Surgical and Pharmacological Outcomes in Acromegaly

Real-Life Data From the Mexican Acromegaly Registry

Moisés Mercado; Coralys Abreu; Alma Vergara-López; Baldomero González-Virla; Ana-Laura Espinosa-de-los-Monteros; Ernesto Sosa-Eroza; Diego Cadena-Obando; Daniel Cuevas-Ramos; Lesly A. Portocarrero-Ortiz; Sara-Patricia Pérez-Reyes; Abraham Mercado-Cherem; Raúl Ibarra-Salce; Juan O. Talavera

Disclosures

J Clin Endocrinol Metab. 2020;105(12) 

In This Article

Abstract and Introduction

Abstract

Context: Acromegaly registries constitute a valuable source of therapeutic outcome information in real-life.

Objective: The objective of this work is to analyze surgical and pharmacological outcomes in the Mexican Acromegaly Registry (MAR).

Design and Methods: Data were extracted from the MAR informatic platform. Surgical remission was defined by a postoperative postglucose (GH) of less than 1 ng/mL and an insulin-like growth factor 1 (IGF-1) of less than 1.2 × upper limit of normal (ULN). Pharmacological remission was defined by a basal GH of less than 1 ng/mL and an IGF-1 of less than 1.2 × ULN.

Results: A total of 650 surgical outcomes were analyzed (94.6% transsphenoidal). Surgical remission was achieved in 40.15%, whereas 44.15% remained biochemically active. Persistently active disease after surgery was significantly associated with harboring an invasive macroadenoma, a basal GH of greater than 10 ng/mL, and/or an IGF-1 of greater than 2 × ULN at diagnosis on bivariate and multivariate analysis. The outcome of monotherapy with first-generation somatostatin analogs (SSAs) was evaluated in 267 patients (adjunctive in 65%), of whom 28.4% achieved remission. Persistently active disease was significantly associated with harboring an invasive macroadenoma as well as with pretreatment basal GH and IGF-1 levels of greater than 10 ng/mL and greater than 2 × ULN, respectively, on bivariate and multivariate analysis. Combined therapy with SSA and cabergoline was analyzed in 100 patients, of whom 19% achieved remission and 44% remained active; in this subset of patients, only a pretreatment IGF-1 of greater than 2 × ULN was significantly associated with persistent disease activity.

Conclusion: Surgical and pharmacological outcomes in acromegaly are highly dependent on tumor size/invasiveness as well as on the degree of hypersomatotropinemia.

Introduction

Acromegaly is a chronic and systemic disease caused in the vast majority of cases by a growth hormone (GH)-secreting pituitary adenoma.[1] Although currently the long-term outlook for patients suffering from this disease has improved along with the refinement of pituitary surgery and radiation techniques, as well as the use of pharmacological therapies, active acromegaly is still associated with significant morbidity and mortality from neoplastic and cardiovascular causes.[2,3] The primary treatment of choice of acromegaly is transsphenoidal resection of the GH-secreting adenoma.[4,5] The outcome of transsphenoidal surgery (TSS) varies according to the surgeon's expertise, with remission rates of more than 70% for microadenomas or macroadenomas confined to the sella turcica, 40% to 50% for noninvasive macroadenomas, and less than 20% for invasive macroadenomas.[4,5] Although pharmacological therapy with somatostatin analogs (SSAs) and to a lesser extent with the GH receptor antagonist pegvisomant, is increasingly being used primarily, it is still regarded as a secondary or adjunctive treatment in patients with persistent disease activity after pituitary surgery.[6] Cabergoline (CBG) as monotherapy or added to ongoing SSA treatment is another treatment alternative.[7] The safety and efficacy of the first-generation SSAs have repeatedly been proven in numerous controlled, prospective clinical trials, and although the majority of patients report significant clinical improvement, achievement of stringent biochemical goals (basal GH < 1 ng/mL and the normalization of insulin-like growth factor 1 [IGF-1]) occurs in 25% to 40% of patients.[8,9] Response to pharmacological therapy, out of the context of such controlled trials is perhaps a better reflection of what occurs in "real-life," everyday practice.[10] As with other low-prevalence conditions, most of what we know about the epidemiology, clinical behavior, and outcome of the different therapeutic strategies derives from national registries and to a lesser extent from large, singlecenter studies.[11]

Despite the heterogeneity of the information found in national registries, these studies provide a realistic, country-specific picture of the epidemiological and clinical behavior of the disease as well as of the outcome of the different therapeutic strategies.[11] The Mexican Acromegaly Registry (MAR) is one of the world's largest databases of the disease, with more than 2700 patients registered from more than 20 centers distributed throughout the whole Mexican territory.[12] In the present report we aim to evaluate the long-term outcome of the pharmacological and surgical treatment of a large subset of acromegaly patients enrolled in this MAR.

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