Abstract
Lymphocytic hypophysitis (LyH) is a rare inflammatory disease, considered to be autoimmune. LyH has mainly been reported in females and in relation to pregnancy or the post-partum period. We describe a 73-yr-old woman and a 63-yr-old male who were evaluated at our clinic because of pituitary hormone deficits. Both patients had pituitary masses suggestive of a pituitary adenoma on magnetic resonance imaging (MRI). Transsphenoidal pituitary surgery was performed and histopathological examinations revealed LyH in both cases. Clinical, laboratory, radiological and the histopathological findings in these two patients are discussed in detail. In addition, we report on a 79-yr-old man with partial hypopituitarism and empty sella. Screening of a human pituitary cDNA library with his serum revealed autoantibodies against secretogranin II. This is a protein commonly present in human gonadotrophs, thyreotrophs and corticotrophs. Since the patient selectively showed the corresponding pituitary insufficiencies, we speculate on an autoimmune background. Further studies may ascertain the importance of secretogranin II autoantibodies as markers for LyH.
Similar content being viewed by others
References
Kristof RA, Van Roost D, Klingmuller D, Springer W, Schramm J. Lymphocytic hypophysitis: non-invasive diagnosis and treatment by high dose methylprednisolone pulse therapy? J Neurol Neurosurg Psychiatry 1999, 67: 398–402.
Leung GK, Lopes MB, Thorner MO, Vance ML, Laws ER Jr. Primary hypophysitis: a single-center experience in 16 cases. J Neurosurg 2004, 101: 262–71.
Beressi N, Beressi JP, Cohen R, Modigliani E. Lymphocytic hypophysitis: a review of 145 cases. An Med Interna (Paris) 1999, 150: 327–41.
Rorsman F, Husebye ES, Winqvist O, Björk E, Karlsson FA, Kämpe O. Aromatic-Lamino-acid decarboxylase, a pyridoxal phosphate-dependent enzyme, is a beta-cell autoantigen. Proc Natl Acad Sci USA 1995, 92: 8626–9.
Altschul SF, Madden TL, Schaffer AA, et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 1997, 25: 3389–402.
Hashimoto K, Takao T, Makino S. Lymphocytic adenohypophysitis and lymphocytic infundibuloneurohypophysitis. Endocr J 1997, 44: 1–10.
Tashiro T, Sano T, Xu B, et al. Spectrum of different types of hypophysitis: a clinicopathologic study of hypophysitis in 31 cases. Endocr Pathol 2002, 13: 183–95.
Caturegli P, Newschaffer C, Olivi A, Pomper MG, Burger PC, Rose NR. Autoimmune hypophysitis. Endocr Rev 2005, 26: 599–614.
Bottazzo GF, Pouplard A, Florin-Christensen A, Doniach D. Autoantibodies to prolactinsecreting cells of human pituitary. Lancet 1975, 2: 97–101.
Unluhizarci K, Bayram F, Colak R, et al. Distinct radiological and clinical appearance of lymphocytic hypophysitis. J Clin Endocrinol Metab 2001, 86: 1861–4.
Iglesias P, Diez JJ. Lymphocytic hypophysitis and diabetes insipidus in non-pregnant women. J Endocrinol Invest 2002, 25: 93–4.
Bellastella A, Bizzarro A, Coronella C, Bellastella G, Sinisi AA, De Bellis A. Lymphocytic hypophysitis: a rare or underestimated disease? Eur J Endocrinol 2003, 149: 363–76.
Ezzat S, Josse RG. Autoimmune hypophysitis. Trends Endocrinol Metab 1997, 8: 74–80.
Stelmach M, O’Day J. Rapid change in visual fields associated with suprasellar lymphocytic hypophysitis. J Clin Neuroophthalmol 1991, 11: 19–24.
Buxton N, Robertson I. Lymphocytic and granulocytic hypophysitis: a single centre experience. Br J Neurosurg 2001, 15: 242–5.
Beressi N, Cohen R, Beressi JP, et al. Pseudotumoral lymphocytic hypophysitis successfully treated by corticosteroid alone: first case report. Neurosurgery 1994, 35: 505.
Flanagan DE, Ibrahim AE, Ellison DW, Armitage M, Gawne-Cain M, Lees PD. Inflammatory hypophysitis — the spectrum of disease. Acta Neurochir (Wien) 2002, 144: 47–56.
Vidal S, Rotondo F, Horvath E, Kovacs K, Scheithauer BW, Vidal S. Immunocytochemical localization of mast cells in lymphocytic hypophysitis. Am J Clin Pathol 2002, 117: 478–83.
Levine S. Allergic adenohypophysitis: new experimental disease of the pituitary gland. Science 1967, 158: 1190–1.
Watanabe K, Tada H, Shimaoka Y, et al. Characteristics of experimental autoimmune hypophysitis in rats: major antigens are growth hormone, thyrotropin, and luteinizing hormone in this model. Autoimmunity 2001, 33: 265–74.
Lecube A, Francisco G, Rodriguez D, et al. Lymphocytic hypophysitis successfully treated with azathioprine: first case report. J Neurol Neurosurg Psychiatry 2003, 74: 1581–3.
Ji JD, Lee SY, Choi SJ, Lee YH, Song GG. Lymphocytic hypophysitis in a patient with systemic lupus erytematosus. Clin Exp Rheumatol 2000, 18: 78–80.
Ruf J, Czarnocka B, DeMicco C, Dutoit C, Ferrand M, Carayon P. Thyroid peroxidase is the organ specific “microsomal” autoantigen involved in thyroid autoimmunity. Acta Endocrinol (Copenh) 1987, 281 (Suppl): 49–56.
Baekkeskov S, Aanstoot HJ, Christgau S, et al. Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase. Nature 1990, 347: 151.
Winqvist O, Karlsson FA, Kämpe O. 21-hydroxylase, a major autoantigen in idiopathic Addison’s disease. Lancet 1992, 339: 1559–62.
Crock PA. Cytosolic autoantigens in lymphocytic hypophysitis. J Clin Endocrinol Metab 1998, 83: 609–18.
O’Dwyer DT, Smith AI, Matthew ML, et al. Identification of the 49-kDa autoantigen associated with lymphocytic hypophysitis as alpha-enolase. J Clin Endocrinol Metab 2002, 87: 752–7.
Kikuchi T, Yabe S, Kanda T, Kobayashi I. Antipituitary antibodies as pathogenic factors in patients with pituitary disorders. Endocr J 2000, 47: 407–16.
Takao T, Nanamiya W, Matsumoto R, Asaba K, Okabayashi T, Hashimoto K. Antipituitary antibodies in patients with lymphocytic hypophysitis. Horm Res 2001, 55: 288–92.
Tanaka S, Tatsumi KI, Kimura M, et al. Detection of autoantibodies against the pituitaryspecific proteins in patients with lymphocytic hypophysitis. Eur J Endocrinol 2002, 147: 767–75.
Strömberg S, Crock P, Lernmark Å, Hulting AL. Pituitary autoantibodies in patients with hypopituitarism and their relatives. J Endocrinol 1998, 157: 475–80.
De Bellis A, Bizzarro A, Conte M, et al. Antipituitary antibodies in adults with apparently idiopathic growth hormone deficiency and in adults with autoimmune endocrine diseases. J Clin Endocrinol Metab 2003, 88: 650–4.
Sugiura M, Hashimoto A, Shizawa M, et al. Heterogeneity of anterior pituitary cell antibodies detected in insulin-dependent diabetes mellitus and adrenocortictropic hormone deficiency. Diabetes Res 1986, 3: 111–4.
Sugiura M, Hashimoto A, Shizawa M, et al. Detection of antibodies to anterior pituitary cell surface membrane with insulin dependent diabetes mellitus and adrenocorticotropic hormone deficiency. Diabetes Res 1987, 4: 63–6.
Sauter NP, Toni R, McLaughlin CD, Dyess EM, Kritzman J, Leuchan RM. Isolated adrenocorticotropin deficiency associated with an autoantibody to a corticotroph antigen that is not adrenocorticotropin or other proopiomelano-cortin-derived peptides. J Clin Endocrinol Metab 1990, 70: 1391–7.
Bensing S, Kasperlik-Zaluska AA, Czarnocka B, Crock PA, Hulting AL. Autoantibodies against pituitary proteins in patients with adrenocorticotropin-deficiency. Eur J Clin Invest 2005, 35: 126–32.
Komatsu M, Kondo T, Yamauchi K, et al. Antipituitary antibodies in patients with the primary empty sella syndrome. J Clin Endocrinol Metab 1988, 67: 633–8.
Rosa P, Hille A, Lee RW, Zanini A, De Camilli P, Huttner WB. Secretogranins I and II: two tyrosine-sulfated secretory proteins common to a variety of cells secreting peptides by the regulated pathway. J Cell Biol 1985, 101: 1999–2011.
Wiedenmann B, Huttner WB. Synaptophysin and chromo granins/secretogranins — widespread constituents of distinct types of neuroendocrine vesicles and new tools in tumor diagnosis. Virchows Arch B Cell Pathol Incl Mol Pathol 1989, 58: 95–121.
Gerdes HH, Rosa P, Phillips E, et al. The primary structure of human secretogranin II, a widespread tyrosine-sulfated secretory granule protein that exhibits low pH and calciuminduced aggregation. J Biol Chem 1989, 264: 12009–15.
Kirchmair R, Hogue-Angeletti R, Gutierrez J, Fischer-Colbrie R, Winkler H. Secretoneurin — a neuropeptide generated in brain, adrenal medulla and other endocrine tissues by proteolytic processing of secretogranin II (Chromogranin C). Neuroscience 1993, 53: 359–65.
Anouar Y, Yon L, Desmoucelles C, et al. Identification of a novel secretogranin II-derived peptide in the adult and fetal adrenal gland. Endocr Res 1998, 24: 731–6.
Vallet VS, Li JY, Duval J. Secretogranin II (SGII) distribution and processing studies in human normal and adenomatous anterior pituitaries using new polyclonal antibodies. Regul Pept 1997, 68: 155–63.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Bensing, S., Hulting, A.L., Höög, A. et al. Lymphocytic hypophysitis: Report of two biopsy-proven cases and one suspected case with pituitary autoantibodies. J Endocrinol Invest 30, 153–162 (2007). https://doi.org/10.1007/BF03347415
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03347415