bluuebunny/crossref_metadata_2025 huggingface dataset:
MON-068 The First Case in Korea, ZC4H2 Gene Mutation in Wieacker-Wolff Syndrome with Recurrent Hypoglycemia
Authors: Lee Gahyun , Kim Sejin , Kang Seokjin , Kim Heungsik
Published: May 2020

Wieacker-Wolff syndrome was first described in 1985 and is a rare congenital syndrome cause by ZC4H2 mutation. It is a X-linked recessive disorder characterized by congenital contracture of the feet, mental retardation, progressive neurologic muscular atrophy, scoliosis, and hypoglycemia. 9-years-old boy with brain atrophy, mental retardation, scoliosis, convulsion and exotropia visited our clinic with recurrent hypoglycemia. Hypoglycemia was developed since infant. Physical examination showed dysmorphism and no hepatomegaly. In the ‘critical sample’, ketoacidosis was present and serum levels of free fatty acid was elevated. Lactate was in the normal range. Hyperinsulinism was excluded with ‘critical sample’ and glucagon stimulation test. Combined pituitary stimulation showed no deficiency of growth hormone and cortisol, respectively. Fatty acid oxidation was excluded by serum levels of acylcarnitines and urine organic acid test. Due to the presence of multiple anomaly and under the suspicion of glycogen storage type 0, whole exome sequencing was performed and p.P154T mutation on the ZC4H2 was observed. Although Sanger sequencing is in processing yet, clinical features are very similar compare to previous cases. In summary, we reported a first Korean male with a novel ZC4H2 mutation, P154T.
MON-379 Diagnostically Significant Relationship Between the Results of Determination of Vitamin D3 and Its Metabolites by the EIA Method and Pure Vitamin D3 by the LC-MS Method
Authors: Terushkin Roman , Kalinchenko Svetlana , Smykalova Anastasia , Vorslov Leonid , Nizhnik Aleksander
Published: May 2020

Diagnostically significant relationship between the results of determination of vitamin D3 and its metabolites by the EIA method and pure vitamin D3 by the LC-MS method.

Introduction: Vitamin D is an important hormone in the human body. He is involved in many physiological body processes. Measuring the level of vitamin D in the patient’s blood is important, diagnostic criteria for identifying and confirming a number of diseases: obesity, hypogonadism, sarcopenia, autoimmune pathologies.

Two methods currently prevail in the laboratory diagnostic market measurement of the level of vitamin D3 in blood plasma: EIA and LC-MS (with its variety - LC-MS / MS).Fundamental differences in the physicochemical nature of these methods are the basis for differing results determined in the same sample.

Objective: In this paper, we set the goal of determining how the results correlate for determining vitamin D3 and its metabolites using the EIA method with the results of determination Pure Vitamin D3 through LC-MS / MS.

Materials and methods: The study was conducted at the clinic of Professor Kalinchenko. Have been selected patients with a clinical picture of vitamin D deficiency. These patients were referred to determination of the level of vitamin D3 using the above methods, subject to preparation rules before analysis. EIA was performed using LC-MS / MS was done using AB SCIEX QTRAP 4500 apparatus connected to Waters Acquity UPLC system. The results were combined for subsequent statistical processing. For a pair of EIA / LC-MS methods, we determined the reliability value of the approximation r ^ 2 and the linear regression equation.

Results: For the presented data, the level of vitamin D3 and its metabolites determined by EIA, and pure vitamin D3, determined by LC-MS, r ^ 2 was 0.9638 (very strong dependence), and the linear regression equation was as follows: LC-MS [nm / ml] = 1.2808 * (EIA) [nmol / ml] + 6.9731.

Discussion: Despite studies by foreign colleagues showing a high level bias and low correlation of results between the EIA and LC-MS methods, our data show a very strong relationship between the two values. By our assumptions, the cause of the various findings is monoclonal antibodies, differing in the global market for reagents for determining the level of hormones derived our linear regression equation allows a practicing endocrinologist to quickly and accurately determine the level of true vitamin D3 in the patient.
MON-721 Crude Protein of Pyropia Yezoensis Protects Against Tumor Necrosis Factor-á-Induced Myotube Atrophy by Regulating the Mitogen-Activated Protein Kinase and Nuclear Factor-Kappab Signaling Pathways in C2C12 Myotubes
Authors: Lee Min-Kyeong , Taek-Jeong Nam , Choi Youn Hee
Published: May 2020

Proinflammatory cytokines induce ubiquitin-proteasome-dependent proteolysis by activating intracellular factors in skeletal muscle, leading to muscle atrophy. Therefore, we investigated the protective effect of Pyropia yezoensis crude protein (PYCP) on tumor necrosis factor (TNF)-α-induced muscle atrophy in vitro. Mouse skeletal muscle C2C12 myotubes were treated for 48 h with TNF-α (20 ng/mL) in the presence or absence of PYCP (25, 50, and 100 μg/mL). PYCP at concentrations up to 100 μg/mL did not affect cell viability. Exposure to TNF-α for 48 h significantly decreased the diameter of myotubes, which was increased by treatment with 25, 50, and 100 μg/mL PYCP. PYCP inhibited TNF-α-induced intracellular reactive oxygen species accumulation in C2C12 myotubes. In addition, PYCP significantly reduced the levels of phosphorylated p38 and JNK. Moreover, by inhibiting the degradation of inhibitor of kappaB-α, PYCP significantly suppressed the TNF-α-induced increased transcriptional activity and nuclear translocation of nuclear factor-kappaB (NF-κB). Furthermore, PYCP inhibited E3-ubiquitin ligases in TNF-α-treated C2C12 myotubes. In conclusion, PYCP ameliorated TNF-α-induced muscle atrophy by inhibiting the mitogen-activated protein kinase-mediated NF-κB pathway, indicating that it has therapeutic potential for related disorders.
SUN-565 The Effect of Leptin Treatment on Blood Pressure and Autonomic Nervous System Function in Patients with Lipodystrophy
Authors: Grover Andrew , Brychta Robert J , Startzell Megan , Chen Kong , Marshall Brandon , Christensen John , Meehan Cristina , Valencia Areli , Gorden Phillip , Brown Rebecca J
Published: May 2020

Leptin is an adipokine that reflects energy storage levels. Patients with obesity have high leptin, hypertension, and increased cardiovascular disease (CVD) risk. In rodents, leptin increases blood pressure (BP), by increasing sympathetic nervous system (SNS) activity, suggesting high leptin may cause hypertension and CVD. Studies of leptin administration in 2 human models of leptin deficiency (weight reduced and congenital leptin deficiency) showed decreased SNS activity in the leptin-deficient state, which increased after leptin replacement. This has clinical relevance as high SNS and low parasympathetic nervous system (PNS) activity correlate with increased risk of hypertension and CVD. In lipodystrophy syndromes adipose tissue is deficient thus leptin is low. We hypothesized that leptin treatment in patients with lipodystrophy would increase SNS activity and BP. SNS and PNS activity in the heart can be assessed using heart rate variability (HRV). The high frequency (HF) component of HRV is directly related to PNS activity whereas the low frequency (LF) component reflects both SNS and PNS. The LF/HF ratio reflects sympathetic-vagal balance. Lower standard deviation of the beat to beat interval (SDNN) inversely correlates with CVD risk. Leptin-naïve patients with lipodystrophy (N=17, 5 generalized, 12 partial) were housed on an inpatient unit for 19 days. Patients were studied without leptin for the first five days. Leptin was administered for the next 14 days. At the end of the OFF-leptin and ON-leptin periods, 24-hr EKG recordings were used to derive HRV parameters and an automated BP monitor measured BP every 30 minutes during the day and every 60 minutes at night. 5 patients had generalized lipodystrophy (median 25th,75th percentile] endogenous leptin [0.5 [0.4, 0.6] ng/mL); 12 had partial lipodystrophy (leptin 7.5 [3.9, 20.3]). In the combined cohort with generalized and partial lipodystrophy, leptin treatment did not alter BP or any measure of autonomic nervous system function after 24 hours, 2 weeks, or 6 months. In exploratory subgroup analyses of generalized vs partial lipodystrophy, those with generalized lipodystrophy had an increase in LF after 2 weeks of leptin and a 4.5 mm Hg increase in systolic BP after 6 months; no changes were observed in those with partial lipodystrophy. Unlike previous human and rodent studies, we did not see increased SNS tone or BP after leptin treatment in patients with lipodystrophy. However, exploratory analyses in patients with generalized lipodystrophy and very low endogenous leptin levels showed small increases in systolic BP and increased LF component of HRV after 2 weeks, which is regulated by both SNS and PNS. This suggests that leptin may alter autonomic function in the transition from very low to normal plasma leptin levels.
SAT-315 CircVPS13c Promotes Tumor Growth and Invasiveness in Pituitary Adenoma by Downregulating IFITM1
Authors: Jiang Xiaobing , zhang weiyu , zhang piaopiao
Published: May 2020

Background and objectives

Invasive nonfunctioning pituitary adenoma (NFPA) remains the major cause of hypopituitarism and infertility. Increasing evidences suggest that circular RNAs (circRNAs) exert crucial functions in regulating gene expression in a wide range of tumors. The present study was designed to explore the role of circRNAs in proliferation and invasion of NFPAs.

Methods

The expression profile of circRNAs was compared with circRNA array between NFPA (n=10) and normal pituitary tissues (n=4), invasive (n=5) and noninvasive (n=5) NFPA samples. A total of 249 circRNAs were shown to be significantly upregulated in human invasive NFPA tissues, comparing to the noninvasive ones. CircVPS13C was identified for further study, whose oncogenic effect were explored with in vitro and in vivo experiments.

Results

CircVPS13C was markedly upregulated in NFPA samples and positively correlated with NFPA invasiveness. Silencing of circVPS13C effectively suppressed NFPA cell proliferation, invasiveness and promoted apoptosis, in vitro, and suppressed tumor growth, in vivo. The oncogenic effects were significantly enhanced when circVPS13C was overexpressed. By whole exome sequencing, interferon induced transmembrane protein 1 (IFITM1) was found significantly increased in cells with circVPS13C knockout. Decreased level of IFITM1 protein was confirmed in NFPAs samples, and negatively correlated with the level of circVPS13C and tumor invasiveness. Upregulation of IFITM1 could partly reverse the effect of IFITM1 on tumor cells, and IFITM1 downregulating enhanced the oncogenic effect of circVPS13C. CHIRP analysis suggested that circVPS13C may inhibit the IFITM1 transcription by competitively binding the RNA-associated proteins.

Conclusions

CircVPS13C promotes NFPA growth and invasiveness by regulating tumor suppressor IFITM1, revealing a therapeutic target in preventing the tumorigenesis of NFPA.
SUN-177 A Silent Bomb: A Case of Severe Primary Adrenal Insufficiency in the Context of Adrenal Metastatic Disease
Authors: Mathew Jilcy Joy , Li Yulong
Published: May 2020

Background: Adrenals glands are the most commonly involved endocrine organ in cancer metastasis due to its abundant lymphatic communication and blood supply. Up to 4% of non-small-cell lung cancers and 71% of lymphomas have bilateral adrenal metastasis. Early detection with hormone replacement can be life-saving.

Clinical Case:

A 58 year old male was admitted for hyperkalemia (potassium 6.4 mmol/L, range: 3.5-5.1) with prolonged PR interval on EKG, hyponatremia (sodium 131 mmol/L, range: 136-145), hypoglycemia (glucose 48mg/dl), and renal function impairment (creatinine level elevation of 1.38 mg/dl from a baseline of 0.94 mg/dl). He had been diagnosed with Stage IVb non-small-cell lung cancer about 20 months prior, and had a known history of chemotherapy, adrenal metastasis and left adrenal gland radiation (20 G in 5 daily fractions) about 10 months ago. For the past 10 months, the patient had reported no weight loss, nausea, vomiting, or other symptoms or signs of adrenal insufficiency, apart from intermittent fatigue, which he had attributed to his lung cancer diagnosis. On review, a previous PET/CT scan showed intense FDG uptake in the bilaterally enlarged adrenal glands, measuring 3.3 x 2.8 cm on the left, and 3.1 x 1.8 cm on the right. His ACTH level was found to be elevated to 1,023 pg/ml (range: 6-63) with borderline low free cortisol level 0.06 mcg/dl (range 0.04-0.35). Aldosterone level was found to be 3.4 ng/dl (range: 4-31), with a renin level of 36.2 ng/ml/hr (range: 0.5-4). Primary adrenal insufficiency was diagnosed, and the patient was started on hormone replacement therapy, which was titrated as outpatient. Now he is continued on a regimen of hydrocortisone 15 mg and 5 mg, at 8 am and 3 pm respectively, and fludrocortisone 0.1 mg daily. In two months, his ATCH level fell from 1,023 to 89 pg/ml with normalization of kidney functions, sodium level (now 137 mmol/L) and potassium level (now 4.8 mmol/L). He gained 4 kg, and has been feeling more energetic and functional on his follow up visits.

Conclusion: Patients with adrenal metastatic cancer may have atypical symptoms and signs despite having severe primary adrenal insufficiency. High risk patients should be monitored, even in the absence of symptoms, for the development of adrenal insufficiency.

Reference:

1. Yamamoto, T. (2018). LATENT ADRENAL INSUFFICIENCY: CONCEPT, CLUES TO DETECTION, AND DIAGNOSIS. Endocrine Practice, 24(8), pp.746-755.

2. Angelousi A, Alexandraki KI, Kyriakopoulos G, et al. Neoplastic metastases to the endocrine glands. Endocr Relat Cancer. 2019.
MON-236 Central Diabetes Insipidus in a Patient with Crohn’s Disease
Authors: Johns Caroline Susan , Weare-Regales Natalia , Fernandez Carlos Pla , Tourtelot John Brooke
Published: May 2020

Unusual Presentation of Central Diabetes Insipidus in a Patient with Crohn’s disease

Introduction

Autoimmune hypophysitis is defined as an inflammatory condition of the pituitary gland of autoimmune etiology that leads to pituitary dysfunction. There are three different histopathological categories of inflammatory hypophysitis including lymphocytic, granulomatous, and xanthomatous hypophysitis. Although, an autoimmune link has been suggested for lymphocytic hypophysitis (LH), the pathogenesis of autoimmune hypophysitis is still incompletely defined. The co-existence of LH and Crohn’s is a rare combination with only a few case reports in the literature.

Case presentation

We present a 39-year-old female with history of Crohn’s disease who presented to the ED with abdominal pain, poor oral intake and headaches. Lab work showed hypernatremia. A neck CT incidentally noted a nodular density along the superior aspect of the pituitary gland. A focused MRI of the pituitary showed abnormal thickening of the pituitary stalk with a prominent and heterogeneous gland. Endocrinology was consulted and on interview patient reported chronic headaches, polyuria and polydipsia for the past year, worsening over the past month. She denied any visual disturbances. Labs showed Na 159, K+ 4.0, serum osmolality 307, urine osmolality 178, specific gravity urine 1.006, cortisol 18, FSH 1.26, LH 0.12, prolactin 55, TSH 1.45 and free T4 0.84. Patient diagnosed with Diabetes Insipidus (DI) from LH and was started on PO desmopressin. Unfortunately, patient continued to have hypernatremia and increased urine output despite increases in the dose and frequency of the oral desmopressin. Given no clinical improvement, decision was made to switch from PO to IV desmopressin considering malabsorption of PO medication in the setting of Crohn’s disease. DI labs including plasma sodium, plasma osmolality, urine osmolality, specific gravity of urine and urine output were closely monitored. Patient’s hypernatremia and increased urine output started to improve with the switch to IV and was ultimately discharged home with intranasal desmopressin.

Discussion

Lymphocytic hypophysitis is a rare disorder predominantly affecting females during the antepartum or postpartum period. This case illustrates the importance of considering its presence in the setting of other autoimmune conditions. It also serves to illustrate the complex management and decision making followed in adjusting the desmopressin formulation in the setting of a malabsorptive disease such as Crohn’s.
MON-470 Biotin Masquerading as Subclinical Hyperthyroidism
Authors: Eapen Anita , Oktaei Hooman
Published: May 2020

Introduction: Thyroid conditions are among the most common endocrine disorders. Diagnosis is dependent on interpretation of laboratory tests. The challenge comes when the clinical picture is discordant with laboratory results.

Case Report: Patient is a 53-year-old male with history of cardiac transplantation, type 2 diabetes mellitus, history of amiodarone-induced hyperthyroidism. He was noted to have labs indicative of hyperthyroidism, while taking amiodarone, in 2016-2017, which was treated with methimazole. He was then noted to have abnormal thyroid function tests with low TSH to 0.3 IU/L, normal T3 and normal T4 levels. Thyroid stimulating immunoglobulin had been checked multiple times, and was normal, which is inconsistent with Graves’ disease. Prior radioactive iodine uptake scan, while off amiodarone, was noted to be normal. He was also scheduled for thyroidectomy at another hospital, which was cancelled due to normalization of thyroid function tests. Consultation was received for suppressed TSH to 0.323 IU/L, without symptoms of hyperthyroidism. He had been taking biotin during this time, which he subsequently stopped taking. Repeat TSH following discontinuation of biotin, was within normal range, most recent TSH 2.48 IU/L, free T4 1.03 ng/dL, free T3 2.7 pg/mL.

Discussion: Thyroid function tests are commonly ordered. Interpretation of these tests relies on the provider’s understanding of thyroid physiology in addition to interferences with medications and other conditions. High doses of biotin, which people take as supplements for multiple sclerosis, or metabolic disorders, or for healthy nails and hair, can cause thyroid function test abnormalities. Streptavidin and biotin are used in some immunoassay platforms to capture antigens (TSH, free T4) or antibodies. High levels of serum biotin can inhibit the formation of T4 antibody complex, which results in a falsely high free T4 result.

Conclusion: Thyroid Function tests should be interpreted very cautiously, especially in the setting of discordant clinical findings. Prior to ordering these tests, should attempt to obtain a detailed history of medications including over-the-counter supplements, which are commonly not reported during medication history.

References:Elston, Marianne S., et al. “Factitious Graves’ Disease Due to Biotin Immunoassay Interference—A Case and Review of the Literature.” The Journal of Clinical Endocrinology & Metabolism, vol. 101, no. 9, 30 June 2016, pp. 3251-3255., doi:10.1210/jc.2016-1971. Koehler, Viktoria F., et al. “Fake News? Biotin Interference in Thyroid Immunoassays.” Clinica Chimica Acta, vol. 484, 30 May 2018, pp. 320-322., doi:10.1016/j.cca.2018.05.053. Soh, Shui-Boon, and Tar-Choon Aw. “Laboratory Testing in Thyroid Conditions - Pitfalls and Clinical Utility.” Annals of Laboratory Medicine, vol. 39, no. 1, 13 Jan. 2019, pp. 3-14., doi:10.3343/alm.2019.39.1.3.
SAT-500 Response to Tocilizumab Retreatment in Refractory Thyroid Eye Disease
Authors: Kaplan Daniel , Erickson Benjamin , Kossler Andrea , Chen Julie , Dosiou Chrysoula
Published: May 2020

Background: The current standard of care for moderate to severe thyroid eye disease (TED) is intravenous methylprednisolone (IVMP), though alternative immunosuppressive options are emerging. In a recent randomized trial, Tocilizumab (TCZ), an anti-IL-6 receptor antibody, demonstrated improved efficacy for corticosteroid-resistant TED compared to placebo. Clinical response to TCZ retreatment, however, has not been previously reported.

Clinical case: A 64-year old man presented with progressive diplopia, eyelid retraction and edema and retrobulbar pain. Initial labs revealed TSH 0.221 uIU/mL, free thyroxine (FT4) 1.11 ng/dL, total T3 172 ng/dL and a thyroid stimulating immunoglobulin (TSI) index of 329 (normal < 140). The patient was a former cigarette smoker who had recently transitioned to e-cigarettes. He was treated with 12 weeks of IVMP with improvement in ocular redness and swelling. Three months following completion of treatment, he presented with worsening left sided proptosis, restrictive strabismus, and compressive optic neuropathy (CON) evidenced by deteriorating central acuity and color vision. He underwent urgent surgical decompression for CON with full restoration of visual acuity. He then received a second 12-week course of IVMP with concomitant orbital radiation. Of note, his hyperthyroidism was well controlled with methimazole. Two months after his second IVMP course, he had a third flare of ophthalmic symptoms. He was then treated with TCZ 8 mg/kg (800mg) IV monthly for six months. The patient’s Clinical Activity Score (CAS) improved from 4 to 2 and TSI index decreased from 610 to 92 (normal). He had significant improvement in periorbital edema, caruncle/plica swelling, and conjunctival injection. However, ten months following completion of the TCZ course he again complained of worsening diplopia and left proptosis. Of note, relapse of his TED symptoms was preceded by an increase in TSI from 92 to 300 two months prior. Orbital CT demonstrated progression of left orbitopathy and increased orbital apex crowding. Following these CT findings he was restarted on TCZ, of which he has now completed 5 additional infusions. His CAS has improved from 3 to 2 and TSI index has decreased from 284 to 100.

Conclusion: This is the first reported case of response to successive courses of TCZ in relapsing, severe, corticosteroid-resistant TED. TCZ can be an effective option for refractory TED though retreatment may be necessary for recurrent inflammation. Further study of TCZ is required to determine its role in relapsing TED and the optimal duration of therapy needed.

References:

Perez-Moreiras et al., 2018. Efficacy of Tocilizumab in patients with moderate to severe corticosteroid resistant Graves’ orbitopathy: a randomized controlled trial. Am J Ophthalmol 195:181
SUN-137 Clonal Status of Multigland Disease Primary Hyperparathyroidism
Authors: Azimzadeh Pedram , Shi Yuhong , St. John Ace , ferlitch Janice , Olson John A
Published: May 2020

Primary hyperparathyroidism (PHPT) is a common endocrine disorder that arises due to single or multiple parathyroid gland disease (MGD). The molecular mechanism(s) of parathyroid neoplasia are incompletely understood and both monoclonal (mono-X) and polyclonal (poly-X) parathyroid tumors have been described using methylation-sensitive PCR of X-linked Human Androgen Receptor (HUMARA) alleles. Our previous investigations of parathyroid tumor clonal status has shown that poly-X tumors are common and are associated with MGD in patients with non-familial PHPT (Shi et al. 2014 & 2018). This work examined the clonal status of the dominant gland and the clonal relationship of multiple tumors from the same patient has not been examined. The goal of the current study was to determine the clonal relationship of parathyroid tumors from PHPT patients with MGD. Banked parathyroid tissues from twenty-nine PHPT patients with MGD were examined in this study. Clonal status (mono-X vs poly-X) of multiple abnormal parathyroid glands from each patient was determined using a modification of the HUMARA assay used in our prior work. Briefly, methylation-sensitive PCR of HUMARA alleles was performed followed by fragment analysis using Capillary-Electrophoresis performed. Raw fragment sizing data analyzed using Peak Scanner software. Classification of samples as either mon-X or poly-X was made as described in (Shattuck et al.) Of 29 PHPT patients with MGD, 13 (45%) had pure mono-X, 5 (17%) had pure poly-X, and 11 (38%) had a mixture of mono-X and poly-X tumors. Five of 29 patients had three or more abnormal glands evaluated: 3 had mixture of poly-X and mono-X, 2 had pure mono-X tumors, and none were pure polyclonal-X. Eighteen (62%) out of 29 patients had paired upper or lower double adenomas. Of these, 9 (50%) were pure mono-X, 4 were pure poly-X, and 5 were mixed mono-X/poly-X. In 2 patients with multiple mono-X tumors, allele distribution was not the same in different abnormal glands. Our previous work has demonstrated that among patients with non-familial PHPT, poly-X parathyroid tumors are common and are associated with MGD. Our new data extend these findings to show that the clonal relationship between multiple parathyroid tumors from the same patient is complex and may reflect the emergence of single or multiple tumors from a background of parathyroid hyperplasia, or other mechanism(s). Future studies to explore the mechanisms behind these apparent clonal relationships are warranted and ongoing. Reference: (1) Shi et al., PNAS 2014, 201319742. (2) Shi et al., Surgery 2018, 9-14. (3) Shattuck. N Engl J Med 2005, 2406-12.
MON-904 Behind the Mask: The Stories of Insulinoma- a Case Series
Authors: Reddy Danda Vijay Sheker , Thaduri Krishna Reddy , konda chaitanya , Verpula Madhavi , Paidipally Srinivasrao
Published: May 2020

Introduction: Insulinoma is a rare, slow growing pancreatic neuroendocrine tumor, leading to hyperinsulinemic hypoglycemia. It runs a very insidious course often masquerading as neurologic, psychological or cardiac disease. We present a series of four cases with varying clinical presentations, diagnoses and latency to diagnosis.

Case Report: This is a retrospective analysis of four cases of Insulinoma diagnosed between Sep 2016 and Mar 2019. All the patients were males and aged 36, 22, 63 and 15 years respectively. Baseline characteristics, duration to diagnosis of Insulinoma, diagnosis and treatment given before definitive diagnosis and post-surgery outcomes were analyzed. All the four patients had relatively long latency to diagnosis despite frequent, spontaneous hypoglycemic episodes, longest being ten years. The patients had a neurological and/or psychiatric diagnosis prior to definitive diagnosis. The symptoms improved with consumption of food. One of the four patients was on antipsychotics for episodic abnormal behavior before the diagnosis of Insulinoma. Two of them were on anti-epileptic medications for seizures. All the insulinomas were localized with CECT without requirement for additional localization techniques. All our patients responded well to surgical resection of the tumor. All insulinomas were benign grade 1 tumors. Acanthosis nigricans regressed in all the patients post-surgery. In addition, all the patients had significant weight loss post-surgery. Two of the four patients developed diabetes mellitus and were on insulin therapy.

Conclusion: A strong index of suspicion of Insulinoma is warranted while dealing with patients presenting with seizure disorders, behavioral abnormalities and neurological symptoms because the spectrum of symptoms is wide and non-specific. Seeking diagnosis is of utmost importance because of implications on treatment and prognosis.

Reference:

Valente LG, Antwi K, Nicolas GP, Wild D, Christ E. Clinical presentation of 54 patients with endogenous hyperinsulinaemic hypoglycaemia: a neurological chameleon (observational study). Swiss Med Wkly. 2018 Nov 18;148:w14682.
SUN-020 Waist Circumference Is Associated with Insulin Resistance in Young Korean Women with Polycystic Ovary Syndrome
Authors: Song Do Kyeong , Lee Hyejin , Hong Young Sun , Sung Yeon-Ah
Published: May 2020

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder and associated with metabolic disturbances such as insulin resistance (IR) and obesity which are risk factors for cardiovascular diseases. Many studies have shown that waist circumference (WC) representing abdominal obesity is an important risk factor for IR. However, there were few studies whether WC were associated with IR in young women with PCOS. We aimed to evaluate the role of WC in IR among young Korean women with PCOS. We enrolled age- and body mass index-matched women with PCOS (n = 100) and controls (n = 100). WC was measured and the 75-gram oral glucose tolerance test (OGTT) was performed. Insulin sensitivity was assessed by the Stumvoll index which was calculated from an OGTT. Multiple linear regression analysis was performed to evaluate the association between WC and IR. WC, fasting glucose, post-load 2-hour glucose, fasting insulin, and post-load 2-hour insulin did not differ between women with PCOS and controls. Women with PCOS had lower values of the Stumvoll index than the controls. In correlation analysis, WC was negatively correlated with the Stumvoll index in women with PCOS, however not in controls. In multiple regression analysis, WC was negatively associated with the Stumvoll index even after adjustment for age, total cholesterol, and total testosterone in women with PCOS. In young Korean women with PCOS, WC was negatively associated with insulin sensitivity independent of hyperandrogenemia. Simply measuring of WC could be used to screen the high risk group having IR in young women with PCOS.
SUN-420 Spontaneous Changes in TSH Levels After Thyroidectomy During Long-Term Follow-Up
Authors: Grani Giorgio , Ramundo Valeria , Armillotta Michele , Falcone Rosa , Filetti Sebastiano , Durante Cosimo
Published: May 2020

Background. Spontaneous serum TSH variations during levothyroxine replacement therapy and multiple dose changes in athyreotic patients seem to be frequent in clinical practice.

Aim. To describe the rate and extent of spontaneous serum TSH variations in patients after total thyroidectomy for differentiated thyroid cancer (DTC) in real-life practice, and the number of resulting levothyroxine (LT4) dose adjustments.

Methods. Data of DTC patients were prospectively collected at a single referral center between January 2005 and May 2019. TSH and fT4 serum levels, LT4 dose and formulation, and concomitant medications were recorded at 1, 3, and 12 months after primary treatment (surgery ± radioiodine therapy), and then yearly; the data were retrospectively evaluated for this study. Visit at one month was used to tailor LT4 dose and was not considered into the data analysis. Patients with structural evidence of disease or during pregnancy were excluded.

Results. Data of 2883 evaluations (472 patients) were collected; at baseline, the median age was 49.7 years, 73.5% were females. The LT4 formulation administered at baseline were tablets (84.9%), liquid solution (11.4%), or soft-gel capsule (3.7%). Overall, in 27.5% of clinical evaluation with unchanged levothyroxine dose (341/1243), there were meaningful spontaneous TSH variations (defined as delta TSH > 1.5 mcUI/ml) at yearly follow-up visit. It is clinically significant: in 6.6% of visits, overt thyrotoxicosis was recorded. Furthermore, the treating clinicians decided to change the LT4 dose in 37.1% of cases. These figures were not significantly higher in the first years, and a rate above 25% persist even after ten years of follow-up. The median maintenance dose needed was 1.61 (interquartile range [IQR] 1.41-1.92) mcg/Kg/day for tablets, 1.54 (IQR 1.39-1.79) mcg/Kg/day for liquid solution, and 1.46 (IQR 1.23-1.71) mcg/Kg/day for soft-gel capsules. After correction for daily dose, there was no difference in the rate of TSH variations > 1.5 mcUI/ml, or in the absolute value of median delta of TSH between the three formulations. In 20.1% of patients, the LT4 formulation was changed during the follow-up: it was more common in patients with a known gastroenteric disease (OR 1.76, p=0.03).

Conclusions. TSH spontaneous variations and dose adjustments are very common in patients after total thyroidectomy, even during long-term follow-up: wide variations happen in more than 1/4 of all visits, and dose changes are needed in more than 1/3 of all evaluations. We were more inclined to change LT4 formulation in patients with known interference in LT4 absorption: however, no difference in TSH variations was recorded between users of three different formulations, even if soft-gel capsules seem to have a lower maintenance dose.
SAT-490 A Case of Unilateral Exophthalmos Due to Thyroid Orbitopathy and Its Association with Chronic Kidney Disease
Authors: Muammar Ahmad R , khan Adeel A
Published: May 2020

Graves ophthalmopathy(GO)is the most common extra-thyroidal manifestation of Graves’ disease (GD). Most cases of GO are bilateral which may be asymmetric, whereas unilateral ophthalmopathy is less common and has been observed in 9-15% cases. Association between chronic kidney disease and unilateral Grave’s ophthalmopathy in a clinically euthyroid patient is rare. We report a case of a 24-year-old male with no previous history of any chronic medical illnesses who presented with protruded right eye for the past 6 months. He did not have any other visual symptoms or symptoms related to thyroid disease. Laboratory results revealed low TSH, normal free T3 and free T4. TSH receptor antibodies were positive. He also had elevated serum creatinine at 418 umol/L (normal levels 64 - 110 umol/L). US KUB showed bilateral small sized kidneys and increased parenchymal echogenicity suggestive of chronic kidney disease. MRI Head showed features suggestive of unilateral thyroid associated orbitopathy. Patient received 1-week course of oral prednisolone 10 mg per day after which his exophthalmos improved.Case report: A 24 year old male with no previous history of any chronic medical illnesses, presented to the clinic with protruded right eye for the past 6 months that was progressively getting worse. There was no eye pain, visual changes, ophthalmoplegia, dryness or discharge from eye. Patient did not report any other symptoms, Physical examination revealed a comfortable man with protruded right eye, lid retraction, normal eye movements and no signs of orbital cellulitis. Neck examination was significant for a mild diffuse goitre. Laboratory studies were significant for haemoglobin of 12.1 g/dl (normal 13-17 g/dl). He also had elevated serum creatinine at 418 umol/L (normal 64 - 110 umol/L). Serum electrolytes, liver function tests and lipid profile were within normal range. 24 hr urine collection showed 3.08 gm/24 hr proteinuria. Serum TSH was 0.04 mIU/L (normal 0.45 - 4.5 mIU/L), free T4 was 13.8 pmol/L (normal 9 - 20 pmol/L) and free T3 was 4.56 pmol/L (normal 2.89 - 4.88 pmol/L). Thyrotropin Receptor Ab titre was 4.69 IU/L (normal 0.00 - 1.75 IU/L). ANA, ANCA, C3, C4, Anti thyroid peroxidase and Anti GBM antibodies were negative. Screening for hepatitis B, C and HIV was negative US KUB showed bilateral small sized kidneys and increased parenchymal echogenicity suggestive of CKD. MRI Head was remarkable for proptosis of the right eye with increased retro-orbital fat, thickening and T2 hyper-intensity with sparing of the tendinous insertion involving the right inferior, medial, superior and lateral rectus muscles with crowding at the orbital apex. Features were suggestive of unilateral thyroid associated orbitopathy. Patient received 1-week course of oral prednisolone 10 mg per day after which his exophthalmos improved. An association between CKD and GO in a clinically euthyroid patient is rare.
MON-242 A Hidden Thirst: Unmasking of Central Diabetes Insipidus
Authors: Dauterive Ellen , Subauste Jose
Published: May 2020

Introduction:

Central diabetes insipidus (CDI) is a common pathology following traumatic brain injury, intracranial operations, medication use, and some infections. This case highlights how CDI can be unmasked when access to free water is restricted.

Case Description:

A 50 yo AAM with history of Down syndrome, hydrocephalus with ventriculo-atrial shunt, and seizure disorder treated with phenytoin, was brought in from home after three back-to-back seizures. EMS was called and intubated the patient in the field. Medical history was significant for ventriculo-peritonal shunt placed shortly after birth with revisions in 2011 and 2016. Revision in 2016 was complicated by infection with klebsiella pneumoniae. He was admitted to NSICU. Shunt evaluation showed no abnormality or obstruction. Lab work on admission at 5 am was significant for low potassium and sodium was normal. Patient was stabilized and extubated later that day. Repeat labs, at 4 pm, showed a sodium of 155 mEq/L with a normal potassium. Urine output was reviewed and significant for greater than 400 cc’s per hour for at least 2 hours. Urine osmoles (264 mOsm/kg, n 50-1200) and serum osmoles (314 mOsm/kg, n 280-295) were consistent with diabetes insipidus (DI). His IV fluid intake during this time was 3 liters bolused on admission followed by continuous fluids at 125 cc’s per hour. On review of systems, patient admitted to polydipsia and polyuria throughout the day for last several years. He reported urinating 2-3 times at night. During an admission 3 years prior for ventriculo-peritoneal shunt revision, serum sodium had risen to 159 mEq/L following his surgery and returned to normal prior to discharge. MRI pituitary during admission was negative for pituitary abnormality. To treat as well as differentiate central versus nephrogenic DI, desmopressin 1mcg IV was given. The patient was allowed to drink to thirst. Urine osmolarity increased from 159 mOsm/kg to 494 mOsm/kg after 2 hours and serum sodium slowly trended down. His urine output and thirst decreased with continued administration of desmopressin. He was discharged on a maintenance dose of 0.1 mg desmopressin twice a day. On follow up in clinic, his sodium has been maintained between 140-145.

Discussion:

This patient with CDI was compensating with large fluid intake daily as an outpatient for at least three years. His risk factors included phenytoin use as well as previous VP shunt occlusion complicated by infection which has been reported to contribute to CDI in other case reports. This case highlighted how CDI can be unmasked when a patient loses access to free water such as with altered mental status or intubation for surgery.

References

1.Central diabetes insipidus: A complication of ventriculoperitoneal shunt malfunction during pregnancy. Goolsby, Lynn et al. American Journal of Obstetrics & Gynecology, Volume 174, Issue 5, 1655-7
SAT-400 Pregnancy Outcome in Women with Hypoparathyroidism:Aswedishpopulation-Based Cohort Study
Authors: Bjornsdottir Sigridur , Clarke Bart Lyman , Makitie Outi , Spelman Tim , Kampe Olle
Published: May 2020

Context: The majority of patients with hypoparathyroidism (HypoPT) are women. It is not known whether the presence of hypoparathyroidism influences the pregnancy outcomes. Sweden has excellent conditions for research in this area, with high-quality population-based registers covering essentially all inpatient care and birth records. In this study, data were linked from the Swedish National Patient Register and Swedish Medical Birth Register to examine the potential influence of maternal hypoPT on the number of childbirths and various pregnancy outcomes.

Design and Setting: Population-based cohort study in Sweden.

Patients: Through the Swedish National Patient Register and the Total Population Register, we identified 1267 women with HypoPT and 12 670 age-matched controls who gave birth between 1997 and 2016.

Results: There was no significant difference in mean age at delivery for women with HypoPT (32 (SD, 5.2)) years and controls (32.5 (5.0)). There were significantly more women with HypoPT who smoked at baseline (p= 0.007) and within 3 months of pregnancy (p=0.022) compared to controls. Significantly more women with HypoPT had part time work or were not working during pregnancy compared to controls (p = 0.002). The mean number of infants per woman was 0.30 (SD, 0.62) in the HypoPT group and 0.33 (SD, 0.60) in the control group (p=0.644). Compared with the control group, the risk of elective cesarean section was higher in the HypoPT group (p=0.002). However, there was no difference in the proportion of women undergoing an acute cesarean section between cases and controls (p=0.754). The mean pregnancy duration in women with HypoPT was 38.87 (2.11) weeks compared to 39.23 (2.04) weeks for the controls (p= 0.001). Infants born to mothers with HypoPT were significantly shorter (p=0.016), but no difference was seen in weight or head circumference compared to infants born to controls. No difference was observed in prevalence of small- or large-for gestational age compared to controls. There were no differences between groups with respect to infant sex or Apgar scores at 1, 5 and 10 min, congenital malformations or stillbirth. There was furthermore no difference in pain medication use by mothers during delivery between the groups (p=0,733).

Conclusion: The majority of women with HypoPT had normal pregnancy outcomes, and the overall risks must be considered to be low. Still, our findings are of importance for antenatal counseling in women with HypoPT as their risk for elective cesarean section was significantly higher compared with controls. Their children were shorter and the higher rate of smoking among HypoPT women may be an additional risk factor.
SAT-172 FDG PET/CT in Benign vs. Malignant Adrenocortical Tumors
Authors: He Xin , Caoili Elaine M , Avram Anca Mihaela , Miller Barbra S , Else Tobias
Published: May 2020

18F-fluorodeoxyglucose positron emission tomography computed tomography (FDG PET/CT) is frequently used for evaluation of indeterminate adrenal nodules.

The objective of this study was to evaluate the diagnostic performance of FDG PET/CT in distinguishing benign adrenocortical adenomas (ACA) from adrenocortical carcinoma (ACC).

We identified 139 patients in our institution who completed both FDG PET/CT and adrenal biopsy or adrenalectomy from 2001 to 2019 using the institutional Electronic Medical Record Search Engine (EMERSE). Patients with adrenal pathology revealing non-adrenocortical tumors were excluded. The imaging characteristics of ACAs were compared with ACCs.

Sixteen patients with ACAs and 50 patients with ACC were identified; of the latter, 30 were excluded, because FDG PET/CT imaging was completed after adrenalectomy. The average age of the ACC vs. ACA group was 48±14 and 52±17 years, respectively, with a gender composition of 35% and 25% men, respectively. All 20 patients with ACC had FDG avid lesions, defined by imaging report and increased ratio of adrenal tumor maximum standardized uptake value (SUVmax) to hepatic parenchymal average SUV (SUVmean) of greater than 2.5. Among those with ACAs, 11 had positive, 1 had mildly positive, 3 had indeterminate, and 1 had negative FDG PET/CT findings according to the report. Ratio of adrenal SUVmax to hepatic SUVmean was greater in ACC compared to ACA (13.5 versus 1.6, respectively, p = 0.13), but did not reach statistical significance, likely due to the small sample size and unavailability of SUV ratios for all lesions.

Our study identified a large number of ACAs that were deemed FDG avid but without adrenal SUVmax to hepatic SUVmean ratio of greater than 2.5. Although the sensitivity, and therefore the negative predictive value, of FDG PET/CT scan is excellent for the diagnosis of ACC, our data does not allow for the calculation of specificity. This is due to the selection bias inherent in our patient population referred for evaluation of unusual adrenal masses, and the fact that ACAs with negative FDG PET/CT often do not undergo surgery or biopsy, and therefore pathology results are not available. Despite this limitation, our findings show that calculation of the ratio of adrenal SUVmax to hepatic SUVmean, rather than lesion SUVmax alone, helps for characterization of adrenal lesions as malignant vs. benign, and that a negative FDG PET/CT is valuable in excluding ACC.
MON-489 Comorbidity of Primary Hyperparathyroidism and Papillary Thyroid Cancer. A Single Center Outcomes
Authors: Papadopoulou Nektaria , Papanikolaou Eleni , Chrousos George P , Karvounis Evangelos
Published: May 2020

Introduction Concurrence of primary hyperparathyroidism in patients with thyroid disease has been previously reported by several studies. However, comorbidity between primary hyperparathyroidism (PHPT) and papillary thyroid cancer (PTC) has been sparsely described by previous, mostly case-series studies, and is considered rare. Since pathophysiological mechanisms behind the two diseases are supposed to be different, any link between these diseases has not been explained as yet. Hypothesis: Aim of the study was to investigate the possible concurrence for the two diseases in people who underwent thyroidectomy for suspected thyroid nodules. Methodology Retrospective observational study that included 2913 patients (24% men with mean age 49.82 yrs, 76% women mean aged 47.73 yrs), who underwent total thyroidectomy during the last 13 years (2005-2018) at the Department of Endocrine Surgery, Euroclinic Hospital, in Greece. The patient-groups were categorised according to histopathology criteria of the thyroid and/ or parathyroid glands (in case of comorbidity of primary hyperparathyroidism (PHPT) diagnosed prior to surgery). Results: Statistical analysis revealed benign histopathology findings in 1945 patients (64%), while papillary cancer was found in 978 (32%). Among patients with non-malignancy, 16 (11 women/5 men) had PHPT, but in those with papillary cancer, PHPT was diagnosed in 38 (33 women/5 men) individuals. The relative risk for the concurrence of PHPT and PTC was 2.033 (95%CI 1.69 to 2.43, P<0.0001). Age groups between 30 and 60 yrs were associated with the highest relative frequency of comorbidity (82%). A significant positive correlation was observed between less aggressive PTC histopathology findings and PHPT concurrence (P<0.0001). Interestingly, no patient with PTC and PHPT had either capsular invasion or regional/distant metastases. Moreover, most patients with comorbidity (92%) had a tumour diameter smaller (mean 6.3 mm) than those with PTC alone (mean 18 mm). Conclusions: Our study found that the comorbidity between primary hyperparathyroidism and PTC may be considered as possible. Endocrinologist’s diagnostic approach may add serum calcium and parathormone levels in patients who undergo evaluation for suspected thyroid nodules. Patients with PHPT and PTC had mostly microcarcinomas, and histopathology findings showed a less aggressive PTC pattern. Further large cohorts as well as genetic studies, are needed to duplicate our results and further highlight possible common pathogenetic pathways behind PHPT and PTC concurrence.