Determinants of immediate and long-term remission after initial transsphenoidal surgery for acromegaly and outcome patterns during follow-up: a longitudinal study on 659 patients

Abstract

OBJECTIVE Treatment outcomes following initial transsphenoidal surgery (TSS) for acromegaly are erratic. Identifying outcome patterns can assist in informing patients about possible treatment outcomes and planning for individualized adjuvant treatments in advance. In this study, the authors aimed to investigate the immediate and long-term endocrine remission rates following initial TSS for acromegaly, identify clinical determinants of treatment outcomes, and explore outcome patterns during a long-term follow-up and the pattern-specific patient features. METHODS This prospective, single-center, longitudinal cohort study enrolled patients with acromegaly who underwent TSS in the period from 2015 to 2018 at the authors’ institution. Immediate remission, assessed on the 2nd postoperative morning, and long-term remission, assessed at least 18 months after TSS, were evaluated according to the strict 2010 consensus criteria (random growth hormone [GH] < 1 ng/ml or GH nadir < 0.4 ng/ml after oral glucose tolerance test, and age- and sex-normalized insulin-like growth factor 1). Univariate and bivariate regression analyses were used to identify determinants of remission. RESULTS A total of 659 patients with acromegaly (average age 42 years, 44% males) underwent TSS for pituitary adenomas (macroadenomas, 85%; invasive tumors, 35%) and were followed up during a median of 51 months. Immediate and long-term remission rates after initial TSS were 37% and 69%, respectively. Older age at diagnosis (OR 1.7), male sex (OR 1.6), smaller tumors (OR 2.0), noninvasive tumors (OR 4.8), and tumors positive for follicle-stimulating hormone/luteinizing hormone (OR 1.5) were predictors of immediate surgical remission. In addition to the above predictors, lower preoperative GH (OR 2.4), absence of preoperative central hypothyroidism (OR 2.6), and endoscopic TSS (OR 10.6) were predictors of long-term remission. Regression analyses revealed that endoscopic TSS (OR 2.8, 95% CI 1.524–5.291, p = 0.001), absence of cavernous sinus invasion (OR 4.1, 95% CI 2.522–6.613, p < 0.001), older age (OR 1.03, 95% CI 1.006–1.048, p = 0.013), and male sex (OR 2.0, 95% CI 1.224–3.247, p = 0.006) were independent determinants of long-term remission. Five outcome patterns were identified based on the changes in hormonal results during follow-up, including continuous remission (34%), refractory acromegaly (28%), delayed remission (21%), remission after adjuvant therapy (14%), and recurrence after initial remission (3%). The clinical characteristics of each subgroup were identified. CONCLUSIONS Cavernous sinus invasion, age at diagnosis, and sex are the best determinants of immediate and long-term remission after initial TSS for acromegaly. Endoscopic TSS predicts a higher long-term remission rate than that with microscopic TSS. The authors identified five outcome patterns in acromegaly and group-specific patient characteristics for clinical decision-making.

Consensus on criteria for acromegaly diagnosis and remission

“…For example, some studies reported approximately 60% of patients achieve biochemical remission in the immediate postoperative period when defined as nadir GH < 1 µg/L during OGTT, with lower rates in patients with macroadenomas and in those treated with a microscopic approach [ 65 , 66 ] (MQ). However, remission rates fell to approximately 40% when using stricter criteria of < 0.4 µg/L on postoperative day 2, and 20% of patients achieved GH below threshold after a delayed period of a median of 24 months of observation [ 67 ] (LQ). Of note, very early (and tighter) GH control might be predictive of later GH outcome, as nadir GH > 0.4 µg/L on postoperative day 2–5 predicted lack of remission after a mean follow-up of 44 months [ 68 ], and nadir < 0.4 µg/L at 2–5 days and at 3–6 months correlated better with remission than did < 1 µg/L [ 68 , 69 ] (LQ).…”

The effect of endoscopic transsphenoidal somatotroph tumors resection on pituitary hormones: systematic review and meta-analysis

“…Clearly, transsphenoidal endoscopic surgery by a senior surgeon and increased surgical experience is important for improving remission rates [31]. Age and sex are predictive of postoperative remission rates in some studies [32][33][34]. But their results were inconsistent and more research is needed.…”

Moving toward a standardized diagnostic statement of pituitary adenoma using an information extraction model: a real-world study based on electronic medical records

“…This was a retrospective study conducted at Peking Union Medical College Hospital (PUMCH). PUMCH is the China Pituitary Disease Registry Center and China Pituitary Adenoma Specialist Council and leads clinical practice and research studies in the field of MDTs for PAs in China [ 17 – 21 ].…”