bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality Improvement Initiative to Enhance Multidisciplinary Management of Malignant Extradural Spinal Cord Compression
Authors: Mattes Malcolm D. , Nieto Josiah D.
Published: May 2020

PURPOSE:

To determine if a quality improvement (QI) initiative could enhance multidisciplinary management of acute malignant extradural spinal cord compression (ESCC) at our institution.

METHODS:

The medical records of all 40 patients who received palliative radiotherapy for malignant ESCC from 2015 to 2017 were reviewed to determine the time course of key National Comprehensive Cancer Network guideline–supported workup and management steps. On the basis of the findings, a multidisciplinary group of physician stakeholders developed a clinical pathway to facilitate expedited care. The efficacy of this clinical pathway and the educational content provided to all relevant departments were then evaluated by comparing outcomes with data from a similarly reviewed follow-up cohort of 25 patients from 2018 to 2019.

RESULTS:

Patients treated for malignant ESCC after our QI intervention were more likely to undergo magnetic resonance imaging (MRI) of the entire spine (64% v 44%; P = .013) and have a radiation oncology (RO) consultation before surgery (100% v 27%; P = .002). Median time from MRI to RO consultation decreased from 3 to 1 days ( P = .03). On subgroup analysis, initial trends toward delays in RO consultation for patients planning for surgery (median, 3 days) or for lack of prior cancer diagnosis (median, 4 days) were reduced to delays of 0 and 1 day, respectively, after the QI intervention. No significant differences were observed in time to surgical consultation or surgery itself.

CONCLUSION:

This QI study was able to stimulate better use of diagnostic imaging and earlier involvement of RO in multidisciplinary decision making, suggesting an effective approach to improving multidisciplinary care in other scenarios as well.
Food Insecurity and Forgone Medical Care Among Cancer Survivors
Authors: McDougall Jean A. , Anderson Jessica , Adler Jaffe Shoshana , Guest Dolores D. , Sussman Andrew L. , Meisner Angela L. W. , Wiggins Charles L. , Jimenez Elizabeth Yakes , Pankratz V. Shane
Published: May 2020

PURPOSE:

Financial hardship is increasingly understood as a negative consequence of cancer and its treatment. As patients with cancer face financial challenges, they may be forced to make a trade-off between food and medical care. We characterized food insecurity and its relationship to treatment adherence in a population-based sample of cancer survivors.

METHODS:

Individuals 21 to 64 years old, diagnosed between 2008 and 2016 with stage I-III breast, colorectal, or prostate cancer were identified from the New Mexico Tumor Registry and invited to complete a survey, recalling their financial experience in the year before and the year after cancer diagnosis. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95%CIs.

RESULTS:

Among 394 cancer survivors, 229 (58%) were food secure in both the year before and the year after cancer diagnosis (persistently food secure), 38 (10%) were food secure in the year before and food insecure in the year after diagnosis (newly food insecure), and 101 (26%) were food insecure at both times (persistently food insecure). Newly food-insecure (OR, 2.82; 95% CI, 1.02 to 7.79) and persistently food-insecure (OR, 3.04; 95% CI,1.36 to 6.77) cancer survivors were considerably more likely to forgo, delay, or make changes to prescription medication than persistently food-secure survivors. In addition, compared with persistently food-secure cancer survivors, newly food-insecure (OR, 9.23; 95% CI, 2.90 to 29.3), and persistently food-insecure (OR, 9.93; 95% CI, 3.53 to 27.9) cancer survivors were substantially more likely to forgo, delay, or make changes to treatment other than prescription medication.

CONCLUSION:

New and persistent food insecurity are negatively associated with treatment adherence. Efforts to screen for and address food insecurity among individuals undergoing cancer treatment should be investigated as a strategy to reduce socioeconomic disparities in cancer outcomes.
SAT-616 Associations Of Body Mass Index And Waist Circumference In Young Adulthood With Later Life Incident Diabetes
Authors: Nair Nandini , Vittinghoff Eric , Pletcher Mark , Oelsner Elizabeth , Allen Norrina , Ndumele Chiadi , West Nancy , Strotmeyer Elsa , Mukamal Kenneth , Siscovick David , Biggs Mary Lou , Laferrère Blandine , Moran Andrew , Zhang Yiyi
Published: May 2020

Background: Overweight and obesity are known risk factors for incident diabetes, but it remains unclear if exposures during young adulthood (age 18 to 39 years) contribute to mid and late-life (age ≥40 years, collectively labeled here as “later-life”) risk of incident diabetes independent of later-life risk factor exposures.

Objective: We sought to assess the independent associations between young adult exposures to overweight and obesity, as assessed by body mass index (BMI) and waist circumference (WC), with later-life incident diabetes, accounting for later-life exposures.

Methods: We pooled data from six US cohorts (ARIC, CARDIA, CHS, Framingham Offspring, Health ABC, and MESA), and imputed life-course risk factor trajectories for BMI and WC, as well as for multiple cardiometabolic risk factors, annually from age 18 years to end of follow-up for each participant. Incident diabetes was defined by observed fasting blood glucose ≥126 mg/dL, non-fasting glucose ≥200, or use of diabetes medications. We used Cox proportional hazards models to examine the independent associations between time-weighted average exposures to BMI and WC during young adulthood and incident diabetes. We also performed mediation analyses to assess whether these associations were mediated by young adult exposures to other cardiometabolic risk factors (blood pressure, lipids, insulin resistance).

Results: 30,780 participants were included (mean age at first in-person visit 53.1±16.2 years; 56.1% female). Over a 9-year median follow-up, 4,323 participants had incident diabetes. Both young adult BMI and WC were associated with diabetes risk in a dose-dependent manner, independent of later-life BMI and WC. Compared to BMI 18.5–24.9 kg/m2, hazard ratios (HR) for incident diabetes were 1.27 (95%CI: 1.14–1.41) and 1.99 (95%CI: 1.67–2.37) for BMI 25–29 kg/m2 and ≥30 kg/m2, respectively. Similarly, compared to normal WC (≤80 cm women; ≤94 cm men), the HRs were 1.42 (95%CI: 1.26–1.59) for WC 81-88cm (women)/95-102cm (men) and 2.13 (95%CI: 1.87–2.43) for WC >88cm (women)/>102cm (men). Young adult homeostatic model of insulin resistance (HOMA-IR) mediated 49% (95%CI: 23–76) and 44% (95%CI: 26–62) of the association between young adult BMI and WC with later-life incident diabetes, respectively.

Conclusions: Elevated BMI or WC during young adulthood were independently associated with later-life incident diabetes, after accounting for later-life BMI and WC, with insulin resistance suggested as a key mediator.
SUN-154 Resistant Hypertension After Shockwave Lithotripsy: The Rude Awakening of an Adrenal Incidentaloma
Authors: Larrazabal Ramon B
Published: May 2020

BACKGROUND

The National Institutes of Health defines adrenal incidentalomas (AIs) as clinically inapparent adrenal masses discovered inadvertently in diagnostic testing or treatment for conditions not related to the adrenal glands. Non-functional adenoma remains the most frequent (60–85%) cause, while functional adenomas at 5–16%.

CLINICAL CASE

A previously healthy 41 year-old female consulted for a 2-month history of left flank pain. Computed tomography (CT) scan of the kidneys revealed left calculi and incidental right adrenal mass. She was asymptomatic at this time. She then underwent shockwave lithotripsy for the renal calculi. However, post-operatively, she had elevated blood pressure and was started on anti-hypertensives. She remained hypertensive despite being on four different medications. Pertinent physical examination findings: plethora of the face and extremities, Moon facies, Buffalo Hump, and pendulous abdomen with grayish striae. Further work-up revealed the AI to be cortisol-secreting. Pertinent laboratories: 1 mg dexamethasone suppression test - 800 nmol/L (<50 nmol/L), 24-hr urine free cortisol - 1014.86 ug/24 hr (20–90 ug/24 hr), Adrenocorticotropic Hormone (ACTH) - 5.0 pg/ml (9–52 pg/ml). She then underwent a right laparoscopic adrenalectomy. Post-operatively, her blood pressure normalized without her anti-hypertensive medications. Tissue biopsy of the mass was consistent with an adrenocortical adenoma. On her follow-up after one month, signs of Cushing’s Syndrome were clinically improving.

CONCLUSION

This is the first case that demonstrated shockwave lithotripsy converting a non-functioning adrenal incidentaloma into a functioning one. It also shows how internists and surgeons (i.e. Urologists) can manage various aspects of patient care through the facilitation of medical treatments, surgical interventions, and ensuring a proper multidisciplinary approach based on the endocrinology clinical guidelines. So as not to delay the delivery of proper management to the patient.

REFERENCES

(1) Grumbach M, Biller B, Braunstein G. et al. “Management of the clinically inapparent adrenal mass (“incidentaloma”).” Annals of internal medicine 2003; 138:424–4292 Herrera M, Grant C, van Heerden J. et al. “Incidentally discovered adrenal tumors: an institutional perspective.” Surgery 1991; 110:1014.
SAT-025 Increased Occurrence of Anemia, Gastrointestinal and Liver Diseases in Women with Turner Syndrome - a Nationwide Registry Study
Authors: Viuff Mette Hansen , Stochholm Kirstine , Grønbæk Henning , Berglund Agnethe , Juul Svend , Gravholt Claus Hojbjerg
Published: May 2020

Background: Gastrointestinal disorders, such as celiac disease, inflammatory bowel diseases and liver disease have previously been described with increased occurrence in women with Turner syndrome. However, evidence towards increased occurrence of bleeding disorders and anemia are sparse. Likewise, the impact of hormone replacement therapy on gastrointestinal disorders remains unknown. Aim: To investigate the risk of bleeding disorders, anemia, gastrointestinal and hepatological disease in women with TS compared with the female background population and to assess the effect of HRT on these conditions. Design: National cohort study Method: 1,156 females with TS diagnosed during 1960–2014 were identified using the Danish Cytogenetic Central Registry and linked with personal-level data from the National Patient Registry and the Medication Statistics Registry. Statistics Denmark randomly identified 115,577 age-matched female controls. Negative binomial regression was used to analyze hospital discharge diagnoses. Medical prescriptions, mortality and the effect of hormone replacement therapy were estimated using stratified Cox regression. Results: The risk of anemia, coagulation disorders and gastrointestinal hemorrhage were all increased three-fold in women with TS compared with controls. Gastrointestinal disorders were twice as frequent in TS individuals, with a three-fold increased risk of inflammatory bowel disease and a twelve-fold increased risk of liver disease and elevated liver enzymes. Both gastrointestinal and hepatological mortality were increased three-fold in TS women. Conclusion: Anemia, gastrointestinal hemorrhage, inflammatory bowel disease is more frequent in women with Turner syndrome compared with controls. The risk of liver disease may be higher than previously reported.
MON-221 Seated Saline Suppression Testing Is Comparable to Captopril Challenge Test for the Diagnosis of Primary Aldosteronism: A Prospective Study
Authors: Hu Jinbo , Liu Bin , Song Ying , He Wenwen , Cheng Qingfeng , Wang Zhihong , Feng Zhengping , Du Zhipeng , Yang Jun , Li Qifu , Yang Shumin
Published: May 2020

Abstract:

Objective: Saline suppression testing (SST) and captopril challenge test (CCT) are commonly used confirmatory tests for primary aldosteronism (PA). Seated SST (SSST) is reported to be superior to recumbent SST (RSST). Whether SSST is better than CCT remains unclear. Therefore we conducted a prospective study to compare the diagnostic accuracy of SSST and CCT.

Methods: Hypertensive patients with high risk of PA were consecutively included. Patients with aldosterone-renin ratio≥1.0 ng•dl-1/μIU•ml-1 were asked to complete SSST, CCT and fludrocortisone suppression test (FST). Using FST as the reference standard (plasma aldosterone concentration [PAC] post-FST ≥6.0 ng•dl-1), area under the receiver-operator characteristic curves (AUC), sensitivity and specificity of SSST and CCT were calculated, and multiple regression analyses were conducted to identify potential factors for false diagnosis.

Results: A total of 183 patients diagnosed as PA and 48 as essential hypertension completed the study. Using PAC post-SSST and PAC post-CCT to confirm PA, SSST and CCT had comparable AUCs (AUCSSST 0.83 [0.78,0.88] vs. AUCCCT 0.86 [0.81,0.90], P=0.308). Setting PAC post-SSST and post-CCT at 8.5 ng•dl-1 and 11 ng•dl-1, respectively, the sensitivity and specificity of SSST [0.71 (95%CI 0.64 to 0.77) and 0.82(0.68,0.90)] and CCT [0.73(0.66,0.79) and 0.80(0.66,0.89)] were not significantly different. In the multiple regression analyses, 1SD increment of sodium intake resulted in 40% lower risk of false diagnosis in SSST.

Conclusions: SSST and CCT have comparable diagnostic accuracy. Insufficient sodium intake decreases the diagnostic efficiency of SSST but not CCT. Since the CCT is simpler and cheaper, it is preferable to the SSST.
SAT-077 Two Cases of Hypoparathyroidism Due to Activating Calcium Sensing Receptor Mutation
Authors: Badran Ahmed , Chin Vivian
Published: May 2020

Introduction

The extracellular calcium-sensing receptor (CaSR) expressed mainly in the parathyroid gland and kidneys regulates calcium (Ca+2) homeostasis through parathyroid hormone (PTH) secretion. Activating mutations of CaSR can lead to autosomal dominant hypocalcemia and severe congenital hypoparathyroidism. Constitutively activated CaSR receptors blocks PTH release leading to hypocalcemia, hyperphosphatemia and decreased Ca+2 reabsorption from the kidney.

Case 1:

14 year old male presented for an evaluation of hypocalcemia and hyperphosphatemia found on routine blood work. He denied symptoms of hypocalcemia. He had normal vital signs, positive Chovstek sign but rest of exam was unremarkable. His lab results showed low Ca+2 8.1 mg/dl (8.6–10 mg/dl), high phosphorus 6 mg/dl (2.7–4.5 mg/dl) and inappropriately normal PTH 26.8 pg/ml (10–65 pg/ml). FISH was negative for DiGeorge. Genetic testing showed heterozygous CaSR gene mutation I822T, variant of uncertain significance. His father with primary hypoparathyroidism has the same CaSR gene mutation; mother is healthy and tested negative for this variant. Given the inheritance pattern of the mutation, it is likely a pathologic mutation. He is maintained on Calcium (1500 mg BID) and Calcitriol (0.5 mcg PO BID) and is doing well.

Case 2:

One day old premature 32-week old infant girl was found to have early onset neonatal hypocalcemia 6.1 mg/dl (6.2–11 mg/dl) during NICU admission for respiratory distress, inappropriately normal PTH 18.5 pg/ml and high phosphorus 8.8 mg/dl (4.6–7.9 mg/dl). She had no symptoms of hypocalcemia in the NICU or at home. She did not have any dysmorphic features. FISH was negative for DiGeorge. Genetic testing to sequence genes including AIRE, AP2S1, CASR, GNAS, HADHA, HADHB, PTH1R, SOX3, STX16, TBCE was done and revealed a novel heterozygous mutation in the CaSR gene for a missense variant c.2495T>C

(p.lle832Thr) and STX16 c.644A>T, possibly benign variant. Unfortunately, the parents have not consented to testing yet. Further familial and functional characterization of this new variant is necessary to confirm its possible pathogenetic role in this hypocalcemic patient. Currently she is maintained on ergocalciferol 800 IU, calcitriol 0.25 mcg and sevelamer 3 packets daily and is doing well.

Conclusion:

In the workup for primary hypoparathyroidism without dysmorphic features and tests negative for DiGeorge, CaSR mutations should be investigated as part of the differential as we have identified variants in the CaSR gene in 2 children with asymptomatic hypocalcemia, one of which is a novel mutation which has never been reported before.
SAT-057 A Novel IGSF1 Variant in a Boy with Central Hypothyroidism and Epiphyseal Dysplasia
Authors: Laurenzano Sarah , Bird Lynne , Demeterco-Berggren Carla
Published: May 2020

Background: IGSF1 deficiency syndrome, also known as X-linked central hypothyroidism and testicular enlargement (CHTE) syndrome, is caused by mutations in the immunoglobulin superfamily, member 1 gene. Recently recognized as the most common genetic cause of isolated central hypothyroidism (CH), its cardinal features include CH and adult macroorchidism. We describe a boy with CH and epiphyseal dysplasia found to have a novel IGSF1 variant.

Clinical case: A male with attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder, obsessive compulsive disorder and obesity was evaluated at age 9y for high total and LDL cholesterol and low T4 with normal TSH. He had short stature for family, high BMI, high sitting height ratio, and short arm span. Laboratory investigation revealed persistently mildly high total and LDL cholesterol, low T4, normal cortisol response to low-dose Cortrosyn stimulation, and normal IGF-1 and IGF-BP3. Bone age at 9y1m chronological age was 8y0m. Skeletal survey showed abnormal epiphyses of the femoral heads, knees, and humeral capitella suggesting primary epiphyseal dysplasia; he was referred to genetics. Growth improved after starting levothyroxine for CH. Multiple epiphyseal dysplasia gene panel (with reflex to clinical exome) did not find any variants known to be pathogenic for his condition. He was found to be a carrier of autosomal recessive Bartter syndrome. Heterozygous variants of unknown significance were found in RMRP, FGFR1, CDT1 and APOB. Whole exome sequencing showed hemizygosity for the p.Q743X (c.2227C>T) variant in IGSF1.

Discussion: The p.Q743X IGSF1 variant has not been reported in the literature and is not present in population databases. It is predicted to cause loss of normal protein function and is considered pathogenic. CH is found in all males with IGSF1 deficiency syndrome. Macroorchidism, another defining feature, develops in adulthood; age of testicular growth onset is normal, but pubertal testosterone rise is delayed. Our patient remains prepubertal at age 11y. Other features sometimes present include hypoprolactinemia (which was found in this child) and transient partial GHD (not seen in this case). Overweight and the metabolic syndrome are common; this child’s cholesterol abnormalities may be due to weight and/or APOB variant found on genetic testing. ADHD has been seen in some patients with this syndrome; this child also has extensive psychiatric/behavioral problems, which have not been described. The skeletal findings in this case have not been previously noted in IGSF1 deficiency syndrome; whether this is a rare feature of IGSF1 deficiency syndrome or a separate entity is unclear. This case adds to the growing list of disease-causing variants in IGSF1. Endocrinologists should consider IGSF1 deficiency syndrome when diagnosing isolated CH in boys, as the characteristic macroorchidism is not present in childhood.
SUN-309 Interleukin-2 Administration in Healthy Men Activates Cortisol Secretion in an Age-, Dose-, and Body Composition-Dependent Way
Authors: Roelfsema Ferdinand , Liu Peter Y , Yang Rebecca , Takahashi Paul , Veldhuis Johannes D
Published: May 2020

Context. Interleukin-2 (IL2), a proinflammatory cytokine, is used for treatment of malignancies. Increased cortisol and ACTH were noted, but not investigated in detail. This is the first study in healthy men which uses moderate high IL2 doses as used in cancer treatment.

Objective. The goal of this study was to quantify cortisol secretion after a single sc injection of IL2 at 1900 h in young and older healthy men in relation to dose, age and body composition. Design. This was a placebo-controlled, blinded, prospectively randomized cross-over study in 17 young subjects (mean age 24.1 yr, range 19–30 yr) and 18 older subjects (mean age 63.9 yr, range 60–75 yr). The subjects underwent 24 h of blood sampling at 10-min intervals, starting at 1800 h. At 2000 h IL2 (3 or 6 million units per m2 body surface) or saline was injected sc. Lights were off between 2300 and 0700 h.

Setting. The study was performed in a Clinical Translational Research Unit.

Outcome measures. Mean concentrations of cortisol, deconvolution analysis, and approximate entropy. Abdominal visceral fat (AVF) and total abdominal fat (TAF) were calculated from single slice CT.

Results. Cortisol concentrations started to rise at 2300 h. The AUC’s during the lights-on periods were unchanged by IL2. Therefore, most analyses were restricted to the 8 h lights-off period. In young volunteers pulsatile cortisol secretion increased from 52.9±5.8 to 77.0±8.0 µg/L/8h and in older subjects from 60.6±3.8 to 70.6±4.6 µg/L/8h (GLM: treatment P <0.0001, treatment x age: P=0.02, mean ± SEM). Thus, the effect was smaller in older subjects. Increasing the IL2 dose increased cortisol secretion in young subjects (P= 0.001), but not in older subjects (P=0.90). In addition, the slopes (mean ± SE) of the linear part of the concentration curves after IL-2 were steeper than after placebo, pointing to accelerated release (young 1.40±0.13 to 3.76±0.11, P<0.0001, in older 1.27±0.04 to 3.28±0.15, P<0.0001).The incremental nocturnal pulsatile cortisol secretion after IL2 was negatively related to body composition (AVF: R= ̶ 0.41, P=0.019; TAF R= ̶ 0.41, P=0.043). Nocturnal ApEn-cortisol did not increase after low dose IL2 (0.981± 0.099 to 0.991±0.046, P=0.92). After high-dose, ApEn increased from 0.877±0.041 to 1.024±0.049, P=0.008, not correlated with body composition, nor with age. The ApEn increase points to decreased secretory regularity imposed by enhanced CRF signaling, rather than diminished cortisol feedback, which leads to greater secretory regularity.

Conclusion. Il2, a paradigm for inflammation, increased pulsatile cortisol secretion, more in young than in older subjects. Higher IL2 doses in young subjects amplified cortisol secretion, but not in older subjects. Cortisol secretion exhibited an advance (earlier) time shift, accompanied by accelerated secretion. Incremental nocturnal cortisol secretion was negatively related to fat mass.
SUN-642 Paracetamol May Increase Cardiac Congenital Malformations Risk in Prediabetic Pregnancy Women
Authors: Guerrero Juan Ariel Jara
Published: May 2020

ABSTRACT

Hyperglycemia can influence the development of the fetal heart, affecting both its structure and its function. Prospective and retrospective cohort studies have demonstrated an increased risk of congenital abnormalities with gestational diabetes. This observation is probably related to the inclusion of women with unrecognized type 2 diabetes (Allen, 2007, Pasarella, 2013).

Substantial literature indicates that diabetes in pregnant rats and mice induces embryo lethality, growth retardation, and a variable incidence of birth defects. Then, the maintenance of normal concentrations of metabolites from all nutrient classes may be important for prevention of adverse fetal outcome in diabetic pregnancy.

Acetaminophen overdose is the most often cause of acute liver injury and obese women are in particular risk, because is able to induce mitochondrial oxidative stress (Rousar, 2012). Acetaminophen (Paracetamol) over doses decreased embryonic low-molecular-weight thiols (glutathione and cysteine), compounds that play a vital role in the detoxication of exogenous and endogenous chemicals (Mitchell, 1973, Beck, 2001, Rousar, 2012, rev).

The apparent safety of Paracetamol drug, a useful analgesic only (with no anti-inflammatory properties) (Neto, 2004; Hamlyn, 1978, Ucheya, 2006, Bessems, 2001) is compromized by its widespread and extensive chronic use, particularly in Peruvian population- Paracetamol though considered safe at a considerable low dose, especially in women, could cause kidney derangement and cardiac malformations during pregnant state (Ucheya, 2006), if the drug is ingested in the first trimester. Major congenital malformations, including those affecting the cardiovascular system, remain the leading cause of mortality and morbidity in infants of diabetic mothers (Pinter, 2001). Thus, there is an overcome potential maternal acetaminophen (paracetamol) toxicity (Horowitz, 1997).
MON-043 Sleep Disturbances in Women with and Without Polycystic Ovary Syndrome (PCOS) and Their Association with Lifestyle Factors (Diet, Physical Activity and Sitting Time)
Authors: Bennett Christie , Mansfield Darren , Mo Lin , Hodge Allison , Joham Anju , Cain Sean , Blumfield Michelle , Teede Helena , Moran Lisa J
Published: May 2020

Sleep disturbances in women with and without polycystic ovary syndrome (PCOS) and their association with lifestyle factors (diet, physical activity and sitting time)

Bennett C1, Mansfield DR2, Mo L2, Hodge A3, Joham A4, 5, Cain SW6, Blumfield M1, Teede H4, 5, Moran LJ4

1. Be Active Sleep and Eat (BASE) Facility, Department of Nutrition and Dietetics, School of Clinical Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria

2. Monash Lung and Sleep, Monash Health, Clayton, Victoria

3. Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria

4. Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Clayton, Victoria

5. Diabetes and Vascular Medicine Unit, Monash Health, Clayton, Victoria

6. Monash Institute of Cognitive and Clinical Neurosciences, School of Psychological Sciences, Monash University, Clayton, Victoria

Sleep disturbances are a risk factor for poorer lifestyle behaviours. While PCOS is associated with a higher prevalence of sleep disturbances, the relationship between sleep and lifestyle behaviours is unknown in PCOS. Self-reported data from the Australian Longitudinal Study on Women’s Health young cohort (31–36 years, n=6067, n=464 PCOS, n=5603 non-PCOS) were collected on PCOS, anthropometry, physical activity, sedentary behaviour, diet (74-item validated food frequency questionnaire) and sleeping behaviour (sleep quantity and adverse sleep symptoms). Multivariate regression models controlled for sleeping behaviour, BMI, age, marital status, education, income and area of residence. Women with PCOS reported greater adverse sleep symptoms, higher energy intake, diet quality (dietary guidelines index (DGI)), fibre intake and sedentary time and lower glycaemic index, compared to women without PCOS. This was not maintained for energy intake and sedentary behaviour on adjustment for confounders. For diet quality, there was an interaction between PCOS and sleep disturbances. Only for women with fewer sleep disturbances (~8 hours sleep/no adverse sleep symptoms) was PCOS associated with better diet quality (DGI higher by 3.14±0.86, p<0.001), with no differences in diet quality for women with poorer sleep. Lifestyle behaviours in women with PCOS appear to be influenced by sleep quality and quantity.

Nothing to disclose: CB, DM, LM, AH, AJ, SC, MB, HT, LM
SUN-430 A Prospective Clinical Trial on the Efficacy of Lithium as Adjuvant Therapy to Radioiodine in the Treatment of Hyperthyroidism (Railit Study)
Authors: Dharan Shalini Sree , Dharan Shalini Sree
Published: May 2020

Background: Radioactive Iodine (RAI) is one of the main treatment modalities of hyperthyroidism. However, its success rate differs between centres. One of the determining factors of RAI success is its intrathyroidal persistence. Lithium has been said to improve efficacy of RAI but it remains debatable till today. Objective: To assess the efficacy and safety of lithium carbonate as an adjuvant therapy to RAI in the treatment of hyperthyroidism. Methods: This is a prospective, interventional, 2 arm parallel-group, open label single centre study carried out in the Endocrinology Unit, Department of Medicine and the Radionuclear Department of Penang General Hospital. The study period was from 30th August 2015 to 30thAugust 2016. The interventional medication is lithium carbonate 300mg twice daily for fourteen days starting on the day of RAI therapy. Lithium carbonate 300mg twice daily was given on the day of RAI (at least 2 hours prior to RAI) to 40 subjects and no added medication to the standard RAI therapy in 40 subjects in the control group. Subjects were followed up for 24 weeks with 6 study visits to assess side effects to medication, compliance to medication, determining cure with adjustments to medications as deemed needed by the study doctors during these study visits. There were 3 drop-outs in the RAI plus Lithium group and 2 drop-outs in the RAI alone group. Results: There were no significant difference in the clinical, demographic and biochemical profile of the two groups. Dose of RAI was a standard 15mCi in both groups. The cure rate in RAI plus lithium group was 62.2% and the cure rate in RAI alone group was 63.2% (p=0.932). Mean time to cure in RAI plus Lithium versus RAI alone group were similar 13.6±6.1weeks vs 13.2±6.5 weeks (p=0.841). There was numerically higher cure rate in Toxic Multinodular goitre in the RAI plus lithium group 10 out of 14 (71.3%) versus RAI alone group 8 out of 15 (53.3%)(P=0.316) though this was not statistically significant. Lithium however was able to prevent thyroid hormone surge 2 weeks post RAI as the median Free T4 was lower at week 2 post RAI compared to baseline (P=0.004) Conclusion: Lithium carbonate does not improve the efficacy of RAI significantly in hyperthyroid patients in our study. Its role in improving efficacy of RAI in toxic multinodular goitre needs further investigations. Lithium is able to prevent thyroid hormone surge post RAI therapy.
SUN-691 Type 2 Diabetes Management in the Context of Smith-Magenis Syndrome: Case Report
Authors: Mulvaney Kylie Tamm , Sathananthan Airani
Published: May 2020

Background: Smith-Magenis syndrome (SMS) is a rare condition caused by microdeletion chromosome 17p11.2 via RAI1 gene mutations, causing disrupted circadian sleep-wake patterns. Characteristic behaviors include: sleep disturbance, anxiety, maladaptive habits with self-injury (biting, picking, self-hugging, page-flipping) and outbursts. Characteristic features include: craniofacial abnormalities, short stature, 2/3 toe syndactyly, scoliosis, cardiac and genitourinary defects, hypotonia, peripheral neuropathy, epilepsy, childhood-onset truncal obesity, toileting difficulties. Management of adults with SMS span multiple disciplines: otolaryngology, audiology, ophthalmology, assessments of scoliosis, seizures, familial psychosocial health, sleep and behavioral changes with each medication. Annual assessments include: fasting lipids, thyroid panel, screening urinalysis. Patients should receive standard treatment for comorbid endocrine conditions, classically: hypercholesterolemia, hypothyroidism, growth hormone deficiency.

Clinical Case: 49-year-old Hispanic female with history of SMS who presented to endocrinology for type 2 diabetes mellitus (T2DM) management. Past medical history includes T2DM with peripheral neuropathy, hypertension, hypercholesterolemia, intellectual disability, anxiety, recurrent genitourinary infections, sleep apnea. Physical exam is remarkable for macroglossia, truncal obesity, scoliosis, extremity excoriations evident of skin picking and xerosis, syndactyly of 2nd-3rd toes. Patient exhibited maladaptive behaviors like page-flipping, self-hugging, tantrums. Over the past 3 years, BMI remained in the obese range (>30 kg/m2) and A1c fluctuated from 7.0 to 10.6% averaging 8.8% (<5.7%). Patient is currently managed on insulin glargine, pioglitazone and liraglutide. She did not tolerate metformin due to dose-dependent diarrhea. Patient’s mother chose against SGLT2 inhibitors due to diminished genitourinary hygiene. T2DM management was complicated by patient behaviors, including nocturnal consumption of fructose-containing food and beverages, exercise intolerance, and associated caregiver fatigue.

Conclusion: This case describes a patient managed for metabolic dysfunction in conjunction with a rare microdeletion disorder causing neurobehavioral disturbance with disrupted circadian sleep-wake patterns. The most difficult aspects of diabetes management included difficulty implementing lifestyle modifications to control the patient’s hyperglycemia.
SAT-286 TSH Synthesis and Secretion Are Unperturbed in Male IRS4 Knockout Mice
Authors: Brule Emilie , Boelen Anita , Bernard Daniel J
Published: May 2020

It was recently reported that mutations in the insulin receptor substrate 4 (IRS4) gene cause a novel form of X-linked congenital central hypothyroidism (OMIM 300904). To date, four different mutations, three frameshift and one nonsense, have been reported, with two affected male patients showing decreased basal, pulsatile, and total thyroid-stimulation hormone (TSH) secretion (PMID 30061370).

Members of the IRS family canonically act as scaffold proteins between tyrosine kinase receptors and their downstream effectors. IRS4/Irs4 expression is enriched in the pituitary; however, its role in the hypothalamic-pituitary-thyroid (HPT) axis has not been studied in detail.

We generated novel whole-body Irs4-knockout mouse lines using CRISPR-Cas9. A specific guide RNA was used to target the Cas9 enzyme to the 5’ end of the single exon Irs4 gene. A two-nucleotide deletion was introduced into Irs4, resulting in a frameshift and premature stop codon. We hypothesized that like IRS4 deficient patients, these mice would exhibit central hypothyroidism. Given that Irs4 is X-linked, we focused our initial characterization on males.

Under normal laboratory conditions, Irs4 knockout mice do not exhibit differences in pituitary expression of Tshb, which encodes one of the subunits of the TSH heterodimer. Expression of the gene encoding the thyrotropin-releasing hormone (TRH) receptor, Trhr1, is also unperturbed in these knockout mice. Additionally, there are no differences in their serum thyroid hormones, T3 (triiodothyronine) and T4 (thyroxine). When Irs4 knockout males were placed on a low-iodine diet supplemented with propylthiouracil (PTU) for 3 weeks and rendered hypothyroid, their serum TSH increased similarly to wild-type males. Overall, Irs4 knockout males do not exhibit central hypothyroidism or phenocopy IRS4 deficient patients. Compensation by another IRS protein may explain euthyroidism in these mice.
SUN-372 Deterioration of Bone Microarchitecture in Prediabetes Is Partly Mediated Through Fibroblast Growth Factor 21
Authors: Lui David T W , Lee Chi Ho , Chau Vicky W K , Fong Carol H Y , Yeung Kristy M Y , Lam Joanne K Y , Lee Alan C H , Chow Wing Sun , Tan Kathryn C B , Woo Yu Cho , Lam Karen S L
Published: May 2020

Introduction: Prediabetes has been reported to be associated with a worse trabecular bone score (TBS). Fibroblast growth factor 21 (FGF21) levels are raised in prediabetes and other insulin-resistant states, and FGF21 has been reported to be implicated in bone metabolism. We compared the bone mineral density (BMD) and TBS between prediabetes and normoglycemia, and studied the correlation of FGF21 with BMD and TBS. Method: Chinese postmenopausal women aged between 55 and 80 and without type 2 diabetes were recruited from the Hong Kong Cardiovascular Risk Factor Prevalence Study between November 2016 and October 2018. Participants were excluded if they were already on anti-osteoporosis therapy, had secondary causes of osteoporosis, had body mass index (BMI) <15 or >37 kg/m2 (when TBS measurement may not be accurate), or had an estimated glomerular filtration rate (eGFR) <30mL/min. They were divided into prediabetes (defined by fasting glucose ≥5.6mmol/L or HbA1c ≥5.7%) and normoglycemia. BMD and TBS were measured by dual-energy X-ray absorptiometry. Serum FGF21 levels were measured with an in-house ELISA kit. Results: 258 participants were included (130 prediabetes and 128 normoglycemia), with a mean age of 61.5±5.1years and mean BMI of 24.2±3.7kg/m2. BMD over lumbar spine, femoral neck and total hip were all comparable between prediabetes and normoglycaemia, while TBS was lower in prediabetes (1.27±0.07 vs 1.30±0.07, p=0.007), which remained significant after adjustment for age and BMI. Serum FGF21 levels did not correlate with BMD but inversely correlated with TBS. On multiple linear regression models, serum FGF21 levels showed an independent inverse correlation with TBS (standardized beta -0.13, p=0.031), which remained significant with the inclusion of homeostasis model assessment of insulin resistance (HOMA-IR) in the model. Conclusion: Among Chinese postmenopausal women, bone quality was worse in prediabetes despite comparable bone density. Serum FGF21 levels showed a significant independent correlation with TBS, suggesting the potential impact of FGF21 on the deterioration of the bone microarchitecture in prediabetes.
MON-365 Novel Use of Abaloparatide to Augment Spinal Fusion in Patient Undergoing Cervicothoracic Revision Surgery
Authors: Parikh Sahil , Lubitz Sara E , Sharma Anupa
Published: May 2020

Objective To present a case of using Abaloparatide (PTHrP 1–34 analogue) to promote spinal fusion in a patient with history of cervical instability s/p multiple cervical operations with non-union. Case Presentation 66 year-old female with a history of multiple sclerosis, obesity and hypothyroidism underwent neurosurgical evaluation of neck pain. She was found to have cervical spinal stenosis causing neck pain, radiculopathy, motor deficits and ataxia. Initially underwent anterior cervical discectomy and fusion which temporarily alleviated symptoms before suffering nonunion. Subsequently underwent two additional surgeries which also eventually failed. She presented to our facility for revision corpectomy and spinal fusion. Given her history of nonunion, endocrinology was consulted for evaluation of metabolic bone disease. No known personal or family history of metabolic bones disease. No history of chronic steroid use. Initial endocrine evaluation excluded common pathologies. A decision was made to pursue anabolic osteoporosis therapy to attempt to augment the spinal fusion process. Patient started on Abaloparatide 80mcg daily 2 weeks post procedure with planned 12-week therapy course. Cervical CT at 3 and 6 months showed post-surgical cervicothoracic fusion with no signs of non-union. Discussion Abaloparatide is a 34 amino acid synthetic analogue of parathyroid hormone related peptide (PTHrP) which works by selectively activating PTH1 receptor found on osteoblasts. Currently anabolic therapies are only FDA approved for treatment of osteoporosis but there is reported off label use in cases of spinal fusions, arthroplasty and fracture healing. Studies have shown that presence of PTH and PTHrP are necessary for fracture healing. Animal studies have also shown that intermittent PTH promotes spinal fusion. This case represents a novel use for Abaloparatide to augment spinal fusion in a human clinical model. Conclusion Further studies are warranted to better understand mechanism of action, drug timing and duration for optimal treatment of anabolic therapies in bone fractures and healing. The use of anabolic therapies like Abaloparatide can be considered in patients undergoing spinal fusion surgery at high risk for non-union or undergoing revision for failed fusion.ReferencesO’Loughlin PF, Cunningham ME, Bukata SV et al. Parathyroid Hormone Augments spinal fusion, fusion mass, and fusion mass quality in a rabbit spinal fusion model. Spine 2009 January; 34: 121–130
SUN-306 The Interaction Between Thiazide-Associated Hyponatremia and Acute Illness in Hospitalised Patients
Authors: Nikoi Ebenezer N A , Drake William , Glynn Nigel
Published: May 2020

Thiazide diuretics, widely used in the management of hypertension, are associated with a five times greater risk of hyponatremia (serum Na <135mmol/L) than in the general population. Hyponatremia in hospitalised patients warrants special consideration since it is associated with increased morbidity and mortality.

The aim of this study was to describe the clinical characteristics and outcomes in acutely ill medical patients with thiazide-associated hyponatremia (TAH).

We performed a retrospective, case control study examining all acute, unselected medical admissions, over a six week period, to The Royal London Hospital. Cases were defined as adults admitted to hospital with TAH (hyponatremia and a history of being prescribed thiazide diuretic pre-admission). Each case was matched by age, gender and degree of hyponatremia to a similar control - admitted with hyponatremia and no pre-admission exposure to thiazide (non-TAH). Clinical characteristics and treatment outcomes were compared between TAH and non-TAH cohorts.

A total of 1,341 consecutive acute medical admissions (49.7% men) were evaluated. Hyponatremia was detected in 240 (17.9%) admissions. Median (±SD) length of stay was longer among patients with hyponatremia compared to normonatremic patients (5.0±12.4 versus 3.0±9.2 days; p=<0.0001). In-hospital mortality was higher in the hyponatremic group (8.8% versus 4.4% p=0.005). Twenty-two cases (11 men) of TAH accounted for 9.2% of patients with hyponatremia. Median age 64±14 years was similar to other patients with hyponatremia 68±20 years. The median admission serum sodium for TAH cases was 131.5 mmol/L (IQR 126.8 - 134) with a discharge serum sodium of 136.5 mmol/L (IQR 133.8 - 139.3). When compared to matched controls, patients with TAH had similar presenting symptoms - most commonly confusion, headache and dizziness. Length of stay among TAH cases was similar to controls; 5.5±5.1 versus 4.0±3.7 days; p=0.24. Mortality (10%) was the same in both groups. Thiazide was withdrawn during admission in 14 (64%) cases.

In conclusion, acute, clinical outcomes for hospitalised patients with TAH are similar to those with comparable degrees of hyponatremia due to other causes.
MON-533 Diffuse Sclerosing Variant Papillary Thyroid Cancer: Clinical and Histopathological Features, Mutational Profile, Management and Outcome
Authors: Aljomaiah Abeer Abdulhadi , Moria Yosra , Aldaej Nora , Alswailem Meshael , Alzahrani Ali Saeed
Published: May 2020

Diffuse sclerosing variant (DSV) is a rare subtype of papillary thyroid cancer (PTC). Whether it represents a higher grade subtype than conventional PTC is not quite clear. Furthermore, there are limited data on its long-term outcome and its molecular genetics. In this report, we studied all cases of DSV PTC seen at our center during the last 20 years. Out of more than 6000 patients (pts) with differentiated thyroid cancer, only 37 were DSV. We reviewed the clinical and histopathological features, management and outcome of these cases. In addition, molecular genetics is partially achieved; 17 out of these 37 cases have been genotyped for BRAFV600E, TERT promotor mutations, NRAS, HRAS and KRAS mutations. The molecular profiling of the other 20 cases is being done. A total of 37 pts were studied {(12 Males:25 Females, median age 21 years (8-89)}. One pt had lobectomy and the other 36 pts (97.3%) had a total thyroidectomy. Central only (4 pts) or central/lateral lymph node dissection (29 pts) were performed. The median tumor size was 4.5 cm (1.5-8.1). The tumor was multifocal in 27 cases (73%), with extrathyroidal invasion in 27 (73%) and lymphovascular invasion in 24 pts (64.8%). A background lymphocytic thyroiditis was present in 12 pts (32.4%). Lymph node metastases were present in 34 pts (92%) and distant metastases in 13 pts (35%). The sites of metastasis are lungs in 12 pts (32.4%) and lungs and bone in 1 pt. Twenty pts (54.1%) were in TNM8 stage 1, 10 pts (27%) in stage 2, 1 (2.7%) in stage 4a, 3 (8.1%) in stage 4b and 3 unstageable. The ATA risk classification for these pts was 4 pts (10.8%) in low, 12 (32.4%) in intermediate, 19 (51.4%) in high-risk groups and 2 could not be assessed. I-131 was administered to 33 pts (89.2%). The median administered activity was 136 mCi (46-218). Fifteen pts (40.5%) received additional therapies (3 surgeries, 7 RAI, 5 surgeries, and RAI). In 17 pts (46%) which were genotyped, only 3 tumors (8.1%) had BRAFV600E mutation, 1 (2.7%) had TERT promotor C228T mutation and none had RAS mutations. At the last follow up, 15 pts (40.5%) achieved an excellent response, 9 (24%) an indeterminate response, 6 (16.2%) with a structural disease, and 7 (19%) were lost for follow up.

Conclusion: DSV PTC is a rare variant, occurs mostly in adolescent and young pts, characterized by aggressive histopathological features and high rates of lymph node and distant metastases but the commonly reported mutations in PTC are rare in DSV and mortality is absent.
SAT-116 An Affair of the Heart - First Case Report of Immune Checkpoint Inhibitor Associated Cardiac Sarcoidosis Presenting with Non-PTH Medicated Hypercalcemia
Authors: Attia Jonven , Goldman Bruce , Sahasrabudhe Deepak , Storozynsky Eugene , Harbuz-Miller Inga
Published: May 2020

Background:

Immune checkpoint inhibitors (ICI) are an effective new tool in the treatment of malignancy by rescuing exhausted T-cells and enhancing anti-tumor immunity. The offset of immune self-tolerance can result in autoimmune adverse effects involving gastrointestinal, pulmonary and endocrine systems. Lung and skin sarcoidosis have been described in association with ICI use. We present the first case of non-PTH medicated hypercalcemia due to cardiac sarcoidosis in the setting of immunotherapy.

Case Presentation:

A 71-year-old man was referred to endocrinology for hypercalcemia. He had a fourteen-year history of scalp melanoma in remission until February 2019, when routine surveillance scans suggested metastatic disease. Computer tomography of the chest showed mediastinal and hilar lymphadenopathy (largest node 5.2 cm) and numerous pulmonary nodules (largest 1.7 cm). Biopsy of the largest pulmonary nodule and mediastinal lymph node (LN) confirmed BRAF wild-type metastatic melanoma. Ipilimumab/nivolumab (antiCTLA4/antiPD-1) combination therapy was started. After two cycles, hypercalcemia was noted on routine laboratory surveillance. He was asymptomatic and physical exam was unremarkable. Initial workup revealed: calcium 10.6 mg/dL (8.6-10.2), albumin 4 g/dL (3.5 - 5.2), phosphorus 3.8 mg/dL (2.7 - 4.5), PTH <0.6 pg/mL (15.0 - 65.0), PTHrP <2.0 pmol/L (0.0 - 2.3), 25 hydroxyvitamin D 22. 9 ng/mL (30 - 60), vitamin A 0.59 mg/L (0.30 - 1.20). He denied taking calcium-containing supplements. He was treated with hydration and immunotherapy was continued for two cycles, followed by single agent nivolumab. After three months on ICI, the metastatic lesions were reduced in size by 30%. His calcium peaked at 12.5 mg/dL and was treated with 4mg of intravenous Zoledronic acid without resolution. He developed worsening functional status, symptomatic hypotension, and elevated troponins. Cardiac MRI demonstrated myocarditis and nivolumab-induced myocarditis was suspected. Surprisingly, endomyocardial biopsy revealed multiple granulomas suggestive of sarcoidosis. AFB, PAS and Congo red stains were negative. He was treated with supportive care and glucocorticoids with resolution of hypercalcemia and improved cardiac function. Unfortunately, serum 1,25 dihydroxy vitamin D was not successfully measured until after the first dose of prednisone and was found at the upper limit of our reference range 62.0 pg/mL (19.9-79.3).

Conclusion:

Immune checkpoint inhibitors are effective agents in treating various cancers. Adverse effects due to autoimmunity are common and early recognition of life-threatening complications is critical. Although cutaneous and pulmonary sarcoidosis have been described with ICI, to our knowledge, this is the first case report of ICI-related cardiac sarcoidosis presenting with PTH-independent hypercalcemia.