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To evaluate the ability of tracheal sound analysis (TSA) to detect airflow obstruction, particularly in patients with acromegaly. A simulated analysis compared free airflow conditions with airflow through orifice plates 6, 8, 10 and 12 mm in diameter. Based on these results, TSA and spirometry examinations were performed on controls (n = 17) and patients with acromegaly (n = 17). The simulated study showed that airway obstruction and airflow values increased the values of power and a progressive displacement of the spectral distribution towards higher frequencies. In agreement with the simulation, airway obstruction in patients with acromegaly also resulted in increased values of power (p < 0.002) and displacement of the spectral distribution (p < 0.01). Significant associations were observed between the TSA parameters and the spirometry indices of obstruction (p < 0.02). In addition, the TSA parameters achieved adequate diagnostic accuracy (AUC ≥ 0.887). The present study provides evidence that TSA during resting breathing would provide adequate biomarkers of early upper airway changes in patients with acromegaly. TSA is carried out during spontaneous ventilation, requires little from the patient, and is fast and inexpensive. Taken together, these practical considerations and the results of the present study suggest that TSA may improve lung function tests for patients with acromegaly. Summary of the study, overall design flow and the main results obtained., (© 2022. International Federation for Medical and Biological Engineering.)

Introduction: Arterial hypertension (AH) is prevalent in acromegaly, but few studies using 24-h ambulatory blood pressure monitoring (24 h-ABPM) suggest that its frequency may be different from office blood pressure (OBP). Left ventricular hypertrophy (LVH) is one of the most frequent cardiac abnormalities. Cardiac magnetic resonance (CMR) is considered the gold standard to evaluate the heart., Objectives: To compare the frequency of AH when measured by 24 h-ABPM and by OBP and to correlate BP with cardiac mass., Methods: Patients over 18 years of age with acromegaly underwent OBP evaluation and were later referred to the 24 h-ABPM. Treatment-naïve patients were submitted to CMR., Results: We evaluated 96 patients. From 29 non hypertensive patients by OBP, 9 had AH on 24 h-ABPM. In the group of patients with a previous diagnosis of AH by OBP, 25 had controlled BP and 42 had abnormal BP on 24 h-ABPM, when analyzed by OBP there were 28 with controlled BP. We observed a positive correlation between diastolic BP measured in 24 h-ABPM and IGF-I levels, but we did not observe the same correlation with age, sex, body mass index and GH levels. The CMR was performed in 11 patients. We found a positive correlation of left ventricular mass (LVM) and BP of 24 h-ABPM. In contrast, there was no correlation of OBP with CMR parameters., Conclusions: We observed, that 24 h-ABPM in acromegaly allows the diagnosis of AH in some patients with normal BP in OBP and also to allow a better treatment. 24 h-ABPM shows a better correlation with VM by CMR., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The patient-reported outcome becomes important to evaluate the situation perceived by the patients and to develop new strategies. This study aims to adapt the Acromegaly Treatment Satisfaction Questionnaire (Acro-TSQ), which was specially developed for patients with acromegaly, into Turkish by conducting a validity and reliability study., Methods: After the translation and back-translation process, Acro-TSQ was filled in by face-to-face interviews with 136 patients diagnosed with acromegaly and currently receiving somatostatin analogue injection therapy. Internal consistency, content validity, construct validity, and reliability of the scale were determined., Results: Acro-TSQ had a six-factor structure and explained 77.2% of the total variance in the variable. The Cronbach alpha value calculated for internal reliability showed high internal consistency (Cronbach's alpha = 0.870). Factor loads of all items were found to be between 0.567 and 0.958. As a result of EFA analysis, one item fell into a different factor in the Turkish version of the Acro-TSQ, different from its original form. CFA analysis shows that acceptable fit values are obtained for fit indices., Conclusion: The Acro-TSQ, a patient-reported outcome tool, shows good internal consistency, and good reliability, suggesting it is an appropriate assessment tool for patients with acromegaly in the Turkish population., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: This systematic literature review investigated whether extended dosing intervals (EDIs) of pharmacological acromegaly treatments reduce patient burden and costs compared with standard dosing, while maintaining effectiveness., Methods: MEDLINE/Embase/the Cochrane Library (2001-June 2021) and key congresses (2018-2021) were searched and identified systematic literature review bibliographies reviewed. Included publications reported on efficacy/effectiveness, safety and tolerability, health-related quality of life (HRQoL), and patient-reported and economic outcomes in longitudinal/cross-sectional studies in adults with acromegaly. Interventions included EDIs of pegvisomant, cabergoline, and somatostatin receptor ligands (SRLs): lanreotide autogel/depot (LAN), octreotide long-acting release (OCT), pasireotide long-acting release (PAS), and oral octreotide; no comparator was required., Results: In total, 35 publications reported on 27 studies: 3 pegvisomant monotherapy, 11 pegvisomant combination therapy with SRLs, 9 LAN, and 4 OCT; no studies reported on cabergoline, PAS, or oral octreotide at EDIs. Maintenance of normal insulin-like growth factor I (IGF-I) was observed in ≥ 70% of patients with LAN (1 study), OCT (1 study), and pegvisomant monotherapy (1 study). Achievement of normal IGF-I was observed in ≥ 70% of patients with LAN (3 studies) and pegvisomant in combination with SRLs (4 studies). Safety profiles were similar across EDI and standard regimens. Patients preferred and were satisfied with EDIs. HRQoL was maintained and cost savings were provided with EDIs versus standard regimens., Conclusions: Clinical efficacy/effectiveness, safety, and HRQoL outcomes in adults with acromegaly were similar and costs lower with EDIs versus standard regimens. Physicians may consider acromegaly treatment at EDIs, especially for patients with good disease control., (© 2022. The Author(s).)

Introduction: Real-world data evaluating patients' injection experiences using the latest devices/formulations of the long-acting (LA) somatostatin analogs (SSAs) lanreotide Autogel/Depot (LAN; Somatuline®) and octreotide LA release (OCT; Sandostatin®) are limited., Methods: PRESTO 2 was a 2020/2021 e-survey comparing injection experience of adults with neuroendocrine tumors (NETs) or acromegaly treated with LAN prefilled syringe versus OCT syringe for > 3 months in Canada, Ireland, the UK and the USA (planned sample size, 304)., Primary Endpoint: the proportion of patients with injection-site pain lasting > 2 days after their most recent injection, analyzed using a multivariate logistic regression model. Secondary endpoints included interference with daily life due to injection-site pain and technical injection problems in patients with current SSA use for ≥ 6 months., Results: There were 304 respondents (acromegaly, n = 85; NETs, n = 219; LAN, n = 168; OCT, n = 136; 69.2% female; mean age, 59.6 years). Fewer patients had injection-site pain lasting > 2 days after the most recent injection with LAN (6.0%) than OCT (22.8%); the odds of pain lasting > 2 days were significantly lower for LAN than OCT, adjusted for disease subgroup and occurrence of injection-site reactions (odds ratio [95% confidence interval]: 0.13 [0.06-0.30]; p < 0.0001). Injection-site pain interfered with daily life "a little bit" or "quite a bit" in 37.2% and 3.8% (LAN) versus 52.5% and 7.5% (OCT) of patients, respectively. Among patients with ≥ 6 months' experience with current SSA (92.4% of patients), technical injection problems never occurred in 76.8% (LAN) and 42.9% (OCT) of patients., Conclusions: Compared with OCT, significantly fewer patients using LAN had injection-site pain lasting > 2 days after their most recent injection. Also, fewer LAN-treated patients experienced technical problems during injection. These findings demonstrate the importance of injection modality for overall LA SSA injection experience for patients with acromegaly or NETs., (© 2022. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

The purpose of this analysis is to assess the use of machine learning (ML) algorithms in the prediction of postoperative outcomes, including complications, recurrence, and death in transsphenoidal surgery. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically reviewed all papers that used at least one ML algorithm to predict outcomes after transsphenoidal surgery. We searched Scopus, PubMed, and Web of Science databases for studies published prior to May 12, 2021. We identified 13 studies enrolling 5,048 patients. We extracted the general characteristics of each study; the sensitivity, specificity, area under the curve (AUC) of the ML models developed as well as the features identified as important by the ML models. We identified 12 studies with 5,048 patients that included ML algorithms for adenomas, three with 1807 patients specifically for acromegaly, and five with 2105 patients specifically for Cushing's disease. Nearly all were single-institution studies. The studies used a heterogeneous mix of ML algorithms and features to build predictive models. All papers reported an AUC greater than 0.7, which indicates clinical utility. ML algorithms have the potential to predict postoperative outcomes of transsphenoidal surgery and can improve patient care. Ensemble algorithms and neural networks were often top performers when compared with other ML algorithms. Biochemical and preoperative features were most likely to be selected as important by ML models. Inexplicability remains a challenge, but algorithms such as local interpretable model–agnostic explanation or Shapley value can increase explainability of ML algorithms. Our analysis shows that ML algorithms have the potential to greatly assist surgeons in clinical decision making. [ABSTRACT FROM AUTHOR]

Transsphenoidal resection of growth hormone-secreting pituitary neuroendocrine tumors remains the first-line treatment for acromegaly. This can be performed through microsurgery or endoscopic surgery. For the past decades, endoscopic surgery has become the preferred technique in an increasing number of centers worldwide. However, whether it offers superior clinical outcomes has yet to be determined. In this paper, we performed a narrative review of the literature comparing both techniques in the treatment of acromegaly. We critically assessed available comparative studies from an objective perspective to determine their suitability for defining superiority of either technique. Available evidence displays substantial methodological variations and reports conflicting findings. Although endoscopic surgery provides a wider exposure and enhanced visibility of the surgical field, this does not consistently translate into better clinical outcomes, as most tumors are equally accessible through both techniques. Postoperative outcomes such as remission and complication rates are similar between both techniques. The management of acromegaly should be performed by experienced pituitary neurosurgeons, regardless of the approach. The involvement of a multidisciplinary team in a dedicated pituitary center is critical to ensure optimal outcomes., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest regarding the elaboration, reporting, or publication of the present work., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Acromegaly is a condition characterized by an overproduction of growth hormone which infers high morbidity and mortality if left untreated. The objective of this review is to analyse and appraise the current evidence for the generalized use of preoperative medications and the various surgical approaches as described in the literature. Design: A thorough search from MEDLINE via PubMed, EMBASE, and Cochrane Library has been performed which identified a total of 37 papers. Conclusion: The preoperative use of somatostatin receptor agonists (SAs) in acromegaly is a controversial topic with current guidelines suggesting against their generalized routine use. Most authors noticed an insignificant long‐term remission of acromegaly when given SAs compared with nil preoperative therapy, except for invasive macroadenomas as SAs have been found to reduce the tumour volume and aid towards the total resection of the adenoma. Furthermore, according to the evidence available, endoscopic transsphenoidal surgery is the optimum method for hypophysectomy in terms of its remission and safety profile. [ABSTRACT FROM AUTHOR]

Only 30% of patients with McCune-Albright syndrome (MAS)-associated acromegaly achieve biochemical control under first-generation somatostatin receptor ligands (fg-SRLs), while pegvisomant fails to normalize insulin-like growth factor 1 (IGF-I) in >20% of cases. Here, we report all the patients with MAS-associated acromegaly treated with pasireotide long-acting release (LAR) in our center. Pasireotide LAR 20 mg/month resulted in rapid and long-term IGF-I normalization in patients #1 and #3. Patient #3 was resistant to fg-SRLs, while patient #1 was also controlled on fg-SRLs. In patient #2, resistant to fg-SRLs and uncontrolled on pegvisomant 40 mg/day combined with cabergoline 0.5 mg/day, pegvisomant was replaced with pasireotide LAR 40 mg/month, resulting in the near normalization of IGF-I levels. All 3 patients developed intermittent impaired fasting glucose, without the need for glucose-lowering drugs. Thus, pasireotide LAR is clearly useful as third-line therapy, and potentially even as second-line therapy, in MAS-associated acromegaly., Competing Interests: Conflict of interest: M.-D.I. and A.B.d.l.P. have no conflict of interest. G.R. has received consulting/speaker fees and/or he has been invited to conferences and/or he has participated in boards and/or clinical trials for Novartis, Pfizer, Ipsen, Recordati Rare Diseases, Amolyt, Crinetic, Novo Nordisk, and Chiasma. All the fees and honoraria are paid to his institution. G.R. is also on the editorial board of EJE. He was not involved in the review or editorial process for this paper, on which he is listed as author., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Keywords: acromegaly arthropathy; heart failure; diabetes; high blood pressure; sleep apnoea EN acromegaly arthropathy heart failure diabetes high blood pressure sleep apnoea 1 2 2 06/29/22 20220627 NES 220627 Acromegaly is a rare endocrine multisystemic disorder, caused in the vast majority of cases by a somatotroph pituitary adenoma. In the broad portfolio of acromegaly complications, the papers in this group are shedding light on new aspects of acromegaly, aiming an earlier diagnosis, a better control of co-morbidities and treatment strategies. Acromegaly arthropathy, heart failure, diabetes, high blood pressure, sleep apnoea. [Extracted from the article]

Standard treatment for acromegaly focuses on the achievement of target absolute levels of growth hormone (GH) and insulin-like growth factor (IGF-I). The appropriateness of these targets when measured using modern assay methods is not well defined. This paper reviews biochemical status assessed using methods available at the time and associated clinical outcomes. GH measurements were shown to provide an indication of changes in tumor size, and failure of GH suppression after glucose stimulation is associated with tumor recurrence. IGF-I levels were more closely associated with changes in symptoms and signs. Reduced GH and IGF-I concentrations were shown to be associated with increased longevity, although the degree of increase has only been analyzed for GH. Lowering of GH and IGF-I has consistently been associated with improved outcomes; however, absolute levels reported in previous studies were based on results from methods and reference ranges that are now obsolete. Applying previously described absolute thresholds as targets (e.g. "normal" IGF-I level) when using current methods is best applied to those with active acromegaly symptoms who could benefit from further lowering of biochemical markers. In asymptomatic individuals with mild IGF-I or GH elevations, targeting biochemical "normalization" would result in the need for combination pharmacotherapy in many patients without proven benefit. Measurement of both GH and IGF-I remains an essential component of diagnosis and monitoring the effectiveness of treatment in acromegaly; however, treatment goals based only on previously identified absolute thresholds are not appropriate without taking into account the assay and reference ranges being employed. Treatment goals should be individualized considering biochemical improvement from an untreated baseline, symptoms of disease, risks, burdens and costs of complex treatment regimens, comorbidities, and quality of life., Competing Interests: DC is a consultant for Amolyt, Crinetics Pharmaceuticals, Inc., and Novo Nordisk. MB reports receiving research support, consultancy, and/or lecture fees from Camurus, Chiasma, Crinetics Pharmaceuticals, Inc., Diasorin, Genexine, Genescience, IDS, Ionis, IPSEN, Merck, Midatech, Novartis, Ono, OPKO, Pfizer, Recordati, Roche, Sandoz, and StrongBridge. The authors declare that this study received funding from Crinetics Pharmaceuticals, Inc. The funder had the following involvement with the study: reviewed the manuscript for scientific accuracy and rigor, and provided funding for technical editorial support of the manuscript., (Copyright © 2023 Clemmons and Bidlingmaier.)

Purpose: Pituitary adenomas are the most common sellar tumors, and may cause adverse outcomes in terms of morbidity and mortality if left untreated or if diagnosis is delayed. No data exists on the prevalence, characteristics, and prognosis of pituitary adenomas in Thailand. The systematic registration of clinical characteristics may improve patient care and prognosis for this disease in Thailand., Methods: This was a retrospective study conducted in 11 academic referral centers. All patients diagnosed with pituitary adenomas during the 2011---2014 period were enrolled in the study. The information was correlated with two national databases., Results: A total of 1,283 pituitary adenoma patients were identified. The adenomas were: non-functioning 50.1%, prolactinoma 29.4%, acromegaly 14.7%, Cushing disease 3.8%, gonadotropin-producing tumor 1.0%, TSH-secreting tumor 0.6%. The mean age was 49.2±15.2 years. Sixty-three percent of patients were female. Most common complaint was visual impairment (27.7%). The average size of the tumor was 22.2±16.1 mm. Fifty-nine percent of patients underwent surgery. Median follow-up was 27.4 months (0-24 years). After treatment, 72.4% improved, and 10.4% were cured. Overall results of treatment in non-functioning adenoma, prolactinoma (medically treated), acromegaly, Cushing, TSH, gonadotropin producing adenoma were: improved/cured in 81/5.5, 86/5.7, 55.9/30, 54.2/31.2, 85.7/14.3, 69.2/15.4% respectively., Conclusion: Pituitary adenomas in academic centers in Thailand were found predominantly in female in the 4th decade of life. After treatment 72.4% of patients improved and 10% had full recovery. A health promotion system aimed to improve patient and physician recognition and physician expertise may improve the prognosis of these diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Endocrine Society of Thailand. Published by Elsevier Ltd.. All rights reserved.)

Aim: Acromegaly is a rare chronic disease, caused by the over-secretion of growth hormone (GH), that creates a pro-inflammatory state, but the exact mechanisms by which GH or insulin-like growth factor 1 (IGF-I) act on inflammatory cells are not fully understood. Aim of the study was to evaluate Interleukin-33 (IL33) and D-series resolvins 1 (RvD1) and the skin perfusion of hands in patients with acromegaly (AP) and healthy controls (HC)., Methods: IL33 and RvD1 have been assessed in 20 AP and 20 HC. Nailfold videocapillaroscopy (NVC) was performed and skin perfusion of hands was assessed by laser speckle contrast analysis (LASCA) in both populations., Results: IL33 was significantly higher in AP compared to HC [73.08 pg/ml (IQR 47.11-100.80 pg/ml) vs 41.5 4 pg/ml (IQR 20.16-55.49 pg/ml), p < 0.05] and RvD1 was significantly lower in AP than HC [36.1 pg/ml (IQR 27.88-66.21 pg/ml) vs 60.01 pg/ml (IQR 46.88-74.69 pg/ml), p < 0.05]. At LASCA, peripheral blood perfusion (PBP) was significantly lower in AP compared to HC [56.66 pU (IQR 46.29-65.44 pU) vs 87 pU (IQR 80-98 pU), p < 0.001]. The median values of ROI1 and ROI3 were significantly lower in AP compared to HC [112.81 pU (IQR 83.36-121.69 pU) vs 131 pU (IQR 108-135 pU), p < 0.05] and [59.78 pU (IQR 46.84-79.75 pU) vs 85 pU (IQR 78-98 pU), p < 0.05], respectively. The proximal-distal gradient (PDG) was observed in 8 of 20 (40 %) AP., Conclusion: Serum IL33 is higher in AP compared to HC; conversely, RvD1 is lower in AP compared to HC. Reduction of PBP of hands was present in AP compared to HC, probably due to endothelial dysfunction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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. [ABSTRACT FROM AUTHOR]

Purpose: Bone is one of the main targets of hormones and endocrine diseases are frequent causes of secondary osteoporosis and fractures in real-world clinical practice. However, diagnosis of skeletal fragility and prediction of fractures in this setting could be a challenge, since the skeletal alterations induced by endocrine disorders are not generally captured by dual-energy X-ray absorptiometry (DXA) measurement of bone mineral density (BMD), that is the gold standard for diagnosis of osteoporosis in the general population. The aim of this paper is to review the existing evidence related to bone quality features in endocrine diseases, proposing assessment with new techniques in the future., Methods: A comprehensive search within electronic databases was performed to collect reports of bone quality in primary hyperparathyroidism, hypoparathyroidism, hyperthyroidism, hypercortisolism, growth hormone deficiency, acromegaly, male hypogonadism and diabetes mellitus., Results: Using invasive and non-invasive techniques, such as high-resolution peripheral quantitative computed tomography or DXA measurement of trabecular bone score (TBS), several studies consistently reported altered bone quality as predominant determinant of fragility fractures in subjects affected by chronic endocrine disorders., Conclusions: Assessment of skeletal fragility in endocrine diseases might take advantage from the use of techniques to detect perturbation in bone architecture with the aim of best identifying patients at high risk of fractures., (© 2023. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Objectives: Calibration is an important source of variability in liquid chromatography mass spectrometry (LC-MS) methods for insulin-like growth factor 1 (IGF-1). This study investigated the impact of different calibrator matrices on IGF-1 measurements by LC-MS. Moreover, the comparability of immunoassays and LC-MS was assessed., Design & Methods: Calibrators from 12.5 to 2009 ng/ml were prepared by spiking WHO international Standard (ID 02/254 NIBSC, UK) into the following matrices: native human plasma, fresh charcoal-treated human plasma (FCTHP), old charcoal-treated human plasma, deionized water, bovine serum albumin (BSA), and rat plasma (RP). A validated in-house LC-MS method was calibrated repeatedly with these calibrators. Then, serum samples from 197 growth hormone excess and deficiency patients were analysed with each calibration., Results: The seven calibration curves had different slopes leading to markedly different patient results. The largest differences in IGF-1 concentration from the median (interquartile range) was observed with the calibrator in water and the calibrator in RP (336.4 [279.6-417.0] vs. 112.5 [71.2-171.2], p < 0.001). The smallest difference was observed with calibrators in FCTHP and BSA (141.8 [102.0-198.5] vs. 127.9 [86.9-186.0], p < 0.049). Compared to LC-MS with calibrators in FCTHP, immunoassays showed relevant proportional bias (range: -43% to -68%), constant bias (range: 22.84 to 57.29 ng/ml) and pronounced scatter. Comparing the immunoassays with each other revealed proportional bias of up to 24%., Conclusions: The calibrator matrix is critical for the measurement of IGF-1 by LC-MS. Regardless of the calibrator matrix, LC-MS shows poor agreement with immunoassays. Also, the agreement between different immunoassays is variable., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Purpose: To evaluate the role of metformin on thyroid cancer risk in patients with acromegaly., Methods: Medical charts of 534 patients with acromegaly that were followed-up between 1983 and 2019 were reviewed. Patients with follow-up duration at least 6 months were included. Cohort entry was defined as first visit date. The date of each case's thyroid cancer diagnosis was defined as index date. Patients were followed until the index date, death, or last visit date, whichever came first. Nested case-control study design was selected to evaluate the association between metformin and the thyroid cancer risk in patients with acromegaly., Results: 291 patients with acromegaly were included into final analysis. The mean age at acromegaly diagnosis was 42.3 ± 1.3 years. The median follow-up duration was 76 [34-132] months. Among 291 patients, 13 patients (4.5%) had thyroid cancer. Thirty-one percent (n = 92) of the patients used metformin for 6 months or longer. One standard deviation (SD) increase in average growth hormone increased the odds of having thyroid cancer by 1.164 folds (p = 0.017). One SD increase of the average insulin-like growth factor 1 to upper limit of normal ratio increased the odds of having thyroid cancer by 1.201 folds (p = 0.004). If a patient used metformin for at least 6 months, the odds to have thyroid cancer was decreased, multiplied by 0.62 with a 95% confidence interval of [0.47, 0.83] (p = 0.0013). The risk of thyroid cancer decreased with increasing duration of metformin use., Conclusion: Metformin may decrease the thyroid cancer risk in patients with acromegaly., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: Acromegaly is a disorder caused by hypersecretion of growth hormone (GH), resulting in excessive levels of insulin-like growth factor 1 (IGF-1), and almost always due to a pituitary tumor. It is classically associated with acral enlargement, prominent facial features and soft tissue overgrowth. Skin manifestations include hirsutism, acne, skin tags, oily skin and acanthosis nigricans. However, other uncommon dermatological features, such as cutis verticis gyrata (CVG), may also occur. Here, we review acromegaly-related CVG aiming to raise awareness for its possible occurrence in this setting, and we discuss its pathophysiology, presentation, management and differential diagnosis., Design: A comprehensive literature search regarding CVG, particularly CVG related to acromegaly, has been carried out. Case reports, original studies and review papers, were considered., Results: CVG is a rare benign skin lesion characterized by thickened and folded scalp, resembling the brain gyri and sulci. The diagnosis of CVG mainly relies on clinical examination, although tissue biopsy may be necessary in case of uncertain etiology. In acromegaly, CVG appears to be driven by the trophic effects of GH and IGF-1 on skin and soft tissues. While CVG is uncommon in acromegaly, it seems to occur more frequently in male patients. The management of acromegaly-related CVG essentially relies on controlling the serum levels of GH and IGF-1. Surgical skin procedures should be reserved for patients with severe aesthetic distress, after achieving the best possible control of acromegaly., Conclusions: CVG is a rare manifestation of acromegaly that may allow an earlier diagnosis and a swifter treatment of these patients, which in turn may improve or entirely reverse such remarkable skin lesions., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Pituitary tumors are rare neoplasms, with a heterogeneous biological and clinical behavior, due to their clinical course, local invasive growth, resistance to conventional therapies and the risk of disease progression. Recent studies on tumor microenvironment (TME) provided new knowledge on the biology of these neoplasia, that may explain the different phenotypes of these tumors and suggest new biomarkers able to predict the prognosis and the treatment outcome. The identification of molecular markers that act as targets for biological therapies may open new perspectives in the medical treatments of aggressive pituitary tumors. In this paper, we will review data of TME and target therapies in somatotropinomas. [ABSTRACT FROM AUTHOR]

Purpose: Acromegaly is a rare disease that often requires drug treatment to achieve control, with pegvisomant being one of the most widely used therapies. In the present paper, we aimed to obtain evidence regarding the effectiveness and safety of pegvisomant by reviewing real-world observational longitudinal studies.Methods: A systematic review was performed with a meta-analysis of event rates (95% confidence interval (CI)) using a random effects model. Sensitivity and subgroup analyses were performed (comprehensive meta-analysis 2.0). The systematic review was performed in accordance to preferred reporting items for systematic reviews and meta-analyses, meta-analysis of observational studies in epidemiology, and Cochrane recommendations (PROSPERO register CRD 42017059880). PubMed, Scopus, Web of Science, and SciELO were used to search for literature. Observational studies in patients using pegvisomant for the treatment of acromegaly were included.Results: Initially, 552 papers were retrieved from the databases; and 31 articles were included in the qualitative analysis and 14 in the quantitative analysis. Eight primary meta-analyses were performed. The overall rate of patients with disease control was of 60.9% (51.8-69.3%; 95% CI). When considering patients under monotherapy, the control rate was 71.7% (64.0-78.4%; 95% CI). Tumor growth was estimated in 7.3% (4.7-11.1%; 95% CI) and elevation of transaminases in 3.0% (1.7-5.2%; 95% CI).Conclusions: The real-world data showed that the effectiveness of pegvisomant is not as high as reported in interventional studies. Acromegaly appears to be better controlled when pegvisomant is used as a monotherapy. No serious adverse events were associated with the use of pegvisomant; however, given the high cost of this drug, further studies are required. [ABSTRACT FROM AUTHOR]

In 1912 physician Leonard Mark published a book titled Acromegaly: A Personal Experience. Within, he documented his life suffering from the titular condition which manifested in symptoms ranging from headaches to the hypertrophic enlargement of the head, hands and feet. As the condition began to affect Mark's ability to perform his medical and artistic work his writing had to contend with his changing identity, body, and the problem of how to effectively explain the experience of his suffering. At the same time as the wider medical profession was becoming fixated on acromegaly as a disease defined almost wholly by its spectacular visible symptoms, Mark's writing invited his reader to go beyond the merely visible and engage with his narrative on a multisensory level. What emerges in Acromegaly , and what this paper explores, is how Mark used contemporary ideas of medical masculinity, particularly in deconstructing them, to invite this sensorial engagement. [ABSTRACT FROM AUTHOR]

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Acromegaly is a rare endocrine disorder caused by excessive and longstanding secretion of growth hormone (GH) by the pituitary somatotroph and resulting from this overproduction of insulin-like growth factor-1 hormone (IGF-1) by the liver. There are few registers and rather limited clinical data about acromegaly treatment. The analysis of acromegaly data is rarely subject to a system of criteria for evaluating acromegaly treatment. The novelty of this paper is that it presents a reallife practice case study about the implementation results of such a system in Bulgaria. The case study analysis illustrates a clinical information approach to manage thousands of records in the Bulgarian Acromegaly Database. The here reported results provide evidence about the difficulties in maintaining both GH and IGF-1 levels inside their reference values in acromegaly treatment. Ongoing research extends the evaluation results by enabling semantic interoperability between acromegaly databases based on openEHR specification. [ABSTRACT FROM AUTHOR]

The delay in controlling the disease in patients who do not respond to first-line treatment with first generation somatostatin receptor ligands (first-generation SRLs) can be quantified in years, as every modification in the medical therapy requires some months to be fully evaluated. Considering this, acromegaly treatment should benefit from personalized medicine therapeutic approach by using biomarkers identifying drug response. Pasireotide has been positioned mostly as a compound to be used in first-generation SRLs resistant patients and after surgical failure, but sufficient data are now available to indicate it is a first line therapy for patients with certain characteristics. Pasireotide has been proved to be useful in patients in which hyperintensity T2 MRI signal is shown and in those depicting low SST2 and high expression of SST5 , low or mutated AIP condition and sparsely granulated immunohistochemical pattern. This combination of clinical and pathological characteristics is unique for certain patients and seems to cluster in the same cases, strongly suggesting an etiopathogenic link. Thus, in this paper we propose to include this clinico-pathologic phenotype in the therapeutic algorithm, which would allow us to use as first line medical treatment those compounds with the highest potential for achieving the fastest control of GH hypersecretion as well as a positive effect upon tumor shrinkage, therefore accelerating the implementation of precision medicine for acromegaly. Moreover, we suggest the development, validation and clinical use of a pasireotide acute test, able to identify patients responsive to pasireotide LAR as the acute octreotide test is able to do for SRLs., Competing Interests: MP-D, IB, CA-E, AP, M-AG, RC, BB, JA, CL, and MM received grants support and participated in speaker bureau for Pfizer, Recordati, Ipsen, and Novartis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Puig-Domingo, Bernabéu, Picó, Biagetti, Gil, Alvarez-Escolá, Jordà, Marques-Pamies, Soldevila, Gálvez, Cámara, Aller, Lamas and Marazuela.)

We present and discuss a late-nineteenth century clinical case described by Professor Taruffi in a scientific paper titled "Scheletro con prosopoectasia e tredici vertebre dorsali" (Skeleton with prosopoectasia and thirteen thoracic vertebrae). Taruffi could not explain the disproportionate skeletal and visceral growth, and the case could therefore be considered an unrecognized case of acromegaly. The anatomopathological specimens and the wax model cited in the paper are currently hosted at the "Luigi Cattaneo" Anatomical Wax Collection of Bologna University; however, some inaccuracies and uncertainties as to their attribution to the same case have remained to this day. The skeletal remains were examined macroscopically to investigate any structural abnormalities and pathological changes. In addition, thanks to archival, museum inventory and literature research, we documented the systematic relationship between the paper and the samples and were able to ascribe the abnormally dilated dried stomach, currently displayed in a different showcase, to the same case. This is, to our knowledge, the first case of acromegaly in the history of medical literature which also includes a visceral specimen. As far as we know, there are no reports of the occurrence of severe gastromegaly in patients with acromegaly. In view of this rare association and, to date, endocrinological research, we hypothesize a further pathogenic mechanism by which acromegaly could have induced this massive dilatation. Taruffi's work represents an immensely valuable scientific/artistic heritage and is still cited in contemporary endocrinological literature, demonstrating its relevant contribution to the historical evolution of the disease through the nineteenth and twentieth centuries.

Introduction: The first long-acting release (LAR) formulation of octreotide was marketed in France in the late 1990s. An injectable formulation of Sandostatin LAR ® (Novartis SAS) with a new diluent has been developed to facilitate its preparation and administration and to improve its use in practice., Methods: We conducted an observational, cross-sectional and multicenter study in France whose main outcome was to compare nurses' satisfaction with the preparation and administration of both previous and new formulations of octreotide LAR. Secondary outcomes included assessment of patient satisfaction (quality of life and pain felt during the injection) and product tolerance. Data were collected at two time points (one for the first formulation group and one for the second formulation group) through paper questionnaires administered to physicians, patients and nurses including a visual analog scale (VAS) from 0 (unsatisfied) to 10 (very satisfied)., Results: Results showed that overall nurse satisfaction improved from 5.3 (95% CI 4.9-5.8) with the previous formulation to 7.5 (95% CI 7-7.9) with the new formulation (p < 0.0001). Regarding secondary outcomes, the simplicity of the injection increased (84% for the previous formulation and 94% for the new formulation) and the purge problem disappeared (36% for the previous formulation and 4% for the new formulation)., Conclusion: The improvement due to the new formulation of Sandostatin LAR ® was reported in terms of handling, ease of use and overall nurse satisfaction. The new formulation greatly reduced treatment administration problems associated with the previous formulation, while maintaining low injection site pain and an equivalent safety profile in both indications.

Objective: The aim of the Acromegaly Consensus Group was to revise and update the consensus on diagnosis and treatment of acromegaly comorbidities last published in 2013., Participants: The Consensus Group, convened by 11 Steering Committee members, consisted of 45 experts in the medical and surgical management of acromegaly. The authors received no corporate funding or remuneration., Evidence: This evidence-based consensus was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence following critical discussion of the current literature on the diagnosis and treatment of acromegaly comorbidities., Consensus Process: Acromegaly Consensus Group participants conducted comprehensive literature searches for English-language papers on selected topics, reviewed brief presentations on each topic, and discussed current practice and recommendations in breakout groups. Consensus recommendations were developed based on all presentations and discussions. Members of the Scientific Committee graded the quality of the supporting evidence and the consensus recommendations using the GRADE system., Conclusions: Evidence-based approach consensus recommendations address important clinical issues regarding multidisciplinary management of acromegaly-related cardiovascular, endocrine, metabolic, and oncologic comorbidities, sleep apnea, and bone and joint disorders and their sequelae, as well as their effects on quality of life and mortality., (© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Biological markers (biomarkers) play a key role in drug development, regulatory approval and clinical care of patients and are linked to clinical and surrogate outcomes. Both acromegaly and Growth Hormone Deficiency (GHD) are pathological conditions related to important comorbidities that, in addition to having stringent diagnostic criteria, require valid markers for the definition of treatment, treatment monitoring and follow-up. GH and insulin-like growth factor-I (IGF-I) are the main biomarkers of GH action in children and adults while, in acromegaly, both GH and IGF-I are established biomarkers of disease activity. However, although GH and IGF-I are widely validated biomarkers of GHD and acromegaly, their role is not completely exhaustive or suitable for clinical classification and follow-up. Therefore, new biological markers for acromegaly and GH replacement therapy are strongly needed. The aim of this paper is to review and summarize the current state in the field pointing out new potential biomarkers for acromegaly and GH use/abuse., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Double adenomas in the pituitary gland are a rare occurrence. The ability to cure a hormone-producing adenoma with surgery is dependent on the ability to identify and completely remove the correct adenoma. The relative frequency of each subtype of hormone-secreting adenomas confirmed with magnetic resonance image (MRI), surgery and immunohistochemistry is not defined. Methods: Following PRISMA guidelines, we performed a systematic review of PubMed Central, Google Scholar, Scopus Database, Cochrane database and Science Research, using the key-words: 'double pituitary adenomas', 'multiple pituitary adenomas' and only papers where multiple or truly separate double pituitary adenomas were identified pre-surgically by MRI and/or confirmed by pathology/immunohistochemistry staining were included. Results: We reviewed papers from 1975 to 2016 and found 17 cases with two pituitary adenomas and 1 with three pituitary adenomas. The ages ranged from 22 to 67 years old, and there were twelve females and five males. Immunohistochemical staining showed that the most common double pituitary adenomas were growth hormone (GH)- followed by adrenocorticotropic (ACTH)-secreting. Conclusion: Double pituitary adenomas are rare but most commonly found with GH- or ACTH-producing tumors. It is critical to remove all identified possible adenomas to achieve biochemical cure and clinicians should have heightened sensitivity in patients with acromegaly or Cushing's Disease. [ABSTRACT FROM AUTHOR]

Laryngeal involvement in acromegaly is a rare occurrence that has been reported in several case reports. The aim of this paper is to present a clinical case followed by a systematic review of the literature. A comprehensive review of the literature was conducted in April 2020. Included articles were reviewed for, type of study, date of publication, age of patient, main symptoms, duration of symptoms, laryngoscopy findings, treatment modalities and outcomes. Twenty-six cases were reported in the literature. Dyspnea was the most reported symptom followed by stridor and dysphonia. Tracheotomy was performed in (17/26) patients and adjunct laryngeal surgeries were performed in 7 (7/26) patients. Although laryngeal manifestations are rare in acromegaly, they sometimes carry functional and vital risks. A structured and multidisciplinary approach is critical for the optimal management of the airway in slowly progressive dyspnea and in acute life-threatening situations. [ABSTRACT FROM AUTHOR]

Acromegaly is a chronic disorder usually diagnosed late in the disease evolution, leading to substantial morbidity and mortality related to this long period of undiagnosed state as well as the difficulty in achieving normalization of GH hypersecretion and controlling tumor mass. First generation somatostatin analogues (SSA) are accepted as the first-line medical therapy or as second-line therapy in patients undergoing unsuccessful surgery. However, because a high percentage of patients experience SSA treatment failure, the inclusion of biomarkers associated with a successful or non-successful response to these drug (as well as to all classes of medical therapy) is necessary to better guide the choice of treatment, potentially allowing for a quicker achievement of disease control. The current treatment algorithms for acromegaly are based upon a "trial and error" approach with additional treatment options provided when disease is not controlled. In many other diseases, their therapeutic algorithms have been evolving towards personalizing treatment with medication that best matches individual disease characteristics, using biomarkers that identify therapeutic response, thus allowing the personalization of the therapy. It is time to introduce this approach to acromegaly treatment algorithms. This paper reviews the potential tools for doing so.

Introduction: Somatostatin analogues (SSAs) are the largest contributor to the direct medical cost of acromegaly management worldwide. The aim of this review was to identify and report available evidence on the cost-effectiveness of SSAs in the treatment of acromegaly., Areas Covered: A literature search on relevant papers published up to April 2018 was performed. A total of 22 eligible studies (10 full-text articles and 12 conference abstracts) conducted in 14 countries were included in the analysis. In majority of studies, modelling technique was the principal research method., Expert Commentary: The results of cost-effectiveness analyses: 1) support published recommendations where SSAs are indicated as first-line medical treatment for patients with persistent disease after surgery or who are not eligible for surgery; 2) suggest that preoperative medical therapy with SSAs may be highly cost-effective in acromegalic patients with macroadenoma, in centres without optimal surgical results 3) indicate that in some countries pasireotide and pegvisomant appeared to be cost-effective or even dominant strategies in comparison to first-generation SSAs. The main limitation of economic evaluations was the lack of high-quality studies designed to directly compare various treatment strategies in acromegaly.