Lipodystrophy in patients with acromegaly receiving pegvisomant

Context: Pegvisomant, a GH receptor antagonist, suppresses serum IGF-I levels into the normal range in more than 95% of patients with acromegaly. Documented side effects in the initial registration studies included headache, injection-site reactions, flu-like syndrome, and reversible elevation of hepatic enzymes. Objective: We report seven patients with acromegaly treated with pegvisomant who developed lipodystrophy at the site of injection (anterior abdominal wall, thigh, buttock, and upper arm). This side effect resulted in discontinuation of pegvisomant in four patients, with subsequent regression of lipohypertrophy. Subjects: Six female and one male patient with acromegaly, aged 24-59 yr, are reported. All patients had undergone prior transsphenoidal surgery, and four received subsequent radiotherapy. Four patients had been treated with maximal doses of somatostatin analogs with partial suppression of IGF-I levels before initiation of pegvisomant therapy. Pegvisomant suppressed IGF-I levels into the normal range in five of seven subjects, before discontinuation of the drug. Two of seven patients received pegvisomant as first-line medical therapy, without prior somatostatin analog treatment, and one received combination therapy with a long-acting somatostatin analog and weekly pegvisomant injections. One patient experienced an erythematous superficial injection-site reaction that responded to application of steroid cream before the onset of lipohypertrophy. Conclusions: We report seven patients with acromegaly who developed lipohypertrophy at the pegvisomant injection site. Pegvisomant was discontinued due to dissatisfaction with lipohypertrophy by four patients. Lipohypertrophy regressed in all patients when the medication was discontinued. Lipohypertrophy recurred when two patients were rechallenged with pegvisomant. Patients receiving pegvisomant should undergo frequent examination of injection sites for lipohypertrophy.     

Long-term experience of pegvisomant therapy as a treatment for acromegaly

Aims  To evaluate the long-term efficacy and safety of pegvisomant as a treatment for acromegaly.
Design  Retrospective analysis of clinical and trial data from all patients treated with pegvisomant since 1997 at two centres with common protocols.
Results  Fifty-seven patients (age range 27–78 years) have been treated with pegvisomant since 1997 for up to 91 months (median 18 months). Before commencing pegvisomant, patients had an IGF-I above the upper limit of normal (ULN) of the age-related reference range (median 1·8 × ULN, range 1·2–4·1). Ninety-five per cent normalized IGF-I using a median dose of 15 mg daily (range 10 mg alternate day to 60 mg daily) with no influence of gender on dose requirement. Five patients had combination therapy with either somatostatin analogues (SSA) or cabergoline. Two patients initially controlled on 10 mg and 20 mg required dose increases (to 20 mg + 40 mg) over 24 months to reduce IGF-I. Twenty-seven patients stopped pegvisomant. Reasons included side-effects [abnormal liver function tests (LFTs)] and patient choice. Two patients developed elevated liver transaminases, which normalized on stopping pegvisomant. Patients had 6–12-monthly pituitary magnetic resonance imaging (MRI) scans. One patient had significant tumour size increase.
Conclusion  This long-term experience in 57 patients indicates pegvisomant to be effective, safe and well-tolerated. Raised transaminases occurred within the first month of therapy in two patients, and tumour growth was seen in one patient (tumour was growing prior to pegvisomant). In two patients increasing doses of pegvisomant were required to keep IGF-I within the target range.     

Pituitary tumor enlargement in two patients with acromegaly during pegvisomant therapy

BACKGROUND: Several classes of pharmacological agents are approved for the medical therapy of acromegaly, including dopamine agonists, somatostatin analogs and a growth hormone receptor antagonist. Pegvisomant, a growth hormone receptor antagonist, suppresses IGF-1 levels into the normal range in over ninety percent of patients. However, increased tumor volume was reported in patients receiving pegvisomant who had not received prior radiotherapy. OBJECTIVES: To describe two patients with acromegaly who developed significant tumor enlargement on pegvisomant and discuss the potential mechanisms involved. INTERVENTION: Both patients received long-acting somatostatin analog (octreotide) therapy subsequent to incomplete transsphenoidal tumor resection. Octreotide did not normalize GH/IGF-1 levels in either patient but did control tumor mass size. Pegvisomant therapy was initiated after discontinuing octreotide. RESULTS: Both patients exhibited suppression of IGF-1 into the normal range during pegvisomant therapy. However, significant tumor enlargement occurred in both. Potential mechanisms for tumor enlargement include the natural tendency of the tumor to grow with time, discontinuation of tumor suppressive effects of the somatostatin analog, or a direct effect of pegvisomant. The presumed mechanism of tumor enlargement is by loss of the inhibitory effect on tumor growth when IGF-1 levels are reduced. This could also explain the increase in circulating GH levels in patients with acromegaly receiving pegvisomant; patient 1 demonstrated an 18-fold increase in circulating GH levels while receiving the drug. CONCLUSIONS: The mechanisms of tumor enlargement in patients with acromegaly on pegvisomant are likely multifactorial. Patients, especially those who have not received prior radiotherapy, should be closely monitored for tumor enlargement.     

Conversion of daily pegvisomant to weekly pegvisomant combined with long-acting somatostatin analogs,in controlled acromegaly patients

The efficacy of combined treatment in active acromegaly with both long-acting somatostatin analogs (SRIF) and pegvisomant (PEG-V) has been well established. The aim was to describe the PEG-V dose reductions after the conversion from daily PEG-V to combination treatment. To clarify the individual beneficial and adverse effects, in two acromegaly patients, who only normalized their insulin like growth factor (IGF-I) levels with high-dose pegvisomant therapy. We present two cases of a 31 and 44 years old male with gigantism and acromegaly that were controlled subsequently by surgery, radiotherapy, SRIF analogs and daily PEG-V treatment. They were converted to combined treatment of monthly SSA and (twice) weekly PEG-V. High dose SSA treatment was added while the PEG-V dose was decreased during carful monitoring of the IGF-I. After switching from PEG-V monotherapy to SRIF analogs plus pegvisomant combination therapy IGF-I remained normal. However, the necessary PEG-V dose, to normalize IGF-I differed significantly between these two patients. One patient needed twice weekly 100 mg, the second needed 60 mg once weekly on top of their monthly lanreotide Autosolution injections of 120 mg. The weekly dose reduction was 80 and 150 mg. After the introducing of lanreotide, fasting glucose and glycosylated haemoglobin concentrations increased. Diabetic medication had to be introduced or increased. No changes in liver tests or in pituitary adenoma size were observed. In these two patients, PEG-V in combination with long-acting SRIF analogs was as effective as PEG-V monotherapy in normalizing IGF-I levels, although significant dose-reductions in PEG-V could be achieved. However, there seems to be a wide variation in the reduction of PEG-V dose, which can be obtained after conversion to combined treatment.     

Treatment of acromegaly with pegvisomant during pregnancy: maternal and fetal effects

OBJECTIVE: Our objective was to describe the first case of the successful use of pegvisomant during pregnancy in a woman with acromegaly. DESIGN: We present the case of a 26-yr-old female with acromegaly who had failed surgical and subsequent medical therapy but whose disease was well controlled on pegvisomant. She then conceived and was continued on pegvisomant throughout pregnancy. We then collected both maternal and cord blood samples at parturition, and later analyzed her breast milk. RESULTS: Maternal IGF-I was well controlled during gestation. Fetal GH and IGF-I were within the normal range. Maternal pegvisomant levels were consistent with a 25-mg daily dosage. Fetal pegvisomant levels were minimal and near the range detected in untreated acromegalic patients, likely representing minimal cross-reactivity from endogenous GH or spurious contamination by maternal blood. GH variant levels in the maternal blood and the cord blood were both within the normal ranges. Pegvisomant levels in breast milk were below the lower limit of quantification of the assay and similar to those observed when analyzing breast milk samples from normal mothers in the same assay. Fetal growth parameters were normal; the baby was healthy and showed no adverse signs. CONCLUSIONS: Pegvisomant therapy during gestation was safe and effective in our patient. Transplacental passage of pegvisomant is either absent or minimal, with a concentration highly unlikely to convey any significant pharmacodynamic effects on the fetal GH and IGF-I system. In addition, there is no evidence of substantial secretion of pegvisomant into breast milk.     

Growth hormone receptor polymorphism and the effects of pegvisomant in acromegaly

Background    Sensitivity to pegvisomant therapy is highly variable in patients with acromegaly but determinants of this variability are still unknown. Lack of exon 3 (d3-) of the growth hormone (GH) receptor (GHR) has been associated with increased biological activity of GH. Objective    To assess whether the presence of d3-GHR haplotype may have a role in predicting dose regimen and response to pegvisomant in acromegaly. Design    Case series. Setting    Institutional referral center at a tertiary care hospital. Patients    Ninenteen acromegalic patients with active disease after unsuccessful neurosurgery and somatostatin analog therapy. Measurements    before and 1, 3, 6 and 12 months after treatment with pegvisomant, IGF-I; GH receptor genotype, determined from peripheral blood by polymerase chain reaction. All patients started treatment with pegvisomant at 10 mg/daily and then increased the dose, according to a fixed schedule, during a 12-month follow-up until normalization of IGF-I levels. Results    d3-GHR patients required a significant lower dose of pegvisomant and shorter treatment time to normalize IGF-I. Conclusion    the GHR genotype could be useful in predicting dose and individual response to pegvisomant in acromegaly.     

Treatment adherence to pegvisomant in patients with acromegaly in Spain: PEGASO study

Pituitary - The burden of chronic daily subcutaneous administration of pegvisomant on adherence has not been previously studied. This study was aimed to determine the adherence to pegvisomant...     

Long-term effects of the combination of pegvisomant with somatostatin analogs (SSA) on glucose homeostasis in non-diabetic patients with active acromegaly partially resistant to SSA

Several recent studies have reported beneficial effects of pegvisomant monotherapy on glucose homeostasis for acromegalic patients resistant to somatostatin analogs (SSA). The aim of our longitudinal study was to test whether these beneficial effects on glucose homeostasis would also occur during combined pegvisomant + SSA treatment amongst partially SSA-resistant acromegalic patients. Ten non-diabetic, partially SSA-resistant acromegalic patients underwent a 12-month SSA+pegvisomant treatment after SSA-only therapy. Glucose homeostasis was evaluated at disease diagnosis, at the end of the SSA treatment and after 6 and 12 months of combined SSA+pegvisomant treatment. The addition of pegvisomant treatment was accompanied by a significant improvement in insulin and glycemic responses to the oral glucose tolerance test, without any significant changes in fasting plasma glucose, glycosylated haemoglobin, homeostatic model assessment-derived insulin resistance index and homeostatic model assessment-derived β-cell function. Moreover, the number of patients with glucose intolerance did not significantly change during the 12-month combined treatment, notwithstanding the significant decrease in serum IGF-1 values. Therefore, our findings suggest that the combined pegvisomant and SSA treatment may not be able to restore normal clinical and biochemical glycometabolic features occurring in acromegalic patients resistant to SSA, while a slight but significant improvement in some biochemical features may be expected.     

Long-term efficacy and safety of combined treatment of somatostatin analogs and pegvisomant in acromegaly

BACKGROUND: We previously reported the efficacy of a combined treatment of active acromegaly with both long-acting somatostatin analogs (SSA) and pegvisomant (PEG-V). OBJECTIVE: Our objective was to assess long-term efficacy and safety in a larger group of acromegalic patients after a period of 138 (35-149) wk [median (range)]. DESIGN: PEG-V was added to high-dose SSA treatment in 32 subjects (13 females) who had not shown a normalization in serum IGF-I concentrations during SSA monotherapy. PEG-V dosage was increased until IGF-I concentration normalized. The maximal dose was 80 mg twice weekly. RESULTS: After dose finding, IGF-I remained within the normal range in all subjects with PEG-V administered once (n = 24) or twice (n = 8) weekly, on a total weekly dose of 60 (40-160) mg. Baseline IGF-I levels were positively correlated with the required dosage of PEG-V (r = 0.48; P = 0.006). PEG-V-dependent liver enzyme disturbances were observed in 11 (6 diabetic) subjects, of which symptomatic gallstones explained two cases. These liver enzyme disturbances were transient in all subjects without discontinuation or dose adaptation of PEG-V. In our series, diabetic patients had a 5.1 times (odds ratio) (confidence interval, 1.02-25.54; P < 0.05) higher risk for developing liver enzyme disturbances. These liver enzyme disturbances seemed to occur earlier. Pituitary adenoma size decreased in four patients. No increase in tumor size was observed in any of the patients. CONCLUSION: Long-term combined treatment with long-acting SSA and (twice) weekly PEG-V for active acromegaly seems to be effective and safe. Patients with acromegaly and diabetes seem to have a higher risk of developing transient liver enzyme disturbances.     

Glucose homeostasis and safety in patients with acromegaly converted from long-acting octreotide to pegvisomant

CONTEXT: In clinical practice, patients with acromegaly may be switched from therapy with long-acting somatostatin analogs to pegvisomant. The effect of changing therapies on glucose homeostasis and safety has not been reported. OBJECTIVES: The objectives of this study were to monitor changes in IGF-I levels, glycemic control, and safety, particularly liver function and tumor size. DESIGN: This was a multicenter, open-label, 32-wk trial study. SETTING: The study was performed at outpatient clinics. PATIENTS: Fifty-three patients with acromegaly previously treated with octreotide long-acting release (LAR) participated in this study. Intervention: Pegvisomant (10 mg/d) was initiated 4 wk after the last dose of octreotide LAR and was adjusted based on serum IGF-I concentrations at wk 12, 20, and 28. MAIN OUTCOME MEASURES: The main outcome measures were changes in IGF-I, glycosylated hemoglobin A1c (HbA1c), fasting plasma glucose, and safety during the first 12 wk after conversion. RESULTS: At the end of pegvisomant treatment, IGF-I was normalized in 78% of patients. At wk 32, median fasting glucose concentration and HbA1c were reduced (-1.4 mmol/liter and -0.4%, respectively; both P < or = 0.0001) in the study population. Improvements in glycemic control occurred in patients with normal IGF-I concentrations at wk 4 [n = 15; fasting glucose, -1.7 mmol/liter (P < or = 0.0001); HbA1c -0.2% (P = 0.03)]. Decreases in fasting glucose and HbA1c levels were observed in patients with and without diabetes. HbA1c was reduced by more than 1.0% in patients with diabetes. Median pituitary tumor volume did not change, although tumor volume increased in two patients with macroadenomas. CONCLUSIONS: Conversion from octreotide LAR to pegvisomant was safe and well tolerated. Improved glycemic control indicates that pegvisomant should be considered in patients with acromegaly and diabetes.     

McCune-Albright syndrome and acromegaly: effects of hypothalamopituitary radiotherapy and/or pegvisomant in somatostatin analog-resistant patients

BACKGROUND: Acromegaly, which may be present in patients with McCune-Albright syndrome (MCAS), in association with café-au-lait spots, precocious puberty, and fibrous dysplasia, is often difficult to treat surgically because skull base bone dysplasia prevents the removal of the pituitary adenoma. Somatostatin analogs (SAs) generally give only partial responses. The use of radiotherapy (RT) is controversial because of a possible risk of bone sarcomatous transformation. AIM: This study was a retrospective analysis of the efficacy and adverse effects of different treatment modalities in six patients with both MCAS and acromegaly. PATIENTS AND METHODS: Because surgery was impossible and SA failed to normalize GH/IGF-I hypersecretion, five of the six patients received fractionated RT (45-55 Grays). Three patients (two with previous RT) were also prescribed pegvisomant. We analyzed the clinical features of acromegaly, GH, and IGF-I concentrations and bone radiological features. RESULTS: GH and IGF-I concentrations fell after RT (median follow-up, 5 yr; range, 0.5-9 yr). Symptoms of acromegaly improved in parallel. Bone sarcomatous transformation was only noted in one patient in a region (the mandible) outside the radiation field. RT alone and/or combined with SA failed to normalize GH/IGF-I levels in the five patients concerned. In contrast, IGF-I levels normalized very rapidly (5-9 months) in the three patients receiving pegvisomant (10-20 mg/d). CONCLUSION: RT may be an option for the treatment of acromegaly in patients with MCAS when surgery is impossible and SA therapy is ineffective. However, although no bone sarcomatous transformation was observed within the radiation field in this series, this risk cannot be ruled out. As shown in this small series of severely affected patients, pegvisomant therapy may thus be useful to normalize IGF-I levels rapidly.     

A randomized, controlled, multicentre trial comparing pegvisomant alone with combination therapy of pegvisomant and long-acting octreotide in patients with acromegaly

Objective For patients with acromegaly who are suboptimally controlled on long‐acting octreotide (LAR), treatment options are to switch to pegvisomant monotherapy (PM) or add pegvisomant to LAR (P‐LAR). Our objective was to evaluate if the safety and efficacy of these regimens differ. Design This was an open‐label, multicentre, randomized, 40‐week outpatient study. The control arm consisted of patients controlled on LAR (n = 28). Patients A total of 27 patients with suboptimally controlled acromegaly [as indicated by a serum IGF‐I level ≥ 1·3 × upper limit of normal (ULN) of the age‐related reference range] were randomized to PM (10 mg once daily initially, then adjusted in 5‐mg increments every 8 weeks based on IGF‐I levels) and 29 to P‐LAR (LAR dosing remained fixed). Measurements The primary end‐point was adverse events (AEs). The secondary end‐point was biochemical IGF‐I‐based efficacy. The RIA for IGF‐I was discontinued by the manufacturer during the study and a chemiluminescent assay was subsequently used. Previously obtained IGF‐I levels were re‐analysed. Results PM and P‐LAR were well tolerated and there were no differences in the number of AEs. Patients receiving P‐LAR tended to be more likely to have clinically significant increases in hepatic transaminase levels, especially those receiving high‐dose LAR. Normalization of IGF‐I was similar with both regimens (56% and 62% of patients for PM and P‐LAR respectively). The change in IGF‐I assay resulted in lower rates of IGF‐I normalization than expected. Reductions in fasting glucose levels were greater with PM than with P‐LAR (−0·8 mmol/l; 95% confidence interval −1·16, −0·53 mmol/l). Conclusions In patients suboptimally controlled on LAR, PM and P‐LAR were equally well tolerated and effective in normalizing IGF‐I, and overall clinical improvement was observed with both regimens. Thus, pegvisomant monotherapy and adjunctive therapy are equally viable options for the treatment of LAR‐resistant acromegaly.     

The impact of pegvisomant treatment on substrate metabolism and insulin sensitivity in patients with acromegaly

CONTEXT: Pegvisomant is a specific GH receptor antagonist that is able to normalize serum IGF-I concentrations in most patients with acromegaly. The impact of pegvisomant on insulin sensitivity and substrate metabolism is less well described. PATIENTS AND METHODS: We assessed basal and insulin-stimulated (euglycemic clamp) substrate metabolism in seven patients with active acromegaly before and after 4-wk pegvisomant treatment (15 mg/d) in an open design. RESULTS: After pegvisomant, IGF-I decreased, whereas GH increased (IGF-I, 621 +/- 82 vs. 247 +/- 33 microg/liter, P = 0.02; GH, 5.3 +/- 1.5 vs. 10.8 +/- 3.3 microg/liter, P = 0.02). Basal serum insulin and plasma glucose levels decreased after treatment (insulin, 54 +/- 5.9 vs. 42 +/- 5.3 pmol/liter, P = 0.001; glucose, 5.7 +/- 0.1 vs. 5.3 +/- 0.0 mmol/liter, not significant), whereas palmitate kinetics were unaltered. During the clamp, the glucose infusion rate increased after pegvisomant (3.1 +/- 0.5 vs. 4.4 +/- 0.6 mg/kg.min, P = 0.02), whereas the suppression of endogenous glucose production tended to increase (0.7 +/- 0.0 vs. 0.5 +/- 0.1 mg/kg.min, not significant). Total resting energy expenditure decreased after pegvisomant treatment (1703 +/- 109 vs. 1563 +/- 101 kcal/24 h, P = 0.03), but the rate of lipid oxidation did not change significantly. CONCLUSIONS: 1) Pegvisomant treatment for 4 wk improves peripheral and hepatic insulin sensitivity in acromegaly. 2) This is associated with a decrease in resting energy expenditure, whereas free fatty acid metabolism is unaltered. 3) The data support the important direct effects of GH on glucose metabolism and add additional benefits to pegvisomant treatment for acromegaly.     

Alternate-day administration of pegvisomant maintains normal serum insulin-like growth factor-I levels in patients with acromegaly

IGF-I levels normalize in the majority of patients with acromegaly treated with the GH receptor antagonist pegvisomant. To date, the efficacy of pegvisomant has been demonstrated with daily administration of doses ranging from 10 to 40 mg. However, given the known long half-life of the drug in circulation, we hypothesized that dosing less frequently than daily would still maintain the drug's efficacy. We studied 10 patients with active acromegaly treated with pegvisomant. This therapy was begun at 10 mg daily but then titrated up in dose or down to alternate-day dosing to try to maintain serum IGF-I levels in the upper half of the patients' age-adjusted normal range. We found that in five of 10 patients, serum IGF-I levels remained normal on less frequent than daily pegvisomant. Signs and symptoms of the disease and a disease-related morbidity, insulin resistance, remained improved in these patients. We demonstrate for the first time the continued efficacy of alternate-day administration of pegvisomant.     

Insulin sensitivity and glucose tolerance improve in patients with acromegaly converted from depot octreotide to pegvisomant

AIM AND METHOD: Insulin resistance leading, in some cases, to glucose intolerance is an important contributory factor to the cardiovascular morbidity and mortality associated with acromegaly. The aim of this study was to document changes in insulin sensitivity (IS) in a group of seven patients with acromegaly (three male, four female, mean+/-s.d. age 59+/-13 Years) treated initially with a stable dose of depot octreotide (OT; median dose 30 mg four times weekly, range 10-30 mg) for a median of 18 Months (range 16-19 Months) and who were then transferred to treatment with pegvisomant (median dose 15 mg daily, range 10-20 mg) for a median of 8 Months (range 7-9 Months). IS was assessed by homeostatic model assessment (HOMA) using fasting glucose and insulin concentrations and by a short insulin tolerance test (sITT). Body composition was assessed by dual energy X-ray absorptiometry. RESULTS: Mean+/-s.d. serum IGF-I concentrations during therapy with OT and with pegvisomant were not statistically different (283+/-119 ng/ml on OT vs 191+/-39 ng/ml on pegvisomant (P=0.4)). However, mean+/-s.d. fasting plasma glucose fell from 6.2+/-1.0 mmol/l on OT to 5.2+/-0.6 mmol/l on pegvisomant (P=0.017) and was lower on pegvisomant in all seven patients. In four patients, fasting plasma glucose fell from values diagnostic of diabetes mellitus or impaired fasting glucose on OT to within the normal range on pegvisomant. Mean+/-s.d. peripheral IS (by sITT) increased from 139+/-39 micromol/l per min on OT to 169+/-59 micromol/l per min on pegvisomant (P=0.037). Mean+/-s.d. IS (by HOMA %S) was unchanged over the course of the study (149.1+/-43.7% on OT vs 139.9+/-76.6% on pegvisomant, P=0.28). Mean+/-s.d. pancreatic beta-cell secretory function (HOMA %B) improved significantly on pegvisomant compared with OT (49.4+/-19.2% vs 82.4+/-43.5%, P=0.01). No statistically significant change in total fat (P=0.3), % fat (P=0.28) or circulating non-esterified fatty acids (P=0.35) was observed. CONCLUSIONS: IS and glucose tolerance improved in patients converted from OT therapy to pegvisomant, without a change in body composition and even when serum IGF-I concentrations remained equally well controlled. This may be an important factor in the choice of medical therapy for patients with acromegaly.     

Effects of pegvisomant and somatostatin receptor ligands on incidence of vertebral fractures in patients with acromegaly

Purpose

Acromegalic osteopathy is an emerging complication of acromegaly characterized by increase in bone turnover, deterioration in bone microarchitecture and high risk of vertebral fractures (VFs). Somatostatin receptor ligands (SRLs) and pegvisomant (PegV) are used for treatment of acromegaly and there is evidence that both drugs may exert direct effects on peripheral targets regardless of biochemical control of disease. However, whether or not SRLs and PegV may directly influence skeletal health its is unknown.

Methods

In this longitudinal study, we evaluated the incidence of radiological VFs in 83 patients (48 females, 35 males; median age 47 years, range 18–80 years) who were treated with SRLs alone (42 cases), PegV alone (6 cases) or in combination with SRLs (35 cases) for median period of 82 months (range 36–126). PegV was given when acromegaly was not controlled by SRLs alone.

Results

During the follow-up, 29 patients (34.9%) developed incident VFs. In patients receiving PegV due to active disease during SRL therapy, incidence of VFs decreased significantly from 43.9 to 26.8% (p?=?0.039). When acromegaly was controlled by PegV, the incidence of VFs was slightly but not significantly lower as compared to that observed in patients with biochemical control of disease by SRLs (10.0 vs. 26.7%; p?=?0.09). In the multivariate logistic regression analysis, incident VFs were independently predicted by pre-existing VFs (odds ratio 61.0; p?=?0.009), duration of active acromegaly (odds ratio 1.01; p?=?0.05) and mean serum IGF-I during the follow-up (odds ratio 5.26; p?=?0.03), regardless of the therapeutic regimen (odds ratio 1.05; p?=?0.94).

Conclusions

PegV and SRLs had comparable effects on VF risk in acromegaly. The activity of disease was the main determinant of VFs independently of the drug used to control acromegaly.