bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-673 Acute Onset Type 1 Diabetes Mellitus Caused by the Checkpoint Inhibitor Nivolumab
Authors: Ansari Mohammad Jamal Uddin , Ahmed Mahreen , Parveen Sanober , Mariam Murtaza Ali , Jabri Hadoun , Rehman Anis , Jakoby Michael G 
Published: May 2020

Abstract
Background. Checkpoint inhibitors are monoclonal antibodies that augment immune system antitumor activity. Nivolumab is a checkpoint inhibitor that targets the programmed cell death receptor 1 (PD-1). Approximately 15% of patients treated with checkpoint inhibitors experience endocrine immune-related adverse events (irAEs), with autoimmune thyroid disorders and hypophysitis the most common endocrine irAEs. We present a case of acute onset type 1 diabetes mellitus (T1D) complicating treatment with nivolumab.
Case. An 84 year old female received nivolumab (Opdivo) for metastatic small cell lung cancer. She tolerated twelve cycles of treatment well, but after the thirteenth cycle, she developed polydipsia and polyuria that prompted her to seek medical attention. Laboratories in the emergency department were notable for plasma glucose 998 mg/dL, bicarbonate 13 mM, anion gap 24, and strongly positive serum and urine ketones. An insulin infusion and parenteral fluids promptly resolved diabetic ketoacidosis (DKA), and the patient was then managed with subcutaneous basal/bolus insulin. Antibody markers (e.g. anti-GAD65) for T1D were undetectable, and evaluation for other endocrine irAEs was unremarkable. Given the rapid onset of DKA and the patient’s advanced age, she was diagnosed with nivolumab-induced T1D and discharged home on exogenous insulin.
Conclusions. In a recent meta-analysis of 38 immune checkpoint inhibitor trials and over 7,500 patients, T1D was the least common endocrine irAE. The incidence of T1D was 0.2% compared to 6.6% for hypothyroidism, 2.9% for hyperthyroidism, 1.3% for hypophysitis, and 0.7% for primary adrenal insufficiency. All but one case (12/13) of T1D occurred in patients treated with a PD-1 inhibitor. Markers of both cellular and humoral diabetes-associated autoimmunity have been demonstrated in patients with T1D during treatment with nivolumab, and autoimmune destruction of beta-cells is the presumed etiology of diabetes. However, diabetes autoantibodies are detected in only about 50% of cases, and the absence of humoral markers does not exclude the diagnosis of nivolumab-induced T1D. There is a slight male predominance among published cases of nivolumab-induced T1D, and though median onset of T1D1 is after 11 weeks of treatment, there is a wide range of recorded times to T1D onset. Approximately 70% of patients present in DKA, and the significant majority of patients have undetectable or low C-peptide levels. Unfortunately, loss of beta-cell function persists after stopping nivolumab, and lifelong exogenous insulin is required for diabetes management. Though nivolumab-induced T1D is rare, the high risk of DKA as in this patient’s case illustrates the importance of recognizing nivolumab as a potential cause of autoimmune diabetes in older patients receiving anti-PD-1 immunotherapy.
SAT-335 New Onset Adult Idiopathic Primary Hypoparathyroidism Concomitant with Severe Aplastic Anemia
Authors: Galustian Sophia , Galappaththy Suguni Loku , Jadhav Kavita , Cabandugama Peminda K 
Published: May 2020

Abstract
Introduction: Primary hypoparathyroidism is a relatively rare cause of hypocalcemia with cases of primary hypoparathyroidism in the US estimated at 24–37 per 100,000 with 75% being due to neck surgery and 25% due to non-surgical causes. The clinical presentation depends on the acuity of development of hypocalcemia and the absolute level of serum calcium. Here is a case of severe hypocalcemia secondary to hypoparathyroidism of unknown etiology followed by the development of severe aplastic anemia.Case report: A 60-year-old Caucasian male presented to our ED with fatigue, tingling, numbness in extremities and was found to have severe hypocalcemia at 6.8 mg/dl and decreased PTH at 11 pg/mL. Calcium levels 8 months prior to presentation were normal. No history of neck surgery, radiation exposure or family history of autoimmune disorders. Initial workup included creatinine, magnesium and TSH were normal. Autoimmune panel (including PTH Abs and CaSR Abs), HIV test, hepatitis panel, serum protein electrophoresis were also negative. Infiltrative causes of hypoparathyroidism including hemochromatosis, malignancy and granulomatous diseases like sarcoidosis were ruled out with tissue sampling and lab workup. Sestamibi scan obtained showed no parathyroid activity in all four glands. Patient was initially treated with IV calcium to improve serum calcium to more than 7.5mg/L and then switched to oral calcium carbonate 500mg TID and calcitriol 0.5mcg BID until the calcium level was brought up to the lower limit of normal. Patient was seen in follow up and was doing well without any adverse effects. Consequently, the patient developed severe aplastic anemia which was treated with steroids and interestingly, has caused a gradual but consistent increase in PTH levels.Discussion: Idiopathic hypoparathyroidism (IHP) is a rare condition with an incidence of 0.02%. IHP can occur sporadically or as part of a familial condition with autosomal dominant, recessive and X-linked recessive patterns. Certain autosomal forms of hypoparathyroidism have mutations in the PTH gene and Calcium-Sensing Receptor (CaSR) gene. The challenging nature of this case is due to the subacute nature of the patient’s presentation along with the lack of a definitive etiology. The patient’s negative family history and older age makes genetic causes less likely, and Abs against PTH and CaSr were also negative. The patient’s diagnosis of severe aplastic anemia has made the case more fascinating, especially since its management with steroids has causes an improvement in the patient’s PTH status. Regardless of etiology, primary hypoparathyroidism is treated with lifelong supplementation of calcium and calcitriol to a goal serum calcium level at the lower limit of normal. Reference: Abate EG,Clarke BL. Review of Hypoparathyroidism. Front Endocrinol (Lausanne). 2017; 7:172. Published 2017 Jan 16
SUN-474 An Unusual Case of Poorly Differentiated Thyroid Carcinoma with an Excellent Prognosis
Authors: Pulipati Vishnu Priya , Amblee Ambika Pinakini 
Published: May 2020

Abstract
Background: Poorly differentiated thyroid carcinoma (PDTC) is a rare and aggressive subtype with morphological/behavioral features between differentiated thyroid carcinoma (DTC) and anaplastic thyroid carcinoma (ATC).
Clinical case: A 43-year-old female presented with 3 cm right thyroid mass noted on US neck. FNA biopsy showed undifferentiated carcinoma, large cell type. Additional immune-stains were suggestive of ATC. Pre-surgery non-stimulated thyroglobulin (NSTG) was 311 (RR 0–55 ng/dl). Pathology post-total thyroidectomy with bilateral level VI lymph node dissection showed a 3.2 x 2.5 x 2.5 cm carcinoma with vascular and capsular invasion. Most of the mass consisted of very atypical pleomorphic cells, mitosis was difficult to find. The tumor did not show the widely invasive-destructive pattern commonly seen in ATC. An adjacent differentiated component showed predominantly follicular pattern and was described as dedifferentiated follicular carcinoma. All lymph nodes were negative for metastatic disease. Post-surgery NSTG was &lt;0.2 (RR &lt;0.1ng/ml as athyreotic), stimulated TG was 2.22 with negative TG antibodies. Four months later, she received 193.5 mCi radioactive iodine (RAI) therapy. The post-therapy scan showed no Iodine-131 avid uptake in neck or distant metastasis. Neck imaging and TG levels done periodically showed no structural or biochemical evidence of recurrence. Currently the patient is cancer-free for 14 years since diagnosis with no need for additional therapies.
Discussion: PDTC accounts for 1–15% of all thyroid cancers. Although PDTC is rare, it is a clinically significant histological diagnosis as it represents the main cause of death from non-anaplastic follicular cell-derived thyroid carcinoma. The Turin proposal published in 2007 suggested three criteria for the diagnosis of PDTC which included the pattern of growth and high-grade features. PDTC presents more frequently with locally invasive extra-thyroidal disease, metastasis to regional lymph nodes and distant organs compared to DTC. Despite the capacity to have RAI uptake, there has been no evidence of significant improvement in survival due to tumor heterogeneity in differentiation. Recent data suggest that age more than 45 years, tumor size more than 4cm, extra-thyroidal extension, higher pathological T stage, positive margins, and distant metastasis predict worse prognosis.
Conclusion: Our patient showed an excellent response to therapy in spite of having PDTC with positive margins. We hypothesize that this could be likely due to young age at the time of diagnosis, early detection of tumor while it was localized in the thyroid without distant metastasis as well as heterogeneity in the tumor with differentiated cells that are responsive to RAI. We conclude that with early detection, timely surgery, and adjuvant therapy, excellent prognosis can be achieved in patients with PDTC.
SUN-205 Pseudo-Cushing Syndrome Secondary to Malnutrition and Gluco-Toxicity Mimicking Type 1 Diabetes Mellitus
Authors: Pulipati Vishnu Priya , Hwang Jessica 
Published: May 2020

Abstract
Background: Pseudo-Cushing Syndrome (PCS) is an under-recognized clinical entity that is a reversible consequence of alterations in cortisol production. We present a case of a patient with presumed type 1 Diabetes Mellitus (DM) who was found to have PCS secondary to malnutrition. Once the nutritional status normalized, the patient’s glycemic control remarkably improved and became well-controlled on metformin alone.
Clinical case: A 54-year-old female with poorly controlled insulin-dependent DM for 10 years was referred for concern for adrenal insufficiency after an ACTH came back elevated in the setting of intractable nausea, vomiting and considerable weight loss over 1 year. Prior HbA1c was 16.2% (RR 4.4–6.7). On exam her vitals were normal, body mass index (BMI) was 15 kg/m2. Workup confirmed an elevated ACTH of 100 pg/ml (RR 6–50 pg/ml), however, random PM cortisol was unexpectedly elevated at 26.58 ug/dL (RR 4.46 – 22.7). 8 AM labs for ACTH and cortisol were similarly elevated at 91 pg/ml and 28.33 ug/dl, respectively. She had no evidence of classic Cushingoid features. Subsequent low dose dexamethasone suppression test and 24-hour urine free cortisol were negative. Over 18 months, with optimization of her insulin therapy, BMI improved to 19 kg/m2, ACTH and cortisol started to downtrend spontaneously. After 30 months, her BMI improved to 20 kg/m2. Repeat blood work showed A1C 6.5%, ACTH and cortisol completely normalized to 42 pg/dl and 8 ug/dL, respectively. After being adherent to insulin for a few years, her gluco-toxicity state resolved. A month prior to following up, she self-discontinued insulin due to hypoglycemia but continued on metformin. Currently she continues to remain off insulin.
Discussion: PCS is a challenging diagnosis to recognize and differentiate from Cushing Disease (CD) especially due to overlap in biochemical profile. It is important to be aware of this clinical condition to avoid misdiagnosis, delay in treatment or over-treatment. Common etiologies causing PCS include depression, chronic alcoholism, obesity, physical stress, malnutrition, eating disorders, uncontrolled DM, obstructive sleep apnea. PCS occurs due to chronic activation of the hypothalamic-pituitary-adrenal axis, it is usually mild and resolves with treatment of underlying etiology. In our case, first-line screening tests could differentiate between PCS and CD hence she did not require late-night salivary cortisol testing or corticotropic-releasing hormone testing.
Conclusion: In our patient, PCS occurred secondary to malnutrition and severe gluco-toxicity which mimicked insulin-dependent type 1 DM. Interestingly, once her nutritional status and insulin compliance improved, cortisol levels normalized, gluco-toxicity state resolved and she no longer required exogenous insulin therapy.
SAT-368 CYP24A1 Mutation Masking Malignancy Mediated Hypercalcemia
Authors: Cheng Cheng , Liu Chienying , Bikle Daniel D , Shoback Dolores M 
Published: May 2020

Abstract
Background: Mutations in CYP24A1, resulting in reduced conversion of 1,25(OH)2D to its inactive metabolite 24,25-(OH)2D3,are rare causes of parathyroid hormone (PTH)-independent hypercalcemia. While manifestations may range from the severe idiopathic infantile hypercalcemia due to biallelic mutations, heterozygous loss-of-function mutations causing milder phenotypes are increasingly reported in adults. Elevated 1,25(OH)2D and hypercalciuria often accompanied by a history of nephrolithiasis are characteristic. Worsening hypercalcemia, under conditions such as pregnancy or sunlight exposure that enhance 1,25(OH)2D and 25(OH)D production, respectively, has been described in CYP24A1 mutations. We describe a patient with hypercalcemia and a history of lymphoma who was found to have elevated 25-OH-D3 and low 24,25-(OH)2D3 levels, suggesting a mutation in CYP24A1. Clinical Case: An 80 year-old Caucasian male with history of indolent non-Hodgkin lymphoma diagnosed in 2016,well controlled after several courses of chemotherapy,was referred for recurrent hypercalcemia. Laboratory studies showed levels of 1,25(OH)2D of 78 (18–72 pg/mL) and PTH 22 (10–65 pg/mL) with calcium ranging from 10.3 to 12.6 (8.5–10.1mg/dL), an undetectable PTHrP, 25(OH)D level of 32.9 (30–100 ng/mL), and 24-hour urinary calcium of 378mg. He was treated with high dose prednisone for presumed 1,25(OH)2D-mediated hypercalcemia. Despite initial good response, hypercalcemia became progressively difficult to control requiring escalating doses of steroids. Repeat 1,25(OH)2D levels improved to 30–40 pg/mL, but subsequently rebounded to &gt;150. Oncologic re-evaluation found low-grade follicular lymphoma in inguinal lymph nodes,which were thought to be the source of 1,25(OH)2D overproduction. Detailed history and records review, however, revealed that onset of hypercalcemia dated back to 2006, concurrent with the development of several episodes obstructive uropathy due to stones. These events preceded the diagnosis of lymphoma by a decade, and resulted in CKD stage 4. Family history is notable for nephrolithiasis in his fatherand son. We suspected CYP 24A1 mutation. Vitamin D metabolite analysis demonstrated a 25-OH-D3 of 27 (20-50ng/mL) and 24,25-(OH)2D3 of 0.56 ng/mL with a ratio elevated to 48.21 (&lt;25), indicative of a defect in vitamin D degradation that potentially exacerbates oversupply of 1,25(OH)2D, mediated via its reduced metabolism. Genetic evaluation is in progress. After initiation of treatment with Rituximab, his serum calcium levels declined along with regression of his lymphoma. Conclusion: Although mutations in CYP24A1 are an uncommon cause of hypercalcemia, they should be considered in the differential diagnosis of elevated 1,25(OH)2D levels without a clear source, as confirming this diagnosis strongly impacts treatment decisions and clinical outcome.
MON-466 Dual Ectopic Thyroid with Normally Located Thyroid Gland in a Patient Presenting with Subclinical Hypothyroidism: A Case Report
Authors: Rueda Stephen M , Joven Mark H , See Nixon , Gharib Hossein 
Published: May 2020

Abstract
Background: Ectopic thyroid involves the presence of thyroid tissue in sites other than its normal anatomic location. Dual ectopic thyroid with normally located thyroid gland is extremely rare with only a few cases reported in the literature.
Clinical Case: A 24-year-old female presented to the clinic with subclinical hypothyroidism (TSH of 10.54 uIU/ml [ref, 0.27–4.2] and free T4 of 12.96 pmol/L [ref, 12–22]). She noted a gradually enlarging submental mass during the preceding year, which had been present since her adolescent years.
Examination was notable for a 2-cm firm, non-tender mass at the submental region that slightly moved with deglutition. The thyroid was not palpable in its normal location. The relaxation phase of the deep tendon reflex was prolonged. Repeat laboratory testing showed persistently elevated TSH of 13.3 uIU/ml and normal free T4 of 13.39 pmol/L. TPO antibody was normal. Thyroid ultrasonography showed a hypoplastic thyroid measuring 2.7 x 0.7 x 0.4 cm on the right and 3.0 x 0.7 x 0.4 cm on the left. A well-circumscribed complex nodule measuring 2.7 x 3.2 x 2.1 cm was noted on the submental region corresponding to the patient’s submental mass. Computed tomography of the neck with contrast showed two hyperdense foci - measuring 3.0 x 2.4 cm at the submental region and 1.4 x 1.2 cm at the base of the tongue. No enhancing thyroid tissue was seen anterior to the thyroid cartilage. 99mTechnetium-pertechnetate scan showed absent focal tracer uptake in the anterior neck and thorax. There were foci of increased tracer activity in the submental and lingual regions. Ultrasound-guided biopsy of the submental area showed cytomorphologic features of a colloid nodule with cystic degeneration (Bethesda Category II). The patient was started on levothyroxine and remained biochemically euthyroid afterwards. The submental neck mass reduced in size.
Conclusion: Dual ectopic thyroid with normally located (eutopic) thyroid gland could present with subclinical hypothyroidism. There is no single diagnostic modality that would best identify dual ectopic thyroid; thus, thyroid scan, ultrasonography, CT scan and biopsy are recommended to be used complementarily. For patients with dual ectopic thyroid and hypothyroidism, levothyroxine replacement is recommended to reduce the size of ectopic thyroid and render the patient euthyroid.
MON-725 Transcriptome Profiling in Postnatal Pituitary Gland Identifies Cell Type-Driven Sex-Specific Changes
Authors: Hou Huayun , Chan Cadia , Uusküla-Reimand Liis , Yuki Kyoko E , Sokolowski Dustin , Roy Anna R , Zhang Zhaolei , Wilson Michael D , Palmert Mark 
Published: May 2020

Abstract
The pituitary gland is integral to the regulation of growth, metabolism, puberty, reproduction, and stress responses. Previously, we found that many genes associated with age-at-menarche in genome-wide association studies (GWAS) displayed increasingly sex-biased expression across the pubertal transition in the mouse pituitary. However, whether this trend exists beyond puberty-related genes was not known. In addition, the regulatory mechanisms underlying these gene expression changes remained to be explored. To answer these questions, we profiled the transcriptome, including microRNAs, of mouse pituitary in both sexes across pubertal transition in an unbiased manner and leveraged a recently published pituitary single cell transcriptome to explore cellular composition changes. We found that the most dynamic temporal changes in both mRNA and miRNA expression occur prior to puberty, underscoring a role for regulation of early pituitary postnatal development. We also observed ~900 genes displaying sex-biased expression patterns, arising during early development and becoming increasingly biased across puberty, including known sex-biased genes such as Fshb and Lhb. However, sex differences in miRNA expression are less pronounced, only 13 miRNAs were found to be sex-biased, suggesting lesser contribution of miRNAs to sex-biased gene expression relative to other forms of regulation. To assess whether pituitary cellular composition could underlie changes in gene expression across pubertal transition, we performed single cell deconvolution of our bulk pituitary gland gene expression. Interestingly, we found that sex differences in cell proportions were estimated to emerge across puberty: a greater proportion of lactotropes was found among females, and greater proportions of gonadotropes and somatotropes were found among males. We observed sex-biased expression patterns of marker genes for these cell types, including Prl, Fshb, and Gh. This finding suggests that cell proportion differences between sexes likely contribute to whole pituitary transcriptome changes we observed, however, to what extent remains to be studied. Together our study indicates that miRNAs play a substantial role in regulation of pituitary postnatal development but that differences in cellular composition may contribute more robustly to sex-biased gene expression.
MON-183 Adrenal Androgen Control and Steroidal Side Effects in Adolescents and Adults with Congenital Adrenal Hyperplasia Treated with Glucocorticoids
Authors: Falhammar Henrik , Farber Robert , Chan Jean L , Farrar Mallory , Yonan Chuck , Kuranz Seth , Auchus Richard J 
Published: May 2020

Abstract
Introduction: Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a rare autosomal recessive disorder that results in little or no cortisol biosynthesis, increased production of precursor steroids, and excess production of adrenal androgens. Glucocorticoid (GC) treatment, the current standard of care for CAH, is used to correct cortisol deficiency and reduce excessive androgens. Elevated 17-hydroxyprogesterone (17OHP) is used for diagnosis and management. GC titration to achieve 17OHP &lt;1000 ng/dL may be targeted for adrenal androgen control; however, patients with 17OHP &lt;1000 ng/dL might be at risk for complications of long-term GC excess. This real-world study evaluated adrenal androgen levels and potential GC complications in adolescents and adults with CAH.
Methods: TriNetX, a research network that includes electronic medical records from &gt;37 million U.S. patients, was searched on 30Aug2019 for patients who met the following criteria: diagnosis code of E25.0 (ICD-10) or 255.2 (ICD-9); history of GC use; available 17OHP laboratory result; and ≥15 years of age (“grown”) at the most recent 17OHP assessment. Patients were categorized as “adequately controlled” (17OHP &lt;1000 ng/dL) or “poorly controlled” (17OHP ≥1000 ng/dL). Assessments included: demographics; laboratory results for 17OHP, adrenocorticotropic hormone (ACTH), and androstenedione (A4); and low-density lipoprotein (LDL). Adequately vs. poorly controlled groups were compared using Chi-square tests and t-tests.
Results: Of 511 grown CAH patients, 352 were adequately controlled and 159 were poorly controlled. Mean concentrations for 17OHP were 244 and 5939 ng/dL in the adequately and poorly controlled cohorts, respectively (p&lt;0.01). Adequately controlled patients also had lower ACTH and A4 than poorly controlled patients: ACTH (72 vs 389 pg/mL, p&lt;0.01); A4 (82 vs 256 ng/dL, p&lt;0.01). Compared to poorly controlled patients, adequately controlled patients were more likely to be female (81% vs 57%, p&lt;0.01) and older (mean birth year: 1981 vs 1986, p&lt;0.01). Adequately controlled patients also had evidence of more metabolic and infection complications, including higher mean LDL (105 vs 94.3 mg/dL, p=0.02), more type 2 diabetes mellitus (9% vs 4%, p=0.08), and more respiratory tract infections (21% vs 11%, p=0.01).
Conclusions: In this retrospective analysis, patients with adequately controlled CAH (17OHP &lt;1000 ng/dL) had better adrenal androgen control (lower A4) but also higher rates of complications potentially related to excessive GC exposure. These findings highlight the current challenges of managing CAH with GC regimens alone.