| 11. |
- Follin, Cecilia, et al.
(author)
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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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In: Current Treatment Options in Oncology. - : Springer Science and Business Media LLC. - 1527-2729 .- 1534-6277. ; 17:9
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Journal article (peer-reviewed)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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| 12. |
- Follin, Cecilia, et al.
(author)
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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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In: Acta Oncologica. - 0284-186X. ; 58:7, s. 1021-1028
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Journal article (peer-reviewed)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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| 13. |
- Follin, Cecilia, et al.
(author)
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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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In: Clinical Endocrinology. - : Wiley. - 0300-0664. ; 87:4, s. 359-366
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Journal article (peer-reviewed)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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| 14. |
- Follin, Cecilia, et al.
(author)
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Moderate dose cranial radiotherapy causes central adrenal insufficiency in long-term survivors of childhood leukaemia.
- 2014
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In: Pituitary. - : Springer Science and Business Media LLC. - 1573-7403 .- 1386-341X. ; 17:1, s. 7-12
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Journal article (peer-reviewed)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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| 15. |
- Follin, Cecilia, et al.
(author)
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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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In: Clinical Endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 79:1, s. 71-78
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Journal article (peer-reviewed)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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| 16. |
- Holmer, Helene, et al.
(author)
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Hypothalamic involvement and insufficient sex steroid supplementation are associated with low bone mineral density in women with childhood onset craniopharyngioma
- 2011
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In: European Journal of Endocrinology. - : Bio Scientifica. - 0804-4643 .- 1479-683X. ; 165:1, s. 25-31
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Journal article (peer-reviewed)abstract
- Context: Data on bone mineral density (BMD) are lacking in adults with childhood onset (CO)-craniopharyngioma (CP) with hypothalamic damage from the tumor. In patients with CO GH deficiency, BMD increases during GH treatment. Objective: The aims were to evaluate BMD in adults with CO-CPs on complete hormone replacement, including long-term GH and to evaluate the impact of hypothalamic damage on these measures. Design and participants: BMD (dual-energy X-ray absorptiometry), markers of bone turn over, physical activity and calcium intake were assessed in 39 CO-CP adults (20 women), with a median age of 28 (17-57) years, in comparison with matched population controls. Results: Late puberty induction was recorded in both genders, but reduced androgen levels in females only. Only CP women had lower BMD (PZ0.03) at L2-L4, and reduced Z-scores at femoral neck (P=0.004) and L2-L4 (P=0.004). Both genders had increased serum leptin levels (P=0.001), which significantly correlated negatively with BMD at L2-L4 (P=0.003; r=-0.5) and 45% of CP women had Z-score levels less than= -2.0 S.D. Furthermore, 75% of those with a Z-score less than= -2.0 S.D. had hypothalamic involvement by the tumor. Calcium intake (P=0.008) and physical activity (P=0.007) levels were reduced in CP men only. Levels of ostecalcin and crossLaps were increased in CP men only. Conclusions: Despite continuous GH therapy, low BMD was recorded in CO-CP females. Insufficient estrogen and androgen supplementation during adolescence was the main cause, but hypothalamic involvement with consequent leptin resistance was also strongly associated with low BMD in both genders.
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| 17. |
- Jørgensen, Jens Otto Lunde, et al.
(author)
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Key Device Attributes for Injectable Somatostatin Receptor Ligand Therapy in Acromegaly and Neuroendocrine Tumours
- 2023
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In: Advances in Therapy. - 0741-238X. ; 40:10, s. 4675-4688
-
Journal article (peer-reviewed)abstract
- Introduction: People living with acromegaly and neuroendocrine tumours (NETs) may be treated with injectable somatostatin receptor ligands (SRLs), administered by either a caregiver or as self-injection via a proprietary or generic device. Injection device attributes that contribute to ease of use and storage, minimise preparation requirements, and reduce injection pain are associated with improved adherence and more favourable therapeutic outcomes. The aim of this study was to assess current opinion surrounding favourable SRL device attributes for people living with acromegaly and NETs as well as that of their caregivers. Methods: Participants (healthcare professionals [HCPs] and patients/non-HCP caregivers) from 11 countries were invited to answer survey questions related to their demographic, experience, and preferences as they relate to the real-world use of injectable SRL devices. Questions were developed based on review of available literature and meetings with a Scientific Committee. Results: Device attributes preferred by the patient/non-HCP caregiver group (n = 211) included confidence that the correct drug amount is delivered (76%), quick administration with minimal pain/discomfort (68%), and device safety (needle-safety and low risk of contamination; 53%). Device attributes preferred by HCPs (n = 52) were quick administration with minimal pain/discomfort (69%), correct use is easy to learn, confidence in handling the device (63%), and confidence that the correct drug amount is delivered (62%). Conclusion: The results identified key features of injection devices for SRL therapy which merit consideration for optimal management and underscore the importance of patient partnership in treatment decisions.
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| 18. |
- Linge, Helena M., et al.
(author)
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Mixed methods assessment of impact on health awareness in adult childhood cancer survivors after viewing their personalized digital treatment summary and follow-up recommendations
- 2021
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In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 21:1
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Journal article (peer-reviewed)abstract
- Background: The survival rate after childhood cancer has improved to 80%. The majority of childhood cancer survivors (CCS) will experience late complications which require follow up care, including access to their individual cancer treatment summary. The need to understand CCS needs and preferences in terms of ways to receive information e.g. digitally, becomes important. This study aims to through a mixed methods approach a) examine how CCS’ health awareness was impacted by viewing their personalized digital treatment summary and follow-up recommendations, b) explore E health literacy, and c) determine self-reported survivorship experiences and health care usage. Methods: Survivors with a recent visit to the Late effects clinic were eligible for the study (n = 70). A representative sample of primary diagnoses were invited (n = 28). 16 CCS were enrolled. Recent medical visits, e health literacy and impressions of the digital treatment summary were assessed by a survey in conjunction with viewing their digital treatment summary on a computer screen. Their experience of reading and understanding their digital treatment summary in the context of their health related survivorship experiences were assessed in focus groups. The transcribed data was analyzed with conventional qualitative content analysis. Results: The self-reported medical problems largely reflected that, only 6,3% reported no cancer-related reasons for seeking medical attention. Of the medical specialists, the primary care physician was the most frequently visited specialist (68.8%). High E health literacy was not associated with treatment features but with educational level (p = 0.003, CI: 3.9–14.6) and sex (p = 0.022, CI: − 13.6- -1.3). All survivors graded the digital treatment summary above average in terms of being valuable, agreeable and comprehensive. The focus group interviews identified three themes: 1) The significance of information, 2) The impact of awareness; and 3) Empowerment. Conclusions: Reading the treatment summaries furthered the survivors understanding of their health situation and consequently aided empowerment. A digital treatment summary, provided by knowledgeable health care professionals, may increase the self-managed care and adherence to follow-up recommendations. Further insights into e health literacy in larger samples of CCS may determine to what extent health-related information can be communicated via digital resources to this at risk population.
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| 19. |
- Papakokkinou, Eleni, et al.
(author)
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Excess Morbidity Persists in Patients With Cushing’s Disease During Long-term Remission : A Swedish Nationwide Study
- 2020
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In: Journal of Clinical Endocrinology and Metabolism. - Washington : Oxford University Press. - 0021-972X .- 1945-7197. ; 105:8, s. 2616-2624
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Journal article (peer-reviewed)abstract
- Context: Whether multisystem morbidity in Cushing's disease (CD) remains elevated during long-term remission is still undetermined.Objective: To investigate comorbidities in patients with CD.Design, setting, and patients: A retrospective, nationwide study of patients with CD identified in the Swedish National Patient Register between 1987 and 2013. Individual medical records were reviewed to verify diagnosis and remission status.Main outcomes: Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were calculated by using the Swedish general population as reference. Comorbidities were investigated during three different time periods: (i) during the 3 years before diagnosis, (ii) from diagnosis to 1 year after remission, and (iii) during long-term remission.Results: We included 502 patients with confirmed CD, of whom 419 were in remission for a median of 10 (interquartile range 4 to 21) years. SIRs (95% CI) for myocardial infarction (4.4; 1.2 to 11.4), fractures (4.9; 2.7 to 8.3), and deep vein thrombosis (13.8; 3.8 to 35.3) were increased during the 3-year period before diagnosis. From diagnosis until 1 year after remission, SIRs (95% CI were increased for thromboembolism (18.3; 7.9 to 36.0), stroke (4.9; 1.3 to 12.5), and sepsis (13.6; 3.7 to 34.8). SIRs for thromboembolism (4.9; 2.6 to 8.4), stroke (3.1; 1.8 to 4.9), and sepsis (6.0; 3.1 to 10.6) remained increased during long-term remission.Conclusion: Patients with CD have an increased incidence of stroke, thromboembolism, and sepsis even after remission, emphasizing the importance of early identification and management of risk factors for these comorbidities during long-term follow-up.
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| 20. |
- Papakokkinou, Eleni, et al.
(author)
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Prevalence of Nelson's syndrome after bilateral adrenalectomy in patients with cushing's disease: a systematic review and meta-analysis
- 2021
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In: Pituitary. - : Springer Science and Business Media LLC. - 1386-341X .- 1573-7403.
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Journal article (peer-reviewed)abstract
- Purpose Bilateral adrenalectomy (BA) still plays an important role in the management of Cushing's disease (CD). Nelson's syndrome (NS) is a severe complication of BA, but conflicting data on its prevalence and predicting factors have been reported. The aim of this study was to determine the prevalence of NS, and identify factors associated with its development. Data sources Systematic literature search in four databases. Study Selection Observational studies reporting the prevalence of NS after BA in adult patients with CD. Data extraction Data extraction and risk of bias assessment were performed by three independent investigators. Data synthesis Thirty-six studies, with a total of 1316 CD patients treated with BA, were included for the primary outcome. Pooled prevalence of NS was 26% (95% CI 22-31%), with moderate to high heterogeneity (I-2 67%, P < 0.01). The time from BA to NS varied from 2 months to 39 years. The prevalence of NS in the most recently published studies, where magnet resonance imaging was used, was 38% (95% CI 27-50%). The prevalence of treatment for NS was 21% (95% CI 18-26%). Relative risk for NS was not significantly affected by prior pituitary radiotherapy [0.9 (95% CI 0.5-1.6)] or pituitary surgery [0.6 (95% CI 0.4-1.0)]. Conclusions Every fourth patient with CD treated with BA develops NS, and every fifth patient requires pituitary-specific treatment. The risk of NS may persist for up to four decades after BA. Life-long follow-up is essential for early detection and adequate treatment of NS.
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