Acromegaly: Assessing the Disorder and Navigating the Therapeutic Options for Treatment

BACKgROUND: somatostatin analogs (ssA) are now considered standard therapy for acromegaly, as primary or adjunctive treatment after pituitary surgery. OBJeCTIve: To evaluate the efficacy of ssA and the effect of dose escalation in non-operated patients with acromegaly as compared to patients treated after pituitary surgery in a Romanian tertiary care center. DesIgN: Retrospective study of 73 consecutively evaluated patients with acromegaly treated with ssA, divided into 2 groups: 11 patients (4M/7f, 21-62 years) with primary treatment and 62 patients (22M/40f, 21-68 years) treated after surgery. They received Octreotide LAR 20-30 mg i.m./28 days or Lanreotide sR 30 mg i.m./14/10/7 days. Random serum growth hormone (GH) was measured using IRMA, sensitivity 0.2-0.01 μg/L IGF-1 was measured using different assays and compared with ULN for age and sex. RESULTS: Overall, random GH ≤2.5 μg/L was attained in 39 patients (53.4%) and optimal GH ≤1 ng/mL) in 30 patients (41%), while normal IGF-1 was recorded in 22/72 patients (30.5%). The final random GH ≤2.5 μg/L was achieved in 27.2% of non-operated patients (3/11) as compared with 58% (36/62) of patients treated medically after pituitary surgery, p<0.05. escalation of doses of ssA applied in 43 patients improved the number of controlled patients by 5 (12.1%, p=0.059) and the number of optimally controlled patients by 9.7%. Of the 8 patients who switched from Lanreotide to Octreotide, 2 patients achieved gh normalization. CONCLUsION: The rate of biochemical control via ssA treatment in patients with acromegaly could be improved by rise of the ssA dose or by debulking surgery. Occasionally, substituting one ssA for another may be of benefit.

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“…20 The most important factor influencing the treatment outcome is pretreatment GH level, as has been shown in this study and in others. 17 …”

Section: Ssa Efficacy On Gh and Igf-1 Secretionsupporting

confidence: 72%

Beneficial effect of dose escalation and surgical debulking in patients with acromegaly treated with somatostatin analogs in a Romanian tertiary care center

Gheorghiu

Găloiu

Vintila

et al. 2016

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“…21 Side effects, such as gastrointestinal symptoms, cholelithiasis, hyperglycemia, and hepatotoxicity, may limit the benefits of those drugs. 32,45 Radiosurgery has been advocated in selected cases in which a small residual lesion is observed and in those with cavernous sinus invasion. However, disease control may require up to 3-5 years to be achieved, and side effects such as visual deterioration and anterior pituitary hormone deficiency may occur in up to 11% and 47% of cases, respectively.…”

Section: Discussionmentioning

confidence: 99%

Reoperation for growth hormone–secreting pituitary adenomas: report on an endonasal endoscopic series with a systematic review and meta-analysis of the literature

Almeida¹,

Ruiz-Treviño²,

Liang³

et al. 2018

Journal of Neurosurgery

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OBJECTIVE Surgery is generally the first-line therapy for acromegaly. For patients with residual or recurrent tumors, several treatment options exist, including repeat surgery, medical therapy, and radiation. Reoperation for recurrent acromegaly has been associated with poor results, with hormonal control usually achieved in fewer than 50% of cases. Extended endonasal endoscopic approaches (EEAs) may potentially improve the results of reoperation for acromegaly by providing increased visibility and maneuverability in parasellar areas. METHODS A database of all patients treated in the authors' center between July 2004 and February 2016 was reviewed. Cases involving patients with acromegaly secondary to growth hormone (GH)-secreting adenomas who underwent EEA were selected for chart review and divided into 2 groups: first-time surgery and reoperation. Disease control was defined by 2010 guidelines. Clinical and radiological characteristics and outcome data were extracted. A systematic review was done through a MEDLINE database search (2000-2016) to identify studies on the surgical treatment of acromegaly. Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, the included studies were reviewed for surgical approach, tumor size, cavernous sinus invasion, disease control, and complications. Cases were divided into reoperation or first-time surgery for comparative analysis. RESULTS A total of 44 patients from the authors' institution were included in this study. Of these patients, 2 underwent both first-time surgery and reoperation during the study period and were therefore included in both groups. Thus data from 46 surgical cases were analyzed (35 first-time operations and 11 reoperations). The mean length of follow-up was 70 months (range 6-150 months). The mean size of the reoperated tumors was 14.8 ± 10.0 mm (5 micro- and 6 macroadenomas). The patients' mean age at the time of surgery was younger in the reoperation group than in the first-time surgery group (34.3 ± 12.8 years vs 49.1 ± 15.7 years, p = 0.007) and the mean preoperative GH level was also lower (7.7 ± 13.1 μg/L vs 25.6 ± 36.8 μg/L, p = 0.04). There was no statistically significant difference in disease control rates between the reoperation (7 [63.6%] of 11) and first-time surgery (25 [71.4%] of 33) groups (p = 0.71). Univariate analysis showed that older age, smaller tumor size, lower preoperative GH level, lower preoperative IGF-I level, and absence of cavernous sinus invasion were associated with higher chances of disease control in the first-time surgery group, whereas only absence of cavernous sinus invasion was associated with disease control in the reoperation group (p = 0.01). There was 1 case (9%) of transient diabetes insipidus and hypogonadism and 1 (9%) postoperative nasal infection after reoperation. The systematic review retrieved 29 papers with 161 reoperation and 2189 first-time surgery cases. Overall disease control for reoperation was 46.8% (95% CI 20%-74%) versus 56.4% (95% CI 49%-63%) for first...

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“…with significant morbidity due to clinical complications involving cardiovascular, respiratory, and metabolic systems (2,3).…”

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confidence: 99%

Landscape of somatic mutations in sporadic GH-secreting pituitary adenomas

Ronchi¹,

Peverelli

Herterich

et al. 2016

European Journal of Endocrinology

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Context: Alterations in the cAMP signaling pathway are common in hormonally active endocrine tumors. Somatic mutations at GNAS are causative in 30-40% of GH-secreting adenomas. Recently, mutations affecting the USP8 and PRKACA gene have been reported in ACTH-secreting pituitary adenomas and cortisol-secreting adrenocortical adenomas respectively. However, the pathogenesis of many GH-secreting adenomas remains unclear. Aim: Comprehensive genetic characterization of sporadic GH-secreting adenomas and identification of new driver mutations. Design: Screening for somatic mutations was performed in 67 GH-secreting adenomas by targeted sequencing for GNAS, PRKACA, and USP8 mutations (nZ31) and next-generation exome sequencing (nZ36). Results: By targeted sequencing, known activating mutations in GNAS were detected in five cases (16.1%), while no somatic mutations were observed in both PRKACA and USP8. Whole-exome sequencing identified 132 protein-altering somatic mutations in 31/36 tumors with a median of three mutations per sample (range: 1-13). The only recurrent mutations have been observed in GNAS (31.4% of cases). However, seven genes involved in cAMP signaling pathway were affected in 14 of 36 samples and eight samples harbored variants in genes involved in the calcium signaling or metabolism. At the enrichment analysis, several altered genes resulted to be associated with developmental processes. No significant correlation between genetic alterations and the clinical data was observed. Conclusion: This study provides a comprehensive analysis of somatic mutations in a large series of GH-secreting adenomas. No novel recurrent genetic alterations have been observed, but the data suggest that beside cAMP pathway, calcium signaling might be involved in the pathogenesis of these tumors.

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Acromegaly: Assessing the Disorder and Navigating the Therapeutic Options for Treatment

Cited by 21 publications

References 52 publications

Beneficial effect of dose escalation and surgical debulking in patients with acromegaly treated with somatostatin analogs in a Romanian tertiary care center

Beneficial effect of dose escalation and surgical debulking in patients with acromegaly treated with somatostatin analogs in a Romanian tertiary care center

Reoperation for growth hormone–secreting pituitary adenomas: report on an endonasal endoscopic series with a systematic review and meta-analysis of the literature

Landscape of somatic mutations in sporadic GH-secreting pituitary adenomas

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