On the basis of these preliminary results, treatment of patients who have acromegaly with a growth hormone-receptor antagonist results in a reduction in serum IGF-I concentrations and in clinical improvement.

An understanding of the events that occur during GH receptor (GHR) signaling has facilitated the development of a GHR antagonist (pegvisomant) for use in humans. This molecule has been designed to compete with native GH for the GHR and to prevent its proper or functional dimerization-a process that is critical for GH signal transduction and IGF-I synthesis and secretion. Clinical trials in patients with acromegaly show GHR blockade to be an exciting new mode of therapy for this condition, and pegvisomant may have a therapeutic role in diseases, such as diabetes and malignancy, in which abnormalities of the GH/IGF-I axis have been observed. This review charts the discovery and development of GHR antagonists and details the experience gained in patients with acromegaly.

ObjectivesThis retrospective cohort study developed a prognostic model incorporating PET texture analysis in patients with oesophageal cancer (OC). Internal validation of the model was performed.MethodsConsecutive OC patients (n = 403) were chronologically separated into development (n = 302, September 2010-September 2014, median age = 67.0, males = 227, adenocarcinomas = 237) and validation cohorts (n = 101, September 2014-July 2015, median age = 69.0, males = 78, adenocarcinomas = 79). Texture metrics were obtained using a machine-learning algorithm for automatic PET segmentation. A Cox regression model including age, radiological stage, treatment and 16 texture metrics was developed. Patients were stratified into quartiles according to a prognostic score derived from the model. A p-value < 0.05 was considered statistically significant. Primary outcome was overall survival (OS).ResultsSix variables were significantly and independently associated with OS: age [HR =1.02 (95% CI 1.01-1.04), p < 0.001], radiological stage [1.49 (1.20-1.84), p < 0.001], treatment [0.34 (0.24–0.47), p < 0.001], log(TLG) [5.74 (1.44–22.83), p = 0.013], log(Histogram Energy) [0.27 (0.10–0.74), p = 0.011] and Histogram Kurtosis [1.22 (1.04–1.44), p = 0.017]. The prognostic score demonstrated significant differences in OS between quartiles in both the development (X2 143.14, df 3, p < 0.001) and validation cohorts (X2 20.621, df 3, p < 0.001).ConclusionsThis prognostic model can risk stratify patients and demonstrates the additional benefit of PET texture analysis in OC staging.Key points• PET texture analysis adds prognostic value to oesophageal cancer staging.• Texture metrics are independently and significantly associated with overall survival.• A prognostic model including texture analysis can help risk stratify patients.Electronic supplementary materialThe online version of this article (doi:10.1007/s00330-017-4973-y) contains supplementary material, which is available to authorized users.

Sex, body weight, previous radiotherapy, and baseline GH/IGF-I influence the dose of pegvisomant required to normalize serum IGF-I in patients with active acromegaly.

In patients with acromegaly, there is a linear association between log10 serum GH and IGF-I. Healthy females secrete three times more GH than males but have broadly similar serum IGF-I levels, and in adult GH deficiency, the dose of exogenous GH required to achieve a given serum IGF-I is significantly greater in females than males. We report the influence of gender on the relationship between serum GH and IGF-I in subjects with active acromegaly. A single, fasted, serum sample was obtained from 153 subjects with active disease (87 males; median age, 47.8 yr; range, 20-82 yr) in whom serum IGF-I was at least 30% above the upper limit of an age-related reference range after washout from medical therapy. A linear correlation between serum IGF-I and log10 serum GH was observed (r = 0.53; P < 0.0001), but this relationship was significantly influenced by gender. For a given serum GH value, females were estimated to have serum IGF-I values 82 ng/ml less than males [P < 0.02; 95% confidence interval (CI), 15.2-149]. In females receiving oral E, mean serum IGF-I for a given GH value was 130 ng/ml lower than in males (P = 0.01; 95% CI, 29.8-230.2) but only 60 ng/ml less than the remaining 45 females (NS; P = 0.2). This study demonstrates a gender difference in the relationship between serum GH and IGF-I in patients with active acromegaly consistent with relative GH resistance observed in normal and GHD females, which may, in part, be mediated by E. This observation has important implications for the use of IGF-I as a measure of disease activity.