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 Ϯ 82 vs. 247 Ϯ 33 g/liter, P ϭ 0.02; GH, 5.3 Ϯ 1.5 vs. 10.8 Ϯ 3.3 g/liter, P ϭ 0.02). Basal serum insulin and plasma glucose levels decreased after treatment (insulin, 54 Ϯ 5.9 vs. 42 Ϯ 5.3 pmol/ liter, P ϭ 0.001; glucose, 5.7 Ϯ 0.1 vs. 5.3 Ϯ 0.0 mmol/liter, not significant), whereas palmitate kinetics were unaltered. During the clamp, the glucose infusion rate increased after pegvisomant (3.1 Ϯ 0.5 vs. 4.4 Ϯ 0.6 mg/kg⅐min, P ϭ 0.02), whereas the suppression of endogenous glucose production tended to increase (0.7 Ϯ 0.0 vs. 0.5 Ϯ 0.1 mg/kg⅐min, not significant). Total resting energy expenditure decreased after pegvisomant treatment (1703 Ϯ 109 vs. 1563 Ϯ 101 kcal/24 h, P ϭ 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. A CTIVE ACROMEGALY IS a hypermetabolic condition characterized by elevated resting energy expenditure (REE), increased lipolysis, and hepatic as well as peripheral insulin resistance with respect to glucose metabolism (1). An increased prevalence of impaired glucose tolerance and overt diabetes mellitus is also well documented (2). It is assumed, albeit not formally demonstrated, that these abnormalities contribute to the observed increase in cardiovascular morbidity and mortality (2). In indirect support of this, successful surgery, which has been shown to normalize the mortality rate, is also associated with a correction of the metabolic aberrations (1). However, surgery is not always an option, and approximately 50% of operated patients are not adequately controlled by this treatment (3). Therefore, medical therapy with somatostatin analogs is justified in many cases and has proven effective regarding control of GH hypersecretion and symptom relief in 60% of patients. The impact of somatostatin analogs on glucose homeostasis in acromegaly is unpredictable (4, 5), which may be explained by the concomitant inhibition of insulin secretion.Pegvisomant is a newly developed GH receptor (GHR) antagonist, which competes with native GH for the GHR and prevents its functional dimerization and thereby also GH signal transduction (6). When administered in high doses, pegvisomant is able to ...

The aim of this study was to evaluate the effect of photodynamic therapy with topical methylaminolevulinate for the treatment of basal cell carcinomas in a single dermatological department. Ninety patients (34.4% men and 65.6% women) with a total of 157 basal cell carcinomas (111 superficial, 40 nodular, 6 unknown) were treated. Primary endpoint was clinically observed recurrence verified by biopsy 3, 6 and 12 months after treatment, then once a year. Estimated patient recurrence rates were 7% at 3 months, 19% at 6 months, 27% at 12 months and 31% at 24 months. Patients aged over 60 years had significantly higher estimated recurrence rates compared with patients aged 60 years or under (at 12 months, 35% vs. 19%, p?=?0.01). Estimated recurrence rates for tumours was 4% at 3 months, 11% at 6 months, 16% at 12 months and 19% at 24 months. There were significantly higher estimated recurrence rates for nodular basal cell carcinomas compared with superficial basal cell carcinomas (at 12 months, 28% vs. 13%, p?=?0.008). In conclusion, photodynamic therapy is only appropriate for treatment of superficial basal cell carcinoma, and, age above 60 years and histology showing nodular basal cell carcinoma are independent risk factors for developing a recurrent basal cell carcinoma.

Background: Active acromegaly is associated with insulin resistance, but it is uncertain whether inflammation in adipose tissue is a contributing factor. Aim: To test if GH/IGF1 promotes inflammation in adipocytes, and if this is relevant for systemic insulin resistance in acromegaly. Furthermore, to investigate the effect of treatment modalities (transsphenoidal surgery (TS), somatostatin analogs (SAs), and pegvisomant (PGV)) on glucose metabolism and inflammatory biomarkers in acromegaly. Methods: The in vitro effects of GH/IGF1 on gene expression of adipokines in human adipocytes were investigated. Body composition, glucose metabolism, and circulating adipokines (adiponectin (AD), high-molecular weight AD (HMWAD), leptin, vascular endothelial growth factor-A (VEGF-A), monocyte chemotactic protein 1 (MCP1), and thioredoxin (TRX)) were measured in 37 patients with active acromegaly before and after treatment. Results: In vitro GH, but not IGF1, increased VEGF and MCP1 in human adipocytes. In all treatment groups, body fat increased and IGF1 decreased to the same extent. Fasting glucose decreased in the TS (PZ0.016) and PGV (PZ0.042) groups, but tended to increase in the SA group (PZ0.078). Insulin and HOMA-IR decreased in both TS and SA groups, while the PGV group showed no changes. Serum VEGF and MCP1 decreased significantly in the TS group only (PZ0.010, PZ0.002), while HMWAD increased with PGV treatment only (PZ0.018). A multivariate analysis model identified the changes in GH and VEGF as predictors of improvement in HOMA-IR after treatment (R

We present a patient who developed pyoderma gangrenosum (PG) twice, initially after a minor trauma and later after reconstructive surgery. This case is presented to address the frequent misdiagnosis and mistreatment of PG by surgeons. It is of great importance that PG is diagnosed and of even great importance that surgery is avoided in order to prevent pathergy. Our case adds to the understanding that the diagnosis is based on the clinical and histopathological findings and by excluding other causes of skin ulcers. When a wound is not healing despite relevant local wound management and systemic treatment if needed, the clinician should always suspect PG. Early diagnosis and treatment is crucial in the management of PG and surgery is contraindicated.