Adult Combined GH, Prolactin, and TSH Deficiency Associated with Circulating PIT-1 Antibody in Humans

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2010 Dec 3

PMID 21123951

Citations 24

Authors

Masaaki Yamamoto

Genzo Iguchi

Ryoko Takeno

Yasuhiko Okimura

Toshiaki Sano

Michiko Takahashi

Hitoshi Nishizawa

Anastasia Evi Handayaningshi

Hidenori Fukuoka

Maya Tobita

Takatoshi Saitoh

Katsuyoshi Tojo

Atsuko Mokubo

Akio Morinobu

Keiji Iida

Hidesuke Kaji

Susumu Seino

Kazuo Chihara

Yutaka Takahashi

Affiliations

Soon will be listed here.

Abstract

The pituitary-specific transcriptional factor-1 (PIT-1, also known as POU1F1), is an essential factor for multiple hormone-secreting cell types. A genetic defect in the PIT-1 gene results in congenital growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH) deficiency. Here, we investigated 3 cases of adult-onset combined GH, PRL, and TSH deficiencies and found that the endocrinological phenotype in each was linked to autoimmunity directed against the PIT-1 protein. We detected anti-PIT-1 antibody along with various autoantibodies in the patients' sera. An ELISA-based screening revealed that this antibody was highly specific to the disease and absent in control subjects. Immunohistochemical analysis revealed that PIT-1-, GH-, PRL-, and TSH-positive cells were absent in the pituitary of patient 2, who also had a range of autoimmune endocrinopathies. These clinical manifestations were compatible with the definition of autoimmune polyendocrine syndrome (APS). However, the main manifestations of APS-I--hypoparathyroidism and Candida infection--were not observed and the pituitary abnormalities were obviously different from the hypophysitis associated with APS. These data suggest that these patients define a unique "anti-PIT-1 antibody syndrome," related to APS.

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References

Saito T, Tojo K, Kuriyama G, Murakawa Y, Fujimoto K, Taniguchi K . A case of acquired deficiency of pituitary GH, PRL and TSH, associated with type 1 diabetes mellitus. Endocr J. 2004; 51(3):287-93. DOI: 10.1507/endocrj.51.287. View

Nagamine K, Peterson P, Scott H, Kudoh J, Minoshima S, Heino M . Positional cloning of the APECED gene. Nat Genet. 1997; 17(4):393-8. DOI: 10.1038/ng1297-393. View

Pfaffle R, DiMattia G, Parks J, Brown M, Wit J, Jansen M . Mutation of the POU-specific domain of Pit-1 and hypopituitarism without pituitary hypoplasia. Science. 1992; 257(5073):1118-21. DOI: 10.1126/science.257.5073.1118. View

Michels A, Gottlieb P . Autoimmune polyglandular syndromes. Nat Rev Endocrinol. 2010; 6(5):270-7. DOI: 10.1038/nrendo.2010.40. View

Cohen L, Wondisford F, Radovick S . Role of Pit-1 in the gene expression of growth hormone, prolactin, and thyrotropin. Endocrinol Metab Clin North Am. 1996; 25(3):523-40. DOI: 10.1016/s0889-8529(05)70339-x. View

Okimura Y, Howard P, Maurer R . Pit-1 binding sites mediate transcriptional responses to cyclic adenosine 3',5'-monophosphate through a mechanism that does not require inducible phosphorylation of Pit-1. Mol Endocrinol. 1994; 8(11):1559-65. DOI: 10.1210/mend.8.11.7877624. View

Pfaffle R, Martinez R, Kim C, Frisch H, Lebl J, Otten B . GH and TSH deficiency. Exp Clin Endocrinol Diabetes. 1997; 105 Suppl 4:1-5. View

Roux M, Bartke A, Dumont F, Dubois M . Immunohistological study of the anterior pituitary gland - pars distalis and pars intermedia - in dwarf mice. Cell Tissue Res. 1982; 223(2):415-20. DOI: 10.1007/BF01258498. View

Lehuen A, Diana J, Zaccone P, Cooke A . Immune cell crosstalk in type 1 diabetes. Nat Rev Immunol. 2010; 10(7):501-13. DOI: 10.1038/nri2787. View

10.

ODwyer D, Smith A, Matthew M, Andronicos N, Ranson M, Robinson P . Identification of the 49-kDa autoantigen associated with lymphocytic hypophysitis as alpha-enolase. J Clin Endocrinol Metab. 2002; 87(2):752-7. DOI: 10.1210/jcem.87.2.8205. View

11.

Takao T, Nanamiya W, Matsumoto R, Asaba K, Okabayashi T, Hashimoto K . Antipituitary antibodies in patients with lymphocytic hypophysitis. Horm Res. 2002; 55(6):288-92. DOI: 10.1159/000050015. View

12.

Michels A, Eisenbarth G . Autoimmune polyendocrine syndrome type 1 (APS-1) as a model for understanding autoimmune polyendocrine syndrome type 2 (APS-2). J Intern Med. 2009; 265(5):530-40. DOI: 10.1111/j.1365-2796.2009.02091.x. View

13.

Nakanishi K, Kobayashi T, Murase T, Nakatsuji T, Inoko H, Tsuji K . Association of HLA-A24 with complete beta-cell destruction in IDDM. Diabetes. 1993; 42(7):1086-93. DOI: 10.2337/diab.42.7.1086. View

14.

Bensing S, Fetissov S, Mulder J, Perheentupa J, Gustafsson J, Husebye E . Pituitary autoantibodies in autoimmune polyendocrine syndrome type 1. Proc Natl Acad Sci U S A. 2007; 104(3):949-54. PMC: 1783420. DOI: 10.1073/pnas.0610070104. View

15.

Eisenbarth G, Gottlieb P . Autoimmune polyendocrine syndromes. N Engl J Med. 2004; 350(20):2068-79. DOI: 10.1056/NEJMra030158. View

16.

Li S, Crenshaw 3rd E, Rawson E, SIMMONS D, Swanson L, Rosenfeld M . Dwarf locus mutants lacking three pituitary cell types result from mutations in the POU-domain gene pit-1. Nature. 1990; 347(6293):528-33. DOI: 10.1038/347528a0. View

17.

Takahashi Y, Shirono H, Arisaka O, Takahashi K, Yagi T, Koga J . Biologically inactive growth hormone caused by an amino acid substitution. J Clin Invest. 1997; 100(5):1159-65. PMC: 508291. DOI: 10.1172/JCI119627. View

18.

Pfaffle R, Kim C, Otten B, Wit J, Eiholzer U, Heimann G . Pit-1: clinical aspects. Horm Res. 1996; 45 Suppl 1:25-8. DOI: 10.1159/000184824. View

19.

. An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. Nat Genet. 1997; 17(4):399-403. DOI: 10.1038/ng1297-399. View

20.

Kobayashi T, Tamemoto K, Nakanishi K, Kato N, Okubo M, Kajio H . Immunogenetic and clinical characterization of slowly progressive IDDM. Diabetes Care. 1993; 16(5):780-8. DOI: 10.2337/diacare.16.5.780. View