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
Dr. Sophie Bensing
Department of Molecular Medicine M1 : 02
Karolinska Institutet · Karolinska Hospital
17176 Stockholm
Sweden
Phone: + 46851773085
Fax: + 46 8 51 77 54 49
Email: Sophie.Bensing@molmed.ki.se