Objective: The GH receptor antagonist pegvisomant is a highly effective new treatment option in acromegaly. The German Pegvisomant Observational Study (GPOS) was started to monitor long-term safety and efficacy of pegvisomant as prescribed in clinical practice. Design: GPOS is an observational, multi-center, surveillance study, which comprises noninterventional data collection. Methods: Of the 229 patients included in the study, 90.4% had previous pituitary surgery, 43.2% were treated by radiation therapy, and 94.3% had previous medical therapy for acromegaly that had been discontinued mainly due to persistent IGF-I elevation or side effects. The intention-to-treat population included 177 patients with at least one post-baseline efficacy measurement. Results: IGF-I levels decreased from 1.75G0.91-fold the upper limit of normal at baseline to 1.05G 0.62 at the 6-month visit, 0.96G0.60 at the 12-month visit, and to 0.89G0.41-fold after 24 months (P!0.0001). Mean duration of pegvisomant therapy was 51.8G35.8 weeks (medianZ51.9 weeks). IGF-I was normalized in 64.4% at 6 months with a median dose of 15.0 mg/day, in 70.9% at 12 months, and in 76.3% at 24 months. Fasting glucose levels improved from 114.4G45.9 to 101.5G 42.8 mg/dl after 6 months (P!0.01) and to 100.6G33.2 mg/ml after 12 months (P!0.01). General physical condition measured by specific signs and symptoms score improved significantly. Adverse events occurring in O1% were injection site reactions in 7.4%, elevated liver enzymes (O3 times of normal) in 5.2% (3.1% spontaneously normalized during continued treatment), reported increase of pituitary tumor volume in 5.2% (which was verified in 3.1%), and headache in 1.7%. Conclusions: Pegvisomant is generally well tolerated with a safety profile similar to that reported in clinical trials and can effectively reduce IGF-I in patients with acromegaly refractory to conventional therapy. 156 75-82 European Journal of Endocrinology

Glucocorticoid pulse therapy is associated with a high recurrence rate. Evidence suggests that surgery is not able to prevent recurrence. Considering the favorable results of observation, conservative management is recommended in PrHy unless symptoms are severe or progressive.

In contrast to the literature, hypogonadism was found to be the most frequent endocrine failure in PrHy. Weight gain was identified as a clinical sign of PrHy. In the majority of patients, PrHy can be reliably identified by characteristic clinical signs and symptoms, obviating histological confirmation. The diagnostic approach should be standardized in PrHy.

Disease control is important to reduce the likelihood for development of coronary heart disease.

Background: Patients with hypothalamic pathology often develop morbid obesity, causing severe metabolic alterations resulting in increased morbidity and mortality. Glucagon-like peptide-1 (GLP-1) analogues improve glycaemic control in type 2 diabetic patients and cause weight loss in obese patients by yet unknown mechanisms. Here we tested whether GLP-1 analogues were also effective in the treatment of obesity and associated metabolic alterations in patients with hypothalamic disease. Methods: Nine patients (eight with type 2 diabetes mellitus) with moderate to severe hypothalamic obesity were treated with GLP-1 analogues for up to 51 months. Body weight, homeostasis model assessment -insulin resistance (HOMA-IR), HbA1c and lipids were assessed. Results: Eight patients experienced substantial weight loss (K13.1G5.1 kg (range K9 to K22)). Insulin resistance (HOMA-IR K3.2G3.5 (range K9.1 to 0.8)) and HbA1c values (K1.3G1.4% (range K4.5 to 0.0)) improved under treatment (24.3G18.9 months (range 6 to 51)). Five patients reported increased satiation in response to the treatment. Two of the eight patients complained about nausea and vomiting and one of them abandoned therapy because of sustained gastrointestinal discomfort after 6 months. One patient suffered from intolerable nausea and vomiting and discontinued treatment within 2 weeks. Conclusion: GLP-1 analogues can cause substantial and sustained weight loss in obese patients with hypothalamic disease. This offers a new approach for medical treatment of moderate to severe hypothalamic obesity and associated metabolic alterations.