No Evidence for Autoimmunity as a Major Cause of the Empty Sella Syndrome

Abstract

Objective: The cause of empty sella syndrome (ESS) remains largely unknown. We measured eleven organ-specific autoantibodies in serum in order to evaluate possible autoimmune components in ESS.

Patients: Thirty patients with ESS and 50 healthy blood donors participated in the study.

Measurements: Detection of pituitary autoantibodies was performed by immunoblotting with human pituitary cytosol as antigen. Thyroid peroxidase (TPO) and TSH receptor (TRAK) autoantibodies were analysed by radioimmunoassay. The remaining eight autoantibodies were detected by in vitro transcription and translation of the autoantigens and immunoprecipitation.

Results: The majority of the ESS patients (18/30) exhibited no immunoreactivity at all. None of the remaining 12 ESS patients reacted against more than one autoantigen. No immunoreactivity was found more frequently among ESS patients than healthy blood donors. Pituitary autoantibodies were not correlated to the ESS patients' pituitary function or sellar size, although the results indicated a tendency of increased autoimmunity in patients with hypopituitarism and normal sella size respectively.

Conclusion: Detection of autoantibodies is a valuable tool in the diagnostic work-up of autoimmune diseases. By analysing a large number of organ-specific autoantibodies we found no evidence of ESS being associated with any specific autoimmune disease. The pathogenesis of ESS is believed to be heterogeneous and our findings suggest autoimmune components to be of minor importance. In some selective cases, ESS in combination with hypopituitarism may be the result of an autoimmune disease in the pituitary gland but this needs further investigation.

Key words

Empty sella syndrome - autoimmunity - autoantibodies

References

• 1 Asa S L, Bilbao J M, Kovacs K, Josse R G, Kreines K. Lymphocytic hypophysitis of pregnancy resulting in hypopituitarism: a distinct clinicopathologic entity.  Ann Intern Med. 1981;  95 166-171
• 2 Beressi N, Beressi J P, Cohen R, Modigliani E. Lymphocytic hypophysitis: a review of 145 cases.  Ann Med Interne. 1999;  150 327-341
• 3 Betterle C, Volpato M, Pedini B, Chen S, Smith B R, Furmaniak J. Adrenal-cortex autoantibodies and steroid-producing cells autoantibodies in patients with Addison's disease: comparison of immunofluorescence and immunoprecipitation assays.  J Clin Endocrinol Metab. 1999;  84 618-622
• 4 Bjerre P, Lindholm J, Videbaek H. The spontaneous course of pituitary adenomas and occurrence of an empty sella in untreated acromegaly.  J Clin Endocrinol Metab. 1986;  63 287-291
• 5 Brismar K, Efendic S. Pituitary function in the empty sella syndrome.  Neuroendocrinology. 1981;  32 70-77
• 6 Brismar K, Bergstrand G. CSF circulation in subjects with the empty sella syndrome.  Neuroradiology. 1981;  21 167-175
• 7 Buchfelder M, Brockmeier S, Pichl J, Schrell U, Fahlbusch R. Results of dynamic endocrine testing of hypothalamic pituitary function in patients with a primary “empty” sella syndrome.  Horm Metab Res. 1989;  21 573-576
• 8 Crock P, Salvi M, Miller A, Wall J, Guyda H. Detection of anti-pituitary autoantibodies by immunoblotting.  J Immunol Methods. 1993;  162 31-40
• 9 Crock P A. Cytosolic autoantigens in lymphocytic hypophysitis.  J Clin Endocrinol Metabol. 1998;  83 609-618
• 10 De Bellis A, Bizzarro A, Di Martino S, Savastano S, Sinisi A A, Lombardi G, Bellastella A. Association of arginine vasopressin-secreting cell, steroid-secreting cell, adrenal and islet cell antibodies in a patient presenting with central diabetes insipidus, empty sella, subclinical adrenocortical failure and impaired glucose tolerance.  Horm Res. 1995;  44 142-146
• 11 Di Chiro G, Nelson K B. The volume of the sella turcica.  Am J Roentgenol. 1962;  87 989-1008
• 12 Ekwall O, Hedstrand H, Haavik J, Perheentupa J, Betterle C, Gustafsson J, Husebye E, Rorsman F, Kämpe O. Pteridine dependent hydroxylases as autoantigens in autoimmune polyendocrine syndrome type 1.  J Clin Endocrinol Metab. 2000;  85 2944-2950
• 13 Falorni A, Örtqvist E, Persson B, Lernmark Å. Radioimmunoassay for glutamic acid decarboxylase (GAD65) and GAD65 autoantibodies using ³⁵S or ³H recombinant human ligands.  J Immunol Methods. 1995;  186 89-99
• 14 Gallardo E, Schächter D, Caceres E, Becker P, Colin E, Martinez C, Henriques C. The empty sella: results of treatment in 76 successive cases and high frequency of endocrine and neurological disturbances.  Clin Endocrinol. 1992;  37 529-533
• 15 Goudie R B, Pinkerton P H. Anterior hypophysitis and Hashimoto's disease in a young woman.  J Pathol Bacteriol. 1962;  83 584-585
• 16 Husebye E S, Gebre-Medhin G, Tuomi T, Perheentupa J, Landin-Olsson M, Gustafsson J, Rorsman F, Kämpe O. Autoantibodies against aromatic L-amino acid decarboxylase in autoimmune polyendocrine syndrome type 1.  J Clin Endocrinol Metab. 1997;  82 147-150
• 17 Keda Y M, Krjukova I V, Ilovaiskaia I A, Morozova M S, Fofanova O V, Babarina M B, Marova E I, Pankov Y A, Kandror V I. Antibodies to pituitary surface antigens during various pituitary disease states.  J Endocrinol. 2002;  175 417-423
• 18 Komatsu M, Kondo T, Yamauchi K, Yokokawa N, Ichikawa K, Ishihara M, Aizawa T, Yamada T, Imai Y, Tanaka K, Taniguchi K, Watanabe T, Takahashi Y. Antipituitary antibodies in patients with the primary empty sella syndrome.  J Clin Endocrinol Metab. 1988;  67 633-638
• 19 Mau M, Phillips T M, Ratner R E. Presence of anti-pituitary hormone antibodies in patients with empty sella syndrome and pituitary tumours.  Clin Endocrinol. 1993;  38 495-500
• 20 O'Dwyer D T, Smith A I, Matthew M L, Andronicos N M, Ranson M, Robinson P J, Crock P A. Identification of the 49-kda autoantigen associated with lymphocytic hypophysitis as alpha-enolase.  J Clin Endocrinol Metab. 2002;  87 752-757
• 21 Strömberg S, Crock P, Lernmark Å, Hulting A L. Pituitary autoantibodies in patients with hypopituitarism and their relatives.  J Endocrinol. 1998;  157 475-480
• 22 Wakai S, Fukushima T, Teramoto A, Sano K. Pituitary apoplexy: its incidence and clinical significance.  J Neurosurg. 1981;  55 187-193
• 23 Ward L, Paquette J, Seidman E, Huot C, Alvarez F, Crock P, Delvin E, Kämpe O, Deal C. Severe autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy in an adolescent girl with a novel AIRE mutation: response to immunosuppressive therapy.  J Clin Endocrinol Metab. 1999;  84 844-852
• 24 Winqvist O, Karlsson F A, Kämpe O. 21-hydroxylase, a major autoantigen in idiopathic Addison's disease.  Lancet. 1992;  339 1559-1562