Skip to main content
SpringerLink
Log in

Lymphocytic panhypophysitis and anti-rabphilin-3A antibody with pulmonary sarcoidosis

  • Published:
Pituitary Aims and scope Submit manuscript

Abstract

Purpose

To explore the clinical significance of anti-rabphillin-3A antibody for the differential diagnosis of lymphocytic panhypophysitis.

Methods and results

A 58-year-old Japanese man developed uveitis of unknown cause in 2017. In 2019, he became aware of polyuria. In August 2020, he noticed transient diplopia and was diagnosed with right abducens nerve palsy. At the same time, he complained of fatigue and loss of appetite. Head magnetic resonance imaging demonstrated enlargement of the pituitary stalk and pituitary gland, corresponding to hypophysitis. Hormone stimulation tests showed blunted responses with respect to all anterior pituitary hormones. Central diabetes insipidus was diagnosed on the basis of a hypertonic saline loading test. Taking these findings together, a diagnosis of panhypopituitarism was made. Computed tomography showed enlargement of hilar lymph nodes. Biopsies of the hilar lymph nodes revealed non-caseating epithelioid cell granulomas that were consistent with sarcoidosis. Biopsy of the anterior pituitary revealed mild lymphocyte infiltration in the absence of IgG4-positive cells, non-caseating granulomas, or neoplasia. Western blotting revealed the presence of anti-rabphilin-3A antibody, supporting a diagnosis of lymphocytic panhypophysitis. Because the patient had no visual impairment or severe uveitis, we continued physiological hormone replacement therapy and topical steroid therapy for the uveitis.

Conclusion

To the best of our knowledge, this is the first case of anti-rabphilin 3A antibody positive lymphocytic panhypophysitis comorbid with sarcoidosis, diagnosed by both pituitary and hilar lymph node biopsy. The utility of anti-rabphilin-3A antibody for the differential diagnosis of hypophysitis like this case should be clarified with further case studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

Not applicable.

Code availability

Not applicable.

References

  1. Caturegli P, Newschaffer C, Olivi A, Pomper MG, Burger PC, Rose NR (2005) Autoimmune hypophysitis. Endocr Rev 26:599–614

    Article  CAS  Google Scholar 

  2. Lupi I, Zhang J, Gutenberg A, Landek-Salgado M, Tzou SC, Mori S, Caturegli P (2011) From pituitary expansion to empty sella: disease progression in a mouse model of autoimmune hypophysitis. Endocrinology 152:4190–4198

    Article  CAS  Google Scholar 

  3. Tzou SC, Lupi I, Landek M, Gutenberg A, Tzou YM, Kimura H, Pinna G, Rose NR, Caturegli P (2008) Autoimmune hypophysitis of SJL mice: clinical insights from a new animal model. Endocrinology 149:3461–3469

    Article  CAS  Google Scholar 

  4. Lupi I, Broman KW, Tzou SC, Gutenberg A, Martino E, Caturegli P (2008) Novel autoantigens in autoimmune hypophysitis. Clin Endocrinol (Oxf) 69:269–278

    Article  CAS  Google Scholar 

  5. Takao T, Nanamiya W, Matsumoto R, Asaba K, Okabayashi T, Hashimoto K (2001) Antipituitary antibodies in patients with lymphocytic hypophysitis. Horm Res 55:288–292

    CAS  PubMed  Google Scholar 

  6. 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 96:1971–1980

    Article  CAS  Google Scholar 

  7. Iwama S, Sugimura Y, Kiyota A, Kato T, Enomoto A, Suzuki H, Iwata N, Takeuchi S, Nakashima K, Takagi H, Izumida H, Ochiai H, Fujisawa H, Suga H, Arima H, Shimoyama Y, Takahashi M, Nishioka H, Ishikawa SE, Shimatsu A, Caturegli P, Oiso Y (2015) Rabphilin-3A as a targeted autoantigen in lymphocytic infundibulo-neurohypophysitis. J Clin Endocrinol Metab 100:E946-954

    Article  CAS  Google Scholar 

  8. Hayashi H, Yamada K, Kuroki T, Katayama M, Shigemori M, Kuramoto S, Nonaka K (1991) Lymphocytic hypophysitis and pulmonary sarcoidosis. Report of a case. Am J Clin Pathol 95:506–511

    Article  CAS  Google Scholar 

  9. Steup-Beekman G, Zweers E (1998) Lymphocytic hypophysitis in a 43-year-old woman. Neth J Med 53:76–79

    Article  CAS  Google Scholar 

  10. Cohen Aubart F, Galanaud D, Haroche J, Psimaras D, Mathian A, Hié M, Le-Thi Huong Boutin D, Charlotte F, Maillart E, Maisonobe T, Amoura Z (2017) Neurosarcoidosis: diagnosis and therapeutic issues. Rev Med Int 38:393–401

    Article  CAS  Google Scholar 

  11. 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 (2015) Diagnosis of primary hypophysitis in Germany. J Clin Endocrinol Metab 100:3841–3849

    Article  CAS  Google Scholar 

  12. Pal R, Rai A, Vaiphei K, Gangadhar P, Gupta P, Mukherjee KK, Singh P, Ray N, Bhansali A, Dutta P (2020) Intracranial germinoma masquerading as secondary granulomatous hypophysitis: a case report and review of literature. Neuroendocrinology 110:422–429

    Article  CAS  Google Scholar 

  13. Morimoto T, Azuma A, Abe S, Usuki J, Kudoh S, Sugisaki K, Oritsu M, Nukiwa T (2008) Epidemiology of sarcoidosis in Japan. Eur Respir J 31:372–379

    Article  CAS  Google Scholar 

  14. Statement on sarcoidosis (1999) Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee. Am J Respir Crit Care Med 160:736–755

    Article  Google Scholar 

  15. Nozaki K, Judson MA (2012) Neurosarcoidosis: clinical manifestations, diagnosis and treatment. Presse Med 41:e331-348

    Article  Google Scholar 

  16. Zajicek JP, Scolding NJ, Foster O, Rovaris M, Evanson J, Moseley IF, Scadding JW, Thompson EJ, Chamoun V, Miller DH, McDonald WI, Mitchell D (1999) Central nervous system sarcoidosis–diagnosis and management. QJM 92:103–117

    Article  CAS  Google Scholar 

  17. Baughman RP, Nagai S, Balter M, Costabel U, Drent M, du Bois R, Grutters JC, Judson MA, Lambiri I, Lower EE, Muller-Quernheim J, Prasse A, Rizzato G, Rottoli P, Spagnolo P, Teirstein A (2011) Defining the clinical outcome status (COS) in sarcoidosis: results of WASOG task FORCE. Sarcoidosis Vasc Diffuse Lung Dis 28:56–64

    CAS  PubMed  Google Scholar 

  18. Anthony J, Esper GJ, Ioachimescu A (2016) Hypothalamic-pituitary sarcoidosis with vision loss and hypopituitarism: case series and literature review. Pituitary 19:19–29

    Article  CAS  Google Scholar 

  19. Christ-Crain M, Bichet DG, Fenske WK, Goldman MB, Rittig S, Verbalis JG, Verkman AS (2019) Diabetes insipidus. Nat Rev Dis Prim 5:54

    Article  Google Scholar 

Download references

Acknowledgements

We thank Mark Cleasby, PhD from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

Funding

The authors did not receive support from any organization for the submitted work.

Author information

Authors and Affiliations

  1. Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo, 060-8638, Japan

    Yuka Takahashi, Hiraku Kameda, Aika Miya, Hiroshi Nomoto, Kyu Yong Cho, Akinobu Nakamura, Hideaki Miyoshi & Tatsuya Atsumi

  2. Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan

    Hiroki Nishimura, Hirokazu Kimura, Masaru Suzuki & Satoshi Konno

  3. Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan

    Ai Shimizu & Yoshihiro Matsuno

  4. Department of Neurosurgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan

    Michinari Okamoto & Hiroaki Motegi

  5. Department of Endocrinology, Diabetes and Metabolism, Fujita Health University, Toyoake, Japan

    Naoko Iwata, Haruki Fujisawa, Atsushi Suzuki & Yoshihisa Sugimura

  6. Division of Diabetes and Obesity, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan

    Hideaki Miyoshi

  7. Department of Endocrinology and Diabetes, Daido Hospital, Nagoya, Japan

    Naoko Iwata

Authors
  1. Yuka Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hiraku Kameda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aika Miya
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hiroshi Nomoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kyu Yong Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Akinobu Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hiroki Nishimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hirokazu Kimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Masaru Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Satoshi Konno
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ai Shimizu
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Yoshihiro Matsuno
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Michinari Okamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Hiroaki Motegi
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Naoko Iwata
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Haruki Fujisawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Atsushi Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Yoshihisa Sugimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Hideaki Miyoshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Tatsuya Atsumi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Not applicable.

Corresponding author

Correspondence to Hiraku Kameda.

Ethics declarations

Conflict of interest

The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent for publication

Written informed consent for publication of their clinical details and clinical images was obtained from the patient.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Takahashi, Y., Kameda, H., Miya, A. et al. Lymphocytic panhypophysitis and anti-rabphilin-3A antibody with pulmonary sarcoidosis. Pituitary 25, 321–327 (2022). https://doi.org/10.1007/s11102-021-01200-0

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11102-021-01200-0

Keywords

Search

Navigation