GH-secreting Adenomas Research Articles

Abstract #1398813: A Rare Case of Acromegaly with Negative Immunohistochemical Staining for Growth Hormone

We are presenting a case of mixed prolactin and growth hormone (GH)-pituitary tumor with negative immunostaining for GH. 81-year-old male with history of type 2 diabetes mellitus, hypertension, obstructive sleep apnea, and colon polyps was found to have a pituitary macroadenoma during evaluation of his visual disturbances. Years before the presentation, he noticed his shoe size had increased and his wife observed his jaw becoming more prominent. Physical exam was notable for enlarged nose, mandibular prognathism, and enlarged hands. Pre-operative laboratory results were remarkable for significantly elevated levels of insulin-like growth factor-1 (IGF-1), GH, and prolactin. He underwent transsphenoidal resection (TSPR) of the mass and pathology demonstrated a lactotroph adenoma, negative for GH immunostaining. After surgery he was started on cabergoline 0.5mg PO twice weekly. Three months afterwards his IGF-1 level remained elevated at 415 ng/mL. Acromegaly was confirmed by an elevated GH level of 13.8 ng/mL 2-hours after oral glucose challenge, then a long-acting somatostatin analogue depot was initiated for treatment. In the first year of therapy, he had weight loss and hypoglycemia that required discontinuation of insulin therapy. His IGF-1 and GH levels decreased to within age-appropriate ranges. His prolactin level returned to normal and cabergoline was stopped after a successful discontinuation trial. Clinical suspicion for acromegaly is confirmed by elevated IGF-1 and GH levels. When a GH-secreting pituitary adenoma is resected, immunocytochemistry with GH staining typically supports the diagnosis. It is not common for these tumors to stain negative for GH in the presence of clinical and biochemical acromegaly. The opposite—termed silent somatotroph— is more common and may represent an early stage in the development of a somatotroph adenoma. Failure to provide adequate diagnostic tissue, histopathology misread, or loss of antigenicity during fixation or embedding may be reasons for false negatives. However, it has been suggested that sparse cytoplasmic stores of GH do not parallel the hypersecretion of GH and may reduce staining capacity. Thus, a diagnosis of acromegaly should be made in patients with clinical and biochemical findings, even in the absence of GH immunostaining.

Predictors of Remission of Acromegaly following Surgical Treatment in Growth Hormone-Secreting Pituitary Adenoma.

Background and Objective Surgery is the treatment of choice for growth hormone (GH)-secreting pituitary adenoma. The remission of random GH depends on various factors. We aimed to evaluate the predictors related to remission of random GH following surgical treatment. Methods We collected the data retrospectively from the chart review from a single unit of neurosurgery. The diagnostic criteria for remission were a random GH < 1 ng/mL or nadir GH < 0.4 ng/mL after an oral glucose tolerance test. Results Data from a total of 110 (females 62 [56.4%]) patients were available for follow-up and were analyzed. The mean age was 36.5 years (14-69 years). Vision impairments were seen in 39 (35.5%) patients. The mean duration of symptoms before surgery was 34 months. The mean volume of the tumor was 7.2 mL (0.44-109.8 mL). Knosp grade 3 and 4 tumors were seen in 41.5% of cases. The mean preoperative random GH level was 68.9 ng/mL. Transsphenoidal surgery was done in 107 (97.3%) cases. The gross total resection could be done in 36 (32.7%) cases. At 3 months, 25 (26%) patients had a biochemical remission. In univariable analysis, lower Knosp grade, preoperative GH level < 40 ng/mL, gross total resection, and male gender were associated with remission at 3 months. In regression analysis, preoperative GH and male gender were related to remission at 3 months. Conclusion The preoperative GH level < 40 ng/mL is associated with higher chances of remission after surgery for GH-secreting pituitary adenoma.

Cognitive Dysfunction, an Increasingly Valued Long-Term Impairment in Acromegaly.

Acromegaly is a chronic disease caused by the overproduction of growth hormone (GH) and accompanying insulin-like growth factor-1 (IGF-1), which is often caused by GH-secreting pituitary adenomas. In addition to its somatic burden, a growing number of studies have found that patients suffering from acromegaly exhibit psychosocial and personality changes. Over the past 70 years, there has been increasing interest in the cognitive impairment and neuropsychological issues of patients with acromegaly, and a variety of neuropsychological and neurophysiological tests have been used to measure cognitive changes in patients. The impact of disease progression status, treatment modalities, and various comorbidities on cognitive function and the mechanisms of cognitive impairment in patients with acromegaly are therefore outlined in this review. Multidisciplinary assessment has important implications for the management of acromegaly, particularly in relation to cognitive function. Here, we summarize the relevant literature concerning cognitive-behavioral research on acromegaly to demonstrate the impact of long-term impairment caused by GH and IGF-1 on the cognitive behavior of patients.

Modern approach to resistant acromegaly.

Targets of acromegaly treatment are normalization of biochemical values, removal/reduction/stabilization of the pituitary mass, control of clinical activity and mortality with a multimodal/multidisciplinary approach. Despite significant technological and pharmacological progress, still several patients with acromegaly bear a resistant somatotroph adenoma and active disease may persist for many years with resultant poor clinical outcomes. To review briefly definition and pathophysiology of resistance to acromegaly treatment and the options of medical treatment in this context, exploring the role of novel clinical and molecular biomarkers in the personalization of therapy and proposing updates to the currently available guidelines for the treatment of resistant GH-secreting adenomas. In the last few years, in parallel with the increased number of medical options available for the therapy of acromegaly, relevant advances occurred in the understanding of the role of novel molecular and clinical biomarkers in predicting the responsiveness to second-line medical treatments, such as Pegvisomant and Pasireotide LAR, and helping clinicians in the personalization of the follow-up and treatment of resistant somatotroph adenomas. The integration of these findings into the existing guidelines may represent a possibly important step forward in the management of "difficult" acromegaly patients.

Pure Endoscopic Endonasal Treatment of Acromegaly; Classification, Remission Rates, Factors Affecting Remission, and Complications

Aim This study aims to evaluate the effectiveness of the pure endoscopic endonasal transsphenoidal (PEET) approach in treating acromegaly, focusing on remission criteria set by the 2002 and 2010 consensus guidelines. It also seeks to identify variables that affect remission and to analyze early postoperative IGF-1 levels 24 hours after surgery to determine their predictive value for remission. Material and Methods The study retrospectively reviewed the medical records of 129 acromegaly patients who underwent the PEET (Pure Endoscopic Endonasal Transsphenoidal) surgical approach between November 2010 and March 2016 at Ankara Numune Training and Research Hospital. Out of these, 124 patients with complete follow-up and laboratory data were included in the analysis. The study evaluated a range of variables including patients' symptoms, pre- and postoperative GH and IGF-1 levels, imaging results, and remission statuses based on the 2002 and 2010 consensus guidelines. Inclusion criteria for the study required patients to have specific preoperative and postoperative data and a minimum follow-up duration of at least 6 months. Results The study found statistically significant differences between the remission rates based on the 2002 and 2010 consensus criteria for acromegaly, with a 73.4% remission rate under the 2002 criteria and a 65.3% remission rate under the 2010 criteria (p=0.002). Multivariate logistic regression analysis indicated that the atypical nature of the adenoma (p=0.018) and surgical intervention due to recurrence (p=0.028) were significant negative factors affecting cure rates. The study also identified that advanced stages in Hardy Wilson (p=0.008) and Knosp (p&lt;0.001) classifications had a statistically significant negative impact on achieving a cure. No statistically significant predictive value was found for early postoperative IGF-1 levels in relation to cure (p=0.612). Conclusion: PEET is currently the preferred treatment option for GH-secreting pituitary adenomas and has high remission rates.

Integrating Methylome and Transcriptome Signatures Expands the Molecular Classification of the Pituitary Tumors.

To explore pituitary tumors by methylome and transcriptome signatures in a heterogeneous ethnic population. In this retrospective cross-sectional study, clinicopathological features, methylome, and transcriptome were evaluated in pituitary tumors from 77 patients (61% women, age 12-72 years) followed due to functioning (FPT: GH-secreting n = 18, ACTH-secreting n = 14) and nonfunctioning pituitary tumors (NFPT, n = 45) at Ribeirao Preto Medical School, University of São Paulo. Unsupervised hierarchical clustering analysis (UHCA) of methylome (n = 77) and transcriptome (n = 65 out of 77) revealed 3 clusters each: one enriched by FPT, one by NFPT, and a third by ACTH-secreting and NFPT. Comparison between each omics-derived clusters identified 3568 and 5994 differentially methylated and expressed genes, respectively, which were associated with each other, with tumor clinical presentation, and with 2017 and 2022 WHO classifications. UHCA considering 11 transcripts related to pituitary development/differentiation also supported 3 clusters: POU1F1-driven somatotroph, TBX19-driven corticotroph, and NR5A1-driven gonadotroph adenomas, with rare exceptions (NR5A1 expressed in few GH-secreting and corticotroph silent adenomas; POU1F1 in few ACTH-secreting adenomas; and TBX19 in few NFPTs). This large heterogenic ethnic Brazilian cohort confirms that integrated methylome and transcriptome signatures classify FPT and NFPT, which are associated with clinical presentation and tumor invasiveness. Moreover, the cluster NFPT/ACTH-secreting adenomas raises interest regarding tumor heterogeneity, supporting the challenge raised by the 2017 and 2022 WHO definition regarding the discrepancy, in rare cases, between clinical presentation and pituitary lineage markers. Finally, making our data publicly available enables further studies to validate genes/pathways involved in pituitary tumor pathogenesis and prognosis.

Vascular anomalies in patients with growth hormone-secreting pituitary adenomas: illustrative case report and systematic review of the literature

PurposeEndonasal resection is the first-line treatment for patients harboring growth hormone (GH)-secreting pituitary adenomas. The complexity of the parasellar neurovascular structures makes pre-operative diagnostic imaging essential to understanding the anatomy of this region. We aimed to describe vascular anomalies in acromegalic patients and emphasize their relevance for surgery and preoperative planning.MethodsA systematic review following the PRISMA statement was performed in July 2021.ResultsThirty-three studies were evaluated. Elevated GH and insulin-like growth factor-1 (IGF-1) levels are linked to the occurrence of cardiovascular risk factors. This is attributed to endothelial dysfunction, mainly caused by changes in flow-mediated dilatation (FMD), which is probably the main cause of vascular anomalies in acromegaly. The occurrence of protrusions of the internal carotid artery (ICA) (35–53%), a narrow intercarotid distance, and an asymmetrical course was described. In 13–18% of acromegalic patients, the presence of an intracerebral aneurysm could be reported (incidence in the general population:0.8–1.3%). The selected studies were however performed with a small patient sample (range:1–257).We present a case report of a 57y/o male patient with anomalies of the ICA (“kissing carotid arteries”) harboring a GH-secreting adenoma, which was resected via an endoscopic endonasal approach.ConclusionsThere is an association between acromegaly and endothelial dysfunction, which increases cardiovascular risk factors and vascular anomalies. Preoperative vascular imaging, e.g., CT angiography, should be implemented as a standard to identify patients at risk and estimate surgical morbidity. However, no evidence-based recommendations exist so far, so future studies are necessary.

Presence of cerebral microbleeds is associated with cognitive decline in acromegaly.

Cognitive decline in acromegaly has gained increasing attention. Cerebral microbleeds (CMBs) as radiographic markers for microvascular injury have been linked to various types of cognitive decline. However, the association between CMB formation and acromegaly has not yet been quantified. This study is designed to investigate the prevalence and the radiographic patterns of CMBs and the association between cognitive function and acromegaly-related CMBs in growth hormone (GH)-secreting pituitary adenoma, which is characterized by acromegaly. In a cohort of 55 patients with GH-secreting pituitary adenoma (acromegaly) and 70 healthy control (HC) patients, we determined the presence of CMBs using a 3.0-T MRI scanner. The numbers, locations, and grades of CMBs were determined via susceptibility-weighted imaging (SWI) and the Microbleed Anatomical Rating Scale. Obstructive sleep apnea (OSA) was assessed using the criteria of the American Academy of Sleep Medicine (AASM) Scoring Manual Version 2.2. The Montreal Cognitive Assessment (MoCA) was used to assess cognitive performance within 3days of admission. The association between CMBs and cognitive function as well as clinical characteristics was explored. The incidence of CMBs was 29.1%, whereas that of OSA was 65.5% in acromegaly. There was a statistically significant difference in the prevalence of CMBs between subjects with and without acromegaly (29.1% and 5.3%, respectively) (p<0.01). The age of acromegaly patients with CMBs was much younger compared with HCs with CMBs. Compared with HCs, a significant cognitive decline and the occurrence of OSA were demonstrated in patients with acromegaly (p<0.01). Binary logistic regression analysis adjusted for age, education, and body mass index (BMI) revealed that CMB was an independent risk factor for cognitive impairment in patients with acromegaly (OR=3.19, 95% CI 1.51-6.76, p=0.002). Furthermore, in the logistic regression models adjusted for age, BMI, diabetes, and hypertension, OSA was independently associated with the occurrence of CMBs in patients with acromegaly (OR=13.34, 95% CI 3.09-57.51, p=0.001). A significant increase of CMBs was demonstrated in patients with acromegaly, which may be a result of OSA in acromegaly. The present study indicated that increasing CMBs are responsible for cognitive decline in patients with acromegaly.

Giant growth hormone-secreting pituitary adenomas from the endocrinologist's perspective.

Since giant (≥40 mm) GH-secreting pituitary adenomas are rarely encountered, data on their characteristics and treatment outcomes are limited. We aimed to investigate the characteristics of giant GH-secreting pituitary adenomas and to compare their clinical, biochemical, imaging and histopathological features with non-giant macroadenomas. We have evaluated 15 (six female/nine male) and 57 (29 female/28 male) patients with acromegaly in giant and <40 mm adenoma groups, respectively. Patients with <40 mm adenoma were further divided into subgroups with adenoma size 20-29 mm and 30-39 mm. In giant adenoma group, median (IQR) preoperative maximal diameter of adenoma was 40 mm (5 mm), median preoperative GH level was 40 (153.4) ng/mL and median baseline IGF-1 level was 2.19 (1.88) × ULN for age and sex. The number of surgeries was significantly higher in giant adenoma group (median 2, IQR 2) in which 66.7% of patients underwent repeated surgeries (p = 0.014). Residual tumor was detected after last operation in all patients with giant adenoma. Total number of treatment modalities administered postoperatively increased as adenoma size increased (p = 0.043). After a median follow-up duration of 10 years (IQR 10), hormonal remission was achieved in six patients (40%) of giant adenoma group, while the rate of hormonal remission in non-giant adenoma group was 37%. Although preoperative GH and IGF-1 levels and Ki-67 index tended to be higher with increasing adenoma size, there was no statistically significant difference between groups in terms of these variables, as well as age, sex and invasion status. Hormonal remission rates of acromegaly patients with ≥20 mm pituitary macroadenoma were comparable. However, giant GH-secreting pituitary adenomas require an aggressive multimodal treatment approach.

PMON105 Giant Growth Hormone (GH)-Secreting Pituitary Tumor with Massive Sphenoid Sinus Invasion and Spontaneous Cerebrospinal Fluid (CSF) Leak: A Case Report

Abstract Introduction Giant pituitary tumor, defined as &amp;gt;4cm, comprise 6-10% of all pituitary tumors. Giant GH-secreting pituitary tumors are rare and difficult to treat. They typically invade surrounding structures ​such as the cavernous sinus, making ​complete resection challenging or impossible. This report highlights a case of giant GH-secreting pituitary tumor with an unusual clinical presentation.CLINICAL CASE: A 56 Y/O male with hypertension, cardiomyopathy, obesity, and OSA presented to the ER with stroke-like symptoms. Brain CT and MRI revealed small acute to subacute infarcts within the left occipital, left frontal, right frontal, right parietal areas, and right cerebellum. An incidental finding was a 4.3 cm T2 hyperintense enhancing mass centered within the skull base with involvement of the sella, extension into bilateral cavernous sinuses, clivus, encasement of bilateral carotid arteries, and invasion through the sphenoid sinus into the nasopharyngeal space resulting in a preoperative CSF. He was overtly acromegalic with coarse facial features, prominent frontal bossing, early prognathism, and macroglossia. Hands and feet were enlarged, but non-edematous. Visual field testing was normal. Laboratory values: IGF-1, 317 ng/mL (NL &amp;lt;170): GH, 4 ng/ml (NL&amp;lt;10); prolactin, 17.6 ng/mL (NL 2.5-17.4); total testosterone, 11 ng/dL (NL 130-810); free testosterone, 2 pg/dL (NL 36-146). ACTH stimulation produced a normal cortisol response. Test for AIP gene mutation was negative. Emergent packing of the CSF leak site was done. He underwent trans-sphenoidal (TSS) debulking of the tumor along with reconstruction of the ​skull base and repair of CSF leak. Postoperatively, IGF-1 level decreased to 216 ng/mL. Immunohistochemical stains of the tumor were strongly positive for GH and somatostatin receptor type2 (SSTR2). Three weeks postoperatively, IGF-1 increased to 482 ng/mL. IGF-1 level decreased to 326 ng/mL after 3 doses of lanreotide 90 mg/month. He will be now monitored on 120 mg/month. Currently, he requires only testosterone replacement. Conclusion This patient had the unique presentation of florid acromegaly and CSF leak mainly related to his delay in seeking medical care. Absence of visual defects has been noted in only 15% of reported patients with giant GH-secreting adenomas. Massive replacement of the sphenoid sinus by a giant pituitary tumor causing a CSF leak with invasion into the ​cavernous sinuses and clivus has been rarely reported. Trans-sphenoidal resection is the preferred first-line treatment for patients with acromegaly. The remission rate decreases and can reach almost 0% for giant GH-secreting tumors. Somatostatin receptor analogs (SRA) are the preferred first-line pharmacological treatment as an adjuvant therapy for residual tumor. Our patient likely will need continued SRA and potentially other modalities to control acromegaly due to unresectable tumor anatomy. This case also highlights the complications of delayed detection and benefits of extensive TSS surgical resection with the goal to enhance his response to SRA. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Frequency of CSF Rhinorrhoea in Patients Undergoing Endoscopic Transsphenoidal Surgery (ETSS) for Pituitary Macroadenoma

Introduction: Pituitary adenoma resection via the transsphenoidal approach (TSS)is a safe and common neurosurgical procedure that can be done both through microscopic and endoscopic methods. Objectives: The main objective of the study is to find the frequency of CSF rhinorrhoea in patients undergoing endoscopic transsphenoidal surgery (ETSS) for pituitary macroadenoma. Material and methods: The study data was collected from 1st Oct to 1st Nov 2022, in the departments of Neurosurgery of Hayatabad Medical complex, Khyber Teaching Hospital, Lady Reading Hospital, Peshawar. The data was collected through non-probability consecutive sampling technique. There were 315 patients which were included in the study. The surgical procedure is done under general anesthesia. All patient data was collected and a standardized form was filled by the attending surgeon caring for the patient. Importantly, the primary end points to be recorded were: (1) techniques of intraoperative cranium base reconstruction used, and (2) postoperative CSF rhinorrhoea biochemically confirmed and/or requiring intervention (CSF diversion and/or operative restoration). Results: Of the 315 consecutive patients diagnosed with pituitary adenomas, a total of 250 patients met the inclusion criteria and were included. The pathology included 187 (74.8%) non-functioning adenomas, 40 (16.0%) GH-secreting pituitary adenomas, 3 (1.2%) PRL-secreting pituitary adenomas, and 20 (8.0%) ACTH-secreting pituitary adenomas. There were 30 (12.0%) cases of microadenomas, 205 (82.0%) cases of macroadenomas, and 15 (6.0%) cases of giant adenomas. Intraoperative CSF leakages were determined throughout surgical procedure in eighty patients (32.0%). Postoperative CSF leaks occurred in 9 patients (3.6%), including seven patients with intraoperative CSF leaks. Practical implication: Practical implications of this study is: (1) easily find the CSF leakage (2) frequency of CSF rhinorrhoea in patients undergoing endoscopic transsphenoidal surgery Conclusion: It is concluded that macroadenoma ETSS surgery should be strictly monitored for post-operative CSF leakage and lumber drain is an effective prophylactic strategy. Keywords: Postoperative CSF Leakage, Pituitary Adenomas, ETSS, Surgery, Lumber

Development and testing of diagnostic algorithms to identify patients with acromegaly in Southern Italian claims databases

Acromegaly is a rare disease characterized by an excessive production of growth-hormone and insulin-like growth factor 1, typically resulting from a GH-secreting pituitary adenoma. This study was aimed at comparing and measuring accuracy of newly and previously developed coding algorithms for the identification of acromegaly using Italian claims databases. This study was conducted between January 2015 and December 2018, using data from the claims databases of Caserta Local Health Unit (LHU) and Sicily Region in Southern Italy. To detect acromegaly cases from the general target population, four algorithms were developed using combinations of diagnostic, surgical procedure and co-payment exemption codes, pharmacy claims and specialist’s visits. Algorithm accuracy was assessed by measuring the Youden Index, sensitivity, specificity, positive and negative predictive values. The percentage of positive cases for each algorithm ranged from 7.9 (95% CI 6.4–9.8) to 13.8 (95% CI 11.7–16.2) per 100,000 inhabitants in Caserta LHU and from 7.8 (95% CI 7.1–8.6) to 16.4 (95% CI 15.3–17.5) in Sicily Region. Sensitivity of the different algorithms ranged from 71.1% (95% CI 54.1–84.6%) to 84.2% (95% CI 68.8–94.0%), while specificity was always higher than 99.9%. The algorithm based on the presence of claims suggestive of acromegaly in ≥ 2 different databases (i.e., hospital discharge records, copayment exemptions registry, pharmacy claims and specialist visits registry) achieved the highest Youden Index (84.2) and the highest positive predictive value (34.8; 95% CI 28.6–41.6). We tested four algorithms to identify acromegaly cases using claims databases with high sensitivity and Youden Index. Despite identifying rare diseases using real-world data is challenging, this study showed that robust validity testing may yield the identification of accurate coding algorithms.

A Comprehensive Review of Four Clinical Practice Guidelines of Acromegaly.

Acromegaly is an endocrine disorder characterized by dysregulated hypersecretion of growth hormone (GH), leading to an overproduction of insulin-like growth factor 1 (IGF-1). The etiology is usually a GH-secreting pituitary adenoma with the resultant presentation of coarse facial features, frontal bossing, arthritis, prognathism (protrusion of the mandible), and impaired glucose tolerance, among others. Most pituitary adenomas arise due to sporadic mutations that lead to unregulated cellular division, subsequent tumor formation, and resultant GH hypersecretion. Major scientific organizations and authorities in endocrinology release regularly updated guidelines for diagnosing and managing acromegaly. We have holistically evaluated four data-driven and evidentiary approaches in the management of acromegaly to compare and contrast these guidelines and show their salient differences. These guidelines have been reviewed because they are major authorities in acromegaly management. In this comprehensive article, differences in the diagnosis and treatment recommendations of the discussed guidelines have been highlighted. Our findings showed that diagnosing modalities were similar among the four approaches; however, some guidelines were more specific about additional supporting investigations to confirm a diagnosis of acromegaly.For management options, each guideline had suggestions about ideal therapeutic outcomes. Treatment options were identical but salient differences were noticed, such as the addition of combination therapy and alternative therapy in the setting of failure to respond to first and second-line treatments. Reviewing clinical guidelines for various pathologies encourages sharing ideas among medical practitioners and ensures that global best practices are adopted. Therefore, a constant review of these clinical practice guidelines is necessary to keep clinicians up to date with the latest trends in patient management.

MicroRNA in Acromegaly: Involvement in the Pathogenesis and in the Response to First-Generation Somatostatin Receptor Ligands.

Acromegaly is a chronic and systemic disease due to excessive growth hormone and insulin-like growth factor type I caused, in the vast majority of cases, by a GH-secreting pituitary adenoma. About 40% of these tumors have somatic mutations in the stimulatory G protein alpha-subunit 1 gene. The pathogenesis of the remaining tumors, however, is still not fully comprehended. Surgery is the first-line therapy for these tumors, and first-generation somatostatin receptor ligands (fg-SRL) are the most prescribed medications in patients who are not cured by surgery. MicroRNAs are small, non-coding RNAs that control the translation of many mRNAs, and are involved in the post-transcriptional regulation of gene expression. Differentially expressed miRNAs can explain differences in the pathogenesis of acromegaly and tumor resistance. In this review, we focus on the most validated miRNAs, which are mainly involved in acromegaly’s tumorigenesis and fg-SRL resistance, as well as in circulating miRNAs in acromegaly.

Surgery for acromegaly: Indications and goals.

Acromegaly is a disease that occurs secondary to high levels of GH, most often from a hormone-secreting pituitary adenoma, with multisystem adverse effects. Diagnosis includes serum GH and IGF-1 levels, and obtaining an MRI pituitary protocol to assess for a functional pituitary adenoma. Attempted gross total resection of the GH-secreting adenoma is the gold standard in treatment for patients with acromegaly for a goal of biochemical remission. Medical and radiation therapies are available when patients do not achieve biochemical cure after surgical therapy.

Abstract #1180171: A case report of acromegaly in a patient with papillary thyroid cancer

Acromegaly is a rare disorder due to hypersecretion of growth hormone (GH) with a prevalence of 4,600 per million and an incidence of 116.9 new cases per million per year. The majority of cases are caused by a somatotroph GH-secreting anterior pituitary adenoma which can have significant morbidity and mortality. Several studies indicate that excess IGF-1 can stimulate proliferation of thyroid follicular cells and increase the risk of thyroid cancer greater than five-fold.

Endocrinological aspects of pituitary adenoma surgery in Europe

Hormone-secreting adenomas are treated in many neurosurgical centers within Europe. The goal of the survey is to understand variance in practice management of pituitary tumors amongst neurosurgical centers. A list of departments performing pituitary surgery was created. The survey consisted of 58 questions. This study focuses on neurosurgical care of hormone-secreting adenomas. For analysis, the departments were divided into four subgroups: academic/non-academic, high-volume/low-volume, “mainly endoscopic/mainly microscopic practice” and geographical regions. Data from 254 departments from 34 countries were obtained. Most centers surgically treat 1–5 hormone-secreting adenomas per year. In prolactinomas this is the case in 194 centers, (76.4%), in GH-secreting adenomas: 133 centers, (52.4%), ACTH-secreting adenomas: 172 centers, (69.8%). Surgery as a primary treatment of prolactinomas is considered in 64 centers (25.2%). In 47 centers (18.8%), GH-secreting microadenomas are often treated pharmacologically first. Debulking surgery for an invasive GH-secreting adenoma in which hormonal remission is not a realistic goal of the surgery and the patient has no visual deficit surgery is always or mostly indicated in 156 centers (62.9%). Routine postoperative hydrocortisone replacement therapy is administered in 147 centers (58.6%). Our survey shows that in most centers, few hormone-secreting adenomas are treated per year. In about 25% of the centers, prolactinoma surgery may be regarded as first-line treatment; in about 20% of the centers, medical treatment is the first-line treatment for GH-secreting adenomas. Pretreatment for ACTH-secreting adenomas is routinely used in 21% of centers. This survey may serve as plea for neurosurgical care centralization of hormone-secreting adenomas.

Methylome Analysis in Nonfunctioning and GH-Secreting Pituitary Adenomas.

Pituitary adenomas (PAs), usually benign lesions, can sometimes present with “aggressive” features (rapid growth, local invasiveness, scarce response to conventional treatments). Despite the fact that a few genetic alterations have been associated to this clinical behavior, the role of epigenetic modifications, mainly methylation and miRNAs activity, is now opening new frontiers in this field. We evaluated the methylation profile of 21 PA (11 GH-omas, 10 nonfunctioning tumors—NFPAs) samples from TNS surgery and 5 normal pituitaries, collected at our neurosurgery between 2015 and 2017. DNA was extracted and sequenced, selecting 184,841 target regions. Moreover, methylation profiles were correlated with demographic, radiological, and clinicopathological features. NFPAs showed higher methylation levels vs. GH-omas, with 178 differentially methylated regions (DMRs) mainly consisting of noncoding and intronic sequences, and mostly localized in the open sea regions. We also found three hypermethylated genes (C7orf50, GNG7, and BAHCC1) involved in tumorigenesis processes and potentially influencing pituitary tumor pathophysiology. Among the clinicopathological features, only the maximum diameter resulted significantly higher in NFPAs. Our data provide further evidence of the complex epigenetic background of pituitary tumors. In line with the current literature, we confirmed a significant prevalence of hypermethylation in NFPAs vs. GH-omas, whose pathophysiological consequence is yet to be defined.

Intraoperative Alcoholization of the Pituitary Gland Does Not Reduce the Recurrence Rate of Growth Hormone Secreting Pituitary Adenomas.

Objective Although the role of intraoperative alcoholization of the pituitary gland has been examined for the management of malignant tumor metastases and Rathke's cleft cysts, no such studies have been conducted relating to growth hormone (GH) secreting pituitary tumors, despite the high rate of recurrence in this cohort of patients. Here, we sought to understand the impact of adjunctive intraoperative alcoholization of the pituitary gland on recurrence rates and perioperative complications associated with resection of GH-secreting tumors. Methods This is a single-institution retrospective cohort study analyzing recurrence rates and complications among patients with GH-secreting tumors who received intraoperative alcoholization of the pituitary gland postresection versus those that did not. Welch's t -tests and analysis of variance (ANOVA) analyses were employed to compare continuous variables between groups, whereas chi-squared tests for independence or Fisher's exact tests were used for comparing categorical variables. Results A total of 42 patients ( n = 22 no alcohol and n = 20 alcohol) were included in the final analysis. The overall recurrence rates did not significantly differ between the alcohol and no alcohol groups (35 and 22.7%, respectively; p = 0.59). The average time to recurrence in the alcohol and no alcohol groups was 22.9 and 39 months, respectively ( p = 0.63), with a mean follow-up of 41.2 and 53.5 months ( p = 0.34). Complications, including diabetes insipidus, were not significantly different between the alcohol and no alcohol groups (30.0 vs. 27.2%, p = 0.99). Conclusion Intraoperative alcoholization of the pituitary gland after resection of GH-secreting pituitary adenomas does not reduce recurrence rates or increase perioperative complications.

Early outcomes of endoscopic endonasal approach pituitary adenomas resection with minimal nasal injury.

To report the results of a consecutive series of pituitary adenomas resected through endoscopic endonasal approach (EEA) with minimal nasal injury.Retrospectively review tumor characteristics and surgical outcomes of a consecutive series of EEA pituitary adenomas resection performed mainly by a single author between March 2018 and June 2019.A total of 75 endoscopic endonasal approach pituitary adenoma resections were performed by the authors’ team. Of the 75 patients, 28 through mononostril EEA, 47 through Binonostril EEA. Hadad-Bassagasteguy vascularized nasoseptal flap was harvested in only 4 (5.3%) patients with a high risk of postoperative cerebrospinal fluid leak, and one side middle turbinate only been resected in 2 (2.7%) patients, other patients preserved bilateral middle turbinate. Of the 75 patients, gross total resection is 74.7%, near-total resection is 16.0%. Endocrinological remission was achieved in 76.9% of GH-secreting adenomas, 61.5% of prolactin-secreting adenomas. The postoperative cerebrospinal fluid leak rate was 2.7%. Two patients had suprasellar hemorrhage, 1 patient had perioperative stroke, 2 patients had permanent diabetes insipidus, no cranial nerve deficits, internal carotid artery injury, anosmia, and death. The sino-nasal function was measured with the Sino-Nasal Outcome Test-22 and visual analog scale for olfaction preoperatively and postoperatively, and there was no statistically significant difference.The EEA is an effective approach to resect pituitary adenomas, the gross total resection and near-total resection rate and endocrinological remission rate are satisfactory. The EEA is a safe approach, as the complication rate is acceptable compared with those reported in the previous series of microscopic and endoscopic approaches. These results can be achieved with minimal nasal injury.