OBJECTIVE:In endoscopic transsphenoidal surgery (ETSS) for pituitary neuroendocrine tumor (Pit-NET), also known as a pituitary adenoma, identification and dissection of the boundary between the tumor and the normal anterior pituitary gland are important surgical techniques. In this study, we introduce the Gauze Swabbing Technique (GST), in which boundary dissection is performed using shear stress, and examine its surgical outcomes. METHODS:A total of 271 patients with nonfunctioning pituitary adenoma/Pit-NET who underwent ETSS at our institution between April 2014 and September 2025 were included. The patients were divided into an early group of 135 cases before the introduction of GST and a later group of 136 cases in which GST was used, and surgical outcomes were compared. Propensity score matching was performed using age, sex, tumor size, Knosp grade, tumor consistency, cavernous sinus invasion, preoperative diabetes insipidus, preoperative ocular motility disorder, and preoperative anterior pituitary dysfunction as covariates, and surgical outcomes were compared in the matched cohort by conditional logistic regression. RESULTS:Propensity score matching yielded 100 patients in each group, and all standardized differences in background factors were less than 0.1, indicating good balance between the groups. In the post-matching comparison, there were no significant differences between the early group and the GST group in gross total resection rate, new pituitary dysfunction, new diabetes insipidus, worsening of ocular motility disorder, or intraoperative cerebrospinal fluid leakage. CONCLUSION:GST is a technique in which boundary dissection is performed by applying gentle shear stress through rotational movement of gauze along the interface between the tumor and the normal anterior pituitary gland, and it may enable tumor removal while preserving the membranous structure. Based on the results of the propensity score matching analysis, GST shows safety and efficacy comparable to those of conventional techniques and may be a useful option for boundary dissection in ETSS for pituitary adenoma/Pit-NET.

BACKGROUND Hemifacial spasm (HFS) associated with a large fenestration of the vertebral artery (VA) is extremely rare. Here, the authors report a case of HFS caused by this vascular anomaly and discuss its embryological background and clinical implications. OBSERVATIONS A man in his 30s presented with a 7-year history of right-sided HFS. MRI demonstrated vascular compression at the root exit zone of the facial nerve. MR angiography revealed an aberrant artery running parallel to the right VA, forming a large fenestration. Three-dimensional CT angiography demonstrated a common trunk giving rise to the anterior inferior cerebellar artery and posterior inferior cerebellar artery. The offending artery was identified as the common trunk.. Microvascular decompression with real-time abnormal muscle response monitoring achieved sufficient arterial transposition, with careful preservation of the brainstem perforators. The patient experienced complete resolution of spasms postoperatively, without complications. LESSONS A large VA fenestration may represent a persistent primitive lateral basilovertebral anastomosis. Successful surgical treatment requires a precise preoperative understanding of the complex vascular architecture and consideration of the limitations imposed by perforating branches during arterial transposition. https://thejns.org/doi/10.3171/CASE25777

Recurrent Cushing's disease is most commonly caused by residual or newly developed pituitary neuroendocrine tumor (PitNET) tissue within the sellar region. Extrasellar recurrence due to postoperative tumor cell seeding is exceedingly rare. We report the unique case of a 30-year-old woman who achieved endocrine remission after gross total resection of an ACTH-secreting PitNET but later developed biochemical and clinical recurrence without radiological evidence of a sellar lesion. Despite long-term medical therapy including cabergoline, metyrapone, and pasireotide, the hypercortisolism gradually progressed. Nearly 10 years after the initial surgery, a reoperation was performed to explore the occult tumor. Intraoperatively, a small soft tumor attached to the posterior surface of the anterior wall of the sphenoid sinus was discovered. Histopathological examination confirmed the presence of a recurrent corticotrophic PitNET. A retrospective review of CT, MRI, and octreotide scintigraphy revealed a subtle lesion that had previously been overlooked. Complete resection resulted in an immediate endocrine remission. This case demonstrates that recurrent Cushing's disease may, although rarely, arise from the implantation of tumor cells that drop into the sphenoid sinus during transsphenoidal surgery. Awareness of this mechanism is crucial for evaluating MRI-negative recurrences. Careful inspection of the sphenoid sinus and meticulous irrigation during surgery may help prevent iatrogenic seeding and improve long-term outcomes.

BACKGROUND AND OBJECTIVES:Deep fascia suturing for skull base reconstruction after extended transsphenoidal surgery (eTSS) remains a technically demanding yet essential step, especially in cases with high-flow intraoperative cerebrospinal fluid (CSF) leaks. Although single-hand techniques with concurrent suctioning are standard, we developed a bimanual two-forceps fascia patchwork closure (BM-FPWC) method to enable precise, efficient deep suturing using both hands. This study aimed to describe the BM-FPWC technique and evaluate the operative time and learning curve associated with the procedure through retrospective analysis.METHODS:Among 120 eTSS cases at Toranomon Hospital between June 2024 and January 2025, 34 patients with intraoperative CSF leaks (Esposito grade >= 2) underwent BM-FPWC. Suturing was performed endoscopically using a needle holder and bayonet forceps with both hands, enabled by an endoscope-holding arm. Suturing time and failure rate were compared between earl (n = 17) and late (n = 17) phases to assess the learning curve.RESULTS:No postoperative CSF leaks were observed. Mean suturing time was significantly reduced from 58.4 +/- 11.1 minutes (early phase) to 44.6 +/- 15.8 minutes (late phase, P = .0075). The number of failed stitches was also significantly lower in the late phase (P = .0409), whereas the total stitch count remained unchanged.CONCLUSION:BM-FPWC is a safe, efficient, and reproducible technique for skull base reconstruction in eTSS. With experience, the procedure becomes faster and more reliable, suggesting its potential as a standard method for bimanual deep suturing in endonasal skull base surgery.

Vertebral artery dissection is a rare but potentially life-threatening condition. However, many cases of mild vertebral artery dissection-an early disease stage-may be overlooked. 3-dimensional T1-weighted black-blood magnetic resonance imaging has recently emerged as a promising diagnostic tool, yet it remains underutilized. This study investigated the impact of vertebral artery dissection screening in patients presenting with headache, the most common chief complaint encountered in general neurosurgery outpatient clinics, and an initial symptom of vertebral artery dissection, in a real-world clinical setting. We retrospectively reviewed 3,049 consecutive patients with headache who visited a neurosurgical outpatient center in Chiba, Japan (October 2021-October 2023). In the first year, 1,527 patients underwent brain magnetic resonance imaging and magnetic resonance angiography. In the second year, 1,522 patients received these examinations as well as brain and neck black-blood magnetic resonance imaging. Vertebral artery dissection detection rates were compared between the 2 groups.Vertebral artery dissection was diagnosed in 0.5% and 1.6% of the former and latter groups, respectively (relative risk: 3.42, 95% confidence interval 1.48-7.92, p = 0.003), indicating an over threefold increase in detection. Among patients with intracranial vertebral artery dissection, 96% reported occipital headache rather than nonspecific/generalized headache. Among high-risk individuals aged 40-55 years with occipital or posterior neck pain, the detection rate reached 7.5%. Vertebral artery dissection accounted for 93% of head and neck arterial dissections. The addition of black-blood magnetic resonance imaging significantly improved early detection and may enhance screening accuracy for patients presenting with headache at elevated risk.

BACKGROUND The optimal treatment for cerebral vasospasm (CV) following traumatic brain injury (TBI) has not been established, and management generally follows strategies developed for aneurysmal subarachnoid hemorrhage. OBSERVATIONS The authors report a case of a patient with traumatic subarachnoid hemorrhage and cerebral contusion who presented with worsening consciousness and disorientation and subsequently developed symptomatic CV on day 6 of hospitalization. MRI and 3D CT demonstrated narrowing of the left internal carotid artery and middle cerebral artery (MCA) with reduced cerebral perfusion. Intra-arterial administration of fasudil hydrochloride yielded a temporary improvement. However, MCA stenosis recurred the next day, requiring percutaneous transluminal balloon angioplasty. Subsequent imaging showed improved cerebral perfusion, and the patient was discharged without delayed cerebral ischemia. LESSONS Fluctuations in consciousness or neuropsychological symptoms after TBI should prompt evaluation for CV using perfusion imaging, even in the absence of focal neurological deficits. When a high risk of severe vasospasm accompanied by perfusion reduction is identified, prompt, stepwise therapeutic intervention should be implemented, beginning with the least invasive treatment option to optimize clinical outcomes. https://thejns.org/doi/abs/10.3171/CASE25943

BACKGROUND Pedicled nasoseptal flap (NSF) is the gold-standard skull base reconstruction method in endoscopic endonasal surgery (EES). Although vascular complications, such as internal carotid artery injury or carotid-cavernous fistula (CCF), are well documented, dural arteriovenous fistula (dAVF) originating from the vascular network of an NSF is exceedingly rare. Herein, the authors report the first case of a cavernous sinus (CS) dAVF supplied by an NSF. OBSERVATIONS A 50-year-old woman underwent EES with NSF reconstruction for tuberculum sellae meningioma. She experienced delayed hemorrhage from the sphenoid sinus on postoperative day 21, requiring bipolar coagulation and packing. Five months later, she developed right-sided pulsatile tinnitus. MRI and digital subtraction angiography revealed a CS dAVF (Borden type I). The primary feeder was the sphenopalatine artery (SPA), which supplies the CS through the vascular network of the transposed NSF. The patient is currently under conservative management, with stable symptoms. LESSONS Pathophysiology likely involved postoperative inflammation and angiogenesis triggered by delayed hemorrhage and subsequent healing. The proximity of the NSF to the medial CS wall may have facilitated abnormal shunting between the SPA-supplied flap and venous sinus. Despite the efficacy of NSF, clinicians must recognize its potential as a vascular source of dAVF. https://thejns.org/doi/10.3171/CASE26300

Surgical management of suprasellar meningiomas is challenging because of their proximity to critical neurovascular structures, including the optic apparatus and internal carotid artery. Ttreatment aims to preserve visual and neurological functions, while achieving durable tumor control. This review classified suprasellar meningiomas into medial and lateral types to clarify surgical strategies. Medial-type tumors, including tuberculum sellae, planum sphenoidale, and olfactory groove meningiomas, often compress the optic nerves inferiorly and may be suitable for endoscopic endonasal approaches in select cases. Contrastingly, lateral-type tumors, such as sphenoid wing and anterior clinoid meningiomas, frequently involve the internal carotid artery and cavernous sinus, and are best managed through transcranial approaches. Keyhole surgery may be considered in select cases to reduce surgical invasiveness. Endoscopic endonasal surgery for lateral-type tumors is generally not indicated, except in combined approaches for selective decompression of medial components. Optimal management requires an individualized approach based on tumor location, extension, and neurovascular involvement, prioritizing functional preservation over radical resection.

Here, we present a comprehensive protocol for analyzing craniopharyngioma subtypes and their tumor microenvironments at single-cell resolution. We describe tumor tissue dissociation, single-cell isolation, RNA sequencing library preparation, and bioinformatics analysis procedures. We also detail immunohistochemistry procedures for validating findings. This approach enables the detailed characterization of tumor cellular composition, immune cell networks, and molecular signatures that distinguish adamantinomatous from papillary craniopharyngiomas. For complete details on the use and execution of this protocol, refer to Matsuda et al.1.

Pasireotide (PAS), a multireceptor somatostatin analog, has been demonstrated to effectively control hormone levels, including those of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), in patients with acromegaly. However, it induces hyperglycemia by inhibiting insulin secretion via somatostatin receptor 5 (SSTR5). Despite the extensive literature on the occurrence of PAS-induced hyperglycemia, there is still no consensus on the optimal first-line treatment for this complication. Herein, we present two cases of acromegaly treated with PAS and highlight its short- and long-term effects on glucose metabolism. In the first case, postprandial hyperglycemia manifested rapidly following the commencement of PAS treatment and was effectively managed with dulaglutide under continuous glucose monitoring (CGM). In the second case, long-term PAS therapy resulted in a dose-dependent glycemic response that was controlled by different GLP-1 receptor agonists (GLP-1RAs), including semaglutide. CGM facilitated the early detection of significant glycemic fluctuations, underscoring the necessity for close monitoring in patients receiving PAS therapy. These cases demonstrate the efficacy of GLP-1RAs in managing PAS-induced hyperglycemia and highlights the value of CGM in early detection and intervention. Our findings suggest that GLP-1RAs, particularly semaglutide, are a valuable treatment option for this condition. Further research is needed to determine the optimal treatment strategy, particularly in East Asian populations, and to establish a clear consensus on the first-line therapy for PAS-induced hyperglycemia.

Gamma knife surgery is useful for treating cerebral arteriovenous malformations. However, some radiation-induced long-term complications have been reported. One of these is a chronic expanding hematoma. We present a case of chronic expanding hematoma, successfully treated with endoscopic resection. The patient, a woman in her 30s, experienced a cerebral hemorrhage 17 years ago associated with an arteriovenous malformation in the corpus callosum. The lesion was completely embolized with n-butyl-2-cyanoacrylate embolization twice, followed 2 years later by gamma knife surgery. The patient presented to the emergency room with headache and left hemiplegia. A computed tomography scan showed hemorrhagic changes consistent with the cystic lesion and worsening edematous changes around it. An endoscopic tumor resection (interhemispheric approach) was performed, and most of the lesion was removed. Pathology did not detect any neoplastic lesions, and a diagnosis of chronic expanding hematoma was performed based on the presence of abnormal vascular neoplasia. The postoperative course was uneventful, and the headache promptly resolved. The pathophysiology of chronic expanding hematoma involves slow and progressive hematoma expansion due to repeated local hemorrhage, causing intense cerebral edema around the lesion. Surgical removal is effective, and edematous changes and neurological symptoms can be quickly relieved after surgery. Endoscopic surgery is particularly effective for deep lesions owing to its ability to manipulate within a narrow surgical field. In this case, the lesion was removed with minimal invasiveness and no complications, leading to early symptom relief and resolution of the surrounding brain edema changes.

Craniopharyngiomas, including adamantinomatous (ACP) and squamous papillary (PCP) types, are challenging to treat because of their proximity to crucial pituitary structures. This study aimed to characterize the cellular composition, tumor tissue diversity, and cell-cell interactions in ACPs and PCPs using single-cell RNA sequencing. Single-cell clustering revealed diverse cell types, further classified into developing epithelial, calcification, and immune response for ACP and developing epithelial, cell cycle, and immune response for PCP, based on gene expression patterns. Subclustering revealed the enrichment of classical M1 and M2 macrophages in ACP and PCP, respectively, with high expression of pro-inflammatory markers in classical M1 macrophages. The classical M1 and M2 macrophage ratio significantly correlated with the occurrence of diabetes insipidus and panhypopituitarism. Cell-cell interactions, particularly involving CD44-SPP, were identified between tumor cells. Thus, we developed a comprehensive cell atlas that elucidated the molecular characteristics and immune cell inter-networking in ACP and PCP tumor microenvironments.

BACKGROUND AND IMPORTANCE:Cholesterol granuloma (CG) is the most common petrous apex (PA) cystic lesion. Posterolateral expansion of a PA CG (PACG) compresses the internal auditory canal (IAC), leading to vestibulocochlear (VC) and facial nerve dysfunction. Even small, symptomatic PACGs are managed surgically. The preferred strategy is not complete removal, but drainage and aeration. PACG with anteromedial expansion using an endoscopic endonasal approach provides natural drainage into the nasal sinus without risking VC and facial dysfunction. Endoscopic endonasal approach is inappropriate for small PACGs without anteromedial expansion because of potential damage to the petrous internal carotid artery. Small PACGs without anteromedial expansion are managed using extradural middle fossa (EMF) approach, which lacks a natural drainage pathway, thus necessitating an artificial drainage pathway for PACG aeration to prevent recurrence. We introduced EMF approach for CG decompression and cyst-to-mastoid antrum (MA) diversion for managing small, symptomatic PACGs without anteromedial expansion.CLINICAL PRESENTATION:A 48-year-old woman presented with headache, vertigo, tinnitus, and left hemifacial spasm with preserved hearing because of IAC compression caused by a small PACG without anteromedial expansion. Using the EMF approach, the CG and IAC were safely decompressed. Effective and long-standing artificial drainage for CG aeration was established by anterior petrosectomy and silicone tubing from the CG into the MA. Surgery resolved the symptoms, which have not recurred in 3 years.CONCLUSION:Granuloma decompression and cyst-to-MA diversion using silicone tubing using the EMF approach is a safe and effective surgical management for small, symptomatic PACG without anteromedial expansion.

Craniopharyngiomas are among the most challenging intracranial tumors for neurosurgeons. Their management is complicated due to growth patterns such as infiltration into the pituitary stalk, chiasma, and hypothalamus. Therefore, patients may present with various conditions such as endocrine disorders, visual disturbances, or hypothalamic dysfunction in the first medical examination. Moreover, surgical management is challenging because of the high risk of recurrence. Two well-known histological subtypes include adamantinomatous and papillary craniopharyngiomas, and recent advances in genetic analysis have provided significant findings about these subtypes. The adamantinomatous subtype can be distinguished by mutations in CTNNB1, whereas the V600E mutation of the BRAF gene characterizes the papillary subtype. This review describes the etiology, genetic features, and clinical presentations of craniopharyngiomas.

OBJECTIVE:Due to the heterogeneous definitions of tumor regrowth and various tumor volume distributions, the nature of small remnants after vestibular schwannoma (VS) surgery and the appropriate timing of adjuvant stereotactic radiosurgery for these remnants remain unclear. In this study, the growth potential of small remnants (< 1 cm3) after VS surgery was compared with that of treatment-naïve (TN) small VSs.METHODS:This retrospective single-center study included 44 patients with VS remnants following subtotal resection (STR) of a large VS (remnant group) and 75 patients with TN VS (< 1 cm3; TN group). A 20% change in tumor volume over the imaging interval indicated radiographic progression or regression. Tumor progression-free survival (TPFS) rates were estimated using the Kaplan-Meier method.RESULTS:In the remnant group, the mean preoperative tumor volume was 13.8 ± 9.0 cm3 and the mean tumor resection rate was 95% ± 5%. The mean tumor volume at the start of the observation period did not differ significantly between the two groups (remnant vs TN: 0.41 ± 0.29 vs 0.34 ± 0.28 cm3, p = 0.171). The median periods until tumor progression was detected were 15.1 (range 4.9-76.2) months and 44.7 (range 12.6-93.2) months in the TN and remnant groups, respectively. In the remnant group, the TPFS rates were 74% and 70% at 3 and 5 years after the surgery, respectively, compared with 59% and 47% in the TN group. The log-rank test demonstrated a significant difference (p = 0.008) in the TPFS rates between the two groups. Furthermore, 42 patients each from the remnant and TN groups were matched based on tumor volume. TPFS was significantly longer in the remnant group than in the TN group (3-year rates, 77% vs 62%; 5-year rates, 73% vs 51%; p = 0.02). In the remnant group, 18% of the tumor remnants demonstrated regression during follow-up, compared with 9% in the TN group, but this intergroup difference was not significant (p = 0.25).CONCLUSIONS:This study demonstrated that the growth potential of small VS remnants was lower than that of TN tumors. Observing for small remnants may be appropriate after STR of a large VS. Given the risk of tumor regrowth, careful observation using MRI should be mandatory during follow-up.

Abstract Background Pathophysiology of corticotroph macroadenomas has not been elucidated. In this study, we present four cases of adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas with extensions to the third ventricle (TV) and investigate their clinical and pathological characteristics. Case 1 A male in his seventies went to a hospital because of a fall. Upon performing computed tomography, a tumor was incidentally noted. Pituitary MRI revealed a macroadenoma with extension to TV. He presented with Cushingoid features (CF). His basal ACTH level was 112 pg/mL, and urinary free cortisol (UFC) was 129.1 μg/day. Cortisol was not suppressed in the 0.5 mg dexamethasone suppression test (0.5 mg DST). ACTH level increased in the corticotropin-releasing hormone (CRH) stimulation test and the desmopressin (DDAVP) stimulation test. He was diagnosed with Cushing's disease (CD), and endoscopic transsphenoidal surgery (ETSS) was performed. Pathological findings showed densely granulated corticotroph adenoma (DGCA). Somatostatin receptor type 5 (SSTR5) was negative, and ubiquitin-specific protease 8 (USP8) was not mutated. Case 2 A female in her fifties had a visual field defect and pigmentation of the face. MRI revealed a macroadenoma with extension to TV. She presented with CF. Her basal ACTH level was 57.9 pg/mL, and UFC was 259.7 μg/day. Cortisol was not suppressed in the 0.5 mg DST. ACTH level increased in the CRH test and the DDAVP test. She was diagnosed with CD. Pathological findings showed DGCA. SSTR5 was moderate positive, and USP8 was suspected to be mutated. Case 3 A female in her fifties had a throbbing headache. MRI showed a macroadenoma with extension to TV. She did not present with CF. Her basal ACTH level was 71.8 pg/mL, and UFC was 134.3 μg/day. Cortisol was not suppressed in the 0.5 mg DST. ACTH showed response to the CRH test and the DDAVP test. She was diagnosed with subclinical Cushing's disease (SCD) and sparsely granulated corticotroph adenoma (SGCA). SSTR5 was slightly positive, and USP8 was not mutated. Case 4 A male in his fifties had general malaise and polyuria. MRI showed a macroadenoma with extension to TV. He did not present with CF. His basal ACTH level was 179 pg/mL, and UFC was 187.4 μg/day. Cortisol was not suppressed in the 0.5 mg DST. ACTH did not show response to the CRH test and the DDAVP test. He was diagnosed with SCD, and the tumor had oncocytic changes. SSTR5 was negative, and USP8 was not mutated. Conclusion The findings from these case reports suggest that phenotypes of CD and SCD are associated with the differences between SGCA and DGCA. Moreover, it is also suggested that USP8 mutations correlate with SSTR5 expression in macroadenomas that extend to the TV. Presentation: No date and time listed

Abstract Context Growth hormone deficiency (GHD) develops early in patients with hypothalamic-pituitary disorder and is frequently accompanied by other anterior pituitary hormone deficiencies, including secondary adrenal insufficiency (AI). A growth hormone–releasing peptide-2 (GHRP2) test, which is widely used for the diagnosis of patients with GHD, is thought to induce release of not only growth hormone (GH) but also ACTH. However, its clinical usefulness in hypothalamic-pituitary disorder is unclear. Objective We aimed to determine the clinical utility of the GHRP2 test in patients with hypothalamic-pituitary disorders, particularly for AI concomitant with GHD. Methods The GHRP2 test, a cosyntropin stimulation test, corticotropin-releasing hormone (CRH) tests, and/or insulin tolerance tests (ITTs) were performed on 36 patients with hypothalamic-pituitary disorder. Results Twenty-two (61%) had severe GHD, and 3 (8%) had moderate GHD by GHRP2. There was no difference in baseline ACTH and cortisol between non-GHD, moderate GHD, and severe GHD participants. However, a cosyntropin stimulation test and subsequent CRH tests and/or ITTs revealed that 17 (47%) had secondary AI and 16/17 (94%) cases of secondary AI were concomitant with severe GHD. ROC curve analysis demonstrated that the ACTH response in the GHRP2 test was useful for screening pituitary-AI, with a cutoff value of 1.55-fold (83% sensitivity and 88% specificity). Notably, the combination of ACTH response and the peak cortisol level in the GHRP2 test using each cutoff value (1.55-fold and 10 µg/dL, respectively) showed high specificity (100%) with high accuracy (0.94) for diagnosis of pituitary-AI. Conclusion We recommend measuring ACTH as well as GH during the GHRP2 test to avoid overlooking or delaying diagnosis of secondary AI that frequently accompanies GHD.

The clinical characteristics of growth hormone (GH)-producing pituitary adenomas/somatotroph pituitary neuroendocrine tumors (GHomas/somatotroph PitNETs) vary across patients. In this study, we aimed to integrate the genetic alterations, protein expression profiles, transcriptomes, and clinical characteristics of GHomas/somatotroph PitNETs to identify molecules associated with acromegaly characteristics. Targeted capture sequencing and copy number analysis of 36 genes and nontargeted proteomics analysis were performed on fresh-frozen samples from 121 sporadic GHomas/somatotroph PitNETs. Targeted capture sequencing revealed GNAS as the only driver gene, as previously reported. Classification by consensus clustering using both RNA sequencing and proteomics revealed many similarities between the proteome and the transcriptome. Gene ontology analysis was performed for differentially expressed proteins between wild-type and mutant GNAS samples identified by nontargeted proteomics and involved in G protein–coupled receptor (GPCR) pathways. The results suggested that GNAS mutations impact endocrinological features in acromegaly through GPCR pathway induction. ATP2A2 and ARID5B correlated with the GH change rate in the octreotide loading test, and WWC3, SERINC1, and ZFAND3 correlated with the tumor volume change rate after somatostatin analog treatment. These results identified a biological connection between GNAS mutations and the clinical and biochemical characteristics of acromegaly, revealing molecules associated with acromegaly that may affect medical treatment efficacy.