Very long-term sequelae of craniopharyngioma Wijnen, Mark; van den Heuvel-Eibrink, Marry M; Janssen, Joseph A M J L ...
European journal of endocrinology
176, Številka:
6
Journal Article
Recenzirano
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Studies investigating long-term health conditions in patients with craniopharyngioma are limited by short follow-up durations and generally do not compare long-term health effects according to ...initial craniopharyngioma treatment approach. In addition, studies comparing long-term health conditions between patients with childhood- and adult-onset craniopharyngioma report conflicting results. The objective of this study was to analyse a full spectrum of long-term health effects in patients with craniopharyngioma according to initial treatment approach and age group at craniopharyngioma presentation.
Cross-sectional study based on retrospective data.
We studied a single-centre cohort of 128 patients with craniopharyngioma treated from 1980 onwards (63 patients with childhood-onset disease). Median follow-up since craniopharyngioma presentation was 13 years (interquartile range: 5-23 years). Initial craniopharyngioma treatment approaches included gross total resection (
= 25), subtotal resection without radiotherapy (
= 44), subtotal resection with radiotherapy (
= 25), cyst aspiration without radiotherapy (
= 8), and
Yttrium brachytherapy (
= 21).
Pituitary hormone deficiencies (98%), visual disturbances (75%) and obesity (56%) were the most common long-term health conditions observed. Different initial craniopharyngioma treatment approaches resulted in similar long-term health effects. Patients with childhood-onset craniopharyngioma experienced significantly more growth hormone deficiency, diabetes insipidus, panhypopituitarism, morbid obesity, epilepsy and psychiatric conditions compared with patients with adult-onset disease. Recurrence-/progression-free survival was significantly lower after initial craniopharyngioma treatment with cyst aspiration compared with other therapeutic approaches. Survival was similar between patients with childhood- and adult-onset craniopharyngioma.
Long-term health conditions were comparable after different initial craniopharyngioma treatment approaches and were generally more frequent in patients with childhood- compared with adult-onset disease.
Most studies in patients with craniopharyngioma did not investigate morbidity and mortality relative to the general population nor evaluated risk factors for excess morbidity and mortality. ...Therefore, the objective of this study was to examine excess morbidity and mortality, as well as their determinants in patients with craniopharyngioma.
Hospital-based retrospective cohort study conducted between 1987 and 2014.
We included 144 Dutch and 80 Swedish patients with craniopharyngioma identified by a computer-based search in the medical records (105 females (47%), 112 patients with childhood-onset craniopharyngioma (50%), 3153 person-years of follow-up). Excess morbidity and mortality were analysed using standardized incidence and mortality ratios (SIRs and SMRs). Risk factors were evaluated univariably by comparing SIRs and SMRs between non-overlapping subgroups.
Patients with craniopharyngioma experienced excess morbidity due to type 2 diabetes mellitus (T2DM) (SIR: 4.4, 95% confidence interval (CI): 2.8-6.8) and cerebral infarction (SIR: 4.9, 95% CI: 3.1-8.0) compared to the general population. Risks for malignant neoplasms, myocardial infarctions and fractures were not increased. Patients with craniopharyngioma also had excessive total mortality (SMR: 2.7, 95% CI: 2.0-3.8), and mortality due to circulatory (SMR: 2.3, 95% CI: 1.1-4.5) and respiratory (SMR: 6.0, 95% CI: 2.5-14.5) diseases. Female sex, childhood-onset craniopharyngioma, hydrocephalus and tumour recurrence were identified as risk factors for excess T2DM, cerebral infarction and total mortality.
Patients with craniopharyngioma are at an increased risk for T2DM, cerebral infarction, total mortality and mortality due to circulatory and respiratory diseases. Female sex, childhood-onset craniopharyngioma, hydrocephalus and tumour recurrence are important risk factors.
Craniopharyngioma is a sellar tumor associated with high rates of pituitary deficiencies (~ 98%) and hypothalamic obesity (~ 50%).
This work aims to determine the efficacy regarding long-term weight ...loss after bariatric surgery in obese craniopharyngioma patients with hypothalamic dysfunction.
This retrospective, case-control, multicenter, international study included obese craniopharyngioma patients (N = 16; of whom 12 are women) with a history of bariatric surgery (12 Roux-en-Y gastric bypass, 4 sleeve gastrectomy; median age 21 years range, 15-52 years, median follow-up 5.2 years range, 2.0-11.3 years) and age/sex/surgery/body mass index-matched obese controls (N = 155). Weight loss and obesity-related comorbidities up to 5 years after bariatric surgery were compared and changes in hormonal replacement therapy evaluated.
Mean weight loss at 5-year follow-up was 22.0% (95% CI, 16.1%-27.8%) in patients vs 29.5% (95% CI, 28.0%-30.9%) in controls (P = .02), which was less after Roux-en-Y gastric bypass (22.7% 16.9%-28.5% vs 32.0% 30.4%-33.6%; P = .003) but at a similar level after sleeve gastrectomy (21.7% -1.8% to 45.2% vs 21.8% 18.2%-25.5%; P = .96). No major changes in endocrine replacement therapy were observed after surgery. One patient died (unknown cause). One patient had long-term absorptive problems.
Obese patients with craniopharyngioma had a substantial mean weight loss of 22% at 5-year follow-up after bariatric surgery, independent of type of bariatric surgery procedure. Weight loss was lower than in obese controls after Roux-en-Y gastric bypass. Bariatric surgery appears to be effective and relatively safe in the treatment of obese craniopharyngioma patients.
Patients with craniopharyngioma are at an increased risk for cardio- and cerebrovascular mortality. The metabolic syndrome (MetS) is an important cardiometabolic risk factor, but barely studied in ...patients with craniopharyngioma. We aimed to investigate the prevalence of and risk factors for the MetS and its components in patients with craniopharyngioma.
Cross-sectional study with retrospective data.
We studied the prevalence of and risk factors for the MetS and its components in 110 Dutch (median age 47 years, range 18-92) and 68 Swedish (median age 50 years, range 20-81) patients with craniopharyngioma with ≥3 years of follow-up (90 females (51%); 83 patients with childhood-onset craniopharyngioma (47%); median follow-up after craniopharyngioma diagnosis 16 years (range 3-62)). In Dutch patients aged 30-70 years and Swedish patients aged 45-69 years, we examined the prevalence of the MetS and its components relative to the general population.
Sixty-nine (46%) of 149 patients with complete data demonstrated the MetS. Prevalence of the MetS was significantly higher in patients with craniopharyngioma compared with the general population (40% vs 26% (
< 0.05) for Dutch patients; 52% vs 15% (
< 0.05) for Swedish patients). Multivariable logistic regression analysis identified visual impairment as a borderline significant predictor of the MetS (OR 2.54, 95% CI 0.95-6.81;
= 0.06) after adjustment for glucocorticoid replacement therapy and follow-up duration. Age, female sex, tumor location, radiological hypothalamic damage,
Yttrium brachytherapy, glucocorticoid replacement therapy and follow-up duration significantly predicted components of the MetS.
Patients with craniopharyngioma are at an increased risk for the MetS, especially patients with visual impairment.
Abstract
Context
Pituitary hormonal deficiencies in patients with craniopharyngioma may impair their bone health.
Objective
To investigate bone health in patients with craniopharyngioma.
Design
...Retrospective cross-sectional study.
Setting
Dutch and Swedish referral centers.
Patients
Patients with craniopharyngioma (n = 177) with available data on bone health after a median follow-up of 16 years (range, 1-62) were included (106 60% Dutch, 93 53% male, 84 48% childhood-onset disease).
Main outcome measures
Fractures, dual X-ray absorptiometry-derived bone mineral density (BMD), and final height were evaluated. Low BMD was defined as T- or Z-score ≤-1 and very low BMD as ≤-2.5 or ≤-2.0, respectively.
Results
Fractures occurred in 31 patients (18%) and were more frequent in men than in women (26% vs. 8%, P = .002). Mean BMD was normal (Z-score total body 0.1 range, -4.1 to 3.5) but T- or Z-score ≤-1 occurred in 47 (50%) patients and T-score ≤-2.5 or Z-score ≤-2.0 in 22 (24%) patients. Men received less often treatment for low BMD than women (7% vs. 18%, P = .02). Female sex (OR 0.3, P = .004) and surgery (odds ratio OR, 0.2; P = .01) were both independent protective factors for fractures, whereas antiepileptic medication was a risk factor (OR, 3.6; P = .03), whereas T-score ≤-2.5 or Z-score ≤-2.0 was not (OR, 2.1; P = .21). Mean final height was normal and did not differ between men and women, or adulthood and childhood-onset patients.
Conclusions
Men with craniopharyngioma are at higher risk than women for fractures. In patients with craniopharyngioma, a very low BMD (T-score ≤-2.5 or Z-score ≤-2.0) seems not to be a good predictor for fracture risk.
Nephrotic Syndrome and a Maculopapular Rash van Herwerden, Michael C.; Wijnen, Mark; Smedts, Frank M.M. ...
American journal of kidney diseases,
April 2019, 2019-04-00, 20190401, Letnik:
73, Številka:
4
Journal Article
Abstract
Context
Patients with craniopharyngioma suffer from obesity and impaired bone health. Little is known about longitudinal changes in body composition and bone mineral density (BMD).
Objective
...To describe body composition and BMD (change).
Design
Retrospective longitudinal study.
Setting
Two Dutch/Swedish referral centers.
Patients
Patients with craniopharyngioma (n = 112) with a dual X-ray absorptiometry (DXA) scan available (2 DXA scans, n = 86; median Δtime 10.0 years; range 0.4-23.3) at age ≥ 18 years (58 52% male, 50 45% childhood onset).
Main outcome measures
Longitudinal changes of body composition and BMD, and associated factors of ΔZ-score (sex and age standardized).
Results
BMI (from 28.8 ± 4.9 to 31.2 ± 5.1 kg/m2, P < .001), fat mass index (FMI) (from 10.5 ± 3.6 to 11.9 ± 3.8 kg/m2, P = .001), and fat free mass index (FFMI) (from 18.3 ± 3.2 to 19.1 ± 3.2 kg/m2, P < .001) were high at baseline and increased. Fat percentage and Z-scores of body composition did not increase, except for FFMI Z-scores (from 0.26 ± 1.62 to 1.06 ± 2.22, P < .001). Z-scores of total body, L2-L4, femur neck increased (mean difference 0.61 ± 1.12, P < .001; 0.74 ± 1.73, P < .001; 0.51 ± 1.85, P = .02). Linear regression models for ΔZ-score were positively associated with growth hormone replacement therapy (GHRT) (femur neck: beta 1.45 95% CI 0.51–2.39); and negatively with radiotherapy (femur neck: beta –0.79 –1.49 to –0.09), glucocorticoid dose (total body: beta –0.06 –0.09 to –0.02), and medication to improve BMD (L2-L4: beta –1.06 –1.84 to –0.28).
Conclusions
Z-scores of BMI, fat percentage, and FMI remained stable in patients with craniopharyngioma over time, while Z-scores of FFMI and BMD increased. Higher glucocorticoid dose and radiotherapy were associated with BMD loss and GHRT with increase.
Craniopharyngioma patients often have poor metabolic profiles due to hypothalamic-pituitary damage. Previously, using BMI as obesity marker, the occurrence of the metabolic syndrome in these patients ...was estimated at 46%. Our aim was to determine if dual X-ray absorptiometry (DXA) scan in evaluation of obesity and metabolic syndrome would be superior.
Retrospective study of craniopharyngioma patients for whom DXA scan results were available.
BMI, fat percentage and fat mass index were used to evaluate obesity and as components for obesity in metabolic syndrome.
Ninety-five craniopharyngioma patients were included (51% female, 49% childhood-onset disease). Metabolic syndrome occurred in 34-53 (45-51%) subjects (depending on the definition of obesity, although all definitions occurred in higher frequency than in the general population). Metabolic syndrome frequency was higher if obesity was defined by fat percentage (52 vs 42%) or fat mass index (51 vs 43%) compared to BMI. Misclassification appeared in 9% (fat percentage vs BMI) and 7% (fat mass index vs BMI) for metabolic syndrome and 29 and 13% for obesity itself, respectively. For metabolic syndrome, almost perfect agreement was found for BMI compared with fat percentage or fat mass index. For obesity, agreement was fair to moderate (BMI vs fat percentage).
Using BMI to evaluate obesity underestimates the true prevalence of metabolic syndrome in patients with craniopharyngioma. Furthermore, fat percentage contributes to a better evaluation of obesity than BMI. The contribution of DXA scan might be limited for identification of the metabolic syndrome.
Background
Impairment of health‐related physical fitness (HRPF) in survivors of acute lymphoblastic leukemia has been shown. However, evidence of impairment in survivors of other pediatric ...malignancies and possible risk factors is limited.
Participants and Methods
HRPF of 17 survivors of pediatric acute myeloid leukemia (AML), 26 survivors of neuroblastoma (NBL), 28 survivors of Wilms tumor (WT) (median age 28.8 18.8–62.6 years) after a median follow‐up time of 24.5 (6.5–43.6) years, and 74 healthy controls (median age 26.9 17.9–61.7 years). Risk factors were investigated. Testing included submaximal cardiovascular endurance (6‐Minute Walk Test (6 MWT), flexibility, and muscle strength.
Results
Results are expressed as mean (standard error). Survivors scored significantly lower than controls on the 6 MWT (588 ± 6.1 m vs. controls 611 ± 6.0 m; P = 0.008), on side flexion of the trunk (20.1 ± 0.4 cm vs. controls 22.4 ±0.4 cm; P < 0.001), and on vertical jump (39.7 ± 0.8 cm vs. controls 43.8 ± 0.8 cm; P < 0.001). Survivors of AML had lower scores on the 6 MWT (563 ± 12.4 m) than survivors of NBL (585 ± 9.9 m) and survivors of WT (606 ± 9.6 m), P = 0.046. Being a survivor, higher body mass index (BMI) and no participation in sports were independently associated with lower scores on the 6 MWT.
Conclusion
Survivors of NBL, WT, and especially AML have impaired HRPF. Higher BMI and physical inactivity at adult age appeared prominent risk factors for impaired HRPF in these survivors.
In craniopharyngioma patients, an important clinical feature is an adverse metabolic profile due to hypothalamic damage and pituitary deficiencies. In our Dutch/Swedish craniopharyngioma cohort, the ...occurrence of the metabolic syndrome (MetS) was higher than in the general population (46% vs.15% in the Swedish and 26% in Dutch population) (Wijnen 2017). However, in previous analysis we have used increased body mass index (BMI) to define adiposity. BMI misclassifies more than 50% of childhood cancer survivors as normal, while DXA measures increased body fat percentage (BF%) as BMI does not take an altered body composition into account (Blijdorp 2012). Our hypothesis was that MetS (defined according to the adjusted Joint Interim Statement) (Alberti 2009) and adiposity are underestimated in our previous study (Wijnen 2017). In the current retrospective cross-sectional study, craniopharyngioma patients (aged ≥ 18 yrs) were included if they had had at least one DXA-scan in the past. BMI, BF% and fat mass index (FMI) at the moment of first and, if available, last DXA-scan were gathered. These measurements or calculated standardized deviation scores (SDS) were used to evaluate obesity. The different definitions of obesity were applied as component in the definition of MetS; the laboratory results evaluating other components of MetS were gathered within 3 years of DXA-scan. We included 95 patients, 51% females and 49% with childhood-onset disease. Between 34 and 53 patients with craniopharyngioma fulfilled the criteria for the MetS (45-51% depending on the different assessment of adiposity), which was higher than the general population independent of the definition (
P
<0.05). Occurrence of MetS was higher if obesity was defined by DXA-measured BF% (52% vs. 42%,
P
=0.031) or FMI (51% vs. 43%, P=0.063) compared to BMI at last DXA-scan. A misclassification appeared in 8-9% (BF% vs. BMI) and 5-7% (FMI vs. BMI) for MetS, and respectively 25-29% and 9-13% for obesity. For MetS, an almost perfect agreement was found if increased BMI was compared with either increased BF% (Cohen’s Kappa 0.82-0.90,
P<
0.001) or FMI (Cohen’s Kappa 0.85-0.88,
P<
0.001). For obesity, agreement was only fair (Kappa 0.37,
P=
0.002 at last DXA-scan) to moderate (Kappa 0.53,
P<
0.001 at first DXA-scan) if increased BMI is compared with increased BF%. An Altman-Bland plot of BMI SDS and BF% SDS shows an upward trend with values outside limits of agreement at low and high averages. In conclusion, craniopharyngioma patients are at high risk for the MetS and obesity. DXA-scan measured BF% contributes to a more precise evaluation of obesity identification. Using BMI to estimate obesity may even underestimate the true prevalence of MetS. However, as craniopharyngioma patients have an extreme metabolic phenotype, the contribution of a better defined obesity component for identification and confirmation of MetS might be limited.
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