Poster Presentation ESA-SRB-APEG-NZSE 2022

A 64 year old man with Stage III non-small cell lung cancer treated with Durvalumab (August 2018-August 2019) presented with diarrhoea, carpopedal spasm and prolongation in QTc interval. There were no contributing medications, including proton pump inhibitor, anti-resorptive agents and diuretics. There was no past history of any surgery or radiotherapy to the head and neck regions, nor was there a family history of autoimmune disorders. Investigations revealed marked hypocalcemia hyperphosphatemia, normomagnesemia, mild Vitamin D deficiency, acute renal impairment and a suppressed parathyroid hormone [PTH] level (Table-1). Repeat testing when normocalcemic (2.31 mmol/L) showed persistently low PTH (0.8 pmol/L). Mild hypocalcemia coincided with the commencement of Durvalumab and had persisted until presentation to hospital. He was diagnosed with Durvalumab-induced hypoparathyroidism. Treatment included intravenous and oral calcium, cholecalciferol and calcitriol.

Increasing use of immune checkpoint inhibitors (ICI), such as Durvalumab that targets programmed death-ligand 1 (PD-L1) has reduced self-tolerance and exposed discrete group of immune-related adverse effects (irAE) [1]. Endocrinopathies are common, but hypoparathyroidism is a rare irAE. Only case reports have described its occurrence, and none have been reported among patients treated with Durvalumab [1-3]. Hypocalcaemia has been reported in a small proportion of patients treated with Durvalumab [4].

Unlike other irAEs, endocrinopathies often require lifelong treatment with permanent hormone replacement for unclear reasons [5]. Persistence of hypoparathyroidism despite discontinuation of immunotherapy has been previously recognised [6]. The mechanism of ICI-related hypoparathyroidism remains unclear. It is postulated that anti-parathyroid and CASR-activating autoantibodies are implicated in its pathophysiology [7]. Further research is needed to elucidate the role of these antibodies and whether ICI-associated hypoparathyroidism is a destructive autoimmune process like in other endocrinopathies.

Further assessment of hypocalcemia is warranted among patients treated with ICI. The aforementioned autoantibodies are not commercially available for use in routine clinical practice.