Assessment of hearing and balance functions in patients with acromegaly by the use of an audiovestibular test battery: a cross-sectional study.

PURPOSE: Patients with acromegaly may have abnormalities in their hearing and balance as a result of modifications in body composition and involvement of the temporal bone. The objective of this study is to examine if there are any changes in the auditory and vestibular systems in individuals with acromegaly by using audiogram and vestibular function tests. METHODS: This prospective study included 33 healthy controls and 33 acromegaly patients who were matched for age and gender distribution. A pure-tone audiometry test was conducted, including frequencies ranging from 250 Hz to 8000 Hz. Videonystagmography (VNG) was employed to assess nystagmus, an essential parameter used for assessing vestibular functions. The Video Head Impulse Test (v-HIT) was used to assess the vestibulo-ocular reflex (VOR). The Dizziness Handicap Inventory (DHI) was applied to evaluate the subjective complaints of the participants. RESULTS: The acromegaly patients had significantly elevated hearing thresholds at all frequencies (250, 500, 1000, 2000, 4000, and 6000 Hz) compared to the control group (p < 0.005). The VNG tests, including gaze horizontal, gaze vertical, saccade, spontaneous nystagmus, optokinetic, smooth pursuit, and positioning tests, did not show any statistically significant difference between the two groups (p values > 0.05). The patient group demonstrated reduced VOR gains compared to the control group in the anterior and posterior channels (p < 0.005). There was no statistically significant difference between the two groups for the occurrence of aberrant eye movements (p values > 0.05). The patient group had a total DHI score of 6.6 ± 3.2, while the control group had a score of 3.2 ± 2.6 (independent samples t-test; p < 0.001). Therefore, The patient group exhibited significantly greater subjective vestibular symptoms. CONCLUSIONS: Patients with acromegaly experience impaired auditory function. The central vestibular system remains unaffected, while the gains of the vestibulo-ocular reflex (VOR) in the posterior and anterior semicircular canals are decreased. Additionally, these patients report experiencing subjective dizziness. Screening for hearing and balance in patients with acromegaly may improve the quality of life of patients and prevent problems related to balance disorders at an early stage.

Octreotide subcutaneous depot for acromegaly: A randomized, double-blind, placebo-controlled phase 3 trial, ACROINNOVA 1.

CONTEXT: Acromegaly, characterized by excessive growth hormone (GH) and insulin-like growth factor-1 (IGF-1), impacts quality of life (QoL) and mortality. Standard of care (SoC; octreotide long-acting repeatable or lanreotide autogel) treatment typically requires healthcare provider administration. CAM2029, a novel subcutaneous octreotide depot with increased bioavailability using FluidCrystal technology, enables self-administration and room-temperature storage. OBJECTIVE: Assess superiority of CAM2029 versus placebo for biochemical control in patients with controlled acromegaly. DESIGN: 24-week, multinational, randomized, double-blind, phase 3 trial (NCT04076462). SETTING: 45 sites; ten countries. PATIENTS: 72 patients on SoC with biochemical control at screening (IGF-1 ≤upper limit of normal [ULN]; mean GH <2.5 µg/L). INTERVENTIONS: Patients were randomized 2:1 to once-monthly CAM2029 (n=48) or placebo (n=24). MAIN OUTCOME MEASURES: Primary endpoint was proportion of patients with IGF-1 ≤ULN (Week 22/24 mean), with dose-reduced patients classified as non-responders; first key secondary endpoint was the same, including dose-reduced responders. Second key secondary endpoint was proportion of patients with IGF-1 ≤ULN (Week 22/24) and mean GH <2.5 µg/L (Week 24). RESULTS: At Week 22/24 (intention-to-treat analysis), CAM2029-treated patients demonstrated superior response rates versus placebo for IGF-1 (72.2% versus 37.5%; risk difference: 34.6, 95% confidence interval: 11.3, 57.9; p=0.0018), and combined IGF-1/GH (70.0% versus 37.5%; p=0.0035). CAM2029-treated patients had well-controlled symptoms, improved QoL and treatment satisfaction versus placebo and baseline. CAM2029 was well tolerated; safety was consistent with SoC. CONCLUSIONS: CAM2029 provides a convenient and effective treatment option for acromegaly, with superior biochemical control versus placebo. Symptom control, QoL and satisfaction were improved from baseline SoC.

Remission of Acromegaly: The Sooner the Better.

Remission of acromegaly is defined by normalization of GH/IGF-1 values according to age and gender. While treatment strategies, biochemical cut-off to reach, and morbidities related to the persistence of the disease are well described in the literature, there is little data focusing on the delay to reach remission and its consequences. In this commentary, the authors discussed the results obtained from the UK acromegaly registry showing that the time to biochemical remission predicts the overall survival of patients in acromegaly.

Ectopic acromegaly with tumoral range hyperprolactinemia and apoplexy with a dramatic regression of pituitary hyperplasia.

Acromegaly due to ectopic secretion of growth hormone-releasing hormone (GHRH) is a rare disorder. The signs and symptoms of ectopic acromegaly are indistinguishable from acromegaly due to a somatotroph adenoma. A 35-year-old female presented with secondary amenorrhea for 10 years, intermittent headache, and reduced vision in both eyes for 4 years, which worsened over 4 months before presentation. Additionally, she was diagnosed with uncontrolled diabetes mellitus. On examination, she had coarse facial features, a fleshy nose, and acral enlargement. She had diminished visual acuity (left>right) and bitemporal hemianopia on perimetry. Biochemical investigations revealed elevated IGF-1 [588 ng/ml, reference range (RR) 100-242], markedly elevated basal growth hormone (>80 ng/ml; RR, 0.12-9.88), and hyperprolactinemia in the tumoral range (832 ng/ml; RR, 5-25). MRI sella demonstrated a 22×30×34mm sellar-suprasellar mass with T2 hypointensity. Chest imaging revealed a 75×87×106mm left lung mass, which was found to be a well-differentiated neuroendocrine tumor (NET) on biopsy. Plasma GHRH levels were elevated [38,088 ng/l; RR, <250-300], and a diagnosis of ectopic acromegaly secondary to lung neuroendocrine tumor was considered. During workup, the patient developed in-hospital pituitary apoplexy, which improved with medical management. After a left pneumonectomy, her clinical features of acromegaly improved, her diabetes underwent remission, and there was a marked reduction in plasma GHRH and pituitary size. Histopathology was suggestive of a neuroendocrine tumor, with immunohistochemistry positive for GHRH and negative for prolactin. Her final diagnosis was ectopic acromegaly due to GHRH secreting a lung NET with pituitary somatotroph and lactotroph pituitary hyperplasia and apoplexy in the hyperplastic pituitary.

Endoscopic endonasal transpterygoid trans lacero-cavernous resection of Knosp 4 functioning pituitary macroadenoma.

In this video, we demonstrate the technique of endoscopic transpterygoid trans lacerum trans cavernous approach for the excision of Knosp 4 functioning pituitary macroadenomas. We highlight the anatomy and key steps of the approach using cadaveric dissection and present two clinical cases. A 42-year-old female with a growth hormone-secreting tumor and Knosp 4 macroadenoma underwent an extended endoscopic endonasal approach and near-total excision of the tumor. Postoperatively she was neurologically intact. Postoperative MR showed a small residue in the lateral compartment of the cavernous sinus and along the right optic tract superiorly. Due to the proximity of the residual tumor near the optic apparatus, she was offered a pterional approach, and the tumor around the optic apparatus was excised. She was given stereotactic radiosurgery for the small residual tumor in the cavernous sinus and is currently doing well, under remission. The second case was a 23-year young male with acromegaly and bilateral Knosp 4 macroadenoma. He underwent endoscopic transpterygoid trans lacerum trans cavernous approach and gross total excision of the tumor was done. He had transient bilateral ophthalmoplegia in the immediate postoperative period which recovered fully within 6 weeks. He is currently in remission without any need for radiotherapy. To conclude, an in-depth knowledge of the anatomy helps in improving surgical outcomes in extended endoscopic endonasal surgeries.

Regression of biventricular hypertrophy in acromegalic cardiomyopathy following management of excessive growth hormone secretion.

Acromegalic cardiomyopathy is a significant cardiovascular complication associated with acromegaly, caused by excessive growth hormone production from a pituitary adenoma. Early diagnosis can be challenging due to its insidious nature. This case underscores the critical significance of timely medical intervention, illustrating favorable outcomes resulting from prompt therapeutic measures.

Variable anatomical features of acromegaly in the nasal cavity and paranasal sinuses: implications for endoscopic endonasal transsphenoidal surgery.

PURPOSE: Growth hormone (GH)-secreting pituitary neuroendocrine tumors (PitNETs) are the most common cause of acromegaly. The endoscopic endonasal transsphenoidal approach (EEA) is commonly employed to remove them. Although morphological differences in the nasal cavity exist between acromegaly patients and those with other types of PitNET, few quantitative studies have been performed. This study aimed to evaluate the anatomical features of the nasal cavity and paranasal sinuses in patients with acromegaly. METHODS: Preoperative computed tomography images of the nasal cavity and paranasal sinuses were compared between 20 patients with a GH-secreting PitNET (acromegaly group) and 22 with a non-functioning PitNET (control group). In the acromegaly group, the relationships between preoperative GH and/or insulin-like growth factor 1 (IGF-1) levels and anatomical characteristics were assessed. RESULTS: In the acromegaly group, the distance between the nostril and dorsum sellae was significantly longer and the distance between the parasellar internal carotid arteries was significantly shorter (p = 0.0022 and 0.0092, respectively). Pneumatization volume in the nasal cavity did not differ between the groups. Nasal mucosa and bony hypertrophy were observed in the acromegaly group. Preoperative GH level was correlated with the width of the piriform aperture (p = 0.0171). CONCLUSION: The nasal and paranasal changes associated with acromegaly can make EEA challenging to perform. Widening the surgical corridor anterior to the sphenoid sinus is important in these patients.

Electrocardiographic ventricular arrhythmia parameters during diagnosis and after the treatment of acromegaly: A case-control study.

Background: The risk of death is increased in acromegaly patients compared to the general population, and cardiovascular system-related complications are among the risk factors decreasing life expectancy. The Tp-e interval, which is the distance between the point where the T-wave peaks and ends on electrocardiography (ECG), shows ventricular rapolarization and, together with the Tp-e/QT and Tp-e/QTc ratios, these are relatively new tools that predict ventricular arrhythmia. We aimed to evaluate the ECG of acromegaly patients at the time of diagnosis and compare the results with current ECG findings. Material and methods: The study included 103 acromegaly patients and 81 control subjects. Of the 103 patients, 41 patients had only baseline ECG, 23 patients had only current ECG and 39 patients had both baseline and current ECGs. Heart rate, QT interval and corrected QT (QTc) interval, Tp-e, Tp-e/QT, Tp-e/QTc values on the ECGs were measured by a cardiologist. Results: In the acromegaly patients with both baseline and current ECGs, heart rate, QRS duration, Tp-e, and Tp-e/QTc ratio were decreased. The decrease in these arrhythmia parameters was similar in active and remission patients. Compared to the control group, in acromegaly patients with only baseline ECG, heart rate, QTc interval, Tp-e, Tp-e/QT, and Tp-e/QTc were decreased. Conclusion: Ventricular arrhythmia parameters improve with treatment in patients with acromegaly. The decrease in ventricular arrhythmia parameters was similar in active and remission patients, which can be explained by the significant decrease in IGF-1 levels compared to the time of diagnosis, even in patients with active disease.

Diagnosis and management of pituitary adenomas in children and adolescents.

BACKGROUND: Pituitary adenomas (PAs)-also now called pituitary neuroendocrine tumours or Pit-NETS-are rare in children and adolescents and exceptional below the age of 10. Most evidence-based high-quality data are derived from larger studies in adult patients. AIMS: We will review recent knowledge on the epidemiology, clinical features, diagnosis, and treatment modalities of the different types of pituitary adenomas diagnosed in children and adolescents, emphasizing the many reasons why these cases should be discussed within pituitary-specific multidisciplinary teams with experts from both paediatric and adult practice. CONCLUSIONS: Paediatric PA presents multiple peculiarities that may challenge their adequate management. They are overall proportionally larger and more aggressive than in adults, with potential mass effects including hypopituitarism. Hormonal hypersecretion is frequent, resulting in clinical syndromes affecting normal growth and pubertal development. Prolactinomas represent the most frequent subtype of PA found during childhood, followed by adrenocorticotropin (ACTH) and growth hormone (GH)-secreting adenomas, while clinically non-functioning adenomas are exceptionally diagnosed before the age of 16. The occurrence of a pituitary tumour in a young individual should also prompt genetic testing in each case, searching for either germline mutations in one of the known genes that may drive inherited/familial PA (such as the multiple endocrine neoplasia type 1 or MEN1 gene, or the aryl hydrocarbon receptor interacting protein or AIP gene), or for a mosaic activating mutation of GNAS as found in the McCune-Albright syndrome.

The association between change in temporal muscle mass and treatment of acromegaly.

PURPOSE: We aimed to evaluate the relationship between temporal muscle thickness and GH/IGF-1 elevation and the effect of acromegaly treatment on temporal muscle thickness. METHODS: Patients with acromegaly and healthy controls were included in the study. While laboratory parameters, clinical findings and temporal muscle thickness of acromegaly patients at the time of diagnosis and one year after treatment were evaluated, laboratory parameters and temporal muscle thickness of healthy controls were evaluated only during the period when they were included in the study. Temporal muscle thickness was measured using pituitary MRI. Temporal muscle thickness of patients with acromegaly was compared with healthy controls. We also evaluated how temporal muscle thickness changes with treatment in patients with acromegaly and the association between laboratory parameters and temporal muscle thickness. RESULTS: In patients with acromegaly, measurements of left, right, and mean temporal muscle thickness at the time of diagnosis were found to be significantly higher than those of healthy controls' measurements at the time of their inclusion in the study (p = 0.007, p = 0.014 and p = 0.018, respectively). However, no significant difference was found when comparing the temporal muscle thickness of the 1st year of acromegaly treatment with the temporal muscle thickness of healthy controls at the time of their inclusion in the study (p = 0.155, p = 0.189, p = 0.198, respectively). In addition, a significant decrease was detected in the left, right and mean temporal muscle thicknesses of patients with acromegaly before and after treatment. While the temporal muscle thickness at the time of diagnosis was thicker in patients with acromegaly receiving surgical + medical treatment than in patients receiving exclusively surgical treatment, statistical significance was only found in the left temporal muscle thickness (p = 0.042). CONCLUSION: Temporal muscle thickness was found to be associated with treatment modalities in patients with acromegaly.

Spliceosome component TCERG1 regulates the aggressiveness of somatotroph adenoma.

PURPOSE: We aimed to identify differentially expressed spliceosome components in growth hormone (GH)-secreting pituitary tumors and investigate their roles in pathogenesis. METHODS: We performed transcriptome analysis of 20 somatotroph adenomas and 6 normal pituitary tissues to select dysregulated spliceosome components. Clinical characteristics were analyzed based on gene expression in 64 patients with acromegaly. Proliferation, invasion, and hormonal activity of GH secreting pituitary adenoma cells were investigated. RESULTS: TCERG1 expression was significantly higher in somatotroph adenomas than in normal pituitaries (log2 fold change 0.59, adjusted P = 0.0002*). Genotype-phenotype analysis revealed that patients with higher TCERG1 expression had lower surgical remission rates than those with lower expression (63.64% vs. 95.45%, P = 0.009*). TCERG1 expression was significantly higher in groups with cavernous sinus (CS) invasion or Ki67 index over 3 (all P>0.05*). TCERG1 overexpression led to a 29.60% increase in proliferation (P<0.001*) and a 249.47% increase in invasion after 48 h in GH3 cells (P = 0.026*). Conversely, TCERG1 silencing significantly decreased cell proliferation (25.76% at 72 h, P<0.001*) and invasion (96.87% at 48 h, P = 0.029*). E-cadherin was decreased, but vimentin was increased in both TCERG1 overexpressed GH3 cells and somatotroph adenomas. And TCERG1 silence reversed the expression of the genes (CDH2, SNAI1, ZEB2, and VIM) in GH3 cells. CONCLUSIONS: Spliceosome machinery provide novel insights into the pathogenesis of GH-secreting pituitary tumor and highlight the potential role of TCERG1 as a biomarker for tumor aggressiveness.

Digital voice analysis as a biomarker of acromegaly.

CONTEXT: There is a considerable diagnostic delay in acromegaly contributing to increased morbidity. Voice changes due to orofacial and laryngeal changes are common in acromegaly. OBJECTIVE: Our aim was to explore the use of digital voice analysis as a biomarker for acromegaly using broad acoustic analysis and machine learning. METHODS: Voice recordings from patients with acromegaly and matched controls were collected using a mobile phone at Swedish university hospitals. Anthropometric and clinical data and the Voice Handicap Index (VHI) were assessed. Digital voice analysis of a sustained and stable vowel [a] resulted in 3274 parameters, which were used for training of machine learning models classifying the speaker as "acromegaly" or "control". The machine learning model was trained with 76% of the data and the remaining 24% was used to assess its performance. For comparison, voice recordings of 50 pairs of participants were assessed by 12 experienced endocrinologists. RESULTS: We included 151 Swedish patients with acromegaly (13% biochemically active and 10% newly diagnosed) and 139 matched controls. The machine learning model identified patients with acromegaly more accurately [area under the receiver operating curve (ROC AUC) 0.84] than experienced endocrinologists (ROC AUC 0.69). Self-reported voice problems were more pronounced in patients with acromegaly than matched controls (median VHI 6 vs 2, P < .01) with higher prevalence of clinically significant voice handicap (VHI ≥20: 22.5% vs 3.6%). CONCLUSION: Digital voice analysis can identify patients with acromegaly from short voice recordings with high accuracy. Patients with acromegaly experience more voice disorders than matched controls.

Integration of big data analytics in the investigation of the relationship between acromegaly and cancer.

OBJECTIVE: To evaluate the association between acromegaly and cancer and different types of cancer by using natural language processing systems and big data analytics. MATERIAL AND METHODS: We conducted an observational, retrospective study utilizing data from the electronic health records (EHRs) of Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain. Information from the EHRs was extracted using artificial intelligence techniques and analyzed using Savana Manager 4.0 software. RESULTS: Out of a total of 708,047 registered patients (54.7% females), 544 patients (0.08%; 330 women, 60.7%; mean age at diagnosis 53.0±15.8 yr) were diagnosed with acromegaly. The incidence of cancer was higher in patients with acromegaly vs those without this condition (7.7% vs 3.9%, p<0.001; OR, 2.047, 95%CI, 1.493-2.804). Male acromegalic patients had a higher prevalence of cancer vs females (57.1% vs 42.9%, p=0.012). A significantly higher prevalence of colorectal cancer (2.9% vs 1.4%, p=0.006), bladder cancer (1.1% vs 0.3%, p=0.005), and lymphoma (1.1% vs 0.3%, p=0.009) was observed in patients with acromegaly vs those without the condition. Acromegalic men had significantly higher prevalence rates of colorectal cancer (4.7% vs 1.3%, p=0.001), bladder cancer (2.8% vs 0.4%, p<0.001), breast cancer (0.9% vs 0.2%, p=0.042), gastric cancer (0.9% vs 0.1%, p=0.011), lymphoma (1.4% vs 0.3%, p=0.037), and liver cancer (0.9% vs 0.1%, p=0.012) vs non-acromegalic men. On the other hand, acromegalic women showed a higher prevalence of thyroid cancer (1.2% vs 0.4%, p=0.043) vs non-acromegalic women. CONCLUSION: Our study, based on artificial intelligence techniques and analysis of real-world data and information, revealed a significant association between acromegaly and cancer in our hospital population, mainly acromegalic men, with a higher frequency of colorectal cancer, bladder cancer and lymphoma in particular.

Mechanical complications and revision following total joint arthroplasty in acromegalic patients: A nationwide US-based study.

BACKGROUND: Acromegaly is associated with significant osteoarthritis (OA) and increased risk of vertebral and hip fractures. There is limited data on total joint arthroplasty (TJA) outcomes in patients with acromegaly. METHODS: In this retrospective study, we identified patients with acromegaly who underwent total hip arthroplasty (THA), total knee arthroplasty (TKA), and total shoulder arthroplasty (TSA) between 2010 and 2022 using the PearlDiver national database. Patients with a prior history of osteoporosis and follow-up duration of less than one year were excluded. Non-acromegalic control groups were selected through matching based on confounding factors. We compared all-cause revision and implant-related complications between the groups using R software integrated with the PearlDiver database. RESULTS: We identified 1440 patients with acromegaly: 665 underwent THA, 618 underwent TKA, and 157 underwent TSA. Compared to the control group (2634 THA, 2445 TKA, and 600 TSA), there was no significant association with post-op revision following THA (OR(1-year) = 0.76[0.42-1.28], OR(5-year) = 0.68[0.42-1.06]), TKA (OR(1-year) = 0.89[0.48-1.55], OR(5-year) = 0.78[0.49-1.17]), and TSA (OR(1-year) = 0.19[0.02-1.40], OR(5-year) = 0.32[0.10-1.07]). Additionally, the risk of mechanical complications did not significantly increase in patients with acromegaly, either one year or five years post-operation. CONCLUSION: The study showed no significant increase in risk of revisions or mechanical complications in patients with acromegaly compared to controls. These findings bridge an important gap in the understanding of post-arthroplasty complications in patients with acromegaly and offer valuable insights into surgical expectations.

Comparative mortality in pituitary adenomas subtypes: a tertiary referral center study.

PURPOSE: Mortality in pituitary adenomas (PAs) has been extensively compared to general population. However, direct comparisons between PA subtypes are scarce. We aimed to compare mortality in various subtypes of PA (acromegaly, Cushing's disease (CD), macroprolactinomas and non-functioning pituitary macroadenomas (MacroNFPA)), within a single referral center. METHODS: We retrospectively analyzed mortality and survival time in all 962 PAs admitted in our department between 2011 and 2023: acromegaly (n = 306), CD (n = 69), macroprolactinoma (n = 168) and MacroNFPA (n = 419). RESULTS: Median follow-up was 10.2 (5.2, 15.2) years. The overall survival probability was 90.9% and 78.1% after 10 and 20 years respectively with age at diagnosis as the only significant predictor. There were no significant differences in survival probability between various PA subtypes in the whole cohort. In patients over 45 years of age at diagnosis there was a significant difference in survival probability between the four groups (p = 0.01) in the first 15 years of follow-up. In head-to-head comparisons CD had a significantly higher mortality risk than patients with acromegaly (HR 3.38 [CI 95% 1.07 to 10.60]) even after adjusting for age and sex. CONCLUSION: Patients diagnosed with CD after 45 years of age have a significantly lower survival probability than other PA subtypes in the first 15 years of follow-up. All other PA subtypes had a similar survival probability after adjusting for age and sex. Due to advances in medical treatment of hormone secreting tumors, mortality in patients with PAs might increasingly depend more on tumor mass than on hormonal hypersecretion.

AB031. Endoscopic transsphenoidal surgery for functional pituitary adenoma: shifting paradigms towards pseudocapsule-based resection.

BACKGROUND: Functional pituitary adenomas (PAs) manifest as intricate clinical syndromes, and surgery emerges as the principal intervention to mitigate associated morbidity and mortality. The endoscopic transsphenoidal surgery (ETS) approach stands as the preferred method for addressing PAs, with postoperative remission acting as a pivotal prognostic factor. METHODS: This study seeks to evaluate the influence of different surgical techniques and complications of ETS on functional PAs, focusing on both Acromegaly and Cushing's disease (CD). Patient records, including characteristics, perioperative assessments, postoperative complications, and follow-up data, were systematically gathered. Tumor resection methods were categorized into: (I) complete pseudocapsule resection; and (II) complete piecemeal resection. Post-surgery, daily monitoring of serum cortisol levels continued for a consecutive 3-day period until values of 2 µg/dL or less were achieved. Growth hormone levels were reassessed 12 weeks later, targeting a level of <0.14 g/L. A follow-up enhanced magnetic resonance imaging examination was conducted 3 months post-surgery to confirm the absence of residual tumors. RESULTS: The study identified 46 patients (23 with acromegaly and 13 with CD) who underwent endoscopic surgery between 2020 and 2023. Twenty-six patients underwent piecemeal resection (January 2020 to December 2022), while 10 patients underwent complete pseudocapsule removal (January to December 2023). No significant changes in surgical complications were observed between the two techniques. No instances of carotid artery injury, epistaxis, intracranial infection, or loss of olfaction were reported. In the pseudocapsule group, one patient experienced transient vision loss. Notably, 80% of patients in the pseudocapsule group achieved remission as compared to 57.7% in the piecemeal group. CONCLUSIONS: Pseudocapsule-based resection exhibited a remarkable remission rate, a low complication rate, and an absence of recurrence in functional adenoma patients. Despite the limited number of cases and our early experience, further studies are warranted to validate its effectiveness and safety.

AB092. Imaging the histopathology subtypes of the growth hormone-secreting pituitary neuroendocrine tumor.

BACKGROUND: Sparsely granulated (SG) growth hormone-secreting pituitary neuroendocrine tumors (GH-PitNETs) often present with a more aggressive clinical course compared to densely granulated (DG) tumors. These subtypes exhibit distinct biological and imaging characteristics. Thus, this study aims to differentiate between the histopathological subtypes of GH-PitNETs using pre-operative magnetic resonance imaging (MRI). METHODS: A retrospective analysis was conducted on 83 acromegalic patients treated at our institution between 2000 and 2010. Tumor volumes were segmented from preoperative MRIs, including T1-weighted, T2-weighted, T1 with contrast, and T2 fluid attenuated inversion recovery (FLAIR) sequences. Reference regions of interest (ROIs) were delineated using gray and white matter from the same sequences. Two pathologists reviewed pathology specimens for anti-cytokeratin (CAM 5.2) and Pit-1 expression. Clinical and radiological biomarkers were compared between SG and DG patients. RESULTS: A total of 83 patients with complete histopathology and 51 patients with complete MRIs were included in the analysis. SG PitNETs exhibited higher rates of supra-sellar invasion (61.5%, P<0.001), larger tumor sizes, lower pre-operative GH levels, and increased post-operative residual tumor (65.4%, P<0.001) compared to DG PitNETs. Additionally, SG PitNETs showed greater hyperintensity on T2-weighted images and enhanced contrast, whereas DG PitNETs exhibited less contrast enhancement. Utilization of these imaging biomarkers demonstrated an 94.1% accuracy in T2 FLAIR and overall of 78.7% predicting the histopathological subtypes of GH-PitNETs. CONCLUSIONS: Distinct histopathological subtypes of GH-PitNETs represent crucial prognostic factors. Utilizing multimodal pre-operative MRIs, clinicians can accurately identify sparsely granulated GH-PitNETs, facilitating improved treatment planning strategies.

Correlation between insulin-like growth factor and complexity of glucose time series index in patients with newly diagnosed acromegaly: a PILOT study.

BACKGROUND: Acromegaly has a high risk of abnormal glucose metabolism. The complexity of the glucose time series index (CGI) is calculated from refined composite multi-scale entropy analysis of the continuous glucose monitoring (CGM) data. CGI is a new indicator of glucose imbalance based on ambulatory glucose monitoring technology, which allows for earlier response to glucose metabolism imbalance and correlates with patient prognosis. OBJECTIVE: To compare the differences in glucose metabolic profile and CGI between acromegaly with normal glucose tolerance (NGT) and healthy subjects. METHODS: Eight newly diagnosed patients with acromegaly (GH group) and eight age- and gender-matched healthy subjects (Control group) were included in this study. All participants underwent oral glucose tolerance test (OGTT) and 72-h CGM. A refined composite multi-scale entropy analysis was performed on the CGM data to calculate the CGI and we compare the differences in glycemic profiles and CGI between the two groups. RESULTS: After OGTT, compared with the control group, patients in the GH group had higher 2 h blood glucose (BG) (mmol/L) [GH vs control, 6.7 (6.1, 7.0) vs 5.2 (3.8, 6.3), P = 0.012], 3 h BG [5.1 (3.8, 6.5) vs 4.0 (3.4, 4.2), P = 0.046], mean BG [6.3 (6.1, 6.5) vs 5.5 (5.1, 5.9), P = 0.002], 2 h insulin (mU/L) [112.9 (46.8, 175.5) vs 34.1 (17.1, 55.6), P = 0.009], and 3 h insulin [26.8 (17.1, 55.4) vs 10.4 (4.2, 17.8), P = 0.016]. CGI was lower in the GH group [2.77 (1.92, 3.15) vs 4.2 (3.3, 4.8), P = 0.008]. Spearman's correlation analysis showed insulin-like growth factor (IGF) (r = -0.897, P < 0.001) and mean glucose (r = -0.717, P = 0.003) were significantly negatively correlated with CGI. Multiple linear stepwise regression showed that IGF-1 (r = -0.652, P = 0.028) was independent factor associated with CGI in acromegaly. CONCLUSION: IGF-1 was significantly associated with CGI, and CGI may serve as a novel marker to evaluate glucose homeostasis in acromegaly with normal glucose tolerance.

The Use of Kidney Biomarkers, Nephrin and KIM-1, for the Detection of Early Glomerular and Tubular Damage in Patients with Acromegaly: A Case-Control Pilot Study.

BACKGROUND: Acromegaly is a rare disorder caused by excessive growth hormone (GH) secreted from a pituitary tumor. High levels of GH and insulin growth factor-1 can lead to renal hypertrophy, as well as to diabetes mellitus and hypertension, which negatively impact kidney function. It is believed that high GH may also be involved in the onset of diabetic nephropathy, the main cause of end-stage kidney disease in developed countries. MATERIAL AND METHODS: This case-control study was conducted on 23 acromegalic patients and on a control group represented by 21 healthy subjects. The following parameters were determined for all the subjects: serum creatinine, serum urea, estimated glomerular filtration rate (eGFR), urinary albumin/creatinine ratio (UACR), nephrin and kidney injury molecule 1 (KIM-1). RESULTS: Patients with acromegaly showed higher levels of UACR and lower levels of eGFR as compared to healthy subjects. No significant correlations were found between clinical or biochemical parameters associated with acromegaly and nephrin or KIM-1. CONCLUSIONS: There was no glomerular or proximal tubular damage at the time of the study, as proven by the normal levels of the biomarkers nephrin and KIM-1. Studies including more patients with uncontrolled disease are needed to clarify the utility of nephrin and KIM-1 for the detection of early kidney involvement in acromegalic patients.