bluuebunny/crossref_metadata_2025 huggingface dataset:
MON-482 Thyroid Tuberculosis - An Unlikely Diagnosis
Authors: Araújo Alexandra Novais , Matos Tânia , Nobre Ema , Bugalho Maria Joao
Published: May 2020

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

Macro-TSH is mainly a complex of TSH with anti-TSH autoantibodies. Due to its large molecular size (>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 <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 > 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

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 <5%), high ALP (163 U/L, NR: 38-126), and high FGF23 (238 RU/mL, NR<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

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 (> 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.
SUN-050 Isolated Hyperprolactinemia Caused by Chest Binding in a Transgender Male
Authors: Cunningham Hayley E , Coviello Andrea D , Kelley Carly E
Published: May 2020

Background: Prolactin levels are routinely measured in patients evaluated for PCOS. Compared with the general population, PCOS is more common among transgender men, with prevalence estimates as high as 30 to 50%1,2. Nipple stimulation is a recognized cause of hyperprolactinemia, and many transgender men engage in chest binding, which involves compressing the breast tissue to produce a more masculine appearance. Clinical Case: A 22-year old natal female with gender dysphoria, who presented to our clinic for initiation of masculinizing hormone therapy, revealed a history of irregular menstrual cycles, hirsutism, and moderate acne. The patient was on a combination OCP to regulate menstrual cycles but no other medications or supplements. Laboratory evaluation revealed normal TSH, creatinine, 24-hour urine cortisol, testosterone, 17 hydroxyprogesterone, and DHEA-S. LH was 2.4 mIU/mL, FSH was 6.0 mIU/mL, and prolactin was elevated at 55.6 ng/mL (4.8-23.3 ng/mL). Polycystic ovaries were not present on pelvic ultrasound. Pituitary MRI was ordered for further evaluation of hyperprolactinemia and no pituitary adenoma or other structural abnormality was seen. The patient denied nipple discharge and tenderness but endorsed chest binding. In the absence of another explanation, nipple stimulation through chest binding was hypothesized to be the cause of hyperprolactinemia. After withholding chest binding for one week, the patient’s prolactin level normalized to 13.95 ng/dL. The patient was diagnosed with PCOS according to Rotterdam criteria after exclusion of alternative etiologies. It was presumed that five years of consistent OCP use had normalized androgen levels and suppressed the appearance of polycystic ovaries on ultrasound. The patient was initiated on testosterone cypionate for gender affirmation. Prolactin increased again to 29.33 ng/mL one year later after resumption of continuous chest binding. Conclusion: This is the second reported case of hyperprolactinemia induced through chest binding.3 Transgender men are at increased risk for irregular periods due to underlying PCOS and therefore more likely to undergo an evaluation that includes prolactin measurement. By recognizing chest binding as a cause of isolated hyperprolactinemia, physicians can minimize unnecessary testing and anxiety in patients who engage in this practice.1. Baba, T. et al. Hum Reprod. 2007;22;1011-16. 2. Becerra-Fernandez, A. et al. Endorinol Nutr. 2014;61; 351-8.3. Patel, S., & Abramowitz, J. (2019, April). Hyperprolactinemia in a Transgender Male. Poster session presented at the Annual Scientific & Clinical Congress of the AACE, LA, CA.
SUN-501 Grave’s Disease Concealing the Diagnosis of Pancreatic Carcinoma
Authors: Unjom Zubina S , Nandu Nitish , Gilden Janice L
Published: May 2020

Background: Hyperthyroidism is a disease that presents with various nonspecific symptoms. Unintentional weight loss can often be the presenting complaint. We present a patient with unexplained weight loss that was attributed to Grave’s hyperthyroidism, but was later discovered to be secondary to pancreatic carcinoma. Case Description: A 58-year-old man with no significant medical history, was referred to the endocrine clinic for weight loss, low energy, and abnormal TFT’s. He reported 45 lb. weight loss over the past one year. Past Medical history was notable for opioid use, and is enrolled in the Methadone program for the past 10 years. Family history is significant for type 2 diabetes. He smokes ½ a pack of cigarettes, denies alcohol or drug use. On exam, heart rate was 84 bpm with fine tremors on outstretched upper extremities, no proptosis, lid lag, thyromegaly, or pretibial edema, normal reflexes. His labs were TSH=0.01; (n=0.270 - 4.20 uIU/mL), FT4=2.1; (n= 0.55 - 1.60 ng/dL), FT3=283;(n=2.52 - 4.34 pg/mL) Thyroglobulin Ab 4 IU/ml, Thyroid peroxidase Ab > 900 IU/ml, TSI 358(n=<140%). He was diagnosed with Grave’s disease and was started with Methimazole and Propranolol, which were titrated to an optimal range over the next few months. However, the patient was lost to follow up, and presented one year later to the ED with complaints of abdominal pain, jaundice for one-week, greasy diarrhea for 6 months, also reporting noncompliance with thyroid medications during this time. On examination, he was icteric and jaundiced with hepatomegaly, trace pedal edema. Although LFT’s were previously normal, the labs now showed alkaline phosphatase=533, (n=40-129 IU/L); AST=107 units (n= 0-32 IU/L), ALT=213units (n= 0-40 IU/L), total bilirubin 11.4 (n= 0-1.0 mg/dl), TSH=0.01, FT4=0.6, FT3=3.2. Ultrasound showed gallbladder sludge, CT abdomen-dilatation of the pancreatic duct in neck and body of pancreas, MRCP- marked pancreatic ductal dilatation and soft tissue fullness within the pancreatic head. CA 19-9= 64.8, he underwent ERCP, and was later diagnosed with adenocarcinoma of the Pancreatic head. He was discharged with referrals to GI and Oncology for further treatment. Discussion:Although weight loss and diarrhea are nonspecific, and can often result from hyperthyroidism, this case highlights the importance of further investigation for other causes and avoiding attribution to a single diagnosis. Other diagnoses were only looked into when the patient presented with painless jaundice and hepatomegaly several months later. The effects of autoimmune hyperthyroidism on the pancreas function remain unclear. However, patients with Grave’s hyperthyroidism have a higher number of islet cell antibodies, as compared to controls. Further studies are required in this regard. We also emphasize the importance of patient education and compliance which can lead to earlier diagnosis, and overall better outcomes.
SAT-165 Sterol O-Acyl Transferase 1 as a Prognostic Marker of Adrenocortical Carcinoma
Authors: Lacombe Amanda Meneses Ferreira , Soares Iberê Cauduro , Charchar Helaine da Silva , Brondani Vânia Balderrama , Neto João Evangelista Bezerra , Tanno Fabio , Srougi Victor , Chambo José Luiz , de Freitas Ricardo Miguel Costa , Hoff Ana Oliveira , Almeida Madson Q , Zerbini Maria Claudia Nogueira , Kroiss Matthias , Fragoso Maria Candida Barisson Villares
Published: May 2020

Background: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with an unfavorable prognosis. Despite the poor prognosis in the majority of patients, no improvements in treatment strategies have been achieved, largely due to the rarity of these tumors. Therefore, the discovery of new prognostic biomarkers that could guide and improve the management of patients with ACC is of enormous interest. Sterol-O-Acyl Transferase 1 (SOAT1) is involved in cholesterol esterification in adrenocortical cells. Recently, it was demonstrated that SOAT1 inhibition leads to impaired steroidogenesis and cell viability in ACC [1]. There are no studies so far addressing the impact of SOAT1 protein expression in ACC prognosis and clinical outcomes.

Methods: We evaluated SOAT1 protein expression by immunohistochemistry (ab39327; 1:4000; Abcam, EUA) in a tissue microarray of 107 adrenocortical carcinomas (Weiss score ≥ 3) from adult patients treated in a single tertiary center in Brazil. Immunohistochemistry results were evaluated through a semiquantitative approach by two independent pathologists. We aimed to evaluate the correlation of SOAT1 protein expression with clinical and biochemical parameters, surgical specimen histological characteristics, recurrence free-survival, progression free-survival and overall survival.

Results: SOAT1 protein expression was heterogenous in this cohort; 38% of ACCs demonstrated strong SOAT1 protein expression while 62% demonstrated weak or absent SOAT1 protein expression. Strong SOAT1 protein expression correlates with known features of high aggressiveness in ACC, such as excessive tumor cortisol secretion (p= 0.007), advanced disease stage [ENSAT 3 and ENSAT 4 (p= 0.009)] and high Ki67 index (0.008). On multivariate analysis, strong SOAT1 protein expression was an independent predictor of lower overall survival (HR 1.71, CI 95% 1.05-2.92; p= 0.04) when considering all cases (n= 107) and of lower progression free survival (HR 3.05, CI 95% 1.05-8.85; p= 0.04) in patients with metastatic disease at diagnosis (n= 22).

Conclusions: Our findings demonstrated that SOAT1 protein expression has prognostic value in ACC and reinforce the importance of investigating SOAT1 as a possible therapeutic target for patients with ACC. Multicentric prospective studies including a larger number of patients are needed in order to validate and consolidate the results found in this cohort.

References:

1.

Sbiera S, Leich E et al. Mitotane inhibits Sterol-O-Acyl Transferase 1 Triggering Lipid-Mediated Endoplasmic Reticulum Stress and Apoptosis in Adrenocortical Carcinoma Cells. Endocrinology. 2015; 156 (11):3895-908.
SAT-397 Characteristics and Outcomes of Severe Hypercalcemia Related Admissions - a Single Centre 5 Years’ Experience
Authors: Ponce Jo-Anne , Lee Myron , Caswell Amanda , Parsons Mclaine O , Acharya Shamasunder
Published: May 2020

Introduction: Severe hypercalcemia (corrected calcium ≥3.5mmol/L) is typically associated with multi-organ dysfunction and increased mortality. We audited 47 consecutive patients who were admitted to a single tertiary referral center over 5 years period (2014-2019) with severe hypercalcemia. Results: The median age 69 years (10-97yrs); 55% females, and median length of stay was 9 days (1-120). Most patients (30%) were admitted under general medicine and 53% received endocrinology consultation. Renal dysfunction (91%) dominated the clinical presentation, but gastrointestinal abnormalities (70%), neuropsychiatric manifestations (53%), and musculoskeletal involvement (45%) were also very common. PTH was measured in 43/47 patients with 37 PTH independent (calcium level 3.82 mmol/L) and 6 PTH dependent (calcium level 3.70mmol/L) hypercalcemia. Recurrence of the condition within five years was recorded for 5 patients (11%), ten (21%) patients died during the admission, and 4 patients (9%) required ICU admission in PTH independent severe hypercalcaemia, majority are due to malignancy; while none of these outcomes were observed in PTH dependent severe hypercalcaemia. The length of hospital stay is longer in PTH independent (15.5 days) as compared to PTH dependent severe hypercalcaemia (12 days). The most common cause of severe hypercalcemia was malignancy (47%) with multiple myeloma as the most common in 32% followed by lung cancer at 27%. The other non-malignancy causes are calcium supplementation, vitamin D toxicity, and hyperparathyroidism implicated in 13% each. Twenty eight patients (65%) were managed by fluid and antiresorptive agent with 26 patients able to decrease calcium level to <3mmol/L (93%). Eight patients (19%) were managed by fluid alone (not effective in 37%), 9% by antiresorptive agent alone (not effective in 25%), and 16% did not receive any fluid nor antiresorptive agent (not effective in 43%). Conclusion: Similar to previous studies, severe hypercalcaemia is commonly seen in patients with malignancy and associated with significant symptoms, recurrence in 5 years, ICU admission and mortality. Calcium and vitamin D supplementation and hyperparathyroidism are also found to commonly cause severe hypercalcemia. The most effective management is combination of fluid resuscitation and antiresorptive agent to decrease the calcium level to <3mmol/L.
SAT-221 50-Year-Old Fungus Suddenly Flourishes in Adrenal Glands: A Case of Sudden-Onset Bilateral Adrenal Masses Due to Latent Disseminated Histoplasmosis
Authors: Carrillo Maritza Elide , Chang Amy , Walsh Christopher L
Published: May 2020

Histoplasma capsulatum is endemic to Africa, Asia, Central and South America, and within the US, to the Ohio and Mississippi River Valley. Disseminated histoplasmosis is less commonly seen in immunocompetent individuals, who usually present with asymptomatic self-limited acute pneumonitis. Time to involvement of the adrenals is unknown. Adrenal insufficiency occurs in 45% of cases involving the adrenals, and is thought to be irreversible even in patients in remission.

A 76-year-old man with no significant past medical history was incidentally found to have large bilateral adrenal masses during routine surveillance of a 7 mm pulmonary nodule on annual Chest CT, which showed normal adrenal glands the year prior. He was asymptomatic. A lifetime non-smoker native to California, whose only significant travel history was in his 20s to Ecuador and Puerto Rico, areas endemic to Histoplasma.

Abdominal CT showed large bilateral adrenal masses with intermediate density and low washout values (right: 4.9 cm, HU 45, absolute washout 30%; left: 4.8 cm, HU 30, absolute washout 25%).

On exam, vital signs were stable with normal orthostatics. Labs revealed normocytic anemia, normal chemistry panel, normal cortisol after 1-mg dexamethasone overnight test 2.6 mcg/dL (n<5 mcg/dL), plasma metanephrine <0.10 nmol/L (n <0.50 nmol/L), plasma normetanephrine 0.89 nmol/L (n <0.90 nmol/L), aldosterone 4.0 ng/dL (n <31 ng/dL), PRA 2.0 ng/ml/hr (n 0.5-4 ng/ml/hr) and random free cortisol 0.38 ug/dL (n 0.022-0.254ug/dL). HIV antigen and antibody, and Histoplasma urinary antigen were negative.

Left adrenal mass biopsy revealed necrotizing granulomatous inflammation with fungal culture revealing budding yeast morphologically consistent with Histoplasmosis, with DNA probe confirming Histoplasma capsulatum.

Treatment with itraconazole was initiated and the patient is tolerating the treatment well.

To our knowledge, this is the first case demonstrating rapid development of large bilateral adrenal masses within a year due to latent disseminated histoplasmosis in an asymptomatic individual, which highlights the need for appropriate testing in patients with known exposure or travel history to endemic areas, regardless of time since exposure.

1.Singh M, Chandy DD, Bharani T, Marak RSK, Yadav S, Dabadghao P, et al. Clinical outcomes and cortical reserve in adrenal histoplasmosis- a retrospective follow-up study of 40 patients. Clin Endocrinol 2019 Jan 17
SAT-450 Essential Role of GATA2 in the Negative Regulation of the Prepro-Thyrotropin-Releasing Hormone Gene by Liganded T3 in the Rat Paraventricular Nucleus
Authors: Kuroda Go , Sasaki Shigekazu , Matsushita Akio , Ohba Kenji , Sakai Yuki , Shinkai Shinsuke , Nakamura Hiroko , Oki Yutaka
Published: May 2020

T3 inhibits thyrotropin-releasing hormone (TRH) synthesis in hypothalamic paraventricular nucleus (PVN). Although T3 receptor (TR) β2 is known to mediate the negative regulation of prepro-TRH gene, its molecular mechanism remains unknown. Our previous studies on the T3-dependent negative regulation of the thyrotropin β subunit (TSHβ) gene indicate the tethering mechanism, where T3-bound TRβ2 interferes with the function of the transcription factor GATA2, which is essential for TSHβ expression. Interestingly, the transcription factor Sim1, a determinant of PVN differentiation in hypothalamus, is reported to induce the expressions of TRβ2 and GATA2. Indeed, our immunohistochemistry revealed the expression of GATA2 in the TRH neuron of the rat PVN. According to the experimental report with transgenic mice, the DNA sequence from nt. -547 to nt. +84 is sufficient for the expression of the prepro-TRH gene in PVN. Using the CAT reporter gene harboring this region, we found that this promoter is activated by GATA2 approximately 6-fold in CV1 cells. The deletion and mutation analyses identified a functional GATA-responsive element (GATA-RE) between nt. -357 and nt. -352. When TRβ2 was co-expressed, T3 reduced GATA2-dependent promoter activity to approximately 30%. T3-dependent repression was maintained after the mutation of the putative negative T3 responsive element (site4). Although the melanocortin 4 receptor signaling is known to stimulate the prepro-TRH promoter via protein kinase A pathway in the PVN, inhibition by T3 was dominant over the 8-bromo-cAMP-induced activation. We observed the in vivo recognition of GATA-RE by GATA2 using chromatin immunoprecipitation assay with CA77 cells, which express endogenous TRH. The electrophoretic mobility shift assay also demonstrated that GATA2 bound to oligonucleotide containing the GATA-RE. These results suggest that, as in the case of the TSHβ gene, GATA2 transactivates the prepro-TRH gene and that T3-bound TRβ2 interferes with its function, resulting in the negative regulation of this gene.
SUN-652 Progesterone Receptor Membrane Component 1 Suppresses Type II Diabetes (T2D) Progression via Induced Insulin Signaling in Muscle
Authors: Lee Sang R , Hong Eui-ju
Published: May 2020

Type II diabetes (T2D) is characterized for insulin resistance in muscle, liver, and fat (1). Progesterone receptor membrane component 1 (Pgrmc1) is novel cell surface receptor which is associated with insulin receptor beta (IRβ) (2). Therefore, we speculated Pgrmc1 might be related to T2D. Using Pgrmc1 KO mice reported in our previous study (3), we observed the decrease of body weight (BW) and increase of muscle weight per body weight. When blood glucose level in post-prandial state was lower, Pgrmc1 KO mice showed improvements in glucose tolerance test (GTT) and insulin tolerance test (ITT). Though insulin level was low, insulin signaling genes were up-regulated in post-prandial Pgrmc1 KO mice, especially in muscle. Regulations of blood glucose level and insulin signaling gene levels by Pgrmc1 were also similarly observed in insulin-deficient state. To induce T2D, C57BL/6 mice were fed with high-fat diet for 8 weeks and injected by low dose of streptozotocin (30mg/kg). As a result, T2D-induced Pgrmc1 KO mice increased lean mass per BW, decreased the blood glucose level, and improved GTT and ITT. The insulin signaling genes were also up-regulated, while cytoplasmic GLUT4 was decreased, but membrane GLUT4 was increased in T2D-induced Pgrmc1 KO muscle. Glycolysis, TCA cycle, and oxidative phosphorylation genes were increased, suggesting energy metabolism was increased in T2D-induced Pgrmc1 KO muscle. Present study suggests that Pgrmc1 loss increases insulin signaling through induction of cytoplasmic IRβ and pAKT, and induces glucose uptake of muscle, thereby showing improvement in T2D progression. This has important clinical value because Pgrmc1 modulation will evade hypoglycemia caused by classic insulin therapy for T2D (4).

References: (1) Fernandez, A. M., Kim, J. K., Yakar, S., Dupont, J., Hernandez-Sanchez, C., Castle, A. L., Filmore, J., Shulman, G. I., and Le Roith, D. (2001) Functional inactivation of the IGF-I and insulin receptors in skeletal muscle causes type 2 diabetes. Genes & development 15, 1926-1934. (2) Hampton, K. K., Anderson, K., Frazier, H., Thibault, O., and Craven, R. J. (2018) Insulin Receptor Plasma Membrane Levels Increased by the Progesterone Receptor Membrane Component 1. Mol Pharmacol 94, 665-673. (3) Lee, S. R., Kwon, S. W., Kaya, P., Lee, Y. H., Lee, J. G., Kim, G., Lee, G. S., Baek, I. J., and Hong, E. J. (2018) Loss of progesterone receptor membrane component 1 promotes hepatic steatosis via the induced de novo lipogenesis. Scientific reports 8, 15711. (4) Zammitt, N. N., and Frier, B. M. (2005) Hypoglycemia in type 2 diabetes: pathophysiology, frequency, and effects of different treatment modalities. Diabetes care 28, 2948-2961.
SUN-418 Patterns of Thyroid Disease in Basrah, Iraq. Retrospective Study
Authors: Mansour Abbas Ali , Ali Alhamza Ali Hussain , Abdullah Almomin Ammar Mohammed Saeed , Zaboon Ibrahim Abbood , Alibrahim Nassar Taha Yaseen , Hussein Rudha Naser , Kadhim Muayad Baheer , Mohammed Adel Gassab , Jabbar Al-Waeli Dheyaa Kadhim , Nwayyir Hussein Ali , Alidrisi Haider Ayad Yassin , Hussein Ibrahim Hani , Odhaib Samih Abed , Altemimi Mahmood Thamer Jallod , Imran Husam Jihad
Published: May 2020

Background: Data on thyroid disease epidemiology in the Middle East are scanty and anecdotal. This study aimed to assess the pattern of thyroid disease seen in Faiha Specialized Diabetes, Endocrine and Metabolism Center (FDEMC) in Basrah,Southern Iraq.

Methods

Retrospective observational study of database retrieval from the FDEMC a tertiary care Center in Basrah for the period of September 2008 to January 2019. Included all adults non pregnant 18 years or older.

Results

Total enrolled patients 17878; of them 4174(23.3%) men and 13705(76.7 %) women. There were 2229(12.5%) patients with hypothyroidism (83.0% women), with subclinical hypothyroidism observed in 364 out of 2229 with hypothyroidism(16.3%).

We found 1087 (6.1%) patients with hyperthyroidism (67.7% women) and subclinical hyperthyroidism observed in 92 of 1087 hyperthyroidism (8.4%).

Thyroid nodularity was seen in 944 (5.2%) patients (807 women in 85.5%). Thyroidectomy was done in 776(4.3%). Differentiated thyroid cancer was seen in 77 (0.4%).

Conclusion: Hypothyroidism was double that of hyperthyroidism. Cross-sectional community-based study can give more information on the epidemiology of thyroid disease in Iraq.Iodine status needed studded in the future.

Keywords: Hyperthyroidism, hypothyroidism,autoimmune thyroid disease, Iraq.
OR17-07 Retinol Binding Protein 4 Predicts Functional Vascular Disease in Early Postmenopausal Women
Authors: Armeni Eleni , Nigdelis Meletios P , Augoulea Areti , Chondrou Asimina , Rizos Dimitrios , Kaparos George , Alexandrou Andreas , Goulis Dimitrios G , Georgiopoulos Georgios , Stamatelopoulos Kimon , Lambrinoudaki Irene
Published: May 2020

Introduction: The impact of gender on the development of cardiovascular disease has long been recognized. The potential effect of sex-specific cardiovascular risk factors on molecular mediators of oxidative stress has received limited attention and the results remain conflicting.

Hypothesis: To assess the link between retinol binding protein 4 (RBP4) and menopause-specific cardiovascular risk factors, on indices of early subclinical atherosclerosis, in a sample of apparently healthy young, postmenopausal women.

Methods: This cross-sectional study included a total of 123 healthy postmenopausal women, recruited from a University Menopause Clinic. Participating women were, not on hormone therapy, antihypertensive or hypolipidemic treatment and had a menopausal age of up to 10 years. Fasting venous blood samples were obtained for hormonal and biochemical assessment, including levels of RBP4. Sonographical studies were performed on the same day and included carotid-femoral pulse wave velocity (PWV) and calculation of the carotid artery stiffness index (SI).

Major results: Univariate analysis showed that RBP4 values correlated positively with age, total cholesterol, triglycerides, LDL-cholesterol, testosterone-to-estrogen ratio; negatively with circulating estrogen and almost significantly with homocysteine levels. Levels of homocysteine were inversely associated with RBP4 (homocysteine: RBP4 <10.5ng/ml vs ≥10.5ng/ml: 11.2±2.81μmol/L vs 12.52±3.44μmol/L, p-value=0.049 ANCOVA, adjusted for age, BMI, HOMA-IR). Multivariate analysis showed that PWV values were predicted by RBP4 (b-coefficient=0.435, p-value=0.006), age, pulse pressure, homocysteine. S.I. beta was predicted independently by RBP4 levels (b-coefficient=0.324, p-value=0.039). Both models were adjusted for menopausal age, LDL-cholesterol, FEI, smoking, HOMA-IR.

Conclusion: RBP4 levels are linked with measures of local carotid and aortic arterial stiffness, in this sample of healthy postmenopausal women. This association seems to be mediated by higher levels of homocysteine, which may interfere with retinoic acid synthesis. Larger studies are required to further elucidate the significance of our findings.

References

1. Majerczyk M, Olszanecka-Glinianowicz M, Puzianowska-Kuznicka M, Chudek J: Retinol-binding protein 4 (RBP4) as the causative factor and marker of vascular injury related to insulin resistance. Postepy Hig Med Dosw 2016;70:1267-1275.

2. Smolders RG, van der Mooren MJ, Sipkema P, Kenemans P: Estrogens, homocysteine, vasodilatation and menopause: basic mechanisms, interactions and clinical implications. Gynecol Endocrinol 2003;17:339-354.

3. Limpach A, Dalton M, Miles R, Gadson P: Homocysteine inhibits retinoic acid synthesis: a mechanism for homocysteine-induced congenital defects. Exp Cell Res 2000;260:166-174.
MON-653 The Effects of DPP IV Inhibitor on Glycemic Variability in Type 2 Diabetic Patients Treated with Twice Daily Premixed Human Insulin
Authors: Tan Florence Hui Sieng , Tong Chin Voon , Kuan Yueh Chien , Lau Bik Kui , Loh Huai Heng
Published: May 2020

Glycemic variability (GV) is emerging as an exciting therapeutic target for diabetes mellitus (DM) with recent evidences showing association of GV with hypoglycemia risk as well as chronic complications.(1,2) Twice daily human premixed insulin is commonly used in developing countries and Asia for treatment of type 2 DM (T2DM). (3) While more convenient and cost saving, human premixed insulin regime may increase GV due to lesser flexibility and less physiological pharmacokinetic profile. Dipeptidyl peptidase IV inhibitors (DPPIV-I) have been shown to improve GV when used for treatment of T2DM but the effects of DPPIV-I when added on human premixed insulin is limited. We therefore evaluated the changes in GV following addition of DPP IV-I among T2DM patients treated with premixed human insulin with or without metformin therapy. This was a prospective study involving adult patients with T2DM on stable doses of premixed human insulin with or without metformin for at least 3 months from two state hospitals in Malaysia. Blinded continuous glucose monitoring (CGM) were performed at baseline and following 6 weeks of adding Vildagliptin to their insulin regime. A total of 12 patients were recruited (50% male). Mean (SD) age was 55.8 (13) years with mean duration of disease of 14 (6.6) years. The addition of Vildagliptin significantly reduced GV indexes including SD 2.98 (1.17) to 2.33 (0.82), p=0.017; MAGE 6.94 (2.61) to 5.72 (1.87), p=0.018; MAG 1.60 (0.76) to 1.23 (0.48), p=0.009 and M Value 13.96 (13.01) to 6.52 (7.45), p=0.037. In addition there were improvements in terms of parameters for glycemic control. Time spent in optimal glycemic range (4-8 mmol/l) improved from 38.33 (19.69) to 58.17 (5.95) %, p=0.001 with reduction in AUC for hyperglycemia from 2.09 (1.73) to 1.06 (1.09) mmol/day, p=0.010. Hypoglycemia events were infrequent and the reduction in time spent in hypoglycemia [5.92(9.74) to 1.91 (2.54)%, p=0.191] as well as AUC for hypoglycemia [0.03(0.54) to 0.01(0.02) mmol/day, p=0.163] were found although these did not reach statistical significance. We concluded that addition of DPP IV-I to commonly prescribed twice daily premixed human insulin regime in patients with T2DM may improve GV and glycemic control and warrant further exploration.

References

(1) Gerry Rayman. Glycaemic control, glucose variability and the triangle of diabetes care. Br J Diabetes 2016;16(Suppl1):S3-S6

(2) Boris P. Kovatchev. Metrics for glycaemic control - from HbA1c to continuous glucose monitoring. Nat Rev Endocrinol. 2017 Jul;13(7):425-436

(3) Kalra S, Balhara YP, Sahay BK, Ganapathy B, Das AK. Why is premixed insulin the preferred insulin? Novel answers to a decade-old question. J Assoc Physicians India. 2013 Jan;61(1 Suppl):9-11
SAT-005 Investigating the Endocrine Disorders in Women with Menstrual Disturbances in Bayelsa State, Niger Delta Region of Nigeria
Authors: Ezeiruaku Ferdinand Chukwuma
Published: May 2020

Background: Many women in Bayelsa State, South-South Nigeria have been presenting with different menstrual disturbances and some with infertility problems that are associated with abnormal uterine bleeding, amenorrhea, dysmenorrhea, premature menopause (primary ovarian insfficiency) and premature syndrome (PMS). It is recognized universally that menstrual disturbances may accompany and most times, succeed endocrine disorders. Objective: The aim of the study was to investigate the various endocrine disorders associated with women of reproductive age experiencing different menstrual disturbances attending the different specialist hospitals in Bayelsa State, Nigeria. This is with the interest of establishing the different hormone disorders and its prevalence in these women of Bayelsa State. Method: A total of 1852 subjects (women with menstrual disturbances) were randomly selected using a questionnaire design containing the information of age, last menstrual date, degree of irregularity, whether on medication for any infertility problem or preventive measures and have had any form of surgery. Excluded from the study were pregnant women, women above 40 years of age, those on infertility and contraceptive medication. Analyses of the different hormones of the hypothalamic - pituitary- gonadal reproductive axis were measured using Enzyme Linked Immunosorbent Assay (ELISA). Results: From the study, it was observed that the menstrual disturbances were accompanied with female reproductive hormone fluctuations; with a high significant (P<0.005) percentage, 79.93% of the women having one form of the endocrine disorders. The study has shown that 63.17% of the studied subjects had hypoestrogenism, 38.66% had hypergonadotropic hypogonadism and a non significant (p>0.05) 1.35% with hypogonadotropic hypogonadism. Analysis of the results also showed 15.12% of the subjects had hypothalamic amenorrhea, 32.02% with hyperprolactinaemia and non significant value of 1.30% with hypoprolactinaemia. From the study, 10.92% of the women with menstrual disturbances studied in Bayelsa State had hyperthyroidism, 4.71% with hypothyroidism, 3.74% with T3 thyrotoxicosis and 2.37% with TBG excess. Conclusion: This study therefore concluded that a significant number (p<0.05) of women in Bayelsa State, Nigeria with menstrual disturbances are associated with endocrine disorders probably due to life style (diet, obesity), environmental factors and an underlying illness(infections, cancer and polycystic ovarian syndrome).
SAT-213 Parotid Carcinoma Ex Pleomorphic Adenoma Can Produce Ectopic ACTH Too
Authors: Adly Hussein , O’Donnell Benjamin M , Kirschner Lawrence S
Published: May 2020

Background: Ectopic ACTH syndrome accounts for about 14% of Cushing syndrome cases. Small cell lung cancer is the most common cause. A few case reports described ectopic ACTH syndrome in patients with parotid acinic cell carcinoma. Parotid carcinoma ex pleomorphic adenoma is a malignant transformation within a pleomorphic adenoma, which is mostly adenocarcinoma not otherwise specified, but other subtypes can occur.

Clinical Case: A 41-year old man with parotid cancer and hypothyroidism was admitted to the hospital for hypokalemia (2.1 mmol/L, n: 3.5-5 mmol/L). Parotid cancer was diagnosed a year before admission. At that time, he underwent left parotidectomy, and pathology showed carcinoma ex pleomorphic adenoma with areas of acinic cell carcinoma. Despite chemoradiation, he was diagnosed with metastasis in the lungs, for which pembrolizumab was started. Over the two months prior to admission, he gained 20 lb, and developed lower extremity weakness, acne, erectile dysfunction and loss of libido. He was also diagnosed with hypertension and started to have mild hypokalemia. Suspecting hyperaldosteronism, oncology team ordered labs just prior to admission, which showed the hypokalemia of 2.1 mmol/L, hypernatremia (147 mmol/L, n: 133-143 mmol/L), normal aldosterone and renin, and high cortisol (59.12 mcg/dL, n: 3-22 mcg/dL) and ACTH (121 pg/mL, n: 9-50 pg/mL).

In the hospital, potassium was slowly improving despite aggressive replacement, and blood pressure was still elevated despite increasing his lisinopril dose. Screening for Cushing syndrome revealed an abnormal 1 mg dexamethasone suppression test (cortisol 51.9 mcg/dL, n: <1.8 mcg/dL), and high 24-hour urinary free cortisol (6495 mcg/24h, n: 3.5-45 mcg/24h) and midnight salivary cortisol (2610 ng/dL and 4250 ng/dL, n: <100 ng/dL). Cortisol was not suppressed after 8 mg dexamethasone (cortisol 47.85 mcg/dL, pretest cortisol 48.73 mcg/dL) pointing toward ectopic ACTH syndrome. Spironolactone was started and titrated up to 100 mg BID with better control of hypertension and normalization of potassium. Ketoconazole was started at 200 mg TID and increased gradually as outpatient to 400 mg TID within three weeks. A repeat 24-hour urinary free cortisol was done five weeks after ketoconazole was started showing significant improvement (110 mcg/24h, n: 3.5-45 mcg/24h). Potassium requirements remarkably decreased from 80 mEq TID to 40 mEq daily. Of note, chest CT done during hospitalization showed new lung lesions despite treatment with pembrolizumab.

Conclusion: This is the first case of ectopic ACTH syndrome to be described in a patient with parotid carcinoma ex pleomorphic adenoma, though areas of acinic cell carcinoma within the tumor can be the source of ACTH. Hypercortisolism due to ectopic ACTH secretion is usually of rapid onset, and can present with severe hypokalemia. Steroid synthesis inhibitors seem to be an effective therapy.
SAT-742 Characterising the Metabolism, Glucuronidation and Sulfation of C11-oxy C19 Steroids
Authors: Toit Therina Du , Swart Amanda C
Published: May 2020

The metabolism of 11β-hydroxyandrostenedione (11OHA4), a major adrenal C19 steroid, was first characterised in our in vitro prostate models showing that 11OHA4, catalysed by 11βHSDs, 17βHSDs and 5α-reductases, yields potent androgens, 11keto-testosterone (11KT) and 11keto-dihydrotestosterone (11KDHT) in the 11OHA4-pathway [1]. Findings have since led to the analysis of C11-oxy steroids in PCOS, CAH and 21OHD. However, the only circulating C11-oxy steroids included to date have been 11OHA4, 11keto-androstenedione (11KA4), 11β-hydroxytestosterone (11OHT) and 11KT, with 11KT reported as the only potent androgen produced from 11OHA4. We have identified higher levels of 11KDHT compared to 11KT in prostate cancer tissue and benign prostatic hyperplasia tissue and serum, with data suggesting impeded glucuronidation of the C11-oxy androgens [2,3]. The assessment of 11KDHT and the inactivation/conjugation of the C11-oxy steroids in clinical conditions is therefore crucial.

We investigated the metabolism of testosterone, 11KT, 11OHT, dihydrotestosterone, 11KDHT and 11OHDHT in JEG-3 placenta choriocarcinoma, MCF-7 BUS and T-47D breast cancer cells, focusing on glucuronidation and sulfation. Steroids were assayed at 1 µM and metabolites were quantified using UPC2-MS/MS. Conjugated steroids were not detected in JEG-3 cells with DHT (0.6 µM remaining) metabolised to 5α-androstane-3α,17β-diol and androsterone (AST), and 11KDHT (0.9 µM remaining) to 11OHAST and 11KAST. 11OHA4 was converted to 11KA4 (12%) and 11KT (2.5%); and 11KT to 11KDHT (14%). In MCF-7 BUS cells, DHT was significantly glucuronidated, whereas 11KDHT was not. 11KAST was the only steroid in the MCF-7 BUS and T-47D cells that was significantly sulfated (p<0.05). In parallel we investigated sulfation in the LNCaP prostate model. Comparing sulfated to glucuronidated levels, only DHT was sulfated, 26%. Analysis showed that C19 steroids were significantly conjugated (glucuronidated + sulfated) compared to the C11-oxy C19 steroids.

As there exists an intricate interplay between steroid production and inactivation, impacting pre- and post-receptor activation, efficient conjugation would limit adverse downstream effects. Our data demonstrates the production and impeded conjugation of active C11-oxy C19 steroids, allowing the prolonged presence of androgenic steroids in the cellular microenvironment. Identified for the first time is the 11OHA4-pathway in placenta and breast cancer cells, and the sulfation of 11KAST. Characterising steroidogenic pathways in in vitro models paves the direction for in vivo studies associated with characterising clinical disorders and disease, which the C11-oxy C19 steroids and their intermediates, including inactivated and conjugated end-products, have highlighted. [1] Bloem, et al. JSBMB 2015, 153; [2] Du Toit & Swart. MCE 2018, 461; [3] Du Toit & Swart, JSBMB 2020, 105497.