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To date, no data are available on the effects of long-term combined treatment with somatostatin analogues (SA) and pegvisomant (PEG) on cardiovascular complications in acromegaly. The current study aimed at investigating the effects of long-term SA + PEG on cardiac structure and performance. Thirty-six patients (14 M, 22 F, aged 52.3 ± 10.2 years) entered this study. Weight, BMI, systolic (SBP) and diastolic (DBP) blood pressure, IGF-I, fasting glucose (FG), fasting insulin (FI), HOMA-IR, HbA 1c , and lipids were evaluated at baseline (T0), after long-term (median 36 months) SA (T1), after 12 (T12) and 60 (T60) months of SA + PEG, and at last follow-up (LFU, median 78 months). At each time point, all patients underwent echocardiography. At T1, induced a slight but not significant decrease in IGF-I (p = 0.077), whereas FI (p = 0.004), HOMA-IR (p = 0.013), ejection fraction (EF, p = 0.013), early (E) to late (A) ventricular filling velocities (E/A, p = 0.001), and isovolumetric relaxation time (IVRT, p = 0.000) significantly improved. At T12, IGF-I (p = 0.000) significantly reduced compared to T0, and FI (p = 0.001), HOMA-IR (p = 0.000), LVMI (p = 0.000), and E/A (p = 0.006) further improved compared to T1. At T60, FI (p = 0.027), HOMA-IR (p = 0.049), and E/A (p = 0.005) significantly improved as compared to T1. At LFU IGF-I normalized in 83.3 %, FI (p = 0.000), HOMA-IR (p = 0.000), LVMi (p = 0.000), and E/A (p = 0.005) further improved as compared to T1. PEG dose significantly correlated with LVMi at T12 (r = 0.575, p = 0.000) and T60 (r = 0.403, p = 0.037). Long-term PEG addition to SA improves cardiac structure and performance, particularly diastolic dysfunction, in acromegalic patients resistant to SA.

Introduction: In patients with acromegaly, somatostatin analogs (SSA) represent the first choice medical treatment. The long-acting SSA have been found to be effective in controlling growth hormone and IGF-I levels in a high percentage of patients, resulting in an improvement in the quality of life; moreover, these peptide analogs have a proven safety record and are generally well tolerated., Areas Covered: The most commonly reported adverse events include injection-site discomfort and erythema, gastrointestinal (GI) disturbances such as diarrhea, abdominal pain, nausea and vomiting, biliary sludge or gallstones, and abnormal glucose metabolism. Most SSA-related adverse events are transient and of mild-to-moderate intensity, and the prevalence of such effects markedly and progressively decreases during treatment, so that treatment discontinuations due to adverse events are rare and commonly related to GI disturbances. Cholelithiasis represents the most serious complication of SSA, but is generally asymptomatic, and has been reported in 3 - 56% of patients. Whereas the effect of SSA on glucose metabolism is still controversial, several pieces of evidence have confirmed a modest and transient negative impact on glucose homeostasis. Also the novel SSA pasireotide has shown a safety profile as expected for a SSA, except for the degree of hyperglycemia., Expert Opinion: On the basis of these findings, a close and careful monitoring of gallbladder ultrasound and glucose levels is recommended in patients receiving SSA for medical treatment of acromegaly.

Introduction: The treatment of acromegaly aims at normalizing growth hormone (GH) and insulin-like growth factor (IGF-I) levels and controlling tumor growth. The approaches to therapy are essentially three: surgery and pharmacotherapy, alone or in combination, and radiotherapy, generally used in more aggressive tumors., Areas Covered: This review focuses on the novel drug formulations being developed for medical therapy of acromegaly. Even though many efficient treatments have been made available to manage acromegaly in the last two decades, a significant number of patients remain still uncontrolled. Medical therapy represents an important therapeutic option and can be used as the first-line treatment in many patients. However, roughly 25% of patients might be considered as poor responsive or resistant to conventional long-acting somatostatin analogs (SSA) treatment. Therefore, new longer-acting SSA, oral SSA formulations, new combined therapies with weekly doses of pegvisomant, combination therapy with pegvisomant (PEG) and cabergoline (CAB) or SSA and new approaches have been proposed. New molecules are currently under investigation in clinical trials, such as the SSA multi-receptor ligand, pasireotide, which represents a promising option therapy, especially in patients not adequately controlled with currently available SSA. Further, temozolomide has been suggested as an efficient drug for treating GH-aggressive pituitary tumors resistant to conventional therapy., Expert Opinion: All these novel SSA formulations and new molecules implement the available options in therapies of acromegaly to improve disease control. However, further studies are needed to define the exact role of these newer agents. The predicting factors for response to these new therapies should also be determined.

Purpose of Review: To discuss the role of medical therapy of acromegaly as a first-line treatment, focusing on recent data on the use of somatostatin analogs (SSAs), the first-choice pharmacotherapy for treating acromegaly., Recent Findings: Despite pituitary surgery and radiotherapy, a significant number of patients with acromegaly needed adjuvant medical therapy, and primary medical therapy nowadays is increasingly considered. According to a recent consensus statement on the management of acromegaly, primary pharmacological therapy with SSAs may be indicated in patients who are otherwise poor surgical candidates or refuse surgery, and in those in whom there is a low probability of a surgical cure. The long-acting SSAs have been found to be effective in improving symptoms and signs of acromegaly in a high percentage of patients and induce normalization of growth hormone and insulin-like growth factor-I levels approximately in 60-80% of patients, respectively. Evidence has suggested that SSAs induce a clinically significant tumor shrinkage when given as first-line, when this reduction of tumor volume could be helpful in improving the outcome of subsequent surgery or improving the clinical syndrome in patients with unacceptable surgical risk, whereas the tumor shrinkage was seen less frequently when the drug was used after surgical resection and/or radiotherapy., Summary: Pharmacological management plays a pivotal role in the treatment of acromegaly, and first-line medical therapy with SSAs is being widely used in clinical practice, either prior to surgery or in patients who are otherwise poor surgical candidates and in those in whom there is a low probability of a surgical cure.

Background: Somatostatin analogs (SA) are the cornerstone in the medical treatment of acromegaly, used as either primary or adjunctive therapy. In particular, SA are effective in inducing the biochemical remission of the disease and tumor shrinkage, although only few cases of complete disappearance of the pituitary tumor in patients treated with SA as long-acting formulations have been reported. SA withdrawal has been demonstrated to keep safe levels of GH and IGF1 at least in a small subset of patients well responsive to SA, although it is generally followed by disease recurrence after several months., Case Report: A 61-year-old female patient bearing a very large GH-secreting pituitary macroadenoma was treated with 12-month lanreotide Autogel (ATG), at the initial dose of 120 mg/28 days. After 3 months, GH and IGF1 levels were fully normalized, to prolong the administration interval from 28 to 56 days. After 6 months of treatment, a significant tumor shrinkage (90% of baseline size) was observed, whereas GH and IGF1 excess was still well controlled. After 12-month therapy, a complete disappearance of the pituitary tumor was observed, and the hormonal evaluation confirmed the complete biochemical remission of acromegaly. Lanreotide ATG treatment was withdrawn. The clinical, biochemical, and radiological remission of acromegaly was maintained 24 months after lanreotide ATG treatment discontinuation, without evidence of disease recurrence., Conclusions: This report represents an exemplary case of the potentiality of treatment with lanreotide ATG in inducing a complete remission of acromegalic disease, persistent after a long period of time from treatment withdrawal.

Objective: The objective of the study was to investigate the impact of first-line somatostatin analogs (SSAs) on glucose tolerance (GT) in acromegaly., Design: The design was open and prospective., Patients: One hundred twelve patients [63 with normal GT (56.2%), 24 with impaired GT (21.4%), and 25 with diabetes (22.3%)] were treated with depot SSAs for 12 months: 54 patients (48.2%) achieved mean fasting GH levels less than 2.5 microg/liter in presence of normal IGF-I levels (controlled) during SSA., Primary Outcome Measures: Fasting glucose and glycosylated hemoglobin levels were measured., Results: At study end, 57 patients had normal GT (50.1% vs. baseline; P = 0.55), 30 had impaired fasting glucose or impaired GT (26.8%, P =0.43) and 25 had diabetes (22.3%; P = 1.0). Twenty-eight patients (25.0%), modified their GT [11 improved (9.8%), 17 worsened (15.2%)]: 90% of the patients with GT improvement achieved control of acromegaly and 89% of those having GT worsening did not (P < 0.0001). The major predictors of GT changing were disease control (t = -4.99; P < 0.0001), baseline GT (t = -2.84; P = 0.0054), and GH levels (t = 2.70; P = 0.008). Fasting glucose levels were predicted by patients' age (t = 2.74; P = 0.0071) and IGF-I levels (t = 2.14; P = 0.035). Glycosylated hemoglobin levels were predicted by disease duration (t = 3.53; P = 0.0006), GH levels (t = 2.70; P = 0.0071), and IGF-I levels (t = 2.11; P = 0.037)., Conclusions: This study showed a similar prevalence of deterioration and improvement of GT 12 months after first-line SSA treatment. Uncontrolled acromegaly during SSA treatment and abnormal GT at baseline were associated with GT worsening.

The efficacy of dopamine-agonists (DA) in patients with prolactinomas and that of somatostatin analogues (SSA) in those with GH- and TSH-secreting adenomas is well established. More recently, data are accumulating suggesting a potential therapeutic role of DA also in patients with ACTH-secreting and clinically non-functioning (NFA) pituitary adenomas. This review aims at summarizing published results of DA and SSA on tumor shrinkage in patients with different histotypes of pituitary adenomas. Results of tumor shrinkage are of clinical relevance as tumor size is the one of the most important determinant of surgical outcome. While reduction of tumor size more than 50% of baseline size in macroprolactinomas treated with DA is a frequent finding in patients with GH-secreting adenomas treated with SSA tumor shrinkage only recently is becoming frequent thanks to the availability of depot formulations. Data on tumor shrinkage in patients with TSH-secreting adenomas treated with SSA are limited because of the rarity of these tumors. Very recently, DA have been reported of some efficacy also in patients with ACTH-secreting adenomas but data are still very limited. NFA respond very scantly to both DA and SSA even if receptors targeting these drugs are present. Whether this is due to limited receptor number or alterations of post-receptor pathway is still unknown.

Objective: The aim of the study was to investigate the 5-yr impact of surgery and somatostatin analogs (SSA) on glucose metabolism in acromegaly., Design: We conducted an observational, prospective, comparative, nonrandomized study., Patients: The 100 patients (48 women, 52 men; median age, 49 yr) in the study were grouped as follows for treatment: SSA only (group A; n = 34); SSA followed by surgery (group B; n = 20); surgery only (group C; n = 30); and surgery followed by SSA (group D; n = 16)., Results: At diagnosis, 28% had impaired glucose tolerance, and 22% had diabetes mellitus; fasting glucose levels (4.13-10.60 mmol/liter) were best predicted by age (t = 2.88; P = 0.0049) and disease duration (t = 1.99; P = 0.049). After 60 months, fasting glucose levels reduced (-4.9 +/- 19.7%) in group A only, whereas they did not change in the other groups. In the 68 nondiabetic patients at baseline, fasting glucose levels increased by 0.7 +/- 11.2%, 7.5 +/- 10.3%, 4.3 +/- 10.4%, and 4.3 +/- 14.8% (P = 0.28), from groups A to D, respectively. Percentage change of fasting glucose in all patients receiving SSA was 1.9 +/- 12.3%, and in those not receiving SSA it was 6.4 +/- 10.8% (P = 0.13). Overall, prevalence of new onset of diabetes during SSA treatment was nine of 55 (16.4%) vs. three of 23 after surgery (13.0%, P = 0.98). Deterioration of glucose tolerance was correlated with increased body mass index (r = 0.49, P < 0.0001) and not with use of SSA or surgery (r = 0.06; P = 0.53), control or not of GH (r = -0.10, P = 0.31) and IGF-I (r = -0.12; P = 0.22)., Conclusions: The results of this study demonstrate a similar deterioration of glucose tolerance after 60 months in patients receiving SSA or cured with surgery. Increase in body mass index was the major predictor of deterioration of glucose tolerance.

Introduction: Therapies for acromegaly aim at normalizing hormonal excess and controlling tumor growth . Therapeutic approaches are surgery, pharmacotherapy and radiotherapy. Area covered: This review focuses on the role of medical therapy of acromegaly, comparing the efficacy of somatostatin analogues (SSA), dopamine-agonists (DA) and pegvisomant (PEG), the three available drug classes for treating acromegaly. To clarify the difference in response rates reported in the literature for these therapies, we performed a search for original articles published in PubMed. SSA represent the first-line approach to medical treatment. This therapy is effective in controlling acromegaly in about 40% of patients, however there are great differences in the reported hormonal efficacy of SSA in the different series. In patients partially resistant to SSA, cabergoline can be added when hormonal levels are close to normalization, resulting effective in control IGF-I levels in 43% of patients. In patients with higher hormonal levels PEG is indicated, normalizing IGF-I levels in 79.8% and 80.6% of cases when used in monotherapy or in combination with SSA. Pasireotide, the newly developed SSA multi-ligand receptor, represents a new option in SSA resistant patients. Expert commentary: Medical therapy represents an important therapeutic option resulting safe and effective in controlling acromegaly in a high percentage of patients. The best treatment should be individually tailored for each patient, taking into account sex, age, comorbidities, tumor characteristics and hormonal levels. [ABSTRACT FROM AUTHOR]