bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT-266 Accelerated Osteoporosis - a Rare Presentation of Cushing’s Disease
Authors: Sekar Vijaykumar , Hughes Joseph , Gouli Sugam
Published: May 2020

Background:

Osteoporosis in post-menopausal women is usually due to bone loss from estrogen deficiency and/or age. Secondary osteoporosis (SO) is less common. Up to 30% of postmenopausal women and 50% of men with osteoporosis may have an underlying cause. Cushing’s disease (CD) is one cause of SO but rarely the presenting symptoms. The prevalence of osteoporosis (69.6% vs 37.8%) is significantly higher in patients with adrenal rather than pituitary CD. Diagnosing CD remains a challenge to physicians in spite of advances in diagnostic techniques. We report a case of CD in a post-menopausal woman presenting as accelerated osteoporosis.

Clinical Case

A 63-year-old Caucasian female with a history of hypertension and hysterectomy in her 50s on transdermal estrogen was referred to our Endocrine clinic for evaluation of osteoporosis and incidental finding of bilateral adrenal hyperplasia on CT spine. The patient rapidly developed kyphoscoliosis within the past 2 years. She was debilitated by pain and decreased mobility from compression fractures and spinal stenosis, and underwent thoracic and lumbar fusion surgery.

On physical examination, her heart rate was 64 beats per minute, blood pressure 130/92 mmHg, weight 188 lbs. and Height 5.1 ft; a year ago it was 5.5 ft. Her face appeared round but not red. Buffalo hump and supraclavicular pad were noted. No striae or bruises noted. Healing surgical scars over the thoracic and lumbar spine were violaceous.

The patient’s urine free cortisol levels, tested a month apart, were 190 mcg and 132 mcg (n 3.5-45 mcg/24h). Midnight salivary cortisol levels taken consecutive nights were 160 ng/dL and 513 ng/dL (n < 100 ng/dL). Morning Serum Cortisol and ACTH were 20.2 ug/dL and 14 pg/mL (n Cortisol 6.0-27.0 ug/dL and ACTH 7.2-63 pg/mL). Following low dose (1mg) dexamethasone suppression testing, her serum cortisol were 12.6 ug/dL, ACTH levels were 32 pg/mL and dexamethasone were 187 ng/dL (n < 30 ng/dL). 25-Hydroxy D total, TSH, Free T4, PTH intact, calcium, renin, aldosterone and SPEP levels were normal. Renal and liver functions were normal except alkaline phosphatase was 142 U/L (n 34-104 U/L). Pituitary MRI with contrast showed pituitary microadenoma. The patient was referred to a neurosurgeon and is planned for an inferior petrosal sinus sampling prior to transsphenoidal resection.

Conclusion

Cushing’s disease as a cause of osteoporosis is rare. Diagnosis of Cushing’s can be challenging in patients without obvious signs, as in our patient who was referred to an endocrinologist due to incidental finding of bilateral adrenal hyperplasia. A high degree of clinical suspicion is needed when investigating CD, as initial test results can be indecisive. As in our patient, initial ACTH and cortisol levels were normal, the low dose dexamethasone suppression test helped us direct our diagnosis towards CD.
SUN-046 Prevalence of Polycythaemia with Different Formulations of Testosterone Therapy in Transmasculine Individuals
Authors: Nolan Brendan J , Leemaqz Shalem Y , Ooi Olivia , Cundill Pauline , Silberstein Nicholas , Locke Peter , Grossmann Mathis , Zajac Jeffrey D , Cheung Ada S
Published: May 2020

Background: Masculinising hormone therapy with testosterone is used to align an individual’s physical characteristics with their gender identity. Testosterone therapy is typically administered via intramuscular or transdermal routes and polycythaemia is the most common adverse event.

Aims: To compare the risk of polycythaemia with different formulations of testosterone therapy in transmasculine individuals.

Methods: A retrospective cross-sectional analysis was undertaken of transmasculine individuals at a primary and secondary care clinic in Melbourne, Australia. 180 individuals who were on testosterone therapy for >6 months were included. Groups included those receiving (1) intramuscular testosterone undecanoate (n=125), (2) intramuscular testosterone enantate (n=31), or (3) transdermal testosterone (n=24). Outcome was prevalence of polycythaemia (defined as haematocrit >0.5).

Results: Mean age was 28.4 (8.8) years with a median duration of testosterone therapy 37.7 (24.2) months. 27% were smokers. There was no difference between groups in serum total testosterone concentration measured. Whilst there was no difference between groups in haematocrit, there was a higher proportion of patients with polycythemia in those who were on intramuscular testosterone enantate (23.3%) than on transdermal testosterone (0%), p=0.040. There was no statistically significant difference in polycythaemia between intramuscular testosterone undecanoate (15%) and transdermal, p=0.066 nor between intramuscular testosterone enantate and undecanoate, p=0.275.

Conclusions: One in four individuals treated with intramuscular testosterone enantate and one in six treated with testosterone undecanoate had polycythaemia. No individual treated with transdermal testosterone had polycythaemia. This highlights the importance of regular monitoring of haematocrit in transmasculine individuals treated with testosterone and findings may inform treatment choices.
MON-340 Isolated Extrapulmonary Sarcoidosis Presenting as Symptomatic Hypercalcemia
Authors: Swami Janya
Published: May 2020

Introduction: Sarcoidosis is a granulomatous disease of unknown etiology often involving multiple organ systems. Sarcoidosis most frequently affects the lungs, but in upto 30% of cases, can present with extrapulmonary manifestations. Less than 10% of patients with sarcoidosis present with disease at extrapulmonary sites. 10%-20% patients with sarcoidosis present with hypercalcemia. Hypercalcemia in sarcoidosis is secondary to increased intestinal calcium absorption due to increased levels of 1,25-dihydroxy Vitamin D. Clinical Case: 71-year-old Caucasian male presenting to his primary care physician with 3-week duration of fatigue, anorexia, mild confusion and unintentional weight loss was found to have moderate hypercalcemia and acute kidney injury. He was admitted the hospital for evaluation and management. Labs at admission revealed albumin-corrected calcium of 13.5 mg/dL (normal 8.5-11.0 mg/dL), creatinine of 1.78 mg/dL (normal 0.7- 1.3mg/dL) and alkaline phosphatase of 173 U/L (normal 45-117 U/L). Workup noted low PTH (3,normal 14-72 pg/mL), normal 25-hydroxy Vitamin D (50.7,normal 30-100 ng/dL), normal PTHrP and normal serum electrophoresis and immunofixation indicating non-PTH dependent hypercalcemia. 1,25-dihydroxy Vitamin D (125, normal 18-64 pg/mL) and ACE levels (159 U/L, normal 16-85 U/L) were elevated. Patient denied being on any Vitamin D supplements. A CT chest, abdomen and pelvis was done to look for occult malignancy and hepatosplenomegaly was noted with only mild compressive atelectasis of lungs. Abdominal ultrasound confirmed hepatomegaly with lobulated outer contour consistent with cirrhosis. Acute hepatitis, infectious and autoimmune work up was negative. Patient was discharged with mild improvement in calcium and mental status with hydration. Due to high suspicion for granulomatous disease, a liver biopsy was done. Liver biopsy confirmed granulomatous hepatitis with stage 2 of 4 fibrosis with numerous foci of non-caseating granulomatous inflammation. With negative acid-fast staining, no fungal organisms, absence of foreign material, normal eosinophil counts and low clinical suspicion for Crohn’s disease, a diagnosis of abdominal sarcoidosis was made. The patient was started on 10 mg prednisone daily and within one week, his albumin- corrected calcium levels improved to 10.4 mg/dL with significant improvement in appetite and mental status. Conclusion: While isolated extrapulmonary sarcoidosis is rare, it is an important cause of hypercalcemia due to elevated 1,25-dihydroxyvitamin D levels. Management of hypercalcemia secondary to sarcoidosis often consists of initiating glucocorticoids which act mainly by inhibition of 1,25-dihydroxy vitamin D synthesis in addition to inhibiting calcium absorption and osteoclast activity.
MON-347 Osteitis Fibrosa Cystica and Pathological Fractures: The Classic but Neglected Skeletal Manifestation of Primary Hyperparathyroidism
Authors: Sirinvaravong Sirinart , Singsumpun Nontouch , Vanitcharoenkul Ekasame , Unnanuntana Aasis
Published: May 2020

Background: Osteitis fibrosa cystica is one of the classic manifestations of primary hyperparathyroidism (PHPT), yet it has become increasingly rare due to early detection of PHPT.

Clinical case: A 37-year-old woman was referred to our hospital for fixation of multiple fractures. Before transferring to our hospital, she was admitted to a local hospital due to right distal humerus and left tibial fractures without history of trauma. During the hospitalization, a new fracture at left femur had occurred. Her past medical history was significant for fractures of right shoulder, left elbow and right femur when she fell on the ground 5 years ago and treated by fixation. She had a history of kidney stones in the remote past. She denied family history of calcium or skeletal disorders.

Clinical examination revealed gross deformities at right elbow, left thigh and painful swelling of the left tibia. On HEENT examination, there were no palpable neck masses.

Upon review of plain radiographs from outside hospital, we found not only fractures but diffuse osteopenia and brown tumors at multiple sites including shaft of right humerus, right proximal radius, left proximal femoral shaft and left tibia. Skull X-ray showed salt-and-pepper appearance. There were prominent subendplate densities at multiple lumbar spines (Rugger-jersey spine). These findings were consistent with osteitis fibrosa cystica which prompted further laboratory investigation for PHPT. The patient had a high corrected serum calcium level of 13.6 (8.6-10.0) mg/dl, low serum phosphate of 2.2 (2.5-4.5) mg/dL, serum creatinine of 1.16 (0.51-0.95) mg/dL, glomerular filtration rate (GFR) of 60.29 ml/min, high serum alkaline phosphatase of 1,482 (35-105) U/L. The serum parathyroid hormone (PTH) level was significantly high at 3,850 (15-65) pg/mL. Vitamin D level was low at 5.98 (≥30) ng/mL.

The patient was diagnosed with PHPT. The left lower parathyroid adenoma was identified by 99mTc-Sestamibi scan with single photon emission computed tomography and neck ultrasound. Given severe skeletal manifestations and extremely elevated PTH level, urgent parathyroidectomy was performed. A 2.5-cm parathyroid adenoma was removed which was histologically confirmed by a pathologist. Postoperatively, she developed a hungry bone syndrome which resolved 10 months after.

Clinical lesson: In current practice, skeletal manifestation of PHPT is uncommon with a reported incidence of 1.4% in US. Osteitis fibrosa cystica is a radiographic feature of PHPT characterized by demineralized skeleton, salt-and-pepper appearance of the skull, subperiosteal resorption of the phalanges, bone cysts, and brown tumors. Although PHPT has evolved to asymptomatic disease in majority of patients, the classic skeletal involvement should not be overlooked, particularly in young patients who present with multiple pathological fractures.
OR32-02 Immune Checkpoint Inhibitor-Induced Hypophysitis Is Associated with Improved Overall Survival in Cancer Patients
Authors: Kotwal Anupam , Rouleau Samuel G , Kottschade Lisa , Ryder Mabel M , Kudva Yogish C , Markovic Svetomir , Erickson Dana Z
Published: May 2020

Context: Immune checkpoint inhibitors (ICIs) are monoclonal antibodies against checkpoints namely CTLA-4, PD-1 and PD-L1. These can cause pituitary dysfunction due to hypophysitis in addition to other endocrinopathies. While the prevalence and course of hypophysitis have been described extensively, the relationship between hypophysitis and cancer prognosis has only been investigated in melanoma patients on ipilimumab. Additionally, the impact of high dose glucocorticoids for hypophysitis treatment on survival has been unclear. Objective: In order to address these important questions, we aimed to characterize the frequency and course of hypophysitis from various ICIs, and to investigate a possible impact on overall survival in cancer patients.Design and Methods: We conducted a single center retrospective cohort study of adult cancer patients that received an ICI from 1/1/2012 - 12/31/2016, followed for a median of 14.8 months. A total of 896 patients were identified that received ipilimumab alone (n=120); ipilimumab and nivolumab (n=50); ipilimumab followed or preceded by pembrolizumab (n=70), pembrolizumab alone (n=406), and nivolumab alone (n=250). Results: Twenty-six patients (2.9%) developed hypophysitis after a median of 2.3 months (range 0.8 to 11.7). Their median age at initiation of ICI was 57.9 years (range 42.4 to 78.5), 54% were males, and the most common malignancy was melanoma (81%). All had hypopituitarism showing secondary adrenal insufficiency (100%), central hypothyroidism (38.5%) and central hypogonadism (28.5% in men, 25% in premenopausal women). Sixty-four percent demonstrated pituitary enlargement on imaging which resolved on follow-up. Mass effects occurred in 50% and were managed by initial high dose glucocorticoids. Thyroiditis occurred in 19.2% of those with hypophysitis. Occurrence of hypophysitis was associated with better overall survival (median 50.7 vs 16.5 months; p value 0.015) and reduced mortality (RR 0.52, 95% CI 0.28 to 0.99; p value 0.036) after adjusting for age, sex and malignancy type. Conclusions: Hypophysitis, usually but not always accompanied by classic MRI features, occurrs within a few weeks in cancer patients most frequently after ipilimumab alone or in combination with a PD-1 inhibitor, rarely after pembrolizumab and never after nivolumab alone. ICI-induced hypophysitis presents as mass effects in half and as hypopituitarism in all patients involving the corticotrophs more commonly than thyrotrophs and gonadotrophs. The improved survival with a 48% lower mortality rate in patients with hypophysitis suggests its possible role as a marker for better efficacy of ICIs against malignancy.
SAT-261 Thyroid Stimulating Hormone-Secreting Pituitary Macroadenoma and Papillary Thyroid Cancer in a 55-Year-Old Male: A Case Report
Authors: Mislang Francis Xavier Fernandez
Published: May 2020

Background: Thyroid-Stimulating Hormone Secreting Pituitary Adenoma (TSHoma) is a rare Endocrinologic finding occurring in 0.5–3% of all pituitary adenomas, and is even rarer to find it coexisting with differentiated thyroid cancer.

Clinical Case: A 55-year-old male consulted last 2012 for palpitations and resting tachycardia. Initial tests revealed an ECG of sinus tachycardia, normal electrolytes and TSH 3.16 uIU/mL (0.27–4.2) and FT4 66 pmol/mL (12–22). He was referred to an Endocrinologist where thyroid ultrasound was done revealing bilaterally enlarged thyroid lobes with diffuse thyroid parenchymal changes, and a thyroid scan consistent with Graves’ Disease. He was started on methimazole and beta-blockers. Persistently elevated FT4 and a non-suppressed TSH prompted work-up for secondary hyperthyroidism. Pituitary MRI revealed a sellar mass measuring 3.4cm x 2.7cm x 2.6cm, noted to be compressing the left side of the optic chiasm and prechiasmatic left optic nerve laterally. The consideration was pituitary macroadenoma. He underwent trans-sphenoidal surgery but operative technique only involved near total excision of the adenoma due to proximity of the mass to the pre-chiasmatic left optic nerve. The tumor was reduced to 2.8cm x 1.6cm x 1.5cm. Histopathologic diagnosis and immuno-histochemical staining revealed pituitary tumor cells reactive to TSH but non-reactive to FSH, LH and GH. He eventually underwent intensity-modulated radiation therapy (IMRT) which reduced the tumor size, but did not obliterate the tumor. His thyroid function tests persistently revealed elevated TSH and FT4 levels. Last January 2019, he manifested with an enlarged anterior neck mass. An ultrasound revealed thyromegaly with multiple nodules, largest at 1.4cm with multiple sub-centimeter nodules, mostly complex and solid in description. He underwent total thyroidectomy. Histopathology results revealed Papillary Thyroid Cancer with no extracapsular or lymphovascular invasion. He was scheduled for radioactive iodine at 100mci a month after. His I-131 whole body scan revealed foci of residual thyroid tissue but without distant mestastases. He is currently on levothyroxine at 225mcg daily therapy and advised annual cranial MRI readings which mostly showed a stable pituitary tumor.

Conclusion: This is a case of TSHoma, S/P trans-sphenoidal surgery and intensity modulated radiation therapy with significant tumor residuals that eventually led to the development of Papillary Thyroid Cancer and subsequent total thyroidectomy and radioactive iodine administration. He is now on frequent tumor monitoring and levothyroxine suppression dose.

Reference:

P. Beck-Peccoz, A. Lania, A. Beckers, K. Chatterjee d, J.-L. Wemeau. 2013 European Thyroid Association Guidelines for the Diagnosis and Treatment of Thyrotropin-Secreting Pituitary Tumors. Eur Thyroid J 2013;2:76–82.
MON-387 Association Between Vitamin D Level and Bone Mineral Density in Korean Adolescents
Authors: Song Kyungchul , CHOI Han saem , Suh Junghwan , Kwon Ah Reum , Chae Hyun-wook , Kim Ho-Seong
Published: May 2020

Introduction

Fractures are common in pediatric population, and lower bone density increases the risk of fracture. Most bone acquisition happens during youth, so juvenile bone mineral density (BMD) assessment is important. There are many factors associated with low BMD, including vitamin D status, calcium intake, low body weight, and physical activity. Among these, our investigation focused on the association of BMD with vitamin D in adolescents.

Methods

This study investigated data of 1,063 adolescents aged 12-18 years from the fifth and sixth Korea National Health and Nutritional Examination Survey (2009-2011). The association of various factors (vitamin D level, calcium intake, body mass index (BMI), lean mass, fat mass, and physical activity) with BMD Z-scores in whole body, lumbar spine, total femur, and femur neck were analyzed. We defined vitamin D deficiency (≤ 12 ng/mL), vitamin D insufficiency (12-20 ng/mL), and sufficiency (> 20ng/mL) according to the 25-hydroxyvitamin D (25-OHD) level. We analyzed association between BMD and vitamin D levels after adjusting for other factors.

Results

The mean 25-OHD level of subjects was low (16.28 ng/ml). Of all subjects, 21.9% were vitamin D deficient, and 58.5% were vitamin D insufficient. Among the vitamin D groups, the vitamin D sufficient group had significantly higher BMD Z-scores than the vitamin D deficient group in whole body, lumbar spine, and femur neck. The sufficient vitamin D group had higher BMD Z-score than the vitamin D insufficient group in femur neck, and the vitamin D insufficient group had higher BMD Z-score than the vitamin D deficient group in whole body. Among various factors, vitamin D status, calcium intake, BMI, lean mass, fat mass, and physical activity were positively associated with BMD Z-scores. In particular, lean mass was the strongest independent factor. Vitamin D levels were positively associated with the BMD Z-scores even after adjusting for other factors.

Conclusions

Vitamin D deficiency and insufficiency were common among adolescents. This study suggested that vitamin D level was positively associated with BMD, and that sufficient vitamin D level was needed to prevent low BMD. Vitamin D status is an important factor of BMD in adolescents.
SUN-656 Hypoglycemic Effect of Oral Administered Superoxide Dismutase
Authors: Liu Shutao , Liu Hangqi
Published: May 2020

Hypoglycemic Effect of Oral Administered Superoxide Dismutase on Type 2 Diabetes via reduction of glucogan and insulin resistance

Background & Objective: Superoxide dismutase (SOD) is carefully used in food industry for the concern of its easy degradation and difficult adsorption in digestive tract, although it plays central role in antioxidant system. It is previous reported that orally administered SOD was effective in alleviating hyperglycemia, cerebral ischemia-reperfusion and chronic hepatitis. This work aimed to investigate in-depth the hypoglycaemic effect and possible mechanism of orally administered SOD in the model of type 2 diabetic rats.

Methods:The model of type 2 diabetic rats were divided into 6 groups and orally administered with different Cu/Zn-SOD (abbreviated as SOD) samples and negative or positive controls. The 6 groups included SOD, SOD hydrolysate (pepsin-treated SOD), L-SOD (liposome-embedded SOD), model group and metformin positive groups, as well as normal group. Results of the body weight, serum indexes (including blood glucose, glycated albumin, insulin, glucagon, AMPK, MDA), SOD enzymatic activity in organs (liver, heart, kidney, skeletal muscle, spleen, and pancreas) as well as intestinal density and HE staining were measured to evaluate the hypoglycemic effect and possible mechanism.

Results: SOD showed substantial hypoglycemic effect and improved serum indicators. Moreover, L-SOD group exhibited better effect than SOD group, though the effect of SOD hydrolysate was not obvious. Colon density and HE staining showed obvious intestinal injury in the model group, and SOD was beneficial to repair intestinal structural integrity. Furthermore, the reparative effect of SOD was much better than that of the SOD hydrolysate, but not as good as that of the L-SOD. The SOD enzymatic activity of tissues was positively correlated with the curative effect of three kinds of SOD samples. The contents of serum MDA were negatively correlated with the curative effect. Compared with the model group, the insulin resistance index of SOD group, L-SOD group and positive group were significantly reduced; and glucagon significantly decreased by 68.38, 77.50 and 65.01%, respectively.

Conclusion: Oral SOD showed obvious hypoglycemic effect on type 2 diabetic rats, and liposome could improve this effect. The mechanism may be that SOD effectively reduces intestinal injury, so as to reduce glucongen and insulin resistance index.
MON-502 Clinical-Pathological and Molecular Prognostic Markers in Aggressive and Poorly Differentiated Thyroid Cancers; A Tertiary-Center Experience
Authors: Radi Suhaib , Filimon Sabin , Tamilia Michael
Published: May 2020

Background:

Aggressive variants of papillary thyroid cancer (AV-PTC) and poorly differentiated thyroid cancers (PDTC) are 2 malignancies that lie in between the well-differentiated and the undifferentiated anaplastic cancers. While management of those well-differentiated cancers is established in the literature, that of AV-PTC and PDTC is less clear as they behave different to their more benign counterparts. The aim of this study is to describe the clinico-pathologic characteristics and genotypic background of AV-PTC and PDTC and to assess their prognostic value.

Methods:

The charts of all patients with thyroid cancer in our center for the last 10 years were retrospectively reviewed. Those with AV-PTC and PDTC were selected and included in the analysis. Clinical presentation, pathologic characteristics, molecular markers, specific treatments and clinical outcomes were compared among groups.

Results:

Out of 3244 thyroid cancer charts reviewed, 87 patients met the criteria for AV-PTC (n=45) and PDTC (n=42). Mean age at diagnosis was 48.1 years (SD 17.8), with female predominance (64.4% vs 35.6%). Median duration of follow up was 3 years (0.1-30). Out of the 75 patients with follow up for more than a year, 42.7% had either persistent disease or recurrence (52.6% in AV-PTC and 32.4% in PDTC) and 4.1% died. Presence of vascular invasion was associated with higher rates of persistent or recurrent disease (74.1% in positive vascular invasion vs 20.5% in negative vascular invasion, p < 0.001). Recurrence rate was 0% in patients with Ki67 < 10% and 40% in those >= 10%. There was no difference in terms of recurrence based on presence of BRAF mutation (33% in BRAF+ & 29% in BRAF-, p=1), or percentage of aggressive/poorly differentiated tumor involvement (48% in > 30% involvement vs 28% in < 30%, p = 0.132).

Discussion and conclusion:

The prevalence of AV-PTC and PDTC in this cohort was low at 1.3% each, and the rate of patients with persistent or recurrent disease at 1 year after primary therapy was also similar to that reported (42.7%). The mortality rates, however, in our study is surprisingly lower than that expected elsewhere (4.1%), most likely attributed to a shorter follow up period. Patients with absent vascular invasion were less likely to have persistent or recurrent disease. Those with lower Ki67 (<10%) also had lower relapse rate, although, the p value was > 0.05. It is worth mentioning that even though there were higher rates of recurrence among those with > 30% tumor involvement, it did not reach statistical significance, supporting recent studies stating that even tumor involvement of > 10% can have adverse outcomes. In conclusion, AV-PTC and PDTC are relatively rare but aggressive tumors. Possible prognostic markers that can be used to guide therapy and monitoring include: vascular invasion, extra-thyroidal extension, response to primary therapy and the proliferative index Ki67.
SAT-566 Avoiding the Heartache: A Case of Familial Hypercholesterolemia
Authors: Kinaan Mustafa , Rivera Arelys Ramos , Yau Hanford
Published: May 2020

More than 70% of individuals with atherosclerotic cardiovascular disease are believed to have underlying gene-linked mechanisms leading to hyperlipidemia. It is estimated that 1 in 200 individuals in the United States has heterozygous Familial Hypercholesterolemia (FH). We present a case that highlights the importance of comprehensive care for a patient with heterozygous FH, from screening and risk stratification, to therapy. Our patient is a 43-year-old gentleman with history of hyperlipidemia. At age 25, he was diagnosed with hyperlipidemia and was started on statin therapy. He has strong family history of cardiovascular disease. His mother had her first myocardial infarction (MI) at age 40 and required coronary artery bypass. She also suffered from three strokes. His maternal aunt and uncle suffered from MIs at age 38 and 40, respectively. Additionally, his maternal grandfather passed away from MI at age 38. The patient’s daughter was found to have total cholesterol level > 300 mg/dL at age 8. He does not have history of obesity, diabetes, previous cardiovascular events, or hypothyroidism. He is athletic and follows a healthy diet. He did not have any xanthomas, xanthelasmas, nor arcus cornealis. At time of initial evaluation, the patient had low-density lipid (LDL) level of 180 mg/dL despite therapy with rosuvastatin, ezetimibe, and niacin. Based on these findings, we proceeded with genetic testing. Results of testing showed a heterozygous c.6delG (p.Trp4Glyfs*202) pathogenic mutation of the LDL receptor. We also obtained cardiovascular risk stratification studies. On cardiac CT angiogram, he was found to have extensive, four-vessel disease with 80-90% stenosis of the left ascending artery (LAD) with coronary calcium score of 136 and total score of 219 (99th percentile). Exercise, stress myocardial perfusion scan showed small reversible anteroseptal perfusion abnormality suggestive of mild to moderate ischemia. LAD stenosis was confirmed on a left heart catheter, but no intervention was required. We proceeded with aggressive lipid-lowering therapy with rosuvastatin 40mg daily and alirocumab 300mg monthly. He was also started on aspirin and beta-blocker given coronary artery disease. Following initiation of therapy, the patient’s LDL level dropped to 51 mg/dL with total cholesterol level of 153 mg/dL, HDL of 47mg/dL, and triglycerides of 109 mg/dL. The patient was encouraged to seek genetic counseling for his children and first degree relatives. His daughter was started on rosuvastatin 7.5mg daily by her pediatrician. The patient has not suffered any cardiovascular events and continues to follow up for therapy. Without aggressive lipid-lowering therapy, the lifespan of FH patients can be significantly shortened. Therefore, identifying FH patients is imperative to prevent cardiovascular disease in these patients and their afflicted family members.
MON-605 Serum CD163, but Not Gal-3, Predicts Response to Liraglutide Therapy in Obese Patients
Authors: Mat Arimin , Tobin Laura , Hogan Andrew , O’Shea Donal Brendan
Published: May 2020

Liraglutide is a GLP-1 Receptor Agonist licensed to treat T2DM and obesity. Soluble CD163 (sCD163) is a marker of macrophage activation, the integral immunological component in inflammation associated with obesity. Gal-3 is a β-galactoside-binding lectin that has been implicated in the development of cardiovascular diseases and insulin resistance. Recent studies have suggested that Gal-3 is raised in obesity with levels correlating with markers of inflammation.

In this study, we aim to elucidate if the levels of sCD163 and Gal-3 can be used to predict treatment outcomes of Liraglutide in obese patients.

Thirty-four obese patients (58.8% female; 44.1% diabetic) were enrolled for 12-week Liraglutide therapy. Anthropometric parameters were assessed before and after. Serum levels for sCD163 and Gal-3 were measured using ELISA.

Pre-treatment age (mean ± SD) was 52.41 ± 10.74y, BMI was 44.97±7.71 kg/m2, HbA1c was 47.18±15.96 mmol/mol, sCD163 was 284059.20 ± 71859.88 pg/ml and Gal-3 was 6584.83 ± 3477.59 pg/ml. Post-treatment, BMI reduced to 43.19±7.92 kg/m2 (p < 0.001), HbA1c to 43.59±16.00 mmol/mol (p<0.001), sCD163 to 249130.45 ± 57972.85 pg/ml (p<0.001) and Gal-3 to to 6254.23 ± 3282.66 pg/ml (p<0.03). We found that pre-treatment sCD163 levels correlate weakly with BMI and HbA1c (r=0.3 & 0.4) while Gal-3 correlates moderately with age only (r=0.36). Percentage of changes in HbA1c (∆HbA1c) correlates strongly with ∆sCD163 (r=0.6). Levels of pre-treatment sCD163 correlates strongly with higher ∆sCD163 (r=0.7). Changes in BMI post-treatment (∆BMI) is negatively correlated with initial sCD163 levels (r=-0.3) and is not correlated with ∆sCD163.

Liraglutide treatment leads to significant improvement in sCD163 and Gal-3 levels in obese patients. Patients with high HbA1c have high levels of sCD163. Reduction in sCD163 predicts reduction in HbA1c. Higher initial sCD163 levels predicts poor weight improvement. Patients most likely to have reduction in sCD163 are the ones with higher initial sCD163 levels. We conclude that sCD163 but not Gal-3 levels can predict response to liraglutide in obese patients.
MON-587 A Case of Pseudoglucagonoma Syndrome Post Bariatric Surgery
Authors: Raghunathan Sapna , Akkireddy Padmaja
Published: May 2020

Introduction

Necrotizing migratory erythema (NME) is hallmark clinical finding of Glucagonoma, an islet cell tumor of the pancreas. NME can sometimes be seen in the absence of Glucagonoma, a condition referred to as Pseudo-glucagonoma syndrome(PGS). We report a case of NME associated with severe nutritional deficiency.

Case

48 y/o female presented to dermatology clinic with diffuse itchy rash of 6 months duration. The rash started on the arms and spread to involve lower abdomen, legs and perioral area. It was unresponsive to both topical and high dose PO steroids. Biopsy of the rash showed confluent parakeratosis and mild spongiosis secondary to nutritional deficiencies vs NME. Her medical history was significant for Nissen fundoplication 20 years ago with a revision to Roux-en Y gastric by-pass, 6 years ago. She did not have a history of Diabetes or Inflammatory Bowel Disease. She was not on any vitamin supplementation, as she did not follow up for post bariatric care. On admission to the hospital for sepsis from secondary infection of the rash, diffuse erythematous, eczematous papules and plaques were noted on bilateral forearms, thighs, calves, buttocks and ankles. She also had perioral erythema and fissuring. Laboratory evaluation showed low prealbumin and multiple nutritional deficiencies including copper, zinc, vitamin B6, Vitamin D, ferritin. Her HbA1c was 5.8 % and fasting glucagon levels were normal. Her liver function was initially normal but later developed transaminitis from septic shock. She was started on enteral feeds with nutritional supplementation. This resulted in significant improvement of her rash with correction of underlying nutritional deficiencies.

Discussion

NME in the absence of Glucagonoma is extremely rare and is seen in hepatic cirrhosis, malabsorption disorders, inflammatory bowel disease and nutritional deficiencies including zinc deficiency, Pellagra, Kwashiorkor. Though the exact mechanism for NME in these conditions is unclear. It is postulated that unabsorbed nutrients in the gut lumen are potent stimulators of enteroglucagon which in turn mediates the development of NME. The treatment of NME associated with PGS is to correct the underlying cause. Our patient had history of gastric bypass surgery and did not get routine post bariatric care. She presented with multiple nutritional deficiencies which likely caused NME. It is important to recognize that post bariatric surgery, patients are at risk for both macro and micronutrient deficiencies and hence need frequent nutrition assessment, supplementation and monitoring.

References

Tierney EP, Badger J. Etiology and pathogenesis of necrolytic migratory erythema: review of the literature. MedGenMed 2004
SUN-307 Partial Secondary Adrenal Insufficiency and Growth Hormone Deficiency in Fibromyalgia
Authors: Gruber Lucinda , Nanda Sanjeev , Nippoldt Todd B , Chang Alice Y , Bancos Irina
Published: May 2020

Introduction: Low or borderline cortisol concentrations and impaired response to dynamic testing have been reported in patients with fibromyalgia, potentially related to hypothalamus-pituitary dysfunction.1,2 Superimposed adrenal insufficiency (AI) may contribute to some fibromyalgia symptoms or delay improvement in patients enrolled in fibromyalgia treatment programs. We hypothesized that a subset of patients with fibromyalgia have: 1) partial secondary AI and concomitant growth hormone (GH) deficiency 2) a discordance in Cosyntropin stimulation test and 3) improvement in fibromyalgia symptoms with initiation of glucocorticoid and/or GH replacement.

Design: This was a retrospective study of patients with fibromyalgia diagnosed with partial secondary AI based on abnormal insulin tolerance test (peak cortisol < 18 mcg/dL) at our institution from June 2002 to August 2019. Patients were excluded if they had other reasons for adrenal insufficiency, including steroid exposure and opioid use.

Results: We identified 22 patients (18 women, 82%) diagnosed with partial AI at a median age of 38 years (range 19-65). The fibromyalgia symptoms included fatigue (n=22, 100%), pain (n=22, 100%), sleep disturbance (n=15, 68%), and bowel changes (n=13, 59%). The median morning cortisol concentration was 8.6 mcg/dL (range 1.1-11); 9 patients (41%) had a morning cortisol concentration below the normal range (7 mcg/dL). The median ACTH level was 15.5 pg/mL (range 7.7-54). Nineteen patients had baseline IGF1 levels, with a median z-score of -0.94 (range -1.96 to 1.70). MRI pituitary imaging was performed in 20 patients and showed no significant pituitary pathology.

All patients achieved hypoglycemia <=40 mg/dL during the insulin tolerance test. Peak median cortisol level was 11 mcg/dL (range 5.4-17). Nineteen patients (86%) also had partial GH deficiency (defined as a peak GH < 4 ng/mL) with a median GH level of 0.36 ng/mL (range 0.03-3.83). Cosyntropin stimulation test was performed in 13 patients (59%) with a 1 mcg dose in 2 patients and 250 mcg dose in 11 patients. The peak cortisol was >=18 mcg/dL in 10 (77%) patients. All patients were started on physiologic glucocorticoid replacement, and 12 patients were started on GH replacement. Endocrinology follow-up information was available for 13 patients, and 8 (62%) reported symptom improvement after starting treatment.

Conclusions: Patients with fibromyalgia can have co-existing partial secondary AI and GH deficiency as defined by insulin-induced hypoglycemia. Cosyntropin stimulation test can be used in patients with fibromyalgia, but a normal test does not rule out partial secondary AI. Replacing the underlying deficiency improved symptoms in some patients demonstrating certain fibromyalgia symptoms may overlap with AI and GH deficiency.

1Gur et al. Ann Rheum Dis. 2004. 63(11):1504-1506.

2Kirnap et al. Clin Endocrinol (Oxf). 2001. 55(4):455-459.
MON-279 Correlation Between Haemolitic Complement Activity (CH50) and Growth Hormone Response to Stimulation in Adult Growth Hormone Deficiency: Preliminary Data
Authors: Bruno Carmine , Basile Umberto , Vergani Edoardo , Napodano Cecilia , Piunno Gaia , Stefanile Annunziata , Gulli Francesca , Mancini Antonio
Published: May 2020

It is known that GH, directly or via IGF-1 activity, influences many aspects of immune response; both humoral and cellular branches are modulated, but no data are available about complement function. CH50 is a screening assay for the activation of the classical complement pathway and it is sensitive to the reduction, absence and/or inactivity of any component of the pathway. The CH50 tests the functional capability of serum complement components of the classical pathway to lyse sheep red blood cells (SRBC) pre-coated with rabbit anti-sheep red blood cell antibody (haemolysin). On the other hand, a low inflammation is present in GH deficiency (GHD) and it is related to cardiovascular risk of such situation, also in partial forms.Therefore, we performed a cohort study in a group of adult GHD patients evaluating CH50 levels to further explore the pattern of inflammatory markers in this condition.We included 17 patients with total GHD (GH peak after stimulation with GHRH+arginine <9 ng/ml with BMI<30 or <4 ng/ml with BMI≥30 Kg/m2; n=15) or partial GHD (peak between 9 and 16 ng/ml with BMI<30 Kg/m2 n=2) with mean±SEM BMI 27.7±2.6 kg/m2 and mean±SEM age 52.5±2.6 ys. The etiology of GHD, assessed by MRI, was: primary empty sella (n=7); post-surgical (n=1) pituitary adenoma (n=4); idiopathic (n=4), pineal cyst (n=1); CH50 has been assayed by turbidimetric method. Mean±SEM CH50 of entire cohort was 50.75±2.5 U/l (normal range 12.5-100 U/ml); however, a significant inverse correlation was observed between GH AUC and CH50 levels (Spearman r=-0.49; p=0.04).This datum joint to our previous observations about increased free light chains of immunoglobulins in GHD, substantiating the hypothesis of chronic low-grade inflammation affecting this condition, which in turn could negatively influence GH secretion. These data could be of interest especially in patients recognized as “idiopathic” GHD, where no pituitary morphologic alterations or anamnestic information (previous surgery, trauma or irradiation) were found. However, these data cannot be conclusive and further studies are needed to establish the causal relationships between these parameters, also in a greater cohort of patients.
MON-504 VEGFA and VEGFR2 Expression in Different Histological Types of Thyroid Nodules: Could Immunohistochemistry Have a Clinical Utility?
Authors: Bufalo Natassia Elena , Peres Karina Colombera , Teodoro Larissa , Latufi-Filho Paulo , Barreto Icleia Siqueira , Assumpção Ligia Vera Montalli , Tincani Alfio José , Maximo Valdemar , Ward Laura Sterian
Published: May 2020

Vascular endothelial growth factors (VEGFs) are a family of proteins involved in several elements that play an important role in the development of blood vessels. Besides acting in angiogenesis, VEGFA has important roles in chemotaxis, for macrophages and granulocytes, and vasodilation. VEGFA binds to VEGFR2, that acts on the MAPK and PI3K pathways, fundamental pathways for thyroid carcinogenesis. In order to assess the expression of VEGFA and VEGFR2, in different thyroid nodules, we used a Tissue MicroArray including 91 benign (74 females, 16 males, 49.84±12.65years old) and 125 malignant thyroid nodules (97 females, 28 males, 46.57±14.87 years old). Clinical and pathology data were obtained from 47 goiters; 43 follicular adenomas (FA) and a total of 104 papillary thyroid carcinomas (PTC), including 35 classic papillary thyroid carcinomas (CPTC), 30 follicular variant of PTC (FVPTC), 25 oxifilic variant of PTC (OVPTC), 14 tall cell papillary thyroid carcinomas (TCPTC); and 21 follicular thyroid carcinomas (FTC). All patients were managed according to a standard protocol based on current guidelines and followed-up for 116.9±70.8 months. VEGFA protein expression did not differentiate benign from malignant thyroid nodules. However, VEGFA was more frequently expressed in the less differentiated thyroid tissues. In fact, 95.8% of the FTC had positive expression. On the contrary, the intensity of this protein expression was progressively lower according to the process of cellular dedifferentiation (Goiter: 21.4%; FA: 16.3%; PTC: 8.7% and FTC: 0.0%; x2 = 0.031). There was no difference in VEGFR2 expression between malignant and benign nodules (x2= 0.108), but this protein showed more intense expression in tissues that also presented Hürthle cells (x2 <0.0001). We were not able to find any correlation, neither of VEGFA nor with VEGFR2 expression, and any other feature of aggressiveness, including invasion, metastasis, lymph node metastasis, and distant metastasis. We conclude that VEGFA and VEGFR2 expression may help identify less differentiated tumors and the analysis of a larger cohort may prove the clinical utility of these markers.
SAT-031 Linking Gonadotropin-Regulated Testicular RNA Helicase (GRTH/DDX25) to Histone Ubiquitination Network and Acetylation During Spermiogenesis
Authors: Kavarthapu Raghuveer , Anbazhagan Rajakumar , Dufau Maria L
Published: May 2020

Gonadotropin Regulated Testicular Helicase (GRTH/DDX25), a testis specific RNA helicase essential for the completion of spermatogenesis. Our early studies discovered a missense mutation (R242H) of GRTH gene in 5.8 % of a Japanese population with azoospermia. This mutation in COS-1 cells showed loss of the 61 kDa cytoplasmic phospho-species with preservation of the 56Kda nuclear non-phospho form of GRTH. Mice with knock-in (KI) of the human GRTH mutation, lack the phospho-form of GRTH, are sterile and lack sperm, with spermatogenic arrest at stage 8 of round spermatids. To determine the impact of phospho-GRTH on gene expression comparative studies of germ cells transcriptome profiles from WT and KI mice were conducted using Illumina RNA sequencing. RNA-Seq analysis revealed 1614 differentially expressed genes of which 886 down-regulated and 728 genes up-regulated genes. Gene Ontology analysis revealed several genes relevant to spermatogenesis, spermatid development and differentiation significantly downregulated. KEGG analysis showed genes related to Ubiquitin mediated proteolysis, protein processing in ER, RNA transport, Glycolysis pathways are down-regulated, and genes related to Focal adhesion and ECM interaction are up-regulated. RealTime-PCR analysis confirmed dramatic reduction in mRNA expression of ubiquitination related genes Ube2j1, Ube2k, Ube2w, Rnf8, Rnf133, Rnf138 and increased expression of Ccnd2, Col1a, Lamb1, Cav1, Igf1, Itga9 mRNA’s in KI mice compared to WT. Western blot analysis revealed marked reduction in protein expression of UBE2J1, RNF8, RNF138 (ubiquitination network), MOF (histone acetyltransferase) and their modified Histone substrates (H2AUb, H2BUb), as well as H4Ac, H4K16Ac in KI mice. Immunohistochemistry analysis showed significantly reduced expression of RNF8, MOF, H4Ac and H4K16Ac in round spermatids of KI mice compared to WT. In KI mice absence of phospho-GRTH impairs RNF8 and MOF dependent ubiquitination and acetylation of histones required for histone replacement, chromatin condensation and spermatid elongation during spermiogenesis which finally results in germ cell arrest in step 8 of round spermatids. Thus, we conclude that phospho-GRTH affects the network which is critical for the replacement of histones during spermiogenesis.
SUN-545 High Prevalence of Cardiometabolic Diseases and Abdominal Aortic Calcification in Psoriasis
Authors: Ramos Sofia , Daya Sheetal , Tikly Mohammed , Crowther Nigel J , Mahyoodeen Nasrin Goolam
Published: May 2020

Psoriasis has been shown to increase the risk of cardiovascular disease. Studies indicate that the presence of abdominal aortic calcification (AAC) is a strong predictor of future cardiovascular events and all-cause mortality. Multi-detector computed tomography provides a reliable and accurate method for the detection of abdominal aortic calcification. The aim of this study was to investigate the prevalence of AAC in patients with psoriasis. Adult psoriasis patients (n=69) and controls (n=80) were recruited from the Dermatology and Rheumatology clinics at 3 academic hospitals in Johannesburg, South Africa. Controls were matched for gender, ethnicity and body mass index (BMI). Non-contrast abdominal CT imaging was performed on patients and controls. The images were then assessed for presence and location (supra-coeliac, supramesenteric, supra-renal, proximal infra-renal, aortic bifurcation) of AAC. Patients had a mean age and disease duration of 53.3 ± 14.5 years and 18.9 ± 13.3 years, respectively. There was a significantly higher prevalence of smoking, hypertension and type 2 diabetes in patients compared to controls (56.5% vs 25.0%, P<0.005; 72.5% vs 55.0%, P<0.005; 24.6% vs 3.80%, P<0.0005, respectively). Furthermore, there was a significantly higher prevalence of AAC at any site in psoriasis patients (47.8% vs 22.5%, P<0.005). The aortic bifurcation was the commonest site for AAC in patients and controls, and the prevalence was significantly higher in the psoriasis group (42.0% vs 21.3%, p<0.005). However, multivariable logistic regression analysis demonstrated that age, smoking and the metabolic syndrome were significantly associated with AAC (P<0.0001, P=0.0002, P=0.027 respectively) and attenuated the relationship between psoriasis and AAC to non-significance (P=0.376). This suggests the increased risk of aortic calcification in psoriasis is mediated by the high prevalence of cardiometabolic disease in this population. These data highlight the increased cardiovascular disease risk within subjects with psoriasis and the need for lifestyle modification to decrease risk factor burden.