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Endocrine Practice : Official Journal... Mar 2015When patients with acromegaly have residual disease following surgery, adjuvant radiation therapy is considered. Both stereotactic radiosurgery (SRS) and conventional...
OBJECTIVE
When patients with acromegaly have residual disease following surgery, adjuvant radiation therapy is considered. Both stereotactic radiosurgery (SRS) and conventional fractionated radiotherapy (RT) are utilized. We conducted a systematic review and meta-analysis to synthesize the existing evidence to compare outcomes with SRS and RT in patients with acromegaly.
METHODS
We searched Medline In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus through April 2014 for studies in which SRS or RT were used in patients with acromegaly. Outcomes evaluated were serum IGF-1 and GH levels, biochemical remission, all-cause mortality, hypopituitarism, headaches and secondary malignancies. We pooled outcomes using the random-effects model.
RESULTS
The final search yielded 30 eligible studies enrolling 2464 patients. When compared to RT, SRS was associated with a non-significant increase in remission rate at the latest follow-up period (52% vs. 36%; p = 0.14), and a significantly lower follow-up IGF-1 level (decline of - 409.72 μg/1 vs. -102 μg/1; p = 0.002). SRS was associated with lower incidence of hypopituitarism than RT; however the difference was not statistically significant [(32% vs.51%, respectively; p = 0.05).
CONCLUSIONS
SRS may be associated with better biochemical remission and lower risk of hypopituitarism with at least one deficient axis when compared with RT; however, the confidence in such evidence is very low due to the non-comparative nature of the studies, high heterogeneity, and imprecision.
PubMed: 25786558
DOI: 10.4158/EP14574.RA -
Neuroendocrinology 2017The common exon 3 deletion polymorphism of the growth hormone receptor (d3-GHR) is associated with disease severity in acromegaly patients. The GHR antagonist... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The common exon 3 deletion polymorphism of the growth hormone receptor (d3-GHR) is associated with disease severity in acromegaly patients. The GHR antagonist pegvisomant (PEGV) is highly effective in treating severe acromegaly. Response to PEGV treatment seems to be influenced by d3-GHR and appears to be more responsive to PEGV, although available results remain conflicting.
OBJECTIVE
To assess the influence of d3-GHR on the responsiveness of acromegaly patients to PEGV by compiling the evidence derived from the largest available studies.
DESIGN
A systematic review of the literature identified three published studies and one conference abstract. Acromegaly patients (n = 324, 49.7% d3-GHR carriers) were treated with either PEGV monotherapy or PEGV combined with long-acting somatostatin analogues and/or cabergoline. A meta-analysis of raw data from these studies was performed.
RESULTS
No significant effect of the d3-GHR was observed while bringing insulin-like growth factor I (IGF-I) levels below the upper limit of normal with PEGV, which was defined as the lowest IGF-I level during PEGV treatment (mean difference: -2.3%; 95% CI: -6.5 to 1.8, p = 0.270). The PEGV dose required to achieve the lowest IGF-I levels was also not significantly influenced by individuals carrying d3-GHR (mean difference: 4.1 mg weekly; 95% CI: -5.1 to 13.2, p = 0.385). For both outcomes, separate analysis of PEGV monotherapy and combination treatment gave similar results.
CONCLUSION
Our findings suggest that the d3-GHR polymorphism has no effect on biochemical disease control in acromegaly, as it is not of added value for either the prediction of PEGV responsiveness or the determination of the required PEGV dose.
Topics: Acromegaly; Exons; Human Growth Hormone; Humans; Receptors, Somatotropin; Sequence Deletion
PubMed: 27513761
DOI: 10.1159/000448844 -
World Neurosurgery Jan 2017The pituitary adenoma causing acromegaly is typically resected through a transsphenoidal approach and visualized with an operating microscope or endoscope. We undertook... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
The pituitary adenoma causing acromegaly is typically resected through a transsphenoidal approach and visualized with an operating microscope or endoscope. We undertook a systematic review and meta-analysis examining the clinical efficacy of endoscopic and microsurgical approaches.
METHODS
Relevant studies using either endoscopic or microscopic transsphenoidal approaches for growth hormone pituitary adenomas were identified until February 2016. Data were extracted and analyzed according to predefined clinical end points.
RESULTS
We identified 31 studies, in which 950 patients underwent endoscopic transsphenoidal resection and 2137 patients underwent microsurgical transsphenoidal resection. Patients undergoing microsurgery were less likely to present with hypothyroidism (10.7% vs. 19.1%, P = 0.033, 462 vs. 156 patients) and less likely to have macroadenomas (66.9% vs. 83.8%, P ≤ 0.001, 1484 vs. 884 patients); adenomas with cavernous sinus invasion (21.3% vs. 44.4%, P = 0.036, 592 vs. 558 patients); and a lower mean tumor volume (17.84 vs. 20.54 mm, P = 0.012, 158 vs. 248 patients). Patients treated via the endoscopic approach were more likely to achieve remission for noninvasive macroadenomas (83.8% vs. 66.9%, P ≤ 0.001, 115 vs. 365 patients). Sinusitis (15.6% vs. 2.6%, P < 0.001, 241 vs. 295 patients) and intraoperative cerebrospinal fluid leak (21.6% vs. 1.0%, P = 0.022, 697 vs. 127 patients) were more common in patients treated endoscopically, and meningitis (0.7% vs. 1.7%, P = 0.027, 511 vs. 1513 patients) was more common in patients undergoing a microsurgical approach.
CONCLUSIONS
Our study shows the clinical utility of the endoscopic approach and demonstrates potential benefits including increased remission rates with noninvasive macroadenomas and a lower rate of meningitis.
Topics: Adenoma; Adult; Aged; Aged, 80 and over; Comorbidity; Female; Growth Hormone-Secreting Pituitary Adenoma; Humans; Male; Microsurgery; Middle Aged; Neuroendoscopy; Postoperative Complications; Prevalence; Risk Factors; Sphenoid Bone; Transanal Endoscopic Microsurgery; Treatment Outcome
PubMed: 27756664
DOI: 10.1016/j.wneu.2016.10.029 -
Journal of Neurosurgery Mar 2022A systematic review was performed to provide objective evidence on the use of stereotactic radiosurgery (SRS) in the management of secretory pituitary adenomas and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
A systematic review was performed to provide objective evidence on the use of stereotactic radiosurgery (SRS) in the management of secretory pituitary adenomas and develop consensus recommendations.
METHODS
The authors performed a systematic review of the English-language literature up until June 2018 using the PRISMA guidelines. The PubMed (Medline), Embase, and Cochrane databases were searched. A total of 45 articles reporting single-institution outcomes of SRS for acromegaly, Cushing's disease, and prolactinomas were selected and included in the analysis.
RESULTS
For acromegaly, random effects meta-analysis estimates for crude tumor control rate, crude endocrine remission rate, and any new hypopituitarism rates were 97.0% (95% CI 96.0%-98.0%), 44.0% (95% CI 35.0%-53.0%), and 17.0% (95% CI 13.0%-23.0%), respectively. For Cushing's disease, random effects estimates for crude tumor control rate, crude endocrine remission rate, and any new hypopituitarism rate were 92.0% (95% CI 87.0%-95.0%), 48.0% (95% CI 35.0%-61.0%), and 21.0% (95% CI 13.0%-31.0%), respectively. For prolactinomas, random effects estimates for crude tumor control rate, crude endocrine remission rate, and any new hypopituitarism rate were 93.0% (95% CI 90.0%-95.0%), 28.0% (95% CI 19.0%-39.0%), and 12.0% (95% CI 6.0%-24.0%), respectively. Meta-regression analysis did not show a statistically significant association between mean margin dose with crude endocrine remission rate or mean margin dose with development of any new hypopituitarism rate for any of the secretory subtypes.
CONCLUSIONS
SRS offers effective tumor control of hormone-producing pituitary adenomas in the majority of patients but a lower rate of endocrine improvement or remission.
Topics: Acromegaly; Humans; Hypopituitarism; Pituitary ACTH Hypersecretion; Pituitary Neoplasms; Prolactinoma; Radiosurgery; Retrospective Studies; Treatment Outcome
PubMed: 34479203
DOI: 10.3171/2021.2.JNS204440 -
Acta Neurochirurgica Nov 2016In 2010, the Acromegaly Consensus Group revised the criteria for cure of acromegaly and thus rates of surgical remission need to be revised in light of these new... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In 2010, the Acromegaly Consensus Group revised the criteria for cure of acromegaly and thus rates of surgical remission need to be revised in light of these new thresholds. Two subgroups consisted of patients with discordant GH and IGF-1 levels and patients in remission according to the 2000 criteria, but not to the 2010 criteria, have been reported after adenomectomy and for these subgroups the precise incidence and management has not been established. The objective of the study was to update rates of surgical remission and complications and to evaluate the incidence, management, and long-term outcome of the two previously described subgroups of patients.
METHODS
Systematic review and meta-analysis of surgical series that defined remission according to the 2010 biochemical criteria.
RESULTS
We included 13 studies (1105 patients). The pooled rate of overall surgical remission was 54.8 % (95 % CI 44.4-65.2 %), and 72.2 % with previous criteria. Remission was achieved in 77.9 % (95 % CI 68.1-87.6 %) of microadenomas; 52.7 % (95 % CI 41-64.4 %) of macroadenomas; 29 % (95 % CI 20.1-37.8 %) of invasive and 68.8 % (95 % CI 60-77.6 %) of non-invasive adenomas. Complication rates were 1.2 % (95 % CI 0.6-1.9 %) for CSF leak, 1.3 % (95 % CI 0.6-2.1 %) for permanent diabetes insipidus, 8.7 % (95 % CI 4.8-12.5 %) for new anterior pituitary dysfunction and 0.6 % (95 % CI 0.1-1.1 %) for severe intraoperative hemorrhage. We identified an intermediate group of patients, defined as: (1) Remission according to one, but not the other biochemical criteria (GH or IGF-1) or 2010 criteria (14.3 % and 47.1 % cases), (2) Remission according to 2000, but not 2010 criteria (13.2-58.8 % cases). Two studies reported a remission rate of 56.5 % and 100 %, in the two subgroups respectively, in a long-term outcome without adjuvant therapy.
CONCLUSIONS
Overall remission with transsphenoidal surgery is achieved in ∼55 % of patients. For the intermediate group of patients, future prospective studies with long-term follow-up are required to determine the long-term biochemical remission rates and clinical implications.
Topics: Acromegaly; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Pituitary Neoplasms; Postoperative Complications
PubMed: 27586125
DOI: 10.1007/s00701-016-2903-4 -
Journal of Research in Medical Sciences... 2019There is a belief that in patients with acromegaly, first-generation somatostatin analogs (SSAs) might improve cardiovascular (CV) structure and function. However, most... (Review)
Review
BACKGROUND
There is a belief that in patients with acromegaly, first-generation somatostatin analogs (SSAs) might improve cardiovascular (CV) structure and function. However, most published clinical trials involved only a few patients and their results are rather variable. We aimed to conduct a systematic review on available studies on the impact of these drugs on CV parameters.
MATERIALS AND METHODS
A literature search was conducted in MEDLINE (OVID), EMBase, Cochrane, and ISI Web of Science for citations published until April 30 2018 to identify studies on our objective that considered changes in CV parameters. For this search, we established a Boolean search strategy using keywords related to "acromegaly," "Somatostatin analog," and "cardiovascular diseases and parameters." All study types except for case reports or conference abstracts were included. Twenty-four studies ( = 558) fulfilled the inclusion criteria and were selected for final analysis.
RESULTS
In 12 studies ( = 350), decrease in heart rate (HR) and in 4 studies ( = 128), decrease in blood pressure (BP) was significant. In 15 studies ( = 320), left ventricular mass index (LVMi) changes were significant. In 9 studies ( = 202), the early diastole to peak velocity flow in late diastole (E/A ratio) was evaluated, and in 5 of them ( = 141), the improvement was significant. Eighteen studies ( = 366) examined changes in left ventricular ejection fraction (LVEF), 5 of which ( = 171) reported that these changes were significant. Decrease of left ventricular end-diastolic diameter was reported in only 2 studies ( = 27).
CONCLUSION
We found that first-generation SSAs have a beneficial effect on cardiac parameters such as HR and LVMi. For other parameters such as LVEF, BP, LV diameter, and E/A ratio, we were not able to draw a firm conclusion.
PubMed: 31143230
DOI: 10.4103/jrms.JRMS_955_18 -
Journal of Endocrinological... Feb 2016Hyperglycemia is a common feature associated with states of increased growth hormone secretion and glucocorticoid levels. The purpose of these guidelines is to assist... (Review)
Review
Hyperglycemia is a common feature associated with states of increased growth hormone secretion and glucocorticoid levels. The purpose of these guidelines is to assist clinicians and other health care providers to take evidence-based therapeutic decisions for the treatment of hyperglycemia in patients with growth hormone and corticosteroid excess. Both the SID and SIE appointed members to represent each society and to collaborate in Guidelines writing. Members were chosen for their specific knowledge in the field. Each member agreed to produce-and regularly update-conflicts of interest. The authors of these guidelines prepared their contributions following the recommendations for the development of Guidelines, using the standard classes of recommendation shown below. All members of the writing committee provided editing and systematic review of each part of the manuscript, and discussed the grading of evidence. Consensus was guided by a systematic review of all available trials and by interactive discussions.
Topics: Acromegaly; Combined Modality Therapy; Consensus; Cushing Syndrome; Diabetes Mellitus; Endocrinology; Evidence-Based Medicine; Glucocorticoids; Human Growth Hormone; Humans; Hyperglycemia; Italy; Precision Medicine; Societies, Scientific
PubMed: 26718207
DOI: 10.1007/s40618-015-0404-6 -
Nutrition, Metabolism, and... Feb 2016Hyperglycemia is a common feature associated with states of increased growth hormone secretion and glucocorticoid levels. (Review)
Review
BACKGROUND
Hyperglycemia is a common feature associated with states of increased growth hormone secretion and glucocorticoid levels.
AIMS
The purpose of these guidelines is to assist clinicians and other health care providers to take evidence-based therapeutic decisions for the treatment of hyperglycemia in patients with growth hormone and corticosteroid excess.
METHODOLOGY
Both the SID and SIE appointed members to represent each society and to collaborate in Guidelines writing. Members were chosen for their specific knowledge in the field. Each member agreed to produce--and regularly update--conflicts of interest. The Authors of these guidelines prepared their contributions following the recommendations for the development of Guidelines, using the standard classes of recommendation shown below. All members of the writing committee provided editing and systematic review of each part of the manuscript, and discussed the grading of evidence. Consensus was guided by a systematic review of all available trials and by interactive discussions.
Topics: Acromegaly; Biomarkers; Blood Glucose; Consensus; Cushing Syndrome; Endocrinology; Humans; Hyperglycemia; Hypoglycemic Agents; Italy; Societies, Medical; Treatment Outcome
PubMed: 26905474
DOI: 10.1016/j.numecd.2016.02.001 -
Neuroendocrinology 2023Acromegaly is characterized by impaired bone quality and increased fracture risk. However, due to the pathophysiology of acromegalic osteopathy, bone mineral density... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acromegaly is characterized by impaired bone quality and increased fracture risk. However, due to the pathophysiology of acromegalic osteopathy, bone mineral density (BMD) does not represent a reliable predictor for fragility fractures in this setting. Trabecular bone score (TBS) has been recently evaluated as an alternative index of skeletal fragility in acromegalic patients. However, no conclusive data are still available in this regard.
METHODS
PubMed/Medline, EMBASE, Cochrane Library, Ovid, and CINAHL databases were systematically searched until June 2022 for studies reporting data either about the comparison of TBS values between acromegalic patients and non-acromegalic controls or about the relationship - within acromegalic patients - between TBS values and fracture risk. Effect sizes were pooled through a random-effect model.
RESULTS
Eight studies were eligible for inclusion in the meta-analysis, encompassing 336 acromegalic patients and 490 non-acromegalic controls. Overall, TBS was significantly lower in acromegalic patients compared to controls (-0.089, 95% CI: [-0.111, -0.067], p < 0.01), irrespective of acromegaly disease activity and gonadal status. With respect to fracture risk, TBS was significantly lower in acromegalic patients with vertebral fractures than in those without (-0.099, 95% CI: [-0.166, -0.032], p < 0.01).
CONCLUSION
In this meta-analysis, we specifically assessed the role of TBS as an index of bone quality and fracture risk in patients with acromegaly. Our results support the notion that TBS could be of value in the assessment and management of skeletal fragility in acromegalic patients, especially in light of the poor information provided in this setting by BMD.
Topics: Humans; Cancellous Bone; Acromegaly; Absorptiometry, Photon; Lumbar Vertebrae; Bone Density
PubMed: 36617407
DOI: 10.1159/000528199 -
World Neurosurgery Jun 2018Plurihormonal adenomas (PHAs) represent 10%-15% of all functioning pituitary adenomas. The most frequent hormonal associations are with prolactin and growth hormone... (Review)
Review
BACKGROUND
Plurihormonal adenomas (PHAs) represent 10%-15% of all functioning pituitary adenomas. The most frequent hormonal associations are with prolactin and growth hormone (GH). Here we describe a rare case of functional adrenocorticotropic hormone (ACTH) and GH microadenoma and report our findings from a systematic literature review of PHA.
METHODS
We searched PubMed using the terms "plurihormonal pituitary adenoma," "ACTH GH pituitary adenoma," and "acromegaly AND Cushing's disease". In the 17 articles that were selected for literature review, only 20% (4/20) of patients presented with clinical signs of both diseases. Histologically, 19 were pituitary adenomas composed of two distinct cell populations, while only in 1 case was there evidence of a single cell producing both ACTH and GH. In the case reported here, a 60-year-old woman was incidentally diagnosed with a pituitary microadenoma. Endocrine assessment documented increased levels of insulin-like growth factor 1 and GH; ACTH and cortisol values were within normal ranges. Echocardiography documented ventricular hypertrophy. Because of clinical and biochemical evidence of acromegaly, surgery was recommended. Postoperatively, hormonal replacement therapy was started because of adrenal insufficiency. Her antihypertensive therapy was discontinued due to evidence of normal blood pressure values. Histological examination revealed an ACTH-GH PHA with 2 distinct populations of secreting cells. At 3-year follow-up, the patient showed stable clinical remission and was no longer receiving hormonal replacement therapy.
CONCLUSIONS
This is an additional case to the 20 previously reported cases of ACTH-GH PHA. Awareness of this relatively rare entity is clinically relevant. The cytogenesis of ACTH-GH PHA remains a matter of debate, and several hypotheses have been postulated.
Topics: Adenoma; Adrenocorticotropic Hormone; Antineoplastic Agents, Hormonal; Female; Growth Hormone; Humans; Middle Aged; Pituitary Neoplasms; Prolactin
PubMed: 29501516
DOI: 10.1016/j.wneu.2018.02.120