Non-functioning pituitary adenomas and hypopituitarism - studies on morbidity and mortality
Background and aims: Hypopituitarism is most commonly caused by benign pituitary tumors, often resulting in insidious symptoms that develop over a long time. Due to either a mass effect exerted by the tumor, or due to the surgical treatment, hormonal deficiencies may arise, requiring hormone replacement. Based on four studies, this dissertation aimed to investigate the influence of glucocorticoid and growth hormone replacement on mortality, morbidity and surrogate markers for cardiovascular disease. Methods: In paper I, the influence of glucocorticoid replacement on mortality was studied in patients with NFPA with standardized mortality ratio, using the general population as reference, and hazard ratio calculated. In paper II, standardized incidence ratio (SIR) for malignant tumors was calculated for patients with NFPA using the general population as reference. In paper III, the influence of growth hormone replacement therapy on comorbidities was studied. Finally, in paper IV, changes in the concentration of LDL-cholesterol were compared between patients with growth hormone replacement and a random population sample of men and women. Results: Paper I showed that glucocorticoid replacement doses of more than 20 mg per day were associated with excess mortality. In paper II, the overall incidence of malignant tumours was increased in NFPA patients. Paper III showed that the risk of type 2 diabetes mellitus and cancer was not increased for growth hormone replaced patients. Finally, in paper IV, LDL-cholesterol in growth hormone replaced patients was decreased above the secular trends seen in the general population. Conclusions: Glucocorticoid replacement doses higher than 20 mg per day are associ-ated with increased mortality. Patients with NFPA have an increased risk of developing cancer. However, growth hormone replacement seems to be safe concerning the risk of developing comorbidities, including cancer. Furthermore, growth hormone replacement can be considered beneficial for the lipid profile.
Parts of work
Paper I. Hammarstrand C, Ragnarsson O, Hallén T, Andersson E, Skoglund T, Nilsson A G, Johannsson G, Olsson D S. Higher glucocorticoid replacement doses are associated with increased mortality in patients with pituitary adenoma. European Journal of Endocrinology. 2017 Sep;177 (3):251-256. https://doi.org/10.1530/EJE-17-0340Paper II. Olsson D S, Hammarstrand C, Bryngelsson IL, Nilsson A G, Andersson E, Johannsson G, Ragnarsson O. Incidence of malignant tumours in patients with a non-functioning pituitary adenoma. Endocrine-Related Cancer. 2017 May;24 (5):227-235. https://doi.org/10.1530/ERC-16-0518Paper III. Hammarstrand C, Ragnarsson O, Bengtsson O, Bryngelsson IL, Johannsson G, Olsson D S. Comorbidities in patients with non-functioning pituitary adenoma: influence of long-term growth hormone replacement. European Journal of Endocrinology. 2018 Oct 1;179(4):229-237. https://doi.org/10.1530/EJE-18-0370Paper IV. Hammarstrand C, Olsson D S, Koranyi J, Trimpou P, Landin-Wilhelmsen K, Johannsson G. Growth hormone replacement therapy in adults with hypopituitarism: A longitudinal case-control study on lipid metabolism. Manuscript.
Doctor of Philosophy (Medicine)
University of Gothenburg. Sahlgrenska Academy
Inst of Medicine. Department of Internal Medicine and Clinical Nutrition
Fredagen den 2 september 2022, kl. 9.00, Hörsal Arvid Carlsson, Academicum, Medicinaregatan 3, Göteborg
Date of defence
Non-functioning pituitary adenomas
Growth hormone replacement