| 1. |
- Holmer,, 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: J Bone Miner Res. - : Wiley. - 0884-0431.
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Tidskriftsartikel (refereegranskat)abstract
- Microabstract Fracture risk in growth hormone-deficient (GHD) patients is not definitely established. Investigating fracture incidence in 832 patients on growth hormone (GH) therapy and 2,581 matched population controls, we recorded a doubled fracture risk in childhood onset (CO) GHD women, but a significantly lower fracture risk in adult onset (AO) GHD men.
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| 2. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
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| 6. |
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| 7. |
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| 8. |
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| 9. |
- Link, Katarina, et al.
(författare)
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Low individualized growth hormone (GH) dose increased renal and cardiac growth in young adults with childhood onset GH deficiency
- 2001
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Ingår i: Clinical Endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 55:6, s. 741-748
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE In childhood onset GH deficiency (GHD) a reduction in left ventricular mass (LV-mass) and impairment of systolic function as well an impairment in glomerular filtration rate (GFR) has been shown. The aim of the present study was to assess if a low GH dose resulted in an improvement in morphological and functional parameters of these organs. DESIGN AND PATIENTS Eleven patients with childhood onset GHD were investigated before and after 10 months of GH treatment at a dose of 1.5 IU/day (range 1-2), corresponding to 0.02 IU/kg/day or 7 mug/kg/day. The GH dose resulted in a serum IGF-I level in the normal range in all but one patient. MEASUREMENTS Doppler echocardiography of the heart and ultrasound examination of the kidneys was performed. Glomerular filtration rate (GFR) was estimated with iohexol clearance and urinary proteinuria was measured with 24-h urinary samples collected for analyses of albumin, alpha-1-microglobulin, IgG and albumin/creatinine clearance ratio. Body composition was measured by bioelectric impedance analysis. RESULTS L V-mass index increased significantly after GH treatment (P = 0.04), and there was a clear trend for a positive correlation between the increase in serum IGF-I and the increase in LV-mass index, although it did not reach significance (r = 0.57, P = 0.07). GH treatment did not increase cardiac fractional shortening. Kidney length increased significantly (P = 0.02) with an average increase of 1 cm (range -0.5-1.5 cm). No significant changes in median GFR or serum creatinine were recorded. Three patients with subnormal GFR before GH treatment normalized after 10 months of treatment. Urine analysis showed no abnormalities before or after GH treatment. A significant decrease in percentage fat mass was recorded (P = 0.03). CONCLUSION A low individualized GH dose to adults with childhood onset GHD resulted in an increase in LV-mass index and kidney length. Re-establishing GH treatment with a low dose in this patient group can lead to a further somatic maturation of these organs, probably not accomplished previously.
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| 10. |
- Allen, David B, et al.
(författare)
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GH Safety Workshop Position Paper: a critical appraisal of recombinant human growth hormone therapy in children and adults.
- 2016
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 174:2, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Recombinant human growth hormone (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, the statement highlighted a number of areas for on-going surveillance of long-term safety including; cancer risk, impact on glucose homeostasis and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk and the need for longterm surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement.
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| 11. |
- Arnardottir, Steinunn, et al.
(författare)
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Long-term outcomes of patients with acromegaly: a report from the Swedish Pituitary Register
- 2022
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Ingår i: European Journal of Endocrinology. - : European Society of Endocrinology. - 1479-683X .- 0804-4643. ; 186:3, s. 329-339
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe the treatment and long-term outcomes of patients with acromegaly from all healthcare regions in Sweden. Design and methods: Analysis of prospectively reported data from the Swedish Pituitary Register of 698 patients (51% females) with acromegaly diagnosed from 1991 to 2011. The latest clinical follow-up date was December 2012, while mortality data were collected for 28.5 years until June 2019. Results: The annual incidence was 3.7/million; 71% of patients had a macroadenoma, 18% had visual field defects, and 25% had at least one pituitary hormone deficiency. Eighty-two percent had pituitary surgery, 10% radiotherapy, and 39% medical treatment. At the 5- and 10-year follow-ups, insulin-like growth factor 1 levels were within the reference range in 69 and 78% of patients, respectively. In linear regression, the proportion of patients with biochemical control including adjuvant therapy at 10 years follow-up increased over time by 1.23% per year. The standardized mortality ratio (SMR) (95% CI) for all patients was 1.29 (1.11-1.49). For patients with biochemical control at the latest follow-up, SMR was not increased, neither among patients diagnosed between 1991 and 2000, SMR: 1.06 (0.85-1.33) nor between 2001 and2011, SMR: 0.87 (0.61-1.24). In contrast, non-controlled patients at the latest follow-up from both decades had elevated SMR, 1.90 (1.33-2.72) and 1.98 (1.24-3.14), respectively. Conclusions: The proportion of patients with biochemical control increased over time. Patients with biochemically controlled acromegaly have normal life expectancy, while non-controlled patients still have increased mortality. The high rate of macroadenomas and unchanged age at diagnosis illustrates the need for improvements in the management of patients with acromegaly.
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| 12. |
- Attanasio, Andrea F, et al.
(författare)
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Prevalence of Metabolic Syndrome in Adult Hypopituitary Growth Hormone (GH)-Deficient Patients Before and After GH Replacement.
- 2010
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 95, s. 74-81
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Tidskriftsartikel (refereegranskat)abstract
- Context and Objective: Metabolic and body compositional consequences of GH deficiency (GHD) in adults are associated with a phenotype similar to the metabolic syndrome (MetS). Patients: We assessed MetS prevalence in adult GHD patients (n = 2531) enrolled in the Hypopituitary Control and Complications Study. Prevalence was assessed at baseline and after 3 yr of GH replacement in a subset of 346 adult-onset patients. Results: Baseline MetS crude prevalence was 42.3%; age-adjusted prevalence in the United States and Europe was 51.8 and 28.6% (P < 0.001), respectively. In the United States, age-adjusted prevalence was significantly higher (P < 0.001) than in a general population survey. Increased MetS risk at baseline was observed for age 40 yr or older (adjusted relative risk 1.34, 95% confidence interval 1.17-1.53, P < 0.001), females (1.15, 1.05-1.25, P = 0.002), and adult onset (1.77, 1.44-2.18, P < 0.001). In GH-treated adult-onset patients, MetS prevalence was not changed after 3 yr (42.5-45.7%, P = 0.172), but significant changes were seen for waist circumference (62.1-56.9%, P = 0.008), fasting glucose (26.0-32.4%, P < 0.001), and blood pressure (59.8-69.7%, P < 0.001). Significantly increased risk of MetS at yr 3 was associated with baseline MetS (adjusted relative risk 4.09, 95% confidence interval 3.02-5.53, P < 0.001) and body mass index 30 kg/m(2) or greater (1.53, 1.17-1.99, P = 0.002) and increased risk (with a P value < 0.1) for GH dose 600 mug/d or greater (1.18, 95% confidence interval 0.98-1.44, P = 0.088). Conclusion: MetS prevalence in GHD patients was higher than in the general population in the United States and higher in the United States than Europe. Prevalence was unaffected by GH replacement, but baseline MetS status and obesity were strong predictors of MetS after GH treatment.
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| 13. |
- Björk, Jonas, et al.
(författare)
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The utility of the GHRH-arginine test for diagnosing GH deficiency in adults with childhood acute lymphoblastic leukemia (ALL) treated with cranial irradiation.
- 2005
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 90:11, s. 6048-6054
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Tidskriftsartikel (refereegranskat)abstract
- Context: The insulin tolerance test ( ITT) is the current standard diagnostic test for the diagnosis of adult GH deficiency ( GHD), but alternative tests, such as the GHRH- arginine test, have been proposed. Objective: We investigated the sensitivity and specificity of the GHRH- arginine test using ITT as the gold standard in diagnosing GHD in a group of young adults treated with cranial irradiation ( CRT) for childhood acute lymphoblastic leukemia ( ALL). We estimated the positive and negative predictive values of the GHRH- arginine test among patients as well as a number of individual characteristics and therapy- related factors during both the GHRH- arginine test and ITT. Design: Forty- three young adults, treated for childhood ALL with 18 - 30 Gy CRT and chemotherapy, were studied, and comparison was made with matched controls. Results and Conclusions: We evaluated four different cutoff levels for GHD in the GHRH- arginine test: 5, 7.5, 9, and 16.5 mu g/ liter. Using 7.5 mu g/liter as the cutoff yielded high specificity ( 94%), but at the same time the sensitivity was only 66%, which leads to a low negative predictive value ( 27%). In contrast, a failed GH response to the GHRH- arginine test accurately reflects the presence of radiationinduced GHD, illustrated by a high positive predictive value ( 95% at 7.5 mu g/ liter). Only age at CRT and body mass index remained significant predictors of the peak GH during the GHRH- arginine test. Because a high proportion of GHD patients show a normal response to the GHRH- arginine test, it cannot be used reliably to exclude GHD in these patients. Complementary ITT is also warranted to confirm GHD in obese patients.
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| 14. |
- Borghammar, Camilla, et al.
(författare)
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Non-functioning pituitary microadenoma in children and adolescents : Is follow-up with diagnostic imaging necessary?
- 2023
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Ingår i: Endocrine. - : Springer Science and Business Media LLC. - 1355-008X .- 1559-0100. ; 79, s. 152-160
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: No consensus exists regarding follow-up recommendations for suspected pituitary microadenoma in children. To address this knowledge gap, we investigated the growth potential of pituitary solid and cystic lesions <10 mm in children and evaluated the accuracy of magnetic resonance imaging (MRI) measurements.METHODS: The children included were <18 years at first pituitary MRI and radiologically diagnosed with a non-functioning microadenoma or cyst <10 mm. Lesion size at first and latest MRI as well as all individual MRI examinations were re-evaluated.RESULTS: In total, 74 children, median age 12 years (range 3-17), had a non-functioning microadenoma, probable microadenoma, or cyst. Of these, 55 underwent repeated MRI (median 3, range 2-7) with a median follow-up of 37 months (range 4-189). None of the pituitary lesions without hormonal disturbances increased significantly during follow-up. Two radiologists agreed that no lesion could be identified in 38/269 (14%) MRI examinations, and in 51/231 (22%) they disagreed about lesion location. In 34/460 (7%) MRI measurements size differed >2 mm, which had been considered significant progression.CONCLUSION: Non-functioning pituitary microadenoma in children has small size variations, often below the spatial resolution of the scanners. We suggest lesions <4 mm only for clinical follow-up, lesions 4-6 mm for MRI after 2 years and ≥7 mm MRI after 1 and 3 years, with clinical follow-up in between. If no progression, further MRI should only be performed after new clinical symptoms or hormonal disturbances.
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| 15. |
- Bülow, Birgitta, et al.
(författare)
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High incidence of mental disorders, reduced mental well-being and cognitive function in hypopituitary women with GH deficiency treated for pituitary disease
- 2002
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Ingår i: Clinical Endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 56:2, s. 183-193
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Previous studies have shown possible neuroendocrine effects of GH. In the present study we investigated the incidence of mental disorders and the prevalence of mental distress and cognitive dysfunction in hypopituitary women with untreated GH deficiency compared to population-based controls.DESIGN AND PATIENTS: Thirty-three hypopituitary women with a median age of 64 years (range 39--77 years) were investigated cross-sectionally, without any change in hormone substitutions. Twenty-nine of the patients had been operated for a pituitary tumour, 25 had received radiotherapy and 15 had visual dysfunction. The patients were with a very high probability GH deficient, as 29 had subnormal IGF-I levels and the other four were GH deficient as assessed by an insulin tolerance test. The patients were compared with 33 controls matched for sex, age, smoking habits, educational level and residence.MEASUREMENTS: The incidence of mental disorders was calculated from the date of diagnosed hypopituitarism to the time of the present investigation. Mental well-being was assessed by three self-rating questionnaires: the Symptom Checklist-90 (SCL-90), the Interview Schedule for Social Interaction (ISSI) and the social network concept. The subjects were examined with neuropsychological tests of vocabulary (SRB:1 vocabulary test), perceptual speed (WAIS-R Digit Symbol), spatial ability (WAIS-R Block Design), verbal memory (Cronholm--Molander verbal memory test), spatial learning (Austin Maze Test) and reaction time (APT Two-way Reaction Time and APT Inhibition).RESULTS: The hypopituitary women had a higher incidence of mental disorders than the controls; Incidence Rate Ratio 4.5 (95% CI 1.0--21). The Global Severity Index, i.e. the average score of all 90 questions of the SCL-90, was higher in patients (P = 0.001), and the patients had significantly more symptoms of somatization, anxiety, depression, obsession--compulsion, hostility--irritability, phobic and psychotic symptoms (all P less-than-or-equal 0.04). Moreover, 14 patients compared to four controls were classified as possible cases of mental distress according to the SCL-90 (P = 0.006). The patients experienced lower availability of both social attachment (P = 0.02) and integration (P = 0.001), but there were no group differences in the adequacy of these dimensions or in emotional support. The patients had lower scores in four of seven neuropsychological tests (all P less-than-or-equal 0.04).CONCLUSIONS: The hypopituitary women had a higher incidence of mental disorders, more symptoms of mental distress and increased prevalence of cognitive dysfunction. The impaired results in the patients could possibly be explained by several factors, such as transfrontal surgery, radiotherapy, visual dysfunction and unphysiological hormone substitution. Moreover, it is probable that GH deficiency contributed, but placebo-controlled double-blind studies are warranted to investigate whether the psychological dysfunction is reversible on GH substitution.
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| 16. |
- Bulow, B., et al.
(författare)
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Increased leptin and tumour necrosis factor alpha per unit fat mass in hypopituitary women without growth hormone treatment
- 2001
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 1479-683X .- 0804-4643. ; 145:6, s. 737-742
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Tidskriftsartikel (refereegranskat)abstract
- Background: The adipocyte products, leptin and tumour necrosis factor (TNF)alpha are associated with atherosclerotic diseases and may be factors contributing to the enhanced cardiovascular risk in hypopituitary patients with growth hormone (GH) deficiency. Objective: To investigate whether leptin and TNF alpha are increased in a group of hypopituitary women previously found to have increased cardiovascular morbidity, and to compare them with matched individuals of the same sex and age and with similar body composition. Design and Patients: Thirty-three GH-deficient women with a median age of 64 years (range 39-77 years) were investigated cross-sectionally. The patients were compared with 33 controls matched for sex, age, smoking habits, educational level and residence. Methods: Body composition was measured by bioimpedance analysis. Fasting concentrations of leptin, TNF alpha and insulin were analysed in patients and controls. Results: There was no significant difference in body mass index or fat mass between patients and controls (both P greater than or equal to 0.4). Serum leptin did not differ significantly between patients and controls. However, when serum leptin concentrations were expressed per kilogram fat mass, the patients had significantly greater concentrations (P = 0.01). Serum TNF alpha and TNF alpha per kilogram fat mass were also significantly greater in the patients (both P = 0.001). In contrast, serum insulin did not differ significantly between patients and controls. In the patients, serum leptin concentrations correlated positively with kilogram fat mass (r = 0.54, P = 0.002). Leptin concentration per kilogram fat mass was positively correlated with insulin (r = 0.40. P = 0.03). Conclusions: In contrast to serum concentrations of TNF alpha. serum leptin did not differ from that in controls, implying that leptin is not a major contributor to the previously found increase in cardiovascular morbidity in the hypopituitary women investigated. However, the patients had increased leptin concentrations per unit fat mass, indicating an altered adipocyte secretory function in this group.
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| 17. |
- Bülow, Birgitta, et al.
(författare)
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Individualized low-dose growth hormone (GH) treatment in GH-deficient adults with childhood-onset disease: metabolic effects during fasting and hypoglycemia
- 1999
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Ingår i: Metabolism, Clinical and Experimental. - 1532-8600. ; 48:8, s. 10-1003
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Tidskriftsartikel (refereegranskat)abstract
- Growth hormone (GH) has insulin-antagonistic effects, and GH secretion is augmented during fasting and hypoglycemia. In the present study, 10 patients aged 21 to 28 years with childhood-onset GH deficiency (GHD) were studied during a 24-hour fast and a hypoglycemic glucose clamp before and after 9 months of GH replacement. During the 24-hour fast, blood glucose, serum insulin, and serum free fatty acid (FFA) levels were measured. In the hypoglycemic clamp, the counterregulatory hormones (plasma catecholamines, serum glucagon, and serum cortisol), serum insulin-like growth factor (IGF) binding protein-1 (IGFBP-1), serum FFA, and glucose uptake were measured. The GH dose was adjusted to the response of serum IGF-I, and the median GH dose was 0.14 IU/kg/wk (range, 0.08 to 0.19). At the end of the study, serum IGF-I levels were normalized in all but one patient, in whom serum IGF-I was above the normal range. Nine months of GH treatment did not cause any significant changes in the blood glucose level, insulin to glucose ratio, or serum FFA level during the 24-hour fast, and none of the patients experienced hypoglycemia either before or after GH treatment. However, GH therapy resulted in increased insulin resistance during hypoglycemia, without changes in the counterregulatory hormonal responses, serum IGFBP-1, or serum FFA.
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| 18. |
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| 19. |
- Bülow, B, et al.
(författare)
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The gender differences in growth hormone-binding protein and leptin persist in 80-year-old men and women and is not caused by sex hormones.
- 2003
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Ingår i: Clinical Endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 59:4, s. 6-482
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Tidskriftsartikel (refereegranskat)abstract
- objective Leptin and growth hormone-binding protein (GHBP) both show gender differences that might be explained by sex hormones. To study the potential relevance of oestradiol and testosterone, we have examined 80-year-old subjects in whom oestradiol is higher in men than in women. The interrelationships between leptin, insulin, GHBP and fat mass in this age group were also investigated. design and subjects Ninety-four subjects (55 females and 39 males), all 80 years old, were investigated in a community-based study. None of the investigated subjects was being treated for diabetes mellitus and none of the women had oestrogen replacement. methods Levels of testosterone, oestradiol, SHBG, IGF-I, GHBP, glucose, insulin and leptin were analysed. Body composition was measured with bioimpedance analysis (BIA). results As in younger age groups, serum leptin, the ratio leptin/kilogram fat mass and serum GHBP were higher in the women (all, P <= 0·007), although serum oestradiol was higher in the men (P < 0·001). There were no significant associations between sex hormones and leptin or GHBP either in women or in men (all, r < 0·13, P > 0·1). Leptin correlated to kilogram fat mass in both women (r = 0·55, P < 0·001) and men (r = 0·47, P = 0·003), but in contrast, there were no significant correlations between GHBP and fat mass and GHBP and IGF-I, either in women or in men (all, r < 0·24, P > 0·2). Insulin and leptin were significantly associated with GHBP, both in women (r = 0·48, P < 0·001 and r = 0·43, P = 0·001, respectively) and in men (r = 0·40, P = 0·01 and r = 0·34, P = 0·03, respectively). conclusions Although the 80-year-old men had higher oestradiol levels than the women, the women had higher levels of leptin and GHBP. There were no correlations between sex hormones and leptin and GHBP, which indicates that the gender differences are not caused by sex hormones in old age. In contrast to studies in younger subjects, GHBP did not correlate to fat mass in the investigated 80-year-old men and women. In the older subjects investigated, as in younger subjects, GHBP was significantly correlated with leptin and insulin.
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| 20. |
- Child, Christopher J., et al.
(författare)
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Assessment of primary cancers in GH-treated adult hypopituitary patients: an analysis from the Hypopituitary Control and Complications Study
- 2011
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 165:2, s. 217-223
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Tidskriftsartikel (refereegranskat)abstract
- Objective: GH and IGFs have mitogenic properties, causing speculation that GH treatment could increase risk of malignancy. While studies in GH-treated childhood cancer survivors have suggested a slight increase in second neoplasms, studies in GH-treated adults have been equivocal. Design: Incidence of de novo and second cancers was evaluated in 6840 GH-treated and 940 non GH-treated adult patients in the Hypopituitary Control and Complications Study pharmacoepidemiological database. Methods: Evident cancer cases were evaluated in the main analysis, with sensitivity analyses including probable and possible cancers. Standardized incidence ratios (SIRs) for cancers were calculated using Surveillance, Epidemiology and End Results for the USA and GLOBOCAN for all other countries. Results: During the mean follow-up of 3.7 years/GH-treated patient, 142 evident cancer cases were identified, giving an overall SIR of 0.88 (95% confidence interval (CI) 0.74-1.04); 95% CIs included the value of 1.0 for each country examined. The SIR for GH-treated patients from the USA (71 cases) was 0.94 (95% CI 0.73-1.18), and for non GH-treated patients from the USA (27 cases) was 1.16 (95% CI 0.76-1.69). For GH-treated patients from the USA aged < 35 years, the SIR (six cases) was 3.79 (1.39-8.26), with SIR not elevated for all other age categories; SIR for patients from the USA with childhood onset (CO) GH deficiency (GHD) was 2.74 (95% CI 1.18-5.41). The SIR for colorectal cancer in GH-treated patients (11 cases) was 0.60 (95% CI 0.30-1.08). Conclusions: With relatively short follow-up, the overall primary cancer risk in 6840 patients receiving GH as adults was not increased. Elevated SIRs were found for subgroups in the USA cohort defined by age < 35 years or CO GHD.
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| 21. |
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| 22. |
- Elfving, Maria, et al.
(författare)
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Ectopic recurrence of a craniopharyngioma in a 15-year-old girl 9 years after surgery and conventional radiotherapy: case report.
- 2011
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Ingår i: Child's Nervous System. - : Springer Science and Business Media LLC. - 1433-0350 .- 0256-7040. ; 27, s. 845-851
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Tidskriftsartikel (refereegranskat)abstract
- This 15-year-old girl was operated due to an ectopic recurrence of a craniopharyngioma along the previous surgical route. She presented with a sellar craniopharyngioma at the age of 4 years and underwent a right subfrontal craniotomy. Two and a half years later she had a local recurrence in the sella that was resected along the same surgical route. Postoperative cranial radiotherapy was administered with 50 Gy divided into 28 fractions. Nine years later, magnetic resonance imaging (MRI) revealed a local recurrence within the sella together with a supraorbital cystic mass. Both tumors were surgically removed. Microscopic examination revealed recurrence of an adamantinous craniopharyngioma at both localisations. Histopathological preparations showed a higher MIB-1 index at the simultaneous recurrences in the sella and in the frontal lobe and also an elevated focal p53 expression, compared to previous operations, suggesting a transformation to a more aggressive tumor. This is the first case report of ectopic recurrence in a child that had received conventional radiotherapy of 50 Gy to the sella. Careful intra-operative procedure is probably crucial for preventing ectopic recurrences. The future will reveal if the transsphenoidal surgical route will put an end to ectopic tumor recurrence in patients with a craniopharyngioma.
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| 23. |
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| 24. |
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| 25. |
- Erfurth, Eva Marie
(författare)
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Diagnosis, Background, and Treatment of Hypothalamic Damage in Craniopharyngioma
- 2020
-
Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 110:9-10, s. 767-779
-
Forskningsöversikt (refereegranskat)abstract
- Craniopharyngiomas (CP) are rare brain tumors managed primarily with surgery and radiotherapy. There are 2 phenotypes of CP, i.e., one with a rather good outcome without hypothalamic damage and another with hypothalamic damage. With hypothalamic damage, progressive disease with recurrent operations and additional cranial radiotherapy often result in hypothalamic obesity, an affected psychosocial life, and cognitive dysfunction. The morbidity and mortality are increased for particularly cerebrovascular diseases. Preoperative hypothalamic involvement to predict hypothalamic damage is important for decision making for hypothalamus-sparing surgery. Also a postoperative hypothalamic damage evaluation with the use of hypothalamus volume measurement can predict hypothalamic obesity, which is important for early treatment options. The morbidity of CP includes cognitive dysfunction with attention deficits and impaired episodic memory and processing speed. Again patients with hypothalamic damage are more affected. Treatment options of hypothalamic obesity in the chronic phase are scarce and not convincingly successful. The most optimal situation is to try to hinder or stop the evolution of hypothalamic obesity. Prevention of hypothalamic damage is recommended, with special regard to hypothalamus-sparing therapeutic approaches that respect the integrity of essential nuclei located in both the medial and the posterior hypothalamic areas.
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| 26. |
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| 27. |
- Erfurth, Eva Marie
(författare)
-
Endocrine aspects and sequel in patients with craniopharyngioma
- 2015
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Ingår i: Journal of Pediatric Endocrinology & Metabolism. - : Walter de Gruyter GmbH. - 2191-0251 .- 0334-018X. ; 28:1-2, s. 19-26
-
Forskningsöversikt (refereegranskat)abstract
- A craniopharyngioma (CP) is an embryonic malformation of the sellar and parasellar region. The annual incidence is 0.5-2.0 cases/million per year and approximately 60% of CP is seen in adulthood. The therapy of choice is surgery, followed by cranial radiotherapy in about half of the patients. Typical initial manifestations at diagnosis in children are symptoms of elevated intracranial pressure, visual disturbances and hypopituitarism. CPs have the highest mortality of all pituitary tumours. The standardised overall mortality rate varies from 2.88 to 9.28 in cohort studies. Adults with CP have a 3-19-fold higher cardiovascular mortality in comparison to the general population. Women with CP have an even higher risk. The long-term morbidity is substantial with hypopituitarism, increased cardiovascular risk, hypothalamic damage, visual and neurological deficits, reduced bone health and reduction in quality of life and cognitive function.
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| 28. |
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| 29. |
- Erfurth, Eva Marie, et al.
(författare)
-
Incidence of a second tumor in hypopituitary patients operated for pituitary tumors
- 2001
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - 1945-7197. ; 86:2, s. 659-662
-
Tidskriftsartikel (refereegranskat)abstract
- Recently, an association between increased blood levels of insulin-like growth factor I (IGF-I) and increased risks of prostate, breast, lung, and colorectal cancers has been suggested. As today adults with GH deficiency are subjected to GH substitution, there is a pressing need for baseline tumor incidence data. The aim of the study was to assess the risk for a second tumor in a cohort of 328 patients with hypopituitarism treated for a pituitary tumor from 1958-1992. The patients were receiving conventional hormone treatment, but without GH substitution. The overall tumor incidence [standardized incidence ratio (SIR)] was lower than expected (0.85), but the 95% confidence interval (CI) did not exclude unity (0.59-1.21). Only two prostate cancers occurred (SIR, 0.34; 95% CI, 0.04-1.24). Two brain tumors (SIR, 1.96; 95% CI, 0.24-7.08) and two endocrine tumors (part of multiple endocrine neoplasm syndromes; SIR, 4.00; 95% CI, 0.48-14.5) had occurred. When excluding brain and endocrine tumors, the overall SIR decreased to 0.77, but did still not differ significantly from unity (0.52-1.13). Thus, a tendency for a decreased overall tumor risk, although not statistically significant, was noted, especially when excluding brain and endocrine tumors. This tendency was more emphasized for prostate cancer, but low numbers hamper a firm conclusion. These results may serve as a baseline for tumor risk among adult patients with pituitary insufficiency supplemented with GH.
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| 30. |
- Erfurth, Eva Marie, et al.
(författare)
-
Is growth hormone deficiency contributing to heart failure in patients with beta-thalassemia major?
- 2004
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 1479-683X .- 0804-4643. ; 151:2, s. 161-166
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Tidskriftsartikel (refereegranskat)abstract
- A 21-year-old woman with beta-thalassemia major (beta-TM) and GH deficiency developed end-stage heart failure, New York Heart Association (NYHA) functional class IV, within 3 months after withdrawal of recombinant human growth hormone (GH). A myocardial biopsy excluded myocarditis and showed moderate iron deposit in the heart. Before her admission, intensified treatments with digoxin, angiotensin-converting enzyme inhibitor, diuretics and extra chelation therapy (desferrioxamine (DFO)) had not improved her progressive heart failure. At admission, GH was reinstituted together with intensified treatment of cardiac drugs and low doses of DFO, and her heart failure reversed. Four months later, NYHA functional class II was reached and within 1 year her cardiac function was normalised. We suggest that GH deficiency due to iron-induced damage to the hypothalamic-pituitary axis can contribute to heart failure in adult patients with beta-TM.
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| 31. |
- Erfurth, Eva Marie, et al.
(författare)
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Is there an increase in second brain tumours after surgery and irradiation for a pituitary tumour?
- 2001
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Ingår i: Clinical Endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 55:5, s. 613-616
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Tidskriftsartikel (refereegranskat)abstract
- Objective To assess the incidence of second brain tumours in patients operated and irradiated for pituitary tumours. Design and patients The study base consisted of a consecutive series of 325 patients operated and irradiated for pituitary tumours, excluding patients with acromegaly and Cushing's disease. Comparison was made with the general population from the same catchment area as the patients. The follow-up period started in 1958 and on an individual basis patients were followed from the onset of postoperative irradiation until December 1995, or until date of death, emigration or a second brain tumour diagnosis, whichever occurred first. Results Three brain tumours (two astrocytomas and one meningioma) were observed, compared with 1.13 expected (standardized incidence ratios (SIR) 2.7; 95% confidence interval (CI) 0.6-7.8). Conclusion The present study gives no firm support for an increased incidence of a second brain tumour in patients operated and irradiated for pituitary tumours. A crude meta-analysis of the present and previously published cohort studies of patients with irradiated pituitary tumours gives an SIR of 6.1 (95% Cl 3.16-10.69). Thus, the results of the meta-analysis are in favour of an increased risk for second brain tumours. A genetic trait that predisposes to both pituitary tumours and brain tumours is an alternative causal factor. There is no definite proof that cranial irradiation per se is the causal factor. This question cannot be fully answered until sufficient cohort studies of nonirradiated pituitary tumour patients have been carried out.
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| 32. |
- Erfurth, Eva Marie, et al.
(författare)
-
Mortality and morbidity in adult craniopharyngioma.
- 2013
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Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1573-7403 .- 1386-341X. ; 16, s. 46-55
-
Tidskriftsartikel (refereegranskat)abstract
- A craniopharyngioma (CP) is an embryonic malformation of the sellar and parasellar region. The annual incidence is 0.5-2.0 cases/million/year and approximately 60 % of CP are seen in adulthood. Craniopharyngiomas have the highest mortality of all pituitary tumors. Typical initial manifestations at diagnosis in adults are visual disturbances, hypopituitarism and symptoms of elevated intracranial pressure. The long-term morbidity is substantial with hypopituitarism, increased cardiovascular risk, hypothalamic damage, visual and neurological deficits, reduced bone health, and reduction in quality of life and cognitive function. Therapy of choice is surgery, followed by cranial radiotherapy in about half of the patients. The standardised overall mortality rate varies 2.88-9.28 in cohort studies. Patients with CP have a 3-19 fold higher cardiovascular mortality in comparison to the general population. Women with CP have an even higher risk.
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| 33. |
- Erfurth, Eva Marie
(författare)
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Obesity and metabolic disturbances in adamantinomatous craniopharyngioma patients
- 2017
-
Ingår i: Basic Research and Clinical Aspects of Adamantinomatous Craniopharyngioma. - Cham : Springer International Publishing. - 9783319518909 - 9783319518886 ; , s. 85-99
-
Bokkapitel (refereegranskat)abstract
- An adamantinous craniopharyngioma (CP) is rare benign pituitary tumour often growing invasively and thereby affecting the hypothalamus. The recurrence rate in CP is high and therapy of choice is surgery, followed by cranial radiotherapy (CRT) in about half of the patients. Patients with CP have a 3-19 fold higher cardiovascular mortality in comparison to the general population. The majority of patients have an extended hypopituitarism that needs balanced hormone supplementation. About half of the patient population suffer from hypothalamic damage due to the tumour or operation. These patients suffer from hypothalamic obesity together with increased vascular morbidity and compromised bone health, thirst disorders as well as somnolence and sleep apnea. Cardiovascular risk factors need up front therapy. There is a need for centralising this rare aggressive and difficult tumour to only a few centres and that it will be managed by a multidisciplinary team with experienced neurosurgeons, endocrinologists, neurooncologists, neuroradiologists, and neuroopthamologists for a better prognosis.
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| 34. |
- Erfurth, Eva Marie, et al.
(författare)
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Pituitary disease mortality: is it fiction?
- 2013
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Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1573-7403 .- 1386-341X. ; 16:3, s. 402-412
-
Tidskriftsartikel (refereegranskat)abstract
- During the last 20 years a tremendous improvement in the care of patients with pituitary tumors and of hypopituitarism has been achieved. If we resolve most of the possible causes of the increased cardiovascular disease and stroke mortality a normal survival is expected in these patients. Recently, a large population based study showed a decline in the risk of non-fatal stroke and of non-fatal cardiac events in GH deficient patients. This improvement was achieved by complete hormone replacement, including long term GH replacement, together with prescription of cardio protective drugs. If we follow the latest achievements in pituitary imaging, surgery techniques, hormone substitutions, cardio protective medications, we would expect a normal longevity in these patients. This review will focus on; (1) pituitary insufficiencies and hormone substitutions, (2) modes of cranial radiotherapy, and (3) new techniques in the surgery of a pituitary adenoma.
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| 35. |
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| 36. |
- Erfurth, Eva Marie
(författare)
-
Uncertainties in endocrine substitution therapy for central endocrine insufficiencies: growth hormone deficiency.
- 2014
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Ingår i: Handbook of Clinical Neurology. - 0072-9752. ; 124, s. 407-416
-
Tidskriftsartikel (refereegranskat)abstract
- The growth hormone deficiency (GHD) syndrome is associated with several metabolic abnormalities and it has been postulated that the increased cardiovascular disease (CVD) morbidity and mortality in GHD patients may be related to the missing metabolic effects of GH. Many CVD risk factors show improvements after GH therapy. Reduced bone mineral density (BMD) has been recorded both in patients with isolated GHD and in those with multiple pituitary deficiencies, indicating that GHD per se is responsible for the low BMD in both types of patients. These matters are, however, more complicated, as hypopituitary patients with GHD may have different phenotypes due to differences in underlying diagnoses. These phenotypes may not be clear-cut in individual patients. Moreover, patients may transit between different phenotypes over time due to extension of the pathology in the pituitary and/or the consequences of the treatment (surgery and/or radiotherapy). Three different phenotypes of hypopituitary patients will be discussed, with a focus on CVD risk and bone health: (1) patients with isolated GHD, e.g. due to prophylactic cranial radiotherapy for lymphoblastic leukaemia in childhood; (2) patients with GHD and multiple hormone deficiencies due to pituitary macroadenomas treated by surgery; (3) patients with GHD caused by craniopharyngiomas with multiple hormone deficiencies and hypothalamic involvement, where hypothalamic damage frequently dominates the positive metabolic effects of GH therapy. These phenotypes illustrate the differential impact of various pituitary pathologies on the phenotype of patients with GHD.
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| 37. |
- Erfurth, Eva Marie
(författare)
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Update in Mortality in GH treated patients.
- 2013
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 98:11, s. 4219-4226
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Tidskriftsartikel (refereegranskat)abstract
- During GH therapy for 2.3-9.6 years a male adult onset (AO) GH deficient (GHD) patient with a diagnosis of a non-functioning adenoma, have no increased all-cause mortality. However, women with AO GHD are still at a slightly higher risk. This general improvement in mortality is due to; more contemporary regiment of cardiovascular drugs, a refinement of surgical procedures, besides GH therapy improved hormone replacement regimens with lowered glucocorticoid replacement, and updated approaches of sex steroids for women, and less use of cranial radiotherapy. The underlying disease is the most important predictor for mortality: e.g. a craniopharyngioma, malignant causes of hypopituitarism, previous Cushing's disease, presence of diabetes insipidus/aggressive tumors. The main cause of increased mortality was cerebrovascular diseases and of infectious/repiratory diseases in ACTH deficient patients. Further, there was a significant impact of young age at disease onset and of death from secondary brain tumors, with a higher risk after cranial radiotherapy.Four cohorts of GH treated childhood onset (CO) GHD patients have been published. Two of them included only patients with idiopathic isolated GH deficiency (IGHD), neurosecretory dysfunction, idiopathic short stature (ISS) or born short for gestational age (SGA). Increased mortality in circulatory disorders, ill defined diseases and bone cancer was recorded in one, but not in the other smaller study, where suicide and accidents caused the majority of deaths. A third CO GHD cohort included patients with a background of malignant tumors, craniopharyngioma, pituitary adenomas, pituitary aplasia/hypoplasia, and trauma. An increase of all cause mortality was recorded in both males and females. The fourth cohort included IGHD and ISS (60%), but also diagnosis e.g. chronic renal failure, and Turner's syndrome. In these latter studies an underlying serious condition was the most important factor for death, with CNS tumors (recurrent or new tumor) being the leading cause of mortality.
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| 38. |
- Fjalldal, Sigridur, et al.
(författare)
-
Brain white matter lesions are associated with reduced hypothalamic volume and cranial radiotherapy in childhood-onset craniopharyngioma
- 2021
-
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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| 39. |
- 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
-
Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Endocrine Society. - 0021-972X .- 1945-7197. ; 98:8, s. 3253-3262
-
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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| 40. |
- Follin, Cecilia, et al.
(författare)
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Associations between Metabolic Risk Factors and the Hypothalamic Volume in Childhood Leukemia Survivors Treated with Cranial Radiotherapy.
- 2016
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Metabolic complications are prevalent in individuals treated with cranial radiotherapy (CRT) for childhood acute lymphoblastic leukemia (ALL). The hypothalamus is a master regulator of endocrine and metabolic control. The aim of this study was to investigate whether the hypothalamic volume would be associated to metabolic parameters in ALL survivors. Thirty-eight (21 women) survivors participated in this study 34 years after diagnosis and with a median age of 38 (27-46) years. All were treated with a median CRT dose of 24 Gy and 11 years (3-13) of complete hormone supplementation. Comparisons were made to 31 matched controls. We performed analyses of fat mass, fat free mass, plasma (p)-glucose, p-insulin, Homa-Index (a measure of insulin resistance), serum (s)-leptin, s-ghrelin and of the hypothalamic volume in scans obtained by magnetic resonance imaging (MRI) at 3 Tesla. Serum leptin/kg fat mass (r = -0.4, P = 0.04) and fat mass (r = -0.4, P = 0.01) were negatively correlated with the HT volume among ALL survivors, but not among controls. We also detected significantly higher BMI, waist, fat mass, p-insulin, Homa-Index, leptin/kg fat mass and s-ghrelin and significantly lower fat free mass specifically among female ALL survivors (all P<0.01). Interestingly, s-ghrelin levels increased with time since diagnosis and with low age at diagnosis for childhood ALL. Our results showed that leptin/kg fat mass and fat mass were associated with a reduced HT volume 34 years after ALL diagnosis and that women treated with CRT after ALL are at high risk of metabolic abnormalities. Taken together our data suggest that the hypothalamus is involved in the metabolic consequences after CRT in ALL survivors.
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| 41. |
- Follin, Cecilia, et al.
(författare)
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Bone loss after childhood acute lymphoblastic leukaemia: an observational study with and without GH therapy
- 2011
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 164:5, s. 695-703
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Bone mineral density (BMD) in survivors of acute lymphoblastic leukaemia (ALL) seems to vary with time, type of treatments and GH status. We aimed to evaluate BMD in ALL patients with growth hormone deficiency (GHD), with and without GH therapy. DESIGN: Case-control study. METHODS: 44 (21 women) GHD patients (median 25 years), treated with cranial radiotherapy (18-24 Gy) and chemotherapy and matched population controls were examined for BMD with DXA (Dual-energy X-ray absorptiometry). Two subgroups; with (0.5 mg/day) (n=16) and without GH therapy (n=13), and matched controls, were followed for 5 and 8 years, respectively. RESULTS: At baseline, no significant differences in BMD or Z-scores at femoral neck and L2-L4 were recorded (all P > 0.3). After another 8 years with GHD, Z-scores at femoral neck had decreased significantly compared to baseline (0.0 to -0.5; P<0.03), and became lower at femoral neck (P=0.05), and at L2-L4 (P<0.03), compared to controls. After 5 years of GH therapy only female ALL patients had a significantly lower femoral neck Z-scores (P=0.03). The female ALL patients reached an IGF-I level of -0.7 SD and in men the level was +0.05 SD. CONCLUSIONS: On average 25 years since diagnosis GH deficient ALL patients experienced a significant decrease in Z-scores at femoral neck and if Z-scores continuous to decrease there is a premature risk for osteoporosis. GH therapy was not shown to have a clear beneficial effect on BMD. Whether higher GH doses, particularly in women, will improve Z-scores needs further investigation.
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| 42. |
- Follin, Cecilia, et al.
(författare)
-
Cardiovascular Risk, Cardiac Function, Physical Activity, and Quality of Life with and without Long-Term Growth Hormone Therapy in Adult Survivors of Childhood Acute Lymphoblastic Leukemia.
- 2010
-
Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 95, s. 3726-3735
-
Tidskriftsartikel (refereegranskat)abstract
- Context: Long-term data are missing in GH-treated acute lymphoblastic leukemia (ALL) patients. GH therapy may result in poorer outcome regarding cardiovascular (CV) and particularly cardiac effects than in patients with hypothalamic-pituitary disease. Objective: Our objective was to evaluate GH therapy on CV risk, cardiac function, physical activity, and quality of life in ALL patients treated with cranial radiotherapy (18-24 Gy) and chemotherapy (anthracycline dose 120 mg/m(2)). Design and Setting: We conducted a 5- and 8-yr open nonrandomized prospective study in a university hospital clinic. Study Participants: Two groups of GH-deficient ALL patients (aged 25 yr; range 19-32 yr) and matched population controls participated. Interventions: One ALL group (n = 16) received GH for 5 yr, and the other ALL group (n = 13) did not receive GH therapy. Main Outcome Measures: We evaluated the prevalence of CV risk factors and metabolic syndrome (International Diabetes Federation consensus), cardiac function (echocardiography), and quality of life and physical activity questionnaires. Results: In comparison with 8 yr without, 5 yr with GH therapy resulted in significant positive changes in plasma glucose (-0.5 vs. 0.6 mmol/liter, P = 0.002), apolipoprotein B/apolipoprotein A1 ratio (-0.1 vs. 0.0, P = 0.03), and high-density lipoprotein-cholesterol (0.20 vs.-0.01 mmol/liter, P = 0.008) and a significant reduction in the prevalence of metabolic syndrome (P = 0.008). No significant difference in the left-ventricular systolic function or in physical activity and quality of life was recorded before and after 5 or 8 yr, respectively (all P > 0.3). Conclusion: GH therapy reduced the CV risk in this young ALL population but resulted in no clear benefit or deterioration in cardiac function.
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| 43. |
- Follin, Cecilia, et al.
(författare)
-
Hypothalamic dysfunction revealed by magnetic resonance diffusion tensor imaging in childhood leukemia survivors treated with cranial radiotherapy but not in craniopharyngeoma survivors
- 2016
-
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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| 44. |
- Follin, Cecilia, et al.
(författare)
-
Impaired brain metabolism and neurocognitive function in childhood leukemia survivors despite complete hormone supplementation in adulthood
- 2016
-
Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 73, s. 157-165
-
Tidskriftsartikel (refereegranskat)abstract
- Cranial radiotherapy is a known risk factor for neurocognitive impairment in survivors of childhood acute lymphoblastic leukemia (ALL). Understanding the nature of cognitive dysfunction during adulthood in ALL survivors is important as it has an impact on major life situations. Thirty-eight (21 women) ALL survivors were investigated 34 years after diagnosis. Median-age was 38 (27–46) years. All were treated with a CRT dose of 24 Gy and 11 years (3–13) of complete hormone supplementation. Comparisons were made to 29 matched controls. Assessments of magnetic resonance spectroscopy (white and grey matter metabolic alterations), brain volume and neuropsychological tests were performed. ALL survivors demonstrate a generally lower performance in neuropsychological tests. ALL survivors scored lower than controls in vocabulary (p < 0.001), memory (p < 0.001), learning capacity (p < 0.001), spatial ability (p < 0.001), executive functions and attention (p < 0.001) 34 years after ALL treatment. Compared to controls ALL survivors had reduced white matter (WM) (492 vs 536 cm3, p < 0.001) and grey matter (GM) volumes (525 vs 555 cm3, p = 0.001). ALL survivors had lower levels of WM N-acetyl aspartate/creatin (NAA/Cr) (1.48 vs 1.63, p = 0.004), WM NAA + NAAG (N-acetylaspartylglutamate)/Cr (1.61 vs 1.85, p < 0.001) and lower levels of GM NAA/Cr (1.18 vs 1.30, p = 0.001) and GM NAA + NAAG/Cr (1.28 vs 1.34, p = 0.01) compared to controls. ALL survivors had higher levels in WM MI (Myoinositol)/NAA (0.65 vs 0.56, p = 0.01) concentrations compared to controls. There was a significantly negative correlation of years since ALL diagnosis to WM NAA + NAAG/Cr (r = −0.4, p = 0.04) in ALL survivors. The present study shows impaired brain metabolism detected by MRS, reduced brain volumes and neurocognitive impairment in childhood ALL survivors treated with cranial radiotherapy and chemotherapy, despite complete hormone substitution. We also report an impairment of metabolites correlated to time since treatment and a progressive impairment in sustained attention, suggesting an accelerated aging in the irradiated brain. Following these survivors many decades, or throughout life, after treatment with cranial radiotherapy and chemotherapy is highly warranted for a broader understanding of long-term outcome in this patient group.
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| 45. |
- Follin, Cecilia, et al.
(författare)
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Improvement in cardiac systolic function and reduced prevalence of metabolic syndrome after 2 years of GH treatment in GH deficient adult survivors of childhood acute lymphoblastic leukaemia.
- 2006
-
Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 91:5, s. 1872-1875
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Tidskriftsartikel (refereegranskat)abstract
- Context: Survivors of childhood- onset ( CO) acute lymphoblastic leukemia ( ALL) treated with prophylactic cranial radiotherapy often exhibit GH deficiency ( GHD), which is associated with increased prevalence of cardiovascular risk factors and cardiac dysfunction. Objective: The objective of the study was to evaluate the effect of GH replacement on cardiovascular risk factors and cardiac function in former CO ALL patients. Design: Eighteen former CO ALL patients ( aged 19 - 32 yr) treated with cranial radiotherapy ( 18 - 24 Gy) and chemotherapy and with confirmed GHD were studied at baseline and after 12 ( n = 18) and 24 months ( n = 13) of GH treatment ( median 0.5 mg/ d). A group of 18 age- and sex- matched subjects served as controls. Results: After 12 months of GH treatment, a significant decrease in serum leptin ( P = 0.002), leptin per kilogram fat mass ( FM) ( P = 0.01),plasma glucose ( P = 0.004), FM ( P = 0.002), and hip ( P = 0.04) and waist ( P = 0.02) circumference and increased muscle mass ( P = 0.004) were recorded in the patients. Before GH treatment six patients had a metabolic syndrome, but after 12 months only one had it and after 24 months none. After 24 months of GH treatment, an increase in left ventricular mass index ( P = 0.06) and significant improvements in cardiac systolic function, measured as fractional shortening ( P = 0.03) and ejection fraction ( P = 0.03), were recorded. Conclusions: Improvement in cardiac systolic function and reduced prevalence of metabolic syndrome were recorded after 2 yr of GH replacement in former CO ALL patients with GHD. Long- term follow-up is highly warranted.
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| 46. |
- Follin, Cecilia, et al.
(författare)
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Long-Term Effect of Cranial Radiotherapy on Pituitary-Hypothalamus Area in Childhood Acute Lymphoblastic Leukemia Survivors
- 2016
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Ingår i: Current Treatment Options in Oncology. - : Springer Science and Business Media LLC. - 1527-2729 .- 1534-6277. ; 17:9
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Tidskriftsartikel (refereegranskat)abstract
- Survival rates of childhood cancer have improved markedly, and today more than 80 % of those diagnosed with a pediatric malignancy will become 5-year survivors. Nevertheless, survivors exposed to cranial radiotherapy (CRT) are at particularly high risk for long-term morbidity, such as endocrine insufficiencies, metabolic complications, and cardiovascular morbidity. Deficiencies of one or more anterior pituitary hormones have been described following therapeutic CRT for primary brain tumors, nasopharyngeal tumors, and following prophylactic CRT for childhood acute lymphoblastic leukemia (ALL). Studies have consistently shown a strong correlation between the total radiation dose and the development of pituitary deficits. Further, age at treatment and also time since treatment has strong implications on pituitary hormone deficiencies. There is evidence that the hypothalamus is more radiosensitive than the pituitary and is damaged by lower doses of CRT. With doses of CRT 50 Gy) may produce direct anterior pituitary damage, which contributes to multiple pituitary deficiencies. The large group of ALL survivors treated with CRT in the 70–80-ties has now reached adulthood, and these survivors were treated mainly with 24 Gy, and the vast majority of these patients suffer from GHD. Further, after long-term follow-up, insufficiencies in prolactin (PRL) and thyroid stimulating hormone (TSH) have also been reported and a proportion of these patients were also adrenocoticotrophic hormone (ACTH) deficient. CRT to the hypothalamus causes neuroendocrine dysfunction, which means that the choice of GH test is crucial for the diagnosis of GHD.
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| 47. |
- Follin, Cecilia, et al.
(författare)
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Microstructural white matter alterations associated to neurocognitive deficits in childhood leukemia survivors treated with cranial radiotherapy–a diffusional kurtosis study
- 2019
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Ingår i: Acta Oncologica. - 0284-186X. ; 58:7, s. 1021-1028
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cranial radiotherapy (CRT) is a known risk factor for neurocognitive impairment in survivors of childhood acute lymphoblastic leukemia (ALL). Diffusion tensor imaging (DTI) and diffusional kurtosis imaging (DKI) are MRI techniques that quantify microstructural changes in brain white matter (WM) and DKI is regarded as the more sensitive of them. Our aim was to more thoroughly understand the nature of cognitive deficits after cranial radiotherapy (CRT) in adulthood after childhood ALL. Material and methods: Thirty-eight (21 women) ALL survivors, median age 38 (27–46) years, were investigated at median 34 years after diagnosis. All had been treated with a CRT dose of 24 Gy and with 11 years of complete hormone supplementation. DTI and DKI parameters were determined and neurocognitive tests were performed in ALL survivors and 29 matched controls. Results: ALL survivors scored lower than controls in neurocognitive tests of vocabulary, memory, learning capacity, spatial ability, executive functions, and attention (p <.001). The survivors had altered DTI parameters in the fornix, uncinate fasciculus, and ventral cingulum (all p <.05) and altered DKI parameters in the fornix, uncinate fasciculus, and dorsal and ventral cingulum (p <.05). Altered DTI parameters in the fornix were associated with impaired episodic verbal memory (r = −0.40, p <.04). The left and right uncinate fasciculus (r = 0.6, p <.001), (r = −0.5, p <.02) as well as the right ventral cingulum (r = 0.5, p <.007) were associated with impaired episodic visual memory. Altered DKI parameters in the fornix, right uncinate fasciculus (r = 0.3, r = 0.05, p =.02), and ventral cingulum (r = 0.3, p =.02) were associated with impaired results of episodic visual memory. Conclusion: ALL survivors with cognitive deficits demonstrated microstructural damage in several WM tracts that were more extensive with DKI as compared to DTI; this might be a marker of radiation and chemotherapy neurotoxicity underlying cognitive dysfunction.
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| 48. |
- 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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| 49. |
- Follin, Cecilia, et al.
(författare)
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Moderate dose cranial radiotherapy causes central adrenal insufficiency in long-term survivors of childhood leukaemia.
- 2014
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Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1573-7403 .- 1386-341X. ; 17:1, s. 7-12
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Tidskriftsartikel (refereegranskat)abstract
- Acute lymphoblastic leukaemia (ALL) is the most common childhood malignancy. The survival rate in the Scandinavian countries is now around 85 %. ALL patients treated with cranial radiotherapy (CRT) are at risk for growth hormone deficiency (GHD), but little is known about other pituitary insufficiencies, e.g. ACTH. Adult ALL patients (median age at study 25 years), treated with 24 Gy (18-30) of CRT during childhood were investigated. We performed an insulin tolerance test (ITT) to evaluate cortisol secretion. We measured basal serum ACTH and cortisol levels before and after 5 years of GH therapy. 14 out of 37 (38 %) ALL patients had a subnormal cortisol response to an ITT (257-478 nmol/L) while there was no significant difference in basal cortisol levels between 44 patients and controls (P > 0.3). Female, but not male ALL patients had significantly lower ACTH levels compared to controls (P = 0.03). After 5 years of GH therapy only male ALL patients had significantly lowered basal plasma cortisol (P = 0.02). ALL survivors, treated with a moderate dose CRT, have a central adrenal insufficiency 20 years after diagnosis. An increased awareness of the risk for an adrenal insufficiency is of importance and life-long surveillance of the entire hypothalamic-pituitary axis is recommended in these patients.
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| 50. |
- Follin, Cecilia, et al.
(författare)
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Prolactin insufficiency but normal thyroid hormone levels after cranial radiotherapy in long-term survivors of childhood leukaemia.
- 2013
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Ingår i: Clinical Endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 79:1, s. 71-78
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Acute lymphoblastic leukaemia (ALL) patients treated with cranial radiotherapy (CRT) have an increased risk of GH deficiency (GHD). Little is known about insufficiencies of prolactin (PRL) and TSH, but also lactation failure has been reported in this population. OBJECTIVE: To study the long-term outcome of CRT on PRL and thyroid hormone levels in GHD ALL patients, and the prevalence of lactation failure. DESIGN: CASE-CONTROL STUDY: PATIENTS: We examined 40 GHD and 4 GH insufficient ALL patients, in median 20 years (range 8-27) after ALL diagnosis and 44 matched population controls. MEASUREMENTS: PRL secretion (area under the curve; AUC) after GHRH-arginine test in all patients and matched controls, and PRL and TSH AUC after a TRH test in 13 patients and 13 controls. And basal PRL and thyroid hormone levels after 5 years with GH therapy and 8 years without GH therapy. RESULTS: Compared to controls ALL patients had significantly lower basal and AUC PRL after GHRH-Arginine (P = 0.03, P = 0.02), and AUC PRL after TRH (P = 0.001). After 5 and 8 years, PRL levels decreased further (P = 0.01, P = 0.03), but thyroid hormones remained normal at baseline and at follow up. PRL insufficiency was significantly associated with increased levels of BMI and insulin. Six out of seven pregnant ALL women reported lactation failure. CONCLUSIONS: Long-term ALL survivors treated with CRT have GHD and PRL insufficiency, and a high prevalence of lactation failure, but thyroid hormones remained normal. PRL insufficiency was associated with cardiovascular risk. © 2012 Blackwell Publishing Ltd.
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