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The Journal of Clinical Endocrinology... Nov 2014Acromegaly is usually treated with surgery as a first-line treatment, although medical therapy has also been used as an alternative primary treatment. (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Acromegaly is usually treated with surgery as a first-line treatment, although medical therapy has also been used as an alternative primary treatment.
OBJECTIVE
We conducted a systematic review and meta-analysis to synthesize the existing evidence comparing these two approaches in treatment-naïve patients with acromegaly.
DATA SOURCES
This study performed a comprehensive search in multiple databases, including Medline, EMBASE, and Scopus from early inception through April 2014.
STUDY SELECTION
The study used original controlled and uncontrolled studies that enrolled patients with acromegaly to receive either surgical treatment or medical treatment as their first-line treatment.
DATA EXTRACTION
Reviewers extracted data independently and in duplicates. Because of the noncomparative nature of the available studies, we modified the Newcastle-Ottawa Scale to assess the quality of included studies. Outcomes evaluated were biochemical remission and change in IGF-1 or GH levels. We pooled outcomes using the random-effects model.
DATA SYNTHESIS
The final search yielded 35 studies enrolling 2629 patients. Studies were noncomparative series with a follow-up range of 6-360 months. Compared with medical therapy, surgery was associated with a higher remission rate (67% vs 45%; P = .02). Surgery had higher remission rates at longer follow-up periods (≥ 24 mo) (66% vs 44%; P = .04) but not the shorter follow-up periods (≤ 6 mo) (37% vs 26%; P = .22) [Corrected].Surgery had higher remission rates in the follow-up levels of GH (65% vs 46%; P = .05). In one study, the IGF-1 level was reduced more with surgery compared with medical treatment (-731 μg/L vs -251 μg/L; P = .04). Studies in which surgery was performed by a single operator reported a higher remission rate than those with multiple operators (71% vs 47%; P = .002).
CONCLUSIONS
Surgery may be associated with higher remission rate; however, the confidence in such evidence is very low due to the noncomparative nature of the studies, high heterogeneity, and imprecision.
Topics: Acromegaly; Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Remission Induction; Treatment Outcome; Young Adult
PubMed: 25356809
DOI: 10.1210/jc.2014-2900 -
Frontiers in Endocrinology 2016PubMed, Scopus, and Web of Science Core Collection databases were systematically searched for studies reporting synchronous double or multiple pituitary adenomas (MPA),... (Review)
Review
PubMed, Scopus, and Web of Science Core Collection databases were systematically searched for studies reporting synchronous double or multiple pituitary adenomas (MPA), a rare clinical condition, with a vague pathogenesis. Multiple adenomas of the pituitary gland are referred to as morphologically and/or immunocytochemically distinct tumors that are frequently small-sized and hormonally non-functional, to account for the low detection rate. There is no general agreement on how to classify MPA, various criteria, such as tumor contiguity, immunoreactivity, and clonality analysis are being used. Among the component tumors, prolactin (PRL)-immunopositive adenomas are highly prevalent, albeit mute in the majority of cases. The most frequent clinical presentation of MPA is Cushing's syndrome, given the fact that in more than 50% of reported cases at least one lesion stains for adrenocorticotrophic hormone (ACTH). Plurihormonal hyperactivity may be diagnosed in a patient with MPA when more than one tumor is clinically active (e.g., ACTH and PRL) or in cases with at least one composite tumor (e.g., GH and PRL), to complicate the clinical scenario. Specific challenges associated with MPA include high surgical failure rates, enforcing second-look surgery in certain cases, and difficult preoperative neuroradiological imaging evaluation, with an overall sensitivity of only 25% for magnetic resonance imaging to detect distinct multiple tumors. Alternatively, minor pituitary imaging abnormalities may raise suspicion, as these are not uncommon. Postoperative immunohistochemistry is mandatory and in conjunction to electron microscopy scanning and testing for transcription factors (i.e., Pit-1, T-pit, and SF-1) accurately define and classify the distinct cytodifferentiation of MPA.
PubMed: 26869991
DOI: 10.3389/fendo.2016.00001 -
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 -
Best Practice & Research. Clinical... Dec 2023Preserving bone health is an important goal of care of patients with acromegaly and growth hormone deficiency (GHD). Both disorders are associated with compromised bone... (Review)
Review
Preserving bone health is an important goal of care of patients with acromegaly and growth hormone deficiency (GHD). Both disorders are associated with compromised bone health and an increased risk of fracture. However, parameters of bone health that are routinely used to predict fractures in other populations, such as aBMD measured by DXA, are unreliable for this in acromegaly and GHD. Additional methodologies need to be employed to assess bone health in these patients. This review summarizes available data on the effects of acromegaly and GHD on parameters of bone health such as aBMD, volumetric bone mineral density (vBMD) and microarchitecture assessed by HRpQCT and other techniques, trabecular bone score (TBS) and fracture assessment. More research is needed to identify reliable predictors of fracture risk and to determine how best to screen for and treat those patients at risk so that bone health is optimized in these patients.
Topics: Adult; Humans; Bone Density; Absorptiometry, Photon; Acromegaly; Bone and Bones; Fractures, Bone; Hypopituitarism; Growth Hormone
PubMed: 37798201
DOI: 10.1016/j.beem.2023.101824 -
Pituitary Feb 2017Purpose Treatment of acromegaly has undergone important progress in the last 20 years mainly due to the development of new medical options and advances in surgical... (Review)
Review
Purpose Treatment of acromegaly has undergone important progress in the last 20 years mainly due to the development of new medical options and advances in surgical techniques. Pituitary surgery is usually first-line therapy, and medical treatment is indicated for persistent disease, while radiation (RT) is often used as third-line therapy. The benefits of RT (tumor volume control and decreased hormonal secretion) are hampered by the long latency of the effect and the high risk of adverse effects. Stereotactic RT methods have been developed with the aim to provide more precise targeting of the tumor with better control of the radiation dose received by the adjacent brain structures. The purpose of this review is to present the updates in the efficacy and safety of pituitary RT in acromegalic patients, with an emphasis on the new stereotactic radiation techniques. Methods A systematic review was performed using PubMed and articles/abstracts and reviews detailing RT in acromegaly from 2000 to 2016 were included. Results Stereotactic radiosurgery and fractionated stereotactic RT (FSRT) for patients with persistent active acromegaly after surgery and/or during medical therapy provide comparable high rates of tumor control, i.e. stable or decrease in size of the tumor in 93-100% of patients at 5-10 years and endocrinological remission in 40-60% of patients at 5 years. Hypofractionated RT is an optimal option for tumors located near the optic structures, due to its lower toxicity for the optic nerves compared to single-dose radiosurgery. The rate of new hypopituitarism varies from 10 to 50% at 5 years and increases with the duration of follow-up. The risk for other radiation-induced complications is usually low (0-5% for new visual deficits, cranial nerves damage or brain radionecrosis and 0-1% for secondary brain tumors) and risk of stroke may be higher in FSRT. Conclusion Although the use of radiotherapy in patients with acromegaly has decreased with advances in medical treatments, it remains an effective treatment option after unsuccessful surgery and/or resistance or unavailability of medical therapy. Long-term studies evaluating secondary morbidity and mortality rate after the new stereotactic techniques are needed, in order to evaluate their potential brain-sparing effect.
Topics: Acromegaly; Female; Humans; Hypopituitarism; Male; Pituitary Neoplasms; Radiosurgery; Treatment Outcome
PubMed: 28210908
DOI: 10.1007/s11102-016-0783-5 -
Pituitary Feb 2023This systematic literature review investigated whether extended dosing intervals (EDIs) of pharmacological acromegaly treatments reduce patient burden and costs compared...
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.
Topics: Adult; Humans; Acromegaly; Octreotide; Insulin-Like Growth Factor I; Cabergoline; Cross-Sectional Studies; Quality of Life; Peptides, Cyclic; Human Growth Hormone
PubMed: 36447058
DOI: 10.1007/s11102-022-01285-1 -
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 -
Advances in Therapy Feb 2021Somatostatin analogs (SSAs) are used to treat neuroendocrine tumors (NETs) and acromegaly. Two first-generation SSAs, octreotide long-acting release (OCT LAR) and... (Review)
Review
Patient and Healthcare Provider Perspectives of First-Generation Somatostatin Analogs in the Management of Neuroendocrine Tumors and Acromegaly: A Systematic Literature Review.
INTRODUCTION
Somatostatin analogs (SSAs) are used to treat neuroendocrine tumors (NETs) and acromegaly. Two first-generation SSAs, octreotide long-acting release (OCT LAR) and lanreotide autogel/depot (LAN), are available. A systematic literature review (SLR) was conducted to investigate which characteristics beyond efficacy are most important in patient and healthcare practitioner (HCP) experience of LAN and OCT when used to treat acromegaly and NETs.
METHODS
MEDLINE, Embase, the Cochrane Library, and Database of Abstracts of Reviews of Effect were searched from database inception to January 2019 with terms for first-generation SSAs, NETs, acromegaly, preferences, decision-making, and human factors. Key congresses in 2016-2018 and SLR bibliographies were hand-searched. Two independent reviewers screened articles at title/abstract and full-text stage. Publications fulfilling pre-specified inclusion criteria reported patient or HCP perspectives of LAN or OCT, or any factors affecting treatment perspectives for NETs or acromegaly.
RESULTS
A total of 1110 unique records were screened, of which 21 studies were included, reporting from the perspectives of patients (n = 18) and/or HCPs (n = 9). Perspectives were collected using shared decision-making frameworks, questionnaires, informal patient opinion, and a Delphi panel. Where patient preference was specifically reported, LAN was preferred in 4/5 studies and OCT LAR in 1/5. Common factors underlying treatment experience included technical problems with injections and associated pain, emotional quality/anxiety of injections, time and convenience of treatment administration, and independence. Immediate aspects of injections appeared most important to patients, though the possibilities of extended dosing intervals and self-/partner-injection with LAN were also notable factors.
CONCLUSIONS
Study outcomes favored LAN in this SLR, with factors surrounding injection administration most influential in treatment experience. The findings of this SLR provide a basis that could inform development of decision-making criteria, with patient and HCP treatment perspectives considered. Future studies should utilize a common method to report preference and associated drivers.
Topics: Acromegaly; Health Personnel; Humans; Neuroendocrine Tumors; Octreotide; Somatostatin
PubMed: 33432541
DOI: 10.1007/s12325-020-01600-x -
The Journal of Clinical Endocrinology... Jan 2021Whereas biochemical response is often used as a primary study outcome, improvement in symptoms and health-related quality of life (HRQoL) is the relevant goal for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Whereas biochemical response is often used as a primary study outcome, improvement in symptoms and health-related quality of life (HRQoL) is the relevant goal for patients to consider treatment successful. We performed a systematic review and meta-analysis to assess the effect of treatment on symptoms and HRQoL in acromegaly.
METHODS
Seven electronic databases were searched for longitudinal studies assessing patient-reported symptoms or HRQoL in acromegaly. Meta-analyses were performed to assess differences during treatment for the Acromegaly Quality of Life Questionnaire (AcroQoL) and Patient-Assessed Acromegaly Symptom Questionnaire (PASQ), and standardized mean difference (SMD) for individual symptoms (interpretation: 0.2 small, 0.5 moderate, and 0.8 large effect). Treatment-naive and previously treated patients were assessed separately.
RESULTS
Forty-six studies with 3301 patients were included; 24 contributed to quantitative analyses. Thirty-six studies used medication as main treatment, 1 transsphenoidal adenomectomy, and 9 various treatments. Symptoms and HRQoL both improved: AcroQoL increased 2.9 points (95% CI, 0.5 to 5.3 points), PASQ decreased -2.3 points (95% CI, -1.3 to -3.3 points), and individual symptom scores decreased for paresthesia -0.9 (95% CI, -0.6 to -1.2), hyperhidrosis -0.4 (95% CI, -0.1 to -0.6), fatigue -0.3 (95% CI, -0.1 to -0.6), arthralgia -0.3 (95% CI, -0.1 to -0.5), headache -0.3 (95% CI, 0.0 to -0.6), and soft-tissue swelling -0.2 (95% CI, 0.0 to -0.4).
CONCLUSION
Symptoms and HRQoL improved during acromegaly treatment. Consensus is needed on which symptoms should be included in a potential core outcome set, taking into account symptom frequency, severity, and sensitivity to change, which can be used in clinical practice and as outcome in trials.
Topics: Acromegaly; Health Status; Humans; Prognosis; Quality of Life
PubMed: 33245343
DOI: 10.1210/clinem/dgaa868 -
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