bluuebunny/crossref_metadata_2025 huggingface dataset:
MON-103 Pattern and Predictors of Thyroid Dysfunction Among Paediatric Endocrine Referrals at Tertiary Care Centre: A Longitudinal Study
Authors: Masoodi Shariq Rashid , Sood Mona , Peerzada Ovais Ahmed , Bhat Moomin , Vasudevan Vishnu
Published: May 2020

Background Post iodisation era has experienced gradual change in pattern of thyroid disorders among paediatric population with autoimmunity taking precedence over iodine deficiency disorders and subclinical hypothyroidism (SCH) now more frequently diagnosed but inappropriately managed. Aims This study was conducted to evaluate pattern of abnormal thyroid function among children referred to our tertiary care centre, to ascertain characteristics that influence treatment decisions and to follow them for various outcome measures. Design It was an observational longitudinal follow up study where all children less than 18 years, referred to our outpatient clinic for suspected thyroid disorder were recruited. Demographic data, personal and family history, clinical features were noted and laboratory tests including TT4, TT3, TSH, anti-thyroid peroxidase(antiTPO) and anti-thyroglobulin(antiTG) antibody were conducted in study subjects. Management was based on the clinical judgment of the attending endocrinologist. Patients were followed at 6 week, 3 months, 6 months and one year with clinical and laboratory work up at each visit. Results A total of 241 subjects aged 18 days to 17 years were included out of which 62.25% were females. Initial evaluation revealed SCH in 40% of refereed subjects, overt hypothyroidism (OH) in 33%, congenital hypothyroidism (CH) in 18% and overt thyrotoxicosis in 5%. Autoimmune thyroiditis constituted the major cause of hypothyroidism in the OH group with significantly higher prevalence of anti-TPO and antiTG antibody in comparison of SCH group (61% vs 31%; 45% vs 21.9%, p<0.05) respectively. All subjects in OH group were treated whereas 76% subjects in SCH group were treated and the mean dose of L thyroxine required to treat OH was significantly higher (2.31+1.1ug/kg/day vs 1.76+1.07ug/kg/day; p<0.001) in comparison of SCH group. A major independent predictor of treatment in SCH was initial TSH which was significantly higher in the treated group (11.65 + 3.80 uIU/ml vs 9.24 + 1.31 uIU/ml; p<0.001). Subjects with congenital hypothyroid presented at a mean age of 6 months (18 days to 2 years) with most common aetiology being thyroid hypoplasia and dyshormonogenesis

(20% each). Graves’ disease was diagnosed in 11 out of 12 subjects with thyrotoxicosis and were treated with antithyroid drugs. Overall 85.5% of refereed subjects were treated and after one-year follow up management was found to be adequate in 81% subjects. Conclusions The evolving trend of diagnosing children having nonspecific symptoms with SCH is a matter of concern as many are subjected to the burden of unwanted prolonged treatment and frequent testing as highlighted in our study. Delayed presentation of CH in our study warrants active surveillance of children at birth for thyroid disorders to avoid long term adverse effects on mental development.
SUN-240 Female Mice Lacking Brain Insulin Production Exhibit Learning Deficits, Anxiety, and Reduced Hippocampal Cyclin D1 Expression
Authors: Baehring Stella Katharina , O’Leary Timothy P , Holenka Danae M , Li Hong , Kim Kyungchan , Mehran Arya E , Pavlidis Paul , Kim Eun-Kyoung , Bamji Shernaz X , Johnson James D
Published: May 2020

Insulin dysregulation independently underlies diabetes and Alzheimer’s Disease (AD) pathology. However, the former has also been shown to be a risk factor for the latter. The ancestral insulin gene (Ins2), but not the pancreas-specific Ins1gene, is transcribed locally within the brain in mice. We confirmed that neuronal expression of Ins2 is most prominent within the hippocampus, a brain region with established roles in learning and memory, and that it was reduced by a diet known to promote neuronal dysfunction. It is not yet clear, however, how insulin produced locally within the brain influences hippocampal function, learning and memory. To eliminate brain-derived insulin, we used young and old mice with germline Ins2knockout (Ins2-/-) and their normal complement of wildtype Ins1 alleles, which had equivalent pancreatic insulin and normal glucose homeostasis. Using the Morris water maze, we found that learning and memory performance of female Ins2-/-mice was significantly impaired relative to wild-type mice, whereas the performance of male Ins2-/-and wild-type mice did not differ. During acquisition training, the swim-speed in female Ins2-/-was faster than wild-type mice, suggesting increased stress reactivity and motivation to escape from water. Indeed, anxiety-like behavior was increased in female mice as assessed by the open-field test. Using RNA sequencing to profile isolated hippocampi, we found that femaleIns2-/-mice had a significant reduction in Cyclin D1 (Ccnd1) compared with littermate controls. This observation points to a possible defect in hippocampal neurogenesis, a physiological hallmark of impaired memory and emotionality implicated in both, diabetes and AD. Together these data suggest that Ins2plays sex- and brain region-specific roles in neuronal function and perhaps adult neurogenesis.
SUN-938 Rare Case of Ectopic Cushing Syndrome Caused by ACTH Secreting Thymic Neuroendocrine Tumor in a Patient with Multiple Endocrine Neoplasia Type 1
Authors: Gorantla Yamuna , Moncada Jorge Soria , Sarmiento Juan , Amblee Ambika , Ganesh Malini
Published: May 2020

Introduction

Cushing syndrome (CS) represents an uncommon manifestation of MEN1 and can be caused by both ACTH dependent or independent etiologies. Among them, ectopic ACTH secretion from a Thymic neuroendocrine tumor (TNET) in MEN1 is rare, with very few cases reported so far in literature. We report a case of Ectopic Cushing syndrome (ECS) in a MEN1 patient (pt) with multiple tumors, secondary to ACTH-secreting TNET.

Case description:

A 44 year old male presented to our institution for nausea, vomiting, dizziness. He had initial workup which revealed multiple tumors (papillary thyroid cancer, thymic mass, parathyroid adenomas, bilateral adrenal nodules, macroprolactinoma, peripancreatic nodules). Given concern for MEN 1, genetic testing was performed which was confirmative. Hormonal workup at this time for adrenal nodules was negative including low dose dexamethasone suppression test(DST). The immobile thymic mass was found to be poorly differentiated NET on biopsy with Ki-67 >50% with vascular invasion and adhesions to lung/chest wall on VATS, not amenable to surgery. The pt declined chemotherapy and radiotherapy due to poor social support. Six months later, he presented with complaints of shortness of breath, proximal muscle weakness, anasarca. Evaluation revealed AM cortisol >60 ug/dL(range 6.7-22), high-dose DST Cortisol >60 ug/dL, 24hr urine free cortisol: 8511mcg (range 4-50) and ACTH level: 278pg/mL(range 6-50) confirming ACTH-dependent CS. Special stains from the previous TNET biopsy demonstrated positive staining for ACTH confirming ectopic ACTH secretion. Ketoconazole and chemotherapy with Etoposide and Carboplatin was started, however he clinically deteriorated and expired a few weeks after diagnosed of ECS.

Discussion:

TNET in MEN 1 is rare, with a prevalence of 3-8%. TNET are unusual neoplasms that account for 2% to 7% of all mediastinal tumors. TNET in MEN1 rarely secrete functional hormones with very few reported Ectopic ACTH secretion. MEN1 associated ECS from TNET is an aggressive disease with local invasion of adjacent mediastinal structures or metastasis being common, resulting in poor prognosis as demonstrated in few case reports including our case. Radical surgery of involved adjacent structures and adjuvant local RT can provide local disease control.

Conclusion:

Our pt is a rare case of ECS from TNET in MEN1 with poor prognosis. A special feature of this case is that the patient had initial negative evaluation for hypercortisolemia, however 6 months later he presented with signs and symptoms of severe hypercortisolism, with evaluation confirming transformation into ACTH producing TNET. This conversion is very rarely found in literature and adds to the unique presentation of the case.
SUN-649 Metabolic and Functional Regulation of T Cells by Insulin and Insulin like Growth Factor 1
Authors: Kiernan Kaitlin , MacIver Nancie J
Published: May 2020

Obesity leads to altered immunity characterized by increased risk of autoimmunity, poor response to infection, and impaired vaccine response. T cells play an important role in this obesity-associated immune response; however, the mechanisms by which T cells are altered in obesity remain unknown. Our goal is to identify nutritionally regulated hormones and cytokines that link whole body nutrition and immunity, and to understand the mechanisms by which such factors can alter T cell response in obesity. To that end, we have identified the hormones insulin and insulin-like growth factor-1 (IGF-1) as potential links between nutritional status and T cell metabolism and function. Insulin is secreted from pancreatic beta cells in response to increasing blood glucose levels, and circulating insulin levels are elevated in obesity due to insulin resistance in metabolic tissues. IGF-1 levels are influenced by protein intake and nutrition status, and free (bioactive) levels of IGF-1 are elevated in obesity. To study the role of insulin and IGF-1 on T cell function and metabolism, we treated activated CD4 T cells with physiologic levels of insulin or IGF-1 in vitro for 24 hours. Treatment of CD4 T cells with insulin or IGF-1 increased glucose uptake, glycolytic metabolism, and mitochondrial metabolism while altering inflammatory cytokine production. In particular, both insulin and IGF-1 decreased IFN-γ production, whereas IGF-1 specifically increased IL-17 production from both bulk activated CD4 T cells and T cells skewed toward a T helper 17 (Th17) phenotype. Using a T cell-specific insulin receptor (IR) conditional knockout mouse, we found that loss of IR signaling decreased glucose uptake and mitochondrial metabolism and increased IFN-γ production by activated T cells. Moreover, IR appears to be required for both insulin and IGF-1 effects on T cells. Lastly, we investigated the CD4 T cell subset-specific expression of both IR and IGF-1 receptor (IGF-1R). We found that each CD4 T cell subset had its own unique expression of both IR and IGF-1R; however Th17 cells had a striking increase in IGF-1R expression compared to the other T cell subsets, indicating a specific role for IGF-1 in promoting inflammation. These findings underscore the ability of the nutritionally-regulated hormones insulin and IGF-1 to modulate CD4 T cell metabolism and function and thereby alter T cell immunity, which has direct clinical relevance in both normal physiology and in obesity.
OR33-02 The Treatment of Partial Lipodystrophy in the Setting of Neutralizing Antibody Against Metreleptin with Leptin Receptor Agonist REGN4461
Authors: Akinci Baris , de Freitas Maria Cristina Foss , Baker Mark , Hench Rita , Neidert Adam , Boutros Sabine , Akinci Efe Yagiz , Oral Elif A
Published: May 2020

Background: An 18-year-old patient with atypical partial lipodystrophy had a transient initial metabolic response to metreleptin that deteriorated when neutralizing antibodies against metreleptin developed. A therapeutic trial with setmelanotide did not result in any metabolic benefit as desired. Because her status continued to deteriorate, we attempted to treat her with REGN4461, a fully human monoclonal antibody that is an agonist to the human leptin receptor (LEPR). Clinical Case: A compassionate use protocol (IND No. 144013) was initiated to treat the patient with REGN4461. The treatment consisted of 5 mg/kg intravenous infusion followed by 300 mg weekly subcutaneous injections of REGN4461. The primary endpoint was achievement of fasting triglycerides < 500 mg/dL without the need for ongoing plasmapheresis. Treatment-emergent adverse events were also followed. Here, we report her first 21-week response to treatment with REGN4461. The treatment resulted in a reduction of triglycerides from 1288 mg/dL to 344 mg/dl and allowed her to discontinue plasmapheresis. She lost 3.4 kilograms so far, and her liver size reduced per liver span measured by physical examination. Also, the liver MRI at week 12 showed a significant reduction in liver size and fat content (from 29.9% to 16.6%). Although her glucose control is still challenging, a slight reduction in her HbA1c was observed at week 12 along with improvements in her average glucose levels and total daily insulin requirement so far. No untoward signals were detected in her safety measurements. Conclusion: To date, treatment with REGN4461 offered substantial clinical benefit by improving the metabolic abnormalities in this unique patient. This experience represents the longest human exposure with REGN4461. The improvements noted in metabolic parameters and hepatic steatosis are similar to previous observations in lipodystrophic humanized LEPR mice. Our results suggest that REGN4461 showed clinical benefit even in the presence of neutralizing antibodies to metreleptin.
SAT-251 New Diagnosis of Acromegaly with DKA as Initial Presentation
Authors: Gundluru Rajani , Verma Ritika , Regunath Hariharan , Gardner Michael J , Huynh Kiet
Published: May 2020

Background: While diabetes mellitus from growth hormone related insulin resistance is not uncommon in GH secreting tumors, initial presentation with diabetic ketoacidosis is rare.

Clinical Case: 31 YO male with no significant past medical history presented with c/o fatigue, 40 lb weight loss, polyuria, polydipsia. Clinical features of acromegaly with frontal bossing, protruding jaw, large hands and feet, thick spade like fingers, hammer toes, high arches and thickened fat pads on both feet were noted. Initial labs were consistent with DKA with anion of 31 mmol/L (0-20), blood glucose 241 mg/dl, bicarb 12 mmol/L (22-29), serum betahydroxy butyrate > 8 mmol/L (0-0.29), urine positive for glucose, ketones, protein. Patient was initially treated with IV insulin per DKA protocol, transitioned to subcutaneous insulin.

MRI brain showed 2.1x1.3x2.1 cm pituitary macro adenoma. Labs showed elevated IGF1 LC/MS, S 1094 ng/ml (54-310), IGFBP3 14 mcg/ml (3.5-7), Z score IGF MS Mayo > 3 (-2 to +2), normal FSH 7.1 m unit/ml (1.5-12.4), normal LH 3.4 m unit/ml (1.7-8.6), normal prolactin 6 ng/ml (4-15), normal ACTH 10 pg/ml, cortisol 13.4 mcg/dl, low total testosterone 48.2 ng/dl (193-836), normal free testosterone 7.92 ng/dl (4.85-19), normal TSH 1.55 mc unit/ml (0.27-4.2) and free T4 1.17 ng/dl (0.93-1.7). The patient was discharged home on 120+ units of total daily dose of insulin, after initial hospital admission.

He underwent trans sphenoidal resection of pituitary macro adenoma one month after his initial presentation. Surgical pathology confirmed growth hormone producing adenoma. He was successfully weaned off from insulin in one month following surgery.

Conclusion: DKA is an unusual initial presentation of growth hormone producing tumors. As more cases are being reported it is important to be vigilant to look for DKA presentation in these patients and adjust/wean patients insulin once the growth hormone producing tumor is treated either with surgery or medications.
SAT-468 Anticoagulation Conundrum: A Case Of Embolic Stroke Due To Thyrotoxic Atrial Fibrillation
Authors: Munshi Laishiya , Gorantla Yamuna , Mascarell Susana
Published: May 2020

Background: Thyrotoxicosis is not incorporated into any of the atrial fibrillation (AF) CVA risk stratification methods, including CHADS2VASc, as neither the American College of Cardiology/American Heart Association nor the American College of Chest Physicians view it as an independent risk factor of CVA. However, the literature has reported numerous cases of patients with thyrotoxic AF and low CHADS2VASc scores who developed CVA. It is unclear which patients with thyrotoxic AF would benefit from prophylactic anticoagulation (AC).

Clinical Case: A 50-year-old male without past medical history presented for palpitations. He was found to be in AF with rapid ventricular rate. Labs revealed thyrotoxicosis (TSH <0.010 [RR 0.34-5.6 μIU/mL], FT4 3.57 [RR 0.61-1.64 ng/dL], FT3 5.26 [RR 2.5-4.5 pg/mL], and TSI negative). He was started on methimazole but no AC, as his CHADS2VASc score was 0. A few hours after admission, he developed a right-sided facial droop and weakness & aphasia. CT head showed acute left MCA infarct. CTA head/neck revealed occlusive embolus in the distal left M1 segment. He underwent IR-guided embolectomy and received intra-arterial tPA. Echocardiogram did not show thrombi or atrial level shunt but showed right atrial dilation. After extensive work-up, etiology of CVA was determined most likely a cardioembolic source due to thyrotoxic AF. Patient was treated with PTU and steroids initially for two days due to recent contrast exposure (CTA and embolectomy) and poor neurologic status, in order to obtain the added benefit of decreased T4 to T3 peripheral conversion. Patient was started on AC two weeks after his CVA (given initial risk of hemorrhagic conversion due to large CVA burden), at which time his weakness and aphasia were slowly improving, but he remained with significant neurologic deficits.

Discussion : The current thought that thyrotoxicosis is not an independent risk factor of CVA in patients with AF has led to recommendations against prophylactic AC for this specific group. Although recent research has suggested that patients with thyrotoxic AF are at a lower risk of CVA than patients with non-thyrotoxic AF, there have still been many reported cases of CVA in patients who have thyrotoxic AF but no other risk factors for CVA. This discrepancy in association between thyrotoxic AF and CVA needs to be clarified.

Conclusion: This case of a middle-aged man with thyrotoxic AF who developed a debilitating CVA after being treated according to his CHADS2VASC score of 0 (he was not given prophylactic AC) mirrors multiple cases in the literature. It highlights the potential benefit of examining thyrotoxic patients with AF more closely in order to more effectively risk stratify them for CVA or further exploring the relationship between thyrotoxicosis and CVA. This may help to identify more patients who could benefit from AC and thus prevent devastating consequences of CVA.
MON-614 Degree of Diabetes Control Determines the Admission Severity of Diabetic Ketoacidosis
Authors: Grover Harshwant , Dhillon Puneet , Gopisetti Neethu , Rosenberg Daniel Evan , Patel Rajeshkumar
Published: May 2020

Objectives: To determine whether the degree of diabetes control correlates with the admission severity of diabetic ketoacidosis (DKA).

Methods: A Retrospective chart review was performed for patients admitted with DKA to the medical ICU at Abington Memorial Hospital between January 1, 2017 and January 1, 2018. Laboratory Data required to determine an acute physiology and chronic health evaluation (APACHE) score, hemoglobin A1C, length of hospital stay was recorded. The APACHE score was used to determine the severity of disease at admission. Patients were divided into two groups: low severity (APACHE <15) and high severity (APACHE >15).

Results: A total of 50 patients were included in the analysis. The mean age of the patients was 47 yrs (range 17-85 yrs). 52%(n=26) of the population were males. The overall mean APACHE II at admission was 15 (range 3-28). The low severity group (APACHE <=15) and high severity group (APACHE >15) were equally matched at 25 patients each. The mean APACHE scores were 9.9 and 18.7 for the low and high severity groups respectively. The mean hemoglobin A1C values for the low and high severity groups were 10.5 and 15 respectively. The average length of ICU/hospital stay was 1.6/3.65 and 1.54/3.61 days for the low and high severity groups respectively.

Conclusions: According to our study, a higher severity of DKA (higher APACHE) was associated with a higher hemoglobin A1C level. However, the study did not find any difference in the average length of ICU/hospital stay between the two groups.
SUN-241 Adult Exposure to Iodoacetic Acid Leads to Abnormal Expression of Key Genes Related to Hypothalamic and Pituitary Control of Reproductive Function
Authors: Gonzalez Rachel , Weis Karen E , Gonsioroski Andressa V , Flaws Jodi A , Raetzman Lori T
Published: May 2020

Water disinfection byproducts (DBPs) are formed when chemicals used to decontaminate water come into contact with natural or synthetic organic material. DBPs have been linked to a range of health concerns including reproductive disfunction. One such DBP, the monohalogenated iodoacetic acid (IAA), is formed when iodide reacts with a disinfectant, for example, chlorine. IAA is of particular health concern; not only is iodide widely present in the water supply, especially in coastal communities and those near fracking sites, but IAA has been found to be one of the most cyto- and genotoxic DBPs. Further, a previous study has indicated that in vitro IAA exposure significantly inhibits antral follicle growth and reduces estradiol levels in ovaries. However, little is known about how IAA affects the other major components of the reproductive axis: the hypothalamus and pituitary. The reproductive axis relies on homeostatic release of hormones to communicate from one organ to another and alterations at any level may impact reproduction. So, we set out to test the hypothesis that exposure to IAA would lead to disrupted expression of key hypothalamic and pituitary genes related to reproductive function. We continually exposed female adult CD1 mice to 0.5, 10, 100, or 500 mg/L IAA in their drinking water for approximately 35 days (postnatal day 40 (P40) to their first day in diestrus following P75.) Whole pituitaries and hypothalamic punches containing the arcuate nucleus (ARC), anteroventral periventricular zone (AVPV), and medial preoptic nucleus (mPOA) were collected and processed for qPCR analysis. We find that while kisspeptin (Kiss1) expression in the AVPV - the population responsible for generating the LH surge - is unchanged, 0.5 mg/L IAA exposure significantly increases Kiss1 in the ARC, which controls pulsatile GnRH release, and there is a trending increase (p=.056) at 10mg/L. We also measured ARC expression of Neurokinin B (NKB; Tac2), a neuropeptide secreted by kisspeptin co-expressing neurons to autosynaptically stimulate Kiss1 release. We found no change in mRNA levels of Tac2. We also saw no significant changes in GnRH (Gnrh1) mRNA expression. At the level of the pituitary, there is no change in Lhb mRNA levels. Exposure to 10 mg/L IAA leads to significantly reduced Fshb expression, however FSH serum levels are not significantly changed. These data, taken together with previous findings in the ovary, indicate that IAA has the potential to disrupt each major level of the reproductive axis: ovarian follicle development and steroid synthesis, hypothalamic arcuate Kiss1 synthesis, and Fshb synthesis from the pituitary. Further research is necessary to elucidate at which levels IAA acts directly and at which it acts through action on another component of the axis. Additionally, future studies can clarify the mechanism through which IAA has these effects.
SAT-119 Targeting Glutamate Metabolism and Signaling in ER+, Endocrine Therapy-Resistant Breast Cancer
Authors: Olukoya Ayodeji O , Stires Hillary , Guerra Yanira , Persaud Sonali , Ma Shihong , Raj Ganesh V , Riggins Rebecca B
Published: May 2020

Estrogen receptor-positive (ER+) breast cancer is the most commonly diagnosed form of this malignancy. Aromatase inhibitors and selective estrogen receptor modulators or degraders (SERMS, SERDs) can be highly effective in treating ER+ breast cancer, but de novo and acquired resistance to these interventions is a persistent clinical problem. Endocrine therapy resistant breast cancer cells rewire their metabolism to support cellular demands associated with rapid proliferation and/or increased invasion and metastasis. An important feature of this metabolic flexibility is conversion of glutamine to glutamate, an amino acid integral to protection of cells from oxidative stress. Consistent with this, we show multiple cellular models of ER+, endocrine resistant breast cancer cells markedly increase glutamate release and upregulate expression of essential glutamine/glutamate metabolic enzymes and transporters, including the glutamate/cystine antiporter xCT, glutamate dehydrogenase (GLUD1/2), and/or the glutamine importer SLC1A5. Riluzole (RIL) is FDA-approved for the treatment of amyotrophic lateral sclerosis (ALS), and has several proposed mechanisms of action, including suppression of glutamate release and increased glutamate uptake. We show ER+, endocrine responsive and resistant breast cancer cells are growth-inhibited by RIL. This is due to an increase in cell death, particularly in endocrine resistant breast cancer cells, and cell cycle arrest. Interestingly, histologic subtype confers a different cell cycle arrest profile, with invasive ductal cancer (IDC) models arresting in G1 but invasive lobular cancer (ILC) models arresting in G2/M. Isobologram analysis of RIL plus SERMs or SERDs shows additive-to-synergistic activity in a subset of ER+ cell line models, and preliminary studies show combination activity in patient-derived explants (PDEs). Mechanistically, we tested whether signaling through metabotropic glutamate receptors (mGluRs, GRMs) and/or cystine import contribute to RIL’s growth-inhibitory phenotype. Antagonists of mGluRs/GRMs don’t phenocopy the effects of RIL, suggesting extracellular glutamate signaling through these receptors is not a key mechanism. Rescue experiments with β-mercaptoethanol to promote cystine uptake through transporters other than xCT show partial reversal of RIL-mediated cell cycle arrest in some cells, suggesting xCT may contribute to RIL-induced growth inhibition. In summary, we show RIL may be a viable addition to endocrine therapy in ER+ breast cancer. Ongoing studies will test additional mechanism(s) by which RIL may attenuate the growth of ER+ breast cancer models in vitro, including inhibition of protein kinase C and casein kinase 1 delta. We are further testing RIL efficacy alone and in combination with a SERD in primary tumors and lung metastases in a ER+ patient-derived xenograft (PDX) model.
SAT-479 Atypical Presentation of Recurrent Cardiac Tamponade Following Pericardial Window in the Setting of Uncontrolled Hypothyroidism
Authors: Khan Sara Atiq , Sarwar Chaudhry M S , Avichal Dipa
Published: May 2020

INTRODUCTION:

Classically, cardiac tamponade presents with hypotension, distant heart sounds and tachycardia (Beck’s triad). Pericardial window is considered effective treatment. Pericardial effusions are relatively common in hypothyroidism (3-6%) (1). Cardiac tamponade, however, is rarely seen in patients with hypothyroidism secondary to pericardial distensibility and the slow accumulation of fluid, allowing significant fluid accumulation without hemodynamic compromise (2).

CLINICAL CASE:

A 84 year-old female with history of post-surgical hypothyroidism (on levothyroxine 150 mcg) following total thyroidectomy for thyroid cancer, cardiac tamponade requiring pericardial window formation two years prior, presented for dyspnea on exertion and pedal edema for several days. She was tachypneic to 22/min with heart rate 47/min and blood pressure 92/62. Distant heart sounds were noted on exam.

EKG demonstrated sinus bradycardia, low voltage QRS and T wave flattening. Further workup revealed TSH elevated to 44 uIU/mL (N:0.27–4.2 uIU/mL), free T4 0.17 ng/dl (N:0.93-1.7 ng/dl) and undetectable T3 (N: 80-100 ng/dl). Echocardiogram unexpectedly demonstrated a large circumferential pericardial effusion with diastolic collapse of the right atrial, right ventricular free wall, significant respiratory variations and interventricular dependence. These findings were consistent with cardiac tamponade physiology. She underwent a video assisted left thoracotomy pericardial window formation along with drainage of 400cc of yellow pericardial fluid. Fluid cytology and tissue histopathology were negative for malignancy. Her uncontrolled hypothyroidism was considered the cause for recurrence of cardiac tamponade and her levothyroxine dose was increased to 175 mcg. At two week follow up, she reported symptomatic improvement on the higher levothyroxine dose. Echocardiogram did not show reaccumulation of fluid.

CONCLUSIONS:

Sinus tachycardia is found in most patients with cardiac tamponade, except in hypothyroid patients (2). A high degree of suspicion is needed to diagnose cardiac tamponade in hypothyroidism, even in patients who have undergone presumed definitive therapy with a pericardial window in the past. The recent onset of pedal edema and low blood pressure were important indicators of impending cardiac compromise in our patient.

Hypothyroid patients may be at higher risk of pericardial window failure compared to patients with cardiac tamponade of other etiologies, especially if thyroid replacement therapy is inadequate. The scientific literature is lacking in this regard and warrants further investigation.

References:

1 Bajaj R, et al. Cardiac tamponade in hypothyroidism. BMJ Case Rep. 2014;:bcr2014204076

2 Wang JL, et al. Hypothyroid cardiac tamponade: clinical features, electrocardiography, pericardial fluid and management. Am J Med Sci 2010;340:276–81.
OR17-02 Changes in Hepatokines and Apolipoproteins Are Associated with Metabolic Response to Metreleptin in Partial Lipodystrophy
Authors: Akinci Baris , Ajluni Nevin , Eldin Abdelwahab Jalal , Swaidan Mario , Hench Rita , Neidert Adam , Luo Yingying , de Freitas Maria Cristina Foss , Oral Elif A
Published: May 2020

Introduction Metreleptin treatment may improve the metabolic aspects of partial lipodystrophy; however, the treatment response is heterogeneous. This study aimed to explore changes in circulating apolipoprotein concentrations, as well as ANGPLT3, ANGPLT4, and IGF-1 levels in patients treated with Metreleptin as part of a clinical study investigating the efficacy of Metreleptin in nonalcoholic steatohepatitis (NASH) associated with partial lipodystrophy (ClinicalTrials.gov identifier: NCT01679197). Methods Serum samples of 18 patients with partial lipodystrophy who underwent a full metabolic evaluation and paired liver biopsies before and after Metreleptin were studied. Patients were tested at baseline, month (M) 3, M6, and M12. Glycemic response was defined as “more than 1% HbA1c reduction from baseline”. Lipid response was defined as “more than 30% decrease in triglycerides from baseline”. The hepatic response was defined as “a decrease of 2 points or more from baseline in NASH score, without an increase in fibrosis”. Patients with “any 2 of 3 above” at M12 were defined as metabolic responders. Results Metreleptin treatment resulted in significant reductions in triglycerides (346 mg/dL vs. 253 mg/dL; F: 8.474; p < 0.001), apo B (145.24 mg/dL vs. 111.09 mg/dL; F: 9.266: p < 0.001), apo CII (18.65 mg/dL vs. 15.95 mg/dL; F: 6.663: p = 0.001), apo CIII (62.95 mg/dL vs. 49.33 mg/dL; F: 5.640, p = 0.002), apo E (8.16 mg/dL vs. 6.52 mg/dL; F: 11.056, p < 0.001), and ANGPLT3 (14.36 ng/mL vs. 12.00 mg/dL; F: 4.348; p = 0.008) over time. IGF-1 levels significantly increased at M3 (134 ng/mL vs. 139 ng/mL; p = 0.001), however the difference was not significant over time. Metabolic responders had lower baseline leptin (12.4 ng/mL vs. 27.8 ng/mL; p = 0.024) and IGF-1 (95 ng/ml vs. 151 ng/mL; p = 0.008), and higher apo CII (39.06 mg/dL vs. 17.90 mg/dL; p = 0.011), apo CIII (173.57 mg/dL vs. 51.51 mg/dL; p = 0.015), apo E (18.41 mg/dL vs. 5.89 mg/dL; p = 0.002), and ANGPLT3 (17.33 ng/mL vs. 10.06 ng/mL; p = 0.04). Metabolic responders had a significant increase in IGF-1 (95 ng/mL vs. 134 ng/mL; p = 0.019), which was statistically distinguished from non-responders (p = 0.004). Responders also had a greater reduction in apo CII (20.51 mg/dL vs. -1.84 mg/dL; p = 0.001), apo CIII (32.59 mg/dL vs. -7.83 mg/dL; p = 0.007), apo E (8.17 mg/dL vs. 0.22 mg/dL; p = 0.001), and ANGPLT3 (6.08 ng/mL vs. -0.16 ng/mL; p = 0.005) early after treatment at M3. Conclusions Metreleptin treatment lowers levels of apolipoproteins associated with triglyceride metabolism as well as ANGPLT3 in patients with partial lipodystrophy. Metabolic response to Metreleptin appears to be correlated with early changes in these factors and an increase in IGF-1 levels.
SUN-188 Intra-Articular Triamcinolone Injections - a “Slipped” Cause of Cushing’s Syndrome
Authors: Shi Melody , Balikcioglu Pinar Gumus , Benjamin Robert , Freemark Michael
Published: May 2020

Background:

Triamcinolone injections are used to treat various orthopedic and rheumatologic conditions; their effects on the hypothalamic pituitary adrenal axis have not been well characterized.

Clinical Case:

A 14 yo female was referred to our clinic for evaluation of low TSH (0.16 µIU/mL) and possible hyperthyroidism. There was no goiter and she appeared euthyroid and had normal free T4 (1.01 ng/dl) but she had typical features of Cushing syndrome (CS), including round facies, thinning of hair, fatigue, truncal adiposity, violaceous striae, facial hirsutism and oligomenorrhea. She was previously healthy and participated in many sports. She did not report any history of exogenous glucocorticoid use but the fasting ACTH (4 pg/ml) and cortisol (0.1 µg/dl) levels were suppressed. Subsequent chart review revealed that she received intra-articular Triamcinolone (TA) to treat “slipping rib” syndrome. This included 3 injections of Kenalog 40 mg/mL, the last in July 2019. Her cumulative TA dose was 440 mg, the equivalent of prednisone 550 mg. Triamcinolone acetonide 1.4 mcg/dL (normal 0-0.1, analyzed by LC-MS/MS) was detected in the urine over 3 months after her last injection.

Conclusion:

- Levels of ACTH and cortisol can be suppressed for several months after intra-articular corticosteroid injections, placing the patient at subsequent risk for adrenal crisis

- In some cases, high doses of Triamcinolone administered by intra-articular injection can cause clinical Cushing syndrome
SUN-167 Treatment Considerations for a Healthy Pregnancy in Women with Classical Congenital Adrenal Hyperplasia (CAH)
Authors: Calzia Megan , Tasnim Shams , Munir Iqbal , Firek Anthony Francis
Published: May 2020

Background:

CAH is caused by an enzyme deficiency involved in cortisol synthesis leading to an increase in ACTH. Increased ACTH causes elevated levels of steroid hormone precursors & chronic stimulation of the adrenal glands resulting in hyperplasia. The most common form of CAH is due to 21OH deficiency (21OHD) with the classic, salt-wasting form causing glucocorticoid & mineralocorticoid deficiency & androgen excess.

Poorly controlled CAH causes increased production of androgens & progesterone & decreased fertility. Fertility in woman with 21OHD can be challenging due to decreased sexual interest & anatomical abnormalities. Despite these challenges, the pregnancy rate is not significantly lower in women with well controlled 21OHD. However, as these patients are uncommon recommendations for pregnancy can be challenging for endocrinologists.

Clinical Case:

A 27-year old G0P0 female with classic, salt losing CAH presented to discuss pregnancy. Her medications were hydrocortisone 10mg qAM & 5mg qHS & fludrocortisone 0.1mg daily. She denied symptoms of dehydration, nausea, vomiting, dizziness, or fatigue.

She was diagnosed with CAH while in-utero & started on steroid therapy after birth. She did not require any surgical genital reconstruction. Menarche occurred at age 11 and she had regular menses every 35-40 days, with no evidence of excessive androgen exposure including excess body hair, deepening of her voice, or cliteromegaly.

On physical exam she was normotensive & had no evidence of virilization or cushingoid features. She exhibited minor darkening of the palmar creases. Her labs were significant for free testosterone of 9.1 pg/ml (0.2-5.0 pg/ml), total testosterone of 115 ng/dl (2-45 ng/dl), ACTH of 780 pg/ml (6-50 pg/ml), androstenedione of 636 ng/dl (41-262 ng/dl), & 17 OHP of 1560 ng/dl (15-290 ng/dl).

Her hydrocortisone dose was increased to 20 mg qAM & 10 mg qHS & fludrocortisone 0.1mg daily was continued. Our objectives were to normalize the androgen level & suppress serum progesterone to less than 2 nmol/L. If the objectives were not reached she would be converted to prednisone BID.

Conclusion:

Endocrine providers are the primary resource for fertility recommendations for 21OHD patients & must understand the challenges in this very rare group of patients. Collaboration with the perinatologist is crucial for success.

The goals of preconception endocrine assessment in a patient with classic CAH are to adjust hormone therapy to ensure optimal endocrine milieu for conception & risk assessment of having a child affected with 21OHD. The patient will need a higher dose of fludrocortisone during the later part of pregnancy. Counseling that stress doses of glucocorticoids for intercurrent illness and during labor and delivery are required for both the patient and the obstetrician.
SUN-600 Presence of LMNA p.R582H Pathogenic Variant in Homozygous State Demonstrates Gene Dosage Effect on the Severity of Fat Loss in Lipodystrophy
Authors: Soyaltin Utku Erdem , Simsir Ilgin Yildirim , Akinci Baris , Altay Canan , Adiyaman Suleyman Cem , Oral Elif A
Published: May 2020

Background Classical heterozygous pathogenic variants of the lamin A/C (LMNA) gene cause familial partial lipodystrophy type 2 (FPLD2). However, recent reports indicate phenotypic heterogeneity among carriers of LMNA pathogenic variants, and a few patients have been associated with generalized fat loss. Clinical Case Here, we report a patient with lamin A specific pathogenic variant at exon 11 LMNA p.R582H present in homozygous state. Fat distribution was compared radiographically to a heterozygote LMNA p.R582H patient from another pedigree, female healthy control, a series of adult female subjects with congenital generalized lipodystrophy type 1 (CGL1, n = 9) and typical FPLD2 (n = 8). The whole body MRI of the index case confirmed near-total loss of subcutaneous adipose tissue with well-preserved fat in the retroorbital area, palms and soles, mons pubis, and external genital region. This pattern resembled the fat loss pattern observed in CGL1 with only one difference: strikingly more fat was observed around mons pubis and the genital region. Also, homozygous p.R582H LMNA variant was associated with lower leptin level and earlier onset of metabolic abnormalities compared to heterozygous p.R582H variant and typical FPLD2 cases. On the other hand, heterozygous LMNA p.R582H variant was associated with partial fat loss which was similar to typical FPLD2 but less severe than the patients with the hot-spot variants at position 482. Conclusions Our observations and radiological comparisons demonstrate a gene dosage effect of LMNA variants on the severity of fat loss and add to the body of evidence that there may be complex genotype-phenotype relationships in this interesting disease known as FPLD2. Although the pathological basis for fat loss is not well understood in patients harboring pathogenic variants in the LMNA gene, our observation suggests that genetic factors modulate the extent of fat loss in LMNA associated lipodystrophy.
MON-518 Institutional Experience with Cytologically Indeterminate Thyroid Nodules: No Molecular Testing Versus Afirma Gene Expression Classifier or Genomic Sequencing Classifier
Authors: Polavarapu Preethi , Fingeret Abbey , Yuil-Valdes Ana , Patel Anery , Goldner Whitney
Published: May 2020

Background: Molecular analysis of indeterminate thyroid nodules has been shown to reduce unnecessary surgeries for benign thyroid nodules. Afirma Gene Expression Classifier (GEC) has a reported benign call rate (BCR) of 38-61%, and the newer generation Genomic Sequencing Classifier (GSC) has a reported BCR of 42-76%. Both GEC and GSC have a high sensitivity of 88-100% and negative predictive value (NPV) of 94-100%. Specificity and positive predictive value (PPV) have improved with GSC when compared to GEC, largely due to improvements in the classification of hurtle cell neoplasms. GSC PPV is reported as 47-76%. The aim of our study was to determine surgical and malignancy rates for patients at our institution with GEC, GSC, or for those who did not undergo molecular testing.

Methods: Retrospective analysis of all Bethesda III and IV nodules with available follow up data at our institution between January 2013 and December 2018. We evaluated cytopathology, molecular testing with Afirma GEC or GSC, surgical rate, and malignancy rate between groups. Univariate descriptive statistics and bivariate analyses were calculated using Chi-squared and Fisher’s exact testing for categorical variables and one-way analysis of variance for continuous variables.

Results: A total of 376 patients had Bethesda III and IV indeterminate thyroid nodule biopsies and met inclusion criteria for analysis. Of these, 262 patients did not undergo molecular testing, 50 underwent GEC, and 64 GSC testing. There was no difference between the groups for gender, age, or BMI. The overall surgical rate was 66.4, 60.0, and 46.9%, respectively (p=0.014). There was no difference in BCR for GEC or GSC with 44.0% versus 54.7% (p=0.38). There was no difference in malignancy rate with no molecular testing 19.5%, 22.7% if GEC suspicious, and 29.2% if GSC suspicious (p=0.619). GEC had a PPV of 22.7%, NPV of 100%, sensitivity of 100%, and specificity of 56.4% compared with GSC with PPV of 29.2%, NPV of 100%, the sensitivity of 100%, and specificity of 67.3%. Our overall rate of incidentally noted malignancy for indeterminate thyroid nodules who ultimately underwent surgery was 23 of 234 (9.9%).

Conclusions: At our institution, the surgical rate was not different between patients who did not have molecular testing and those with GEC, however, there was a significant reduction in overall surgeries when using GSC. GSC BCR improved when compared to GEC, consistent with previous studies, but PPV remained low at 29.2%, which is lower than previously reported.
SAT-189 Pheochromocytoma as a Rare Cause of Elevated Blood Pressure During Pregnancy
Authors: Alquadan Hammam F , Stefanovic-Racic Maja
Published: May 2020

Endocrine causes of elevated blood pressure during pregnancy are considered a rare, mainly when compared to the more frequent pregnancy-related hypertensive disorders. Thus, the diagnosis of endocrine-related secondary hypertension cases and the outcome of pregnancy will largely depend upon a high clinical suspicion.

A 28 year-old female, presented in pregnancy with elevated, difficult to control blood pressure, leading to induced delivery of a preterm 32 week baby. The baby was admitted to the NICU, where she stayed for 3 weeks.

After delivery, Patient was evaluated in the Endocrine Clinic. She reported episodes of pulsatile headaches, palpitations and excessive sweating for the past 1 year. Each episode would last around 10 minutes and resolved spontaneously. Systolic blood pressure during these episodes was in the 200s and would return back to normal afterwards.

Past medical, surgical and social history was unremarkable. She reported that her mother died suddenly in her 30s from an unknown cause. Physical exam, including blood pressure, was unremarkable in the clinic.

The patient underwent a work up for secondary causes of hypertension after delivery. Tests included plasma metanephrines: 327pg/ml (<57pg/ml), plasma normetanephrines: 7,135pg/ml (<148pg/ml), Chromogranin A 768 ng/ml (<93ng/ml) and a 24 Hour fractionated total metanephrines: 10,170 mcg/24hrs (40-412mcg/24h). She had normal TSH, aldosterone, renin and AM cortisol level.

CT scan of chest, abdomen and pelvis showed a large right retroperitoneal, heterogeneously enhancing mass, measuring 5.8 x 3.7 x 8.3 cm, which encircles the aorta approximately 180 degrees, without evidence of vascular invasion.

Diltiazem three times a day was initiated for preoperative blood pressure control. After 2 weeks, she underwent laparoscopic resection. Pathology showed lesional cells that are positive for synaptophysin and chromogranin while negative for AE1/3 and sustentacular cells that are highlighted by S100, thus supporting a diagnosis of paragangliomas.

Postoperatively, the patient was weaned off all blood pressure medications. Repeat testing showed plasma metanephrines: 26 pg/ml and plasma normetanephrines: 164 pg/ml. The patient is scheduled to establish care with Endocrine Genetics Clinic.

A timely diagnosis of pheochromocytoma during pregnancy can dramatically affect maternal and fetal mortality rates (1). This case illustrates the importance of a high clinical suspicion for pheochromocytoma as a cause of elevated blood pressure during pregnancy, particularly in patients who lack other characteristics typical of pregnancy related hypertension disorders (proteinuria, edema, etc.) or present with an elevated blood pressure early in pregnancy.

References: (1) Van der Weerd et al., Pheochromocytoma in pregnancy: case series and review of literature. European Journal of Endocrinology (2017) 177, R49–R58
SUN-381 Cortical Porosity Is Associated with Peripheral Small Vessel Disease in Adult Patients with Type 2 Diabetes
Authors: Samakkarnthai Parinya , Sfeir Jad G , Wennberg Paul W , Dyck Peter J , Achenbach Sara J , Atkinson Elizabeth J , Tweed Amanda J , Volkman Tammie L , Drake Matthew T , Farr Joshua N , Khosla Sundeep
Published: May 2020

Patients with Type 2 Diabetes (T2D) are at higher fracture risk despite having relatively normal or even increased BMD by DXA. Increased cortical porosity has emerged as a potential factor contributing to fragility fractures in T2D. However, there is conflicting evidence whether T2D patients have increased cortical porosity. We hypothesized that microvascular complications have an important role in cortical porosity. Thus, we performed high-resolution peripheral quantitative computed tomography imaging at the distal radius and tibia to evaluate bone microarchitecture in men with T2DM age ≥ 50 yrs or postmenopausal women with T2DM and nondiabetic controls. Comprehensive diabetic complications were assessed in all patients including urine microalbuminuria, retinopathy, neuropathy (touch, temperature, and vibration sensation), ankle brachial index (ABI) and transcutaneous oxygen tension (TcPO2). Percent differences between groups were obtained from linear regression models adjusting for age, BMI, and sex. Relationships between variables were assessed using adjusted Spearman correlations. A total of 164 T2D patients (mean age 68.9 ±7.8 yrs.; 56.7% men; HbA1C=7.7 ±0.9%; mean diabetes duration 15.2 yrs.) and 107 nondiabetic controls (mean age 67.3±8.8 yrs.; 42.1% men; HbA1C =5.4 ±0.3%) were recruited to the study. Overall, there was a trend for increased cortical porosity at the distal tibia in the T2D group (+12.2%; p=0.063) compared with nondiabetic controls. Of note, TcPO2 was negatively correlated with cortical porosity at the distal radius (r= -0.17; p= 0.039) and distal tibia (r= -0.15; p= 0.073). In particular, the Low TcPO2 (≤40 mmHg) group (n=29) had greater cortical porosity at the distal tibia (+19.6 %; p=0.037) compared with the High TcPO2 (>40 mmHg) group (n=133). In addition, the low TcPO2 group had a significant increase in cortical porosity in the distal tibia (+24.8% p=0.020) compared with nondiabetic controls. In conclusion, this is the first evidence in humans indicating that TcPO2, a measure of microvascular blood flow, is linked to cortical porosity in the distal radius and tibia in T2D patients. Our findings may explain the conflicting findings regarding cortical porosity in T2D because only T2D patients with impaired microvascular blood flow have increased cortical porosity. Collectively, our data indicate that cortical porosity is a microvascular complication of longstanding T2D.