bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT-LB83 Amiodarone Induced Myxedema Coma
Authors: Kim Keun Young , Syed Sabah
Published: May 2020

Introduction Amiodarone is widely used as a rhythm-conversion agent in atrial fibrillation. It’s low negative inotropic activity and low risk of ventricular arrhythmia makes it an advantageous agent for atrial arrhythmia. One of the major limiting factors in the use of amiodarone can be its thyroid toxicity leading to thyroid-dysfunction; ranging from thyrotoxicosis to myxedema coma. Myxedema coma, although rare, is a deadly complication of hypothyroidism with a mortality rate as high as 60%. It is considered an endocrinologic emergency that requires prompt attention and treatment. We present a case of myxedema coma in the setting of chronic amiodarone intake.

Case Presentation A 75-year-old female with a past medical history significant for atrial fibrillation, hypothyroidism, end stage renal disease from diabetic nephropathy on hemodialysis, Hepatitis C, hypertension, and hyperlipidemia was admitted to the hospital for evaluation of generalized weakness. Her medications included amiodarone 200mg/day among others. The next day, the rapid response team was called when the patient became hypotensive, bradycardic and unresponsive. She was transferred to the ICU and intubated immediately. On exam, her skin was dry and cold. Her laboratory findings revealed a markedly elevated TSH level of 185uIU/mL. Her most recent TSH level was 9.044uIU/mL from a year back. Other laboratory tests revealed WBC count of 9.0k/mm cu, hemoglobin 13.7 g/dL, platelet count 48 k/mm cu. A diagnosis of myxedema coma was made based on her presentation and lab findings. The patient was started on intravenous levothyroxine 100mg daily with intravenous hydrocortisone 100mg every 8 hours. T4 levels were 0.38ng/dL, T3 levels were 1.83pg/mL and TPO antibodies were negative. A decision was made not to administer intravenous T3 because of the patient’s advanced age and underlying atrial fibrillation. Over the course of the hospitalization, the patient was showing signs of clinical improvement and attempts were being made to wean her off the ventilator. However, later she died due to hemorrhagic shock.

Conclusion Myxedema coma may manifest nonspecifically as lethargy and altered mental status and can present without the more specific symptoms of skin changes or myxedematous soft tissue changes. It is therefore, very important for physicians to consider myxedema coma as one of the differential diagnoses in patients on amiodarone with underlying thyroid disease. Administering amiodarone for elderly patients with underlying thyroid problems warrants attention to polypharmacy. The treatment guidelines for myxedema coma are yet to be established. While intravenous levothyroxine with intravenous hydrocortisone remains the mainstay of therapy, there are no consensus on T3 administration.
SUN-LB93 Mineralocorticoid Receptor Mediates Sex-Dependent Anticontractile Effect of Perivascular Adipose Tissue in Obese Mice
Authors: Victorio Jamaira A , Freitas Israelle Netto , Guizoni Daniele Mendes , Davel Ana Paula
Published: May 2020

Obesity, a condition of excessive fat mass and subclinical inflammation, reached epidemic proportions with higher prevalence in women compared to men worldwide. Expansion of the perivascular adipose tissue (PVAT) is observed in obesity and clinical studies indicate a positive correlation between PVAT amount and body mass index. PVAT, a fat depot surrounding most of the vessels, modulates vascular function by releasing PVAT-derived factors such as adipokines that exert anticontractile effect in health individuals. Despite sexual dimorphism on PVAT morphology, it is still unknown whether or not there is sex differences in the PVAT modulating vascular function in the setting of obesity. Aldosterone-mineralocorticoid receptor (MR) signaling pathway has been demonstrated to be adipogenic and proinflammatory in classical fat depots and treatment with MR antagonists (A) might reverse vascular dysfunction and remodeling in obese models, especially in female sex. Therefore, we aimed to evaluate the anticontractile effect of PVAT in male and female obese mice and hypothesized that MR signaling would be involved in possible sex differences in PVAT dysfunction in obesity. Male and female C57Bl6/J mice were fed a chow or a high-fat diet (HFD, 60% energy from fat) for 20 weeks. At the last 4 weeks of HFD, female and male mice were treated with the MRA spironolactone (Spi, 100 mg/kg/day). HFD feeding significantly increased body weight and visceral adipose tissue, which was not modified by Spi treatment in both sexes. Resistance mesenteric arteries were isolated with or without PVAT and mounted in a wire myograph to evaluate vascular contractile responses. Lean male and female mice PVAT had an anticontractile effect in the response to phenylephrine that was greater in females than males. The anticontractile effect of PVAT was significantly impaired in obese females but not modified in males. HFD-induced dysfunctional PVAT was prevented by Spi treatment in females. Next, we evaluated the protein expression of aldosterone-synthase CYP11B2, serum and glucocorticoid-regulated kinase 1 (SGK1), and epithelial sodium channel subunits (ENaCs) in isolated mesenteric PVAT of lean and obese male and female mice. There was an increased expression of CYP11B2, SGK1 and ENaCs only in obese female PVAT. Protein expression of adiponectin, a major PVAT-released adipokine was also increased in female mesenteric PVAT. In conclusion, the findings suggest sexual dimorphism in PVAT function in health and in obesity. Although anticontractile role of PVAT was exacerbated in lean female mice, female sex was more susceptible to develop PVAT dysfunction in the setting of obesity which was prevented by MR blockade. HFD-induced PVAT dysfunction in females was associated with increased expression of SGK1 and ENaCs. Therefore, data suggest MR activation as a mechanism mediating sex differences in PVAT dysfunction.

FAPESP, CAPES.
MON-LB69 Calcitriol-Mediated Hypercalcemia in a Patient With Metastatic Gastrointestinal Stromal Tumor
Authors: Betlachin Anna , Kim Sarah Sangnim Rhee , Oxman Rachael
Published: May 2020

Background: Hypercalcemia is a common complication of advanced malignancy, affecting up to 30% of cancer patients through various mechanisms (1). Hypercalcemia has rarely been described in gastrointestinal stromal tumors (GIST), with fewer than ten case reports as of 2018 (1,2). We describe a case of calcitriol-mediated hypercalcemia in a patient with GIST. Clinical Case: An 80-year-old woman with a history of metastatic GIST and nivolumab-induced type 1 diabetes and thyroiditis presented with dramatic progression of metastatic peritoneal disease and new severe hypercalcemia with acute kidney injury. On hospital admission, calcium (Ca) was 15.1 mg/dL (8.6-10.3 mg/dL), ionized Ca was 1.98 mmol/L (1.09-1.29 mmol/L), and creatinine was 2.56 mg/dL (0.6-1.3 mg/dL, baseline 1.8 mg/dL). She was treated with IV fluids and 45 mg of IV pamidronate with initial Ca improvement to 10.7 mg/dL over the next 48 hours. Additional workup showed that 25-hydroxyvitamin D was 18 ng/dL (20-50 ng/dL), PTH was 9 pg/mL (11-51 pg/mL), PTHrP was 3.1 pmol/L (0.0-3.4 pmol/L), and calcitriol was elevated to 172 pg/mL (19.9-79.3 pg/mL). Prior chest/abdomen/pelvis CT scans had not shown bony metastases or granulomas. After stopping IV fluids, Ca rose to 12.2 mg/dL the next day. Prednisone 20 mg daily was started which stabilized Ca levels and lowered calcitriol to 17.4 pg/mL after two weeks. She also began a new regimen of cabozantinib. Prednisone was tapered to 10 mg daily and she continues to maintain normal Ca levels with the addition of home health IV fluids three times a week. Conclusion: GIST tumors are a rare cause of hypercalcemia of malignancy. Although hypercalcemia of malignancy is most often due to tumor-secreted PTHrP or bony metastases, a small percentage of cases are mediated by excess calcitriol production. There is a growing number of case reports, including this case, to suggest that calcitriol-mediated hypercalcemia is the most common cause of hypercalcemia in GIST tumors (2-4). Glucocorticoids may be used to decrease calcitriol production and help maintain eucalcemia. Definitive therapy for hypercalcemia in these patients involves decreasing tumor burden by treatment of the underlying malignancy (3). References: (1) Stewart AF. Clinical practice. Hypercalcemia associated with cancer. N Engl J Med. 2005;352(4):373-9. (2) Hart T, Sinitsky D, Shamsiddinova A, Rohatgi A. Refractory hypercalcaemia secondary to localised gastrointestinal stromal tumour. Ann R Coll Surg Engl. 2018;100(6):e136-e138. (3) Hygum K, Wulff CN, Harsløf T, et al. Hypercalcemia in metastatic GIST caused by systemic elevated calcitriol: a case report and review of the literature. BMC Cancer. 2015;15:788. (4) Barbaryan A, Bailuc S, Poddutoori P, et al. Gastrointestinal Stromal Tumor Induced Hypercalcemia. Case Rep Oncol Med.2017;4972017.
SAT-LB308 Primary Hyperparathyroidism and Meningioma as a Part of Multiple Endocrine Neoplasm Type 1 (MEN Type 1)
Authors: ElEbrashy Shady Ibrahim , Ehab ElRefaay
Published: May 2020

Background: Meningioma is a rare association of Multiple endocrine neoplasia type 1 (MEN 1) and very few cases has been reported in literature. Clinical Case: a 75-year-old woman showed severe headache, disturbed consciousness and convulsions. A diagnosis of cerebral meningioma was made and surgical excision was done, histopathological examination confirmed meningioma; patient was transferred to the ICU postoperatively for monitoring. Patient’s consciousness was not regained in full and remained in delirium, follow up investigations revealed: serum calcium of 13.2 mg/dl (8.5 to 10.5 mg/dl), serum sodium 141 mmol/L (135-145 mmol/L) and potassium 4.9 mmol/L (3.5-5 mmol/L), serum parathormone of 850 pg/mL (10-65 pg/mL), primary hyperparathyroidism was suspected; further investigations revealed inferior parathyroid adenoma on ultrasound which elicited focal tracer uptake on sesta-mibi parathyroid scintigraphy. Patient did excision of the lesion and was confirmed by histopathological examination to be parathyroid adenoma. Patient recovered well postoperatively, consciousness was regained and no neurological defects ware present. Genetic studies where performed and was found positive for MEN type 1 gene. Whole body Ga-DOTATATE PET/CT was then done to exclude any associated tumors and no tracer uptake was found. Patient was discharged, family members were offered genetic analysis and were counselled on the importance of screening. Conclusion: MEN type 1 can rarely present with meningiomas with symptoms very similar and easily confused with hypercalcemia and the diagnosis can be missed.
MON-LB75 Stratifying the Risk of Malignancy in Indeterminate Thyroid Nodules
Authors: Imam Shahnawaz , Paparodis Rodis , Jaume Juan Carlos
Published: May 2020

Background Thyroid cancer is the most common endocrine cancer globally, and accounts for 3.4% of all new cancer cases in the US. Although several clinical guidelines to detect/manage thyroid nodules are available, a great deal of controversy still exists around the optimal approach for diagnosis. Approximately 20-30% of cytology results from thyroid fine-needle aspiration (FNA) fall into one of three indeterminate diagnostic categories. In recent years, a number of molecular and gene mutation diagnostic tests have been developed to diagnose the indeterminate thyroid nodules in FNA specimens. However, nearly half of patients recommended for surgery based on these tests were found to have a benign nodule. Therefore, there is a need for a more accurate predictive and prognostic test for thyroid cancer. In case of Euthyroid Hashimoto Thyroiditis condition (EHT), where patient required a partial thyroxin replacement dose, having about 48% risk of thyroid cancer. However, there is still not a very accurate predictive marker for early detection of thyroid cancer in EHT. Invention DescriptionResearchers at the University of Toledo have found that thyroid nodule microenvironment cell profiling can be used as a predictive and prognostic marker for thyroid cancer. This approach uniquely focuses on the phenotype, rather than the genotype, of the microenvironment. Recently described Double Negative (DN) T-cells were significantly more abundant in lymphocytic infiltrates of thyroid cancer. They were shown to downregulate proliferation and cytokine production of activated effector T cells present in the tumor microenvironment and contribute to tumor tolerance and active avoidance of tumor immunity. If the quantify of DN T cells exceeds the defined threshold, it indicates a likelihood of cancer presence. Aside from immune cell profiling, our approach further establishes an integration of the information derived from transcriptome/meta-analysis of the genome and cytokine/chemokine signal analysis all from thyroid FNA. Applications[[Unsupported Character - Symbol Font •]] Diagnosis of thyroid cancer from FNA samples[[Unsupported Character - Symbol Font •]] Predictive tool of severity of disease Advantages[[Unsupported Character - Symbol Font •]] Microenvironment profiling can provide a unique way to diagnose and assess disease progression[[Unsupported Character - Symbol Font •]] Sheds light on cellular cross-talk; more accurate diagnose; can prevent unnecessary surgery IP Status:​Patent Pending
SUN-LB98 RAAS Triple-A Analysis for the Screening of Primary Aldosteronism
Authors: Burrello Jacopo , Buffolo Fabrizio , Domenig Oliver , Tetti Martina , Pecori Alessio , Monticone Silvia , Poglitsch Marko , Mulatero Paolo
Published: May 2020

Primary aldosteronism (PA) is recognized as the most frequent cause of secondary hypertension, and its screening is expected to become a routine evaluation in most patients with hypertension. The interference of antihypertensive therapies with the aldosterone-to-renin ratio (ARR) during screening process is a major confounder. Renin-Angiotensin-Aldosterone System Triple-A (RAAS Triple-A) testing is a novel mass-spectrometry based assay for quantification of Angiotensin I (Ang I), Angiotenisn II (Ang II) and Aldosterone in a single sample of serum by RAAS equilibrium analysis. Obtained hormone levels are used to calculate markers for plasma-renin-activity (PRA-S, Ang I + Ang II), plasma angiotensin-converting-enzyme activity (ACE-S, Ang II-to-Ang I ratio) and adrenal function (AA2-Ratio, Aldosterone-to-Ang II ratio), with the latter being useful to screen for PA in hypertension. We performed a comparative evaluation of the diagnostic performance of the AA2-Ratio and 5 renin-based diagnostic ratios, differing in methods to determine aldosterone levels and renin activity in a cohort of 110 patients with hypertension (33 patients with confirmed primary aldosteronism and 77 with essential hypertension). All ratios showed comparable areas under the curves ranging between 0.924 and 0.970 without significant differences between each other. The evaluation of the ACE-S revealed persistent drug intake in some patients as cause for suppressed renin-based diagnostic ratios, while the AA2-Ratio remained unaffected. The Youden index optimal cutoff value for the AA2-Ratio was 6.6 ([pmol/L]/[pmol/L]) with a sensitivity of 90% and a specificity of 93%, proving non-inferiority compared with the ARR while pointing to the potential for an interference-free application in patients under ACE inhibitor therapy. This study shows for the first time the accuracy and reliability of RAAS Triple-A analysis for the screening of primary aldosteronism that can be applied in clinical routine.
SUN-LB132 Frequency and Impact of Mutations in Tumor Suppressor Gene CDC73 in General Population and Malignant Tumors
Authors: Li Yulong , Chen Haobin
Published: May 2020

Background: CDC73 gene is a putative tumor suppressor gene, and somatic and germline mutations of this gene have been linked with parathyroid tumors. There are also some reports suggesting that germline CDC73 mutations may increase risk of jaw, kidney and uterine tumors. However, the incidence and significance of CDC73 somatic mutations is largely unknown in tumors other than parathyroid tumors.

Methods/Design: 1) Assess CDC73 germline mutation frequency and genotypes in general population using ExAC (Exome Aggregation Consortium) and gnomAD (Genome Aggregation Database); 2) Assess CDC73 somatic mutation frequency in various type of tumors using the Cancer Genome Atlas (TCGA) and non-TCGA datasets; 3) Examine significance of CDC73 mutation in uterine endometrial carcinoma (UCEC). Overall survival, CDC73 mutation signature, gene expression profile (GEP) and tumor immune microenvironment were compared between the UCEC samples with and without CDC73 mutations.

Results: In ExAC and gnomAD databases, most of CDC73 germline mutations were mapped to the intron regions of the CDC73 gene and nonsynonymous CDC73 mutations are very rare, with allele frequency ranging from 8.24e-06 to 9.92e-05 and 3.97e-06 to 7.43e-05, respectively. Missense mutations accounted for more than 95% of the nonsynonymous mutations in the CDC73 gene in both databases. 2) In 155 cancer genomics studies including both TCGA and non-TCGA datasets with no overlapping samples, CDC73 was mutated in 0.7% cases and missense mutations comprised 78% of the CDC73 mutations. CDC73 somatic mutations were undetected or rarely detected in endocrine tumors except for parathyroid tumors. 3) UCEC is the tumor type that has the second highest CDC73 somatic mutation rate (8%) after parathyroid tumors. The UCEC with CDC73 mutations had a significantly better overall survival with a logrank p-value of 0.033 compared to the tumors with CDC73 WT. GEP analysis revealed that the CDC73-mutated UCEC tumors had significant upregulation of immunological markers and enriched immunologic signature compared to the CDC73-WT tumors. In silico analysis of tumor immune microenvironment showed higher fractions of cytotoxic CD8 cells, T follicular helper cells and M1 macrophage in the CDC73-mutated UCEC tumors. The majority of the CDC73-mutated tumors were POLE ultra-mutated and microsatellite instability (MSI) subtypes, which likely account for a better survival and an increased immune-cell infiltrate of these tumors. Conclusion: CDC73 mutations is rare in general population and tumors except for parathyroid carcinoma and UCEC. CDC73 mutation is a marker for better prognosis in UCEC and is associated with increased immune cell infiltrate in tumor microenvironment, likely due to majority of the CDC73-mutated tumors were POLE ultra-mutated and microsatellite instability (MSI) subtypes.
SUN-490 Mass Cord Compression: Metastasis of Insular Thyroid Cancer
Authors: Jaber Dina , Vazques Bianca , Nagamoto Gary , Horani Mohamad Hosam
Published: May 2020

Intro: Insular thyroid cancer is a rare and complex form of thyroid cancer, often referred to as poorly differentiated carcinoma. The exact incidence of insular thyroid cancers is difficult to assess due to controversial classification of this thyroid cancer over the years. It is termed poorly differentiated as it falls between the well-differentiated and undifferentiated carcinomas both morphologically and biologically[1].

Case: A 41 year old Hispanic female, with a history of prolactinoma and hyperparathyroidism, presented to the hospital with 10 days of progressive lower extremity weakness and paresthesias from T4 downwards, inability to bear weight, and no bowel movement for 12 days. MRI revealed a large thoracic soft tissue mass (7x4x4cm) centered in the posterior and medial aspect of the chest wall at T4-T5 with involvement of the spinal cord and vertebral bodies. She was also found to have a right sided thyroid mass (4.5x5x4 cm) with tracheal deviation-

HerThyoid function test, were normal Intact PTH was 261, Thyroglobulin over 300, and Thyroid Antibodies were negative. Patient underwent T3-T6 laminectomy, T2-T7 fusion, and T4-T5 tumor resection, which was subtotal due to vascularity. Second procedure included a right thoracotomy, chest wall resection of ribs 4 and 5 with full resection of paraspinal mass, total thyroidectomy, parathyroidectomy with central cervical lymphadenectomy. Pathology results of paraspinal mass showed insular thyroid carcinoma.

Post operatively, the patient reported improvement of sensation and strength in lower extremities. Genetic testing for MEN syndrome was negative.

Discussion: Insular thyroid carcinoma, also referred to as poorly differentiated carcinoma is a rare form of thyroid cancer. Insular carcinoma was characterized by to include the following complex histologic features, “formation of solid clusters (insulae) of tumor cells containing a variable number of small follicles; variable but consistently present mitotic activity, capsular and blood vessel invasion; and frequent necrotic foci, sometimes leading to formation of peritheliomatous patterns”[1]. The cells originate from follicular epithelium and possess the potential to concentrate radioiodine[2]. Unlike anaplastic carcinoma of the thyroid, p53 and p21 staining was negative in insular carcinomas[3]. Thyroglobulin staining is generally positive[4]. Distant metastasis occurs in about 31% of patients with insular thyroid carcinoma[5]. In cases of distant metastasis, treatment with thyroidectomy and radioiodine therapy were shown to independently improve survival[5].

The Constellation of Insular thyroid cancer, hyperparathyroidism and Prolactinoma, has not been reported before.

References:

[1]. Am J Surg Pathol. 1984;8:655-

[2] J of Nuc Med 32(7), 1358

[3] Ann of Surg vol. 231,3 (2000): 329

[4] JCEM 99. 1167–9. 10.1210/jc.2014

[5] Cancer. 2012 Jul;118(13) 3260
SUN-LB118 Mice With Skeletal Muscle-Specific DRP1 Deficiency Are Resistant to Obesity and Diabetes Induced by a High Fat Diet
Authors: Jensen Renato Daniel , Peterson Joshua , Allington Benjamin , Dieter Alayna , Cheng Linhai , Soto Jamie , Alambert Renata Pereira , Correia Marcelo , Abel Evan Dale
Published: May 2020

The skeletal muscle of type 2 diabetics exhibits mitochondrial dysfunction associated with increased mitochondrial fission. Dynamin-related protein 1 (DRP1) is responsible for mitochondrial division, whereas mitochondrial-endoplasmic reticulum contacts (MERCs) mark mitochondrial sites where fission occurs. Here, we have shown that skeletal muscle-specific DRP1 knock out (KO) mice are partly protected from high fat diet-induced obesity and diabetes, and exhibit increased insulin and glucose tolerance along with lower insulinemia. We also found that KO mice exhibit increased energy expenditure per unit of lean mass. Isolated DRP1-deficient skeletal muscle fibers from KO mice fed high fat diet have reduced respiratory capacity when exposed to ADP and palmitoyl-carnitine, but not when exposed to ADP, pyruvate, and malate. Additionally, the skeletal muscle of KO mice fed normal chow exhibited altered expression of genes associated with MERCs and increased expression of genes linked to ER stress. We observed substantial increases in gene expression of FGF21, a downstream signal of the ER stress response, in KO mice. However, FGF21 plasma concentration in KO mice was not elevated. Additionally, changes in MERC gene expression could potentially alter calcium signaling between the mitochondria and endoplasmic reticulum, changing insulin sensitivity in KO mice. In conclusion, we have shown that skeletal muscle-specific DRP1 KO mice are resistant to high fat diet-induced obesity and diabetes, perhaps due to elevated energy expenditure and differential mitochondrial respiratory adaptations to different substrates. Although FGF21 does not appear to contribute to this effect, it is possible that other ER-stress signals might help explain the observed phenotype in KO mice.
SUN-LB27 Interleukin-8 - a Possible Target for Melanoma Treatment? In-Vitro Studies Based on Human Melanoma Cell Models
Authors: Ramaraj Pandurangan
Published: May 2020

Previous clinical studies showed that menstruating females were better protected in melanoma than post-menopausal women and men of any age. In addition, epidemiological studies showed an increased male mortality in melanoma. But these studies did not correlate with steroid status in females. Our in-vitro study showed female sex hormone progesterone significantly inhibited human melanoma cell growth. Further in-vitro study showed that progesterone action was mediated by a specific suppression of pro-inflammatory cytokine IL-8. Our research also showed that addition of IL-8 (1 ng/ml) to melanoma cells stimulated cell growth (117%) and suppression of IL-8 by curcumin (100 μM) pre-treatment suppressed human melanoma cell growth (26%) in-vitro. This observation prompted us to check the effect of male sex hormones androstenedione (AD) and testosterone (T) on melanoma cell growth. AD and T also suppressed cell growth and IL-8 secretion, but not as significantly as that of progesterone. However, addition of progesterone (10 μM) along with androgens showed an additive effect on the inhibition of melanoma cell growth and suppression of IL-8 secretion. As steroids (P, AD, T) targeted IL-8 for their action, it was decided to check whether vitamin-D3 also targeted IL-8 secretion and cell growth. Active form of vit-D3 (25 μM) also suppressed IL-8 secretion and cell growth. But, addition of progesterone (50 μM) along with D3 significantly suppressed cell growth and IL-8 secretion. This brought IL-8 into focus as a key molecule regulating melanoma cell growth. In order to check whether IL-8 was the molecule involved in regulating melanoma cell growth, IL-8 rescue experiment after curcumin (25 μM) pre-treatment was carried out. IL-8 (100 ng/ml) was able to rescue cell growth completely after pre-treatment with curcumin, suggesting IL-8 was the molecule involved in regulating melanoma cell growth. Literature also suggested important role for IL-8 in regulating melanoma cell growth. Conditional expression of IL-8 in nude mouse by Dr. Singh et al., indicated in-vivo role of IL-8 in melanoma growth and metastasis. Conclusion: Both, in-vitro and in-vivo studies suggested an important role for IL-8 in regulating melanoma growth and metastasis. So, IL-8 could be targeted to arrest melanoma growth and metastasis in-vivo. Hence, IL-8 could be a potential target for melanoma treatment.
MON-LB126 A Benign and Favorable Diagnosis: Glycogen Hepatopathy Causing Transient Transaminitis During Diabetic Ketoacidosis in Type 1 Diabetes Mellitus
Authors: Yau Alice , Elayaperumal Pramma , Butala Ashvin , Bahtiyar Gul , Rodriguez Giovanna
Published: May 2020

Background: Transient transaminitis is a rarely discussed complication of uncontrolled diabetes mellitus (DM). Known as glycogenic hepatopathy (GH), it is belived to be caused by build-up of glycogen in hepatocytes. Recognized as benign and reversible, GH is associated with hepatomegaly (>90% cases) and primarily seen in patients with type 1 DM during periods of inadequate hyperglycemic control. Differential diagnoses include glycogen storage diseases, nonalcoholic fatty liver disease, hepatosclerosis, autoimmune hepatitis, hemochromatosis, Wilson disease, and acute viral hepatitis.1

Case Report: A 26-year-old African American female with type 1 DM and sickle cell presented on multiple occasions to the emergency department with abdominal pain associated with nausea, vomiting and diarrhea. Initial labs consistently included glucose levels >600 mg/dL (70-105 mg/dL), elevated anion gap ranging 20-40s mEq/L (5-15 mEq), and severe metabolic acidosis reflective of diabetic ketoacidosis (DKA). Labs were also significant for repeated mild transaminitis despite adequate fluid hydration.

After several admissions, we observed a distinct pattern of mild transaminitis that directly fluctuated with her levels of blood glucose. With some minor lag, the patient’s liver enzymes normalized when her glucose levels normalized and DKA resolved.

Further work-up ruled out more common etiologies of liver injury. Multiple abdominal ultrasounds and CT scans showed a normal sized liver without obvious structural abnormalities. Labs were significant for negative hepatitis B and hepatitis C; several negative anti-smooth muscle, anti-nuclear antibody, centromere antibody, and liver kidney microsomal type 1 antibody; normal levels of ceruloplasmin and alpha 1 anti-trypsin; low iron levels 23 ug/dL (60-180 ug/dL); borderline low IgG 627 mg/dL (700-1600 mg/dL).

We hypothesized that the patient likely had GH by exclusion of other liver pathologies and given the context of transient transaminitis during DKA.

Conclusion: GH is a benign and favorable diagnosis in diabetic patients with elevated transaminases.1 Given the small number of cases of GH reported, there is a need to record and analyze more patients with likely GH in order to better understand the condition. Appropriate clinician awareness of GH can also eliminate the need for time consuming and costly workup.

References:1. Sherigar, Jagannath M et al. “Glycogenic Hepatopathy: A Narrative Review”. World Journal Of Hepatology, vol 10, no. 2, 2018, pp. 172-185. Baishideng Publishing Group Inc., doi:10.4254/wjh.v10.i2.172.
MON-LB311 Clinical Guidelines for the Research on the Endocrinology of Physical Activity and Sport
Authors: Cadegiani Flavio A , da Silva Pedro Luiz H
Published: May 2020

Background: The importance of physical activity has achieved levels that has been recognized by as a major world public health game changer, which positively engaged a growing number of subjects to become physically active. While effects of exercise on cardiovascular and musculoskeletal systems are well described, little is known regarding hormonal adapted physiology in athletes, as well as how to detect and manage endocrine abnormalities in physically active subjects. Methodological issues and inconsistent findings precluded from a structured understanding of the endocrinology physiology of physical activity and sport. The objective of the present guideline is to uniformize the design and assessment methods of further studies in the field, based on standardized hormonal and metabolic parameters, and dynamic testings. Methods: Guidelines were actively searched within endocrinology, sports medicine, and cardiology societies. Systematic search on PubMed and Cochrane databases for the expressions “(name of the parameter or test)” + “exercise” or “athlete(s)” or “sport(s)” or “validation” or “standardization. Guidelines, consensus, statements, original studies, and reviews that standardized, validated, or proposed parameters and tests that could be potentially employed for the research on physical activity and sport were included.Results: Parameters of the hypothalamic-pituitary-gonadal (HPG), hypothalamic-pituitary-adrenal (HPA), growth hormone-insulin-like growth factor-1 (GH-IGF1), and hypothalamic-pituitary-thyroid (HPT) axes, prolactin, renin-angiotensin-aldosterone system (RAAS), catecholamines and adrenal medulla, bone, water, glucose, and lipid metabolism, and adipose tissue and muscle endocrine profile were analyzed and classified according to the level of standardization, feasibility, and potential roles in physical activity and sport, and recommended accordingly. Recommendations on the characterization of the studied population, including eating, sleeping, social, psychological, and training patterns were depicted. Conclusion: The research on the endocrinology of physical activity and sport requires standardization and uniformization regarding the description of baseline and training characteristics, and which parameters and tests should be employed. These improvements will allow the development of a more structured and comprehensive knowledge on the field, based on comparative joint analyses of further researches, that should employ well-established parameters and adequately controlled for confounding variables.
SAT-347 Diagnosis of Autosomal Dominant Hypocalcemia Type 1 Following the Initiation of Imatinib for Treatment of Chronic Myeloid Leukemia
Authors: Jones-Ryan Madeline L , Desouza Cyrus V
Published: May 2020

Background: Autosomal Dominant Hypocalcemia Type 1 is an underdiagnosed condition due to the vast majority of patients being asymptomatic and having mild hypocalcemia. Imatinib has been associated with hypophosphatemia and hypocalcemia.

Clinical Case: 69-year-old man who had a long history of asymptomatic mild hypocalcemia, calcium level of 7.9 mg/dL (8.4 – 10.2 mg/dL) diagnosed with chronic myeloid leukemia and developed symptoms of hypocalcemia within 2 months of treatment with imatinib. After the initiation of imatinib, his calcium reduced to 6.8 mg/dL (8.4 – 10.2 mg/dL) with a corresponding ionized calcium of 0.98 mmol/L (1.12–1.32 mmol/L) within 2 months. He developed tetany. With the reduced calcium level his PTH was unexpectedly low-normal at 34 pg/mL (16–62 pg/mL). He also had a higher than expected urinary calcium of 342 mg/24 hours. The PTH and 24-hour urinary calcium levels raised concern for an underlying diagnosis of autosomal dominant hypocalcemia type 1. His phosphorous was normal at 3.3 mg/dL (2.6–4.9 mg/dL). He never had hypophosphatemia, which is common with imatinib.

After two doses of IV calcium and initiation of oral calcium replacement, 1000 mg BID, his level continued to be reduced with symptoms. Given his symptoms, laboratory results, and continued hypocalcemia he underwent genetic testing. Results of his genetic testing showed a p.Thr151Met mutation in the CASR gene consistent with autosomal dominant hypocalcemia type 1. With this diagnosis, there is concern for nephrolithiasis with over treatment. His symptoms resolved with treatment with calcium 1000mg TID, calcitriol 0.25 mg BID and vitamin D3 2000 IU daily. He has not developed nephrolithiasis and his urinary calcium increased to 424mg/24 hours. A thiazide diuretic is being considered to decrease urinary calcium excretion.

He continues on imatinib with an excellent response to therapy. It is likely that the trigger for symptomatic severe hypocalcemia was initiation of imatinib superimposed on the hypocalcemia type 1. Possible mechanisms for this are decreased intestinal absorption, increased urinary loss, or decreased dissolution from bone. 1 These mechanisms are also associated with hypophosphatemia, which our patient did not have. Another possible cause could be an immune mediated destruction of the parathyroid gland, a rare finding seen with other tyrosine kinase inhibitors.2

Conclusion: This is the first reported case of imatinib triggering severe symptomatic hypocalcemia leading to the diagnosis of underlying autosomal dominant hypocalcemia type 1.

References:

1.

Vandyke, Kate, et al. “Dysregulation of Bone Remodeling by Imatinib Mesylate.” Blood, vol. 115, no. 4, 2010, pp. 766–774., doi:10.1182/blood-2009-08-237404.

2.

Petrić, Marija, et al. “A Rare Case of Hypocalcemia Induced by Nilotinib.” Endocrine Oncology and Metabolism, 3 Mar. 2017, pp. 32–53., doi:10.21040/eom/2017.3.5.1.
SUN-525 Successful Surgical Management of Graves’ Disease in Pregnancy
Authors: Ali Dalal , Balan Gabriela , Wan Mahmood Wan Aizad , McDermott Enda , Crowley Rachel
Published: May 2020

Background: Total thyroidectomy in pregnancy is not a widely used approach for management of Graves’ disease (GD) but is indicated when thyrotoxicosis persists in spite of efforts to optimise thyroid status.

Clinical case: A 27-year-old lady with history of GD, presented at the 9th week of her second pregnancy. She had been counselled about anti-thyroid medications but was on carbimazole (CBZ) 30 mg tds and propranolol LA 80 mg od at presentation. She complained of palpitations, heat intolerance, irritability, weight loss and difficulty swallowing. On clinical examination, she had a heart rate of > 100/min and diffusely enlarged goiter with a bruit. Thyroid Ultrasound showed a right lobe of 6.5 x 2.8 x 2.7 cm and left lobe 5.3 x 2.6 x 2.4 cm. Free thyroxine (FT4) was 42.3 pmol/L (12–22), free triiodothyronine (FT3) 9.09 nmol/L (1.3–3.1), and TSH < 0.01 mIU/L (0.27–4.2). TRAB titer was >40 IU/L (0.0–1.75). She was advised to switch to propylthiouracil (PTU) and labetalol to minimize fetal adverse outcomes. She reported that she was unable to afford PTU and requested a switch back to CBZ.

During her course of therapy, she had recurrent admissions with thyrotoxicosis, tachycardia, panic attacks and difficulty in swallowing. A decision was made to manage her with total thyroidectomy in the second trimester. She was treated with Lugol’s iodine, beta blockers and CBZ 2 weeks prior to her surgery and there were no immediate post-operative adverse events. Histology was consistent with GD. Her post-op TRAB titer remained >40 IU/L until present.

She delivered at 28 weeks of gestation due to threatened premature labor a baby boy who had neonatal thyrotoxicosis, required admission to the neonatal ICU and therapy with flecanide and CBZ. His TSH was 0.09 mIU/L, (FT4) 68.7 pmol/L and TRAB 19.4 IU/L. He is currently 18 months old, well and not on any medications.

Conclusion: Poor control of thyrotoxicosis is associated with pregnancy loss, prematurity, stillbirth, thyroid storm, and maternal congestive heart failure. Therefore, pre-pregnancy counseling is crucial to establish Euthyroid state for the safety of mother and fetus.

Reference: (1) Davis LE, Lucas MJ, Hankins GD, Roark ML, Cunningham FG. Thyrotoxicosis complicating pregnancy. Am J Obstet Gynecol. 1989;160:63–70. doi: 10.1016/0002-9378(89)90088-4. (2) Vini L, Hyer S, Pratt B, et al. Management of differentiated thyroid cancer diagnosed during pregnancy. Eur J Endocrinol. 1999;140:404–406.
MON-250 Late Diagnosis of ACTH-secreting Pulmonary Neuroendocrine Tumor by Repeated 68Ga Dotatate Pet/ct: Influence of Tumor Size in Abnormal Uptake?
Authors: Andrade Natália Xavier S , Pereira Ana Julia Garcia , Villares Fragoso Maria Candida Barisson , Bronstein Marcello Delano , Machado Marcio Carlos
Published: May 2020

Background: 68Ga DOTATATE PET/CT (68Ga-PET) has been proposed as a superior method in identifying ectopic ACTH syndrome (EAS). However, recent systematic review suggests its sensitivity is not as high as believed (1). We report a challenging case of EAS whose source was uncovered only after repeated 68Ga-PET. Clinical Case: A 15-year-old male presented with rapid onset of typical features of Cushing’s syndrome (CS) and metabolic impairment. Hormone evaluation confirmed severe ACTH-dependent CS. Pituitary transsphenoidal surgery was performed due to positive responses in desmopressin stimulation and high dose dexamethasone suppression test, in addition to a 4 mm nodule in pituitary MRI. No tumor was found in surgical specimen and no hormonal improvement was observed after surgery. Inferior petrosal sinus sampling demonstrated no central to peripheral ACTH gradient. Neck US, thorax/abdomen/pelvis CT were negative and PET-CT/FDG was inconclusive. OctreoScan® identified anomalous uptake on left mediastinum and led the patient to a thoracic surgery (TS) with nodule resection at left hilum. Pathology confirmed ACTH positive 10 mm neuroendocrine tumor (NET) infiltrating a lymph node. The patient had transient clinical and hormonal improvement, with recurrence 7 months later. Thoracic CT (T-CT) showed a 7 mm nodule on inferior segment of superior left lobe, PET-CT/FDG and OctreoScan® were negative but abnormal uptake was verified by 68Ga-PET in subcarinal area. A sub centimetric lymph node was resected and pathology confirmed ACTH positive NET, although the patient did not achieve remission. Octreotide LAR, cabergoline and ketoconazole did not control hypercortisolism and bilateral adrenalectomy was performed. Then, T-CT showed stable lung nodule and 2nd 68Ga-PET was negative. One year later, T-CT evidenced growth of lung nodule to 15 mm and 3rd 68Ga-PET demonstrated for the first time, abnormal uptake in this area. The patient underwent resection of left superior lung lobe along with ipsilateral hilar lymph nodes, and histopathology study revealed an ACTH-secreting atypical pulmonary carcinoid tumor with Ki67 of 10% and 5 out of 11 lymph nodes affected. ACTH fell from 288 to 64 pg/mL after surgery. Conclusion: Despite the high sensitivity attributed to 68Ga-PET, false negatives have been reported. In the present case, primary tumor was evidenced by 68Ga-PET seven years after the first resection of a metastatic lymph node, in the 3rd 68Ga-PET assessment and after tumor growth. This adds to the evidence that further studies are needed to better assess the accuracy of 68Ga-PET for EAS. Reference: [1] Varlamov et al. Diagnostic utility of Gallium-68-somatostatin receptor PET/CT in ectopic ACTH-secreting tumors: a systematic literature review and single-center clinical experience. Pituitary 2019; 22:445–455
MON-671 Embarrassed to Eat: Two Cases of Gustatory Hyperhidrosis
Authors: Tarar Omer H , Munoz Andres J
Published: May 2020

Introduction

Diabetic Gustatory Hyperhidrosis is characterized by profuse sweating with eating and may be a manifestation of Diabetic autonomic dysfunction. Most patients have evidence of other microvascular complications including nephropathy, retinopathy, peripheral neuropathy and other signs of autonomic neuropathy.

We present 2 cases of gustatory hyperhidrosis associated with longstanding poorly controlled type 1 diabetes.

Case 1: 49 year old Male with past medical history of longstanding type 1 diabetes with poor control, complicated with diabetic retinopathy, polyneuropathy, albuminuria presented to endocrine clinic for management of diabetes. His hemoglobin A1c was 10.8%. He was on basal-bolus Insulin at home. However, he admitted to missing most doses of prandial Insulin. On further questioning, he mentioned having episodes of profuse head and neck sweating while eating any type of food. He attributed these episodes to “low blood sugars” without checking and therefore tried to avoid Insulin. However, he continued having these episodes. He was diagnosed with Diabetic gustatory hyperhidrosis and started on topical Aluminum hexahydrate.

Case 2: 34 year old Female with past medical history of long-standing DM type 1 complicated with poly- neuropathy, autonomic dysfunction, nephropathy, Retinopathy, chronic kidney disease stage III presented for follow up of her diabetes. Her hemoglobin A1c was 9.8%. She was on basal-bolus Insulin at home and reported good compliance. Given her extensive polyneuropathy, she was questioned about hyperhidrosis. She reported having profuse facial and neck sweating with eating all types of food which led to increased embarrassment while eating in public. She was diagnosed with diabetic gustatory hyperhidrosis and started on topical aluminum hexahydrate, with plans for Botox if symptoms persisted.

Discussion

Diabetic Gustatory Hyperhidrosis is an under- recognized condition and may be misdiagnosed as hypoglycemia, anxiety, gastroparesis or other conditions. This gustatory sweating is a source of severe distress and embarrassment for patients and can have serious emotional, social and professional implications. Associated symptoms may also be mistaken for hypoglycemia and in turn lead to nonadherence with Insulin and other diabetic medications causing suboptimal glycemic control.

Topical anti-perspirants like Aluminum Chloride hexahydrate are often used as first line therapy. Second line treatment options include glycopyrrolate, Oxybutynin and Botulinum toxin.

Conclusion

Most patients are reluctant to mention these symptoms to health care providers and diligent history taking with specific questions in high risk patients may help in early identification and management of this condition.

Early identification and management can also help promote overall confidence, quality of life and better glycemic control.
SUN-498 A Case of Thyroid Storm with Systemic Thromboembolism
Authors: Maung Aye Chan , Tan Daphne Gardner Su-Lyn
Published: May 2020

Background

Thyroid storm is a rare but potentially life-threatening complication of hyperthyroidism. Whilst a thyroid storm is known to be a hypercoagulable state, it remains unclear if routine anticoagulation should be initiated, especially in the absence of atrial fibrillation.

Case presentation

A 22-year-old seaman presented to Accident and Emergency Department with a history of severe generalized abdominal pain and vomiting for 9 days. He was previously well with no significant past medical history. On examination, he appeared very anxious and agitated. He had sinus tachycardia (170 beats/min), was normotensive (Blood pressure 116/90 mmHg). He had exophthalmos, lid lag, a diffusely enlarged goiter with bruit and fine tremors on outstretched hands. There was generalized abdominal tenderness with guarding and sluggish bowel sounds. Electrocardiogram confirmed sinus tachycardia. Laboratory results showed primary hyperthyroidism [Free T4 66.2 (0.8–14.4 pmol/L), TSH <0.010 (0.65–3.70 MU/L)]. TSH Receptor Antibody was elevated at 6.23 IU/L (<1.76 IU/L), consistent with Grave’s Disease. He had acute renal impairment [urea 10.8 (2.7–6.9 mmol/l), creatinine 221 (54–101 umol/l)]. Burch & Wartofsky score was 60. Treatment with rectal propylthiouracil (PTU), i.v sodium iodide and i.v hydrocortisone were initiated.

An initial CT Abdomen on Day 1 of admission demonstrated a long segment of jejunitis and marked distension of the duodenum, stomach and oesophagus. 4 days later, fT3 and fT4 levels had improved as did tachycardia and his confusion state, yet he remained febrile. Blood and urine cultures did not reveal any causative organisms. A contrast-enhanced CT revealed extensive thromboses of the portal, superior mesenteric, right external iliac, common femoral veins with left lower lobe pulmonary embolism. Thrombophilia screen was normal. He was given low-molecular-weight heparin and required total parenteral nutrition in view of prolonged bowel ileus from mesenteric ischaemia. Rectal PTU was continued to treat thyrotoxicosis. He made sufficient progress with improvement of the bowel ileus with s.c enoxaparin and was discharged 6 weeks later on oral carbimazole (on discharge: fT4 10pmol/L, TSH<0.010). However, due to extensive thromboses within the mesenteric venous system and consequent ischaemic jejunitis, he required a jejunectomy eventually 2 weeks later. Radioiodine ablation was subsequently given and he is currently hypothyroid requiring thyroxine replacement.

Conclusion

Extensive systemic thromboembolism may occur in the setting of a thyroid storm. Routine prophylactic anticoagulation should be considered, even in the absence of atrial fibrillation.

References

1. Lin HC et al. Journal of Thrombosis and Haemostasis 2010, 8: 2176–2181

2.Kootte et al. Thromb Haemost 2012; 107: 417–422

3. Franchini et al. Clinical and Applied Thrombosis 2010, 17(4) 387–392