis was made and oral Itraconazole was started. We commenced Tolvaptan 7.5 mg once daily dose (smaller dose) given drug interaction between Itraconazole (CYP3A4 Inhibitor) and Tolvaptan. Hyponatraemia improved back to baseline within 48 h and patient was discharged on Tolvaptan (7.5 mg OD). Trials of stopping Tolvaptan therapy were unsuccessful (2017, 2019). Patient presented with increased fatigue and low basal cortisol (9 nmol/l) in 2018 despite normal serum electrolytes. Diagnosis of Secondary adrenal Insufficiency was made (250 microgram Short Synacthen test - Cortisol 0 Minutes- 73 nmol/l, 30 minutes- 131 nmol/l, Serum ACTH < 3 ng/l). This is due to known interaction of potent CYP3A4 inhibitor (Itraconazole) with Seretide Inhaler therapy (Fluticasone dipropionate) in our patient. Steroid replacement therapy with Hydrocortisone was commenced. Tolvaptan dose frequency was gradually reduced to 7.5 mg twice weekly (since 2020). There were only 15 endocrine clinic appointments over 246 weeks with no adverse effects and no further admissions since 2017.

Conclsion: We present our experience of longest use of Tolvaptan in an elderly patient with no adverse events. Clinicians must be aware of potential Cytochrome P450 drug interactions to avoid complications. Long term Tolvaptan use in chronic refractory SIAD appears to be safe, feasible and cost effective. More prospective studies are needed for guidance in using vasopressin receptor antagonists in chronic disabling SIAD.