| 1. |
- Holmer, Helene, et al.
(författare)
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Fracture incidence in GH-deficient patients on complete hormone replacement including GH
- 2007
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 22:12, s. 1842-1850
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Tidskriftsartikel (refereegranskat)abstract
- Fracture risk in GHD patients is not definitely established. Studying fracture incidence in 832 patients on GH therapy and 2581 matched population controls, we recorded a doubled fracture risk in CO GHD women, but a significantly lower fracture risk in AO GHD men. Introduction: The objective of this study was to evaluate fracture incidence in patients wilh confirmed growth hormone deficiency (GHD) on replacement therapy (including growth hormone [GH]) compared with population controls, while also taking potential confounders and effect modifiers into account. Materials and Methods: Eight hundred thirty-two patients with GHD and 2581 matched population controls answered a questionnaire about fractures and other background information. Incidence rate ratio (IRR) and 95% CI for first fracture were estimated. The median time on GH therapy for childhood onset (CO) GHD men and women was 15 and 12 yr, respectively, and 6 and 5 yr for adult onset (AO) GHD men and women, respectively. Results: A more than doubled risk (IRR, 2.29; 95% CI, 1.23-4.28) for nonosteoporotic fractures was recorded in women with CO GHD, whereas no risk increase was observed among CO GHD men (IRR. 0.61) and AO GHD women (IRR, 1.08). A significantly decreased incidence of fractures (IRR, 0.54; 95% CI 0.34-0.86) was recorded in AO GHD men. Conclusions: Increased fracture risk in CO GHD women can most likely be explained by interaction between oral estrogen and the GH-IGF-I axis. The adequate substitution rate of testosterone (90%) and GH (94%) may have resulted in significantly lower fracture risk in AO GHD men.
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| 2. |
- Holmer, Helene, et al.
(författare)
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Nonfatal stroke, cardiac disease, and diabetes mellitus in hypopituitary patients on hormone replacement including growth hormone
- 2007
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 92:9, s. 3560-3567
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Tidskriftsartikel (refereegranskat)abstract
- Context: The impact of long-term GH replacement on cerebrovascular and cardiovascular diseases and diabetes mellitus in hypopituitary patients is unknown. Objective: The incidence of nonfatal stroke and cardiac events, and prevalence of type 2 diabetes mellitus ( T2D) and cardioprotective medication were compared between cohorts of GH-deficient (GHD) patients and population controls. Design and Participants: The incidence of nonfatal stroke and cardiac events was estimated retrospectively from questionnaires in 750 GHD patients and 2314 matched population controls. A prevalence of T2D and cardioprotective medication was recorded at the distribution of questionnaires. Time since first pituitary deficiency to start of GH therapy was 4 and 2 yr, and time on GH therapy was 6 yr for GHD women and men, respectively. Results: Lifelong incidence of nonfatal stroke was tripled in GHD women and doubled in GHD men, but a decline was seen in both genders during periods after first pituitary hormone deficiency and GHD, during which most patients had GH therapy. The lifelong incidence of nonfatal cardiac events declined in GHD men during first pituitary hormone deficiency and GHD periods. GHD women had a higher prevalence of T2D and lipid-lowering medication, whereas GHD men had a higher prevalence of antihypertensive medication. Conclusions: The declined risks of nonfatal stroke in both genders and of nonfatal cardiac events in GHD men during periods on GH replacement may be caused by prescription of cardioprotective drugs and 6-yr GH replacement. GHD women had an increased prevalence of T2D, partly attributed to higher body mass index and lower physical activity.
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| 3. |
- Holmer, Helene, et al.
(författare)
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Psychosocial health and levels of employment in 851 hypopituitary Swedish patients on long-term GH therapy
- 2013
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Ingår i: Psychoneuroendocrinology. - : Elsevier. - 0306-4530 .- 1873-3360. ; 38:6, s. 842-852
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Tidskriftsartikel (refereegranskat)abstract
- Context: The psychosocial health and working capacity in hypopituitary patients receiving long-term growth hormone (GH) therapy are unknown. less thanbrgreater than less thanbrgreater thanObjective: Psychosocial health and levels of employment were compared between GH deficient (GHD) patients on long-term replacement and the general population. less thanbrgreater than less thanbrgreater thanDesign and participants: In a Swedish nationwide study, 851 GHD patients [101 childhood onset (CO) and 750 adult onset (AO)] and 2622 population controls answered a questionnaire regarding current living, employment and educational level, alcohol consumption and smoking habits. The median time on GH therapy for both men and women with CO GHD was 9 years and for AO GHD 6 years, respectively. less thanbrgreater than less thanbrgreater thanResults: As compared to the controls, the GHD patients were less often working full time, more often on sick leave/disability pension, and to a larger extent alcohol abstainers and never smokers (all; P andlt; 0.05). Predominantly CO GHD women and men, but to some extent also AO GHD women and men, lived less frequently with a partner and more often with their parents. Particularly AO GHD craniopharyngioma women used more antidepressants, while AO GHD men with a craniopharyngioma used more analgesics. less thanbrgreater than less thanbrgreater thanConclusions: A working capacity to the level of the general population was not achieved among hypopituitary patients, although receiving long-term GH therapy. Patients were less likely to use alcohol and tobacco. The CO GHD population lived a less independent life.
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| 4. |
- Fjalldal, Sigridur, et al.
(författare)
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Brain white matter lesions are associated with reduced hypothalamic volume and cranial radiotherapy in childhood-onset craniopharyngioma
- 2021
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Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 94:1, s. 48-57
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Tidskriftsartikel (refereegranskat)abstract
- Context: White matter lesions (WML) are caused by obstruction of small cerebral vessels associated with stroke risk. Craniopharyngioma (CP) patients suffer from increased cerebrovascular mortality. Objective: To investigate the effect of reduced HT volume and cranial radiotherapy (CRT) on WML in childhood-onset CP patients. Design: A cross-sectional study of 41 patients (24 women) surgically treated childhood-onset CP in comparison to controls. Setting: The South Medical Region of Sweden (2.5 million inhabitants). Methods: With magnetic resonance imaging (MRI), we analysed qualitative measurement of WML based on the visual rating scale of Fazekas and quantitative automated segmentation of WML lesion. Also, measurement HT volume and of cardiovascular risk factors were analysed. Results: Patients had a significant increase in WML volume (mL) (P =.001) compared to controls. Treatment with cranial radiotherapy (CRT) vs no CRT was associated with increased WML volume (P =.02) as well as higher Fazekas score (P =.001). WML volume increased with years after CRT (r = 0.39; P =.02), even after adjustment for fat mass and age. A reduced HT volume was associated with increased WML volume (r = −0.61, P <.001) and explained 26% of the variation (r2 = 0.26). Altogether, 47% of the WML volume was explained by age at investigation, HT volume and CRT. Patients with more WML also had higher cardiovascular risk. Conclusions: CRT may be associated directly with increased WML volume or indirectly with reduced HT volume associated with higher cardiovascular risk. Risk factors should be carefully monitored in these patients.
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| 5. |
- Fjalldal, Sigridur, et al.
(författare)
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Hypothalamic Involvement Predicts Cognitive Performance and Psychosocial Health in Long-term Survivors of Childhood Craniopharyngioma
- 2013
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Endocrine Society. - 0021-972X .- 1945-7197. ; 98:8, s. 3253-3262
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Tidskriftsartikel (refereegranskat)abstract
- Context: Hypothalamic damage caused by craniopharyngioma (CP) is associated with poor functional outcome. less thanbrgreater than less thanbrgreater thanObjective: To assess cognitive function and quality of life in childhood-onset CP on hormonal replacement, including GH treatment. less thanbrgreater than less thanbrgreater thanDesign: A cross-sectional study with a median follow-up time of 20 years (1-40). less thanbrgreater than less thanbrgreater thanSetting: Patients were recruited from the South Medical Region of Sweden. less thanbrgreater than less thanbrgreater thanParticipants: The study included 42 patients (20 women) surgically treated for a childhood-onset CP between 1958 and 2000. Patients were aged andgt;= 17 years. Equally many controls, matched for age, sex, residence, and smoking habits, were included. Tumor growth into the third ventricle was found in 25 patients. less thanbrgreater than less thanbrgreater thanMain Outcome Measures: All subjects were examined with a battery of cognitive tests and the following questionnaires: Symptom Checklist-90, the Interview Schedule for Social Interaction, and the Social Network concept. less thanbrgreater than less thanbrgreater thanResults: The CP patients had lower cognitive performance, reaching statistical significance in 12 of 20 test variables, including executive function and memory. Comparison of patients with tumor growth into the third ventricle to controls revealed a significant lower mean total score (P = .006). A significant negative correlation was recorded between mean z-score of cognitive performance and years since operation (r = -0.407; P = .014). No statistically significant group differences were observed across any of the 9 Symptom Checklist-90 subscales. less thanbrgreater than less thanbrgreater thanConclusions: Adults with childhood-onset CP, on hormone replacement, including GH treatment, have memory defects, disturbed attention, and impaired processing speed. Patients with hypothalamic involvement are more affected. Patients rated their quality of life as good as their matched controls.
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| 6. |
- Follin, Cecilia, et al.
(författare)
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Hypothalamic dysfunction revealed by magnetic resonance diffusion tensor imaging in childhood leukemia survivors treated with cranial radiotherapy but not in craniopharyngeoma survivors
- 2016
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Konferensbidrag (refereegranskat)abstract
- Background: Metabolic complications with obesity are frequent in childhood acute lymphoblastic leukemia (ALL) survivors treated with cranial radiotherapy (CRT). Childhood onset Craniopharyngioma (CP) survivors without hypothalamic (HT) involvement are spared gross obesity. Magnetic resonance diffusion tensor imaging (DTI) provides information of microstructure function of the brain and quantified as fractional anisotrophy (FA), mean diffusivity (MD), axial and radial diffusivity (AD, RD). Since MD in HT is reportedly impaired (increased) in obese compared to non-obese subjects, we investigated DTI in the HT.Methods: Twenty nine ALL survivors on hormone supplementation were investigated 34 years after CRT (24 Gy). 17 CO-CP survivors with hormone supplementation but without HT damage were investigated. Comparisons were made with these two patient populations to 27 matched controls regarding DTI parameters in the HT and for BMI, fat mass, fat free mass and waist/hip measurements.Results: We recorded reduced FA (0.27 vs 0.29, P=0.04), and increased MD (1.13 vs 1.00, P<0.001), AD (1.41 vs 1.25, P<0.001), and RD (0.99 vs 0.86, P<0.001) in the right HT and increased MD (1.42 vs 1.25, P<0.001), AD (1.75 vs 1.58, P<0.001), and RD (1.25 vs 1.04, P<0.001) in left HT in ALL survivors compared to matched controls. The CPs showed no difference in the HT for these parameters compared to controls. ALL survivors with a BMI ≥ 25 showed elevated MD (P=0.03) and AD (P=0.02) compared to ALL survivors with a BMI < 25 and compared to controls with BMI ≥ 25 in the right HT. This was not the case in CP survivors or in controls.Conclusions: Thirty four years after CRT for ALL, DTI measures are deranged in the HT. ALL survivors with a BMI ≥ 25 were presented with worse HT dysfunction. CP survivors were unaffected. The present data suggests changes in the microstructure of the HT in these ALL survivors.
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| 7. |
- Follin, Cecilia, et al.
(författare)
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Microstructure alterations in the hypothalamus in cranially radiated childhood leukaemia survivors but not in craniopharyngioma patients unaffected by hypothalamic damage
- 2017
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Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664. ; 87:4, s. 359-366
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Metabolic complications are frequent in childhood leukaemia (ALL) survivors treated with cranial radiotherapy (CRT). These complications are potentially mediated by damage to the hypothalamus (HT), as childhood onset (CO) craniopharyngioma (CP) survivors without HT involvement are spared overt obesity. Diffusion tensor imaging (DTI) shows brain tissue microstructure alterations, by fractional anisotrophy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). We used DTI to determine the integrity of the microstructure of the HT in ALL survivors. Design: Case-control study. Patients: Three groups were included: (i) 27 CRT treated ALL survivors on hormone supplementation, (ii) 17 CO-CP survivors on hormone supplementation but without HT involvement and (iii) 27 matched controls. Measurements: DTI parameters of the HT were measured and body composition. Results: Microstructural alterations in the HT were more severe in ALL survivors with a BMI ≥25 than with BMI <25. Compared to controls, ALL survivors had reduced FA (P=.04), increased MD (P<.001), AD (P<.001) and RD (P<.001) in the right and left HT. In the right HT, ALL survivors with a BMI ≥25 showed elevated MD (P=.03) and AD (P=.02) compared to ALL survivors with BMI <25. In contrast, DTI parameters did not differ between CP survivors and controls. Conclusions: Long-term follow-up after CRT for ALL DTI measures were affected in the HT despite complete hormone replacement. The present data suggest that ALL survivors have demyelination and axonal loss in the HT.
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| 8. |
- Rylander, Lars, et al.
(författare)
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Associations between CB-153 and p,p'-DDE and hormone levels in serum in middle-aged and elderly men.
- 2006
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Ingår i: Chemosphere. - : Elsevier BV. - 1879-1298 .- 0045-6535. ; 65:3, s. 375-381
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Tidskriftsartikel (refereegranskat)abstract
- Background: Animal and epidemiologic data indicate that exposure to persistent organochlorine pollutants (POPs) may disrupt the hypothalamus-pituitary-thyroid (HPT) and the hypothalamus-pituitary-gonadal (HPG) axes. We have assessed whether the POP-biomarkers 2,2'4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis(4-chlorophenyl)-ethene (p,p'-DDE) affect thyrotropin (TSH), thyroid hormones, gonadotropins or sex hormone concentrations in men. Methods: Lipid adjusted serum concentrations of CB-153, and p,p'-DDE, were determined in 196 men (median age 59 years, range 48-82). Hormone analyses in serum were performed with immunoassays. The effect of CB-153 and p,p'-DDE (as continuous or categorized variables) were evaluated by linear regression models, adjusting for potential confounders. Results: There was a significant positive association between p,p'-DDE and TSH. An increase of 100 ng/g lipid of p,p'-DDE corresponded to an increase of 0.03 mU/l (95% Confidence Interval (CI) 0.01, 0.05) in TSH level. The explanatory value (R 2) of the multi-variate model was only 7%. Moreover, there was a significant negative association between p,p'-DDE and estradiol. An increase of 100 ng/g lipid of p,p'-DDE corresponded to a decrease of 0.57 pmol/l (95% CI -1.0, -0.12) in estradiol level. The R-2-value was only 4%. No associations were observed between any of the POP biomarkers and the other hormones. Conclusions: The positive association between p,p'-DDE and TSH and the negative association between p,p'-DDE and estradiol, among middle-aged and elderly men, were not accompanied by associations between the POP-markers and thyroxin, testosterone, and gonadotropins, respectively. The results gives some additional support for that POP exposure may affect HPT- and HPG-axes also in humans, but the overall epidemiological data are still not coherent enough to allow any firm conclusions. (c) 2006 Elsevier Ltd. All rights reserved.
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