Lymphocytic hypophysitis was first recognized postmortem, then by biop
sy, but detection of antipituitary autoantibodies by immunofluorescenc
e has proved unsatisfactory. Immunoblotting has the dual advantages of
increased specificity and identification of the mol wt of autoantigen
s. Sera from 115 patients and 52 normal subjects were immunoblotted ag
ainst human autopsy pituitary cytosolic proteins. Among the neurosurgi
cal cohort (30), 10 patients had biopsy-proven lymphocytic hypophysiti
s, and 20 had hypopituitarism secondary to tumor. There were 22 cases
with suspected hypophysitis; 47 with either Hashimoto's, Graves', or A
ddison's diseases; and 15 with rheumatoid arthritis. Antipituitary aut
oantibodies reactive to a 49-kDa pituitary cytosolic protein were foun
d in 70% of biopsy-proven lymphocytic hypophysitis, 55% of suspected h
ypophysitis, 42% of Addison's disease, 20% of pituitary tumors, 15% of
patients with thyroid autoimmunity, 13% of rheumatoid arthritis patie
nts, and 9.8% of normal subjects. Reactivity to a 40-kDa cytosolic pro
tein was also found in 50% of patients with biopsy-proven disease. The
se 49- and 40-kDa autoantigens are conserved across species and are no
t exclusive to pituitary tissue. Immunoblotting has demonstrated antip
ituitary autoantibodies to 49- and 40-kDa cytosolic proteins in biopsy
-proven cases of lymphocytic hypophysitis.