Masses of the pituitary gland (sellar masses) are common, representing approximately 15% of all intracranial masses. About half of the sellar masses are caused by a hormone-secreting adenoma and more easily diagnosed because of classical signs and symptoms. The remaining sellar masses, however, do not secrete any hormone (32% are non-functioning pituitary adenomas, and 10% are non-adenomatous lesions), and are therefore more difficult to differentiate. Often their diagnosis is established only after transsphenoidal surgery and pathological examination. Among the group of non-functioning pituitary masses, autoimmune (lymphocytic) hypophysitis is the only disease that has an immune pathogenesis. The pituitary autoantigens targeted in hypophysitis remain unknown. If discovered, they can lead to the development of a serum test useful to distinguish hypophysitis from the other non-functioning pituitary masses. This distinction is critical for patient care: in fact, hypophysitis can be usually managed medically, whereas the other conditions typically require surgery. The proposal reports our human and mouse studies aimed to discover the pituitary autoantigens and therefore develop an antibody-based serologic test for the differential diagnosis of non-functioning pituitary masses.

Public Health Relevance

Pituitary masses are common. Because most of them do not secrete any pituitary hormone, they can often be diagnosed only after surgery and pathological examination. Autoimmune hypophysitis is the only disease entity among the non-functioning pituitary masses that has an immune pathogenesis. This grant is designed to develop an antibody- based serologic test to aid in the differential diagnosis of these common conditions. Such test could avoid unnecessary pituitary surgeries to patients with autoimmune hypophysitis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DK080351-01A1
Application #
7629887
Study Section
Special Emphasis Panel (ZRG1-EMNR-A (02))
Program Officer
Malozowski, Saul N
Project Start
2009-05-10
Project End
2011-04-30
Budget Start
2009-05-10
Budget End
2010-04-30
Support Year
1
Fiscal Year
2009
Total Cost
$205,000
Indirect Cost
Name
Johns Hopkins University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Iwama, Shintaro; Sugimura, Yoshihisa; Kiyota, Atsushi et al. (2015) Rabphilin-3A as a Targeted Autoantigen in Lymphocytic Infundibulo-neurohypophysitis. J Clin Endocrinol Metab 100:E946-54
De Remigis, Alessandra; de Gruijl, Tanja D; Uram, Jennifer N et al. (2015) Development of thyroglobulin antibodies after GVAX immunotherapy is associated with prolonged survival. Int J Cancer 136:127-37
Ricciuti, Adriana; De Remigis, Alessandra; Landek-Salgado, Melissa A et al. (2014) Detection of pituitary antibodies by immunofluorescence: approach and results in patients with pituitary diseases. J Clin Endocrinol Metab 99:1758-66
Iwama, Shintaro; De Remigis, Alessandra; Callahan, Margaret K et al. (2014) Pituitary expression of CTLA-4 mediates hypophysitis secondary to administration of CTLA-4 blocking antibody. Sci Transl Med 6:230ra45
Bose, Vivek; Caturegli, Patrizio; Conrad, Jens et al. (2013) Use of a clinicoradiological score to determine the presurgical diagnosis of autoimmune hypophysitis in a teenage girl. J Neurosurg Pediatr 11:335-9
Iwama, Shintaro; Welt, Corrine K; Romero, Christopher J et al. (2013) Isolated prolactin deficiency associated with serum autoantibodies against prolactin-secreting cells. J Clin Endocrinol Metab 98:3920-5
Gutenberg, Angelika; Caturegli, Patrizio; Metz, Imke et al. (2012) Necrotizing infundibulo-hypophysitis: an entity too rare to be true? Pituitary 15:202-8
Guaraldi, Federica; Caturegli, Patrizio; Salvatori, Roberto (2012) Prevalence of antipituitary antibodies in acromegaly. Pituitary 15:490-4
Landek-Salgado, M A; Leporati, P; Lupi, I et al. (2012) Growth hormone and proopiomelanocortin are targeted by autoantibodies in a patient with biopsy-proven IgG4-related hypophysitis. Pituitary 15:412-9
Landek-Salgado, Melissa A; Rose, Noel R; Caturegli, Patrizio (2012) Placenta suppresses experimental autoimmune hypophysitis through soluble TNF receptor 1. J Autoimmun 38:J88-96

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