OBJECTIVE:Assessment of treatment outcome in current de-escalation for differentiated thyroid cancer (DTC) according to the 2015 Dutch thyroid cancer guidelines (NL-15) and American Thyroid Association guidelines (ATA-15).DESIGN:Retrospectively, the recommendations of the NL-15 and ATA-15 guidelines were evaluated to estimate potentially adequate, under- and overtreatment of DTC in patients treated in the University Medical Center Groningen between 2007 and 2017.PATIENTS:A total of 240 patients with a cT1-T3aN0-1aM0 DTC fulfilled the inclusion criteria.MEASUREMENTS:After actual treatment was given, patients were again categorized according to both guidelines into low, intermediate, or high-risk based on tumour status. Next, they were categorized into a congruent low-risk (n = 60), congruent high-risk (n = 73), or incongruent risk group (n = 107). Follow-up data were used to estimate the proportion of potentially adequate, under-, and overtreatment according to both guidelines.RESULTS:Comparing treatment recommended by NL-15 and ATA-15 showed significantly more over- and adequate treatment when following NL-15 recommendations, and more undertreatment following ATA-15 (all: p < .001). Subanalysis of the congruent low-risk group showed overtreatment in 64% when following NL-15 guidelines (p < .001). No treatment differences were found in the congruent high-risk group. Undertreatment was most often seen in the incongruent risk group when following ATA-15 (p < .001).CONCLUSIONS:Low-risk patients were treated too aggressively when following NL-15 recommendations, where the less aggressive ATA-15 approach seemed more adequate. Treatment of intermediate risk DTC patients varies greatly, with a relative higher rate of undertreatment according to the recommendations of the ATA-15, advocating further refining of the risk classification in this patient group.

BACKGROUND:Measurements of plasma free metanephrines are recommended for diagnosing pheochromocytomas and paragangliomas (PPGL). Metanephrines can be detected in saliva with LC-MS/MS with sufficient analytical sensitivity and precision. Because collecting saliva is noninvasive and less cumbersome than plasma or urine sampling, we assessed the diagnostic accuracy of salivary metanephrines in diagnosing PPGL.METHODS:This 2-center study included 118 healthy participants (44 men; mean age: 33 years (range: 19--74 years)), 44 patients with PPGL, and 54 patients suspected of PPGL. Metanephrines were quantified in plasma and saliva using LC-MS/MS. Diagnostic accuracy; correlation between plasma and salivary metanephrines; and potential factors influencing salivary metanephrines, including age, sex, and posture during sampling, were assessed.RESULTS:Salivary metanephrines were significantly higher in patients with PPGL compared with healthy participants (metanephrine (MN): 0.19 vs 0.09 nmol/L, P < 0.001; normetanephrine (NMN): 2.90 vs 0.49 nmol/L, P < 0.001). The diagnostic sensitivity and specificity of salivary metanephrines were 89% and 87%, respectively. Diagnostic accuracy of salivary metanephrines was 88%, with an area under the ROC curve of 0.880. We found a significant correlation between plasma and salivary metanephrines (Pearson correlation coefficient: MN, 0.86, P < 0.001; NMN, 0.83, P < 0.001). Salivary NMN concentrations were higher when collected in a seated position compared with supine (P < 0.001) and increased with age (P < 0.001).CONCLUSIONS:Salivary metanephrines are a promising tool in the biochemical diagnosis of PPGL. Salivary metanephrines correlate with plasma free metanephrines and are increased in patients with PPGL. At this time, however, salivary metanephrines cannot replace measurement of plasma free metanephrines.

Background The role of postoperative external beam radiotherapy (EBRT) in patients with residual iodine refractory-differentiated thyroid cancer (IR-DTC) is still inconclusive. The aim of this retrospective study was to evaluate locoregional control (LRC) and overall survival (OS), and potential side effects after postoperative EBRT for both microscopic and macroscopic non-radically resected, locally advanced IR-DTC. Methods Between 1990 and 2016, 49 patients with locally advanced IR-DTC received EBRT for microscopic (R1; n = 28) or macroscopic (R2; n = 21) locoregional residual disease. For more insight into the added effect of EBRT, we performed an intrapatient sub-analysis in 32 patients who had undergone more than 1 surgical intervention, comparing LRC after primary, curative-intended surgery with LRC after repeated surgery plus EBRT. To estimate LRC and OS, we used Kaplan–Meier curves. From 2007 onward, we prospectively recorded toxicity data in our head and neck cancer database ( n = 10). Results LRC rates 5 years after EBRT were higher for R1 (84.3%) than for R2 (44.9%) residual disease ( P = 0.016). The 5-year OS rate after EBRT was 72.1% for R1 and 33.1% for R2 disease ( P = 0.003). In the intrapatient analysis ( n = 32), LRC rates were 6.3% 5 years after only initial surgery and 77.9% after repeated surgery with EBRT ( P < 0.001). Acute toxicity was limited to grade I and II xerostomia, mucositis, and hoarseness; only one patient developed late grade III dysphagia. Conclusions Postoperative EBRT is associated with long-lasting LRC and OS with acceptable toxicity in patients with locally advanced IR-DTC, especially in microscopic residual disease.

Von Hippel-Lindau (VHL) disease is an autosomal dominant rare tumor syndrome characterized by high penetrance. VHL mutation carriers develop numerous manifestations in multiple organs during life. The natural course of development of new and growth of existing VHL-related manifestations is still unclear. In this study we aimed to gain insight into the development of subsequent manifestations in VHL disease. We retrospectively scored each new VHL-related manifestation as detected by standard follow-up (retina, central nervous system, kidneys and pancreas, excluding adrenal and endolymfatic sac manifestations) in 75 VHL mutation carriers. The Kaplan-Meier method was used to plot the cumulative proportions of all consecutive manifestations in each organ against age. The cumulative average number of manifestations in all organs during life was calculated by summating these cumulative proportions. Poisson model parameters were used to calculate average time to the detection of consecutive VHL manifestations in each organ. Consecutive VHL-related kidney and retina manifestations during life occur linearly according to Poisson distribution model. The total number of VHL manifestations rises linearly, with an average of seven VHL-related lesions at age 60years. The incidence of consecutive VHL-related manifestations is constant during life in VHL mutation carriers. Our data is consistent with the notion that somatic inactivation of the remaining allele (Knudson's two-hit hypothesis) is the determining factor in developing new VHL-related manifestations.

Evidence accumulates that an active lifestyle positively influences cancer treatment outcome. A “smartphone application” (app) such as “RunKeeper,” to self-monitor physical activity (PA) might be helpful. This study aimed to examine whether using RunKeeper to increase self-reported PA is feasible in cancer patients and to evaluate patients’ opinion about using RunKeeper in a 12-week program.

BACKGROUNDThyroglobulin (Tg) is an established tumor marker in differentiated thyroid carcinoma (DTC). However, Tg assays can be subject to interference by autoantibodies against Tg (TgAbs). No clinical consensus exists on the cutoff value of TgAb positivity and its relationship to Tg assay interference. The aims of this study were to investigate the most applicable cutoff value for TgAb positivity in clinical practice and to evaluate whether tumor characteristics differ between TgAb+ and TgAb- patients during ablation therapy using the manufacturer's cutoff (MCO) and institutional cutoff (ICO).METHODSThis single-center cohort study included 230 DTC patients diagnosed between January 2006 and December 2014. Serum Tg and TgAbs were measured with the Tg-IRMA (Thermo Fisher Scientific) and ARCHITECT Anti-Tg (Abbott Laboratories) assays. Patients were divided into TgAb- and TgAb+ based on the limit of detection (LoD; ≥0.07 IU/mL), functional sensitivity (FS; ≥0.31 IU/mL), MCO (≥4.11 IU/mL), and ICO (≥10 IU/mL).RESULTSAll patients were TgAb+ based on the LoD; one patient was negative on FS. Fifty-five (23.9%) and 34 (14.8%) patients had TgAbs above the MCO and ICO, respectively. Histology, presence of multifocality, tumor-node-metastasis, and American Thyroid Assocation risk stratification did not differ between TgAb- and TgAb+ patients using MCO and ICO during ablation.CONCLUSIONSThis study supports the use of a higher cutoff value than that of the FS for TgAb positivity in clinical settings. The LoD and FS are too sensitive to discriminate TgAb positivity and negativity in DTC patients during ablation therapy. The presence of TgAbs during ablation is not related to tumor characteristics and risk profile. This implies that TgAb positivity should not be considered a separate risk factor.

Metastatic melanoma patients can have durable responses to systemic therapy and even long-term survival. However, a large subgroup of patients does not benefit. Tumour metabolic alterations may well be involved in the efficacy of both targeted and immunotherapy. Knowledge on in vivo tumour glucose uptake and its heterogeneity in metastatic melanoma may aid in upfront patient selection for novel (concomitant) metabolically targeted therapies. The aim of this retrospective study was to provide insight into quantitative 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) parameters and corresponding intra- and inter-patient heterogeneity in tumour 18F-FDG uptake among metastatic melanoma patients. Consecutive, newly diagnosed stage IV melanoma patients with a baseline 18F-FDG PET/CT scan performed between May 2014 and December 2015 and scheduled to start first-line systemic treatment were included. Volume of interests (VOIs) of all visible tumour lesions were delineated using a gradient-based contour method, and standardized uptake values (SUVs), metabolically active tumour volume (MATV) and total lesion glycolysis (TLG) were determined on a per-lesion and per-patient basis. Differences in quantitative PET parameters were explored between patient categories stratified by BRAFV600 and RAS mutational status, baseline serum lactate dehydrogenase (LDH) levels and tumour programmed death-ligand 1 (PD-L1) expression.

BACKGROUND:Primary aldosteronism (PA) may confer increased cardiovascular risk beyond effects on systemic blood pressure, but contributing mechanisms remain incompletely understood. We compared plasma (apo)lipoproteins and lipoprotein particle characteristics, GlycA, a pro-inflammatory glycoprotein biomarker of enhanced chronic inflammation, and plasma total branched-chain amino acids (BCAA), measured using nuclear magnetic resonance (NMR) spectroscopy, between patients with PA, control subjects without hypertension, subjects with untreated hypertension and subjects with treated hypertension.METHODS:Twenty PA patients were individually matched with 2819 control subjects without hypertension, 501 subjects with untreated hypertension and 878 subjects with treated hypertension participating in the PREVEND (Prevention of Renal and Vascular End-Stage Disease) cohort study with respect to age, sex, body mass index, smoking and statin use. The Vantera® Clinical Analyzer was used to determine NMR-based laboratory parameters.RESULTS:Total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein (apo) B, apolipoprotein A-I (apoA-I), LDL particle and HDL particle concentrations were all decreased in PA subjects vs control subjects and subjects with untreated hypertension (P < 0.016). Triglycerides (TG) and triglyceride-rich lipoprotein (TRL) concentrations were lower in PA subjects vs subjects with (untreated) hypertension. GlycA was increased in PA vs the three comparator groups (P < 0.016). Total BCAA concentrations were unaltered in PA.CONCLUSIONS:Primary aldosteronism is associated with lower concentrations of LDL and HDL particles and to some extent also with lower TG and TRL particle concentrations. PA is also characterized by increased GlycA levels, indicating enhanced low-grade chronic inflammation. Low HDL particle concentrations and increased GlycA could contribute to accelerated cardiovascular disease development in PA.

Objective: Elevated circulating levels of pro-inflammatory biomarkers are associated with adverse health effects, but the extent to which enhanced low-grade inflammation influences remaining life expectancy (LE) is uncertain. GlycA is a novel pro-inflammatory marker. We determined effects of GlycA and high sensitivity C-reactive protein (hsCRP) on LE. Methods: GlycA and hsCRP were determined in 5526 subjects. LE was compared in the upper quartile of both GlycA and hsCRP vs. the respective lower three quartiles combined, adjusted for LE of individuals in the Dutch general population of the same birth cohort and sex. Results: Median follow up was 8.5 years [interquartile range 7.9-9.0], during which 348 (6.3%) subjects had deceased. LE at the end of follow up was lower in the highest vs. the lower three quartiles of GlycA (P < .001) and hsCRP (P < .001). Both men as well as women in the highest GlycA quartile had reduced LE vs. the lowest three quartiles combined (P < .001 and P = .02). For hsCRP, this was only observed in men (P < .001) but not in women (P = .67). Conclusions: This population-based cohort study demonstrates that higher plasma levels of GlycA were associated with reduced LE in men and women. With regard to hsCRP this only applied to men.

Objective To assess the effect of somatostatin analogs (SSAs) on mortality in relation to disease control of acromegaly after pituitary surgery. Design A retrospective study in two large tertiary referral centers in The Netherlands. Methods Overall, 319 patients with acromegaly in whom pituitary surgery was performed as primary therapy between January 1980 and July 2017 were included. Postoperative treatment with SSA was prescribed to 174 (55%) patients because of persistent or recurrent disease. Disease control at last visit was assessed by IGF1 standard deviation score (SDS). Adequate disease control was defined as IGF1 SDS ≤2. Univariate determinants of mortality and standardized mortality ratios (SMRs) were calculated for groups with and without SSA at any moment postoperatively and at last visit. Results In total, 27 deaths were observed. In univariate analysis, determinants of mortality were inadequate disease control (relative risk (RR): 3.41, P = 0.005), surgery by craniotomy (RR: 3.53, P = 0.013) and glucocorticoid substitution (RR: 2.11, P = 0.047). There was a strong trend toward increased mortality for patients who used SSA (RR: 2.01, P = 0.067) and/or dopamine agonists (RR: 2.54, P = 0.052) at last visit. The SMR of patients with adequate disease control who used SSA at any moment postoperatively (1.07, P = 0.785) and at last visit (1.19; P = 0.600) was not increased. Insufficiently controlled patients had a significantly raised SMR (3.92, P = 0.006). Conclusions Postoperative use of SSA is not associated with increased mortality in patients with acromegaly who attain adequate disease control. In contrast, inadequate disease control, primary surgery by craniotomy and glucocorticoid substitution are associated with increased mortality.

Germline mutations of the gene encoding succinate dehydrogenase subunit B (SDHB) predispose to head-and-neck-paraganglioma (HNPGL), sympathetic PGL, pheochromocytoma and renal cell carcinoma for which regular surveillance is required. SDHB-associated tumors harbor germline and somatic mutations, consistent with Knudson's two-hit hypothesis. To assess the penetrance and optimal surveillance for different manifestations of SDHB mutation carriers. This study included all SDHB mutation carriers who were followed at the Department of Endocrinology at the University Medical Center of Groningen. Kaplan–Meier curves were used to assess the penetrance. Poisson process was used to assess the optimal age to start surveillance and intervals. Ninety-one SDHB-mutation carriers (38 men and 53 women) were included. Twenty-seven mutation carriers (30 %) had manifestations, with an overall penetrance 35 % at the age of 60 years. We calculated that optimal surveillance for HNPGL could start from an age of 27 years with an interval of 3.2 years. This study underscores the relatively low penetrance of disease in SDHB mutation carriers. Use of the Poisson approach provides a more accurate estimation of the age to initiate surveillance and length of intervals for HNPGL. These results may give rise to reconsider the current guidelines regarding the screening of these mutation carriers.

4550 Background: Four decades have passed since the introduction of cisplatin-based chemotherapy for metastatic TC, providing the opportunity to evaluate very long-term survival. Although 80-90% of the patients are cured, the effect of treatment on residual life span is unknown. Aim of the study was to investigate life expectancy after TC treatment: from prolonging survival after cancer diagnosis, focus shifts to regaining a normal residual life span. Methods: Patients with metastatic TC treated with cisplatin-based chemotherapy > 20 years ago (1977 - 1996) at the University Medical Center Groningen were included. Survival status and cause of death were obtained from medical records, Netherlands Cancer Registry and general practitioners. Events were defined as death due to any cause (overall mortality) and death due to TC or TC treatment complications (TC specific mortality). Standardized mortality ratios (SMR) were calculated as ratio between observed and expected deaths, derived from the age-matched nationwide male population (Dutch Central Office of Statistics). SMRs were calculated for overall mortality, non TC specific mortality (censoring death from TC or treatment-related complications), mortality from cardiovascular disease (censoring death from other causes than cardiovascular disease (ICD-10 I0-I99)) and mortality from secondary malignancies (censoring death from other causes than secondary malignancies (ICD-10 C0-C99 excluding C62: TC)). Results: We included 321 metastatic TC patients with a median age of 28 years (range 16 - 64) at start of chemotherapy. After a median follow-up of 25 years (range 0 - 38) 106 patients died (33%). SMR for overall mortality was 4.0 (95% CI 3.6 - 4.4) and for non TC specific mortality 1.5 (95% CI 1.1 - 1.9). SMR for secondary malignancies was 1.7 (95% CI 1.0 - 2.2) and for cardiovascular diseases 1.5 (95% CI 0.7 - 2.2). Median age at death was 5-10 years lower in TC patients than expected. Conclusions: Twenty years after cisplatin-based chemotherapy, TC patients have a 50% increased risk of dying from non TC causes compared to the general population. These findings suggest that cisplatin-based treatment for TC comes at the expense of about 7.5 life years and induces early aging.

Thoracic aortic aneurysms are life-threatening and often diagnosed too late, underscoring the need to identify the underlying molecular sequence of events. We therefore examined the molecular mecha...

BACKGROUND: Cholesterol, required for adrenal steroid hormone synthesis, is at least in part derived from circulating lipoproteins. The contribution of high-density lipoproteins (HDL) and low-density lipoproteins (LDL) to adrenal steroidogenesis in humans is unclear.OBJECTIVE: The aim of the study was to determine the extent to which HDL and LDL are taken up by the adrenal glands using samples obtained during adrenal venous sampling (AVS).METHODS: AVS was successfully performed in 23 patients with primary aldosteronism. Samples were drawn from both adrenal veins and inferior vena cava (IVC). HDL cholesterol (HDL-C) and lipoprotein particle profiles were determined by nuclear magnetic resonance spectroscopy. Apolipoprotein (apo) A-I and apoB were assayed by immunoturbidimetry.RESULTS: Plasma HDL-C and HDL and LDL particle concentrations (HDL-P and LDL-P) were not lower in samples obtained from the adrenal veins compared with the IVC (HDL-C, P =.59; HDL-P, P = .06; LDL-P, P =.93). ApoB was lower in adrenal venous plasma than in IVC (P = .026; P < .05 for right adrenal vein). In 13 patients with an aldosterone producing adenoma (APA), apoB was also lower (P = .045) and LDL-P tended to be lower (P = .065) in the APA adrenal vein compared with the IVC. ApoA-I was not lower in adrenal venous plasma compared with the IVC, neither in the whole group (P = .20) nor in the APA subgroup (P = .075).CONCLUSION: These in vivo observations suggest that circulating LDL may contribute to adrenal steroidogenesis in humans as inferred from adrenal venous-IVC apoB concentration differences. AVS is a feasible method to investigate the relationships between lipoproteins and steroidogenesis. (C) 2017 National Lipid Association. All rights reserved.

OBJECTIVEAmiodarone is used for the maintenance of sinus rhythm in patients with arrhythmias, but thyroid dysfunction (amiodarone-induced thyrotoxicosis (AIT) or amiodarone-induced hypothyroidism (AIH)) is a common adverse effect. As the onset of AIT and AIH may be unpredictable, the value of long-term regular monitoring of amiodarone treated patients for thyroid dysfunction is still uncertain.DESIGNWe retrospectively documented the frequency at which overt thyroid dysfunction was preceded by subclinical thyroid dysfunction.METHODSWe included 303 patients treated with amiodarone between 1984 and 2007. AIT was defined as a lowered TSH level with an elevated free thyroxine (FT4) and AIH was defined as an elevated TSH level with a decreased or subnormal FT4. Subclinical AIT was defined as a lowered TSH level with a normal FT4 and subclinical AIH as an elevated TSH level with a normal FT4.RESULTS200 men and 103 women, aged 62 ± 12.0 years, suffering from atrial (260) or ventricular (43) arrhythmias, were evaluated. During a median follow-up of 2.8 (1.0-25) years, 44 patients developed AIT and 33 AIH. In 42 (55%) patients who developed AIT/AIH, earlier thyroid function tests showed no subclinical AIT or subclinical AIH. In 35 (45%) patients, AIT/AIH was preceded by subclinical AIT or subclinical AIH (16/44 for AIT and 19/33 for AIH).CONCLUSIONSIn a considerable proportion of patients who developed AIT/AIH, earlier thyroid function tests showed no subclinical AIT/AIH. Less than half of the patients with a subclinical event subsequently developed overt AIT/AIH. This study provides data to reconsider the yield of regular testing of thyroid function to predict overt thyroid dysfunction in amiodarone treated patients.

4561 Background: Testicular cancer (TC) survivors are at risk to develop early cardiovascular morbidity. Close collaboration between oncologists and primary care physicians (PCPs) is mandatory for optimal cardiovascular risk management. We designed a simple shared survivorship care program in which TC patients regularly visit their PCP instead of their oncologist. The primary aim of this study was to test safety and feasibility of shared-care follow-up after chemotherapy for metastatic TC. Methods: TC patients with complete remission after chemotherapy and age ≥18 years were eligible. Participants received a personalized survivorship care plan with scheduled visits to the oncologist and PCP, which was available both on paper and as a mobile application. During PCP visits, signals indicating cancer recurrence, cardiovascular risk and psychosocial issues were assessed. Safety boundaries were defined for the occurrence of failed response to signals indicating cancer recurrence. Patient data were monitored real-time to check if the shared-care follow-up was carried out within these boundaries. Secondary outcomes were satisfaction among TC patients and PCPs, measured with an evaluation questionnaire, and anxiety levels, measured with the Hospital Anxiety and Depression Scale. Results: 64% of eligible TC patients and 99% of the approached PCPs were willing to participate; 162 patients were enrolled in the shared-care program and 241 primary care visits took place. No failures occurred in the detection of relapsed TC. Therefore, the safety boundary was crossed, indicating that shared-care follow-up is a safe alternative to hospital-only follow-up. Four primary care visits were deemed as failed visits because of logistic issues.Anxiety levels did not increase during shared-care follow-up (3.6 vs 3.3 (p = 0.38). Patients were satisfied with the knowledge of PCPs and appreciated this regular contact. 78% of the PCPs would like to extend their role in shared-care follow-up. Conclusions: This easy to use shared survivorship care program is safe and feasible in the follow-up of TC patients. Communication within this patient-centered follow-up program may be further supported with e-health tools. Clinical trial information: NCT01783145.

Thyroglobulin (Tg) is an excellent tumour marker, as detectable or increasing Tg levels are highly indicative of persistent or recurrent differentiated thyroid carcinoma (DTC). The clinical value of a highly sensitive (hs)-Tg assay in patients with DTC has not yet been established. The aim of this study was to investigate the additional value of unstimulated hs-Tg measurements (Tg-on) compared to stimulated IRMA-Tg measurements (Tg-off) in the follow-up of patients with DTC. We retrospectively studied patients treated for DTC between 2006 and 2013 and compared hs-Tg and IRMA-Tg measurements. The study group consisted of 99 DTC patients in remission; Tg-on was measured 3 months after remnant ablation and Tg-off 6 months after ablation. In the study group, 44 patients showed a hs-Tg-on <0·15 μg/l (functional sensitivity); of these, 43 had an IRMA-Tg-off measurement <1·0 μg/l, resulting in a negative predictive value of 97·7% and a positive predictive value of 56·4%. The hs-Tg-on measurement is able to predict patients with an IRMA-Tg-off <1·0 μg/l, and therefore decreases the need for Tg stimulation after ablation.

BACKGROUND:There is a major lack of randomized controlled trials (RCTs) evaluating the effects of hydrocortisone (HC) substitution therapy in patients with secondary adrenal insufficiency. Therefore, we evaluated the effects of two different replacement doses of HC on health-related quality of life (HRQoL) in a RCT.METHODS:This RCT with a double-blind cross-over design was performed at the University Medical Center Groningen. Forty-seven patients (29 men, age 51 ± 14 years, range 19-73 years) with secondary adrenal insufficiency participated. Patients received both a lower and a higher dose of HC (0.2-0.3 and 0.4-0.6 mg/kg body weight/day) for 10 weeks in random order. HRQoL was assessed with a daily mood and symptom checklist (Patient Health Questionnaire-15 [PHQ-15], Generalized Anxiety Disorder-7 [GAD-7], Patient Health Questionnaire-9 [PHQ-9]) and with questionnaires assessing general well-being (RAND 36-Item Health Survey [RAND-36]), mood (Hospital Anxiety and Depression Scale [HADS]) and fatigue (Multidimensional Fatigue Inventory-20 [MFI-20]). ClinicalTrials.gov identifier: NCT01546922.RESULTS:Patients receiving the higher dose of HC reported significantly fewer symptoms of depression (p = 0.016 and p = 0.045 for HADS and PHQ-9, respectively), less general and mental fatigue (p = 0.004 and p = 0.003, respectively, both MFI-20), increased motivation (p = 0.021, MFI-20), better physical functioning (p = 0.041), better general health (p = 0.013) and more vitality (p = 0.025) (all RAND-36). In addition, while on the higher dose, fewer somatic symptoms (p = 0.022) and less pain (p < 0.001) (both PHQ-15) were experienced.CONCLUSIONS:On the higher dose of HC, patients reported a better HRQoL on various domains as compared to the lower dose of HC. The fact that a higher dose of HC may improve patient well-being should be taken into consideration when individualizing the HC substitution dose.

BACKGROUND:Patients with von Hippel-Lindau (VHL) disease are prone to develop pancreatic neuroendocrine tumors (pNETs). However, the best imaging technique for early detection of pNETs in VHL is currently unknown. In a head-to-head comparison, we evaluated endoscopic ultrasound (EUS) and (11)C-5-hydroxytryptophan positron emission tomography ((11)C-5-HTP PET) compared with conventional screening techniques for early detection of pancreatic solid lesions in VHL patients.METHODS:We conducted a cross-sectional, prospective study in 22 patients at a tertiary care university medical center. Patients with VHL mutation or with one VHL manifestation and a mutation carrier as first-degree family member, with recent screening by abdominal computed tomography (CT) or magnetic resonance imaging (MRI) and somatostatin receptor scintigraphy (SRS), were eligible. Patients underwent EUS by linear Pentax echoendoscope and Hitachi EUB-525, and (11)C-5-HTP PET. Patient-based and lesion-based positivity for pancreatic solid lesions were calculated for all imaging techniques with a composite reference standard.RESULTS:In 10 of the 22 patients, 20 pancreatic solid lesions were detected: 17 with EUS (P < 0.05 vs CT/MRI+ SRS), 3 with (11)C-5-HTP PET, 3 with SRS, 9 with CT/MRI, and 9 with CT/MRI + SRS. EUS evaluations showed solid lesions with a median size of 9.7 mm (range 2.9-55 mm) and most of them were homogeneous, hypoechoic, isoelastic, and hypervascular. Moreover, EUS detected multiple pancreatic cysts in 18 patients with a median of 4 cysts (range 1-30).CONCLUSIONS:EUS is superior to CT/MRI + SRS for detecting pancreatic solid lesions in VHL disease.(11)C-5-HTP PET has no value as a screening method in this setting. EUS performs well in early detection of pNETs, but its role in VHL surveillance is unclear.