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Casper Hammarstrand, Oskar Ragnarsson, Olivia Bengtsson, Ing-Liss Bryngelsson, Gudmundur Johannsson and Daniel S Olsson

Background: Patients with hypopituitarism have an increased mortality. The aim of this study was to investigate comorbidities including cerebral infarction, type 2 diabetes mellitus (T2DM) and malignant tumours in patients with non-functioning pituitary adenomas (NFPA) with and without growth hormone replacement therapy (GHRT).

Method: Observational cohort study in patients with NFPA within the western region of Sweden. Subjects were identified through the National Patient Registry and followed between 1987-2014. Patient records were reviewed and standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) for comorbidities were calculated.

Results: In total, 426 patients were included, 206 with GHRT and 219 without. Median (range) follow-up time for patients with and without GHRT was 12.2 (0-24) and 8.2 (0-27) years, respectively. Mean±SD body mass index (BMI) was 28.5±4.5 and 26.5±4.4 for patients with and without GHRT, respectively (P<0.001). Incidence of cerebral infarction was increased (SIR 1.39; 95% CI 1.03-1.84; P=0.032), with no difference between patients with and without GHRT. SIR for T2DM in patients not receiving GHRT was increased (1.65; 1.06-2.46; P=0.018), whereas the incidence in patients receiving GHRT was not (0.99; 0.55-1.63; P=0.99). The incidence of malignant tumours was not increased, neither in patients with nor without GHRT.

Conclusion: The incidence of cerebral infarction is increased in patients with NFPA irrespective of GHRT. Patients without GHRT had an increased risk of T2DM, whereas patients with GHRT, had a normal incidence of T2DM, despite having higher BMI. Incidence of malignant tumours was not increased. Thus, long-term GHRT seems to be safe regarding risk of comorbidities.

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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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Mark Wijnen, Daniel S Olsson, Marry M van den Heuvel-Eibrink, Casper Hammarstrand, Joseph A M J L Janssen, Aart J van der Lely, Gudmundur Johannsson and Sebastian J C M M Neggers

Objective

Most studies in patients with craniopharyngioma did not investigate morbidity and mortality relative to the general population nor evaluated risk factors for excess morbidity and mortality. Therefore, the objective of this study was to examine excess morbidity and mortality, as well as their determinants in patients with craniopharyngioma.

Design

Hospital-based retrospective cohort study conducted between 1987 and 2014.

Methods

We included 144 Dutch and 80 Swedish patients with craniopharyngioma identified by a computer-based search in the medical records (105 females (47%), 112 patients with childhood-onset craniopharyngioma (50%), 3153 person-years of follow-up). Excess morbidity and mortality were analysed using standardized incidence and mortality ratios (SIRs and SMRs). Risk factors were evaluated univariably by comparing SIRs and SMRs between non-overlapping subgroups.

Results

Patients with craniopharyngioma experienced excess morbidity due to type 2 diabetes mellitus (T2DM) (SIR: 4.4, 95% confidence interval (CI): 2.8–6.8) and cerebral infarction (SIR: 4.9, 95% CI: 3.1–8.0) compared to the general population. Risks for malignant neoplasms, myocardial infarctions and fractures were not increased. Patients with craniopharyngioma also had excessive total mortality (SMR: 2.7, 95% CI: 2.0–3.8), and mortality due to circulatory (SMR: 2.3, 95% CI: 1.1–4.5) and respiratory (SMR: 6.0, 95% CI: 2.5–14.5) diseases. Female sex, childhood-onset craniopharyngioma, hydrocephalus and tumour recurrence were identified as risk factors for excess T2DM, cerebral infarction and total mortality.

Conclusions

Patients with craniopharyngioma are at an increased risk for T2DM, cerebral infarction, total mortality and mortality due to circulatory and respiratory diseases. Female sex, childhood-onset craniopharyngioma, hydrocephalus and tumour recurrence are important risk factors.

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Mark Wijnen, Daniel S Olsson, Marry M van den Heuvel-Eibrink, Casper Hammarstrand, Joseph A M J L Janssen, Aart-Jan van der Lely, Gudmundur Johannsson and Sebastian J C M M Neggers

Objective

Patients with craniopharyngioma are at an increased risk for cardio- and cerebrovascular mortality. The metabolic syndrome (MetS) is an important cardiometabolic risk factor, but barely studied in patients with craniopharyngioma. We aimed to investigate the prevalence of and risk factors for the MetS and its components in patients with craniopharyngioma.

Design

Cross-sectional study with retrospective data.

Methods

We studied the prevalence of and risk factors for the MetS and its components in 110 Dutch (median age 47 years, range 18–92) and 68 Swedish (median age 50 years, range 20–81) patients with craniopharyngioma with ≥3 years of follow-up (90 females (51%); 83 patients with childhood-onset craniopharyngioma (47%); median follow-up after craniopharyngioma diagnosis 16 years (range 3–62)). In Dutch patients aged 30–70 years and Swedish patients aged 45–69 years, we examined the prevalence of the MetS and its components relative to the general population.

Results

Sixty-nine (46%) of 149 patients with complete data demonstrated the MetS. Prevalence of the MetS was significantly higher in patients with craniopharyngioma compared with the general population (40% vs 26% (P < 0.05) for Dutch patients; 52% vs 15% (P < 0.05) for Swedish patients). Multivariable logistic regression analysis identified visual impairment as a borderline significant predictor of the MetS (OR 2.54, 95% CI 0.95–6.81; P = 0.06) after adjustment for glucocorticoid replacement therapy and follow-up duration. Age, female sex, tumor location, radiological hypothalamic damage, 90Yttrium brachytherapy, glucocorticoid replacement therapy and follow-up duration significantly predicted components of the MetS.

Conclusions

Patients with craniopharyngioma are at an increased risk for the MetS, especially patients with visual impairment.