Abstract
Purpose
Fifteen cases of lymphocytic hypophysitis due to IgG4-related disease have been reported demonstrating marked improvement with corticosteroid therapy. This is the first case of IgG4-related hypophysitis demonstrating improvement with azathioprine, where corticosteroids were initially tried but ceased due to concern regarding enlargement of the pituitary infiltrate.
Methods
Case description and review of 15 cases reported in the literature. A 40 year old male was diagnosed with IgG-4 related disease based on pituitary and lacrimal gland biopsies associated with raised serum concentration of IgG4. The patient was commenced on prednisolone 30 mg/day, as rapid response to prednisolone treatment has been described in the literature for other cases of IgG4-related hypophysitis. Over the next 3 months, prednisolone treatment resulted in a reduction of serum IgG4 levels, but repeat MRI scan showed an enlarging pituitary mass with new optic nerve compression. Azathioprine 75 mg twice daily was commenced and in the subsequent 3 months, IgG4 levels normalised (0.58 g/L) and MRI scan showed 50 % shrinkage of the pituitary mass. After 10 months of azathioprine treatment the MRI showed a normal sized pituitary but persistence of the infraorbital nerve thickening.
Conclusions
Hypophysitis due to IgG4-related disease usually demonstrates prompt response to corticosteroids. This case highlights the need to image promptly after starting treatment to exclude an enlarging pituitary mass despite corticosteroid treatment. Alternative therapy with azathioprine can result in marked improvement. It should be remembered that IgG-4 related hypophysitis is part of a multi-organ disease.
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References
Stone JH, Khosroshahi A, Deshpande V, Chan JK, Heathcote JG, Aalberse R et al (2012) Recommendations for the nomenclature of IgG4-related disease and its individual organ system manifestations. Arthr Rheum 64(10):3061–3067
Umehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T et al (2012) A novel clinical entity, IgG4-related disease (IgG4RD): general concept and details. Mod Rheumatol 22(1):1–14
Deshpande V, Zen Y, Chan JK, Yi EE, Sato Y, Yoshino T et al (2012) Consensus statement on the pathology of IgG4-related disease. Mod Pathol 25(9):1181–1192
Ryu JH, Horie R, Sekiguchi H, Peikert T, Yi ES (2012) Spectrum of disorders associated with elevated serum IgG4 levels encountered in clinical practice. Int J Rheumatol 2012:232960
Hamano H, Kawa S, Horiuchi A, Unno H, Furuya N, Akamatsu T et al (2001) High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med 344(10):732–738
Kamisawa T, Egawa N, Nakajima H (2003) Autoimmune pancreatitis is a systemic autoimmune disease. Am J Gastroenterol 98(12):2811–2812
van der Vliet HJ, Perenboom RM (2004) Multiple pseudotumor in IgG4-associated multifocal systemic fibrosis. Ann Intern Med 141(11):896–897
Yamamoto M, Takahashi H, Ohara M, Suzuki C, Naishiro Y, Yamamoto H et al (2006) A case of Mikulicz’s disease (IgG4-related plasmacytic disease) complicated by autoimmune hypophysitis. Scand J Rheumatol 35(5):410–411
Tanabe T, Tsushima K, Yasuo M, Urushihata K, Hanaoka M, Koizumi T et al (2006) IgG4-associated multifocal systemic fibrosis complicating sclerosing sialadenitis, hypophysitis, and retroperitoneal fibrosis, but lacking pancreatic involvement. Intern Med 45(21):1243–1247
Ralli S, Lin J, Farrell J (2007) Autoimmune pancreatitis. N Engl J Med 356(15):1586; author reply 7
Wong S, Lam WY, Wong WK, Lee KC (2007) Hypophysitis presented as inflammatory pseudotumor in immunoglobulin G4-related systemic disease. Hum Pathol 38(11):1720–1723
Isaka Y, Yoshioka K, Nishio M, Yamagami K, Konishi Y, Inoue T et al (2008) A case of IgG4-related multifocal fibrosclerosis complicated by central diabetes insipidus. Endocr J 55(4):723–728
Tsuboi H, Inokuma S, Setoguchi K, Shuji S, Hagino N, Tanaka Y et al (2008) Inflammatory pseudotumors in multiple organs associated with elevated serum IgG4 level: recovery by only a small replacement dose of steroid. Intern Med 47(12):1139–1142
Osawa S, Ogawa Y, Watanabe M, Tominaga T (2009) Hypophysitis presenting with atypical rapid deterioration: with special reference to immunoglobulin G4-related disease-case report. Neurol Med Chir (Tokyo) 49(12):622–625
Hori M, Makita N, Andoh T, Takiyama H, Yajima Y, Sakatani T et al (2010) Long-term clinical course of IgG4-related systemic disease accompanied by hypophysitis. Endocr J 57(6):485–492
Haraguchi A, Era A, Yasui J, Ando T, Ueki I, Horie I et al (2010) Putative IgG4-related pituitary disease with hypopituitarism and/or diabetes insipidus accompanied with elevated serum levels of IgG4. Endocr J 57(8):719–725
Leporati P, Landek-Salgado MA, Lupi I, Chiovato L, Caturegli P (2011) IgG4-related hypophysitis: a new addition to the hypophysitis spectrum. J Clin Endocrinol Metab 96(7):1971–1980
Patel SM, Szostek JH (2011) IgG4-related systemic disease in a Native American man. Intern Med 50(8):931–934
Hsing MT, Hsu HT, Cheng CY, Chen CM (2013) IgG4-related hypophysitis presenting as a pituitary adenoma with systemic disease. Asian J Surg 36(2):93–97
Hattori Y, Tahara S, Ishii Y, Kitamura T, Inomoto C, Osamura RY, et al (2013) A case of IgG4-related hypophysitis without pituitary insufficiency. J Clin Endocrinol Metab 98(5):1808–1811
Masaki Y, Kurose N, Yamamoto M, Takahashi H, Saeki T, Azumi A et al (2012) Cutoff values of serum IgG4 and histopathological IgG4+ plasma cells for diagnosis of patients with IgG4-related disease. Int J Rheumatol 2012:580814
Bosco JJ, Suan D, Varikatt W, Lin MW (2013) Extra-pancreatic manifestations of IgG4-related systemic disease: a single-centre experience of treatment with combined immunosuppression. Intern Med J 43(4):417–423
Khosroshahi A, Carruthers MN, Deshpande V, Unizony S, Bloch DB, Stone JH (2012) Rituximab for the treatment of IgG4-related disease: lessons from 10 consecutive patients. Medicine (Baltimore) 91(1):57–66
Wong PC, Fung AT, Gerrie AS, Moloney G, Maberley D, Rossman D et al (2013) IgG4-related disease with hypergammaglobulinemic hyperviscosity and retinopathy. Eur J Haematol 90(3):250–256
Gutenberg A, Hans V, Puchner MJ, Kreutzer J, Bruck W, Caturegli P et al (2006) Primary hypophysitis: clinical-pathological correlations. Eur J Endocrinol 155(1):101–107
Caturegli P, Newschaffer C, Olivi A, Pomper MG, Burger PC, Rose NR (2005) Autoimmune hypophysitis. Endocr Rev 26(5):599–614
Caturegli P, Lupi I, Landek-Salgado M, Kimura H, Rose NR (2008) Pituitary autoimmunity: 30 years later. Autoimmun Rev 7(8):631–637
Kamisawa T, Okazaki K, Kawa S, Shimosegawa T, Tanaka M (2010) Japanese consensus guidelines for management of autoimmune pancreatitis: III. Treatment and prognosis of AIP. J Gastroenterol 45(5):471–477
Church NI, Pereira SP, Deheragoda MG, Sandanayake N, Amin Z, Lees WR et al (2007) Autoimmune pancreatitis: clinical and radiological features and objective response to steroid therapy in a UK series. Am J Gastroenterol 102(11):2417–2425
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Caputo, C., Bazargan, A., McKelvie, P.A. et al. Hypophysitis due to IgG4-related disease responding to treatment with azathioprine: an alternative to corticosteroid therapy. Pituitary 17, 251–256 (2014). https://doi.org/10.1007/s11102-013-0498-9
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DOI: https://doi.org/10.1007/s11102-013-0498-9