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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 -
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 -
European Journal of Endocrinology Dec 2020Neurosurgery is the first-line treatment for acromegaly. Whether metabolic disorders are reversible after neurosurgery is still debated. The meta-analysis aimed to... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Neurosurgery is the first-line treatment for acromegaly. Whether metabolic disorders are reversible after neurosurgery is still debated. The meta-analysis aimed to address the following questions: (i) Does neurosurgery affect glycolipid metabolism? (ii) Are these effects related to disease control or follow-up length?
DESIGN
A meta-analysis and systematic review of the literature.
METHODS
Three reviewers searched databases until August 2019 for prospective trials reporting glycometabolic outcomes after neurosurgery. Three other extracted outcomes, all assessed the risk of bias.
RESULTS
Twenty studies were included. Neurosurgery significantly reduced fasting plasma glucose (FPG) (effect size (ES): -0.57 mmol/L, 95% CI: -0.82 to -0.31; P < 0.001), glucose load (ES: -1.10 mmol/L, 95% CI: -1.66 to -0.53; P < 0.001), glycosylated haemoglobin (HbA1c) (ES: -0.28%, 95% CI: -0.42 to -0.14; P < 0.001), fasting plasma insulin (FPI) (ES: -10.53 mU/L, 95% CI: -14.54 to -6.51; P < 0.001), homeostatic model assessment of insulin resistance (HOMA-IR) (ES: -1.98, 95% CI: -3.24 to -0.72; P = 0.002), triglycerides (TGDs) (ES: -0.28 mmol/L, 95% CI: -0.36 to -0.20; P < 0.001) and LDL-cholesterol (LDLC) (ES: -0.23 mmol/L, 95% CI: -0.45 to -0.02 mmol/L); P = 0.030) and increased HDL-cholesterol (HDLC) (ES: 0.21 mmol/L, 95% CI: 0.14 to 0.28; P < 0.001). Meta-regression analysis showed that follow-up length - not disease control - had a significant effect on FPG, with the greatest reduction in the shortest follow-up (beta = 0.012, s.e. = 0.003; P = 0.001).
CONCLUSIONS
Neurosurgery improves metabolism with a significant decrease in FPG, glucose load, HbA1c, FPI, HOMA-IR, TGDs, and LDLC and increase in HDLC. The effect on FPG seems to be more related to follow-up length than to disease control.
Topics: Acromegaly; Cholesterol; Follow-Up Studies; Glucose; Glycated Hemoglobin; Humans; Neurosurgical Procedures; Prospective Studies; Randomized Controlled Trials as Topic
PubMed: 33075752
DOI: 10.1530/EJE-20-0497 -
Neuroendocrinology 2021This study described a Chinese case of X-linked acrogigantism (X-LAG) and summarized the characteristics and treatment of all reported cases.
INTRODUCTION
This study described a Chinese case of X-linked acrogigantism (X-LAG) and summarized the characteristics and treatment of all reported cases.
METHODS
Clinical materials and biological samples from a 5-year and 2-month-old female due to "growth acceleration for 4 years" were collected. Array comparative genomic hybrid (aCGH) and further verification were performed. All X-LAG cases from the PubMed and Web of Science databases were collected and summarized with available data.
RESULTS
The patient presented accelerating growth since 1 year, and her height reached 134.6 cm (+5.24 standard deviation score [SDS]) when she was 5-year and 2-month old. She also had coarsening facial features, snoring, and acral enlargement. Growth hormone (GH) was not suppressed by the glucose-GH inhibition test, and insulin-like growth factor 1 (IGF-1) and prolactin (PRL) levels were elevated. Pituitary MRI revealed a pituitary enlargement with a maximum diameter of 22.3 mm. Octreotide imaging indicated the presence of a pituitary adenoma. The tumor shrank slightly after 3 courses of somatostatin analog but without clinical or biochemical remissions, of which the GH nadir value was 9.4 ng/mL, and IGF-1 was elevated to 749 ng/mL. Therefore, she underwent transsphenoidal surgery. Immunohistochemistry showed GH-positive and PRL-positive cells in the pituitary adenoma. Xq26.3 microduplication of the patient's germline DNA was identified by aCGH. Of all 35 reported cases, females accounted for 71.43%. There were 93.10% and 53.83% patients with hyperprolactinemia and hyperinsulinemia, respectively. Pathology showed that 75.00% of cases were adenomas. Ninety percent of cases had germline variants. The clinical and biochemical remission rates were 78.26% and 82.61%, respectively. However, the rate of complication occurrence during therapy reached 80%.
CONCLUSION
It is important to recognize the possibility of X-LAG when a child under 2-year old presents overgrowth. Early diagnosis and treatment are of great importance for better treatment efficacy and clinical outcome.
Topics: Acromegaly; Child, Preschool; China; Female; Genetic Diseases, X-Linked; Humans
PubMed: 33049741
DOI: 10.1159/000512240 -
European Journal of Endocrinology Nov 2019
Meta-Analysis
Topics: Acromegaly; Human Growth Hormone; Humans; Mortality
PubMed: 31539872
DOI: 10.1530/EJE-19-0509 -
Frontiers in Endocrinology 2021Epithelial-mesenchymal transition (EMT) is a dynamic process by which epithelial cells loss their phenotype and acquire mesenchymal traits, including increased migratory...
Epithelial-mesenchymal transition (EMT) is a dynamic process by which epithelial cells loss their phenotype and acquire mesenchymal traits, including increased migratory and invasive capacities. EMT is involved in physiological processes, such as embryogenesis and wound healing, and in pathological processes such as cancer, playing a pivotal role in tumor progression and metastasis. Pituitary tumors, although typically benign, can be locally invasive. Different studies have shown the association of EMT with increased tumor size and invasion in pituitary tumors, and in particular with a poor response to Somatostatin Receptor Ligands (SRLs) treatment in GH-producing pituitary tumors, the main cause of acromegaly. This review will summarize the current knowledge regarding EMT and SRLs resistance in acromegaly and, based on this relation, will suggest new biomarkers and possible therapies to SRLs resistant tumors.
Topics: Acromegaly; Biomarkers; Cadherins; Cytoskeleton; Drug Resistance; Endocrine Gland Neoplasms; Epithelial-Mesenchymal Transition; Growth Hormone-Secreting Pituitary Adenoma; Humans; Ligands; Phenotype; Pituitary Neoplasms; Receptors, Somatostatin; Somatostatin
PubMed: 33790868
DOI: 10.3389/fendo.2021.646210 -
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 -
Pituitary Jun 2024Prolactinomas are common tumours that significantly reduce quality-of-life (QOL) due to sellar mass effect, secondary hypogonadism, and the peripheral effects of...
BACKGROUND
Prolactinomas are common tumours that significantly reduce quality-of-life (QOL) due to sellar mass effect, secondary hypogonadism, and the peripheral effects of prolactin. Understanding the factors that influence QOL would provide insights into therapeutic targets to optimise patient outcomes and improve wellbeing in prolactinoma.
METHODS
A systematic review was performed in accordance with the PRISMA statement. Studies that reported patient QoL using validated metrics were included. Bias and methodological rigour were assessed using the MINORS criteria.
RESULTS
A total of 18 studies were identified studies were available for review, comprising 877 patients. Most were small cross-sectional studies at high risk of bias. Prolactinoma exhibit worse QOL than healthy controls, particularly mental and psychosocial wellbeing. QOL is also worse than patients with non-functional adenomas, but better than those with Cushing's disease and acromegaly. QOL correlates with prolactin levels, and approaches population baseline with prolonged biochemical control. Dopamine agonists and surgery both improve overall QOL, however improvements are more rapid with surgery.
CONCLUSION
Poor quality of life in prolactinoma is multifactorial, related to biochemical control, side effects of therapy, and sellar mass effect. Targeting persistent symptoms, reducing healthcare costs, and reducing side-effects of therapy are avenues to improving QOL in patients with prolactinoma.
Topics: Prolactinoma; Humans; Quality of Life; Pituitary Neoplasms; Dopamine Agonists
PubMed: 38656635
DOI: 10.1007/s11102-024-01392-1 -
Endocrine Jul 2023The current study aimed to report cases of McCune Albright syndrome (MAS) with growth hormone (GH) hyper secretion along with a systematic review of literature to...
PURPOSE
The current study aimed to report cases of McCune Albright syndrome (MAS) with growth hormone (GH) hyper secretion along with a systematic review of literature to elucidate challenges and intricacies in its diagnosis and management.
METHODS
It was a single centre study carried out in individuals with MAS and autonomous GH secretion (AGHS). In addition, a systematic search of literature across three databases (PubMed, Scopus and EMBASE) was performed from inception until May 31, 2021 to identify cases of MAS with AGHS in the pediatric age group (<18 years).
RESULTS
Three cases from authors centre and 42 cases identified from systematic literature review were analysed. Precocious puberty was the most common presenting endocrinopathy seen in 56.8% (25/44) cases, followed by hyperthyroidism (10/45), hypophosphatemia (4/45), and hypercortisolism (2/45). Cranio-facial fibrous dysplasia (CFFD) was seen in all while polyostotic fibrous dysplasia and Café au lait macule was seen in 40/45 (88.9%) and 35/45 (77.8%), respectively. Pituitary adenoma (58.3% microadenoma) was localized in 53.3% (24/45) cases on pituitary imaging. Biochemical and clinical remission of AGHS was achieved in 61.5% (24/45) cases with medical therapy.
CONCLUSION
Diagnosing AGHS in MAS is challenging because of concomitant presence of CFFD, non-GH endocrinopathies associated height spurt and elevated serum IGF-1. GH-GTT should be performed in presence of elevated growth velocity and serum IGF-1 (>1 X ULN) despite adequate control of non-GH endocrinopathies. Medical management can lead to disease control in substantial number of cases and often entails use of multiple agents.
Topics: Child; Humans; Adenoma; Fibrous Dysplasia, Polyostotic; Growth Hormone; Insulin-Like Growth Factor I; Pituitary Neoplasms
PubMed: 36877453
DOI: 10.1007/s12020-023-03333-7 -
Endocrine Mar 2023A systematic literature review was conducted to assess the use of home injections (self/partner/healthcare provider [HCP]-administered) of somatostatin analogs (SSAs) as...
PURPOSE
A systematic literature review was conducted to assess the use of home injections (self/partner/healthcare provider [HCP]-administered) of somatostatin analogs (SSAs) as an alternative to healthcare-setting injections in patients with acromegaly and neuroendocrine tumors (NETs).
METHODS
MEDLINE/Embase/the Cochrane Library (2001-September 2021), key congresses (2019-2021), and bibliographies of relevant systematic reviews were searched. Eligible studies reported on efficacy/effectiveness, safety, adherence, patient-reported outcomes (PROs), and economic outcomes in populations receiving home injections of SSAs.
RESULTS
Overall, 12 studies were included, all reporting on SSAs (lanreotide Autogel/Depot or octreotide long-acting release) in acromegaly or NETs. Across four studies, home injection was associated with similar disease control in patients with acromegaly/NETs compared with healthcare-setting administration. High rates of treatment adherence were shown in two studies of patients with acromegaly receiving lanreotide injections at home. Two studies reported non-serious adverse events; incidence of adverse reactions was similar in both the home and healthcare administration settings. Preference for injection setting varied between studies and indications; nonetheless, higher satisfaction/convenience (>75% patients) was reported for home injections. Self- or partner-injection was associated with economic savings compared with administration in the healthcare setting across five studies.
CONCLUSION
Efficacy/effectiveness, adherence, and safety outcomes of SSAs in the home injection setting were similar to those in the healthcare setting, with high reported satisfaction and convenience. Self/partner injection also resulted in cost savings. These findings provide a basis to understand outcomes related to home injection and encourage healthcare providers to discuss optimal treatment choices with their patients.
Topics: Humans; Somatostatin; Acromegaly; Peptides, Cyclic; Octreotide; Injections, Subcutaneous; Neuroendocrine Tumors
PubMed: 36369434
DOI: 10.1007/s12020-022-03227-0