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.
Summary
Childhood cancer survivors (CCS) are at increased risk to develop metabolic syndrome (MetS), diabetes, and cardiovascular disease. Common criteria underestimate adiposity and possibly ...underdiagnose MetS, particularly after abdominal radiotherapy. A systematic literature review and meta‐analysis on the diagnostic and predictive value of nine newer MetS related biomarkers (adiponectin, leptin, uric acid, hsCRP, TNF‐alpha, IL‐1, IL‐6, apolipoprotein B (apoB), and lipoprotein(a) lp(a)) in survivors and adult non‐cancer survivors was performed by searching PubMed and Embase. Evidence was summarized with GRADE after risk of bias evaluation (QUADAS‐2/QUIPS). Eligible studies on promising biomarkers were pooled. We identified 175 general population and five CCS studies. In the general population, valuable predictive biomarkers are uric acid, adiponectin, hsCRP and apoB (high level of evidence), and leptin (moderate level of evidence). Valuable diagnostic biomarkers are hsCRP, adiponectin, uric acid, and leptin (low, low, moderate, and high level of evidence, respectively). Meta‐analysis showed OR for hyperuricemia of 2.94 (age‐/sex‐adjusted), OR per unit uric acid increase of 1.086 (unadjusted), and AUC for hsCRP of 0.71 (unadjusted). Uric acid, adiponectin, hsCRP, leptin, and apoB can be alternative biomarkers in the screening setting for MetS in survivors, to enhance early identification of those at high risk of subsequent complications.
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.
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.
Abstract
Introduction
Craniopharyngioma (CP) are benign tumors originating from the sellar/hypothalamic region that are associated with neurological damage, epilepsy and endocrinopathies, which all ...could negatively affect bone health. Our objective was to determine fracture risk, bone mineral density (BMD) and final height in CP and evaluate independent determinants for fractures.
Methods
In this retrospective study, Dutch/Swedish patients with CP were included if data was available on fractures, bone mineral density (BMD) (T/Z-score), or final height (age >18 years). Data is presented as mean±SD unless stated otherwise. Logistic regression models were developed to evaluate determinants for fractures and osteoporosis. Low BMD was defined as T- or Z-score ≤-1 and osteoporosis as ≤-2.5 or ≤-2.0, respectively.
Results
We included 177 patients (48% female, 48% childhood-onset disease), with a median age at last follow-up of 45 years (range 15-92 years). Fractures occurred in 31 patients (18%); a fracture rate of 5.8 per 1000 person years. Eight patients suffered from multiple fractures (26%). In a multivariable logistic regression model for fractures, significant protective factors were female sex (OR 0.3 P=0.004) and surgery (OR 0.1, P=0.009), whereas a risk factor was use of anti-epileptics (OR 3.0, P=0.07). A significant risk factor for osteoporosis was age (OR 1.03, P=0.03); growth hormone replacement therapy tended to be protective (OR 0.2, P=0.10). Osteoporosis was not an explanatory variable for fractures (OR 2.1, P=0.21). Mean BMD T- and Z-scores were normal: Z-scores for L2-L4, femur neck and total body were 0.0±2.0 (range -3.5 - 6.8), -0.1±1.3 (range -2.7 - 4.7) and 0.1±1.5 (range -4.1 - 3.5), respectively. Osteoporosis occurred in 22 patients (24%); mean age of patients with osteoporosis was 53 ± 20 years. Low BMD occurred in 47 patients (50%). Medication to improve BMD was less often used in men than in women(7% vs. 18%, P=0.02). Mean final height was normal and did not differ between males/females, or adulthood/childhood-onset patients.
Conclusions
Patients with CP have a high fracture rate. In this population, epilepsy treatment was a risk factor, female sex a protective factor whereas osteoporosis did not affect the risk for fractures. Mean BMD Z-score was normal, but with a very wide range, resulting in low BMD in 50% and osteoporosis in 24% of the patients. Male CP patients are potentially undertreated with medication to improve bone health.
Objective 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. Design Retrospective study of craniopharyngioma patients for whom DXA scan results were available. Methods BMI, fat percentage and fat mass index were used to evaluate obesity and as components for obesity in metabolic syndrome. Results 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). Conclusion 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.
Our objective was to describe the clinical course and treatment challenges in a very young patient with a pituitary adenoma due to a novel aryl hydrocarbon receptor–interacting protein (AIP) gene ...mutation, highlighting the limitations of somatostatin receptor immunohistochemistry to predict clinical responses to somatostatin analogs in acromegaly.
We report the case of a 7-year-old boy presenting with headache, visual field defects, and accelerated growth following failure to thrive. The laboratory results showed high insulin-like growth factor I (IGF-I) (standardised deviation scores ( +3.49) and prolactin levels (0.5 nmol/L), and magnetic resonance imaging identified a pituitary macroadenoma. Tumoral/hormonal control could not be achieved despite 3 neurosurgical procedures, each time with apparent total resection or with lanreotide or pasireotide. IGF-I levels decreased with the GH receptor antagonist pegvisomant. The loss of somatostatin receptor 5 was observed between the second and third tumor resection. In vitro, no effect on tumoral GH release by pasireotide (with/without cabergoline) was observed. Genetic analysis revealed a novel germline AIP mutation: p.Tyr202∗ (pathogenic; class 4).
In vitro response of tumor tissue to somatostatin may better predict tumoral in vivo responses of somatostatin analogs than somatostatin receptor immunohistochemistry.
We identified a novel pathologic AIP mutation that was associated with incipient acrogigantism in an extremely young patient who had a complicated course of disease. Growth acceleration can be masked due to failure to thrive. Tumoral growth hormone release in vivo may be predicted with in vitro exposure to somatostatin receptor analogs, as it cannot be assumed that all AIP-mutated somatotropinomas respond well to pasireotide.
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.
BackgroundOur objective was to describe the clinical course and treatment challenges in a very young patient with a pituitary adenoma due to a novel aryl hydrocarbon receptor-interacting protein ...(AIP) gene mutation, highlighting the limitations of somatostatin receptor immunohistochemistry to predict clinical responses to somatostatin analogs in acromegaly. Case ReportWe report the case of a 7-year-old boy presenting with headache, visual field defects, and accelerated growth following failure to thrive. The laboratory results showed high insulin-like growth factor I (IGF-I) (standardised deviation scores ( +3.49) and prolactin levels (0.5 nmol/L), and magnetic resonance imaging identified a pituitary macroadenoma. Tumoral/hormonal control could not be achieved despite 3 neurosurgical procedures, each time with apparent total resection or with lanreotide or pasireotide. IGF-I levels decreased with the GH receptor antagonist pegvisomant. The loss of somatostatin receptor 5 was observed between the second and third tumor resection. In vitro, no effect on tumoral GH release by pasireotide (with/without cabergoline) was observed. Genetic analysis revealed a novel germline AIP mutation: p.Tyr202∗ (pathogenic; class 4). DiscussionIn vitro response of tumor tissue to somatostatin may better predict tumoral in vivo responses of somatostatin analogs than somatostatin receptor immunohistochemistry. ConclusionWe identified a novel pathologic AIP mutation that was associated with incipient acrogigantism in an extremely young patient who had a complicated course of disease. Growth acceleration can be masked due to failure to thrive. Tumoral growth hormone release in vivo may be predicted with in vitro exposure to somatostatin receptor analogs, as it cannot be assumed that all AIP-mutated somatotropinomas respond well to pasireotide.
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