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OBJECTIVE Opioid-minimizing or nonopioid therapy using nonsteroidal antiinflammatory drugs (NSAIDs) or tramadol has been encouraged for pain management. This study aimed to examine the noninferiority of NSAIDs to tramadol for pain management following transsphenoidal surgery for pituitary adenomas in terms of analgesic efficacy, adverse events, and rescue opioid use. METHODS This was a randomized, single-center, double-blind noninferiority trial. Patients 18–70 years old with planned transsphenoidal surgery for pituitary adenomas were randomly assigned (in a 1-to-1 ratio) to receive NSAIDs (parecoxib injection and subsequent loxoprofen tablets) or tramadol (tramadol injection and subsequent tramadol tablets). The primary outcome was pain score assessed by a visual analog scale (VAS) for 24 hours following surgery; the secondary outcomes were VAS scores for 48 and 72 hours. Other prespecified outcomes included nausea, vomiting, dizziness, upset stomach, skin rash, peptic ulcer, gastrointestinal bleeding, and pethidine use to control breakthrough pain. Noninferiority of NSAIDs to tramadol was established if the upper limit of the 95% confidence interval (CI) of the VAS score difference was < 1 point and the rate difference of adverse events and pethidine use < 5%. The superiority of NSAIDs was assessed when noninferiority was verified. All analyses were performed on an intention-to-treat basis. RESULTS Two hundred two patients were enrolled between November 1, 2020, and May 31, 2021 (101 in the NSAIDs group, 101 in the tramadol group). Baseline characteristics between groups were well balanced. Mean VAS scores for 24 hours following transsphenoidal surgery were 2.6 ± 1.8 in the NSAIDs group and 3.5 ± 2.1 in the tramadol group (−0.9 difference, 95% CI −1.5 to −0.4; p value for noninferiority < 0.001, p value for superiority < 0.001). Noninferiority and superiority were also achieved for both secondary outcomes. VAS scores improved over time in both groups. Incidences of nausea (39.6% vs 61.4%, p = 0.002), vomiting (3.0% vs 42.6%, p < 0.001), and dizziness (12.9% vs 47.5%, p < 0.001) were significantly lower, while incidence of upset stomach (9.9% vs 2.0%, p = 0.017) was slightly higher in the NSAIDs group compared with the tramadol group. The percentage of opioid use was 4.0% in the NSAIDs group and 15.8% in the tramadol group (−11.8% difference, 95% CI −19.9% to −3.7%; p value for noninferiority < 0.001, p value for superiority = 0.005). CONCLUSIONS NSAIDs significantly reduced acute pain following transsphenoidal surgery, caused few adverse events, and limited opioid use compared with tramadol.

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.

OBJECTIVECushing’s disease (CD) involves brain impairments caused by excessive cortisol. Whether these impairments are reversible in remitted CD after surgery has long been controversial due to a lack of high-quality longitudinal studies. In this study the authors aimed to assess the reversibility of whole-brain changes in remitted CD after transsphenoidal surgery (TSS), and its correlations with clinical and hormonal parameters, in the largest longitudinal study cohort to date for CD patient brain analysis.METHODSFifty patients with pathologically diagnosed CD and 36 matched healthy controls (HCs) were enrolled in a tertiary comprehensive hospital and national pituitary disease registry center in China. 3-T MRI studies were analyzed using an artificial intelligence–assisted web-based autosegmentation tool to quantify 3D brain volumes. Clinical parameters as well as levels of serum cortisol, adrenocorticotrophic hormone (ACTH), and 24-hour urinary free cortisol were collected for the correlation analysis. All CD patients underwent TSS and 46 patients achieved remission. All clinical, hormonal, and MRI parameters were reevaluated at the 3-month follow-up after surgery.RESULTSWidespread brain volume loss was observed in active CD patients compared with HCs, including total gray matter (p = 0.003, with false discovery rate [FDR] correction) and the frontal, parietal, occipital, and temporal lobes; insula; cingulate lobe; and enlargement of lateral and third ventricles (p < 0.05, corrected with FDR). All affected brain regions improved significantly after TSS (p < 0.05, corrected with FDR). In patients with remitted CD, total gray matter and most brain regions (except the frontal and temporal lobes) showed full recovery of volume, with volumes that did not differ from those of HCs (p > 0.05, corrected with FDR). ACTH and serum cortisol changes were negatively correlated with brain volume changes during recovery (p < 0.05).CONCLUSIONSThis study demonstrates the rapid reversal of total gray matter loss in remitted CD. The combination of full recovery areas and partial recovery areas after TSS is consistent with the incomplete recovery of memory and cognitive function observed in CD patients in clinical practice. Correlation analyses suggest that ACTH and serum cortisol levels are reliable serum biomarkers of brain recovery for clinical use after surgery.

OBJECTIVE: The objective of this study was to investigate microstructural damage caused by pituitary macroadenomas by performing probabilistic tractography of the optic tracts and radiations using 7-T diffusion-weighted MRI (DWI). These imaging findings were correlated with neuro-ophthalmological results to assess the utility of ultra–high-field MRI for objective evaluation of damage to the anterior and posterior visual pathways. METHODS: Probabilistic tractography employing 7-T DWI was used to reconstruct the optic tracts and radiations in 18 patients with adenomas and in 16 healthy volunteers. Optic chiasm compression was found in 66.7% of the patients and visual defects in 61.1%. Diffusion indices were calculated along the projections and correlated with tumor volumes and results from neuro-ophthalmological examinations. Primary visual cortical thicknesses were also assessed. RESULTS: Fractional anisotropy was reduced by 21.9% in the optic tracts (p < 0.001) and 17.7% in the optic radiations (p < 0.001) in patients with adenomas. Patients showed an 8.5% increase in mean diffusivity of optic radiations compared with healthy controls (p < 0.001). Primary visual cortical thickness was reduced in adenoma patients. Diffusion indices of the visual pathway showed significant correlations with neuro-ophthalmological examination findings. CONCLUSIONS: Imaging-based quantification of secondary neuronal damage from adenomas strongly correlated with neuro-ophthalmological findings. Diffusion characteristics enabled by ultra–high-field DWI may allow preoperative characterization of visual pathway damage in patients with chiasmatic compression and may inform prognosis for vision recoverability.