Adult combined GH, prolactin, and TSH deficiency associated with circulating PIT-1 antibody in humans.
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.
Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Masaaki
M
Yamamoto
Genzo
G
Iguchi
Ryoko
R
Takeno
Yasuhiko
Y
Okimura
Toshiaki
T
Sano
Michiko
M
Takahashi
Hitoshi
H
Nishizawa
Anastasia Evi
AE
Handayaningshi
Hidenori
H
Fukuoka
Maya
M
Tobita
Takatoshi
T
Saitoh
Katsuyoshi
K
Tojo
Atsuko
A
Mokubo
Akio
A
Morinobu
Keiji
K
Iida
Hidesuke
H
Kaji
Susumu
S
Seino
Kazuo
K
Chihara
Yutaka
Y
Takahashi
D000328:Adult; D000368:Aged; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood*; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D010902:Pituitary Gland / Q000378:metabolism; D016884:Polyendocrinopathies, Autoimmune / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D011388:Prolactin / Q000172:deficiency*; D013972:Thyrotropin / Q000172:deficiency*; D050817:Transcription Factor Pit-1 / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000276:immunology*
D001323:Autoantibodies; C494187:POU1F1 protein, human; D050817:Transcription Factor Pit-1; D019382:Human Growth Hormone; D011388:Prolactin; D013972:Thyrotropin