IgG4 Related Disease associated with hypophysitis not responding to prednisolone: Alternative treatment with azathioprine

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 163-194-Pituitary Disorders & Case Reports
Basic/Clinical
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-164
Carmela Caputo*1, Charles Su2, Penelope McKelvie1, Ali Bazargan3 and Warrick J Inder4
1St Vincent's Hospital, Melbourne, Australia, 2Royal Victoria Eye and Ear Hospital, East Melbourne, Australia, 3St Vincent's Hospital, Melbourne, Fitzroy, Australia, 4Princess Alexandra Hospital, Woolloongabba QLD, Australia
Introduction: Previous cases of IgG4 lymphocytic hypophysitis have responded extremely well to prednisolone treatment.  We describe a case where prednisolone treatment was associated with increasing pituitary mass size, requiring alternative immunosuppression with azathioprine.

Case: A 40 year old male presented with 4 month history of lethargy, polyuria and polydipsia.  Past history was unremarkable apart from an “eyelid” lump removed in 2010.  The patient underwent hormonal assessment with basal hormones, an ITT and overnight water deprivation. He had panhypopituitarism and diabetes insipidus and commenced on hydrocortisone, thyroxine, oral dDAVP, GH and hCG (as he was seeking fertility). MRI pituitary demonstrated a homogeneous dumbbell shaped lesion 13.7mm in height, not compressing the optic chiasm, with florid enhancement post contrast. Pituitary biopsy showed eosinophils, macrophages, lymphocytes and occasional plasma cells, and a diagnosis of lymphocytic hypophysitis was made.

Five months later the patient complained of paraesthesia under the right eye. CT orbit revealed bilaterally enlarged infraorbital nerves. Nerve biopsy showed 40 IgG4+ plasma cells / HPF and ratio of IgG4+/ IgG+ plasma cells of >70% . Retrospective staining of the pituitary biopsy showed 70 IgG4+ plasma cells / HPF and ratio of IgG4+/ IgG+ plasma cells of >90% consistent with IgG4 lymphocytic hypophysitis. Serum IgG4 levels were markedly raised at 5.92 g/L (0.04-0.86). The patient was commenced on prednisolone 30mg/day. IgG4 levels reduced over the next 3 months to 1.72 g/L(0.04-0.86), but repeat MRI scan showed an enlarging pituitary mass with new optic nerve compression. Azathioprine 75mg bd was commenced whilst weaning prednisolone. Over the next 3 months, IgG4 levels normalised (0.58 g/L) and MRI scan showed 50% shrinkage of the pituitary mass. After 10 months of azathioprine the MRI showed a normal sized pituitary with improvement of the infraorbital nerve thickening. The patient remains only on thyroxine, testosterone and oral dDAVP. Serum IgG4 increased to 1.14 g/l, so azathioprine has been increased to 100mg bd.

Clinical Lesson: In the literature, all 12 reported cases of IgG4 lymphocytic hypophysitis treated with 30-50mg/day prednisolone demonstrated treatment response (1, 2). Our case is the first to demonstrate enlargement of the pituitary mass during glucocorticoid treatment, and that a switch to azathioprine resulted in disease control.

1.            Leporati P, Landek-Salgado MA, Lupi I, Chiovato L, Caturegli P. IgG4-related hypophysitis: a new addition to the hypophysitis spectrum. J Clin Endocrinol Metab. 2011 Jul;96(7):1971-80. 2.            Wong S, Lam WY, Wong WK, Lee KC. Hypophysitis presented as inflammatory pseudotumor in immunoglobulin G4-related systemic disease. Hum Pathol. 2007 Nov;38(11):1720-

Nothing to Disclose: CC, CS, PM, AB, WJI

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