Roman Trepp

Assessment of quality of life in patients with uncontrolled vs. controlled acromegaly using the Acromegaly Quality of Life Questionnaire (AcroQoL)

Objective Acromegaly is a chronic disease with an important impact on quality of life. An acromegaly disease‐generated quality of life questionnaire (AcroQoL) has recently been developed. We aimed to confirm reliability, construct validity and disease‐specificity of the AcroQoL questionnaire. Second, we investigated the effect of remission status on health‐related quality of life (HRQoL) in patients with acromegaly.

Treatment outcomes and mortality of 94 patients with acromegaly

SummaryBackground. Due to new therapeutic modalities and modified therapeutic goals outcome of patients with acromegaly may change over time and differ by centre. We analysed treatment outcomes and mortality of our patients with acromegaly seen between 1971 and 2003.Method. The cohort consisted of 94 patients who had been followed for 0.3–31 years (mean 10.6 years). Remission criteria were a normalized IGF-I concentration, a nadir GH level during oral glucose load of <1.0 µg/l and a random GH value of <2.5 µg/l.Findings. Transsphenoidal surgery achieved remission in 80% of patients with micro-adenomas (<1 cm), 65% with meso-adenomas (≥1 cm to <2 cm) and 27% with macro-adenomas (≥2 cm). Patients with meso-adenomas operated on after 1995 tended to have a better outcome compared to those operated on before 1995 (Remission in 83% vs. 38%). Radiotherapy resulted in disease control in 22 of 47 patients (47%). Intramuscular depot formulation of octreotide (Sandostatin® LAR®) led to disease control in 17 of 26 patients (65%). After multimodal therapy persistent acromegalic activity remained in 18% of the patients; only one of them had an adenoma of <2 cm. The standardized mortality ratio was 1.30 (95% CI 0.52–2.67) for patients in remission and 1.38 (95% CI 0.51–3.00) for patients with persistent acromegalic activity.Conclusions. Most patients with adenomas of <2 cm can be expected to achieve remission by transsphenoidal surgery alone. Furthermore, virtually all patients with adenomas of <2 cm and more than 80% of patients with adenomas of ≥2 cm can be expected to achieve remission by adjuvant treatment. Aggressive multimodal therapy is critical in the management of acromegaly reducing mortality risk close to that of the general population.

Exercise capacity in subjects with type 1 diabetes mellitus in eu- and hyperglycaemia

Circumstantial evidence suggests that an increase in plasma glucose availability improves exercise capacity in subjects with type 1 diabetes mellitus. The aim of this study was to assess exercise capacity in eu‐ and hyperglycaemic conditions in subjects with type 1 diabetes.

Effect of GH on human skeletal muscle lipid metabolism in GH deficiency

Adult-onset growth hormone (GH) deficiency (GHD) is associated with insulin resistance and decreased exercise capacity. Intramyocellular lipids (IMCL) depend on training status, diet, and insulin sensitivity. Using magnetic resonance spectroscopy, we studied IMCL content following physical activity (IMCL-depleted) and high-fat diet (IMCL-repleted) in 15 patients with GHD before and after 4 mo of GH replacement therapy (GHRT) and in 11 healthy control subjects. Measurements of insulin resistance and exercise capacity were performed and skeletal muscle biopsies were carried out to assess expression of mRNA of key enzymes involved in skeletal muscle lipid metabolism by real-time PCR and ultrastructure by electron microscopy. Compared with control subjects, patients with GHD showed significantly higher difference between IMCL-depleted and IMCL-repleted. GHRT resulted in an increase in skeletal muscle mRNA expression of IGF-I, hormone-sensitive lipase, and a tendency for an increase in fatty acid binding protein-3. Electron microscopy examination did not reveal significant differences after GHRT. In conclusion, variation of IMCL may be increased in patients with GHD compared with healthy control subjects. Qualitative changes within the skeletal muscle (i.e., an increase in free fatty acids availability from systemic and/or local sources) may contribute to the increase in insulin resistance and possibly to the improvement of exercise capacity after GHRT. The upregulation of IGF-I mRNA suggests a paracrine/autocrine role of IGF-I on skeletal muscle.

REGULATION OF WHOLE-BODY ENERGY HOMEOSTASIS WITH GROWTH HORMONE REPLACEMENT THERAPY AND ENDURANCE EXERCISE

We hypothesized that network analysis is useful to expose coordination between whole body and myocellular levels of energy metabolism and can identify entities that underlie skeletal muscles contribution to growth hormone-stimulated lipid handling and metabolic fitness. We assessed 112 metabolic parameters characterizing metabolic rate and substrate handling in tibialis anterior muscle and vascular compartment at rest, after a meal and exercise with growth hormone replacement therapy (GH-RT) of hypopituitary patients (n = 11). The topology of linear relationships (| r | ≥ 0.7, P ≤ 0.01) and mutual dependencies exposed the organization of metabolic relationships in three entities reflecting basal and exercise-induced metabolic rate, triglyceride handling, and substrate utilization in the pre- and postprandial state, respectively. GH-RT improved aerobic performance (+5%), lean-to-fat mass (+19%), and muscle area of tibialis anterior (+2%) but did not alter its mitochondrial and capillary content. Concomitantly, connectivity was established between myocellular parameters of mitochondrial lipid metabolism and meal-induced triglyceride handling in serum. This was mediated via the recruitment of transcripts of muscle lipid mobilization (LIPE, FABP3, and FABP4) and fatty acid-sensitive transcription factors (PPARA, PPARG) to the metabolic network. The interdependence of gene regulatory elements of muscle lipid metabolism reflected the norm in healthy subjects (n = 12) and distinguished the regulation of the mitochondrial respiration factor COX1 by GH and endurance exercise. Our observations validate the use of network analysis for systems medicine and highlight the notion that an improved stochiometry between muscle and whole body lipid metabolism, rather than alterations of single bottlenecks, contributes to GH-driven elevations in metabolic fitness.

Effect of Growth Hormone (GH) on Fasting and Postprandial Metabolism in GH Deficiency

OBJECTIVE Hypopituitarism with adult-onset growth hormone deficiency (GHD) is associated with increased cardiovascular morbidity and mortality due to premature and progressive atherosclerosis. An underlying cause of atherosclerosis is increased insulin resistance. Elevated fasting and postprandial glucose and lipid levels may contribute to premature atherosclerosis. We studied effects of growth hormone replacement (GHRT) on fasting and postprandial metabolic parameters as well as on insulin sensitivity in patients with adult-onset GHD. DESIGN Using a standardized mixed meal, we studied insulin, glucose, non-esterified free fatty acid (NEFA) and triglycerides (TG) concentrations in the fasting state and during a 4 h postprandial period in 15 patients with adult-onset GHD before and after 4 months of GHRT. Identical investigations were performed in healthy matched control subjects. RESULTS GHD patients before and after GHRT: GHRT did not result in significant changes in fasting glucose, insulin, NEFA and TG concentrations. In the postprandial period GHRT resulted in a non-significant increase in glucose and a decrease in NEFA levels in the presence of unchanged postprandial insulin and TG concentrations. GHD patients vs. control subjects: GHD patients showed similar fasting glucose, insulin and NEFA concentrations, but TG were increased. In the postprandial period GHD patients exhibited similar glucose and TG, but increased insulin and NEFA concentrations. GHRT patients vs. control subjects: Patients after GHRT had similar fasting glucose, insulin and NEFA, but increased TG concentrations. In the postprandial period patients after GHRT had increased glucose and insulin levels in the presence of similar NEFA and TG concentrations. CONCLUSIONS While impaired insulin action in patients with GHD translates mainly by an impaired fasting TG metabolism, GHRT induced insulin resistance additionally encompasses postprandial glucose metabolism.

Histology of Nivolumab induced Thyroiditis

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