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Casey Jo Anne Smith, Sophie Bensing, Christine Burns, Phillip J Robinson, Anna A Kasperlik-Zaluska, Rodney J Scott, Olle Kämpe and Patricia A Crock

Background

Lymphocytic hypophysitis is an organ-specific autoimmune disease of the pituitary gland. A specific and sensitive serological test currently does not exist to aid in the diagnosis.

Objective

To identify target autoantigens in lymphocytic hypophysitis and develop a diagnostic assay for these proteins.

Design/methods

A pituitary cDNA expression library was immunoscreened using sera from four patients with lymphocytic hypophysitis. Relevant cDNA clones from screening, along with previously identified autoantigens pituitary gland-specific factor 1a and 2 (PGSF1a and PGSF2) and neuron-specific enolase (NSE) were tested in an in vitro transcription and translation immunoprecipitation assay. The corticotroph-specific transcription factor, TPIT, was investigated separately as a candidate autoantigen.

Results

Significantly positive autoantibody reactivity against TPIT was found in 9/86 hypophysitis patients vs 1/90 controls (P=0.018). The reactivity against TPIT was not specific for lymphocytic hypophysitis with autoantibodies detectable in the sera from patients with other autoimmune endocrine diseases. Autoantibodies were also detected against chromodomain-helicase-DNA binding protein 8, presynaptic cytomatrix protein (piccolo), Ca2 +-dependent secretion activator, PGSF2 and NSE in serum samples from patients with lymphocytic hypophysitis, but at a frequency that did not differ from healthy controls. Importantly, 8/86 patients with lymphocytic hypophysitis had autoantibodies against any two autoantigens in comparison with 0/90 controls (P=0.0093).

Conclusions

TPIT, a corticotroph-specific transcription factor, was identified as a target autoantigen in 10.5% of patients with lymphocytic hypophysitis. Further autoantigens related to vesicle processing were also identified as potential autoantigens with different immunoreactivity patterns in patients and controls.

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Patricia A. Crock, Richard G. Pestell, Anthony J. Calenti, Eric J. Gilford, J. Keith Henderson, James D. Best and Frank P. Alford

Abstract. Pre-operative bilateral simultaneous inferior petrosal sinus sampling with assessment of ACTH levels in the left and right sinuses and the periphery was performed in 9 patients with pituitary dependent Cushing's disease who were subsequently found at surgery to have basophil microadenomata. The novel observation of this study was the pattern of secretion of other pituitary hormones so that significant inter-sinus gradients ≥ 1.4:1 were seen for β-endorphin (2.8 ± 1.3, mean ± sem), PRL (4.2 ± 1.3) and GH (6.9 ± 2.4) as well as for ACTH (5.1 ± 1.1). There was no inter-sinus gradient for LH, FSH and TSH. In these 9 patients with adenomata, the correlations between the inter-sinus gradients for ACTH and β-endorphin were r = 0.95 (P <0.01), ACTH and PRL r = 0.90 (P < 0.01) and for ACTH and GH r = 0.89 (P <0.05). This close association between the gradients for ACTH and other anterior pituitary hormones could be due either to cosecretion of β-endorphin, PRL and GH by the ACTH-producing pituitary adenomata or to a paracrine effect of β-endorphin from the tumours on adjacent pituitary tissue. By reflecting the central pituitary hormone milieu, petrosal sinus sampling can give information about pituitary function unobtainable from peripheral hormone levels.