bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-511 Thyroid Storm Caused by Subacute Thyroiditis in a Patient with Methicillin-Resistant Staphylococcus Aureus Septicemia
Authors: Assaad Mansur , Zuhdi Bisher , Groubert Jordan , Al-Shoha Ahmad 
Published: May 2020

Abstract
Introduction:
Thyroid storm is a rare disorder with high mortality risk. It is often precipitated by an acute event in a patient with longstanding untreated hyperthyroidism. However, thyroid storm is rarely reported as a result of subacute thyroiditis (SAT). To the best of our knowledge, there are only three documented cases of thyroid storm caused by SAT. Herein we report the first patient with thyroid storm caused by SAT associated with methicillin-resistant Staphylococcus aureus (MRSA) septicemia and intravenous drug abuse (IVDA).
Case:
A 19-year old Caucasian woman with a history of IVDA presented with right upper extremity abscess. Symptoms included confusion, agitation, fever, chills, generalized pain, malaise, nausea, and vomiting. Heart rate was over 140, and she was found to have fever and leukocytosis. She was admitted with severe sepsis and acute encephalopathy. On exam, she had a diffusely enlarged and exquisitely tender thyroid gland without discrete nodules or bruit. Thyroid tests were consistent with primary thyrotoxicosis (TSH 0.026 IU/mL, free T3 16.90 pg/mL, and free T4 &gt; 6.99 ng/dL). Burch-Wartofsky score was 75, highly suggestive of thyroid storm. In addition to treating her sepsis, the patient was started on a beta blocker, high dose hydrocortisone, and methimazole. Thyroid ultrasound showed a diffusely enlarged heterogeneous thyroid gland with decreased flow on color Doppler. Upon improvement, the patient admitted to symptoms of anterior neck pain, heat intolerance, palpitations, excessive sweating, and anxiety for two days prior to presentation. Blood cultures later grew MRSA. Methimazole was discontinued when the thyrotropin-receptor antibody result came back negative. The patient continued to improve clinically. Her thyroid tenderness improved, and her free T4 and T3 decreased over a 3-week period. Steroids were tapered off.
Discussion:
SAT usually causes mild to moderate thyrotoxicosis. It is unusual for SAT to cause thyroid storm. Identifying such a diagnosis in a patient with sepsis is complex. In a septic patient, it is crucial to obtain detailed history, perform a comprehensive physical exam (including neck exam), and have a high level of clinical suspicion for thyroid storm in order to reach the diagnosis early and institute appropriate interventions. Establishing the underlying etiology of the thyrotoxicosis would have long term implications regarding prognosis and treatment.
References:
Salih AM, Kakamad FH, Rawezh QS, et al. Subacute thyroiditis causing thyrotoxic crisis; a case report with literature review. Int J Surg Case Rep. 2017;33:112-114.
Swinburne JL, Kreisman SH. A rare case of subacute thyroiditis causing thyroid storm. Thyroid. 2007;17(1):73-6.
Sherman SI, Simonson L, Ladenson PW. Clinical and socioeconomic predispositions to complicated thyrotoxicosis: a predictable and preventable syndrome?. Am J Med. 1996;101(2):192-8.
MON-203 Aldosterone Biosynthesis Among Patients with Overt or Subclinical Cushing’s Syndrome
Authors: Inoue Kosuke , Omura Masao , Hirfumi Horikoshi , Tsurutani Yuya , Saito Jun , Nishikawa Tetsuo 
Published: May 2020

Abstract
Background: Hypertension is one of the most common and distinguishing clinical features of patients with overt Cushing’s syndrome (CS) and subclinical Cushing’s syndrome (SCS). Although hypertension can be triggered by excess cortisol levels, it is unclear whether the cortisol is sufficient to explain the hypertension among these diseases (particularly SCS in which cortisol is slightly elevated) indicating the potential contribution of aldosterone to the elevated blood pressure. In this study, we aimed to examine the aldosterone biosynthesis among patients with CS or SCS.
Methods: We conducted the prospective study enrolling 90 patients (21 CS and 69 SCS) from 2016 to 2019 at Yokohama Rosai Hospital. We diagnosed patients with CS when they showed clinical features of CS and serum cortisol levels (F) after 1 mg dexamethasone (1-mg DST) was &gt;5 μg/dl. SCS was defined as F after 1-mg DST was &gt;1.8 μg/dl. For patients who are considered to be appropriate for adrenalectomy, we performed the segment-selective ACTH-loading adrenal venous sampling (AVS) to find the laterality of cortisol producing adenoma (CPA). The resolution of hypertension was assessed 1-year after the adrenalectomy.
Results: The median [interquartile range] age was 51 [46–62] years and males were 28%. Hypertension was observed in 21 (100%) CS and 58 (84%) SCS patients. Median F after 1mg-DST were 16.4 [14.3–18.7] mg/dl and 5.1 [3.4–7.5] mg/dl among CS and SCS patients, respectively. Median plasma renin activity among CS and SCS patients were 0.7 [0.4–1.3] ng/ml/h and 0.5 [0.2–0.9] ng/ml/h, respectively. Median plasma aldosterone concentrations (PAC) among CS and SCS patients were 8.3 [7.2–9.8] ng/dl and 9.3 [7.2–17.0] ng/dl at baseline, rising to 24.7 [18.6–32.3] ng/dl and 32.9 [25.8–48.3] ng/dl after ACTH stimulation. During the AVS, all SCS cases with hypertension showed the aldosterone excess (i.e. effluent aldosterone concentrations ≥1400 ng/dl after ACTH stimulation) in at least one adrenal segmental tributary vein. All CS cases showed the hypertension resolution after the resection of CPA except one case showing aldosterone excess on the opposite side of CPA. Among 39 SCS cases who underwent adrenalectomy, hypertension remained in 10 cases, and all of them showed aldosterone excess on the opposite side of CPA.
Conclusion: We found that aldosterone was likely to be elevated (or hyper-responsive to ACTH) among CS or SCS patients with hypertension. The proportion of the hypertension resolution after the CPA resection was lower when patients showed aldosterone excess on the opposite side of CPA. These findings indicate that elevated aldosterone may contribute to the high prevalence of hypertension and its resolution rate after adrenalectomy for patients with CPA. Further studies are needed to examine the clinical effectiveness of the intervention targeting aldosterone among patients with CS and SCS.
SUN-074 Loss-Of-Function Mutations in GATA4 in Patients with 46,XY Disorders of Sex Development Without Cardiac Defects
Authors: Lee Yena , Oh Arum , Yoo Han-Wook , Choi Jin-Ho 
Published: May 2020

Abstract
Background: Disorders of sex development (DSD) encompass a wide range of conditions associated with numerous causative genes. In about 50-60% of 46,XY DSD individuals, the underlying molecular cause remains uncertain. GATA4 haploinsufficiency has been described in patients with congenital heart defects (CHD), while only a few studies reported mutations related to 46,XY DSD phenotype. This study investigated clinical phenotypes and molecular characteristics of two 46,XY DSD patients with GATA4 mutations. Methods: Mutation analysis was performed in patients with 46,XY DSD by whole exome sequencing (WES) using Illumina NextSeq platform. Clinical and endocrine characteristics were reviewed retrospectively. GATA4 variants identified by WES were verified by Sanger sequencing. Functional activity of GATA4 variants was tested by luciferase reporter assay on the SRY and AMH promoter using two different cell systems including HEK293 and NCI-H295R. Results: Subject 1 presented with micropenis and hypospadias at the age of 5 months. Karyotype was 46,XY. Mullerian duct remnants were not found in pelvic ultrasound. The patient underwent urethroplasty at the age of 10 months and was reared as a male. Subject 2 with complete female external genitalia was referred to our hospital because of 46,XY karyotype on G-scanning. The patient underwent laparoscopic orchiectomy at the age of 1.8 years and was assigned as a female. Both patients were responsive to hCG stimulation tests and did not have CHD. Subject 1 harbored a novel heterozygous variant of c.643A&gt;G (p.R215G)] in GATA4, whereas a previously reported variant of c.1220C&gt;A (p.P407Q) was identified in Subject 2. In vitro luciferase reporter assays using SRY and AMH promoter revealed decreased transcriptional activity of both p.P407Q and p.R215G. Conclusions: This study expanded phenotypic spectrum of mutations in GATA4 in patients with 46,XY DSD without CHD. GATA4 mutations in patients with 46,XY DSD may not be associated with CHD. Possible explanations for phenotypical variability comprise incomplete penetrance, variable expressivity, and oligogenic mechanisms.
MON-096 Endocrine Complications Following Cancer Treatment in Survivors of Pediatric Solid Tumors: 18 Years’ Experience of a Single Academic Center
Authors: Lee Yena , Oh Arum , Choi Jin-Ho , Yoo Han-Wook 
Published: May 2020

Abstract
Background: Survival rates of pediatric cancer have been significantly improved over recent decades because of advances in chemotherapy and radiotherapy. The endocrine consequences of cancer treatment have become the major medical issues in the childhood cancer survivors. This study was performed to investigate the long-term endocrine complications in survivors of pediatric solid tumors. Methods: From 2000 to 2018, 402 patients were diagnosed with solid tumors including hepatoblastoma (n = 72), neuroblastoma (n = 117), Wilms tumor (n = 57), Ewing sarcoma (n = 40), osteosarcoma (n = 65), and rhabdomyosarcoma (n = 51) in our institute. Among them, 96 patients (24%) were expired during the follow-up period. Growth profiles and endocrinologic findings were analyzed by retrospective chart review in 306 survivors of solid tumors. Results: The median age at diagnosis of primary cancer was 3 years (range, 0 month to 18 years). The mean treatment duration was 11.7 ± 12.6 months, and the mean follow-up duration after cancer treatment was 7.1 ± 4.8 years. Short stature,which was defined by height-SDS below -2.0, was found in 39 patients (12.7%) with the mean height-SDS of -2.59 ± 0.45. Primary hypothyroidism was detected in 19 patients (6.2%), and 15 of them were treated with radiotherapy or 131I-MIBG therapy due to the metastatic neuroblastoma. Sixteen patients (5.2%) developed hypergonadotropic hypogonadism, whereas three patients (1%) were diagnosed with central precocious puberty. Vitamin D deficiency and osteoporosis were found in 4 patients (1.3%) and 3 patients (1%), respectively. Primary adrenal insufficiency was found in one patient who underwent bilateral adrenalectomy because of bilateral neuroblastoma. One patient with rhabdomyosarcoma in the nasal cavity underwent high dose radiotherapy (50.4 Gy) around the tumor site, eventually leading to multiple pituitary hormone deficiency. In multivariable analysis, longer duration of treatment (≥24 months) was associated with the endocrine complications (OR = 3.94; CI 1.41-11.06) and hematopoietic stem cell transplantation was a major risk factor for endocrine complications (OR = 4.70; CI 2.14-10.29). Conclusions: Various endocrine complications can occur in survivors of solid tumors in children and adolescents caused by treatment modalities including surgery, chemotherapy, and radiotherapy, rather than the tumor itself. Lifetime monitoring is necessary to detect endocrine consequences such as growth retardation, hypergonadotropic hypogonadism, and thyroid dysfunctions.
MON-482 Thyroid Tuberculosis - An Unlikely Diagnosis
Authors: Araújo Alexandra Novais , Matos Tânia , Nobre Ema , Bugalho Maria Joao 
Published: May 2020

Abstract
Background: Mycobacterium tuberculosis (MTB) is an aerobic bacillus responsible for the most cases of tuberculous infection. Approximately one-third of the world’s population is infected. Tuberculosis (TB) of the thyroid gland is an unusual diagnosis with an estimated prevalence of 0.1 to 0.6%. The thyroid TB can mimic different pathologies (thyroid neoplasms, lymphoma, infectious or granulomatous thyroiditis, Graves’ disease or bacterial abscess) and the diagnosis can be easily disregarded, especially in non-endemic countries and if the patient doesn’t have systemic symptoms. The fine needle aspiration and histopathological examination, with acid-fast bacilli staining and TB culture, are the gold standard exams.
Clinical Case: A 71-year-old female was referred to our Endocrinology department after a diagnosis of nodular thyroid disease. She had complaints of slight cervical discomfort, with 6 months of duration. She hadn’t personal or familiar relevant antecedents. At observation, a movable, elastic and non-tender nodule of 15mm at the right superior thyroid lobe was identified. Blood tests including a thyroid profile were normal. The neck ultrasound showed, at the right lobe of the thyroid, multiple solid nodules; the dominant had 18mm, was heterogeneous and had multiple calcifications. Moreover, lymph nodes with suspicious ultrasonographic features along the right internal jugular chain were reported. The patient underwent fine-needle aspiration (FNA) of the suspicious thyroid nodule and one lymph node. Results were respectively: non-diagnostic (Bethesda I) and reactive pattern. FNA was repeated on a different occasion and results were similar. Due to ultrasound suspicious of malignancy, a total thyroidectomy was performed and a lymph node from level IV was sampled for extemporaneous examination. Necrotizing granulomas were documented; the Ziehl-Neelson staining (ZNS) was negative; material was sent to microbiology. Following this finding, ganglion emptying was not performed. The thyroid histology showed tuberculoid type granulomas with lymphoid border and central necrosis. However, the ZNS was negative. The diagnosis was definitely established by a positive culture of the lymph node tissue and molecular detection, by polymerase chain reaction (PCR), of MTB. Pulmonary involvement was excluded and she started antituberculous agents planned for 9 months (rifampicin and isoniazid during 9 months and ethambutol and pyrazinamide for 2 months).
Conclusion: Thyroid TB is a rare presentation of extrapulmonary tuberculosis. In presence of systemic or specific complaints or history of exposition the diagnosis may be suspected and confirmatory tests requested in order to ensure an adequate treatment. However, sometimes, histopathology remains a key step and the use of cultures improves the sensitivity and specificity of TB tests.
SAT-426 Macro-Thyroid Stimulating Hormone (TSH) in Children
Authors: Hattori Naoki , Matsuda Takeshi , Chihara Kazuhisa , Nishioka Junko , Elmaoğulları Selin , Shimatsu Akira 
Published: May 2020

Abstract
Macro-TSH is mainly a complex of TSH with anti-TSH autoantibodies. Due to its large molecular size (&gt;150 kDa), it accumulates in the circulation resulting in elevated serum TSH concentrations. Because the bioactivity of macro-TSH is low, treatment with thyroxine is not necessary. The prevalence of macro-TSH is no more than 1% in adult patients with subclinical hypothyroidism. However, the prevalence of macro-TSH in children is not known. We report here two cases of macro-TSH in pediatric setting.
[Case reports]
Case 1. Six-year and eight-month-Japanese boy visited a pediatric hospital because of hyperactivity disorder. Physical examination revealed that he had a slight mental retardation (IQ 63 by Tanaka-Binet test). Thyroid tests showed that fT4 1.21 ng/dL, TSH 120.4 µU/mL, Tg antibody 1.9 IU/mL, TPO antibody &lt;0.1 IU/mL. His serum was sent to our laboratory to examine the causes of inappropriate high serum TSH concentration.
Case 2. Eight-year and three-month-Turkish girl was brought to a pediatric hospital by her parents because of her yellowish palms, which was not identified at the hospital. She did not have any complaints and physical signs attributable to thyroid dysfunction. Laboratory data disclosed that fT4 1.5 ng/dL, TSH 19.6 µU/mL, Tg Ab negative, TPO Ab negative. Levothyroxine treatment started but serum TSH concentration was still high (39.0 µU/mL) after two months. Her serum sample was sent to our laboratory to examine the causes of inappropriate high serum TSH concentrations.
[Lab. Tests for macro-TSH]
When serum was mixed with the same amount of 25% polyethylene glycol (PEG) and γ-globulin fraction was precipitated, TSH concentration in the supernatant decreased significantly from 109.3 µU/mL to 2.3 µU/mL (PEG precipitation ratio 97.9%) in case 1, and from 17.3 µU/mL to 0.15 µU/mL (PEG precipitation ratio 99.1%) in case 2. HAMA blockers did not significantly change TSH concentration in both cases. High proportion of serum TSH bound to a protein G column, which binds IgG, in case 1 (91.3%) and in case 2 (57.7%), indicating that TSH was associated with IgG. Gel filtration chromatography (GFC) revealed that TSH was mostly eluted at the fraction &gt; 150 kDa rather than 28 kDa of authentic TSH in both cases. Serum was incubated with 37.7 µU of TSH for one hour and subjected to GFC. TSH concentration in the fraction of 150 kDa (macro-TSH) increased from 2.8 µU/mL to 5.6 µU/mL in case 1 and from 0.4 µU/mL to 2.0 µU/mL in case 2, suggesting that macro-TSH was produced by the binding of exogenous TSH to anti-TSH autoantibodies.
[Conclusion]
Macro-TSH exists in children and careful evaluation is required in patients with inappropriate high serum TSH concentrations to avoid unnecessary treatment.
SAT-337 Ga-DOTATATE and Tumor Induced Osteomalacia: Finding the Culprit Lesion
Authors: Berman Jessica , Turin Christie Gloria , Walker Michelle , Wilson Robert , Rosenspire Karen , Mangone Ciera , Amaravadi Ravi , Mukaddam Mona Al 
Published: May 2020

Abstract
Introduction
Tumor-induced osteomalacia (TIO) is a very rare paraneoplastic disorder caused by tumors that produce fibroblast growth factor 23 (FGF23) resulting in phosphate wasting and inadequate bone mineralization. Complete resection can be curative; however, these tumors are typically difficult to identify due to size and location.
Clinical case
A 43-year-old man was referred to Endocrinology for evaluation of recurrent fractures and hypophosphatemia. First stress fracture was diagnosed at age 41, followed by musculoskeletal pain in several locations. Lower extremity MRI showed chronic left fibular stress fracture, new stress fracture in fifth metatarsal and right tibia. Tc99m-MDP bone scan revealed multiple foci of increased tracer uptake in bilateral ribs, hips, and lower extremities. Laboratory evaluation showed normal calcium (9.3 mg/dL, normal range [NR]: 8.7-10.2), low phosphorus (1.5 mg/dL, NR: 2.5-4.7), low 1,25-dihydroxyvitamin D (13 pg/mL, NR: 19.9-79.3), low 24-hour urine calcium (78mg), high phosphate excretion fraction in urine (27%, normal &lt;5%), high ALP (163 U/L, NR: 38-126), and high FGF23 (238 RU/mL, NR&lt;180). 25 OH vitamin D (36 ng/mL) and iPTH (5.7 pmol/L, NR: 1.6-6.9) were normal. Patient was started on calcitriol and phosphate supplements. Due to concern for TIO, a PET scan with 68Ga-DOTATATE was performed which showed multiple somatostatin avid lesions concerning for metastatic disease. However, after re-review with radiology, it was felt that other areas of uptake were due to fractures and not tumor given remarkably higher SUV in left acetabular lesion (SUV 20 vs 4-5). The left acetabular lesion was biopsied, followed by surgical resection. Pathology was consistent with phosphaturic mesenchymal tumor with uninvolved margins. FGF23 normalized within 24 hours after surgery (127 RU/mL) and calcitriol and phosphate supplements were discontinued on post-operative day 10.
Clinical lesson
TIO is a rare paraneoplastic syndrome commonly caused by phosphaturic mesenchymal tumors that secrete FGF23. Once the diagnosis of TIO is confirmed, the tumor is localized by anatomical or functional imaging. 68Ga-DOTATATE scan is currently the imaging modality of choice for localization. However, there are other pathologic processes, such as fractures, that could affect the interpretation of PET scans. Osteoblastic activity is increased in fractures, which results in increased uptake in Ga-DOTATATE PET scan since osteoblasts express somatostatin receptor. Our patient was initially thought to have multiple avid lesions concerning for metastatic disease, but culprit lesion was differentiated based on SUVs and confirmed with biopsy. Clinical and biochemical abnormalities resolved after surgery. Early recognition of culprit lesion in TIO is crucial, as successful surgery is curative and would lead to significant improvement in the quality of life of patients.
SUN-487 A Case of Type 2 Anaplastic Spindle Cell Squamous Cancer
Authors: Rodriguez Valentina , Rivero Ailyn 
Published: May 2020

Abstract
Background: Papillary thyroid carcinoma (PTC) is generally considered a relatively slow-growing, indolent cancer; however, an important subset of these cancers known as the tall cell variant (TCV), portend a more aggressive prognosis. TCV PTC is characterized by cells, which are at least twice as tall as they are wide. Patients diagnosed with TCV PTC fare worse than those with the classic variant. A less common thyroid cancer, spindle cell squamous cell carcinoma (SCSC), may arise as a primary tumor, but rarely also alongside or from a previous TCV PTC (1). It may also occur as a component of an anaplastic thyroid cancer, the most aggressive and rarest thyroid malignancy. There are three main types of anaplastic SCSC arising from TCV PTC based on histological characteristics: Type 1 is defined by the presence of both TCV and SCSC within the initial resection; type 2 refers to when the SCSC arises as a recurrence or metastasis in patients with a known history of TCV PTC; type 3 occurs when SCSC presents as a primary laryngeal SCC in patients with or without a known history of TCV. We report a case of type 2 anaplastic SCSC.
Clinical Case: A 76 yr old man with hx of invasive TCV PTC (diagnosed 2011) s/p total thyroidectomy with b/l neck dissection and laryngectomy, as well as 200 mci of I-131 (in 2012), returns to clinic in 2019, with worsening unexplained weight loss (&gt; 20 lbs). He had been lost to follow-up since 2015. Now, chest CT showed a new, necrotic, left lower lobe mass obstructing the bronchus, as well as bony erosion of the right clavicle and manubrium. Bronchoscopy of the mass was performed, and pathology was consistent with metastatic anaplastic thyroid cancer with squamous nests. Immunohistochemistry was positive for PAX-8, p40, p63 and negative for TTF-1, Napsin A, TG and PDL-1. The endobronchial tumor tissue was compared to the prior resection specimen from 2011, showing morphologic similarity to the squamoid nests. In retrospect, these nests likely represented small foci of anaplastic thyroid cancer arising in association with TCV PTC. The positive staining for PAX-8 and lack of expression for TTF-1 and Napsin A supports this interpretation and is evidence against a primary pulmonary squamous cell carcinoma. Next Gen Sequencing was positive for BRAF V600E mutation, which allowed us to offer BRAF inhibitor and MEK inhibitor therapy. Unfortunately, due to patient’s non-adherence to therapy and follow-up clinic visits, we are not able to assess his response.
Conclusion: This is a case of the rarely described type 2 anaplastic SCSC and is an example of the very poor prognosis associated with TCV PTC. It is a reminder that this variant of PTC should be treated more aggressively from the time it is first identified on biopsy.
Reference: (1) Gopal PP et al. The variable presentations of anaplastic spindle cell squamous carcinoma associated with tall cell variant of papillary thyroid carcinoma. Thyroid. 2011;21(5):493–499.