Long-Term Mortality after Transsphenoidal Surgery and Adjunctive Therapy for Acromegaly

Abstract

To analyze the long term outcome after multimodality therapy for acromegaly, a retrospective review was performed on 162 patients who underwent transsphenoidal surgery at Massachusetts General Hospital between 1978 and 1996. The surgical cure rate for microadenomas was 91%, that for macroadenomas was 48%, and it was 57% overall. The surgical cure rate was significantly dependent on tumor size, but was not dependent on age or sex. An improvement in the surgical cure rate was noted over the course of the review, from 45% before 1987 to 73% since 1991. Long term follow-up was obtained in 99% of U.S. residents (149 of 151), with a mean follow-up period of 7.8 yr. Adjuvant radiation and/or pharmacological therapy was given to 61 patients. Of the entire group, 83% (124 of 149) were in biochemical remission as determined by normalization of serum insulin-like growth factor I levels or by GH suppression after oral glucose tolerance testing at last contact or at death. The recurrence rate was 6% at 10 yr and 10% at 15 yr after surgery in those patients who initially met the criteria for surgical cure. The 10-yr survival rate was 88%, and there were 12 deaths at postoperative intervals of 2-12 yr, with the most common cause of death being cardiovascular disease. A Cox proportional hazards model showed that patient-years with persistent disease carried a 3.5-fold [95% confidence interval (CI), 1.0-12; P = 0.02] relative mortality risk compared to those patient-years in remission. A Poisson person-years regression analysis showed no significant difference in survival between those 86 patients cured at operation and an age- and sex-matched sample from the U.S. population [standardized mortality ratio (SMR), 0.84; 95% CI, 0.3-2.2; P = 0.35]. A similar analysis on the entire group of 149 patients showed no significant difference in survival from that in a control sample (SMR, 1.16; 95% CI, 0.66-2.0; P = 0.3). Mortality risk for patient-years with persistent active disease after unsuccessful treatment vs. that in the U.S. population sample remained increased (SMR, 1.8; 95% CI, 0.9-3.6; P = .05). This analysis suggests that the decreased survival previously reported to be associated with acromegaly can be normalized by successful surgical and adjunctive therapy.

Efficacy and safety of monotherapy by pegvisomant, a growth hormone receptor antagonist, in Japanese patients with acromegaly

“…The normalization of serum IGF-I is a useful predictor of clinical outcome, as well as morbidity and mortality, in patients with active acromegaly [7][8][9]. The high IGF-I level is indeed adapted as one of the diagnosis criteria for acromegaly and a sole biomarker to asssess the efficacy of the GH receptor antagonist [3].…”

Conventional and novel biomarkers of treatment outcome in patients with acromegaly: discordant results after somatostatin analog treatment compared with surgery

“…We could not record a difference in adenoma size between the two groups, but this most likely reflects that the imaging data were limited and based on routine measurements. The outcome of surgery depends strongly on tumor size and localization (1,20), and it is probable that the true prevalence of large and/or invasive adenomas was higher in the patients on SA treatment as compared with the patients treated with surgery only. Secondly, our inclusion criterion for all patients was achievement of a normalized serum IGF1 level at the time of follow-up.…”

“…The diagnosis is based on clinical symptoms, elevated serum levels of GH and/or insulin-like growth factor 1 (IGF1), and a magnetic resonance imaging (MRI) of the pituitary region. Surgery has stood the test of time as primary therapy, but not all patients are eligible and surgery by itself provides sufficient disease control in only 60% (1). Medical treatment, in particular slow-release formulations of somatostatin analog (SA), therefore plays an important role.…”

Long term effect of external pituitary irradiation on IGF1 levels in patients with acromegaly free of adjunctive treatment

“…The effect of EPI in normalising serum IGF1 levels has been a cause of dispute (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)30) (Table 1). Barkan et al reported that following radiotherapy for acromegaly only 2 out of 38 patients (5%) taken off medical therapy for 2-3 weeks normalized IGF1 over 10 years despite attenuation of GH levels (14).…”