Clinical Characteristics and Therapeutic Responses in Patients with Germ-Line AIP Mutations and Pituitary Adenomas: An International Collaborative Study

AF Daly; MA Tichomirowa; P Petrossians; E Heliovaara; ML Jaffrain-Rea; A Barlier; LA Naves; T Ebeling; A Karhu; A Raappana; L Cazabat; E De Menis; CF Montanana; G Raverot; RJ Weil; T Sane; D Maiter; S.J.C.M.M. Neggers; M Yaneva; A Tabarin; E Verrua; E Eloranta; A Murat; O Vierimaa; PI Salmela; P Emy; RA Toledo; MI Sabate; C Villa; M Popelier; R Salvatori; J Jennings; AF Longas; JIL Aizpun; Marianthi Georgitsi; R Paschke; C Ronchi; M Valimaki; C Saloranta; W.W. de Herder; R Cozzi; M Guitelman; F Magri; MS Lagonigro; G Halaby; V Corman; MT Hagelstein; JF Vanbellinghen; GB Barra; AP Gimenez-Roqueplo; FJ Cameron; F Borson-Chazot; I Holdaway; SPA Toledo; GK Stalla; A Spada; S Zacharieva; J Bertherat; T Brue; V Bours; P Chanson; LA Aaltonen; A Beckers

doi:10.1210/jc.2009-2556

Clinical Characteristics and Therapeutic Responses in Patients with Germ-Line AIP Mutations and Pituitary Adenomas: An International Collaborative Study

AF Daly, MA Tichomirowa, P Petrossians, E Heliovaara, ML Jaffrain-Rea, A Barlier, LA Naves, T Ebeling, A Karhu, A Raappana, L Cazabat, E De Menis, CF Montanana, G Raverot, RJ Weil, T Sane, D Maiter, S.J.C.M.M. Neggers, M Yaneva, A TabarinE Verrua, E Eloranta, A Murat, O Vierimaa, PI Salmela, P Emy, RA Toledo, MI Sabate, C Villa, M Popelier, R Salvatori, J Jennings, AF Longas, JIL Aizpun, Marianthi Georgitsi, R Paschke, C Ronchi, M Valimaki, C Saloranta, W.W. de Herder, R Cozzi, M Guitelman, F Magri, MS Lagonigro, G Halaby, V Corman, MT Hagelstein, JF Vanbellinghen, GB Barra, AP Gimenez-Roqueplo, FJ Cameron, F Borson-Chazot, I Holdaway, SPA Toledo, GK Stalla, A Spada, S Zacharieva, J Bertherat, T Brue, V Bours, P Chanson, LA Aaltonen, A Beckers

Research output: Contribution to journal › Article › Academic › peer-review

268 Citations (Scopus)

Abstract

Context: AIP mutations (AIPmut) give rise to a pituitary adenoma predisposition that occurs in familial isolated pituitary adenomas and less often in sporadic cases. The clinical and therapeutic features of AIPmut-associated pituitary adenomas have not been studied comprehensively. Objective: The objective of the study was to assess clinical/therapeutic characteristics of AIPmut pituitary adenomas. Design: This study was an international, multicenter, retrospective case collection/database analysis. Setting: The study was conducted at 36 tertiary referral endocrine and clinical genetics departments. Patients: Patients included 96 patients with germline AIPmut and pituitary adenomas and 232 matched AIPmut-negative acromegaly controls. Results: The AIPmut population was predominantly young and male (63.5%); first symptoms occurred as children/adolescents in 50%. At diagnosis, most tumors were macroadenomas (93.3%); extension and invasion was common. Somatotropinomas comprised 78.1% of the cohort; there were also prolactinomas (n = 13), nonsecreting adenomas (n = 7), and a TSH-secreting adenoma. AIPmut somatotropinomas were larger (P = 0.00026), with higher GH levels (P = 0.00068), more frequent extension (P = 0.018) and prolactin cosecretion (P = 0.00023), and occurred 2 decades before controls (P < 0.000001). Gigantism was more common in the AIPmut group (P < 0.000001). AIPmut somatotropinoma patients underwent more surgical interventions (P = 0.00069) and had lower decreases in GH (P = 0.00037) and IGF-I (P = 0.028) and less tumor shrinkage with somatostatin analogs (P < 0.00001) vs. controls. AIPmut prolactinomas occurred generally in young males and frequently required surgery or radiotherapy. Conclusions: AIPmut pituitary adenomas have clinical features that may negatively impact treatment efficacy. Predisposition for aggressive disease in young patients, often in a familial setting, suggests that earlier diagnosis of AIPmut pituitary adenomas may have clinical utility. (J Clin Endocrinol Metab 95: E373-E383, 2010)

Original language	Undefined/Unknown
Pages (from-to)	E373-E383
Journal	Journal of Clinical Endocrinology and Metabolism
Volume	95
Issue number	11
DOIs	https://doi.org/10.1210/jc.2009-2556
Publication status	Published - 2010

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10.1210/jc.2009-2556

http://hdl.handle.net/1765/21584

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Daly, AF., Tichomirowa, MA., Petrossians, P., Heliovaara, E., Jaffrain-Rea, ML., Barlier, A., Naves, LA., Ebeling, T., Karhu, A., Raappana, A., Cazabat, L., De Menis, E., Montanana, CF., Raverot, G., Weil, RJ., Sane, T., Maiter, D., Neggers, S. J. C. M. M., Yaneva, M., ... Beckers, A. (2010). Clinical Characteristics and Therapeutic Responses in Patients with Germ-Line AIP Mutations and Pituitary Adenomas: An International Collaborative Study. Journal of Clinical Endocrinology and Metabolism, 95(11), E373-E383. https://doi.org/10.1210/jc.2009-2556

@article{98567a3e626048f694193c0dbffe7ba1,

title = "Clinical Characteristics and Therapeutic Responses in Patients with Germ-Line AIP Mutations and Pituitary Adenomas: An International Collaborative Study",

abstract = "Context: AIP mutations (AIPmut) give rise to a pituitary adenoma predisposition that occurs in familial isolated pituitary adenomas and less often in sporadic cases. The clinical and therapeutic features of AIPmut-associated pituitary adenomas have not been studied comprehensively. Objective: The objective of the study was to assess clinical/therapeutic characteristics of AIPmut pituitary adenomas. Design: This study was an international, multicenter, retrospective case collection/database analysis. Setting: The study was conducted at 36 tertiary referral endocrine and clinical genetics departments. Patients: Patients included 96 patients with germline AIPmut and pituitary adenomas and 232 matched AIPmut-negative acromegaly controls. Results: The AIPmut population was predominantly young and male (63.5%); first symptoms occurred as children/adolescents in 50%. At diagnosis, most tumors were macroadenomas (93.3%); extension and invasion was common. Somatotropinomas comprised 78.1% of the cohort; there were also prolactinomas (n = 13), nonsecreting adenomas (n = 7), and a TSH-secreting adenoma. AIPmut somatotropinomas were larger (P = 0.00026), with higher GH levels (P = 0.00068), more frequent extension (P = 0.018) and prolactin cosecretion (P = 0.00023), and occurred 2 decades before controls (P < 0.000001). Gigantism was more common in the AIPmut group (P < 0.000001). AIPmut somatotropinoma patients underwent more surgical interventions (P = 0.00069) and had lower decreases in GH (P = 0.00037) and IGF-I (P = 0.028) and less tumor shrinkage with somatostatin analogs (P < 0.00001) vs. controls. AIPmut prolactinomas occurred generally in young males and frequently required surgery or radiotherapy. Conclusions: AIPmut pituitary adenomas have clinical features that may negatively impact treatment efficacy. Predisposition for aggressive disease in young patients, often in a familial setting, suggests that earlier diagnosis of AIPmut pituitary adenomas may have clinical utility. (J Clin Endocrinol Metab 95: E373-E383, 2010)",

author = "AF Daly and MA Tichomirowa and P Petrossians and E Heliovaara and ML Jaffrain-Rea and A Barlier and LA Naves and T Ebeling and A Karhu and A Raappana and L Cazabat and {De Menis}, E and CF Montanana and G Raverot and RJ Weil and T Sane and D Maiter and S.J.C.M.M. Neggers and M Yaneva and A Tabarin and E Verrua and E Eloranta and A Murat and O Vierimaa and PI Salmela and P Emy and RA Toledo and MI Sabate and C Villa and M Popelier and R Salvatori and J Jennings and AF Longas and JIL Aizpun and Marianthi Georgitsi and R Paschke and C Ronchi and M Valimaki and C Saloranta and {de Herder}, W.W. and R Cozzi and M Guitelman and F Magri and MS Lagonigro and G Halaby and V Corman and MT Hagelstein and JF Vanbellinghen and GB Barra and AP Gimenez-Roqueplo and FJ Cameron and F Borson-Chazot and I Holdaway and SPA Toledo and GK Stalla and A Spada and S Zacharieva and J Bertherat and T Brue and V Bours and P Chanson and LA Aaltonen and A Beckers",

year = "2010",

doi = "10.1210/jc.2009-2556",

language = "Undefined/Unknown",

volume = "95",

pages = "E373--E383",

journal = "Journal of Clinical Endocrinology and Metabolism",

issn = "0021-972X",

publisher = "Endocrine Society",

number = "11",

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Daly, AF, Tichomirowa, MA, Petrossians, P, Heliovaara, E, Jaffrain-Rea, ML, Barlier, A, Naves, LA, Ebeling, T, Karhu, A, Raappana, A, Cazabat, L, De Menis, E, Montanana, CF, Raverot, G, Weil, RJ, Sane, T, Maiter, D, Neggers, SJCMM, Yaneva, M, Tabarin, A, Verrua, E, Eloranta, E, Murat, A, Vierimaa, O, Salmela, PI, Emy, P, Toledo, RA, Sabate, MI, Villa, C, Popelier, M, Salvatori, R, Jennings, J, Longas, AF, Aizpun, JIL, Georgitsi, M, Paschke, R, Ronchi, C, Valimaki, M, Saloranta, C, de Herder, WW, Cozzi, R, Guitelman, M, Magri, F, Lagonigro, MS, Halaby, G, Corman, V, Hagelstein, MT, Vanbellinghen, JF, Barra, GB, Gimenez-Roqueplo, AP, Cameron, FJ, Borson-Chazot, F, Holdaway, I, Toledo, SPA, Stalla, GK, Spada, A, Zacharieva, S, Bertherat, J, Brue, T, Bours, V, Chanson, P, Aaltonen, LA & Beckers, A 2010, 'Clinical Characteristics and Therapeutic Responses in Patients with Germ-Line AIP Mutations and Pituitary Adenomas: An International Collaborative Study', Journal of Clinical Endocrinology and Metabolism, vol. 95, no. 11, pp. E373-E383. https://doi.org/10.1210/jc.2009-2556

Clinical Characteristics and Therapeutic Responses in Patients with Germ-Line AIP Mutations and Pituitary Adenomas: An International Collaborative Study. / Daly, AF; Tichomirowa, MA; Petrossians, P et al.
In: Journal of Clinical Endocrinology and Metabolism, Vol. 95, No. 11, 2010, p. E373-E383.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Clinical Characteristics and Therapeutic Responses in Patients with Germ-Line AIP Mutations and Pituitary Adenomas: An International Collaborative Study

AU - Daly, AF

AU - Tichomirowa, MA

AU - Petrossians, P

AU - Heliovaara, E

AU - Jaffrain-Rea, ML

AU - Barlier, A

AU - Naves, LA

AU - Ebeling, T

AU - Karhu, A

AU - Raappana, A

AU - Cazabat, L

AU - De Menis, E

AU - Montanana, CF

AU - Raverot, G

AU - Weil, RJ

AU - Sane, T

AU - Maiter, D

AU - Neggers, S.J.C.M.M.

AU - Yaneva, M

AU - Tabarin, A

AU - Verrua, E

AU - Eloranta, E

AU - Murat, A

AU - Vierimaa, O

AU - Salmela, PI

AU - Emy, P

AU - Toledo, RA

AU - Sabate, MI

AU - Villa, C

AU - Popelier, M

AU - Salvatori, R

AU - Jennings, J

AU - Longas, AF

AU - Aizpun, JIL

AU - Georgitsi, Marianthi

AU - Paschke, R

AU - Ronchi, C

AU - Valimaki, M

AU - Saloranta, C

AU - de Herder, W.W.

AU - Cozzi, R

AU - Guitelman, M

AU - Magri, F

AU - Lagonigro, MS

AU - Halaby, G

AU - Corman, V

AU - Hagelstein, MT

AU - Vanbellinghen, JF

AU - Barra, GB

AU - Gimenez-Roqueplo, AP

AU - Cameron, FJ

AU - Borson-Chazot, F

AU - Holdaway, I

AU - Toledo, SPA

AU - Stalla, GK

AU - Spada, A

AU - Zacharieva, S

AU - Bertherat, J

AU - Brue, T

AU - Bours, V

AU - Chanson, P

AU - Aaltonen, LA

AU - Beckers, A

PY - 2010

Y1 - 2010

N2 - Context: AIP mutations (AIPmut) give rise to a pituitary adenoma predisposition that occurs in familial isolated pituitary adenomas and less often in sporadic cases. The clinical and therapeutic features of AIPmut-associated pituitary adenomas have not been studied comprehensively. Objective: The objective of the study was to assess clinical/therapeutic characteristics of AIPmut pituitary adenomas. Design: This study was an international, multicenter, retrospective case collection/database analysis. Setting: The study was conducted at 36 tertiary referral endocrine and clinical genetics departments. Patients: Patients included 96 patients with germline AIPmut and pituitary adenomas and 232 matched AIPmut-negative acromegaly controls. Results: The AIPmut population was predominantly young and male (63.5%); first symptoms occurred as children/adolescents in 50%. At diagnosis, most tumors were macroadenomas (93.3%); extension and invasion was common. Somatotropinomas comprised 78.1% of the cohort; there were also prolactinomas (n = 13), nonsecreting adenomas (n = 7), and a TSH-secreting adenoma. AIPmut somatotropinomas were larger (P = 0.00026), with higher GH levels (P = 0.00068), more frequent extension (P = 0.018) and prolactin cosecretion (P = 0.00023), and occurred 2 decades before controls (P < 0.000001). Gigantism was more common in the AIPmut group (P < 0.000001). AIPmut somatotropinoma patients underwent more surgical interventions (P = 0.00069) and had lower decreases in GH (P = 0.00037) and IGF-I (P = 0.028) and less tumor shrinkage with somatostatin analogs (P < 0.00001) vs. controls. AIPmut prolactinomas occurred generally in young males and frequently required surgery or radiotherapy. Conclusions: AIPmut pituitary adenomas have clinical features that may negatively impact treatment efficacy. Predisposition for aggressive disease in young patients, often in a familial setting, suggests that earlier diagnosis of AIPmut pituitary adenomas may have clinical utility. (J Clin Endocrinol Metab 95: E373-E383, 2010)

AB - Context: AIP mutations (AIPmut) give rise to a pituitary adenoma predisposition that occurs in familial isolated pituitary adenomas and less often in sporadic cases. The clinical and therapeutic features of AIPmut-associated pituitary adenomas have not been studied comprehensively. Objective: The objective of the study was to assess clinical/therapeutic characteristics of AIPmut pituitary adenomas. Design: This study was an international, multicenter, retrospective case collection/database analysis. Setting: The study was conducted at 36 tertiary referral endocrine and clinical genetics departments. Patients: Patients included 96 patients with germline AIPmut and pituitary adenomas and 232 matched AIPmut-negative acromegaly controls. Results: The AIPmut population was predominantly young and male (63.5%); first symptoms occurred as children/adolescents in 50%. At diagnosis, most tumors were macroadenomas (93.3%); extension and invasion was common. Somatotropinomas comprised 78.1% of the cohort; there were also prolactinomas (n = 13), nonsecreting adenomas (n = 7), and a TSH-secreting adenoma. AIPmut somatotropinomas were larger (P = 0.00026), with higher GH levels (P = 0.00068), more frequent extension (P = 0.018) and prolactin cosecretion (P = 0.00023), and occurred 2 decades before controls (P < 0.000001). Gigantism was more common in the AIPmut group (P < 0.000001). AIPmut somatotropinoma patients underwent more surgical interventions (P = 0.00069) and had lower decreases in GH (P = 0.00037) and IGF-I (P = 0.028) and less tumor shrinkage with somatostatin analogs (P < 0.00001) vs. controls. AIPmut prolactinomas occurred generally in young males and frequently required surgery or radiotherapy. Conclusions: AIPmut pituitary adenomas have clinical features that may negatively impact treatment efficacy. Predisposition for aggressive disease in young patients, often in a familial setting, suggests that earlier diagnosis of AIPmut pituitary adenomas may have clinical utility. (J Clin Endocrinol Metab 95: E373-E383, 2010)

U2 - 10.1210/jc.2009-2556

DO - 10.1210/jc.2009-2556

M3 - Article

SN - 0021-972X

VL - 95

SP - E373-E383

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 11

ER -