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

Xiaopeng Guo MD1,2,3,4, Ruopeng Zhang MD1,2,5, Duoxing Zhang MD1,2,5, Zihao Wang MD1,2,3,4, Lu Gao MD1,2,3,4, Yong Yao MD1,2,3,4, Kan Deng MD1,2,3,4, Xinjie Bao MD1,2,3,4, Ming Feng MD1,2,3,4, Zhiqin Xu MD1,2,3,4, Yi Yang MD1,2,3,4, Wei Lian MD1,2,3,4, Renzhi Wang MD1,2,3,4, Wenbin Ma MD1,2,3,4, and Bing Xing MD1,2,3,4
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  • 1 Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing;
  • | 2 Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing;
  • | 3 China Pituitary Disease Registry Center, Beijing;
  • | 4 China Pituitary Adenoma Specialist Council, Beijing; and
  • | 5 Peking Union Medical College, Tsinghua University, Beijing, China
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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.

ABBREVIATIONS

FDR = false discovery rate; FSH = follicle-stimulating hormone; GH = growth hormone; IGF-1 = insulin-like growth factor 1; LH = luteinizing hormone; OGTT = oral glucose tolerance test; PRL = prolactin; PUMCH = Peking Union Medical College Hospital; TSS = transsphenoidal surgery; ULN = upper limit of normal.

Supplementary Materials

    • Supplementary Tables 1 and 2 (PDF 419 KB)

Schematics of transseptal interforniceal resection of a superiorly recessed colloid cyst. ©Mark Souweidane, published with permission. See the article by Tosi et al. (pp 813–819).

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