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

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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 languageUndefined/Unknown
Pages (from-to)E373-E383
JournalJournal of Clinical Endocrinology and Metabolism
Issue number11
Publication statusPublished - 2010

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  • EMC MM-01-39-01

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