Predictors of therapeutic failure in GH and prolactin co-secreting pituitary adenomas.

IF 2.8 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Endocrine Connections Pub Date : 2025-07-15 Print Date: 2025-07-01 DOI:10.1530/EC-25-0103

Marta Araujo-Castro, Betina Biagetti, Edelmiro Menéndez, Iría Novoa-Testa, Fernando Cordido, Víctor Rodríguez Berrocal, Eider Pascual-Corrales, Fernando Guerrero-Pérez, Almudena Vicente, Rogelio García-Centeno, Laura González, María Dolores Ollero García, Ana Irigaray Echarri, María Dolores Moure Rodríguez, Cristina Novo-Rodríguez, María Calatayud, Rocío Villar-Taibo, Ignacio Bernabéu, Cristina Alvarez-Escola, Carmen Tenorio Jimenéz, Pablo Abellán-Galiana, Eva Venegas, Inmaculada González-Molero, Pedro Iglesias, Concepción Blanco, Fernando Vidal-Ostos De Lara, María Paz de Miguel Novoa, Elena López-Mezquita Torres, Felicia Hanzu, Cristina Lamas, Silvia Aznar Rodríguez, Anna Aulinas, José María Recio, María Dolores Aviles-Pérez, Miguel Antonio Sampedro Núñez, Rosa Camara, Miguel Paja Fano, Carmen Fajardo, Luís Cardoso, Pedro Marques, Elena Martínez-Sáez, Ignacio Ruz-Caracuel, Mónica Marazuela, Manel Puig-Domingo

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引用次数: 0

Abstract

Aim: To evaluate which factors are associated with a higher probability of failure to surgical and first-generation somatostatin receptor ligands (fgSRLs) treatment in patients with growth hormone and prolactin co-secreting pituitary adenomas (GH&PRL-PAs).

Methods: Acromegaly patients with GH&PRL-PAs included in the ACRO-SPAIN study were enrolled. GH&PRL-PAs were defined as tumors with serum PRL levels above the upper limit of normal and positive immunostaining for GH and PRL, or with PRL levels ≥100 ng/mL when immunostaining data were not available.

Results: A total of 126 acromegaly patients with GH&PRL-PAs who underwent transsphenoidal pituitary surgery were included, and 42.1% (n = 53) were biochemically cured at the immediate postoperative evaluation. Knosp grade >2 (odds ratio (OR) 3.48, 95% CI 1.28-9.38), higher serum GH (OR 1.01, 95% CI 1.01-1.08) and IGF-1 (OR 1.60, 95% CI 1.05-2.45) levels were associated with a lower probability of surgical cure. Sixty-eight patients received first-line medical therapy as follows: fgSRLs in monotherapy (n = 22), fgSRL plus cabergoline (n = 37), cabergoline in monotherapy (n = 7) and pegvisomant in monotherapy (n = 2). Among the cases treated with fgSRL in monotherapy, 18.2% (n = 4/22) were resistant. We identified as predictors of fgSRL resistance (in monotherapy and combined with cabergoline) a Knosp grade >2 (OR 8.75, P = 0.003), high GH levels at acromegaly diagnosis (OR 1.02, P = 0.031) and higher postoperative GH levels (OR 1.05, P = 0.006), but no predictors of response to fgSRL in monotherapy were identified.

Conclusion: The clinical predictors of surgical failure and of fgSRL resistance in patients with GH&PRL-PAs are similar to those described in acromegaly without PRL, co-secretion.

Significance statement: In this article focused on GH&PRL pituitary adenomas, we found that a Knosp grade >2, and higher serum GH and IGF-1 levels were associated with a lower probability of surgical cure in these tumors. Regarding the response to fgSRL in monotherapy, 18% of the patients with GH&PRL pituitary adenomas were classified as resistant. Knosp grade >2 (OR 8.75, P = 0.003), high GH levels at acromegaly diagnosis (OR 1.02, P = 0.031), and higher postoperative GH levels (OR 1.05, P = 0.006) were predictors of non-response to fgSRL (monotherapy or combined with cabergoline), while no predictors of response to fgSRL in monotherapy were identified. Thus, we concluded the clinical predictors of surgical failure and of fgSRL resistance in patients with GH&PRL-PAs are similar to those described in acromegaly without PRL co-secretion.

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共同分泌GH和催乳素垂体腺瘤治疗失败的预测因素。

目的：评估哪些因素与生长激素和催乳素共分泌垂体腺瘤（GH+PRL-PAs）患者手术失败和第一代生长抑素受体配体（fgsrl）治疗失败的可能性较高相关。方法：纳入ACRO-SPAIN研究中GH+PRL-PAs肢端肥大患者。GH+PRL- pas定义为血清PRL水平高于GH和PRL免疫染色正常和阳性上限或在免疫染色数据不可用时PRL水平≥100ng/mL的肿瘤。结果：共纳入126例GH+PRL- pas肢端肥大患者，其中42.1% （n=53）在术后立即评估时生化治愈。Knosp分级bbb2（比值比[OR] 3.48, 95%CI 1.28-9.38）、较高的血清GH （OR 1.01, 95%CI 1.01-1.08）和IGF-1 （OR 1.60, 95%CI 1.05-2.45）水平与手术治愈的可能性较低相关。68例患者接受了以下一线药物治疗：fgSRL单药治疗（n=22）、fgSRL联合卡麦角林（n=37）、卡麦角林单药治疗（n=7）和pegvisomant单药治疗（n=2）。在单药fgSRL治疗的病例中，18.2% （n=4/22）耐药。我们发现Knosp分级>2 （OR 8.75， P=0.003）、肢端肥大症诊断时的高GH水平（OR 1.02， P=0.031）和术后较高的GH水平（OR 1.05， P=0.006）是fgSRL耐药性（单药治疗和卡麦角林联合治疗）的预测因素，但未发现单药治疗中fgSRL反应的预测因素。结论：GH+PRL- pas患者手术失败和fgsrl抵抗的临床预测因素与无PRL共分泌肢端肥大患者相似。

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来源期刊

Endocrine Connections Medicine-Internal Medicine

CiteScore

5.00

自引率

3.40%

发文量

361

审稿时长

6 weeks

期刊介绍： Endocrine Connections publishes original quality research and reviews in all areas of endocrinology, including papers that deal with non-classical tissues as source or targets of hormones and endocrine papers that have relevance to endocrine-related and intersecting disciplines and the wider biomedical community.