Download PDF
Horm Metab Res 2018; 50(04): 296-302
DOI: 10.1055/s-0044-101036
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Clinical, Endocrine and Imaging Characteristics of Patients with Primary Hypophysitis

Anna Angelousi
1   Department of Pathophysiology, Endocrine Oncology Unit, Laiko Hospital, National and Kapodistrian University of Athens, Greece
,
Carolina Cohen
2   Division of Endocrinology, Hospital de Clínicas, University of Buenos Aires, Argentina
,
Soledad Sosa
2   Division of Endocrinology, Hospital de Clínicas, University of Buenos Aires, Argentina
,
Karina Danilowicz
2   Division of Endocrinology, Hospital de Clínicas, University of Buenos Aires, Argentina
,
Lina Papanastasiou
3   Department of Endocrinology and Diabetes Center, “G. Gennimatas”, General Hospital of Athens, Athens Greece
,
Marina Tsoli
1   Department of Pathophysiology, Endocrine Oncology Unit, Laiko Hospital, National and Kapodistrian University of Athens, Greece
,
Aparna Pal
4   Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
,
Georgios Piaditis
3   Department of Endocrinology and Diabetes Center, “G. Gennimatas”, General Hospital of Athens, Athens Greece
,
Ashley Grossman
4   Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
,
Gregory Kaltsas
1   Department of Pathophysiology, Endocrine Oncology Unit, Laiko Hospital, National and Kapodistrian University of Athens, Greece
› Author Affiliations
Further Information

Publication History

received 15 November 2017

accepted 09 January 2018

Publication Date:
19 February 2018 (online)

Also available at
    Permissions and Reprints

Abstract

Primary hypophysitis (PH) is a rare disease with a poorly-defined natural history. Our aim was to characterise patients with PH at presentation and during prolonged follow-up. Observational retrospective study of 22 patients was conducted from 3 centres. In 14 patients, PH was confirmed histologically and in the remaining 8 clinically, after excluding secondary causes of hypophysitis. All patients had hormonal and imaging investigations before any treatment. Median follow up was 48 months (25–75%: 3–60). There was a female predominance with a female/male ratio: 3.4:1. Eight out of 22 patients had another autoimmune disease. Headaches and gonadal dysfunction were the most common symptoms. Five patients presented with panhypopituitarism; 17 patients had anterior pituitary deficiency, and 7 had diabetes insipidus. At presentation, 9 patients were treated surgically, 5 received replacement hormonal treatment, and 8 high-dose glucocorticoids from whom 5 in association with other immunosuppressive agents. Six patients showed complete recovery of pituitary hormonal deficiencies while 6 showed a partial recovery during a 5-year follow-up period. No difference was found between patients treated with surgery and those treated medically. The overall relapse rate was 18%. PH can be manifested with a broad spectrum of clinical and hormonal disturbances. Long-term follow-up is required to define the natural history of the disease and response to treatment, since pituitary hormonal recovery or relapse may appear many years after initial diagnosis. We suggest that surgery and immunosuppressive therapy be reserved for exceptional cases.

Key words

pituitary - hypophysitis - autoimmunity - glucocorticoids
 

  • References

  • 1 Bellastella G, Maiorino MI, Bizzarro A, Giugliano D, Esposito K, Bellastella A, De Bellis A. Revisitation of autoimmune hypophysitis: knowledge and uncertainties on pathophysiological and clinical aspects. Pituitary 2016; 19: 625-642
    CrossrefPubMedGoogle Scholar
  • 2 Fukuoka H. Hypophysitis. Endocrinol Metab Clin North Am 2015; 44: 143-149
    CrossrefPubMedGoogle Scholar
  • 3 De Bellis A, Bellastella G, Colella C, Bizzarro A, Bellastella A, Esposito K. Use of serum pituitary antibodies to improve the diagnosis of hypophysitis. Exp Rev Endocrinol Metab 2014; 9: 465-476
    PubMedGoogle Scholar
  • 4 Falorni A, Minarelli V, Bartoloni E, Alunno A, Gerli R. Diagnosis and classification of autoimmune hypophysitis. Autoimmun Rev 2014; 13: 412-416
    CrossrefPubMedGoogle Scholar
  • 5 Takao T, Nanamiya W, Matsumoto R, Asaba K, Okabayashi T, Hashimoto K. Antipituitary antibodies in patients with lymphocytic hypophysitis. Horm Res 2001; 55: 288-292
    CrossrefPubMedGoogle Scholar
  • 6 Caturegli P, Lupi I, Landek-Salgado M, Kimura H, Rose NR. Pituitary autoimmunity: 30 years later. Autoimmun Rev 2008; 7: 631-637
    CrossrefPubMedGoogle Scholar
  • 7 Crock PA. Cytosolic autoantigens in lymphocytic hypophysitis. J Clin Endocrinol Metab 1998; 83: 609-618
    PubMedGoogle Scholar
  • 8 O'Dwyer DT, Smith AI, Matthew ML, Andronicos NM, Ranson M, Robinson PJ, Crock PA. Identification of the 49-kDa autoantigen associated with lymphocytic hypophysitis as alpha-enolase. J Clin Endocrinol Metab 2002; 87: 752-757
    PubMedGoogle Scholar
  • 9 Caturegli P, Newschaffer C, Olivi A, Pomper MG, Burger PC, Rose NR. Autoimmune hypophysitis. Endocr Rev 2005; 26: 599-614
    CrossrefPubMedGoogle Scholar
  • 10 Sautner D, Saeger W, Ludecke DK, Jansen V, Puchner MJ. Hypophysitis in surgical and autoptical specimens. Acta Neuropathol (Berl) 1995; 90: 637-644
    CrossrefPubMedGoogle Scholar
  • 11 Leung GK, Lopes MB, Thorner MO, Vance ML, Laws Jr. ER. Primary hypophysitis: a single-center experience in 16 cases. J Neurosurg 2004; 101: 262-271
    CrossrefPubMedGoogle Scholar
  • 12 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: 363-376
    CrossrefPubMedGoogle Scholar
  • 13 Lecube A, Francisco G, Rodríguez D, Ortega A, Codina A, Hernández C, Simó R. Lymphocytic hypophysitis successfully treated with azathioprine: first case report. J Neurol Neurosurg Psychiatry 2003; 74: 1581-1583
    CrossrefPubMedGoogle Scholar
  • 14 Papanastasiou L, Pappa T, Tsiavos V, Tseniklidi E, Androulakis I, Kontogeorgos G, Piaditis G. Azathioprine as an alternative treatment in primary hypophysitis. Pituitary 2011; 14: 16-22
    CrossrefPubMedGoogle Scholar
  • 15 Schreckinger M, Francis T, Rajah G, Jagannathan J, Guthikonda M, Mittal S. Novel strategy to treat a case of recurrent lymphocytic hypophysitis using rituximab. J Neurosurg 2012; 116: 1318-1323
    CrossrefPubMedGoogle Scholar
  • 16 Imber BS, Lee HS, Kunwar S, Blevins LS, Aghi MK. Hypophysitis: a single-center case series. Pituitary 2015; 18: 630-641
    CrossrefPubMedGoogle Scholar
  • 17 Khare S, Jagtap VS, Budyal SR, Kasaliwal R, Kakade HR, Bukan A, Sankhe S. LilaAR Bandgar T, Menon PS, Shah NS. Primary (autoimmune) hypophysitis: a single centre experience. Pituitary 2015; 18: 16-22
    CrossrefPubMedGoogle Scholar
  • 18 Chiloiro S, Tartaglione T, Angelini F, Bianchi A, Arena V, Giampietro A, Mormando M, Sciandra M, Laino ME, De Marinis L. An overview of diagnosis of primary autoimmune hypophysitis in a prospective single-center experience. Neuroendocrinology 2017; 104: 280-290
    CrossrefPubMedGoogle Scholar
  • 19 Muhsin SA, Mount DB. Diagnosis and treatment of hypernatremia. Best Pract Res Clin Endocrinol Metab 2016; 30: 189-203
    CrossrefPubMedGoogle Scholar
  • 20 Gutenberg A, Larsen J, Lupi I, Rohde V, Caturegli P. A radiologic score to distinguish autoimmune hypophysitis from nonsecreting pituitary adenoma preoperatively. Am J Neuroradiol 2009; 30: 1766-1772
    CrossrefPubMedGoogle Scholar
  • 21 Asa SL, Bilbao JM, Kovacs K, Josse RG, Kreines K. Lymphocytic hypophysitis of pregnancy resulting in hypopituitarism: A distinct clinicopathologic entity. Ann Intern Med 1981; 95: 166-171
    CrossrefPubMedGoogle Scholar
  • 22 Pouplard-Barthelaix A, Lepinard V, Luxembourger L, Rohmer V, Berthelot J, Bigorgne JC. Circulating pituitary autoantibodies against cells secreting luteinising and follicle stimulating hormones in children with cryptorchidism. Lancet 1984; 2: 631-632
    PubMedGoogle Scholar
  • 23 Elias KA, Weiner RI. Direct arterial vascularization of estro- gen-induced prolactin-secreting anterior pituitary tumors. Proc Natl Acad Sci U S A 1984; 81: 4549-4553
    CrossrefPubMedGoogle Scholar
  • 24 Lin HH, Gutenberg A, Chen TY, Tsai NM, Lee CJ, Cheng YC, Cheng WH, Tzou YM, Caturegli P, Tzou SC. In situ activation of pituitary-infiltrating t lymphocytes in autoimmune hypophysitis. Sci Rep 2017; 7: 434-492
    CrossrefPubMedGoogle Scholar
  • 25 Molitch ME, Gillam MP. Lymphocytic hypophysitis. Horm Res 2007; 68: 145-150
    PubMedGoogle Scholar
  • 26 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
    CrossrefPubMedGoogle Scholar
  • 27 Wang S, Wang L, Yao Y, Feng F, Yang H, Liang Z, Deng K, You H, Sun J, Xing B, Jin Z, Wang R, Pan H, Zhu H. Primary lymphocytic hypophysitis: Clinical characteristics and treatment of 50 cases in a single centre in China over 18 years. Clin Endocrinol (Oxf) 2017; 87: 177-184
    CrossrefPubMedGoogle Scholar
  • 28 Abe T. Lymphocytic infundibulo-neurohypophysitis and infundibulo-panhypophysitis regarded as lymphocytic hypophysitis variant. Brain Tumor Pathol 2008; 25: 59-66
    CrossrefPubMedGoogle Scholar
  • 29 McCutcheon IE, Oldfield EH. Lymphocytic adenohypophysitis presenting as infertility. Case report. J Neurosurg 1991; 74: 821-826
    CrossrefPubMedGoogle Scholar
  • 30 Guaraldi F, Giordano R, Grottoli S, Ghizzoni L, Arvat E, Ghigo E. Pituitary Autoimmunity. Front Horm Res 2017; 48: 48-68
    PubMedGoogle Scholar
  • 31 Lupi I, Cosottini M, Caturegli P, Manetti L, Urbani C, Cappellani D, Scattina I, Martino E, Marcocci C, Bogazzi F. Diabetes insipidus is an unfavorable prognostic factor for response to glucocorticoids in patients with autoimmune hypophysitis. Eur J Endocrinol 2017; 177: 127-135
    CrossrefPubMedGoogle Scholar
  • 32 Wada Y, Hamamoto Y, Nakamura Y, Honjo S, Kawasaki Y, Ikeda H, Takahashi J, Yuba Y, Shimatsu A, Koshiyama H. Lymphocytic anhypophysitis: its clinical features. Jpn Clin Med 2011; 2: 15-20
    PubMedGoogle Scholar
  • 33 Patel MC, Guneratne N, Haq N, West TE, Weetman AP, Clayton RN. Peripartum hypo- pituitarism and lymphocytic hypophysitis. QJM 1995; 88: 571-580
    PubMedGoogle Scholar
  • 34 Bayram F, Kelestimur F, Ozturk F, Selcuklu A, Patiroglu TE, Beyhan Z. Lymphocytic hypophysitis in a patient with Graves' disease. J Endocrinol Invest 1982; 21: 193-197
    PubMedGoogle Scholar
  • 35 Sobrinho-Simoes M, Brandao A, Paiva ME, Vilela B, Fernandes E, Carneiro-Chaves F. Lymphoid hypophysitis in a patient with lymphoid thyroiditis, lymphoid adrenalitis, and idiopathic retroperitoneal fibrosis. Arch Pathol Lab Med 1985; 109: 230-233
    PubMedGoogle Scholar
  • 36 Piñol V, Cubiella J, Navasa M, Fernández J, Halperin I, Bruguera M, Rodés J. Autoimmune hepatitis associated with thyroiditis and hypophysitis. A case report. Gastroenterol Hepatol 2000; 23: 123-125
    PubMedGoogle Scholar
  • 37 Ward L, Paquette J, Seidman E, Huot C, Alvarez F, Crock P, Delvin E, Kämpe O, Deal C. Severe autoimmune polyendocrinopathy– candidiasis–ectodermal dystrophy in an adolescent girl with a novel AIRE mutation: responsive to immunosuppressive therapy. J Clin Endocrinol Metab 1999; 84: 844-852
    PubMedGoogle Scholar
  • 38 Imura H, Nakao K, Shimatsu A, Ogawa Y, Sando T, Fujisawa I, Yamabe H. Lymphocytic infundibuloneurohypophysitis as a case of central diabetes insipidus. N Engl J Med 1993; 329: 683-689
    CrossrefPubMedGoogle Scholar
  • 39 Gutenberg A, Hans V, Puchner MJA, Kreutzer J, Bruck W, Caturegli P, Buchfelder M. Primary hypophysitis: clinical-pathological correlations. European J Endocrinol 2006; 155: 101-107
    CrossrefPubMedGoogle Scholar
  • 40 Honegger J, Buchfelder M, Schlaffer S, Droste M, Werner S, Strasburger C, Störmann S, Schopohl J, Kacheva S, Deutschbein T, Stalla G, Flitsch J, Milian M, Petersenn S, Elbelt U. Pituitary Working Group of the German Society of Endocrinology . Treatment of Primary Hypophysitis in Germany. J Clin Endocrinol Metab. 2015; 100: 3460-3469
    CrossrefPubMedGoogle Scholar
  • 41 Joshi MN, Whitelaw BC, Palomar MT, Wu Y, Carroll PV. Immune checkpoint inhibitor-related hypophysitis and endocrine dysfunction: clinical review. Clin Endocrinol (Oxf) 2016; 85: 331-339
    CrossrefPubMedGoogle Scholar
  • 42 Iwama S, De Remigis A, Callahan MK, Slovin SF, Wolchok JD, Caturegli P. Pituitary expression of CTLA-4 mediates hypophysitis secondary to administration of CTLA-4 blocking antibody. Sci Transl Med 2014; 6: 230
    PubMedGoogle Scholar
  • 43 Bernreuther C, Illies C, Flitsch J, Buchfelder M, Buslei R, Glatzel M, Saeger W. IgG4-related hypophysitis is highly prevalent among cases of histologically confirmed hypophysitis. Brain Pathol 2017; 27: 839-845
    CrossrefPubMedGoogle Scholar
  • 44 Iwata N, Iwama S, Sugimura Y, Yasuda Y, Nakashima K, Takeuchi S, Hagiwara D, Ito Y, Suga H, Goto M, Banno R, Caturegli P, Koike T, Oshida Y, Arima H. Anti-pituitary antibodies against corticotrophs in IgG4-related hypophysitis. Pituitary 2017; 20: 301-310
    CrossrefPubMedGoogle Scholar
  • 45 Gu WJ, Zhang Q, Zhu J, Li J, Wei SH, Mu YM. Rituximab was used to treat recurrent IgG4-related hypophysitis with ophthalmopathy as the initial presentation: A case report and literature review. Medicine (Baltimore) 2017; 96: 6934
    CrossrefPubMedGoogle Scholar