, Volume 18, Issue 5, pp 630–641 | Cite as

Hypophysitis: a single-center case series

  • Brandon S. Imber
  • Han S. Lee
  • Sandeep Kunwar
  • Lewis S. Blevins
  • Manish K. AghiEmail author



The authors review their treatment experience and summarize clinical outcomes for patients with hypophysitis over the past 15 years.


A retrospective analysis was conducted on patients with lymphocytic, granulomatous or IgG4-related hypophysitis treated from 1997 to 2014 at a single academic center. Patients’ medical records were reviewed and binary logistic regression analysis was used to assess whether various clinical parameters were associated with improved outcomes including endocrine function, radiographic appearance and disease recurrence.


Twenty-one patients (13 women and 8 men) were identified with a median diagnosis age of 37.4 years. All but two patients (90 %) were diagnosed histopathologically and the remaining two were diagnosed clinically with lymphocytic hypophysitis. 16 patients (76 %) had lymphocytic hypophysitis, 3 (14 %) had granulomatous hypophysitis, 1 (5 %) had IgG4-related hypophysitis and 1 (5 %) had mixed lymphocytic-granulomatous. Patients presented with various symptoms of expanding sellar mass with most common signs including headache (57 %), polyuria/polydipsia (52 %), vision changes (52 %) and amenorrhea or decreased libido (48 %). Pre-treatment endocrine evaluation revealed that 12 (57 %) patients had complete anterior hypopituitarism, 11 patients (52 %) had diabetes insipidus, ten patients (48 %) had mild hyperprolactinemia and three patients (14 %) had isolated endocrine axis deficiencies with partial gland function. We observed a broad diversity in pre-treatment imaging with common findings including uniform contrast enhancement (62 %), thickened infundibulum (57 %) and loss of hypophysis bright spot on T1 imaging (43 %). Patients were treated with steroids and hormone supplementation as needed. 16 patients (76 %) had recorded post-treatment MRI scans which revealed that half had radiographic improvement and half had stable or worsened post-treatment imaging. Only female gender was found to significantly predict improved odds of post-steroid radiographic improvement. For post-treatment endocrine evaluation, six patients (29 %) did not have an evaluation on record, four patients (19 %) had some improvement in at least one axis, seven patients (33 %) had stable but non-worsened endocrine function and four patients (19 %) had worsened endocrine function post-steroids.


Hypophysitis is an increasingly recognized diagnosis that can present with a broad array of radiographic and clinical features. Surgical biopsy can be helpful to make definitive diagnosis and may guide treatment decision-making.


Autoimmune hypophysitis Pituitary inflammation Sellar mass Stalk thickening Granulomatous Lymphocytic 



We thank Jeffrey Wagner, BS for his assistance with identification of cases.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11102_2014_622_MOESM1_ESM.docx (25 kb)
Supplementary material 1 (DOCX 25 kb)


  1. 1.
    Caturegli P, Newschaffer C, Olivi A et al (2005) Autoimmune hypophysitis. Endocr Rev 26:599–614CrossRefPubMedGoogle Scholar
  2. 2.
    Caturegli P, Lupi I, Landek-Salgado M et al (2008) Pituitary autoimmunity: 30 years later. Autoimmun Rev 7:631–637PubMedCentralCrossRefPubMedGoogle Scholar
  3. 3.
    Leporati P, Landek-Salgado MA, Lupi I et al (2011) IgG4-related hypophysitis: a new addition to the hypophysitis spectrum. J Clin Endocrinol Metab 96:1971–1980PubMedCentralCrossRefPubMedGoogle Scholar
  4. 4.
    Rivera J-A (2006) Lymphocytic hypophysitis: disease spectrum and approach to diagnosis and therapy. Pituitary 9:35–45CrossRefPubMedGoogle Scholar
  5. 5.
    Khare S, Jagtap VS, Budyal SR et al (2013) Primary (autoimmune) hypophysitis: a single centre experience. PituitaryGoogle Scholar
  6. 6.
    Falorni A, Minarelli V, Bartoloni E et al (2014) Diagnosis and classification of autoimmune hypophysitis. Autoimmun Rev 13:412–416CrossRefPubMedGoogle Scholar
  7. 7.
    Goudie RB, Pinkerton PH (1962) Anterior hypophysitis and Hashimoto’s disease in a young woman. J Pathol Bacteriol 83:584–585CrossRefPubMedGoogle Scholar
  8. 8.
    Shi J, Zhang J, Wu Q et al (2009) Granulomatous hypophysitis: two case reports and literature review. J Zhejiang Univ Sci B 10:552–558PubMedCentralCrossRefPubMedGoogle Scholar
  9. 9.
    Hamnvik O-PR, Laury AR, Laws ER, Kaiser UB (2010) Lymphocytic hypophysitis with diabetes insipidus in a young man. Nat Rev Endocrinol 6:464–470CrossRefPubMedGoogle Scholar
  10. 10.
    Bellastella A, Bizzarro A, Coronella C et al (2003) Lymphocytic hypophysitis: a rare or underestimated disease? Eur J Endocrinol Eur Fed Endocr Soc 149:363–376CrossRefGoogle Scholar
  11. 11.
    De Bellis A, Sinisi AA, Conte M et al (2007) Antipituitary antibodies against gonadotropin-secreting cells in adult male patients with apparently idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab 92:604–607CrossRefPubMedGoogle Scholar
  12. 12.
    De Bellis A, Dello Iacovo A, Bellastella G et al (2014) Characterization of pituitary cells targeted by antipituitary antibodies in patients with isolated autoimmune diseases without pituitary insufficiency may help to foresee the kind of future hypopituitarism. Pituitary 17:457–463Google Scholar
  13. 13.
    Torino F, Barnabei A, De Vecchis L et al (2012) Hypophysitis induced by monoclonal antibodies to cytotoxic T lymphocyte antigen 4: challenges from a new cause of a rare disease. Oncologist 17:525–535PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    Shimatsu A, Oki Y, Fujisawa I, Sano T (2009) Pituitary and stalk lesions (infundibulo-hypophysitis) associated with immunoglobulin G4-related systemic disease: an emerging clinical entity. Endocr J 56:1033–1041CrossRefPubMedGoogle Scholar
  15. 15.
    Van der Vliet HJJ, Perenboom RM (2004) Multiple pseudotumors in IgG4-associated multifocal systemic fibrosis. Ann Intern Med 141:896–897CrossRefPubMedGoogle Scholar
  16. 16.
    Wong S, Lam WY, Wong WK, Lee KC (2007) Hypophysitis presented as inflammatory pseudotumor in immunoglobulin G4-related systemic disease. Hum Pathol 38:1720–1723CrossRefPubMedGoogle Scholar
  17. 17.
    Bando H, Iguchi G, Fukuoka H et al (2014) The prevalence of IgG4-related hypophysitis in 170 consecutive patients with hypopituitarism and/or central diabetes insipidus and review of the literature. Eur J Endocrinol Eur Fed Endocr Soc 170:161–172CrossRefGoogle Scholar
  18. 18.
    Honegger J, Fahlbusch R, Bornemann A et al (1997) Lymphocytic and granulomatous hypophysitis: experience with nine cases. Neurosurgery 40:713–722. Discussion 722–723Google Scholar
  19. 19.
    Leung GKK, Lopes M-BS, Thorner MO et al (2004) Primary hypophysitis: a single-center experience in 16 cases. J Neurosurg 101:262–271CrossRefPubMedGoogle Scholar
  20. 20.
    Gutenberg A, Hans V, Puchner MJA et al (2006) Primary hypophysitis: clinical-pathological correlations. Eur J Endocrinol Eur Fed Endocr Soc 155:101–107CrossRefGoogle Scholar
  21. 21.
    Menon SK, Sarathi V, Bandgar TR et al (2009) Autoimmune hypophysitis: a single centre experience. Singap Med J 50:1080–1084Google Scholar
  22. 22.
    Gutenberg A, Larsen J, Lupi I et al (2009) A radiologic Score to distinguish autoimmune hypophysitis from nonsecreting pituitary adenoma preoperatively. Am J Neuroradiol 30:1766–1772CrossRefPubMedGoogle Scholar
  23. 23.
    Leporati P, Landek-Salgado MA, Lupi I et al (2011) IgG4-related hypophysitis: a new addition to the hypophysitis spectrum. J Clin Endocrinol Metab 96:1971–1980PubMedCentralCrossRefPubMedGoogle Scholar
  24. 24.
    Umehara H, Okazaki K, Masaki Y et al (2012) Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol Jpn Rheum Assoc 22:21–30CrossRefGoogle Scholar
  25. 25.
    Asa SL, Bilbao JM, Kovacs K et al (1981) Lymphocytic hypophysitis of pregnancy resulting in hypopituitarism: a distinct clinicopathologic entity. Ann Intern Med 95:166–171CrossRefPubMedGoogle Scholar
  26. 26.
    Landek-Salgado MA, Gutenberg A, Lupi I et al (2010) Pregnancy, postpartum autoimmune thyroiditis, and autoimmune hypophysitis: intimate relationships. Autoimmun Rev 9:153–157PubMedCentralCrossRefPubMedGoogle Scholar
  27. 27.
    Sautner D, Saeger W, Lüdecke DK et al (1995) Hypophysitis in surgical and autoptical specimens. Acta Neuropathol (Berl) 90:637–644CrossRefGoogle Scholar
  28. 28.
    Fehn M, Sommer C, Ludecke DK et al (1998) Lymphocytic hypophysitis: light and electron microscopic findings and correlation to clinical appearance. Endocr Pathol 9:71–78CrossRefPubMedGoogle Scholar
  29. 29.
    Buxton N, Robertson I (2001) Lymphocytic and granulocytic hypophysitis: a single centre experience. Br J Neurosurg 15:242–245. Discussion 245–246Google Scholar
  30. 30.
    Yamamoto M, Takahashi H, Ohara M et al (2006) A case of Mikulicz’s disease (IgG4-related plasmacytic disease) complicated by autoimmune hypophysitis. Scand J Rheumatol 35:410–411CrossRefPubMedGoogle Scholar
  31. 31.
    Zen Y, Kitagawa S, Minato H et al (2005) IgG4-positive plasma cells in inflammatory pseudotumor (plasma cell granuloma) of the lung. Hum Pathol 36:710–717CrossRefPubMedGoogle Scholar
  32. 32.
    Fujiu K, Sakuma H, Miyamoto H, Yamaguchi B (2010) Immunoglobulin G4-related inflammatory pseudotumor of the lung. Gen Thorac Cardiovasc Surg 58:144–148CrossRefPubMedGoogle Scholar
  33. 33.
    Nishikawa G, Nakamura K, Yamada Y et al (2011) Inflammatory pseudotumors of the kidney and the lung presenting as immunoglobulin G4-related disease: a case report. J Med Case Rep 5:480PubMedCentralCrossRefPubMedGoogle Scholar
  34. 34.
    Albini CH, MacGillivray MH, Fisher JE et al (1988) Triad of hypopituitarism, granulomatous hypophysitis, and ruptured Rathke’s cleft cyst. Neurosurgery 22:133–136PubMedGoogle Scholar
  35. 35.
    Wearne MJ, Barber PC, Johnson AP (1995) Symptomatic Rathke’s cleft cyst with hypophysitis. Br J Neurosurg 9:799–803CrossRefPubMedGoogle Scholar
  36. 36.
    Roncaroli F, Bacci A, Frank G, Calbucci F (1998) Granulomatous hypophysitis caused by a ruptured intrasellar Rathke’s cleft cyst: report of a case and review of the literature. Neurosurgery 43:146–149CrossRefPubMedGoogle Scholar
  37. 37.
    Hama S, Arita K, Tominaga A et al (1999) Symptomatic Rathke’s cleft cyst coexisting with central diabetes insipidus and hypophysitis: case report. Endocr J 46:187–192CrossRefPubMedGoogle Scholar
  38. 38.
    Daikokuya H, Inoue Y, Nemoto Y et al (2000) Rathke’s cleft cyst associated with hypophysitis: MRI. Neuroradiology 42:532–534CrossRefPubMedGoogle Scholar
  39. 39.
    Nishikawa T, Takahashi JA, Shimatsu A, Hashimoto N (2007) Hypophysitis caused by Rathke’s cleft cyst case report. Neurol Med Chir (Tokyo) 47:136–139CrossRefGoogle Scholar
  40. 40.
    Komatsu F, Tsugu H, Komatsu M et al (2010) Clinicopathological characteristics in patients presenting with acute onset of symptoms caused by Rathke’s cleft cysts. Acta Neurochir (Wien) 152:1673–1678CrossRefGoogle Scholar
  41. 41.
    Myers JL, Kurtin PJ, Katzenstein AL et al (1995) Lymphomatoid granulomatosis. Evidence of immunophenotypic diversity and relationship to Epstein–Barr virus infection. Am J Surg Pathol 19:1300–1312CrossRefPubMedGoogle Scholar
  42. 42.
    Jaffe ES, Wilson WH (1997) Lymphomatoid granulomatosis: pathogenesis, pathology and clinical implications. Cancer Surv 30:233–248PubMedGoogle Scholar
  43. 43.
    Roschewski M, Wilson WH (2012) Lymphomatoid granulomatosis. Cancer J Sudbury Mass 18:469–474CrossRefGoogle Scholar
  44. 44.
    Tagliavini E, Rossi G, Valli R et al (2013) Lymphomatoid granulomatosis: a practical review for pathologists dealing with this rare pulmonary lymphoproliferative process. Pathologica 105:111–116PubMedGoogle Scholar
  45. 45.
    Katzenstein AL, Carrington CB, Liebow AA (1979) Lymphomatoid granulomatosis: a clinicopathologic study of 152 cases. Cancer 43:360–373CrossRefPubMedGoogle Scholar
  46. 46.
    Patsalides AD, Atac G, Hedge U et al (2005) Lymphomatoid granulomatosis: abnormalities of the brain at MR imaging. Radiology 237:265–273CrossRefPubMedGoogle Scholar
  47. 47.
    Bushunow PW, Casas V, Duggan DB (1996) Lyphomatoid granulomatosis causing central diabetes insipidus: case report and review of the literature. Cancer Invest 14:112–119CrossRefPubMedGoogle Scholar
  48. 48.
    Carmichael JD (2012) Update on the diagnosis and management of hypophysitis. Curr Opin Endocrinol Diabetes Obes 19:314–321CrossRefPubMedGoogle Scholar
  49. 49.
    Lecube A, Francisco G, Rodríguez D et al (2003) Lymphocytic hypophysitis successfully treated with azathioprine: first case report. J Neurol Neurosurg Psychiatry 74:1581–1583PubMedCentralCrossRefPubMedGoogle Scholar
  50. 50.
    Curtò L, Torre ML, Cotta OR et al (2010) Lymphocytic hypophysitis: differential diagnosis and effects of high-dose pulse steroids, followed by azathioprine, on the pituitary mass and endocrine abnormalities—report of a case and literature review. Sci World J 10:126–134CrossRefGoogle Scholar
  51. 51.
    Lu Z, Yang G, Ba J et al (2011) Spontaneous pregnancy in a patient with a relapse of lymphocytic hypophysitis successfully treated with azathioprine and glucocorticoids. Endocrine 39:296–297CrossRefPubMedGoogle Scholar
  52. 52.
    Papanastasiou L, Pappa T, Tsiavos V et al (2011) Azathioprine as an alternative treatment in primary hypophysitis. Pituitary 14:16–22CrossRefPubMedGoogle Scholar
  53. 53.
    Yang G-Q, Lu Z-H, Gu W-J et al (2011) Recurrent autoimmune hypophysitis successfully treated with glucocorticoids plus azathioprine: a report of three cases. Endocr J 58:675–683CrossRefPubMedGoogle Scholar
  54. 54.
    Caputo C, Bazargan A, McKelvie PA et al (2014) Hypophysitis due to IgG4-related disease responding to treatment with azathioprine: an alternative to corticosteroid therapy. Pituitary 17:251–256CrossRefPubMedGoogle Scholar
  55. 55.
    Schreckinger M, Francis T, Rajah G et al (2012) Novel strategy to treat a case of recurrent lymphocytic hypophysitis using rituximab. J Neurosurg 116:1318–1323CrossRefPubMedGoogle Scholar
  56. 56.
    Selch MT, DeSalles AAF, Kelly DF et al (2003) Stereotactic radiotherapy for the treatment of lymphocytic hypophysitis: report of two cases. J Neurosurg 99:591–596CrossRefPubMedGoogle Scholar
  57. 57.
    Ray DK, Yen CP, Vance ML et al (2010) Gamma knife surgery for lymphocytic hypophysitis. J Neurosurg 112:118–121CrossRefPubMedGoogle Scholar
  58. 58.
    Howlett TA, Levy MJ, Robertson IJ (2010) How reliably can autoimmune hypophysitis be diagnosed without pituitary biopsy. Clin Endocrinol (Oxf) 73:18–21Google Scholar
  59. 59.
    Swearingen B, Barker FG 2nd, Katznelson L et al (1998) Long-term mortality after transsphenoidal surgery and adjunctive therapy for acromegaly. J Clin Endocrinol Metab 83:3419–3426PubMedGoogle Scholar
  60. 60.
    Jahangiri A, Wagner JR, Pekmezci M et al (2013) A comprehensive long-term retrospective analysis of silent corticotrophic adenomas vs hormone-negative adenomas. Neurosurgery 73:8–17. Discussion 17–18Google Scholar
  61. 61.
    Jahangiri A, Wagner J, Han SW et al (2014) Morbidity of repeat transsphenoidal surgery assessed in more than 1000 operations. J Neurosurg 121:67–74Google Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Brandon S. Imber
    • 1
  • Han S. Lee
    • 2
  • Sandeep Kunwar
    • 1
    • 3
  • Lewis S. Blevins
    • 1
    • 3
  • Manish K. Aghi
    • 1
    • 3
    Email author
  1. 1.Department of Neurological SurgeryUniversity of California at San FranciscoSan FranciscoUSA
  2. 2.Neuropathology Division, Department of Anatomic PathologyUniversity of California at San FranciscoSan FranciscoUSA
  3. 3.California Center for Pituitary Disorders at The University of California at San FranciscoSan FranciscoUSA

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