Background: Autoimmune hypophysitis is a rare disease with a natural progression that is not well known. Aim: To collect representative data on clinical features of autoimmune hypophysitis and better characterize the disease. Patients and Methods: A prospective single-center study was designed. Autoimmune hypophysitis-affected patients evaluated from 2011 at our tertiary care Pituitary Unit were enrolled. After ruling out other pituitary masses and secondary causes of hypophysitis, autoimmune hypophysitis was the diagnosis of exclusion. Autoimmune hypophysitis was classified as adenohypophysitis, panhypophysitis, and infundibuloneurohypophysitis according to clinical and neuroradiological findings. Results: A total of 21 patients met the inclusion criteria: 9 were diagnosed with adenohypophysitis, 4 with panhypophysitis, and 8 with infundibuloneurohypophysitis. The frequency of secondary hypoadrenalism was similar in adenohypophysitis, panhypophysitis, and infundibuloneurohypophysitis. Growth hormone deficit and secondary hypogonadism occurred more frequently in infundibuloneurohypophysitis than in adenohypophysitis and panhypophysitis (p = 0.009; p = 0.04). All cases of multiple pituitary secretion deficits occurred in cases of infundibuloneurohypophysitis (p = 0.04). No correlations between hypophysitis subtype and anti-pituitary and anti-hypothalamus autoantibodies were found. A higher frequency of extractable nuclear antigens (ENA) and anti-nuclear antibodies (ANA) was found in cases of panhypophysitis (OR 5.0, 95% CI 0.86-28.8, p < 0.001, and OR 1.8, 95% CI 1.1-3.2, p = 0.02, respectively) as compared to adenohypophysitis and infundibuloneurohypophysitis. Conclusion: Infundibuloneurohypophysitis should be taken into account in the etiological diagnosis of hypopituitarism, particularly if it is associated with diabetes insipidus and in cases of growth hormone deficit, secondary hypogonadism, or multiple hormone deficits. Contrast-enhanced MRI is crucial for the clinical and noninvasive diagnosis of hypophysitis. Screening for autoantibodies, particularly anti-ENA and anti-ANA, is strongly suggested in the clinical context of hypophysitis.

1.
Caturegli P, Lupi I, Landek-Salgado M, Kimura H, Rose NR: Pituitary autoimmunity: 30 years later. Autoimmun Rev 2008;7:631-637.
2.
Tang F, Liu H, Zhou S, Liu J, Xiao E, Tan C: MRI manifestation of xanthomatous hypophysitis: a case report and review of the literature. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2015;40:228-232.
3.
Imber BS, Lee HS, Kunwar S, Blevins LS, Aghi MK: Hypophysitis: a single-center case series. Pituitary 2015;18:630-641.
4.
Johnston PC, Chew LS, Hamrahian AH, Kennedy L: Lymphocytic infundibulo-neurohypophysitis: a clinical overview. Endocrine 2015;50:531-536.
5.
Khare S, Jagtap VS, Budyal SR, Kasaliwal R, Kakade HR, Bukan A, Sankhe S, Lila AR, Bandgar T, Menon PS, Shah NS: Primary (autoimmune) hypophysitis: a single centre experience. Pituitary 2015;18:16-22.
6.
Caturegli P, Iwama S: From Japan with love: another tessera in the hypophysitis mosaic. J Clin Endocrinol Metab 2013;98:1865-1868.
7.
Al-Haddad S, Fandino R, Scheithauer BW, Galvis L, Syro LV, Kovacs K: Necrotizing granulomatous hypophysitis presenting as a sellar mass. Endocr Pathol 2011;22:6-9.
8.
Caturegli P, Newschaffer C, Olivi A, Pomper MG, Burger PC, Rose NR: Autoimmune hypophysitis. Endocr Rev 2005;26:599-614.
9.
Barbarino A, De Marinis L, Maira G, Menini E, Anile C: Serum prolactin response to thyrotropin-releasing hormone and metoclopramide in patients with prolactin-secreting tumors before and after transsphenoidal surgery. J Clin Endocrinol Metab 1978;47:1148-1151.
10.
Barbarino A, De Marinis L, Menini E, Anile C, Sterzi S, Maira G: Validità dei test dinamici nella diagnosi degli adenomi ipofisari secernenti prolattina. Estratto degli atti del X congresso della società Italiana di fertilità e sterilità ‘D. Guanella', 1980, pp 356-363.
11.
Manetti L, Lupi I, Morselli LL, Albertini S, Cosottini M, Grasso L, Genovesi M, Pinna G, Mariotti S, Bogazzi F, Bartalena L, Martino E: Prevalence and functional significance of antipituitary antibodies in patients with autoimmune and non-autoimmune thyroid diseases. J Clin Endocrinol Metab 2007;92:2176-2181.
12.
De Bellis A, Sinisi AA, Pane E, Dello Iacovo A, Bellastella G, Di Scala G, Falorni A, Giavoli C, Gasco V, Giordano R, Ambrosio MR, Colao A, Bizzarro A, Bellastella A; Italian Autoimmune Hypophysitis Network Group: Involvement of hypothalamus autoimmunity in patients with autoimmune hypopituitarism: role of antibodies to hypothalamic cells. J Clin Endocrinol Metab 2012;97:3684-3690.
13.
Bellastella G, Rotondi M, Pane E, Dello Iacovo A, Pirali B, Dalla Mora L, Falorni A, Sinisi AA, Bizzarro A, Colao A, Chiovato L, De Bellis A; Italian Autoimmune Hypophysitis Network Study: Predictive role of the immunostaining pattern of immunofluorescence and the titers of antipituitary antibodies at presentation for the occurrence of autoimmune hypopituitarism in patients with autoimmune polyendocrine syndromes over a five-year follow-up. J Clin Endocrinol Metab 2010;95:3750-3757.
14.
De Bellis A, Pane E, Bellastella G, Sinisi AA, Colella C, Giordano R, Giavoli C, Lania A, Ambrosio MR, Di Somma C, Zatelli MC, Arvat E, Colao A, Bizzarro A, Bellastella A; Italian Autoimmune Hypophysitis Network Study: Detection of antipituitary and antihypothalamus antibodies to investigate the role of pituitary or hypothalamic autoimmunity in patients with selective idiopathic hypopituitarism. Clin Endocrinol (Oxf) 2011;75:361-366.
15.
Gutenberg A, Hans V, Puchner MJA, Kreutzer J, Brück W, Caturegli P, Buchfelder M: Primary hypophysitis: clinical-pathological correlations. Eur J Endocrinol 2006;155:101-107.
16.
Wada Y, Hamamoto Y, Nakamura Y, Honjo S, Kawasaki Y, Ikeda H, Takahashi J, Yuba Y, Shimatsu A, Koshiyama H: Lymphocytic panhypophysitis: its clinical features in Japanese cases. Jpn Clin Med 2011;2:15-20.
17.
Sautner D, Saeger W, Lüdecke DK, Jansen V, Puchner MJ: Hypophysitis in surgical and autoptical specimens. Acta Neuropathol 1995;90:637-644.
18.
Fehn M, Sommer C, Lüdecke DK, Plockinger U, Saeger W: Lymphocytic hypophysitis: light and electron microscopic findings and correlation to clinical appearance. Endocr Pathol 1998;9:71-78.
19.
Honegger J, Fahlbusch R, Bornemann A, Hensen J, Buchfelder M, Müller M, Nomikos P: Lymphocytic and granulomatous hypophysitis: experience with nine cases. Neurosurgery 1997;40:713-722; discussion 722-723.
20.
Leung GK, Lopes MB, Thorner MO, Vance ML, Laws ER Jr: Primary hypophysitis: a single-center experience in 16 cases. J Neurosurg 2004;101:262-271.
21.
Buxton R, Robertson I: Lymphocytic and granulocytic hypophysitis: a single center experience. Br J Neurosurg 2001;15:242-245; discussion 245-246.
22.
Tsagarakis S, Vassiliadi D, Malagari K, Kontogeorgos G, Thalassinos N: Lymphocytic hypophysitis: late recurrence following successful transsphenoidal surgery. Endocrine 2004;25:85-90.
23.
Honegger J, Schlaffer S, Menzel C, Droste M, Werner S, Elbelt U, Strasburger C, Störmann S, Küppers A, Streetz-van der Werf C, Deutschbein T, Stieg M, Rotermund R, Milian M, Petersenn S; Pituitary Working Group of the German Society of Endocrinology: Diagnosis of primary hypophysitis in Germany. J Clin Endocrinol Metab 2015;100:3841-3849.
24.
De Bellis A, Bizzarro A, Bellastella A: Pituitary antibodies and lymphocytic hypophysitis. Best Pract Res Clin Endocrinol Metab 2005;19:67-84.
25.
Akahori H, Sugimoto T: Lymphocytic hypophysitis with a long latent period from onset of central diabetes insipidus to development of pituitary enlargement. Intern Med 2010;49:1565-1571.
26.
Caturegli P: Autoimmune hypophysitis: an underestimated disease in search of its autoantigen(s). J Clin Endocrinol Metab 2007;92:2038-2040.
27.
Crock PA: Cytosolic autoantigens in lymphocytic hypophysitis. J Clin Endocrinol Metab 1998;83:609-618.
28.
Glezer A, Bronstein MD: Pituitary autoimmune disease: nuances in clinical presentation. Endocrine 2012;42:74-79.
29.
Kleinschmidt-DeMasters BK, Lopes MB: Update on hypophysitis and TTF-1 expressing sellar region masses. Brain Pathol 2013;23:495-514.
30.
Su SB, Zhang DJ, Yue SY, Zhang JN: Primary granulomatous hypophysitis: a case report and literature review. Endocr J 2011;58:467-473.
31.
Kasperlik-Zaluska AA, Jeske W, Bednarek-Papierska L, Czarnocka B: Isolated secondary adrenal insufficiency - an underestimated consequence of asymptomatic autoimmune hypophysitis. Letters to the Editor. Clin Endocrinol (Oxf) 2011;74:406.
32.
Abe T: Lymphocytic infundibulo-neurohypophysitis and infundibulo-panhypophysitis regarded as lymphocytic hypophysitis variant. Brain Tumor Pathol 2008;25:59-66.
33.
Katayama S, Yokota C: Diabetes insipidus and lymphocytic hypophysitis. Intern Med 2003;10:924-925.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.