Necessity of Multimodal Treatment of Acromegaly and Outcomes

Diane Mary Donegan, MB, Bch; Nicole Iñiguez-Ariza, MD; Anu Sharma, MD; Todd Nippoldt, MD; William Young, MD; Jamie Van Gompel, MD; John Atkinson; Fredric Meyer, MD; Bruce Pollock, MD; Neena Natt, MD; Nadia Laack, MD; Dana Erickson, MD

Disclosures

Endocr Pract. 2018;24(7):668-676. 

In This Article

Abstract and Introduction

Abstract

Objective: Uncontrolled acromegaly is associated with increased morbidity and mortality. Despite multimodal therapeutic options, adequate control can be challenging and lead to prolonged exposure to growth hormone excess. The aim of this study was to assess treatment patterns and outcomes in patients with acromegaly following surgery at a single institution.

Methods: A retrospective analysis of response to treatment modalities for patients with a new diagnosis of acromegaly at the Mayo Clinic in Rochester, Minnesota, from 1995–2015.

Results: A total of 245 patients with newly diagnosed acromegaly (mean age at diagnosis, 47 ± 14 years; mean follow-up, 5.5 ± 5 years) were evaluated. Primary surgical intervention was performed in 236 patients; 117 (54%) did not achieve remission. Among those with ≥3 months follow-up, 76/217 (35%) patients required three or more forms of treatment. Mean tumor size at diagnosis was 1.6 ± 0.8 cm (80% macroadenomas), and 35% (75/217) had cavernous sinus invasion on pre-operative imaging. The most common second-line treatment was radiation treatment (RT) (50%, 59/117). Among those with persistent disease following surgery, a normal insulin-like growth factor 1 (IGF-1) was achieved in 52% (61/117), with a median time to acromegaly control of 4.5 years. The rate of IGF-1 normalization was 2.1-fold higher in those who received RT compared to those who did not.

Conclusion: In patients with persistent acromegaly following surgery, multiple treatment modalities, including RT, may be required to achieve remission. Treatment outcome uncertainty and the need for multiple interventions add to the disease burden associated with persistent acromegaly.

Introduction

Acromegaly is a rare disease caused by excess growth hormone (GH) production, most commonly as a result of a GH-secreting pituitary tumor. Excess GH and consequently elevated insulin-like growth factor (IGF)-1 are associated with significant morbidity, reduced quality of life, and premature mortality.[1–3] Many studies have demonstrated that normalization of GH and/or IGF-1 is associated with a reduction in mortality similar to that of the general population.[4–9]

Surgery is recommended as first-line treatment in the majority of patients with acromegaly,[10] as it offers the highest rates of remission with a rapid reduction in GH concentration. The overall remission rate is reported to be between 34 and 85%,[11] with greatest surgical success in smaller tumors confined to the sella. In addition, reported recurrence occurs in 0.4 to 13.8% of patients, depending on the criteria used for remission.[2,12–14] Therefore, additional treatment modalities such as medical therapy, radiation treatment (RT), or repeat surgery are often required.

Adequate control of persistent acromegaly can be very challenging.[15–17] This may be due to limited access to treatment options (due to logistic or economic reasons), or historical data may underestimate rates of remission/disease control due to advances in radiotherapy and medical treatment. In addition, definitive outcome predictors of various therapeutic options in clinical practice with the goal of safe individualized treatment plans are sparse. Studies reporting on longitudinal and necessary stepwise multimodality treatment in patients with acromegaly as seen from a patient's perspective are few.[18] Hence, in the current study, we sought to assess treatment patterns and outcomes in patients with acromegaly at a single institution with access to all available modes of treatment.

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