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Surgical treatment of acromegaly according to the 2010 remission criteria: systematic review and meta-analysis

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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.
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CLINICAL ARTICLE - BRAIN TUMORS
Surgical treatment of acromegaly according to the 2010 remission
criteria: systematic review and meta-analysis
Daniele Starnoni
1
&Roy Thomas Daniel
1
&Laura Marino
2
&Nelly Pitteloud
2
&
Marc Levivier
1
&Mahmoud Messerer
1
Received: 27 April 2016 /Accepted: 19 July 2016 /Published online: 2 September 2016
#Springer-Verlag Wien 2016
Abstract
Background In 2010, the Acromegaly Consensus Group re-
vised 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 inci-
dence and management has not been established. The objec-
tive 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 sub-
groups of patients.
Methods Systematic review and meta-analysis of surgical se-
ries 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 68.187.6 %) of
microadenomas; 52.7 % (95 % CI 4164.4 %) of
macroadenomas; 29 % (95 % CI 20.137.8 %) of invasive
and 68.8 % (95 % CI 6077.6 %) of non-invasive adenomas.
Complication rates were 1.2 % (95 % CI 0.61.9 %) for
CSF leak, 1.3 % (95 % CI 0.62.1 %) for permanent diabetes
insipidus, 8.7 % (95 % CI 4.812.5 %) for new anterior pitu-
itary dysfunction and 0.6 % (95 % CI 0.11.1 %) 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
(13.258.8 % 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 requiredto determine the long-term biochemical remission
rates and clinical implications.
Keywords Acromegaly .Growth hormone-secreting pituitary
adenoma .Transsphenoidal surgery .Remission
Introduction
Acromegaly is a rare condition with an underestimated inci-
dence per year of five cases per million and, if uncontrolled, the
disease leads to an almost 2- to 4-fold higher mortality [26].
The necessity of treatment is imperative and the normali-
zation of the biochemical parameters alleviates the symptoms
and reduces the mortality and morbidity rates to those of the
general population. According to the most recent 2014 guide-
lines on acromegaly management, surgery represents the first-
line treatment option with medical and radiation therapy as
second and third lines of treatment, respectively [20].
Criteria of biochemical remission are in constant evolution;
in 1999, the first consensus conference in Cortina defined cure
criteria as insulin-like growth factor-I (GF-I) level in age- and
*Mahmoud Messerer
mahmoud.messerer@chuv.ch
1
Service de Neurochirurgie, Centre Hospitalier Universitaire Vaudois
(CHUV) and University of Lausanne (Unil), Rue du Bugnon 46,
1011 Lausanne, Switzerland
2
Service dEndocrinologie, Centre Hospitalier Universitaire Vaudois
(CHUV) and University of Lausanne (Unil), Lausanne, Switzerland
Acta Neurochir (2016) 158:21092121
DOI 10.1007/s00701-016-2903-4
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
... At the beginning of the observation, only 2.0 (1.7%) of the patients met the definition of biochemical control, even though most had already received some intervention, which is well below the control levels, regardless of the type of treatment [16]. If only the surgical intervention is evaluated at the beginning of the registry, 73 (62%) of the patients underwent previous surgery, and of these, only three (4.1%) had biochemical control, a situation that is lower than that reported in the literature, where biochemical control especially of IGF-1 is observed in 54.8% of the patients [17]. ...
... At six months, almost half of the surgeries corresponded to first interventions, while at 12 months, approximately a quarter were. Biochemical control, after the first surgery, was reported in 12 (77%) of patients with microadenomas and 50 (57%) of patients with macroadenomas [17]. In those patients who undergo a new surgical intervention, biochemical control is expected in 67 (57%) of cases [18]. ...
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Acromegaly, although rare, is associated with multiple manifestations and complications; its high morbidity and mortality makes it a challenge. Treatment involves surgery and pharmacological therapies, focusing on biochemical normalization. This study analyzes the biochemical control in Colombian patients with acromegaly, seeking to improve the understanding of the effects of treatments in the management of the disease. Methods: A multicenter retrospective cohort study was conducted with data from a national acromegaly registry in Colombia (2017-2023), analyzing the biochemical control for 12 months according to the treatment modalities received. Results: A total of 117 patients were analyzed, with 54 individuals from Valle del Cauca and 63 being women, representing different population groups in Colombia. The median age was 52 years, and the median disease duration was six years. Clinically, arterial hypertension and sleep apnea were observed in 53.8% (n = 63) and 45.3% (n = 53) of the cohort, respectively. Biomarker analysis revealed elevated levels of insulin-like growth factor-1 (IGF-1) and growth hormone (GH). The majority of tumors were macroadenomas, and among the 103 surgically removed tumors, all secreted GH. Of these, 58.3% (n = 60) had GH as the sole marker, while 12.6% (n = 13) co-expressed prolactin (PRL). At first, 92.3% (n = 108) of patients had no biochemical control. At six and 12 months, 34.1% (n = 40) and 21.2% (n = 25) achieved biochemical control, respectively. The reduction in tumor size was significant during follow-up, with a median size at the month of admission of 16 mm, with a reduction >20% at month 12 in 92.3% (n = 108) of patients. Conclusion: In Colombian patients with acromegaly, biochemical control at 12 months is lower than that reported in the literature, suggesting that pharmacological management could be associated with greater biochemical control.
... Surgery is the main treatment for most functional pituitary adenoma with oncologic control in 60-90% of cases depending on published series [8]. Invasion of the CS is one of the limiting factors for total resection for PitNet tumors with cure rates less than 30% [8]. ...
... Surgery is the main treatment for most functional pituitary adenoma with oncologic control in 60-90% of cases depending on published series [8]. Invasion of the CS is one of the limiting factors for total resection for PitNet tumors with cure rates less than 30% [8]. Extended approaches may be considered in selective and well-studied cases of secreting adenomas and only in tertiary centers. ...
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... In our series, remission at one year was achieved by 11 out of 20 patients, representing 55% of the study population-a percentage fully comparable to that reported in the literature. Starnoni et al. [26], in fact, in their meta-analysis published in 2016 (evaluating 1,105 acromegalic patients), reported a cure rate of approximately 55% (95% CI 44.4-65.2%). Although invasion of the dura mater did not prove to be a significant predictor of recovery during the postoperative period, we highlighted interesting differences between patients who achieved remission and those with persistent disease. ...
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... Transsphenoidal surgery is the first-line treatment for GH PitNETs, with the primary goals of reducing growth hormone levels to less than 1 µg/L, normalizing insulin-like growth factor 1 levels to the age-adjusted range, reducing tumor size and alleviating acromegaly symptoms [26]. Remission is achieved in approximately 78% of patients with microadenomas and 53% 10 of those with macroadenomas [58]. For patients who do not achieve remission, options include repeat surgery, pharmacological therapy, or radiotherapy [26,59]. ...
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... A recent systematic review shows that tumor size and invasiveness are the two main criteria for nonremission of acromegaly due to incomplete resection in more than 70 percent of cases. But this is due more to the difculties of the surgical technique itself than to the intrinsic characteristics of the tumor [46]. Bianchi et al. recently presented a helpful fow chart for the management of difcult/aggressive GH-secreting PitNETs [47]. ...
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Introduction: Acromegaly is a rare endocrine disorder usually caused by a benign growth hormone‒secreting pituitary adenoma. Surgical adenoma resection is typically the first line of treatment, and medical therapy is used for patients with persistent disease following surgery, for adenoma recurrence, or for patients ineligible for, or declining, surgery. Approved somatostatin receptor ligands (SRLs) have been limited to injectable options, until recently. Oral octreotide capsules (OOC) are the first approved oral SRL for patients with acromegaly. Areas covered: We review published reports and provide case study examples demonstrating practical considerations on the use of OOC. Using two hypothetical case scenarios, we discuss current treatment patterns, breakthrough symptoms and quality of life (QoL), efficacy of SRLs, OOC dose titration, evaluation of OOC treatment response, and incidence and management of adverse events. Expert opinion: OOC are an option for patients with acromegaly including those who experience breakthrough symptoms, who have preference for oral therapies, or other reasons for declining injectable SRLs. OOC have been associated with improved patient-reported QoL measures compared with those reported for lanreotide and octreotide. Continued real-world experience will determine whether OOC, alone or in combination with other therapies, provides further advantages over current injectable acromegaly treatments.
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Objective: The aim was to formulate clinical practice guidelines for acromegaly. Participants: The Task Force included a chair selected by the Endocrine Society Clinical Guidelines Subcommittee (CGS), five experts in the field, and a methodologist. The authors received no corporate funding or remuneration. This guideline is cosponsored by the European Society of Endocrinology. Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. The Task Force reviewed primary evidence and commissioned two additional systematic reviews. Consensus process: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society and the European Society of Endocrinology reviewed drafts of the guidelines. Conclusions: Using an evidence-based approach, this acromegaly guideline addresses important clinical issues regarding the evaluation and management of acromegaly, including the appropriate biochemical assessment, a therapeutic algorithm, including use of medical monotherapy or combination therapy, and management during pregnancy.
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Introduction: Surgical remission rates for acromegaly depend on tumor morphology, definition of disease remission, and surgical expertise. A previous report from Manchester in 1998 reported an overall surgical remission rate of 27%. We assessed the impact of establishing a specialist pituitary surgery service in Manchester in 2005, with reduced surgeon numbers and use of the 2010 consensus criteria for remission in acromegaly. Methods: Patients with acromegaly undergoing endoscopic transsphenoidal surgery by a single surgeon between 2005 and 2010 were studied. Review of the acromegaly database was performed with documentation of pre- and postoperative biochemical tests (oral glucose tolerance test [OGTT] and IGF-1). Definition of disease remission was according to the 2010 consensus criteria (GH nadir < 0.4 mg/L following an OGTT and normalized population matched IGF-1). Results: There were 43 consecutive acromegaly patients, with 13 (30%) microadenomas and 12 (28%) invasive adenomas. Surgical remission was achieved in 29 (67%) patients. The remission rates were similar between micro (77%), macro (63%), and giant (67%) adenomas. There were nonsignificant trends toward higher remission rates for noninvasive tumors compared with invasive tumors (74% vs. 50%) and for patients with a preoperative GH nadir less than 10üg/L (73% vs. 54%) and IGF-1 SD score less than 15 (72% vs. 54%). Conclusions: Remission rates for acromegaly surgery have improved following establishment of a specialist surgical service, with a reduction in surgeon numbers. Endoscopic transsphenoidal surgery remains an effective first-line treatment for achieving biochemical remission in acromegaly, despite the introduction of the more stringent 2010 consensus guidelines.
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Purpose: The Acromegaly Consensus Group recently released updated guidelines for medical management of acromegaly patients. We subjected these guidelines to a cost analysis. Methods: We conducted a cost analysis of the recommendations based on published efficacy rates as well as publicly available cost data. The results were compared to findings from a previously reported comparative effectiveness analysis of acromegaly treatments. Using decision tree software, two models were created based on the Acromegaly Consensus Group's recommendations and the comparative effectiveness analysis. The decision tree for the Consensus Group's recommendations was subjected to multi-way tornado analysis to identify variables that most impacted the value analysis of the decision tree. Results: The value analysis confirmed the Consensus Group's recommendations of somatostatin analogs as first line therapy for medical management. Our model also demonstrated significant value in using dopamine agonist agents as upfront therapy as well. Sensitivity analysis identified the cost of somatostatin analogs and growth hormone receptor antagonists as having the most significant impact on the cost effectiveness of medical therapies. Conclusion: Our analysis confirmed the value of surgery as first-line therapy for patients with surgically accessible lesions. Surgery provides the greatest value for management of patients with acromegaly. However, in accordance with the Acromegaly Consensus Group's recent recommendations, somatostatin analogs provide the greatest value and should be used as first-line therapy for patients who cannot be managed surgically. At present, the substantial cost is the most significant negative factor in the value of medical therapies for acromegaly.
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Background To describe outcomes and complications in patients undergoing transsphenoidal surgery for acromegaly using the 2010 consensus criteria for biochemical remission. Methods Retrospective review of 113 treatment naïve patients who underwent transsphenoidal surgery with the endoscopic (n = 66) and the endonasal microscopic technique (n = 47). Cure was defined if the age and sex-adjusted IGF-1 level was normal and either the basal GH was <1 ng/ml or the nadir GH was <0.4 ng/ml following oral glucose suppression at last follow-up. Results The mean age at presentation was 38.1 ± 7.1 years and 86% of tumors were macroadenomas. Adenoma sizes averaged 21.1 ± 9.7 mm, but 56% of all tumors were ≥2 cm in size and 43.4% were invasive. Remission rates between endoscopic and microscopic transsphenoidal surgery did not differ significantly overall (28.8% versus 36.2%). On univariate analysis, a preoperative GH level <40 ng/ml, adenoma size <20 mm and non-invasiveness were predictors of remission at follow-up. Although there were no statistically significant differences in remission rates between the endoscopic and microsurgical groups, surgically induced hypopituitarism was less frequent with the former. Conclusions We report our surgical experience with predominantly large, invasive GH adenomas using the 2010 criteria for cure. Patients with smaller, non-invasive tumors with lower preoperative GH levels are most likely to achieve remission. Outcomes with either the microscopic or endoscopic approach do not differ significantly, although the rate of surgically induced hypopituitarism may be higher with the former. Transsphenoidal surgery remains the first line of treatment for patients with acromegaly, but invasive adenomas will frequently require adjuvant therapy.