Novel strategy to treat a case of recurrent lymphocytic hypophysitis using rituximab

Abstract

Lymphocytic hypophysitis is an uncommon autoimmune condition that often results in significant morbidity. Although most cases resolve spontaneously or after a short course of steroids, rarely, refractory cases can cause persistent neurological deficits despite aggressive medical and surgical management. A 41-year-old woman presented with progressive visual loss in the left eye and was found to have a sellar mass. She underwent transsphenoidal surgery because of lesion enlargement. Histopathology was consistent with adenohypophysitis with B-cell predominance. Despite steroid treatment, her neurological condition worsened and she experienced loss of vision in the right eye. Craniotomy with decompression of the right optic nerve was performed. Her condition improved initially, but she continued to have progressive visual compromise over the following months. She was therefore treated with rituximab, a monoclonal antibody against B cells. Her vision improved significantly within a few weeks. There was no clinical or radiographic exacerbation 2 years after starting immunotherapy. Rituximab, an anti-CD20 antibody that specifically depletes B lymphocytes, can be an effective treatment strategy for patients with steroid-refractory, B cell-predominant lymphocytic hypophysitis.

Hypophysitis: a single-center case series

“…Relapse rate in our series was almost 30 %, and there is no standard management approach for recurrent hypophysitis [48]. Treatment options include additional corticosteroids, other immunosuppressive agents such as azathioprine [49][50][51][52][53][54] or rituximab [55], surgery or radiosurgery [56,57].…”

Treatment of Primary Hypophysitis in Germany

“…The scope includes immunosuppressive therapy (12,13), fractionated radiotherapy (14), radiosurgery (15), and therapy with monoclonal antibodies (16).…”

New Molecular, Biological, and Immunological Agents Inducing Hypophysitis

“…In the acute phase, glucocorticoid replacement is mandatory and in some cases transsphenoidal surgery may be employed in patients with symptoms and/or signs of severe compression to nearby structures [2,3] . Other immunosuppressive drugs, including azathioprine, methotrexate, cyclosporine A, and recently rituximab [83] and infliximab [21] have also been used successfully in corticosteroid-resistant cases, but data are scanty with these agents [1][2][3] . In the chronic phase, therapeutic strategy aims at the appropriate replacement therapy in cases of permanent pituitary deficiency.…”

“…Concerning mild forms (grade 1) of immune checkpoint-related hypophysitis, continuation of immunotherapy and close observation are recommended [84] . For all other toxicity grades, it is recommended that ipilimumab be withheld and not resumed until the resolution of adverse events to grade 1 [83] . However, this recommendation has recently been debated following a large study suggesting continuation of immunotherapy with concomitant hormonal replacement [31] .…”

“…For severe hypophysitis (grade 3 or 4), most authors use high-dose systemic steroids (prednisolone 1 mg/kg/ day or equivalent) with sequential tapering to a physiological replacement dose of hydrocortisone or prednisolone [30,43,83] . However, the use of high-dose steroids did not alter the recovery of the pituitary function [31] .…”