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This version published online on March 6, 2007
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2006-2748
A more recent version of this article appeared on June 1, 2007
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Submitted on December 13, 2006
Accepted on February 26, 2007

Prevalence and functional significance of antipituitary antibodies in patients with autoimmune and non-autoimmune thyroid diseases

Luca Manetti*, Isabella Lupi, Lisa L. Morselli, Sonia Albertini, Mirco Cosottini, Lucia Grasso, Maura Genovesi, Giovanni Pinna, Stefano Mariotti, Fausto Bogazzi, Luigi Bartalena, and Enio Martino

Department of Endocrinology (L.M, I.L., L.L.M., S.A., L.G., M.G., F.B., E.M.), University of Pisa; Departments of Neuroscience (M.C.), University of Pisa; Endocrinology Unit, Department of Medical Sciences "M. Aresu" (G.P, S.M.), San Giovanni di Dio Hospital, University of Cagliari; Department of Clinical Medicine (L.B.), University of Insubria, Italy

* To whom correspondence should be addressed. E-mail: lmanetti{at}endoc.med.unipi.it.

Background: Circulating antipituitary antibodies (APAs) are markers of autoimmune hypophysitis, which may cause deficient pituitary function. The prevalence of APAs in autoimmune thyroid disorders (AITD) is uncertain.

Objectives: The aims of this study were: i) To evaluate APAs prevalence in a large series of patients with AITD and non-autoimmune thyroid disorders (non-AITD); ii) To investigate the functional significance of APAs by assessing pituitary function in APA-positive patients.

Design: Health survey on consecutive AITD and non-AITD patients.

Setting: Tertiary referral center (Department of Endocrinology, Pisa).

Patients: 1290 consecutive patients with thyroid disorders (961 AITD, 329 non-AITD), and 135 controls were enrolled in the study.

Methods: APAs (indirect immunofluorescence), FT4, FT3, TSH, organ-specific autoantibodies were assayed in all patients. Functional pituitary evaluation was performed in most APA-positive patients.

Results: APAs frequency was higher in AITD (11.4%) than in non-AITD (0.9%; p<0.0001) patients; all control subjects had negative APA tests. APAs were more frequently found in Hashimoto's thyroiditis (13%) than in Graves' disease (7.1%; p=0.05). Of 110 APA-positive AITD patients, 20 (18.2%) had autoimmune polyglandular syndrome (APS), while 90 (81.8%) had apparently isolated AITD. APA positivity increased percentage of APS in our series from 10.4% to 13.5%. Of 110 APA-positive patients, 102 were submitted to dynamic testing for functional pituitary assessment: 36 patients (35.2%) had mild or severe growth hormone deficiency (GHD). No additional anterior pituitary hormone deficiencies were found; one patient had central diabetes insipidus. Pituitary abnormalities at MRI were found in most APA-positive GHD patients.

Conclusions: APAs are frequently present in patients with AITD. Patients should be tested for APAs since positive tests are associated with GHD.
Key words: antipituitary antibodies • lymphocytic hypophysitis • autoimmune thyroid disease • nodular thyroid disease • GH deficiency




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