Predictive role of the immunostaining pattern of immunofluorescence and the titers of antipituitary antibodies at presentation for the occurrence of autoimmune hypopituitarism in patients with autoimmune polyendocrine syndromes over a five-year follow-up

Giuseppe Bellastella, Mario Rotondi, Elena Pane, Assunta Dello Iacovo, Barbara Pirali, Liliana Dalla Mora, Alberto Falorni, Antonio Agostino Sinisi, Antonio Bizzarro, Annamaria Colao, Luca Chiovato, Annamaria De Bellis, M. R. Ambrosio, E. Arvat, P. Beck-Peccoz, C. Betterle, S. Cannavò, E. Degli Uberti, R. Giordano, E. GhigoG. Lombardi, M. Maghnie, F. Mantero, L. Persani, A. Spada, F. Santeusanio, M. Delvecchio

Research output: Contribution to journalArticle

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Abstract

Context: Antipituitary antibodies (APA) are frequently present in patients with autoimmune polyendocrine syndrome (APS). Design: The aim was to evaluate the predictive value of APA for the occurrence of hypopituitarism. A total of 149 APA-positive and 50 APA-negative patients with APS and normal pituitary function were longitudinally studied for 5 yr. Methods: APA, by indirect immunofluorescence, and anterior pituitary function were assessed yearly in all patients. The risk for developing autoimmune pituitary dysfunction was calculated using survival and multivariate analysis. Results: Hypopituitarism occurred in 28 of 149 (18.8%) APA-positive patients but in none of the 50 APA-negative patients. The immunostaining pattern in APA-positive patients involved either isolated pituitary cells [type 1 pattern; n = 99 (66.4%)] or all pituitary cells [type 2 pattern; n = 50 (33.6%)]. All patients developing pituitary dysfunction throughout the study span had a type 1 pattern. Kaplan-Meier curves for cumulative survival showed a significantly higher rate for developing hypopituitarism in relation to positive APA tests (P <0.005), pattern of immunostaining (P <0.0001), and APA titers (P <0.000001). Cox regression analysis in APA-positive patients with a type 1 pattern demonstrated a significantly (P <0.0001) higher risk for the onset of hypopituitarism in relation to increasing titers of APA. Conclusions: APA measurement by immunofluorescence may help to predict the occurrence of hypopituitarism but only when considering the immunostaining pattern and their titers. Combined evaluation of these parameters allows identifying patients at higher risk for pituitary autoimmune dysfunction, thus requiring a strict pituitary surveillance to disclose a preclinical phase of hypopituitarism and possibly interrupt therapeutically the progression to clinically overt disease.

Original languageEnglish
Pages (from-to)3750-3757
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume95
Issue number8
DOIs
Publication statusPublished - Aug 2010

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Hypopituitarism
Fluorescent Antibody Technique
Antibodies
Kaplan-Meier Estimate
Indirect Fluorescent Antibody Technique
Survival Analysis
Regression analysis

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

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Predictive role of the immunostaining pattern of immunofluorescence and the titers of antipituitary antibodies at presentation for the occurrence of autoimmune hypopituitarism in patients with autoimmune polyendocrine syndromes over a five-year follow-up. / Bellastella, Giuseppe; Rotondi, Mario; Pane, Elena; Dello Iacovo, Assunta; Pirali, Barbara; Dalla Mora, Liliana; Falorni, Alberto; Sinisi, Antonio Agostino; Bizzarro, Antonio; Colao, Annamaria; Chiovato, Luca; De Bellis, Annamaria; Ambrosio, M. R.; Arvat, E.; Beck-Peccoz, P.; Betterle, C.; Cannavò, S.; Degli Uberti, E.; Giordano, R.; Ghigo, E.; Lombardi, G.; Maghnie, M.; Mantero, F.; Persani, L.; Spada, A.; Santeusanio, F.; Delvecchio, M.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 95, No. 8, 08.2010, p. 3750-3757.

Research output: Contribution to journalArticle

Bellastella, G, Rotondi, M, Pane, E, Dello Iacovo, A, Pirali, B, Dalla Mora, L, Falorni, A, Sinisi, AA, Bizzarro, A, Colao, A, Chiovato, L, De Bellis, A, Ambrosio, MR, Arvat, E, Beck-Peccoz, P, Betterle, C, Cannavò, S, Degli Uberti, E, Giordano, R, Ghigo, E, Lombardi, G, Maghnie, M, Mantero, F, Persani, L, Spada, A, Santeusanio, F & Delvecchio, M 2010, 'Predictive role of the immunostaining pattern of immunofluorescence and the titers of antipituitary antibodies at presentation for the occurrence of autoimmune hypopituitarism in patients with autoimmune polyendocrine syndromes over a five-year follow-up', Journal of Clinical Endocrinology and Metabolism, vol. 95, no. 8, pp. 3750-3757. https://doi.org/10.1210/jc.2010-0551
Bellastella, Giuseppe ; Rotondi, Mario ; Pane, Elena ; Dello Iacovo, Assunta ; Pirali, Barbara ; Dalla Mora, Liliana ; Falorni, Alberto ; Sinisi, Antonio Agostino ; Bizzarro, Antonio ; Colao, Annamaria ; Chiovato, Luca ; De Bellis, Annamaria ; Ambrosio, M. R. ; Arvat, E. ; Beck-Peccoz, P. ; Betterle, C. ; Cannavò, S. ; Degli Uberti, E. ; Giordano, R. ; Ghigo, E. ; Lombardi, G. ; Maghnie, M. ; Mantero, F. ; Persani, L. ; Spada, A. ; Santeusanio, F. ; Delvecchio, M. / Predictive role of the immunostaining pattern of immunofluorescence and the titers of antipituitary antibodies at presentation for the occurrence of autoimmune hypopituitarism in patients with autoimmune polyendocrine syndromes over a five-year follow-up. In: Journal of Clinical Endocrinology and Metabolism. 2010 ; Vol. 95, No. 8. pp. 3750-3757.
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abstract = "Context: Antipituitary antibodies (APA) are frequently present in patients with autoimmune polyendocrine syndrome (APS). Design: The aim was to evaluate the predictive value of APA for the occurrence of hypopituitarism. A total of 149 APA-positive and 50 APA-negative patients with APS and normal pituitary function were longitudinally studied for 5 yr. Methods: APA, by indirect immunofluorescence, and anterior pituitary function were assessed yearly in all patients. The risk for developing autoimmune pituitary dysfunction was calculated using survival and multivariate analysis. Results: Hypopituitarism occurred in 28 of 149 (18.8{\%}) APA-positive patients but in none of the 50 APA-negative patients. The immunostaining pattern in APA-positive patients involved either isolated pituitary cells [type 1 pattern; n = 99 (66.4{\%})] or all pituitary cells [type 2 pattern; n = 50 (33.6{\%})]. All patients developing pituitary dysfunction throughout the study span had a type 1 pattern. Kaplan-Meier curves for cumulative survival showed a significantly higher rate for developing hypopituitarism in relation to positive APA tests (P <0.005), pattern of immunostaining (P <0.0001), and APA titers (P <0.000001). Cox regression analysis in APA-positive patients with a type 1 pattern demonstrated a significantly (P <0.0001) higher risk for the onset of hypopituitarism in relation to increasing titers of APA. Conclusions: APA measurement by immunofluorescence may help to predict the occurrence of hypopituitarism but only when considering the immunostaining pattern and their titers. Combined evaluation of these parameters allows identifying patients at higher risk for pituitary autoimmune dysfunction, thus requiring a strict pituitary surveillance to disclose a preclinical phase of hypopituitarism and possibly interrupt therapeutically the progression to clinically overt disease.",
author = "Giuseppe Bellastella and Mario Rotondi and Elena Pane and {Dello Iacovo}, Assunta and Barbara Pirali and {Dalla Mora}, Liliana and Alberto Falorni and Sinisi, {Antonio Agostino} and Antonio Bizzarro and Annamaria Colao and Luca Chiovato and {De Bellis}, Annamaria and Ambrosio, {M. R.} and E. Arvat and P. Beck-Peccoz and C. Betterle and S. Cannav{\`o} and {Degli Uberti}, E. and R. Giordano and E. Ghigo and G. Lombardi and M. Maghnie and F. Mantero and L. Persani and A. Spada and F. Santeusanio and M. Delvecchio",
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T1 - Predictive role of the immunostaining pattern of immunofluorescence and the titers of antipituitary antibodies at presentation for the occurrence of autoimmune hypopituitarism in patients with autoimmune polyendocrine syndromes over a five-year follow-up

AU - Bellastella, Giuseppe

AU - Rotondi, Mario

AU - Pane, Elena

AU - Dello Iacovo, Assunta

AU - Pirali, Barbara

AU - Dalla Mora, Liliana

AU - Falorni, Alberto

AU - Sinisi, Antonio Agostino

AU - Bizzarro, Antonio

AU - Colao, Annamaria

AU - Chiovato, Luca

AU - De Bellis, Annamaria

AU - Ambrosio, M. R.

AU - Arvat, E.

AU - Beck-Peccoz, P.

AU - Betterle, C.

AU - Cannavò, S.

AU - Degli Uberti, E.

AU - Giordano, R.

AU - Ghigo, E.

AU - Lombardi, G.

AU - Maghnie, M.

AU - Mantero, F.

AU - Persani, L.

AU - Spada, A.

AU - Santeusanio, F.

AU - Delvecchio, M.

PY - 2010/8

Y1 - 2010/8

N2 - Context: Antipituitary antibodies (APA) are frequently present in patients with autoimmune polyendocrine syndrome (APS). Design: The aim was to evaluate the predictive value of APA for the occurrence of hypopituitarism. A total of 149 APA-positive and 50 APA-negative patients with APS and normal pituitary function were longitudinally studied for 5 yr. Methods: APA, by indirect immunofluorescence, and anterior pituitary function were assessed yearly in all patients. The risk for developing autoimmune pituitary dysfunction was calculated using survival and multivariate analysis. Results: Hypopituitarism occurred in 28 of 149 (18.8%) APA-positive patients but in none of the 50 APA-negative patients. The immunostaining pattern in APA-positive patients involved either isolated pituitary cells [type 1 pattern; n = 99 (66.4%)] or all pituitary cells [type 2 pattern; n = 50 (33.6%)]. All patients developing pituitary dysfunction throughout the study span had a type 1 pattern. Kaplan-Meier curves for cumulative survival showed a significantly higher rate for developing hypopituitarism in relation to positive APA tests (P <0.005), pattern of immunostaining (P <0.0001), and APA titers (P <0.000001). Cox regression analysis in APA-positive patients with a type 1 pattern demonstrated a significantly (P <0.0001) higher risk for the onset of hypopituitarism in relation to increasing titers of APA. Conclusions: APA measurement by immunofluorescence may help to predict the occurrence of hypopituitarism but only when considering the immunostaining pattern and their titers. Combined evaluation of these parameters allows identifying patients at higher risk for pituitary autoimmune dysfunction, thus requiring a strict pituitary surveillance to disclose a preclinical phase of hypopituitarism and possibly interrupt therapeutically the progression to clinically overt disease.

AB - Context: Antipituitary antibodies (APA) are frequently present in patients with autoimmune polyendocrine syndrome (APS). Design: The aim was to evaluate the predictive value of APA for the occurrence of hypopituitarism. A total of 149 APA-positive and 50 APA-negative patients with APS and normal pituitary function were longitudinally studied for 5 yr. Methods: APA, by indirect immunofluorescence, and anterior pituitary function were assessed yearly in all patients. The risk for developing autoimmune pituitary dysfunction was calculated using survival and multivariate analysis. Results: Hypopituitarism occurred in 28 of 149 (18.8%) APA-positive patients but in none of the 50 APA-negative patients. The immunostaining pattern in APA-positive patients involved either isolated pituitary cells [type 1 pattern; n = 99 (66.4%)] or all pituitary cells [type 2 pattern; n = 50 (33.6%)]. All patients developing pituitary dysfunction throughout the study span had a type 1 pattern. Kaplan-Meier curves for cumulative survival showed a significantly higher rate for developing hypopituitarism in relation to positive APA tests (P <0.005), pattern of immunostaining (P <0.0001), and APA titers (P <0.000001). Cox regression analysis in APA-positive patients with a type 1 pattern demonstrated a significantly (P <0.0001) higher risk for the onset of hypopituitarism in relation to increasing titers of APA. Conclusions: APA measurement by immunofluorescence may help to predict the occurrence of hypopituitarism but only when considering the immunostaining pattern and their titers. Combined evaluation of these parameters allows identifying patients at higher risk for pituitary autoimmune dysfunction, thus requiring a strict pituitary surveillance to disclose a preclinical phase of hypopituitarism and possibly interrupt therapeutically the progression to clinically overt disease.

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