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Eva Jennische and Göran L. Andersson

Abstract.

Expression of growth hormone receptor mRNA was investigated by in situ hybridization in skeletal muscle from normal and hypophysectomized rats during the first seven days of regeneration after ischemic injury. A digoxigenin-labelled RNA probe directed against the extracellular part of the rat GH receptor was used. In both normal and hypophysectomized rats distinct expression of GH receptor mRNA could be demonstrated in the regenerating muscle cells at the myoblast/myotube stage. The GH receptor expression appeared to decline with increasing maturation of the regenerated muscle fibres. In hypophysectomized rats, the regeneration process and the expression of GH receptor mRNA was delayed compared with that in normal animals. It is concluded that growth hormone may affect also the early phase of muscle regeneration in normal animals. To what extent lack of growth hormone contributes to the delayed regeneration observed in the hypophysectomized rats remains to be elucidated.

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Göran L. Andersson, Anna Skottner and Eva Jennische

Abstract. The localization of insulin-like growth factor I (IGF-I, somatomedin C) was investigated in the kidney of adult rats during normal conditions and after nephrectomy, using immunocytochemical and biochemical methods. In the normal kidney, IGF-I immunoreactivity could be demonstrated mainly in cells in the medullary collecting ducts and in those parts of the thin limb of Henle's loop located in the outer medulla. During compensatory growth all parts of the collecting ducts, including those in the cortex, showed IGF-I immunoreactivity, as did cells in the entire thin limb of Henle's loop. No IGF-I immunoreactivity could be demonstrated in the proximal or distal tubules, either in the control kidney or during compensatory growth. Biochemical measurements showed a significantly higher content of IGF-I in the inner medulla than in the cortex in the normal kidney. Uninephrectomy resulted in significantly increased IGF-I content in the cortex. It is suggested that IGF-I is produced mainly in the collecting ducts and in the thin limb of Henle's loop and exerts its effect on other parts of the nephron by paracrine mechanisms.

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Casper Hammarstrand, Oskar Ragnarsson, Tobias Hallén, Eva Andersson, Thomas Skoglund, Anna G Nilsson, Gudmundur Johannsson and Daniel S Olsson

Objective

Patients with secondary adrenal insufficiency (AI) have an excess mortality. The objective was to investigate the impact of the daily glucocorticoid replacement dose on mortality in patients with hypopituitarism due to non-functioning pituitary adenoma (NFPA).

Methods

Patients with NFPA were followed between years 1997 and 2014 and cross-referenced with the National Swedish Death Register. Standardized mortality ratio (SMR) was calculated with the general population as reference and Cox-regression was used to analyse the mortality.

Results

The analysis included 392 patients (140 women) with NFPA. Mean ± s.d. age at diagnosis was 58.7 ± 14.6 years and mean follow-up was 12.7 ± 7.2 years. AI was present in 193 patients, receiving a mean daily hydrocortisone equivalent (HCeq) dose of 20 ± 6 mg. SMR (95% confidence interval (CI)) for patients with AI was similar to that for patients without, 0.88 (0.68–1.12) and 0.87 (0.63–1.18) respectively. SMR was higher for patients with a daily HCeq dose of >20 mg (1.42 (0.88–2.17)) than that in patients with a daily HCeq dose of 20 mg (0.71 (0.49–0.99)), P = 0.017. In a Cox-regression analysis, a daily HCeq dose of >20 mg was independently associated with a higher mortality (HR: 1.88 (1.06–3.33)). Patients with daily HCeq doses of ≤20 mg had a mortality risk comparable to patients without glucocorticoid replacement and to the general population.

Conclusion

Patients with NFPA and AI receiving more than 20 mg HCeq per day have an increased mortality. Our data also show that mortality in patients substituted with 20 mg HCeq per day or less is not increased.

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Daniel S Olsson, Penelope Trimpou, Tobias Hallén, Ing-Liss Bryngelsson, Eva Andersson, Thomas Skoglund, Bengt-Åke Bengtsson, Gudmundur Johannsson and Anna G Nilsson

Objective

Hypopituitarism has been associated with increased mortality. The excess mortality may be due to untreated growth hormone (GH) deficiency but also due to various underlying disorders. We therefore analysed mortality in patients with only one underlying disorder, non-functioning pituitary adenoma (NFPA), with and without GH replacement therapy (GHRT).

Design and method

Patients with NFPA in the western region of Sweden, 1997–2011, were identified through the National Patient Registry and cross-referenced with several National Health Registries. All patient records were reviewed. Standardised mortality ratios (SMRs) with 95% confidence intervals (CIs) were calculated using the general population as reference. Cox-regression models were performed to identify predictors of mortality.

Results

A total of 426 NFPA patients with 4599 patient-years were included, of whom 207 had used GHRT and 219 had not received GHRT. Median (range) follow-up in patients with and without GHRT was 12.2 (0–25) and 8.2 (0–27) years, respectively. Other pituitary hormone deficiencies were more frequent in the GHRT group than those in the non-GHRT group. SMR was 0.65 (95% CI, 0.44–0.94; P = 0.018) for the GHRT group and 1.16 (0.94–1.42; P = 0.17) for the non-GHRT group. Direct comparison between the groups showed reduced mortality among those who were GH replaced (P = 0.0063). The SMR for malignant tumours was reduced in the GHRT-group (0.29; 0.08–0.73; P = 0.004) but not in untreated patients.

Conclusions

Selection bias explaining some of the results cannot be excluded. However, NFPA patients with GHRT had reduced overall mortality compared with the general population, and death due to malignancy was not increased. This suggests that long-term GHRT is safe in adult patients selected for treatment.