Biochemical Control in Acromegaly With Multimodality Therapies: Outcomes From a Pituitary Center and Changes Over Time

Abstract

Purpose: To determine the prevalence of insulin-like growth factor-1 (IGF-1) normalization with long-term multimodality therapy in a pituitary center and to assess changes over time.

Methods: Patients with acromegaly (N = 409), with ≥1 year of data after surgery and at least 2 subsequent clinic visits were included in long-term analysis (N = 266). Biochemical data, clinical characteristics, and therapeutic interventions were reviewed retrospectively.

Results: At diagnosis, mean [standard deviation] age was 43.4 [14.3] years, body mass index was 28.5 (24.9-32.1) kg/m2 (median, interquartile range), serum IGF-1 index (IGF-1 level/upper limit of normal) was 2.3 [1.7-3.1], and 80.5% had macroadenomas. Patients with transsphenoidal surgery after 2006 were older [46.6 ± 14.3 vs 40.0 ± 13.4 years; P < 0.001]. Age and tumor size correlated inversely. Overall (N = 266), 93.2% achieved a normal IGF-1 level during 9.9 [5.0-15.0] years with multimodality therapy. The interval to first normal IGF-1 level following failed surgical remission was shorter after 2006: 14.0 (95% confidence interval, 10.0-20.0) versus 27.5 (22.0-36.0) months (P = 0.002). Radiation therapy and second surgery were rarer after 2006: 28 (22%) versus 62 (47.0%); P < 0.001 and 12 (9.4%) versus 28 (21.2%); P = 0.010, respectively. Age at diagnosis increased over time periods, possibly reflecting increased detection of acromegaly in older patients with milder disease. Male gender, older age, smaller tumor and lower IGF-1 index at diagnosis predicted long-term sustained IGF-1 control after surgery without adjuvant therapies.

Conclusion: The vast majority of patients with acromegaly can be biochemically controlled with multimodality therapy in the current era. Radiotherapy and repeat pituitary surgery became less frequently utilized over time. Long-term postoperative IGF-1 control without use of adjuvant therapies has improved.

Keywords: Acromegaly; IGF-1; medical therapy; pituitary center; pituitary surgery; radiation therapy.

Figure 1.

Flow diagram of study inclusion criteria included symptoms and signs of acromegaly, pituitary adenoma on magnetic resonance imaging, biochemical confirmation of acromegaly and pathological confirmation in patients who had surgery. *Exclusion criteria included less than 2 follow-up visits and/or less than 1 year of follow-up after initial therapy

Figure 2.

Clinical characteristics and age of diagnosis.Tumor size was defined as maximal diameter (cm) on magnetic resonance imaging at time of diagnosis. Age groups shown include quartiles 1 through 4 corresponding to age Q₁ (0–33), Q₂ (34–43), Q₃ (44–54), Q₄ (≥55) years old, respectively. A. Tumor size and age of diagnosis for all the patients (N = 325), *P < 0.001 B. Tumor size and age of diagnosis in women (N = 178), *P = 0.004, **P = 0.002. C. Tumor size and age of diagnosis in men (N = 147) (no significant difference between groups).

Figure 3.

Time to first normal IGF-1 after surgery in patients who did not achieve normal IGF-1 after surgery. IGF-1, insulin-like growth factor-1.

Figure 4.

Predictors of sustained postoperative normalization of IGF-1. IGF-1, insulin-like growth factor.