Assessing quality assurance of multi-leaf collimator using the structural similarity index.

PURPOSE: This study aims to evaluate the viability of utilizing the Structural Similarity Index (SSI*) as an innovative imaging metric for quality assurance (QA) of the multi-leaf collimator (MLC). Additionally, we compared the results obtained through SSI* with those derived from a conventional Gamma index test for three types of Varian machines (Trilogy, Truebeam, and Edge) over a 12-week period of MLC QA in our clinic. METHOD: To assess sensitivity to MLC positioning errors, we designed a 1 cm slit on the reference MLC, subsequently shifted by 0.5-5 mm on the target MLC. For evaluating sensitivity to output error, we irradiated five 25 cm × 25 cm open fields on the portal image with varying Monitor Units (MUs) of 96-100. We compared SSI* and Gamma index tests using three linear accelerator (LINAC) machines: Varian Trilogy, Truebeam, and Edge, with MLC leaf widths of 1, 0.5, and 0.25 mm. Weekly QA included VMAT and static field modes, with Picket fence test images acquired. Mechanical uncertainties related to the LINAC head, electronic portal imaging device (EPID), and MLC during gantry rotation and leaf motion were monitored. RESULTS: The Gamma index test started detecting the MLC shift at a threshold of 4 mm, whereas the SSI* metric showed sensitivity to shifts as small as 2 mm. Moreover, the Gamma index test identified dose changes at 95MUs, indicating a 5% dose difference based on the distance to agreement (DTA)/dose difference (DD) criteria of 1 mm/3%. In contrast, the SSI* metric alerted to dose differences starting from 97MUs, corresponding to a 3% dose difference. The Gamma index test passed all measurements conducted on each machine. However, the SSI* metric rejected all measurements from the Edge and Trilogy machines and two from the Truebeam. CONCLUSIONS: Our findings demonstrate that the SSI* exhibits greater sensitivity than the Gamma index test in detecting MLC positioning errors and dose changes between static and VMAT modes. The SSI* metric outperformed the Gamma index test regarding sensitivity across these parameters.

Prediction of adrenal insufficiency after pituitary surgery: a retrospective study using beckman access cortisol assay.

PURPOSE: Identifying patients requiring glucocorticoid replacement therapy after pituitary surgery is challenging as the tests commonly used for the diagnosis of secondary adrenal insufficiency (SAI) are not recommended in the immediate postoperative period. There are controversial data on the role of postoperative days' morning cortisol, with no specific data for each cortisol assay. The aim of this study is to investigate the reliability of 8.00 a.m. cortisol of the first and second postoperative days in predicting SAI. METHODS: Data of patients underwent pituitary surgery in Humanitas Research Hospital in Italy, from March 2017 to August 2022, were retrospectively analyzed. Definitive diagnosis of SAI was made through ACTH test 1 µg six weeks after surgery. Cortisol was measured through Beckman Access Cortisol and the diagnosis of SAI was made if cortisol peak was below 14.8 µg/dL (408 nmol/L) at 30 or 60 min after stimulus. RESULTS: Of the sixty-four patients enrolled, seven developed SAI. The ROC curves demonstrated that both first- and second-day postoperative 8.00 a.m. cortisol predict SAI (AUC 0.94 and 0.95, respectively). The optimal thresholds were 15.6 µg/dL (430.3 nmol/L; accuracy 89%) for the first day and 11.5 µg/dL (317.2 nmol/L, accuracy 81%) for the second day. Patients who developed SAI had larger tumors (p = 0.004) and lower fT4 (p = 0.038) before surgery. CONCLUSIONS: Clinicians might rely on the first- and second- postoperative days 8.00 a.m. cortisol to identify patients to discharge with glucocorticoid replacement therapy waiting for the confirmation of SAI through the ACTH test.

A randomized prospective comparative study on sinonasal morbidity and quality of life of transsphenoidal endoscopic surgery for pituitary adenomas: endonasal versus trans-septal approach.

PURPOSE: Endoscopic endonasal transsphenoidal approach (Endonasal approach) is commonly used to treat pituitary adenomas. The extent of dissection possibly changes the anatomy and the physiology of the nasal cavities and could give rise to post-operative morbidity and the quality of life (QoL). The purpose of this study was to investigate sinonasal morbidity and general QoL in patients who underwent surgery for treatment of pituitary adenoma, comparing Endonasal and endoscopic trans-septal transsphenoidal approach (Trans-septal approach). METHODS: A prospective observational study, recruiting 40 patients undergoing surgery for pituitary adenoma, 20 via Endonasal approach and 20 via Trans-septal approach at our institution. Surveys with Sinonasal Outcome Test-22 (SNOT-22), Chronic Sinusitis Survey (CSS), and Short Form Health Survey 36 version 2 (SF-36v2) were obtained to collect QoL data pre- and postoperatively. RESULTS: All the 40 patients completed the questionnaires. At 6 months postoperatively, the SNOT-22 and CSS score shows significant improvements both in Endonasal approach (p = 0.01) and in Trans-septal approach (p = 0.02). No significant difference in sinonasal morbidity is observed between the two groups for SNOT-22 (p = 0.13) and CSS scores, except for sinus headache (p = 0.49), with a better score in Endonasal approach. The mean SF-36v2 scores remain the same in pre- and post-operative periods, but an improvement in time is seen in general health (p = 0.027), and general health compared to one year ago (p < 0.001). CONCLUSIONS: Endoscopic transsphenoidal surgery has negligible morbidity and does not negatively affect the nasal function in the long term. Endonasal approach and Trans-septal approach are comparable in terms of morbidity outcomes and general QoL, leaving the choice of the approach to the surgeon preference.

A novel somatostatin receptor ligand for human ACTH - and GH -secreting pituitary adenomas.

OBJECTIVE: Somatostatin receptor ligands have come to play a pivotal role in the treatment of both ACTH- and GH-secreting pituitary adenomas. Clinical efficacy averages 30-50%, thus a considerable number of patients with Cushing's disease or acromegaly remain unresponsive to this therapeutic approach. HTL0030310 is a new somatostatin receptor ligand selective for subtype 5 over subtype 2, thus with a different receptor profile compared to clinical somatostatin receptor ligands. DESIGN: Assessment of the effect of HTL0030310 on hormone secretion in human ACTH- and GH-secreting pituitary adenomas in vitro. METHODS: Primary cultures from 3 ACTH-secreting and 5 GH-secreting pituitary adenomas were treated with 1, 10 and 100 nM HTL0030310 alone or with 10 nM CRH or GHRH, respectively. Parallel incubations with 10 nM pasireotide were also carried out. ACTH and GH secretion were assessed after 4 and 24 hour incubation; SSTR2, SSTR3, SSTR5, GH and POMC expression were evaluated after 24 hours. RESULTS: HTL0030310 reduced unchallenged ACTH and POMC levels up to 50% in 2 ACTH-secreting adenomas and blunted CRH-stimulated ACTH/POMC by 20-70% in all 3 specimens. A reduction in spontaneous GH secretion was observed in 4 GH-secreting adenomas and in 2 specimens during GHRH co-incubation. SSTRs expression was detected in all specimens. CONCLUSIONS: This first study on a novel somatostatin receptor 5-preferring ligand indicates that HTL0030310 can inhibit hormonal secretion in human ACTH- and GH-secreting pituitary adenomas. These findings suggest a potential new avenue for somatostatin ligands in the treatment of Cushing's disease and acromegaly.

Staged Gamma Knife radiosurgery for a rosette-forming glioneuronal tumor of the fourth ventricle: a case report.

BACKGROUND: Rosette-forming glioneuronal tumor (RGNT) is a rare slow-growing neoplasm with mixed glial and neurocytic components. Surgical resection is the mainstay of treatment, whereas the role of adjuvant radiation therapies for residual or recurrent tumors has been poorly investigated. CASE PRESENTATION: We describe the case of a patient with a recurrent fourth ventricular RGNT who was treated with two-staged Gamma Knife radiosurgery (GKRS). GKRS was effective in controlling tumor growth and safe up to seven years from treatment. CONCLUSIONS: This case suggests that GKRS may be a safe and effective treatment for patients with recurrent or residual RGNT.

Intracranial Hypotension Syndrome after Lumbar Drainage in Skull Base Surgery: Diagnosis and Correct Management.

Lumbar drainage is commonly used in skull base surgery; however, very few cases of intracranial hypotension syndrome are reported to be caused by this procedure. We present a clinical case of lumbar drainage-assisted orbital and optic canal decompression surgery for a recurrent voluminous spheno-orbital meningioma, together with a literature review. A 49-year-old woman became confused and drowsy on postoperative day 3, after initially experiencing neurologic stability. Computed tomography (CT) scan of the head showed extradural frontotemporal fluid collection with moderate right to left midline shift. Magnetic resonance imaging (MRI) of the brain showed signs of intracranial hypotension, such as brain sagging and diffuse dural contrast enhancement. Conservative treatment with bed rest, aggressive hydration, steroids, and aminophylline led to progressive neurologic improvement. A systematic literature review was also performed, and previous reported cases were analyzed. Overall, neurosurgeons must be aware of the lumbar drainage-induced hypotension syndrome in skull base surgeries, because immediate diagnosis is essential for therapeutic decision-making. In this setting, conservative management is the first-line treatment as surgery may lead to severe complications.

Towards a common language in neurosurgical outcome evaluation: the NEON (NEurosurgical Outcome Network) proposal.

BACKGROUND: The aim of this study was to achieve a consensus on the minimum set of outcome measures and predictors to be used in the neurosurgical practice and on the timing of outcome assessment. METHODS: A consensus building approach was employed. All neurosurgical departments in Lombardy (Italy) were invited to participate by the Carlo Besta Neurologic Institute IRCCS Foundation. Three workshops were organized during which a multidisciplinary group called Neurosurgical Outcome Network (NEON) was created and the methodology to select outcome measures, predictors, and timing of outcome assessment was established. Eight working groups were created for the different neurosurgical diseases (neuro-oncological, skull base, vascular, traumatic, spinal, peripheral nervous system, malformation, functional) and 8 workshops were organized to identify the outcome measures and predictors specific for each of the neurosurgical diseases based on the experts' clinical practice and the existing literature. RESULTS: A total of 20 neurosurgical departments participated in this study. Specific outcome measures, predictors and the timing of outcome assessment were identified for each of the 8 neurosurgical diseases. Moreover, a list of variables common to all pathologies were identified by the NEON group as further data to be collected. CONCLUSIONS: A consensus on the minimum set of outcome measures and predictors and the timing of outcome assessments for 8 neurosurgical diseases was achieved by a group of neurosurgeons of the Lombardy region, called NEON. These sets could be used in future studies for a more homogeneous data collection and as a starting point to reach further agreement also at national and international level.

Silibinin, an HSP90 Inhibitor, on Human ACTH-Secreting Adenomas.

INTRODUCTION: The glucocorticoid receptor is pivotal to control corticotrophin (ACTH) secretion, and its function is closely linked to the heat shock protein 90 (HSP90) chaperone complex. Impaired sensitivity to glucocorticoid feedback is a hallmark of human corticotroph adenomas, i.e., Cushing's disease, a disorder with few medical treatment options. Silibinin, a HSP90 inhibitor, has been studied in tumoral corticotroph cells and its use proposed in Cushing's disease. Aim of the present study was to further investigate the effect of silibinin on human corticotroph adenomas in vitro. METHODS: Seven human ACTH-secreting pituitary adenomas were established in culture and treated with 10-50 µm silibinin with/without dexamethasone for up to 72 h. ACTH medium levels were measured, and POMC and glucocorticoid receptor, i.e., NR3C1, gene expression assessed. RESULTS: Silibinin reduced spontaneous ACTH secretion and restored sensitivity to steroid negative feedback to a different extent in individual adenomas. POMC expression was decreased in both control and dexamethasone-treated wells in specimens sensitive to silibinin. Interestingly, silibinin reduced constitutive NR3C1 expression and reversed the dexamethasone-induced inhibition. CONCLUSIONS: Our findings indicate that silibinin can inhibit ACTH synthesis and secretion in individual human corticotroph adenomas and directly affects NR3C1 gene expression. These results reveal promising effects of this HSP90 inhibitor on human corticotroph adenomas and support an innovative target treatment for patients with Cushing's disease.

Use of CBCT plus plan robustness for reducing QACT frequency in intensity-modulated proton therapy: Head-and-neck cases.

PURPOSE: Anatomic variation has a significant dosimetric impact in intensity-modulated proton therapy. Weekly or biweekly computed tomography (CT) scans, called quality assurance CTs (QACTs), are used to monitor anatomic and resultant dose changes to determine whether adaptive plans are needed. Frequent CT scans result in unwanted QACT dose and increased clinical workloads. This study proposed utilizing patient setup cone-beam CTs (CBCTs) and treatment plan robustness to reduce the frequency of QACTs. METHODS: We retrospectively analyzed data from 27 patients with head-and-neck cancer, including 594 CBCTs, 136 QACTs, and 19 adaptive plans. For each CBCT, water-equivalent thickness (WET) along the pencil-beam path was calculated. For each treatment plan, the WET of the first-day CBCT was used as the reference, and the mean WET changes (ΔWET) in each following CBCT was used as the surrogate of proton range change. Using CBCTs acquired prior to a QACT, we predicted the ΔWET on the QACT day by a linear regression model. The impact of range change on target dose was calculated as the predicted ΔWET weighted by the monitor units of each field. In addition, plan robustness was estimated from the robust dose-volume histograms (DVHs) and combined with ΔWET to reduce QACT frequency. Robustness was estimated from the distance between the DVH curves of the nominal and worst scenarios. RESULTS: When the estimated mean ΔWET was <6.5 mm (or <7.5 mm if the robustness was >95%), the QACT could be skipped without missing any adaptive planning; otherwise a QACT was required. Overall, 41% of QACTs could be eliminated when ΔWET was <6.5 mm and 56% when ΔWET was <7.5 mm, and robustness was >95%. At least one QACT could have been omitted in 25 of the 27 cases under skipping thresholds at ΔWETs <7.5 mm and R > 95%. CONCLUSION: This study suggests that the number of QACTs can be greatly reduced by calculating range change in patient setup CBCTs and can be further reduced by combining this information with analyses of plan robustness.

Italian Association of Clinical Endocrinologists (AME) and International Chapter of Clinical Endocrinology (ICCE). Position statement for clinical practice: prolactin-secreting tumors.

Prolactinomas are the most frequent pituitary adenomas. Prolactinoma may occur in different clinical settings and always require an individually tailored approach. This is the reason why a panel of Italian neuroendocrine experts was charged with the task to provide indications for the diagnostic and therapeutic approaches that can be easily applied in different contexts. The document provides 15 recommendations for diagnosis and 54 recommendations for treatment, issued according to the GRADE system. The level of agreement among panel members was formally evaluated by RAND-UCLA methodology. In the last century, prolactinomas represented the paradigm of pituitary tumors for which the development of highly effective drugs obtained the best results, allowing to avoid neurosurgery in most cases. The impressive improvement of neurosurgical endoscopic techniques allows a far better definition of the tumoral tissue during surgery and the remission of endocrine symptoms in many patients with pituitary tumors. Consequently, this refinement of neurosurgery is changing the therapeutic strategy in prolactinomas, allowing the definitive cure of some patients with permanent discontinuation of medical therapy.

Semi-Supervised Segmentation of Radiation-Induced Pulmonary Fibrosis From Lung CT Scans With Multi-Scale Guided Dense Attention.

Computed Tomography (CT) plays an important role in monitoring radiation-induced Pulmonary Fibrosis (PF), where accurate segmentation of the PF lesions is highly desired for diagnosis and treatment follow-up. However, the task is challenged by ambiguous boundary, irregular shape, various position and size of the lesions, as well as the difficulty in acquiring a large set of annotated volumetric images for training. To overcome these problems, we propose a novel convolutional neural network called PF-Net and incorporate it into a semi-supervised learning framework based on Iterative Confidence-based Refinement And Weighting of pseudo Labels (I-CRAWL). Our PF-Net combines 2D and 3D convolutions to deal with CT volumes with large inter-slice spacing, and uses multi-scale guided dense attention to segment complex PF lesions. For semi-supervised learning, our I-CRAWL employs pixel-level uncertainty-based confidence-aware refinement to improve the accuracy of pseudo labels of unannotated images, and uses image-level uncertainty for confidence-based image weighting to suppress low-quality pseudo labels in an iterative training process. Extensive experiments with CT scans of Rhesus Macaques with radiation-induced PF showed that: 1) PF-Net achieved higher segmentation accuracy than existing 2D, 3D and 2.5D neural networks, and 2) I-CRAWL outperformed state-of-the-art semi-supervised learning methods for the PF lesion segmentation task. Our method has a potential to improve the diagnosis of PF and clinical assessment of side effects of radiotherapy for lung cancers.

Primary Endoscopic Endonasal Management of Giant Pituitary Adenomas: Outcome and Pitfalls from a Large Prospective Multicenter Experience.

PURPOSE: To evaluate factors influencing clinical and radiological outcome of extended endoscopic endonasal transtuberculum/transplanum approach (EEA-TTP) for giant pituitary adenomas (GPAs). METHODS: We recruited prospectively all consecutive GPAs patients undergoing EEA-TTP between 2015 and 2019 in 5 neurosurgical centers. Preoperative clinical and radiologic features, visual and hormonal outcomes, extent of resection (EoR), complications and recurrence rates were recorded and analyzed. RESULTS: Of 1169 patients treated for pituitary adenoma, 96 (8.2%) had GPAs. Seventy-eight (81.2%) patients had visual impairment, 12 (12.5%) had headaches, 3 (3.1%) had drowsiness due to hydrocephalus, and 53 (55.2%) had anterior pituitary insufficiency. EoR was gross or near-total in 46 (47.9%) and subtotal in 50 (52.1%) patients. Incomplete resection was associated with lateral suprasellar, intraventricular and/or cavernous sinus extension and with firm/fibrous consistence. At the last follow-up, all but one patient (77, 98.7%) with visual deficits improved. Headache improved in 8 (88.9%) and anterior pituitary function recovered in 27 (50.9%) patients. Recurrence rate was 16.7%, with 32 months mean recurrence-free survival. CONCLUSIONS: EEA-TTP is a valid option for GPAs and seems to provide better outcomes, lower rate of complications and higher EoR compared to one- or multi-stage microscopic, non-extended endoscopic transsphenoidal, and transcranial resections.

Microsurgical versus endoscopic trans-sphenoidal approaches for clivus chordoma: a pooled and meta-analysis.

Chordoma is a rare slow-growing neoplastic bone lesion. However, they show an invasive local growth and high recurrence rate, leading to an overall survival rate of 65% at 5 years and 35% at 10 years. We conducted a pooled and meta-analysis comparing recurrence rate, post-operative-complications, and survival in patients undergoing either microsurgical (MA) or endoscopic approaches (EA). Search of literature was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify surgical series of clivus chordomas published between January 1990 and March 2018 on Pubmed, Scopus, and Cochrane. Two different statistical analyses have been performed: a pooled analysis and a single-arm meta-analysis of overall recurrence rate and subgroup meta-analysis of complications in the subgroups open surgery and endoscopic surgery. After full-text screening, a total of 58 articles were included in the pooled analysis and 27 studies were included for the study-level meta-analysis. Pooled analysis-the extent of resection was the only association that remained significant (subtotal: HR = 2.18, p = 0.004; partial: HR = 4.40, p < 0.001). Recurrence was more prevalent among the surgical patients (45.5%) compared to endoscopic ones (23.7%). Meta-analysis-results of the cumulative meta-analysis showed an overall rate of recurrence of 25.6%. MA recurrence rate was 31.8% (99% CI 14-52.8), EA recurrence rate was 19.4% (5.4-39.2). CSF leak rate for the endoscopic group was 10.3% (99%CI 5-17.3) and 9.5% (99%CI 1.2-24.6) for the open surgery group. The partial removal versus total removal has an influence on recurrence rate (p < 0.001). MA recurrence rate was 31.8%; EA recurrence rate was 19.4%. The extent of resection is confirmed as a statistically significant factor affecting the risk for recurrence both with the pooled analysis and with the meta-analysis. Meta-analysis demonstrated that older patients tend to recur more than young patients, especially in surgical group.

Incidental Coronary Artery Calcium on Breast Radiation Therapy Planning Scans Identifies Patients for Cardiac Preventive Therapy.

PURPOSE/OBJECTIVE(S): The presence of coronary artery calcium (CAC>0) is associated with increased cardiac-related mortality and is a common indication to initiate statin therapy to prevent future long-term cardiac-related adverse events. CAC is also well visualized on noncontrast chest computed tomography simulation (CT sim) scans used for breast radiation planning. We hypothesize that by screening for incidental CAC on CT sims, radiation oncologists could help identify patients who may benefit from additional preventive medical interventions with their primary care physician or cardiologist. METHODS: A retrospective analysis of 126 consecutive patients with breast cancer treated with external beam radiation therapy at a single institution was performed. Noncontrast CT sim scans were reviewed for the presence of CAC and the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) was calculated to identify patients who may benefit from initiating statin therapy. Patients with CAC>0 and/or ASCVD risk >20% were identified as those who may benefit from statin therapy. RESULTS: Out of 72 patients with CAC>0, only 12(16%) had reported pre-existing coronary artery disease and 32(44%) were not already on recommended statin therapy. CAC>0 visualized on CT sim was able to identify 29 additional patients who would benefit from statin beyond what the ASCVD risk calculator could identify. CONCLUSION: Observation of incidental CAC on breast radiation-planning CT scans identified patients who could benefit from cardiac-related preventive strategies. By increasing attention, awareness, and reporting of incidental CAC visible on CT sims, radiation oncologists may fulfill a unique role to bridge a potential gap in cardiovascular preventive medicine.

Malignancy course of pituitary adenoma in MEN1 syndrome: Clinical-Neuroradiological signs.

Pituitary carcinomas (PCa) are extremely rare, indistinguishable from pituitary adenomas on histopathological grounds and have a poor prognosis. Most PCa start as PRL or ACTH secreting tumors in males, with relapsing invasive behaviour, refractoriness to medical and radiotherapy and increasing hormonal levels. The presence of distant metastases is still required for the diagnosis of PCa. The association with genetic endocrine diseases must be taken into account, since it adds further risk of evolution towards malignancy. Intradural spinal metastases have also been reported, so a complete craniospinal MR evaluation is recommended, when clinically indicated. We report a case of PCa, associated with MEN1 syndrome, with evidence of meningeal spread to the tentorium cerebelli, clival dura and spinal drop metastases mimicking spinal nerves schwannomas.

Sexual Dimorphism in Cellular and Molecular Features in Human ACTH-Secreting Pituitary Adenomas.

(1) Background. Cushing's disease presents gender disparities in prevalence and clinical course. Little is known, however, about sexual dimorphism at the level of the corticotrope adenoma itself. The aim of the present study was to evaluate molecular features of ACTH-secreting pituitary adenomas collected from female and male patients with Cushing's disease. (2) Methods. We analyzed 153 ACTH-secreting adenomas collected from 31 men and 122 women. Adenomas were established in culture and ACTH synthesis and secretion assessed in basal conditions as well as during incubation with CRH or dexamethasone. Concurrently, microarray analysis was performed on formalin-fixed specimens and differences in the expression profiles between specimens from male and female patients identified. (3) Results. ACTH medium concentrations in adenomas obtained from male patients were significantly lower than those observed in adenomas from female patients. This could be observed for baseline as well as modulated secretion. Analysis of corticotrope transcriptomes revealed considerable similarities with few, selected differences in functional annotations. Differentially expressed genes comprised genes with known sexual dimorphism, genes involved in tumour development and genes relevant to pituitary pathophysiology. (4) Conclusions. Our study shows for the first time that human corticotrope adenomas present sexual dimorphism and underlines the need for a gender-dependent analysis of these tumours. Differentially expressed genes may represent the basis for gender-tailored target therapy.

Italian Association of Clinical Endocrinologists (AME) and Italian AACE Chapter Position Statement for Clinical Practice: Acromegaly - Part 2: Therapeutic Issues.

Any newly diagnosed patient should be referred to a multidisciplinary team experienced in the treatment of pituitary adenomas. The therapeutic management of acromegaly always requires a personalized strategy. Normal age-matched IGF-I values are the treatment goal. Transsphenoidal surgery by an expert neurosurgeon is the primary treatment modality for most patients, especially if there are neurological complications. In patients with poor clinical conditions or who refuse surgery, primary medical treatment should be offered, firstly with somatostatin analogs (SSAs). In patients who do not reach hormonal targets with first-generation depot SSAs, a second pharmacological option with pasireotide LAR or pegvisomant (alone or combined with SSA) should be offered. Irradiation could be proposed to patients with surgical remnants who would like to be free from long-term medical therapies or those with persistent disease activity or tumor growth despite surgery or medical therapy. Since the therapeutic tools available enable therapeutic targets to be achieved in most cases, the challenge is to focus more on the quality of life.

Italian Association of Clinical Endocrinologists (AME) and Italian AACE Chapter Position Statement for Clinical Practice: Acromegaly - Part 1: Diagnostic and Clinical Issues.

Acromegaly is a rare disease. Improvements in lifespan in these patients have recently been reported due to transsphenoidal surgery (TSS), advances in medical therapy, and strict criteria for defining disease remission. This document reports the opinions of a group of Italian experts who have gathered together their prolonged clinical experience in the diagnostic and therapeutic challenges of acromegaly patients. Both GH and IGF-I (only IGF-I in those treated with Pegvisomant) are needed in the diagnosis and follow-up. Comorbidities (cardio-cerebrovascular disease, sleep apnea, metabolic derangement, neoplasms, and bone/joint disease) should be specifically addressed. Any newly diagnosed patient should be referred to a multidisciplinary team experienced in the treatment of pituitary adenomas.