SAT-495 1-α-Hydroxylase Activity-Mediated Hypercalcemia Associated with Ovarian Dysgerminoma

Background: Humoral hypercalcemia of malignancy is classically associated with increased tumor production of parathyroid hormone-related peptide (PTHrP). While 1,25 dihydroxy vitamin D (1,25D) mediated hypercalcemia has been demonstrated with a range of granulomatous disorders and lymphomas, there have only been 11 cases reported in ovarian dysgerminomas, of which only 2 were in adults. Ovarian dysgerminoma is the most common ovarian malignancy in childhood but is much more infrequent in adults. We present a case of a rare ovarian malignancy in an adult woman with an even more rare presentation of 1,25D mediated hypercalcemia. Case: A 23 year old African American female with a history of intravenous drug abuse was admitted for dilation and curettage for suspected molar pregnancy. Her operative course was complicated by uterine perforation requiring diagnostic laparoscopy which revealed a large, firm, irregular left ovarian mass concerning for malignancy. Laboratory findings were pertinent for calcium 13.4mg/dl (8.5-10.5), albumin 3.5g/dl (3.5-5.0), creatinine 1.61mg/dl (0.6-1.2), phosphorus 4.0mg/dl (2.5-4.5), alkaline phosphatase elevated at 170 Units/L (25-125) and appropriately suppressed PTH of 4 pg/ml (10-65). Previous calcium levels were all normal. Additional work-up revealed normal PTHrP, 25-OH Vitamin D 14.2 mg/dl (20-50) and high-normal 1,25 dihydroxy vitamin D at 76pg/ml (19.9-79.3). Tumor markers β-hCG, LDH, α-fetoprotein, and CA 19-9 were all elevated. CT scan of the abdomen and pelvis characterized the lesion to be a heterogenous 16.5 x 10.0 x 18.3 cm pelvic mass. The patient was initially given intravenous isotonic fluids and 4mg of intravenous zoledronic acid which decreased calcium to 10mg/dl. Biopsy of the mass performed during initial laparoscopy confirmed the suspected diagnosis of ovarian dysgerminoma. A left salpingo-oophorectomy was performed and the patient developed mild hypocalcemia post-operatively to a nadir of 6.7mg/dl (adjusted for albumin: 7.7) requiring calcium supplementation. The 1,25D level on post-operative day 2 was low at 9.1 pg/ml. Surgical pathology demonstrated metastatic ovarian dysgerminoma with para-aortic lymph node involvement. Conclusion: Our case demonstrates an unusual case of humoral hypercalcemia of malignancy. Exogenous 1-α-hydroxylase expression has been reported exceedingly rarely in solid tumors other than lymphomas. While we were unable to stain the tumor for 1-α-hydroxylase, the abrupt drop in 1,25D and calcium levels post resection strongly support our diagnosis. To our knowledge, our patient is the second oldest patient reported in literature to have 1,25D mediated hypercalcemia associated with an ovarian dysgerminoma

Development of an objective tool for the diagnosis of myxedema coma

Myxedema coma, a rare entity, with a reported 25%–65% mortality had no objective criteria for making the diagnosis when we began our study. We developed an objective screening tool for myxedema coma to more easily identify patients and examine the best treatment method in future prospective studies to reduce the mortality of this entity. We conducted a retrospective chart review to find all patients aged ≥18 years admitted with myxedema coma from January 1, 2005 through June 13, 2010 at Indiana University Health Methodist Hospital. On the basis of both our retrospective chart review and on literature accounts, we identified 6 criteria to diagnose myxedema coma. We identified 10 patients initially diagnosed with myxedema coma and established a control group consisting of 13 patients identified with altered mental status and increased thyroid-stimulating hormone (TSH) levels. The 6 variables we created for the screening tool were heart rate, temperature, Glasgow coma scale, TSH, free thyroxine, and precipitating factors. The screening tool has a sensitivity and specificity of about 80%. We ran a logistic regression model using the 10 study patients and 13 controls with the 6 variables. No variables alone significantly contributed to the model. However, the overall model was highly significant (P = 0.012), providing strong support for a scoring system that uses these variables simultaneously. This screening tool enables physicians to rapidly diagnose myxedema coma to expedite treatment. A more refined diagnostic tool may be used in future clinical studies designed to determine the optimal treatment

Hypothyroidism Prolongs Hospitalization Following Surgery

Objective: Each year 45 million surgical procedures are performed in the United States, and a significant number of these are performed on hypothyroid patients. Little guidance is available to determine the postoperative risk to these subjects. We hypothesized that new surgical techniques and modern anesthesia would lead to no differences in outcome between hypothyroid patients and euthyroid controls. Methods: We queried surgical databases in our health system for patients who underwent an operative procedure between January 1, 2010 and December 31, 2015 with a TSH > 10 mcU/mL or a FT4 < 0.6 ng/dL. Identified patients were matched to euthyroid controls selected for age, sex, surgical procedure, and search interval. Predicted length of hospital stay (LOS) was determined using the American College of Surgeons National Surgical Quality Improvement Program surgical risk calculator. Results: We identified 29 hypothyroid patients. The LOS was significantly longer for the hypothyroid patients compared to the predicted LOS (14.4 vs 6.7 days, P < 0.001). The LOS in the matched controls was not significantly different than their predicted LOS (9.6 vs 7.1 days, P = 0.11). Other complications were not different between the hypothyroid and control patients. Conclusions: In contrast to our initial hypothesis, hypothyroidism is associated with a 2-fold longer LOS following surgery. Hypothyroidism continues to place patients at increased surgical risk

Relacorilant, a Selective Glucocorticoid Receptor Modulator in Development for the Treatment of Patients With Cushing Syndrome, Does Not Cause Prolongation of the Cardiac QT Interval

Objective: To assess the effect of relacorilant, a selective glucocorticoid receptor modulator under investigation for the treatment of patients with endogenous hypercortisolism (Cushing syndrome [CS]), on the heart rate–corrected QT interval (QTc). Methods: Three clinical studies of relacorilant were included: (1) a first-in-human, randomized, placebo-controlled, ascending-dose (up to 500 mg of relacorilant) study in healthy volunteers; (2) a phase 1 placebo- and positive-controlled thorough QTc (TQT) study of 400 and 800 mg of relacorilant in healthy volunteers; and (3) a phase 2, open-label study of up to 400 mg of relacorilant administered daily for up to 16 weeks in patients with CS. Electrocardiogram recordings were taken, and QTc change from baseline (ΔQTc) was calculated. The association of plasma relacorilant concentration with the effect on QTc in healthy volunteers was assessed using linear mixed-effects modeling. Results: Across all studies, no notable changes in the electrocardiogram parameters were observed. At all time points and with all doses of relacorilant, including supratherapeutic doses, ΔQTc was small, generally negative, and, in the placebo-controlled studies, similar to placebo. In the TQT study, placebo-corrected ΔQTc with relacorilant was small and negative, whereas placebo-corrected ΔQTc with moxifloxacin positive control showed rapid QTc prolongation. These results constituted a negative TQT study. The model-estimated slopes of the concentration-QTc relationship were slightly negative, excluding an association of relacorilant with prolonged QTc. Conclusion: At all doses studied, relacorilant consistently demonstrated a lack of QTc prolongation in healthy volunteers and patients with CS, including in the TQT study. Ongoing phase 3 studies will help further establish the overall benefit-risk profile of relacorilant.</p

A decade of shaping the futures of polar early career researchers: A legacy of the International Polar Year

The Association of Polar Early Career Scientists (APECS) is an important legacy of the International Polar Year (IPY). APECS continues to foster engagement in education, outreach and communication (EOC) activities relating to the polar regions and provide training for early career researchers (ECRs). We highlight opportunities for training, leadership and skills development, such as the annual Polar Weeks and Antarctica Day celebrations. Participation and engagement in EOC activities actively contributes to career development by enabling ECRs to develop valuable soft skills such as networking, communication and interdisciplinary knowledge. A pilot survey on EOC engagement highlighted that those who organise events also gain leadership skills such as team management. We discuss several factors contributing to the success of APECS in training the next generation of polar leaders. These include the geographical rather than discipline-specific focus of the organisation, utilisation of online resources, including social media, and the strong links with partner organisations. These examples demonstrate how the EOC legacy of IPY has continued due to APECS’ targeted efforts to create EOC opportunities and provide skills and leadership training for ECRs

First circumpolar assessment of Arctic freshwater phytoplankton and zooplankton diversity : Spatial patterns and environmental factors

Arctic freshwaters are facing multiple environmental pressures, including rapid climate change and increasing land-use activities. Freshwater plankton assemblages are expected to reflect the effects of these stressors through shifts in species distributions and changes to biodiversity. These changes may occur rapidly due to the short generation times and high dispersal capabilities of both phyto- and zooplankton. Spatial patterns and contemporary trends in plankton diversity throughout the circumpolar region were assessed using data from more than 300 lakes in the U.S.A. (Alaska), Canada, Greenland, Iceland, the Faroe Islands, Norway, Sweden, Finland, and Russia. The main objectives of this study were: (1) to assess spatial patterns of plankton diversity focusing on pelagic communities; (2) to assess dominant component of beta diversity (turnover or nestedness); (3) to identify which environmental factors best explain diversity; and (4) to provide recommendations for future monitoring and assessment of freshwater plankton communities across the Arctic region. Phytoplankton and crustacean zooplankton diversity varied substantially across the Arctic and was positively related to summer air temperature. However, for zooplankton, the positive correlation between summer temperature and species numbers decreased with increasing latitude. Taxonomic richness was lower in the high Arctic compared to the sub- and low Arctic for zooplankton but this pattern was less clear for phytoplankton. Fennoscandia and inland regions of Russia represented hotspots for, respectively, phytoplankton and zooplankton diversity, whereas isolated regions had lower taxonomic richness. Ecoregions with high alpha diversity generally also had high beta diversity, and turnover was the most important component of beta diversity in all ecoregions. For both phytoplankton and zooplankton, climatic variables were the most important environmental factors influencing diversity patterns, consistent with previous studies that examined shorter temperature gradients. However, barriers to dispersal may have also played a role in limiting diversity on islands. A better understanding of how diversity patterns are determined by colonisation history, environmental variables, and biotic interactions requires more monitoring data with locations dispersed evenly across the circumpolar Arctic. Furthermore, the importance of turnover in regional diversity patterns indicates that more extensive sampling is required to fully characterise the species pool of Arctic lakes.Peer reviewe

Increasing dominance of terrigenous organic matter in circumpolar freshwaters due to permafrost thaw

Climate change and permafrost thaw are unlocking the vast storage of organic carbon held in northern frozen soils. Here, we evaluated the effects of thawing ice-rich permafrost on dissolved organic matter (DOM) in freshwaters by optical analysis of 253 ponds across the circumpolar North. For a subset of waters in subarctic Quebec, we also quantified the contribution of terrestrial sources to the DOM pool by stable isotopes. The optical measurements showed a higher proportion of terrestrial carbon and a lower algal contribution to DOM in waters affected by thawing permafrost. DOM composition was largely dominated (mean of 93%) by terrestrial substances at sites influenced by thawing permafrost, while the terrestrial influence was much less in waterbodies located on bedrock (36%) or with tundra soils unaffected by thermokarst processes (42%) in the catchment. Our results demonstrate a strong terrestrial imprint on freshwater ecosystems in degrading ice-rich permafrost catchments, and the likely shift toward increasing dominance of land-derived organic carbon in waters with ongoing permafrost thaw.Peer reviewe