Experience with pegvisomant treatment in acromegaly in a single Brazilian tertiary reference center: efficacy, safety and predictors of response.

Objective: To describe the safety and efficacy of pegvisomant therapy and the predictors of treatment response in acromegaly patients at a single tertiary reference center in Brazil. Materials and methods: We retrospectively reviewed the clinical, hormonal and radiological data of acromegaly patients treated with pegvisomant in our center. We also evaluated the presence of the d3 isoform of the growth hormone receptor (d3GHR). Results: Twenty-seven patients were included (17 women). Pegvisomant was used in combination with octreotide LAR in 20 patients (74%), in combination with cabergoline in one (4%) and as monotherapy in six (22%). IGF-I normalization was achieved in 23 patients (85%). Mild and transitory elevation of liver enzymes was observed in two patients (7.4%), tumor growth in one (3.4%) and lipodystrophy in two (7.4%). One patient stopped the drug due to headaches. The GHR isoforms were evaluated in 14 patients, and the presence of at least one d3GHR allele was observed in 43% of them, but it was not a predictor of treatment response. Only pre-treatment IGF-I level was a predictor of treatment response. Conclusion: Pegvisomant treatment was highly effective and safe in our series of Brazilian patients. A better chance of disease control can be expected in those with lower pre-pegvisomant IGF-I levels.

Experience with pegvisomant treatment in acromegaly in a single Brazilian tertiary reference center: efficacy, safety and predictors of response

ABSTRACT Objective To describe the safety and efficacy of pegvisomant therapy and the predictors of treatment response in acromegaly patients at a single tertiary reference center in Brazil. Materials and methods We retrospectively reviewed the clinical, hormonal and radiological data of acromegaly patients treated with pegvisomant in our center. We also evaluated the presence of the d3 isoform of the growth hormone receptor (d3GHR). Results Twenty-seven patients were included (17 women). Pegvisomant was used in combination with octreotide LAR in 20 patients (74%), in combination with cabergoline in one (4%) and as monotherapy in six (22%). IGF-I normalization was achieved in 23 patients (85%). Mild and transitory elevation of liver enzymes was observed in two patients (7.4%), tumor growth in one (3.4%) and lipodystrophy in two (7.4%). One patient stopped the drug due to headaches. The GHR isoforms were evaluated in 14 patients, and the presence of at least one d3GHR allele was observed in 43% of them, but it was not a predictor of treatment response. Only pre-treatment IGF-I level was a predictor of treatment response. Conclusion Pegvisomant treatment was highly effective and safe in our series of Brazilian patients. A better chance of disease control can be expected in those with lower pre-pegvisomant IGF-I levels.

Prevalence of obstructive sleep apnea in patients with prolactinoma before and after treatment with dopamine agonists.

OBJECTIVES: Obesity is the main risk factor for the development of obstructive sleep apnea (OSA). Hyperprolactinemia has also been related to obesity. To determine the OSA prevalence in patients with prolactinoma before and after dopamine agonist (DA) and to evaluate the correlation between the apnea-hypopnea index (AHI) and prolactin levels, body mass index (BMI), waist circumference (WC), visceral fat volume (VFV), subcutaneous fat volume, and other metabolic parameters. METHODS: Thirty-five patients with prolactinoma at baseline and twenty-one who completed the 6-month DA treatment were submitted to clinical/laboratorial evaluations, polysomnography and abdominal imaging. RESULTS: Before treatment, the prevalence of obesity/overweight and OSA were, respectively, 68.5 and 34.2 %. We found a positive correlation between AHI and weight (r = 0.57; p < 0.001), BMI (r = 0.56; p < 0.001), WC (r = 0.61; p < 0.001), VFV (r = 0.55; p = 0.002), insulin levels (r = 0.57; p < 0.001), and HOMA-IR index (r = 0.57; p < 0.001); and a negative correlation between AHI and HDL-cholesterol (r = -0.47; p = 0.005). After multivariate analysis, VFV and insulin levels were the most important predictors for AHI (p = 0.001 and p = 0.02, respectively). After DA, the obesity/overweight and OSA prevalence did not change. CONCLUSIONS: The OSA prevalence in patients with prolactinoma is similar to the obese subjects and did not change after treatment. Higher BMI and visceral obesity, but not prolactin levels, seem to be the major factor involved in the occurrence of OSA in these patients.

Giant prolactinomas: the therapeutic approach.

BACKGROUND: Giant prolactinomas are an unusual subset of macroprolactinomas and are more commonly found in men. The goal of this review is to propose a giant prolactinoma definition and discuss the available therapeutic options for biochemical and tumour volume control. METHODS: A comprehensive search of all published studies was performed between April and November 2012 in electronic databases (PubMed and Ovid). RESULTS: A giant prolactinoma should be defined as an adenoma with a maximum diameter of more than 4 cm that is associated with serum prolactin above 5300 mIU/l. Regarding treatment, cabergoline is the preferred dopamine agonist for medical management of giant prolactinomas because of its excellent efficacy and tolerability. Normalization of prolactin level and significant tumour reduction may be achieved in the majority of patients. Combined therapy, particularly cabergoline and surgery, may be necessary due to the large tumour load. Radiotherapy and temozolomide may be used for patients with aggressive giant prolactinomas in whom tumour volume control is not achieved with cabergoline and surgery. CONCLUSION: There is a scarcity of large studies about the management of giant prolactinoma. Cabergoline is the first-line treatment. However, caution should be exercised when comparing efficacy rates among the different treatment modalities due to the variability in study design and data quality. In this scenario, a 'standard' definition for giant prolactinomas and larger series may be helpful to assess the real efficacy and safety of each therapeutic modality.