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Manfredi Rizzo, Roman Trepp, Kaspar Berneis, and Emanuel R Christ

Objective: Patients with growth hormone deficiency (GHD) have increased cardiovascular risk and may show elevated triglyceride and reduced high density lipoprotein (HDL) cholesterol concentrations, two lipid abnormalities usually accompanied by increased small dense LDL in the ‘atherogenic lipoprotein phenotype’ (ALP). In the present study, we directly investigated () whether hypopituitary patients with GHD have increased small dense LDL; () whether growth hormone replacement therapy (GHRT) beneficially impact on such particles; () the prevalence of ALP in GHD and GHRT patients.

Design and methods: In 14 hypopituitary patients with GHD (44 ± 13 years, body mass index (BMI) 27 ± 3) before and after 4 months of GHRT, and in 11 healthy age- and BMI-matched controls we measured plasma lipids and LDL size and subclasses by gradient gel electrophoresis.

Results: Compared with controls, GHD showed increased triglycerides (P = 0.0024), similar total and LDL cholesterol levels and a tendency towards reduced HDL cholesterol concentrations (P = 0.0894). GHRT reduced total and LDL cholesterol levels (P = 0.0303 and 0.0120 respectively), but no effect was found on triglycerides and HDL cholesterol levels. LDL size was unchanged in GHD versus controls (269 ± 9 vs 274 ± 6 Å, P = ns), but LDL subclass analysis revealed a shift towards more dense particles (P = 0.0046). GHRT had no significant impact on LDL size and subclasses. The prevalence of ALP was 14% in GHD and 7% in GHRT.

Conclusions: In GHD patients, individual features of ALP (including increased small dense LDL) may be common, but complete ALP is relatively uncommon. Short-term replacement therapy seems to be ineffective on such lipid alterations, but the effect of a longer GHRT remains to be assessed.

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Manfredi Rizzo, Roman Trepp, Kaspar Berneis, and Emanuel R Christ

The authors and journal apologize for an error in the above paper which appeared in 361-367. The acknowledgements should appear as below.

Acknowledgements

The study was funded by grant from the Swiss National Foundation to Emanuel R. Christ (No. #32000B0-100146). Kaspar Berneis was supported by a grant from Swiss National Foundation (3200BO-105258). The authors gratefully acknowledge the excellent technical assistance of S. Vosmeer.

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Thomas Zueger, Sabin Alleman, Emanuel R Christ, and Christoph Stettler

Objective

The role of exercise testing in the assessment of GH deficiency (GHD) in adult patients is currently unclear. This study aimed at evaluating the diagnostic value of exercise-induced GH levels in the detection of severe GHD in adult patients.

Methods

Fourteen patients confirmed to have severe GHD according to current guidelines and 20 healthy control individuals (CI) exercised for 120 min at 50–60% of their individual VO2max. GH was measured before and every 30 min throughout exercise. The diagnostic value of predicting GHD was assessed by performing receiver operating characteristics (ROC) analysis for each time point of GH assessment. To optimise comparability within the study population a sub-analysis with ten individuals specifically matched for gender, age, body mass index and waist was performed.

Results

Exercise-induced GH secretion was significantly lower in patients with GHD than in CI (P<0.001). Area under the ROC curve (AUCROC) was 0.954±0.033, 0.993±0.009, 0.989±0.012 and 0.992±0.009 for the overall population and 0.870±0.086, 0.980±0.024, 0.970±0.034 and 0.978±0.027 for the matched individuals at 30, 60, 90 and 120 min of exercise respectively. At 60 min of exercise a cut off GH value of 2.4 ng/ml translates into a sensitivity of 100% and a specificity of 95 and 90% in the diagnosis of GHD for the overall population and matched individuals respectively.

Conclusion

GH assessment during a standardised aerobic exercise of moderate intensity is a reliable test with high diagnostic accuracy in predicting severe GHD in adult individuals. Based on the current findings exercise duration of 60 min appears to be sufficient for diagnostic purposes.

Free access

Emanuel R Christ, Monica Zehnder, Chris Boesch, Roman Trepp, Primus E Mullis, Peter Diem, and Jacques Décombaz

In view of the growing health problem associated with obesity, clarification of the regulation of energy homeostasis is important. Peripheral signals, such as ghrelin and leptin, have been shown to influence energy homeostasis. Nutrients and physical exercise, in turn, influence hormone levels. Data on the hormonal response to physical exercise (standardized negative energy balance) after high-fat (HF) or low-fat (LF) diet with identical carbohydrate intake are currently not available. The aim of the study was to investigate whether a short-term dietary intervention with HF and LF affects ghrelin and leptin levels and their modulators, GH, insulin and cortisol, before and during aerobic exercise. Eleven healthy, endurance-trained male athletes (Wmax 365 ± 29 W) were investigated twice in a randomized crossover design following two types of diet: 1. LF – 0.5 g fat/kg body weight (BW) per day for 2.5 days; 2. HF – 0.5 g fat/kg BW per day for 1 day followed by 3.5 g fat/kg BW per day for 1.5 days. After a standardized carbohydrate snack in the morning, metabolites and hormones (GH, ghrelin, leptin, insulin and cortisol) were measured before and at regular intervals throughout a 3-h aerobic exercise test on a cycloergometer at 50% of W max. Diet did not significantly affect GH and cortisol concentrations during exercise but resulted in a significant increase in ghrelin and decrease in leptin concentrations after LF compared with HF diet (area under the curve (AUC) ghrelin LF vs HF: P < 0.03; AUC leptin LF vs HF: P < 0.02, Wilcoxon rank test). These data suggest that acute negative energy balance induced by exercise elicits a hormonal response with opposite changes of ghrelin and leptin. In addition, the hormonal response is modulated by the preceding intake of fat.

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Emanuel R Christ, Michael H Cummings, Michael Stolinski, Nicola Jackson, Peter J Lumb, Anthony S Wierzbicki, Peter H Sönksen, David L Russell-Jones, and A Margot Umpleby

Background: Epidemiological studies suggest that hypopituitary patients have an increased risk for cardiovascular mortality. The dyslipidaemia associated with this condition is often characterised by an increase in total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol (LDL-C) and may contribute to these findings. The underlying mechanisms are not fully elucidated.

Materials and Methods: LDL apolipoprotein B (apoB) production rate and metabolic clearance rate were measured in seven patients with hypopituitarism (including GH deficiency) under stable conventional replacement therapy (three males and four females; age 40–16.1 years; body mass index 29.0–6.1 kg/m2 (means ± s.d.)) and seven age-, gender- and body mass index-matched control subjects with an infusion of 1-13C-leucine. Fasting lipid profile and lipid composition of LDL were also measured.

Results: Fasting TC, triglycerides (TG), high-density lipoprotein-C, LDL-C and free fatty acid concentrations were not different between hypopituitary patients and control subjects. LDL-TG (P < 0.006) and LDL-TG/LDL apoB ratio (P < 0.02) were significantly increased in hypopituitary patients. LDL apoB pool size was not statistically different between patients and control subjects. In the hypopituitary patients, LDL apoB metabolic clearance rate (P < 0.05) and LDL apoB production rate (P < 0.02) were lower than in the control subjects.

Conclusions: The present results suggest that LDL apoB turnover and LDL composition is altered in hypopituitary patients. Whether these findings explain the increased risk for cardiovascular disease in hypopituitary patients remains to be established.

Free access

Ann McCormack, Olaf M Dekkers, Stephan Petersenn, Vera Popovic, Jacqueline Trouillas, Gerald Raverot, Pia Burman, and ESE survey collaborators

Objective

To collect outcome data in a large cohort of patients with aggressive pituitary tumours (APT)/carcinomas (PC) and specifically report effects of temozolomide (TMZ) treatment.

Design

Electronic survey to ESE members Dec 2015–Nov 2016.

Results

Reports on 166 patients (40 PC, 125 APT, 1 unclassified) were obtained. Median age at diagnosis was 43 (range 4–79) years. 69% of the tumours were clinically functioning, and the most frequent immunohistochemical subtype were corticotroph tumours (45%). Ki-67 index did not distinguish APT from PC, median 7% and 10% respectively. TMZ was first-line chemotherapy in 157 patients. At the end of the treatment (median 9 cycles), radiological evaluation showed complete response (CR) in 6%, partial response (PR) in 31%, stable disease (SD) in 33% and progressive disease in 30%. Response was more frequent in patients receiving concomitant radiotherapy and TMZ. CR was seen only in patients with low MGMT expression. Clinically functioning tumours were more likely to respond than non-functioning tumours, independent of MGMT status. Of patients with CR, PR and SD, 25, 40 and 48% respectively progressed after a median of 12-month follow-up. Other oncological drugs given as primary treatment and to TMZ failures resulted in PR in 20%.

Conclusion

This survey confirms that TMZ is established as first-line chemotherapeutic treatment of APT/PC. Clinically functioning tumours, low MGMT and concurrent radiotherapy were associated with a better response. The limited long-term effect of TMZ and the poor efficacy of other drugs highlight the need to identify additional effective therapies.