Pituitary autoantibodies in endocrine disorders

Abstract: Autoimmune endocrine disorders are characterised by the development of autoantibodies to specific autoantigens in the target organs. Lymphocytic hypophysitis (LyH) is a disease characterised by inflammation of the pituitary gland, often resulting in hypopituitarism. The aetiology of LyH is considered to be autoimmune. However, only a few pituitary autoantigens have so far been identified. Reliable autoantibody markers are requested in the diagnostic procedure of LyH to avoid unnecessary surgical intervention. The aim of this study was to evaluate the occurrence of pituitary autoantibodies in patients with nonadenomatous pituitary disease and also to identify novel pituitary autoantigens. Autoantibodies to human pituitary cytosolic proteins were determined by immunoblotting. Reactivity to a M, 49 000 pituitary autoantigen was significantly more frequent in patients with idiopathic pituitary hormone deficiency (6/21 (28%) p< 0.05) as well as their relatives (10/35 (28%) p<0.02) compared to control subjects (3/44 (6.8%)). The importance of these pituitary autoantibodies as markers for LyH remains to be confirmed. Autoantibodies against human pituitary cytosol and ten additional organspecific autoantigens were measured in sera from 30 patients with empty sella syndrome (ESS). None of the autoantibodies tested was more frequently found in ESS patients compared to healthy controls. Thus, by analysing autoantibodies we did not find evidence of ESS being associated with any autoimmune disease. Autoantibodies to a novel 36-kDa pituitary cytosolic autoantigen were more common in patients with ACTH-deficiency (12/65 (18.5%) compared to control subjects (2/57 3.5%) (p<0.0214). In addition, autoantibodies to thyroglobulin (M) were positively correlated to immunoreactivity against the 36-kDa pituitary autoantigen. A human pituitary cDNA expression library was successfully constructed. Immunoscreening identified secretogranin II as a pituitary autoantigen in a patient with partial pituitary insufficiency and empty sella. By immunohistochemistry, autoantibodies against ACTH and gonadotrophs were detected in sera from patients with autoimmune polyendocrine syndrome type 1 (APS1) and GHdeficiency. Sera from these patients also showed staining of monoamine and GABA nerve terminals in the pituitary intermediate lobe, in agreement with immunoreactivity towards enzymes involved in the biosynthesis of neurotransmittors. By screening of the human pituitary cDNA expression library we identified TDR136 as a major autoantigen in APS 1.