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Endocrine Practice : Official Journal... Jun 2020Radiotherapy for patients with acromegaly was considered when patients have residual disease or tumor recurrence after surgery, or when surgery can't be carried out....
Comparing Stereotactic Radiosurgery and Fractionated Stereotactic Radiotherapy in Treating patients with Growth Hormone-Secreting Adenomas: A Systematic Review and Meta-analysis.
Radiotherapy for patients with acromegaly was considered when patients have residual disease or tumor recurrence after surgery, or when surgery can't be carried out. There are two main modes of radiotherapy, including stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT). We conducted a systematic review and meta-analysis to present the effectiveness and safety of SRS and FSRT for GH secreting pituitary adenoma in clinical practice. We searched the published literature using following databases: Pub Med, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and EMBASE up to March 22, 2020, for studies in which SRS or FSRT were used in patients with GH secreting pituitary. A total of 33 studies were eligible, involving 2016 participants. No significant differences were observed in tumor shrinkage rate, local tumor control rate and adverse effect rate between SRS and FSRT. Compared to FSRT, SRS showed significant increase in biochemical remission rate (43% vs. 28%; p=0.023) and significant lower follow-up GH level (SMD: -1.20 vs. -0.37, p=0.006). SRS and FSRT showed comparable effectiveness and safety in the management of GH secreting pituitary adenoma patients. SRS might be associated with better biochemical remission.
PubMed: 32576046
DOI: 10.4158/EP-2020-0110 -
Journal of Neuro-oncology Jul 2020We performed a systematic review and meta-analysis of clinical outcomes for patients with acromegaly treated with stereotactic radiosurgery (SRS). (Meta-Analysis)
Meta-Analysis
INTRODUCTION
We performed a systematic review and meta-analysis of clinical outcomes for patients with acromegaly treated with stereotactic radiosurgery (SRS).
METHODS
Primary outcomes were 5- and 10-year endocrine remission (ER) and endocrine control (EC). Secondary outcomes were 10-year radiographic local control (LC), visual toxicity, and hypopituitarism rates. Weighted random effects meta-analyses using the DerSimonian and Laird methods were conducted to characterize and compare effect sizes. Mixed effects regression models were used to examine correlations between potential prognostic factors and primary and secondary outcomes.
RESULTS
In total, 1533 patients across 20 published studies with acromegaly treated with SRS were included. At 5-years, estimated ER and EC rates were 43.2% (95% CI 31.7-54.6%) and 55.0% (95% CI 27.6-82.4%), respectively. At 10-years, estimated ER and EC rates were 56.9% (95% CI 47.5-66.4%) and 69.7% (95% CI 47.7-91.8%), respectively. The estimated 10-year LC rate was 92.8% (95% CI 83.0-100%). Visual toxicity and hypopituitarism following SRS were estimated to be 2.7% (95% CI 1.3-4.2%) and 26.8% (95% CI 16.9-36.7%), respectively. Every 1 Gy increase in margin prescription dose beyond 17 Gy was estimated to result in a 0.41% increased risk of visual toxicity (p = 0.03). No prognostic factors were associated with EC, ER, LC, or hypopituitarism.
CONCLUSIONS
SRS was well-tolerated in the management of pituitary acromegaly resulting in gradually improving ER and EC rates over time that approached 60% and 70%. SRS-related visual loss is an uncommon treatment-related side effect, and patient-specific clinical decision making remains critical.
Topics: Acromegaly; Humans; International Agencies; Radiosurgery; Treatment Outcome
PubMed: 32506372
DOI: 10.1007/s11060-020-03552-2 -
Pituitary Aug 2020Acromegaly is usually due to growth hormone (GH)-secreting pituitary adenomas, but it may be exceptionally caused by GH-secreting ectopic pituitary adenomas (EPA). EPA...
PURPOSE
Acromegaly is usually due to growth hormone (GH)-secreting pituitary adenomas, but it may be exceptionally caused by GH-secreting ectopic pituitary adenomas (EPA). EPA are defined as extra-sellar pituitary tumours, extra- or intra-cranially sited, entirely separated from the pituitary stalk and gland. The aim of the study is to address the challenges in the management of clival GHEPA.
METHODS
We reported a case of a 53-year-old acromegalic patient with a primary clival GHEPA and reviewed systematically the relevant English literature between 1975 and 2019, in keeping with the PRISMA guidelines.
RESULTS
Four cases of primary clival GHEPA have been described in literature apart from ours. All patients presented with acromegalic features, elevated circulating GH and/or insulin-like growth factor-1 levels. Hyperprolactinemia and empty sella were described in two cases, respectively. These tumours show the typical imaging characteristics of pituitary adenomas, but their neuroradiological diagnosis may be challenging due to their sizes and the difficulty in defining the absence of connections with the pituitary fossa.
CONCLUSION
Although primary clival GHEPA are exceedingly rare, even if likely under-reported in literature, they should be considered in the differential diagnosis of clival tumours because of their specific management. Surgery represents the first-line treatment option, while medical and radiation therapies can be adopted as neo-adjuvant, adjuvant or primary treatments according to tumour and patient characteristics.
Topics: Acromegaly; Adenoma; Bone Diseases; Choristoma; Cranial Fossa, Posterior; Empty Sella Syndrome; Glucose Tolerance Test; Growth Hormone-Secreting Pituitary Adenoma; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Male; Middle Aged; Pituitary Gland; Skull Base Neoplasms
PubMed: 32504302
DOI: 10.1007/s11102-020-01057-9 -
Experimental and Clinical Endocrinology... Dec 2020Phenotype transformation in pituitary adenomas (PA) is a little known and unexpected clinical phenomenon. We describe two illustrative cases and performed a systematic...
PURPOSE AND METHODS
Phenotype transformation in pituitary adenomas (PA) is a little known and unexpected clinical phenomenon. We describe two illustrative cases and performed a systematic review of cases reported in literature.
RESULTS
: A 24-year-old woman underwent surgery because of Cushing's disease. A complete tumor resection and hypercortisolism resolution was achieved. Two years later, tumor recurred but clinical and hormonal hypercortisolism were absent. : A 77-year-old woman underwent surgery due to acromegaly. A complete tumor resection and GH excess remission was achieved. Four years later, tumor recurred but clinical and hormonal acromegaly was ruled out. : From 20 patients (including our cases), 75% were female with median age 45 (19) years. Ten patients (50%) had initially functioning PA: 8 switched to NFPA (5 ACTH-secreting PA, 2 prolactinomas and 1 acromegaly) and 2 exchanged to acromegaly from TSH-secreting PA and microprolactinoma. One patient developed a pituitary carcinoma from ACTH-secreting PA. Ten patients (50%) initially had NFPA; 9 developed Cushing's disease (4 silent corticotroph adenomas, 4 null cell PA and 1 managed conservatively). One patient with silent somatotroph PA changed to acromegaly. Treatments before transformation were surgery (80%), radiotherapy (40%), pharmacological (40%) and in 2 patients switching happened without any treatment. Median follow-up until transformation was 72 months (range 12-276).
CONCLUSION
PA can change from functioning to (NF) non-functioning (vice versa) and even exchange their hormonal expression. Clinicians should be aware and a careful lifelong follow-up is mandatory to detect it.
Topics: Adult; Aged; Disease Progression; Female; Humans; Male; Middle Aged; Pituitary Neoplasms; Young Adult
PubMed: 32289831
DOI: 10.1055/a-1120-8277 -
PharmacoEconomics Jun 2020The use of patient-reported outcome measures (PROMs) to monitor the effects of disease and treatment on patient symptomatology and daily life is increasing in rare...
BACKGROUND
The use of patient-reported outcome measures (PROMs) to monitor the effects of disease and treatment on patient symptomatology and daily life is increasing in rare diseases (RDs) (i.e. those affecting less than one in 2000 people); however, these instruments seldom yield health state utility values (HSUVs) for cost-utility analyses. In such a context, 'mapping' allows HSUVs to be obtained by establishing a statistical relationship between a 'source' (e.g. a disease-specific PROM) and a 'target' preference-based measure [e.g. the EuroQol-5 Dimension (EQ-5D) tool].
OBJECTIVE
This study aimed to systematically review all published studies using 'mapping' to derive HSUVs from non-preference-based measures in RDs, and identify any critical issues related to the main features of RDs, which are characterised by small, heterogeneous, and geographically dispersed patient populations.
METHODS
The following databases were searched during the first half of 2019 without time, study design, or language restrictions: MEDLINE (via PubMed), the School of Health and Related Research Health Utility Database (ScHARRHUD), and the Health Economics Research Centre (HERC) database of mapping studies (version 7.0). The keywords combined terms related to 'mapping' with Orphanet's list of RD indications (e.g. 'acromegaly') in addition to 'rare' and 'orphan'. 'Very rare' diseases (i.e. those with fewer than 1000 cases or families documented in the medical literature) were excluded from the searches. A predefined, pilot-tested extraction template (in Excel) was used to collect structured information from the studies.
RESULTS
Two groups of studies were identified in the review. The first group (n = 19) developed novel mapping algorithms in 13 different RDs. As a target measure, the majority used EQ-5D, and the others used the Short-Form Six-Dimension (SF-6D) and 15D; most studies adopted ordinary least squares (OLS) regression. The second group of studies (n = 9) applied previously published algorithms in non-RDs to comparable RDs, mainly in the field of cancer. The critical issues relating to 'mapping' in RDs included the availability of very few studies, the relatively high number of cancer studies, and the absence of research in paediatric RDs. Moreover, the reviewed studies recruited small samples, showed a limited overlap between RD-specific and generic PROMs, and highlighted the presence of cultural and linguistic factors influencing results in multi-country studies. Lastly, the application of existing algorithms developed in non-RDs tended to produce inaccuracies at the bottom of the EQ-5D scale, due to the greater severity of RDs.
CONCLUSIONS
More research is encouraged to develop algorithms for a broader spectrum of RDs (including those affecting young children), improve mapping study quality, test the generalisability of algorithms developed in non-RDs (e.g. HIV) to rare variants or evolutions of the same condition (e.g. AIDS wasting syndrome), and verify the robustness of results when mapped HSUVs are used in cost-utility models.
Topics: Algorithms; Cost-Benefit Analysis; Health Status; Humans; Neoplasms; Patient Reported Outcome Measures; Quality of Life; Rare Diseases; Research Design; Surveys and Questionnaires
PubMed: 32152892
DOI: 10.1007/s40273-020-00897-4 -
Endocrine Practice : Official Journal... Apr 2020Comprehensive evidence comparing different medications for acromegaly is scarce. The aim of this study was to perform a network meta-analysis based on evidence from...
Comprehensive evidence comparing different medications for acromegaly is scarce. The aim of this study was to perform a network meta-analysis based on evidence from both randomized trials and observational studies of medical treatments for acromegaly. Electronic databases were searched for both observational studies and randomized trials that enrolled acromegaly patients treated with medications of interest. Simulated trials were generated by a machine learning algorithm and then synthesized with Bayesian random-effects network meta-analyses. The main outcome was the rate of insulin-like growth factor 1 (IGF-1) control after medical treatment. We included 90 studies (100 arms, 4,523 patients) before matching. After matching, 28 simulated trials were generated. Balance of matched arms was checked by spatial distance and correlation matrix. Cotreatment with somatostatin receptor ligands and pegvisomant was the most effective treatment compared with other treatments. In unselected patients, pegvisomant was better than octreotide long-acting release (logOR, 0.85; 95% credible interval [CrI], 0.05 to 1.65) or lanreotide (logOR, 1.09, 95% CrI, 0.05 to 2.14), and the mean absolute IGF-1 control rate ranged from 40 to 60%. In partially responsive patients, cotreatment with somatostatin receptor ligands and pegvisomant was similar to pegvisomant monotherapy, ranking as the most two effective treatments, and the mean absolute IGF-1 control rate was over 60%. Our analysis suggested that the combination of data from observational studies and randomized trials in network meta-analysis was feasible. The findings of this network meta-analysis provided robust evidence supporting the current guidelines in treatment strategy for acromegaly. = credible interval; = dopamine agonist; = growth hormone; = insulin-like growth factor 1; = intention-to-treat; = lanreotide; = lanreotide autogel; = octreotide; = octreotide long acting repeatable; = odds ratio; = pegvisomant; = per-protocol; = somatostatin receptor ligand.
Topics: Acromegaly; Bayes Theorem; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Network Meta-Analysis; Observational Studies as Topic; Octreotide; Peptides, Cyclic; Randomized Controlled Trials as Topic
PubMed: 32045295
DOI: 10.4158/EP-2019-0528 -
The Journal of Clinical Endocrinology... Mar 2020Obstructive sleep apnea (OSA) is a common disorder characterized by upper airway collapse requiring nocturnal ventilatory assistance. Multiple studies have investigated... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Obstructive sleep apnea (OSA) is a common disorder characterized by upper airway collapse requiring nocturnal ventilatory assistance. Multiple studies have investigated the relationship between acromegaly and OSA, reporting discordant results.
AIM
To conduct a meta-analysis on the risk for OSA in acromegaly, and in particular to assess the role of disease activity and the effect of treatments.
METHODS AND STUDY SELECTION
A search through literature databases retrieved 21 articles for a total of 24 studies (n = 734). Selected outcomes were OSA prevalence and apnea-hypopnea index (AHI) in studies comparing acromegalic patients with active (ACT) vs inactive (INACT) disease and pretreatment and posttreatment measures. Factors used for moderator and meta-regression analysis included the percentage of patients with severe OSA, patient sex, age, body mass index, levels of insulin-like growth factor 1, disease duration and follow-up, and therapy.
RESULTS
OSA prevalence was similar in patients with acromegaly who had ACT and INACT disease (ES = -0.16; 95% CI, -0.47 to 0.15; number of studies [k] = 10; P = 0.32). In addition, AHI was similar in ACT and INACT acromegaly patients (ES = -0.03; 95% CI, -0.49 to 0.43; k = 6; P = 0.89). When AHI was compared before and after treatment in patients with acromegaly (median follow-up of 6 months), a significant improvement was observed after treatment (ES = -0.36; 95% CI, -0.49 to -0.23; k = 10; P < 0.0001). In moderator analysis, the percentage of patients with severe OSA in the populations significantly influenced the difference in OSA prevalence (P = 0.038) and AHI (P = 0.04) in ACT vs INACT patients.
CONCLUSION
Prevalence of OSA and AHI is similar in ACT and INACT patients in cross-sectional studies. However, when AHI was measured longitudinally before and after treatment, a significant improvement was observed after treatment.
Topics: Acromegaly; Body Mass Index; Humans; Prevalence; Sleep Apnea, Obstructive; Treatment Outcome
PubMed: 31722411
DOI: 10.1210/clinem/dgz116 -
Scientific Reports Oct 2019Biochemical remission after transsphenoidal surgery is still unsatisfied in acromegaly patients with macroadenomas, especially with invasive macroadenomas. Concerning... (Comparative Study)
Comparative Study Meta-Analysis
Biochemical remission after transsphenoidal surgery is still unsatisfied in acromegaly patients with macroadenomas, especially with invasive macroadenomas. Concerning the impact of preoperative somatostatin analogues (SSAs) on surgical outcomes, previous studies with limited cases reported conflicting results. To assess current evidence of preoperative medical treatment, we performed a systematic review and meta-analysis of comparative studies. A literature search was conducted in Pubmed, Embase, and the Cochrane Library. Five randomized controlled trials (RCT) and seven non-RCT comparative studies were included. These studies mainly focused on pituitary macroadenomas though a small number of microadenoma cases were included. For safety, preoperative SSAs were not associated with elevated risks of postoperative complications. With respect to efficacy, the short-term cure rate was improved by preoperative SSAs, but the long-term cure rate showed no significant improvement. For invasive macroadenomas, the short-term cure rate was also improved, but the long-term results were not evaluable in clinical practice because adjuvant therapy was generally required. In conclusion, preoperative SSAs are safe in patients with acromegaly, and the favorable impact on surgical results is restricted to the short-term cure rate in macroadenomas and invasive macroadenomas. Further well-designed RCTs to examine long-term results are awaited to update the finding of this meta-analysis.
Topics: Acromegaly; Combined Modality Therapy; Growth Hormone-Secreting Pituitary Adenoma; Humans; Somatostatin; Treatment Outcome
PubMed: 31575930
DOI: 10.1038/s41598-019-50639-6 -
European Journal of Endocrinology Nov 2019
Meta-Analysis
Topics: Acromegaly; Human Growth Hormone; Humans; Mortality
PubMed: 31539872
DOI: 10.1530/EJE-19-0509 -
Neurosurgical Review Aug 2020Neurocognitive and psychological dysfunctions associated with pituitary adenomas (PAs) are clinically relevant, though probably under-reported. The aim of the current... (Meta-Analysis)
Meta-Analysis
Neurocognitive and psychological dysfunctions associated with pituitary adenomas (PAs) are clinically relevant, though probably under-reported. The aim of the current review is to provide an update on neuropsychological status, psychopathology, and perceived quality of life (QoL) in patients with PAs. A systematic research was performed in PubMed and Scopus in order to identify reports on neurocognitive, psychiatric, and psychological disorders in PAs. Prevalence of alterations, QoL evaluation, and used tests were also recorded. PRISMA guidelines were followed. Of 62,448 identified articles, 102 studies were included in the systematic review. The prevalence of neurocognitive dysfunctions was 15-83% in Cushing's Disease (CD), 2-33% in acromegaly, mostly affecting memory and attention. Memory was altered in 22% of nonfunctioning (NF) PAs. Worsened QoL was reported in 40% of CD patients. The prevalence of psychiatric disorders in CD reached 77% and in acromegaly 63%, mostly involving depression, followed by psychosis, and anxiety. The prevalence of psychopathology was up to 83% in CD, and 35% in acromegaly. Postoperative improvement in patients with CD was observed for: learning processes, overall memory, visuospatial skills, and language skills. Short-term memory and psychomotor speed improved in NFPAs. Postoperative improvement of QoL, somatic symptoms, obsessive-compulsive disorder, and coping strategies was seen in CD and acromegaly. Reports after radiotherapy are discordant. There is wide variability in used tests. PAs have been recently shown to be associated with altered neurocognitive and neuropsychological functions, as well as QoL. These data suggest the importance of a multidisciplinary evaluation for an optimal management.
Topics: Cognition Disorders; Humans; Neuropsychological Tests; Pituitary Neoplasms; Quality of Life
PubMed: 31250149
DOI: 10.1007/s10143-019-01134-z