To assess the impact of baseline body mass index (BMI) on the outcomes of patients with neuroendocrine neoplasms (NENs) in a population-based setting. Linked provincial administrative databases (within the province of Alberta, Canada), 2004–2019, were accessed, and patients with NENs and complete information about BMI near the time of diagnosis were reviewed. The impact of BMI on overall survival was evaluated through the use of Kaplan–Meier survival estimates and multivariable Cox regression modeling. A total of 1010 patients with NENs and BMI information were included. Using Kaplan–Meier survival estimates, survival outcomes were best with individuals with obesity and were worst with underweight individuals (P < 0.0001). The following factors were associated with worse overall survival, older age (HR: 1.02; 95% CI: 1.01–1.03), male sex (HR: 1.60; 95% CI: 1.32–1.93), higher Charlson comorbidity index (HR: 1.22; 95% CI: 1.13–1.31), non-small intestinal primary (HR for gastric primary versus small intestinal primary: 2.36; 95% CI: 1.44–3.85), stage 4 disease (HR: 2.67; 95% CI: 2.16–3.31), neuroendocrine carcinoma histology (HR: 1.76; 95% CI: 1.43–2.17), and underweight BMI (HR versus normal BMI: 1.74; 95% CI: 1.11–2.73). When the model was repeated using BMI as a continuous variable (rather than as a categorical variable), increasing BMI was associated with better overall survival (HR with increasing BMI: 0.97; 95% CI: 0.95–0.98). Lower BMI is associated with worse overall survival among patients with NENs. This finding was demonstrable regardless of the tumor’s stage or histology.

Background Thyroid nodules are common in clinical practice, and it is important to distinguish benign nodules, the vast majority, from malignant ones. Non-diagnostic (ND) samples have the potential to delay or mis-diagnose or lead to unnecessary surgeries, and it is important to examine what factors influence the ND rate. Prior literature has suggested that the impact of bedside cytology on ND rate is dependent on the initial adequacy rate, whereby higher ND rates benefit most from bedside cytology. We aim to compare the impact of bedside adequacy review between specialist groups who perform high volume thyroid biopsies with low initial ND rates. Methods We reviewed the cytopathology results of 1975 thyroid nodule FNAs performed between January 1, 2017 to December 31, 2017 in a multi-centre Canadian city, and the corresponding histopathology reports of 340 resected nodules. Descriptive variables were used to describe the data along with chi-squared testing and univariate logistic regression. Results The FNA biopsies were performed by three different speciality groups, which differed by procedural volume: radiology performed the most at 1171, pathology performed 655 and surgery performed 103. We could not define the operator for 45 of the nodules. The ND rate was lowest in the speciality groups with highest procedural volume, 3.4 % in pathology and 8.3 % in radiology, compared to 37.9 % in surgery ( p < 0.001). Completion of bedside cytology rapid onsite evaluation (ROSE) significantly reduced the ND rate from 16.7 to 4.2 % for all samples ( p < 0.001). When ROSE was compared with non-ROSE within a high procedural group (radiology), it further reduced the ND rate from 12.5 to 5.1 % ( p < 0.001). Of the 340 resected nodules, 10.7 % (18) were in the ND category, of which 28 % (5/18) of these were found to be malignant (4 papillary carcinoma and 1 lymphoma). Conclusions The results from this study demonstrate that thyroid FNAs performed with bedside ROSE can significantly reduce the ND rate compared with non-ROSE, even in experienced groups with low initial ND rates. It is therefore imperative that care providers managing patients with thyroid nodules ensure that thyroid FNAs are referred to specialized individuals/groups who do high volume, and ideally with the use of bedside ROSE, whether provided by a cytotechnologist or a pathologist.

Thyroid cancer is the most common type of endocrine malignancy. Cornerstones of thyroid cancer treatment include surgery, radioactive iodine ablation, and thyroid stimulating hormone suppression. The National Comprehensive Cancer Network guidelines recommend two tyrosine kinase inhibitors for thyroid cancer patients who are non-responsive to iodine: sorafenib and lenvatinib. Another oral kinase inhibitor, regorafenib, is not considered standard of care treatment for differentiated thyroid cancer. The chemical structures of regorafenib and sorafenib differ by a single fluorine atom. Given the significant improvement in progression-free survival (PFS) of sorafenib compared to placebo demonstrated in the phase 3 DECISION trial, we report on a patient with iodine-refractory follicular thyroid cancer treated with regorafenib as part of a phase 1 clinical trial. A 75 year old woman was diagnosed with follicular thyroid carcinoma in 2006 and initiated on treatment with regorafenib in 2011. She has completed 76 cycles with stable disease and pulmonary metastases 34% smaller than baseline.

Many neuromuscular diseases (NMD) result in muscle weakness, immobility and greater fracture risk. The objective of this study is to determine the fracture risk of adult patients at a multidisciplinary NMD clinic. Fracture risk was calculated using the Fracture Risk Assessment Tool, the presence of osteoporosis was quantified using bone densitometry and contributing co-morbidities were screened through serum markers. Of the 36 patients studied, 47% were found to be of moderate and high fracture risk. Two thirds of these patients had not been previously screened or treated for osteoporosis. These findings suggest that NMD patients warrant routine screening for osteoporosis and early treatment to reduce fragility fracture.

Purpose of the study: To compare efficacy of thyroid remnant ablation using 30 mCi or 50 mCi 131-I in papillary thyroid cancer patients. Materials and methods: Five hundred and fifteen consecutive patients with Tumor-Node-Metastasis (TNM) stages T1-T3 N1/N0/NX receiving either 30 mCi or 50 mCi I-131 were analyzed for the effectiveness of remnant ablation using rhTSH-stimulated serum thyroglobulin. One hundred and five consecutive patients receiving 100 mCi I-131 were analyzed for the incidence of radiation thyroiditis and sialadenitis. Results and conclusions: Doses of 30 mCi and 50 mCi were equally effective for low- and moderate-risk disease but 30 mCi was less effective for T1T2NX disease, and 50 mCi was less effective for T3 compared to T1T2 disease. Low dose radiation hypersensitivity or unknown more extensive disease may have accounted for observed differences. Radiation thyroiditis and sialadenitis were more common in a comparison series of 100 mCi dose compared to 30 mCi, but not more common than in 50 mCi doses.

Purpose: Steroids, inhaled and systemic, are used to treat airway inflammation in patients with asthma; however, steroids are recognized to cause a number of side effects, including osteoporosis. We evaluated the prevalence of osteopenia/osteoporosis in patients with moderate-severe asthma managed through the Edmonton Regional Severe Asthma Centre. Methods: We performed a retrospective chart review and analyzed 57 charts on patients with moderate-severe asthma followed through the specialty clinic, and recorded their bone mineral density (BMD). Steroid use was reviewed and the frequency of osteopenia/osteoporosis was compared in patients requiring continuous systemic steroids (Group 1, n=15), intermittent systemic steroids (Group 2, n=15) or inhaled steroids only (Group 3, n=27). Results: The mean age (mean±SD) was 50±14.8 years. Cumulative systemic steroid dose of prednisone equivalent was higher in Group 1 (12.5 mg/day) than Group 2 (3.2 mg/day) (p=0.002). The frequency of osteopenia / osteoporosis was not significantly different between patients in Group 1(67%) and Group 2 (53%, p=0.46) but was significantly greater in patients from Group 1 in comparison with Group 3 (33%, p=0.038). Conclusion: Patients with moderate-severe asthma have a high prevalence of reduced bone density. Many patients treated with intermittent systemic steroids for exacerbations, or who were stable on inhaled steroids, had either osteopenia or osteoporosis before the age of 50. National and international osteoporosis guidelines should emphasize earlier screening for asthma patients; and increase awareness of the detrimental effects of short-term systemic steroids and inhaled steroids on BMD, especially when started at an early age and in northern climates.

Introduction: The study was aimed to determine the response and predictive risk factors of differentiated thyroid cancer (DTC) with measurable (0.4-2.0 mu g/L) stimulated serum thyroglobulin (sTg) during the 10-24 months after radioiodine remnant ablation (RRA) and their long-term outcomes. Methods: Out of 839 retrospectively reviewed patients, 95 eligible DTC patients were included. Patients were classified as having incomplete response or no evidence of disease (NED). The sTg cut-off values with highest predicted accuracy for incomplete response at 10-24 months were calculated with receiver operator characteristics curve analysis. Results and Conclusion: At 10-24 months after RRA, incomplete response was identified in 54 patients (57%) and 38/54 (70.4%) patients were found with structural evidence of disease. The remaining 16 patients (29.6%) had biochemical evidence of disease without structural evidence of disease. Forty-one patients (43%) were classified as having NED at 10-24 months after RRA and 27 patients (66%) did not receive further radioactive iodine (RAI) therapy and remained disease free at median follow-up of 6.5 years. Fourteen patients received second RAI treatment after 6 months and before the 10-24 months assessment time point. Of these, 2 had persistent tumor 6 years later. The sTg >0.6 mu g/L at 6-10 months after RRA had optimal sensitivity (83.3%), specificity (56%) and negative predictive value (72%) of detecting incomplete response at 10-24 months after RRA. A total of 23/43 patients in the American Thyroid Association low-risk category had incomplete response after first RRA and 5/23 (21.7%) had recurrent/persistent disease at long-term follow-up.

Background: In addition to increasing the risk of adverse birth outcomes, diabetes in pregnancy is thought to be an important driver of the epidemic of type 2 diabetes affecting Canada's First Nations population. The relative contributions of gestational diabetes mellitus (GDM) and pre-existing diabetes are not well understood. We generated a comprehensive epidemiological profile of diabetes in pregnancy over a 10-year period among the First Nations population of Alberta, Canada.Methods: De-identified administrative data for 427,058 delivery records were obtained for the years 2000-2009. Pregnancy risk factors and delivery outcomes were described and compared by ethnicity (First Nations vs. non-First Nations) and diabetes status. Age-adjusted prevalence values for GDM and pre-existing diabetes were calculated and were compared by ethnicity. Longitudinal changes over time were also examined. Predictors were explored using logistic regression analysis.Results: First Nations women had more antenatal risk factors and adverse infant outcomes that were compounded by diabetes. First Nations descent was an independent predictor of diabetes in pregnancy (p < 0.001). GDM prevalence was significantly higher among First Nations (6.1%) compared to non-First Nations women (3.8%; p < 0.001), but prevalence values increased significantly over time only in non-First Nations women (4.5 average annual percent change; p < 0.05). The prevalence of pre-existing diabetes was stable over time in both groups, but First Nations women experienced a 2.5-fold higher overall prevalence compared with non-First Nations women (1.5% vs. 0.6%, respectively; p < 0.001).Conclusions: Although First Nations women experience a higher overall prevalence of diabetes in pregnancy, the lack of increase in the prevalence over time is encouraging. However, because high-risk pregnancies and poor outcomes are more common among First Nations women, particularly those with diabetes, strategies to improve perinatal care must be implemented.

206 Objectives To compare the successful thyroid remnant ablation rate of 1850 MBq and 3700 MBq 131I prepared with thyroid hormone withdrawal (THW) and recombinant human thyroid stimulating hormone (rhTSH) in patients with DTC. Methods 732 DTC patients after total/near total thyroidectomy were consecutively assigned to the 3 treatment groups: in the 1st group, patients (n =218) were ablated with 1850 MBq RAI after THW; in the 2nd group, patients (n =141) were ablated with 3700 MBq RAI after THW; in the 3rd group, patients (n =373) were ablated with 1850 MBq RAI after rhTSH. The outcome of thyroid remnant ablation was retrospectively compared by conventional 131I scan and/or serum thyroglobulin (Tg) in the absence of Tg-antibody performed under TSH stimulation 2-27 months after ablation. Results At the first follow-up, Tg Conclusions 1850 MBq RAI after THW or rhTSH is equally effective as 3700 MBq after THW for thyroid remnant ablation in DTC patients. 1850 MBq RAI under rhTSH is recommend for post-surgical ablation and is safe, effective and avoids hypothyroidism. Research Support Alberta Cancer Foundation, Canada Foundation for Innovatio

Bisphosphonate treatment rates were examined before and after admission to long-term residential care. Bisphosphonate treatment rates were low (16%) pre-admission but doubled after long-term residential care admission (30%). Men were very undertreated for osteoporosis, while a history of falls with injury was not associated with treatment.

2110 Objectives Following surgical treatment of PTC, the use of adjuvant therapy with radioiodine ablation, and degree of TSH suppression, will depend on the patient9s risk of recurrent disease. The demographic and histologic features associated with early recurrence in PTC are not well understood. We have attempted to determine the factors associated with recurrence within five years of initial diagnosis. Methods A retrospective cohort study of PTC patients treated and followed at a single tertiary centre. 263 patients with PTC were examined using a fixed time window restriction protocol to identify 81 recurrent and 182 non-recurrent patients. All were treated and followed at a single center for the duration of the study.Demographic, histologic, surgical and adjuvant treatment data were collected on all patients and examined for univariate and multivariate correlations with recurrent PTC. Risk factors for recurrent PTC are defined by patient age, sex and tumour histologic characteristics. Results In the patient cohorts defined by tumours of similar size and with similar treatment regimes, it was clear that recurrent disease was favoured in younger patients ( Conclusions Patients at risk of early recurrence of PTC may be identified by young age, lymph node metastases and extra-thyroidal extension

2111 Objectives To investigate the usefulness of 18F-FDG-PET and therapeutic effects of high dose I-131 in differentiated thyroid cancer (DTC) with elevated serum thyroglobulin (Tg) but negative radioactive iodine scan (RAI). Methods One hundred and twenty nine patients who had FDG-PETs for elevated Tg and negative RAI from February 2002 to December 2009 were included after total thyroidectomy followed by radioiodine ablation. Results 69 patients had positive findings on FDG-PET, true positive in 58 patients, false positive in 11 patients, true negative and false negative in 32, 28 patients, respectively. The overall sensitivity, specificity, and accuracy of FDG-PETs were 67%, 74%, and 70%, respectively. FDG-PET had a high specificity (94%) in patients with positive post-therapy scan. Clinical management changed for 58 of 129 (45%) patients, including surgery, radiation therapy, or chemotherapy. Of 129 patients included, 101 patients received I-131 treatment. The post-therapy scans were positive in 54/101 (53%) patients, and 51/101 (50%) patients had 50% decrease in stimulated Tg. The change of stimulated Tg before (15.2, range from 2 to 1349) and after (5.55, range from 0.4 to 7666) I-131 treatment was statically significant after 26 ±22.1 months period of follow-up (p=0.001). In 13 patients without any treatment, 8 patients (8/13, 62%) had 50% decrease in Tg. Conclusions FDG-PET scan is useful in the diagnosis of recurrence and metastases of DTC with elevated Tg and negative scan, and have a high specificity in patients with positive post-therapy scan. Iodine-131 treatment achieved 53% positive post-therapy scan and 50% decrease in stimulated Tg, which suggests that I-131 therapy has a therapeutic effect for half of patients when the Tg level is considered an index of tumour burden. However, the spontaneous decrease of Tg in limited patients (8/13, 62%) with relatively low Tg without any treatment indicated that iodine-131 therapy should be individualised according to clinical characteristics. Research Support Alberta Cancer Foundation, Canada Foundation for Innovatio

Proteomics were performed using highly (99.99%) purified cytotrophoblasts from six normal and six pre‐eclamptic placentas. Eleven proteins were found which decreased in pre‐eclampsia (actin, glutathione S ‐transferase, peroxiredoxin 6, aldose reductase, heat shock protein 60 (Hsp60), two molecular forms of heat shock protein 70 (Hsp70) β‐tubulin, subunit proteasome, ezrin, protein disulfide isomerase, and phosphoglycerate mutase 1). Only one protein, α‐2‐HS‐glycoprotein (fetuin), was found to increase its expression. Western blots of actin, Hsp70, ezrin, and glutatione S ‐transferase confirmed decrease in protein expression. Many of the proteins that decreased are consistent with a state of oxidative stress in the pre‐eclamptic placenta and a decreased cytotrophoblast defense against and response to oxidative stress.

Intravenous bisphosphonates reduce mortality following hip fracture. We determined whether new use of oral bisphosphonates was also associated with reductions in mortality in 209 hip fracture patients. Oral bisphosphonate exposure led to relative reduction of 8% per month of use (p = 0.001) or about a 60% reduction in mortality per year of use.

RATIONALE: Prevalence of osteopenia/ osteoporosis in selected population of moderate to severe asthma followed through a regional asthma referral center. METHODS: A retrospective chart review was carried out in a subgroup of patients managed through the Edmonton Regional Severe Asthma Clinic (ERSAC) with a confirmed primary respiratory diagnosis of moderate to severe asthma, with or without the presence of chronic rhinosinusitis. Subjects were categorized into 2 groups based on their steroid use: Group 1 utilizing continuous systemic steroids; Group 2 utilizing locally administered steroids therapy with or without intermittent systemic steroids. RESULTS: Twenty three subjects were reviewed. They compromised 14 females and 9 males with a median age 48. Eighteen subjects had concomitant chronic rhinosinusitis. In Group 1, with an average cumulative dose equal to 9.5 mg/d prednisone equivalent, 8 of 10 subjects had below normal bone density in their last scan. However, 6 of these individuals had either improved or stable bone density compared to their previous study while on bisphosphanates. In the 2nd group, 6 out of 13 were classified as osteopenia/ osteoporosis based on their last study. CONCLUSIONS: Corticosteroid-induced osteoporosis is prevalent in patients with moderate to severe asthma both with continuous systemic steroids as well as those on high dose steroids (with or without intermittent needs for short course of systemic steroids). This was notable even at a young age. Annual monitoring including bone density is suggested to be incorporated into the standard of care. Additionally, evaluation of better prospective biomarkers is recommended for those with moderate to severe asthma.

BACKGROUND Opioid analgesia impairs gonadal function in men and women, but the correlation with symptoms and hormonal measurements of hypogonadism is not well established. OBJECTIVE To determine the frequency of impaired gonadal function in men and women using opioids for chronic pain, and to determine the correlation of symptoms with hormonal measurements of gonadal function. METHODS A prospective study of patients attending a multidisciplinary pain clinic was conducted. A total of 65 women (47 opioid users and 18 nonopioid analgesic controls) and 32 men (26 opioid users and six controls) were enrolled. Histories of sexual dysfunction and hormonal testing (men: total testosterone [TT], free testosterone [FT], prolactin and luteinizing hormone; women: FT, TT, prolactin, dehydroepiandrosterone sulphate, sex hormone- binding globulin, progesterone, luteinizing hormone and follicle- stimulating hormone, and estradiol) were obtained. RESULTS In men, a low FT level was more common in opioid users (20⁄26; P=0.04). In men with abnormal hormone levels, there was no difference in the frequency of sexual dysfunction compared with men with normal hormone levels, and no difference in the frequency of opioid versus nonopioid use. In women, opioid users had lower FT levels (P=0.02). Low dehydroepiandrosterone sulphate was more frequent in women on opioids (P=0.03) in the menopausal group only (P=0.046). Premenopausal women taking opioids more frequently had a low TT level (P=0.03). The frequency of female sexual dysfunction was the same in opioid users (32⁄47) and controls (13⁄18; P=0.75), and also did not relate to any hormone abnormality. DISCUSSION Men taking opioids had lower FT and higher prolactin levels, and women taking opioids had lower FT levels. Frequency of sexual dysfunction did not correlate with hormone levels in either men or women taking opioids. CONCLUSION Opioids frequently cause low FT levels in men, but there is no relationship between abnormal hormone levels and symptoms of sexual dysfunction. Therefore, all men should be screened for low FT levels. Women on opioids had lower FT levels, but this did not correlate with sexual dysfunction symptoms. Therefore, measurements of FT or other hormones were not considered to be useful in women.

In a randomized trial, a multifaceted intervention tripled rates of osteoporosis treatment in older patients with wrist fracture. An economic analysis of the trial now demonstrates that the intervention tested “dominates” usual care: over a lifetime horizon, it reduces fracture, increases quality-adjusted life years, and saves the healthcare system money.