bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT-483 Levothyroxine Absorption Test: A Potential Therapeutic Tool for Levothyroxine Malabsorption
Authors: Arora Tanureet , Chua Lorayne Ann , Ismail-Beigi Faramarz , Singh Tanveer
Published: May 2020

INTRODUCTION

Persistent hypothyroidism (PH) even on high doses of levothyroxine is a common clinical problem and it is difficult to treat. Levothyroxine absorption test has been used to distinguish between pseudo-malabsorption and malabsorption as one of its causes. This test uses 1000 mcg of levothyroxine to calculate the percentage of levothyroxine absorbed. We present a case of malabsorption in which we used the levothyroxine absorption test to diagnose as well as treat malabsorption.

Case:

55-year-old male with history of papillary thyroid cancer status post total thyroidectomy, postsurgical hypothyroidism, recurrent small bowel obstruction, status post jejunal resection, complicated by high output entero-cutaneous fistula, distal high-grade obstruction status post placement of jejunal tube, chronic abdominal pain on narcotics, who initially presented with sepsis and was also found to be hypothyroid.

The thyroid stimulating hormone (TSH) level was 45.25 with free thyroxine (FT4) level of 0.54. He was adherent to his levothyroxine (LT4) 175 mcg once daily which is given one hour after tube feeds have been stopped or one hour prior to any administration of other medications.

Levothyroxine absorption test was done to distinguish between malabsorption versus pseudo-malabsorption. Three different doses of LT4 were used with results all consistent with malabsorption. The percentage of absorption with 175 mcg, 500 mcg, and 1000 mcg LT4 were 3.4%, 7.2%, and 18% respectively. The formula used to determine the percentage of absorption was (total T4 at 2 hour after LT4 administration - baseline total T4 prior to administration in mcg/L) x plasma volume in liter/dose of administered LT4 in mcg. The final prescription dose of 700 mcg once daily was then derived from the available data, which eventually corrected the patient’s hypothyroidism. Repeat testing after 2 weeks showed TSH of 0.17, FT4 of 1.29 and total T4 of 6.5. The suppressed TSH at this point was attributed to chronic narcotic use but FT4 and total T4 improved appropriately.

Conclusion:

There is no gold standard protocol for levothyroxine absorption test so we used a different protocol for LT4 dosing compared to the conventional regimen (1000 mcg of LT4). Our patient did show appropriate levothyroxine absorption on the calculated dose. Hence, the Levothyroxine absorption test may be used both as a diagnostic as well as a therapeutic tool for the patients with LT4 malabsorption causing PH.

References:

G.E. Sun, K.M. Pantalone, C. Faiman, M. Gupta, L. Olansky, B. Hatipoglu, The clinical utility of free thyroxine in oral levothyroxine absorption testing. Endocr. Pract. 20(9), 925–929 (2014)
SAT-199 Diagnostic Dilemma: An Adrenal Incidentaloma in a Young Adult
Authors: Sharma Sonia , Levine Steven N , Gu Xin
Published: May 2020

Introduction:

In an adult endocrine clinic, the majority of patients referred for evaluation of an adrenal incidentaloma are older than 30 years of age. It is important to be reminded that a patient may be diagnosed with an adrenal mass at any age but the etiology may vary depending on the age at presentation.

Clinical case:

An 18 year-old African American female with no significant past medical problems presented with a 2 month history of flank and abdominal pain associated with nausea and vomiting. An abdominal CT scan and a dedicated adrenal CT showed a right adrenal mass measuring 2.2 x 2.6 cm. The noncontrast Hounsfield units were 23, enhanced Hounsfield units 210, and delayed Hounsfield units 72. The calculated washout was 44%, not consistent with an adrenal adenoma. An MRI of the abdomen showed a 2.5 cm right adrenal nodule. The lesion did not demonstrate significant loss of signal between in and out of phase imaging, therefore the characteristics were not consistent with a lipid rich adenoma. Laboratory tests included an ACTH of 31 pg/mL (6-48 pg/mL), cortisol 8.7 ug/mL at 10:57 am (7-9 am 5.27-22.45 ug/mL), aldosterone 10.1 ng/dL (6-48 ng/dL), renin 2.2 ng/mL/hr (upright 0.5-4.0 ng/mL/hr), DHEA-sulfate 129 ug/dL (44-248 ug/dL), plasma free metanephrine 0.10 nmol/L (0.00-0.49 nmol/L), and plasma free normetaneprhine 0.41 nmol/L (0.00-0.89 nmol/L). The 24-hour urine norepinephrine, epinephrine, and metanephrine were all normal, however the 24-hour urine dopamine was elevated, 824 ug/24 hrs (52-480 ug/24 hrs). Subsequently, plasma dopamine, norepinephrine, and epinephrine were all within the reference range. The patient had a robotic-assisted right adrenalectomy removing a 5.7 x 3.5 x 1.7 cm gland, weighing 16.3 grams. The pathology demonstrated a ganglioneuroma within the right adrenal gland measuring 2.2 x 2.0 x 2.7 cm, negative for neuroblastoma or blastic components. Focal hemorrhage was noted, there was no tumor necrosis, and no mitotic figures were present. The tumor appeared to be encapsulated in the adrenal gland and the Ki-67 stain was negative in ganglioneuroma cells.

Conclusion:

Adrenal adenomas that appear as incidentalomas in young adulthood are extremely rare. Evaluating younger versus older adults found to harbor an adrenal “incidentaloma“ requires a unique approach for each age group, as the differential diagnosis varies widely. In our patient, the imaging was extremely concerning and diagnostic considerations included neuroblastoma, adrenocortical malignancy, pheochromocytoma, or ganglioneuroma. Adrenal ganglioneuromas are most frequently diagnosed in fourth and fifth decades of life. In younger adults ganglioneuromas are usually found in the retroperitoneum and posterior mediastinum. For our patient, surgical resection of the adrenal mass confirmed the pathologic diagnosis and provided definitive cure.
SAT-498 Graves’-Associated Takotsubo Cardiomyopathy: An Uncommon Condition
Authors: Mortensen Michael , Bryer-Ash Michael , Vinales Karyne Lima , Correa Ricardo Rafael
Published: May 2020

Introduction Graves’ disease is an autoimmune disorder that causes excess thyroid hormone (T4 and T3). T4 is converted into T3 (active hormone) in the peripheral tissues by the deiodinase enzyme. T3 has an effect on the cardiac electrical system as well as myocyte contractility. Excess T3 can result in cardiac arrythmias as well as ventricular dysfunction (heart failure). Takotsubo cardiomyopathy is a subtype of nonischemic cardiomyopathy related to severe physiologic or mental stress. Excess catecholamine levels have been reported to cause this disease as well. Takotsubo cardiomyopathy has rarely been reported in Graves’-associated thyrotoxicosis.

Case report 55-year-old female who presented to the ED with palpitations and difficulty breathing. She had been seen by her PCP within the past two weeks with complaint of recent 30 lb weight. TSH was noted to be < 0.001 and a neck ultrasound revealed a diffusely enlarged, hypervascular thyroid. She was referred for outpatient endocrinology consultation for further workup. Prior to her initial endocrinology appointment, she developed palpitations and shortness of breath. She did not have any known family history of thyroid disease or other autoimmune conditions. She drinks 1-2 glasses of wine per week and quit smoking in 2017. Physical exam on admission revealed a heart rate of 133 bpm and a blood pressure of 145/93, normal temperature, and normal respirations. Thyroid was diffusely enlarged and without nodularity. No evidence of orbitopathy. Heart was tachycardic but without murmur. Lungs clear. Abdomen soft, nontender. No significant peripheral edema or pretibial rash. No neurological dysfunction. Labs revealed TSH < 0.001, Free T4 > 7.77, Free T3 12.0, TRAb 44.4%, TSI 433%, Anti-TPO 614, high-sensitivity troponin of 112. EKG showed nonspecific infero-lateral T wave changes, rate 123. Echocardiogram demonstrated left ventricular apical hypokinesis but preserved basilar contractility. Ejection fraction was estimated at 40-45%. Nuclear stress test did not reveal any indication of myocardial hypoperfusion.

Discussion/Conclusion Takotsubo cardiomyopathy can mimic acute myocardial infarction both clinically as well as on EKG/serum biomarkers. Troponin levels are typically elevated as a result of myocardial stretch and subsequent troponin “leak”. Echocardiogram demonstrates apical ballooning of the left ventricle, and by definition coronary arteries will be free of significant occlusive disease. A small number of cases have been reported in association with endocrine conditions including thyrotoxicosis due to Graves’ disease. The majority of cases associated with thyrotoxicosis will resolve spontaneously with 1-3 weeks. Treatment consists of medication to decrease cardiac preload as well as afterload (ACE inhibitor, beta blocker, diuresis as needed), similar to medical treatment of other nonischemic cardiomyopathies.
SAT-442 The Impact of Chronic Excess Iodine Intake in Adult Mice Behavior
Authors: Amano Izuki , Takatsuru Yusuke , Haijima Asahi , Haraguchi Shogo , Koibuchi Noriyuki
Published: May 2020

Iodine is one of the essential micronutrient which is required for the synthesis of thyroid hormones. Thus, iodine deficiency may result in the hypothyroidism. Iodine deficiency is one of the most common causes of preventable mental retardation and brain damage in the world. On the other hand, Japanese iodine intake exceeds that of most other countries, due to the significant seaweed consumption such as kelp. The Japanese Ministry of Health, Labour and Welfare estimates average iodine consumption at 1.2mg/day in Japan. In contrast, the recommended tolerable upper intake levels for adult is 1.1 mg / day in the United States. Generally, Japanese takes twenty times higher amount of iodine than Americans. Iodine tolerance among individual humans varies greatly, and the excess iodine can cause both hyper- and hypo- thyroidism. Furthermore, the effect of thyroid dysfunction due to iodine excess on brain function has not been clarified. In this study, we generated a mouse models for chronic iodine excess and evaluated its effect on brain development. C57BL/6 dams and their pups mice were treated with KIO3 37.4mg/l through drinking water. Behavioral experiments (novel object recognition test, novel object in location test, visual discrimination test, and three-room social behavior test) were conducted at 10-weeks-old. After the behavioral analysis, mice were sacrificed to collect trunk blood and tissues. Excess iodine intake caused hypertrophy of thyroid follicles regardless of the administered dose. However, there were no differences in thyroid hormone status among groups. Thyroid hormone responsive genes in the hippocampus were also not affected in experiment group. In the behavioral analysis, female mice showed an increase in learning ability. In summary, although the chronic overdose of iodine does not affect thyroid hormone levels, it may affect cognitive learning function. The gender difference in the consequence was also observed. These results indicate that the chronic iodine excess may cause various changes, although the body is tolerable with excess iodine.
MON-506 Assessment of Quality of Life in Persons with Thyroid Cancer and Thyroid Nodules: A Single Center Experience
Authors: Raghunathan Sapna , Ouellette Caroline , Fingeret Abbey , Goldner Whitney
Published: May 2020

INTRODUCTION: Despite an excellent prognosis and survival rate, quality of life (QOL) in thyroid cancer is lower than expected. QOL in thyroid cancer survivors is similar to persons with colon and gynecologic cancers, but worse than breast cancer.1 The SF-36 QOL questionnaire has shown to be a valid tool for assessing QOL in thyroid cancer subjects.2 We evaluated QOL in both thyroid nodule and thyroid cancer patients in an institutional cancer registry.

METHODS: The Short Form-36 data version 2 (SF-36) QOL data was obtained from single institution prospective bioinformatics thyroid cancer and benign nodule registry. Physical and mental health scores from the SF-36 questionnaire were obtained from both thyroid cancer and nodule patients. Physical and mental QOL responses were scored on a scale from 20-80 and categorized as either “the same or better than the average population,”; “below average,”; or “well below average.” A two sample Wilcoxon rank sum test and a chi-squared test were used to compare QOL between thyroid cancer and nodule subjects, using QOL as a continuous or categorical variable. Univariate descriptive statistics and bivariate analyses were performed using a Wilcoxon Rank Sum and Chi-squared test for categorical QOL data and Kruskal-Wallis for continuous QOL data.

RESULTS: We analyzed 321 thyroid cancer and 32 nodule subjects who completed the SF-36 at a single point in time after diagnosis. There was no difference between the groups with regard to sex, age or QOL scores overall. Average age was 43 and 48 years in cancer and nodule groups respectively. Average Physical QOL score was 50.8 (standard deviation SD + 8.8) and 29.6 (SD+ 12.1), respectively (p=0.42). Average Mental QOL score was 48.9 (SD + 9.9) and 48.3 (SD + 8.1) respectively, p=0.16. Physical QOL score was significantly decreased as cancer stage increased when evaluating results as a continuous variable: Stage 1: 51.8 + 8.7; Stage 2: 50.6 +9.5; Stage 3: 48.7 + 7.2; Stage 4: 47.4 + 9.2. Results for mental QOL as a continuous variable by cancer stage showed improvement in reported QOL with increasing cancer stage: Stage 1: 48 (SD+ 9.9); Stage 2: 50.6 (SD + 11.1); Stage 3: 51.1 (SD + 9.13); Stage 4: 53 (SD+ 6.4), p=0.03.

CONCLUSIONS: We found no overall difference in physical nor mental QOL between patients with thyroid cancer or benign thyroid nodules. Overall, QOL was in the “same or better than average” for all respondents, but low cancer stage was associated with higher physical and lower mental QOL scores.

REFERENCES:

1. Barbus, Elena & Peştean, Claudiu & Iulia Larg, Maria & Piciu, Doina. (2016). Quality of life in thyroid cancer patients: A literature review. Clujul Medical. 90. 10.15386/cjmed-703

2. Lubitz CC, De Gregorio L, Fingeret AL, et al. Measurement and Variation in Estimation of Quality of Life Effects of Patients Undergoing Treatment for Papillary Thyroid Carcinoma. Thyroid. 2017;27(2):197-206. doi:10.1089/thy.2016.0260
MON-683 Assessment of Features Associated with Diabetic Foot Risk in General Hospital in Lima-Peru
Authors: Yovera-Aldana Marlon Augusto , Perez-Cavero Sonia Helen , Sipiran Candy Ivoone , Barrios Haydee , Callacna Eduardo , Cruz-Estacio Delia , Flores Diana Consuelo , Roncal Lorena , Huayta Julio , Damas-Casani Lucy Nelly , Zubiate Carlos
Published: May 2020

Objectives: To determine the frequency of diabetic foot risk of ulceration and associated factors in patients with type 2 diabetes mellitus.

Methods and materials: We used a cross-sectional descriptive design. Data collection was performed in the foot at risk office at Maria Auxiliadora hospital over a period of 3 years, dating from the october 2016 to september 2019.

Foot risk assessment was based on the International Working Group of Diabetic Foot (IWGDF) system, which evaluates peripheral neuropathy (with monofilament or tuning fork), biomechanical deformity, peripheral arterial disease (altered pulse or ankle branchial index) or a history of foot ulcer1,2. Foot risk frequency was found according to epidemiological characteristics, and the prevalence ratios with 95% confidence interval were calculated to association analysis, we perform bivariate and multivariate analysis using a generalized linear model. This study has the approval of the María Auxiliadora HospitaĹs Ethics Committee.

Results: a total of 402 subjects were included in this study, 63.3% were women, average age 62 yo and diabetes duration <10 years in 56%. 76.6% presented risk to develop ulcer, of which 54.7% presented biomechanical deformation, 37.3% Peripheral Neuropathy (NP), 35.4% Peripheral Arterial Disease (PAD), and 12.7% history of foot ulcer. Patients with foot at risk were associated with older age (RP 1,006, 95% CI 1,001-1.01), and with a score> 5 with respect to <5 in the Total Symptom Score (RP 1.26, 95% CI 1.05-1.51).

Conclusions: 3 of 4 patients have a foot at risk of ulceration, predominantly due to biomechanical deformation and peripheral neuropathy, and this risk was associated with older age and greater pain symptomatology.

References

1. Bakker K, Apelqvist J, Schaper NC. Practical Guidelines on the management and prevention of the diabetic foot 2011. International Working Group on the Diabetic Foot Guidelines. Diabetes Metab Res Rev. 2012; 28(1):225-231

2. Peters E, Lavery L. Effectiveness of the Diabetic Foot Risk Classification System of the International Working Group on the Diabetic Foot. Diabetes Care. 2001 24:1442–7.
SAT-062 Twins with a Homozygous Variant of ARNT2, This Is a Known Saudi Mutation (KSM) of Webb- Dattani Syndrome
Authors: Aljasser Abdullah Abdulruhman
Published: May 2020

Webb-Dattani syndrome (WEDAS) is an autosomal recessive disorder caused by mutation in the ARNT2 gene characterized by frontotemporal hypoplasia, globally delayed development, and pituitary and hypothalamic insufficiency. The condition is reported to be associated with consanguinity and with Saudi Arabian ancestry. We presented twin baby girls with developmental delayment seizures, and microcephaly. They have also hypopituitarism in the form of diabetes insipidus and hypocortlisim. also they have cortical blindness. Their brain MRI shows brain atrophic changes and delayed myelination thin corpus callosum,and small pituitary gland ad absence posterior high signal spot and pituitary stalk. Genetic testing by Exome sequencing was done and it shows A homozygous variant of ARNT2 (ARNT2:NM_014862:exon3:c.147-1G>A). One of this twin her condition deteriorated with uncontrolled seizures and spasticity and died at age 22 months. Conclusion: we report another cases of the ARNT2 mutation in a Saudi family illustrating the disease of webb-dattani Syndrome with seizures and hypopituitarism and severe visual impairment and global developmental delayment.
MON-594 The Peculiarity of the Gut Microbiota in Patients with Different Phenotypes of Obesity (Pilot Study)
Authors: Volkova Natalia , Naboka Julia , Ganenko Lilia , Oksenuk Oksana , Davidenko Ilia , Dzherieva Irina , Zibarev Alexander , Reshetnikov Igor , Sorokina Julia , Degtyareva Julia
Published: May 2020

Recent studies have shown that obesity is not a homogeneous condition and that there is a subgroup of people with obesity, but without metabolic disturbance. This phenotype of obesity is called “metabolically healthy obesity” (MHO) [1]. More and more data are appearing in the scientific literature, indicating that quantitative and qualitative changes in the gut microbiota (GM) can be a trigger in the development of obesity and metabolic disorders [2]. In order to study the role of GM in the development of various types of obesity, 37 patients were examined, divided into 3 groups: group 1 (n = 11) - healthy people without obesity and overweight (control), group 2 (n = 13) - patients with MHO, group 3 (n = 13) - patients with metabolically unhealthy obesity (MUHO). The basic metabolic parameters were determined for all of them and a quantitative assessment of the condition of the GM was performed using the Real-time PCR method. Results: 1. In people from the control group (group 1) in the GM, compared with formal normative indicators, the number of Lactobacillus spp., Bifidobacterium spp., B. thetaiotaomicron was reduced (p<0.05) and indicators of the total bacterial mass and Enterobacter spp./Citrobacter spp. were increased (p<0.05). 2. In subjects with MHO (group 2), GM changes similar to group 1 were observed. However, in comparison to group 1, Klebsiella spp. and Proteus spp. were recorded in feces in quantities exceeding the formal regulatory. In patients with MUHO (group 3), in addition to changes detected in group 2, C. difficile was found in feces, as well as a significant (p <0.05) decrease in F. prausnitzii and an increase (p <0.05) in the detection frequency of banal E.coli, as well as the more diverse composition of the microbiota. Thus, the data obtained as a result of a pilot study certainly indicate changes in the GM in people with different phenotypes of obesity and in healthy ones. Further study of the GM in patients with various types of obesity, but in a larger groups, is required. Reference: 1) Phillips C.M. Metabolically healthy obesity across the life course: epidemiology, determinants and implications. Ann N.Y. Acad Sci 2017 Mar;139(1):85-100.doi:10.1111/nyas.13230. 2). Giovanna Muscogiuri, Elena Cantone, Sara Cassarano, Dario Tuccinardi, Luigi Barrea, Silvia Savastano, Annamaria Colao & on behalf of the Obesity Programs of nutrition, Education, Research and Assessment (OPERA) group. Gut microbiota: a new path to treat obesity. International Journal of Obesity Supplements 2019 Apr;9(1):10-19. doi: 10.1038/s41367-019-0011-7
MON-244 Adenocarcinoma Pituitary Metastasis with Suprasellar Extension
Authors: Reddy Nithin Modhugu , Sethi Bipin Kumar , Kandula Srinivas G N S V , Modi Kirtikumar D , Praveen Kumar
Published: May 2020

Background

Metastasis to the pituitary gland (MP) is an infrequent clinical problem, however, during the last few decades, MPs is increasing in frequency, due both to the improved cancer survival rates and availability of better imaging techniques. Breast cancer, lung cancer and lymphoma are the most common primary sites. MP mimics pituitary adenoma making the diagnosis difficult, especially when clinical evidence of the primary malignancy is absent. We report a case of histologically confirmed pituitary metastasis (adenocarcinoma) from carcinoma of unknown primary, leading to and presenting as panhypopituitarism.

Case details

54 year male HBV carrier, asthmatic, non smoker, non alcoholic was seen elsewhere with complaints of increased frequency of micturition associated with nocturia, increased thirst, asthenia and weight loss of 05 kg since 06 months. He also had loss of libido and erectile dysfunction. Patient never experienced headache, vomiting or visual disturbances. There was no personal or family history of malignancy. On physical examination skin was pale, atrophic with fine wrinkles around the eyes. He had BP of 96/60mmHg and PR 100/min but system examination was otherwise unremarkable. Biochemical evaluation confirmed diabetes insipidus, secondary hypothyroidism, adrenal insufficiency and hypogonadism. MRI Brain showed a mass like thickening (11.6 x 11 x 16mm) of the infundibulum and posterior portion of the pituitary gland with upward displacement of optic chiasm. Workup for granulomatous conditions (sarcoidosis/ disseminated Koch’s) was negative. He was initiated on desmopressin, thyroxine, hydrocortisone, testosterone and managed elsewhere as hypophysitis.

At presentation to us after 3 months of treatment, visual field examination showed decrease in peripheral vision involving right superior temporal quadrant and an attempt was made to delineate the size and etiology of the lesion. Repeat imaging revealed increase in size of the lesion to 12 x 15 x 18mm. He underwent TSS and the lesion was biopsied. Histopathology showed infiltrative adenocarcinoma with CK20 +, CK7 -, and GATA3 + on IHC. Post procedure WB-PET CT, showed metabolically active residual tumor in suprasellar region and negative for metabolically active disease in other areas. Upper GI Endoscopy, Colonoscopy and Bronchoscopy were also normal. Currently he is on adjuvant radiation therapy for residual suprasellar lesion.

Conclusion

Pituitary metastasis may be difficult to differentiate from other lesions in the sellar/parasellar region, presentation as DI and thickened stalk confounded the diagnosis, given that it is a feature of the commoner lesion- hypophysitis. This case reports the rare occurrence of CK20 positive, CK7 negative adenocarcinoma metastasis to pituitary and no evidence of primary.
MON-713 Nuclear Corepressor; SMRT Acts as an Important Regulator for Both Beta-Oxidation and the Maturation of Myogenesis in Mouse C2C12 Cell
Authors: Shimizu Hiroaki , Horibata Yasuhiro , Aoyama Chieko , Amano Izuki , Ritter Megan , Ando Hiromi , Sugimoto Hiroyuki , Hollenberg Anthony Neil
Published: May 2020

Background: Silencing Mediator of Retinoid and Thyroid hormone receptors (SMRT; NCoR2) is a transcriptional corepressor which has been recognized as an important player in the regulation of hepatic lipogenesis and the somatic development in mouse embryo. SMRT protein is also widely expressed in the mouse connective tissues, for example adipocyte and skeletal muscle, and we recently reported that the mouse of global deletion of SMRT causes significant obesity which is independent from thyroid hormone signaling and thermogenesis. However, the tissue specific role of SMRT in skeletal muscle is still unelucidated. Methods: To clarify this, we took the gene targeting strategy for SMRT using CRISPR Cas9, and made the myogenic C2C12 clone which lacks SMRT protein (C2C12-SMRTKO; SKO). For this study, wild type C2C12 cell (WT) and SKO cell were cultured in differentiation medium (DMEM+2% horse serum) for 5-6 days, and analyses for gene expression compared two cell types were performed. Results: We found the significant up-regulations of muscle specific beta-oxidation related genes (ex. Ppar delta, Ampk2), and higher protein level of PGC-1A in the SKO cell, suggesting that SKO cell had similar gene profile to that of rodent skeletal muscle in the exercise test. On the other hand, confocal microscopic analysis showed SKO cell had decreased cell-fusion and loss of myotube, indicating that the morphology was similar to immature mouse myoblasts. Further gene analyses compared between WT and SKO cell demonstrated that SKO cell had higher expressions of myogenic markers; MyoD and Myogenin. However, interestingly, the lower expressions of muscle constitutive genes; MHC, Actin, and Alpha-dystrobrevin were found in the SKO cell. These data indicate that the SKO cell has incomplete muscle fiber formation. Conclusion: Taken together, we demonstrate that SMRT works as a pivotal transcriptional mediator for both beta-oxidation and the process of myotube formation in C2C12 cell. Further inquiry for the cause of sarcopenia-like phenotype manifested in the SKO cell will be needed.
MON-486 Polygenic Susceptibility to Papillary Thyroid Cancer in Italian Subjects
Authors: Brigante Giulia , Lazzaretti Clara , Paradiso Elia , Foersti Asta , Hemminki Kari , Elisei Rossella , Romei Cristina , Rochira Vincenzo , Simoni Manuela , Landi Stefano , Casarini Livio
Published: May 2020

INTRODUCTION AND AIM. Thyroid cancer is the most common endocrine neoplasia, with an estimated age-standardized incidence rate of 6.7 per 100000 worldwide in 2018 [1]. This rate is rapidly increasing and papillary thyroid carcinoma (PTC) is the main histotype. PTC susceptibility is the result of genetic predisposition, environmental factors and lifestyle. We studied the genetic combination that characterizes PTC affected subjects, differentiating them from healthy controls.

METHODS AND RESULTS. We considered the genetic variants (SNPs) significantly associated with PTC on the PubMed database. 184 informative SNPs were selected, considering linkage disequilibrium. Then, SNPs data were extracted from the online 1000 Genomes database, comprising genome of 2504 unselected individuals collected worldwide. The combination of 184 SNPs associated with PTC was used to group individuals in different risk-clusters according to their genetic structure, calculated by Bayesian statistics, as previously performed for polycystic ovary syndrome [2]. Individuals were distributed among 7 groups worldwide, indicating different degree of genetic predisposition to PTC. We then considered genetic data from about 1200 individuals (697 PTC versus 497 healthy controls) of Central/South Italian origin registered in a GWAS, specific for PTC [3]. This first analysis was refined using the 33 SNPs reasonably most causative of genetic clustering (26 with p<0.05 at trend test in GWAS and 7 with p<0.05 in the model of recessive inheritance). At multivariate logistic regression analysis, PTC and healthy controls resulted genetically different (ODDS RATIO 188.6, 95%CI 64.35-552.8), revealing diverse predisposition to develop cancer. Afterwards, these results have been confirmed in an independent cohort of Italian subjects (234 PTC and 100 controls). Then, the genetic structure of each subject was indicated as a percentage of affinity to each risk-cluster and re-analyzed together with other risk factors: sex, body-mass index, area of origin and familiarity (quantified in a growing score as the degree of kinship increases). These data were analyzed together by principal component analysis and clustering of the two groups was even more pronounced. The most contributive factors to the diversity between PTC and healthy controls were genetics and familiarity.

CONCLUSION. We demonstrated that PTC affected subjects are genetically different from healthy controls, and that the difference is identifiable in a peculiar combination of genetic variants.

REFERENCES

1. Bray F et al. CA: a cancer journal for clinicians. 2018; 68 (6):394-424

2. Casarini and Brigante. JCEM. 2014; 99:E2412-20

3. Köhler et al. Genome-wide association study on differentiated thyroid cancer. J Clin Endocrinol Metab. 2013;98:E1674-81.
SAT-265 An Asynchronous Double Growth Hormone Secreting Pituitary Adenoma as a Cause of Rapid Tumor Regrowth After Initially Successful Surgery
Authors: Trofimiuk-Muldner Malgorzata , Lukasz Kluczynski , Zielinski Grzegorz , Sokolowski Grzegorz , Maksymowicz Maria , Pekul Monika , Hubalewska-Dydejczyk Alicja
Published: May 2020

Background. Double pituitary adenomas are a rare entity, which requires clinical attention and a careful follow-up. Case report. A 37-year-old man presented with left-sided painful gynecomastia. He denied typical symptoms of excessive growth hormone (GH) secretion and did not show any acromegalic features. Due to low testosterone and LH levels with mild hyperprolactinaemia, the patient was referred to pituitary MR, which revealed an 11x13 mm right-sided sellar tumor. An increased IGF-1 was noted subsequently (1482 ng/mL; N 109-284 ng/mL), together with the lack of GH suppression in OGTT. Transphenoidal resection of pituitary tumor performed in 2012 led to biochemical (IGF-1 260 ng/mL, GH 0.08 ng/mL) and radiological remission of the disease. A histopathology report revealed a densely granulated somatotropic pituitary adenoma with mild nuclear atypia, expressing somatostatin receptors [sstr2A (+), sstr5 (+/-)]. Due to gradually increasing IGF-1 levels (with low, although rising, GH values ranging from 0.07 to 0.92 ng/mL) in subsequent years, OGTT was repeated in 2015, showing appropriate GH suppression. In 2016, however, acromegaly recurrence was confirmed both biochemically (increasingly high IGF-1 - 664 ng/mL - and unsuppressed post-OGTT growth hormone) and in MR imaging. The patient was reoperated in June 2017. The second histopathology reported an oncocytic somatotropic acidophil stem cell pituitary adenoma with Ki-67 >3% and mitotic figures. Subsequent anterior pituitary lobe insufficiency (adrenal, thyroid and gonadal axis) was found and adequately treated. Complete tumor removal was confirmed by MR performed three months after repeated surgery, as well as a low GH level (0.97 ng/mL), although accompanied by borderline IGF-1 values (277 ng/mL). Eighteen months after surgery, the recurrence of acromegaly was again confirmed, with adenoma regrowth and increased GH (2.31 ng/mL) and IGF-1 (474 ng/mL) levels. Octreotide LAR was started (despite retina wrinkling which was observed when lanreotide was administered before the first surgery), which led to a normalization of GH (0.96 ng/mL) and IGF-1 levels (152 ng/mL), as well as partial pituitary tumor regression after six months therapy. Conclusion. In a case of GH-secreting pituitary adenoma recurrence after apparent successful surgery, a double pituitary tumor with more aggressive histology should be considered.
SUN-397 The Osteosee System Measurements, Based on Parametric Electrical Impedance Tomography, Correlate with Dual X-Ray Absorptiometry Results for the Diagnosis of Osteoporosis
Authors: Rouach Vanessa , Pushevsky Yuliana , Mayboroda Alla , Osherov Alina , Guindy Michal
Published: May 2020

Introduction: Dual X-Ray Absorptiometry (DXA) is the gold standard for the diagnosis of osteoporosis, but it has its pitfalls. The OsteoSee @Clinic is a novel portable and user-friendly system, which uses parametric Electrical Impedance Tomography (pEIT), being developed to allow screening and diagnosis of osteoporosis at the primary care clinic

Aim: To test the new system and compare its results to those of the DXA system.

Methods and Subjects: This prospective study was conducted between 01/01/2019 and 01/06/2019. Subjects who presented for a routine DXA scan (lumbar spine and proximal femur with Lunar Prodigy GE healthcare system) were enrolled. After signing an informed consent form, they were scanned with the OsteoSee @Clinic system (OsteoSee Ltd., Israel) using 5 electrodes placed around the left distal forearm and around the pelvis.

Results: OsteoSee @Clinic data were compared to DXA total hip bone mineral density (BMD). Correlations were examined between pEIT-index of the pelvis versus DXA total hip BMD. Sensitivity and specificity were calculated according to the diagnosis obtained by DXA based on the total hip T-score. An analysis based on 182 subjects (35 healthy, 115 osteopenia, 32 osteoporosis) scanned on the wrist showed an R-value of 0.795 (p-value < 0.001) representing the correlation between the pEIT-wrist index and DXA results. From the ROC plot, we obtained a sensitivity of 84% and specificity of 71% to diagnose osteoporotic vs osteopenic & normal subjects, and a sensitivity of 82% and specificity of 86% for identifying osteopenic & osteoporotic vs normal subjects. An analysis of 98 subjects (17 healthy, 66 osteopenic, 15 osteoporosis) scanned on the pelvis showed an R-value of 0.740 (p-value < 0.001), representing the correlation between the pEIT-pelvis index and DXA BMD. From the ROC plot, we obtained a sensitivity of 80% and specificity of 81% to diagnose osteoporotic vs osteopenic & normal subjects, and a sensitivity of 70% and specificity of 76% for identifying osteopenic & osteoporotic Vs normal subjects.

Conclusions: The OsteoSee @Clinic system results correlate well with DXA measurements, especially when taking into account clinical interpolations. Sensitivity and specificity values indicate that the OsteoSee @Clinic system can provide screening and diagnosis of osteoporosis. With the DXA system being costly to operate and inaccessible to many patients, the OsteoSee @Clinic system may address the unmet need for diagnosing and treating osteoporosis, and offer an alternative for a broader screening of the population at risk of fractures.

Disclosure: The study was funded by OsteoSee Ltd., Israel
OR27-02 An Exploration of Novel Clinical Benchmarks for Assessing the Practice of Gonadectomy in Conditions Affecting Sex Development - on Behalf of the I-DSD Consortium
Authors: Lucas-Herald Angela K , Bryce Jillian , Cools Martine , Ahmed S Faisal
Published: May 2020

Introduction: Although the practice of gonadectomy in the field of differences/disorders of sex development (DSD) has undergone intense scrutiny, objective knowledge regarding current practice of gonadectomy is lacking in conditions affecting sex development. Methods: The International DSD Registry (www.I-DSD.org) was examined for clinical information reported by the DSD specialist centre on age at presentation, year of birth, diagnosis, karyotype, sex of rearing and age at gonadectomy in all cases over the age of 16 years at the time of search and who had a disorder of androgen action or synthesis, gonadal dysgenesis or a non-specific DSD.Results: Of the 3,618 cases available in the registry, 757 (21%) met the inclusion criteria and data regarding gonadectomy status were available in 668 (88%) from 44 participating centres. Of these, 248 (37%) with a median age of 24 years (range 17, 75) were registered as male and 420 (63%) with a median age of 26 years (16, 86) were registered as female. Gonadectomy was reported from 36 centres in 351 of these 668 cases (53%) of whom 302 (86%) had a 46 XY karyotype. Females were more likely to undergo gonadectomy (n=311, p<0.0001) and the most common diagnoses were complete androgen insensitivity syndrome (n=161, 24%) and partial gonadal dysgenesis (n=94, 14%). Of the 351 cases, the primary indication for gonadectomy was reported in 268 (76%) cases and included mitigation of tumourigenesis risk in 172 (64%), conformity to sex assignment in 74 (28%) and another indication in 22 (8%). Gonadectomy was bilateral in 295 (84%), unilateral in 16 (5%) and unknown in 40 (11%). The median ratio for age at first presentation to age at gonadectomy in those who presented before the age of 5 years and those who presented after the age of 10 years was 0.1 (range) and 0.9 (range), respectively (p<0.0001). Of the 351 cases, 17 (5%) had undergone a gonadectomy before their first presentation to the specialist centre and these cases were distributed across 9 of the 36 centres. Conclusions: Not only does the rate of gonadectomy vary according to underlying diagnosis and sex of rearing, it also seems that there is a variable discrepancy between the age at presentation and age at gonadectomy. The use of this objective marker to identify trends in practice may improve our understanding of the causes of variation.
SAT-744 Spiral Steroid Lactones Are Synthesized by Condensation of a Steroid Precursor with Coenzyme a Derivatives
Authors: Chasalow Fred I
Published: May 2020

Background: Szent-Gyorgyi proposed that digoxin wasn’t really drug but was a substitute for an endogenous cardiotonic steroid (ECS). Endogenous ouabain and marinobufagenin have been proposed as ECS.

Hypothesis: Ionotropin, our first candidate for the ECS, is unique among steroids because it is the phosphocholine ester of a steroid with 23 carbon atoms. Logically, either there must be a novel mechanism for adding carbon atoms to a pregnenolone-like precursor or a novel mechanism for side-chain cleavage from a cholesterol-like precursor.

Experimental design: Serum samples were extracted with acetonitrile, filtered and analyzed by MS-N on an LTQ-XL ion trap mass spectrometer. The instrument permits multiple rounds of fragmentation and identification of the parent ion and each fragment ion. This process permitted recognition of ions that were phosphocholine esters and of the mass of the steroid fragments. The chemical formula of each steroid fragment was determined by trial and error analysis. Although not every mass ion has a unique chemical formula, in fact, each of the steroid ions had a unique formula. Possible isomers were resolved by consideration of knowledge of steroid biosynthetic pathways.

Major results: In brief, human serum samples had steroid fragment ions consistent with 23 (354 Da) and 25 (398 Da) carbon atoms. This provides an additional constraint as the synthetic mechanism must account for both products. These mass ions were consistent with condensation of either acetyl-CoA or acetoacetyl-CoA with the phosphocholine ester of pregna-5,7-diene-3β,17α-diol-20-one. After condensation, the steroid adduct would be dehydrated and cyclized to form the corresponding spiral steroid phosphocholine ester. This pathway is similar to the mechanism of addition of 2 carbon fragments to a long chain fatty acid. This is the first explanation for the biosynthesis of endogenous mammalian ECS. Spiral lactones would be expected to cross react with many antibodies specific for digoxin, ouabain or marinobufagenin. Either one of the spiral lactones would satisfy Szent-Gyorgyi’s suggestion as the endogenous digoxin-like material.

Conclusions: In summary, we have isolated 2 spiral steroid lactones from mammals and identified the mechanism of their biosynthesis. We propose, as the spiral steroids share structural features with the spironolactone class of potassium sparing diuretics, that they also share functions. Nicholls proposed that a candidate for ECS should not be accepted without [a] isolation, [b] precursors, and [c] a biosynthetic path. As there has been no satisfaction of these requirements for ouabain or marinobufagenin, their existence as ECS in mammals needs to be reconsidered.
SUN-610 Acquired Generalized Lipodystrophy: A Rare Side Effect of PD1-Inhibitor Therapy
Authors: Shah Amy , Rodriguez Juan Pablo Perdomo
Published: May 2020

Background:Program cell death-1 (PD1) inhibitors, such as nivolumab and pembrolizumab, have shown efficacy as adjuvant treatment for cancers, including melanoma, and their frequency of use is increasing. A potential, but rare, side effect of PD1-inhibitors is acquired generalized lipodystrophy (AGL), an immune-related adverse event characterized by loss of subcutaneous adipose tissue (SAT) and insulin resistance-associated complications. AGL can result in irreversible endocrinopathies, including diabetes. Clinical Case: A 60-year-old overweight female (BMI 29.2), with no related metabolic complications or medical history of autoimmune disorders, was treated with nivolumab (240mg IV q2 weeks) for 1 year for metastatic melanoma on her right arm (staged T4bN2a) that underwent wide local resection. She completed therapy with no complications or lab abnormalities.One-month post-treatment, she noticed rapid weight loss and facial atrophy. Within 3 months, she had a 58% weight loss withsignificant loss of SAT; insulin resistance and diabetes(impaired fasting glucose 201; A1c 9.2%);hepatic steatosis diagnosed by liver biopsy; hypertriglyceridemia (5,309 mg/dL,); and undetectable leptin levels. She also developed prominent forearm muscles and leg veins. GAD antibody was negative. The loss of SAT and rapid weight loss, physical exam findings, onset of diabetes, steatosis and hypertriglyceridemia—all closely following therapy with nivolumab—led to a diagnosis of nivolumab-associated AGL. In addition to treatment for hypertriglyceridemia, the patient was placed on multiple oral and parenteral antihyperglycemic medications, including metformin, SGLT2i, GLP-1, and DPP4, but all were discontinued due to side effects. Ultimately, her A1c increased to 12.4% and she was placed on basal/bolus therapy. Discussion: AGL is associated with an increased risk of lymphoma. Metreleptin, a recombinant analogue of human leptin, is approved for treatment of metabolic complications of AGL. Some instances of lymphoma in AGL have occurred while the patient was receiving metreleptin, but data is inconclusive as to whether development of lymphoma is a side effect of metreleptin.(Brown RJ, Chan JL, Jaffe ES, et al, 2016) We believe treatment with metreleptin would have benefited our patient, but she declined due to potential side effects, including lymphoma. Nine months after nivolomuab therapy, her melanoma is in remission but she still has lipodystrophic characteristics with insulin resistant diabetes. She is being treated with pioglitazone and multiple daily insulin injections but has not achieved euglycemia despite a total daily insulin dose of 2 u/kg. Of note, injecting insulin and use of a continuous glucose monitor have been a challenge given the lack of SAT. Although AGL resulting from PD1-inhibitor therapy is rare, it is a condition for which this patient will need life-long treatment.
SAT-391 Safety and Efficacy of Conventional Therapy with Calcium and Activated Vitamin D in Patients with Chronic Post-Operative Hypoparathyroidism: Results of a Cross-Sectional Case-Control Study
Authors: Mazoni Laura , Apicella Matteo , Matrone Antonio , Saponaro Federica , Biagioni Isabella , Cosci Bianca , Cetani Filomena , Marcocci Claudio
Published: May 2020

Introduction: Conventional therapy of chronic post-operative hypoparathyroidism (PO-HypoPT) with calcium and activated vitamin D is suboptimal and associated with several complications, including impairment of the quality of life. Aim of this study was to compare clinical, biochemical and instrumental parameters in 120 patients who underwent total thyroidectomy for differentiated thyroid cancer, 60 with PO-HypoPT (Group A) treated with conventional therapy and 60 without (Group B), matched for age and sex, followed a tertiary referral center. Matherials and methods: An “ad hoc” CRF was used to collect epidemiological, clinical (symptoms, treatment) and biochemical data (total and ionized calcium, albumin, phosphate, magnesium, calcium/phosphate product, creatinine, 25-OH vitamin D, PTH, TSH, eGFR, 24-h urinary calcium and creatinine), and renal ultrasound. Results: The median duration of PO-HypoPT was 7 years (IQR 4-13). All patients of group A were treated with calcitriol (median 0.5 μg/daily; IQR 0.5-1.0), and 33/60 (55%) were also given calcium carbonate supplementation (median 1000 mg/daily; IQR 500-1000). Hypocalcemia related symptoms were more frequent in group A (27/60 - 45%) than in group B (1/60 - 1.7%) (p<0.01). Total and ionized serum calcium [median 8.9 (IQR 8.5-9.1) vs 9.3 (IQR 9.0-9.5) mg/dl; median 1.16 (IQR 1.1-1.2) vs 1.23 (IQR 1.21-1.27) mmol/L] (p<0.01), magnesium [median 1.9 (IQR 1.8-2.0) vs 2 (IQR 1.9-2.1) mg/dl - p<0.01] and PTH [median 10 (IQR 8-13) vs 29 (IQR 22-35) pg/ml - p<0.01] were significantly lower in Group A vs Group B. Conversely, serum phosphate [median 3.7 (IQR 3.4-4.1) vs 3.3 (IQR 3.0-3.6) mg/dl - p<0.01], calcium-phosphate product [median 33 (IQR 30-36) vs 30 (IQR 27-34) - p=0.012] and 25-OH vitamin D [median 34.1 (IQR 29.2-41.3) vs 26.7 (IQR 18.1-33.4) - p<0.01) were significantly higher in Group A vs Group B. Twenty-four hour urinary calcium was higher in group A [median 248 mg (IQR 166-363)] than in group B [median 165 mg (IQR 94-229)] (p<0.01). The rate of nephrolithiasis was significantly higher in group A (21/60 pts - 35%) than in group B (7/60 pts - 11.7%) (p<0.01). Moreover, there was a significant correlation of neprholithiasis with 24h urinary calcium but not with total and ionized serum calcium. Conclusions: This cross-sectional case-control study confirms that treatment of chronic PO-HypoPT with conventional therapy is suboptimal, even in a tertiary referral center, and associated with an increased risk of nephrolithiasis. Following the recent publication of treatment guidelines, the question of whether a better quality of care, including the use of rhPTH, will improve the biochemical control and decrease the rate of hypercalciuria and the risk of nephrolithiasis remains to be established.