MON-006 - Loss of Desmopressin Responsiveness in Central Diabetes Insipidus: A Rare Case of Tachyphylaxis

Reports of tachyphylaxis in the DDAVP response for von Willebrand disease have been reported; however, tachyphylaxis secondary to long-term intravenous IV DDAVP in central diabetes Insipidus (CDI) is exceedingly rare.

A 44-year-old man presented with acute mental status changes. Diagnostic workup revealed a germinoma causing obstructive hydrocephalus. The patient underwent ventriculoperitoneal shunt placement for obstruction alleviation.

Postoperatively, he developed persistent CDI, manifested by marked polyuria (>4 L/day), polydipsia, hypernatremia (serum sodium 176 mmol/L), elevated serum osmolality (354 mOsm/kg), and urine osmolality (126 mOsm/kg). The patient was treated with IV 0.25 mcg DDAVP daily with excellent response and fluid restriction given wide fluctuations in sodium with higher doses.

He continued daily IV DDAVP dosing for 3 weeks; however, he started developing tachyphylaxis requiring more frequent redosing eventually decreasing to 4 hours after previous dose. To overcome the tachyphylaxis, the route of administration of the DDAVP was changed to oral, which resulted in improved biochemical control. He was eventually discharged on DDAVP 50 mcg orally twice daily and 2L/day fluid restriction, and upon outpatient follow-up, he was stable with this regimen.

Patterns of development of tachyphylaxis in patients with Hemophilia and vWD after repeated doses of IV DDAVP have been reported [1]. This phenomenon is explained because DDAVP works by stimulating the release of VWF stored in Weibel-Palade bodies within endothelial cells and these storage pools after repeated doses become progressively depleted, resulting in diminished response [2]. On the contrary, tachyphylaxis is rarely reported in the treatment of CDI. The mechanism of tachyphylaxis involves local inactivation of the angiotensin II peptide rather than the development of binding anti-drug antibodies. It is characterized by decreased responsiveness or shortened duration of effect, typically occurring over a period greater than 6 months with intranasal formulations rather than oral formulations [3]. Tachyphylaxis to IV DDAVP in patients with CDI is not reported in the medical literature apart from one case report from 1978, though specific details about the mechanism or frequency are not provided [4]. Also, animal studies have shown that in rats whose blood vasopressin concentration was experimentally elevated by IV infusion, there was significant desensitization of their kidney vasopressin receptors [5].

In our case, the tachyphylaxis was treated by changing the route of administration from IV to oral. Given that the mechanisms underlying tachyphylaxis with DDAVP in CDI remain poorly understood, further research is warranted to elucidate its pathophysiology and clinical implications.

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