Introduction Treatment of acromegaly resistant to first generation somatostatin analogues (first gen-SSA) is often difficult. We aimed to investigate the role of partial response and resistance to first gen-SSA in the choice of second line treatments and their outcomes. Patients and methods A retrospective and multicenter study was conducted on 100 SSA-resistant acromegaly patients and treated with Pasireotide Lar (Pasi-Lar), Peg-V in monotherapy (m-Peg-V) or in combination with first gen-SSA (c-Peg-V). Results Thirty-three patients (33%) were treated with m-Peg-V, 36 (36%) with c-Peg-V and 31 with Pasi-Lar (31%). According to logistic regression, m-Peg-V was chosen in older patients (p = 0.01) and with not-invasive adenomas (p = 0.009), c-Peg-V therapy in younger patients (p = 0.001), with invasive adenomas (p = 0.02), Pasi-Lar was in invasive adenomas (p = 0.01) and in patients partially responsive to first-gen SSA (p = 0.01). At the last follow-up, 68 patients (68%) reached the acromegaly control: 22 with m-Peg-V (32.4%), 23 with c-Peg-V (33.8%) and 23 with Pasi-Lar (33.8%). Patients non-responsive to c-Peg-V had higher IGF-I levels (median 3.2 x ULN, IQR: 1.6, p < 0.001) and required higher Peg-V dosage (median 30 mg/daily IQR: 10, p = 0.002) as compared to responsive patients (median IGF-I x ULN: 2.1 IQR: 1.4; median Peg-V dosage 20 mg/daily IQR: 10). All patients responsive to Pasi-Lar were partially responsive to first gen-SSAs (p = 0.02). Conclusion Our data showed that c-Peg-V and Pasi-Lar are chosen for the treatment of invasive tumors. The partial response to first gen-SSA seems to be the main determinant for the choice of Pasi-Lar and positively predicts the treatment outcome.
Background Acromegaly is a rare disease due to chronic growth hormone (GH) excess and the consequent increase in insulin-like growth factor-1 (IGF-1) levels. Both GH and IGF-1 play a role in intermediate metabolism affecting glucose homeostasis. The association between hyperinsulinemia/impaired glucose tolerance and an increased risk of cancer has been clarified. Insulin has a mitogenic effect through its interaction with the IGF-1 receptor (IGF-1R) that also binds IGF-1. On the other hand, metformin, an anti-hyperglycemic drug that decreases serum levels of insulin and IGF-1, could have a protective role in the treatment of endocrine tumors. Methods A retrospective, observational, multicenter study in 197 acromegalic patients, receiving/not receiving metformin, was performed to assess whether the prevalence of neoplasms might be correlated with insulin resistance and could eventually be modified by metformin treatment. Results In general, the occurrence of secondary neoplasia among our patients was significantly (pV = 0.035) associated with a positive family history of malignancy and with disease duration; a trend towards significance was observed in patients aged > 50 years. Acromegalic subjects who had undergone surgery showed a lower probability of developing a malignant tumor, whereas a higher prevalence of malignancies was observed in obese patients. No significant statistical difference was found when comparing metformin-treated or -untreated subjects for the presence of a second tumor. More interestingly, a trend towards statistical significance (pV = 0.065) was demonstrated in the metformin-treated group for the onset of a benign neoplasm. Conclusion Metformin could act directly on tumor cell metabolism and may have an adjuvant role in benign lesion progression.
Purpose: To evaluate the prevalence and clinical performance of obstructive sleep apnoea syndrome (OSAS) in acromegalic patients, focusing on the possible correlation between alterations of pulmonary microcirculation and patient's clinical and hormonal parameters. Methods: We enrolled 22 acromegalic patients with apnea hypopnea index (AHI) ≥ 5 if symptomatic, or ≥15 in the absence of sleep related symptoms. Patients underwent the following evaluations: GH and IGF-1 serum levels, arterial blood gas test, spirometry, carbon monoxide diffusing capacity (DLCO), home-based cardiorespiratory sleep and pulmonary function test. Results: The prevalence of OSAS was 66.6%. Patients with a severe form of OSAS appeared to be affected from acromegaly for more years than those with a lower severity of disease and those with acromegaly duration > 10 years had significantly higher levels of glycated hemoglobin. We observed a positive correlation between GH level at diagnosis and DLCO value, showing that acromegalic patients have an increase in static and dynamic respiratory volumes and alveolar-capillary exchange surface compared to the general population. We also observed a positive correlation between baseline serum IGF-1 level and DLCO/VA and between years of disease and DLCO/VA, showing the association of increased lung volume and increase of the exchange surface. Conclusions: The results of this study add new information on lung volume and alveolar gas exchange in acromegaly. Our findings highlight the role of SSA as therapy with positive impact on complication and comorbidities of acromegaly.
Background: Acromegaly is characterized by an insulin resistance condition. There is a significant difference between the different types of therapy in relation to the glycometabolic framework. The blinded continuous glucose monitoring system (CGMS), throughout a period of maximum 6 days for a total of 288 glycemic registrations per day, identifies glycemic excursions and could constitute a valid device to understand the 24-hour glycemic profiles. Aim of the study: To compare the oral glucose tolerance test (OGTT) and CGMS methods in acromegalic patients to evaluate their glycemic profiles, in relation to different treatments for acromegaly. Methods: Thirty-five acromegalic patients were divided into 18 somatostatin analogs (SSA), 9 pegvisomant, and 8 successfully surgically treated. A 72-hour CGM was performed and, immediately after, an OGTT. Results: Results obtained from OGTT: 11/35 impaired fasting glucose, 6/35 impaired glucose tolerance, and 4/35 diabetes mellitus. A positive significant correlation was demonstrated between the OGTT peak and CGM peak in all of the patients, CGM peak of patients treated with SSA and those surgically treated, OGTT average and CGM area under concentration–time curve (AUC) for hyperglycemia of patients treated with SSA and those surgically treated, and CGM AUC for hyperglycemia of patients treated with SSA and those surgically treated. Conclusions: Our results show a significantly higher response in terms of mean and peak OGTT in patients treated with SSA, both compared to the CGM study, and compared to the group of patients receiving pegvisomant. The CGM system could represent an instrument for the evaluation of the glycemic trend of acromegalic patients.
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