bluuebunny/crossref_metadata_2025_split huggingface dataset:
MON-093 Pleuropulmonary Blastoma and Multinodular Goiter in a 22 Yr Old Male with DICER1 Syndrome
Authors: Lhamu Ugen , Phornphutkul Chanika , Massingham Lauren , Quintos Jose Bernardo 
Published: May 2020

Abstract
Background
DICER1 syndrome is an autosomal dominant condition due to mutations in the DICER1 gene, located on chromosome 14q32.13. Patients are at increased risk for malignant and benign tumors, including pleuropulmonary blastoma (PPB), cystic nephroma, ovarian Sertoli-Leydig cell tumors, multinodular goiter (MNG) and differentiated thyroid cancer (DTC). MNG is very common in patients with DICER1 Syndrome but data on incidence is lacking. MNG is more common in females than males.
Case presentation:
22 year old man who originally presented with pleuropulmonary blastoma, Type 3 at 3 years of age. His treatment included pulmonectomy, radiation of 46.6 Gy to thorax, and alkylating agents including Cisplatin, Ifosphamide and Cytoxan. He developed frontal lobe metastasis over the course of 3 years and was treated with focal cranial radiation. His father and maternal uncle had history of lung cancer.
He was evaluated at the Endocrine clinic at 12 years 10 months for short stature. His height was 132.5 cm (SDS -2.96), weight 29.7 kg (SDS -2.40), and BMI 16.99kg/m² (SDS -0.61). On examination he had normal thyroid exam and Tanner 2 bilateral 4 cc testicles. He was treated with Levothyroxine for subclinical hypothyroidism (TSH: 5.96 uIU/ml (0.35–5.5) and Free T 4: 0.99 ng/dl (0.8–1.80) and growth hormone (GH) for growth hormone deficiency (peak GH was 7.7 ng/ml after Arginine and Clonidine GH stimulation test).
At 14 years 10 month he developed respiratory distress. CT scan of chest showed right lower pole nodule 1.6 x 1.5 x 1.4 cm. Ultrasound of thyroid showed right thyroid solid mid pole isoechoic nodule 1.4 x 1.7 x 1.3 cm with multiple enlarged bilateral cervical nodes, largest left supraclavicular region &gt; 1 cm. Biopsy of the right nodule was negative for malignancy. Over the course of 2 years he developed new right thyroid isoechoic nodule in the lower pole 2.1 x 2.5 x 1.9 cm and new left thyroid isoechoic nodule in the upper pole 1.0 x 0.5 x 0.5 cm. Biopsy was negative for malignancy.
Due to his PPB, MNG and family history of lung cancer he was evaluated at our genetic cancer clinic and tested positive for germline DICER1 pathogenic variant c.4605_4606del (p.Cys1535Trpfs*3)
Conclusion:
Our 22 year old male presented with pleuropulmonary blastoma and over the course of few years developed MNG. Genetic testing was positive for germline DICER1 pathogenic variant c.4605_4606del (p.Cys1535Trpfs*3). Our case illustrates the importance of consideration of: 1) Testing children with PPB for DICER1 Syndrome as there are screening recommendations including regular thyroid ultrasound and examinations to look for MNG or other features concerning for thyroid gland neoplasia. 2) MNG is uncommon in children and detection of this should raise suspicion for consideration of testing for DICER1 Syndrome.
OR29-05 A Natural History Study of Fibrodysplasia Ossificans Progressiva (FOP): 12-Month Outcomes
Authors: Mukaddam Mona Al , Pignolo Robert J , Baujat Geneviève , Brown Matthew A , De Cunto Carmen , Rocco Maja Di , Hsiao Edward C , Keen Richard W , Sang Kim-Hanh Le Quan , Strahs Andrew , Marino Rose , Kaplan Frederick S 
Published: May 2020

Abstract
Background: FOP is an ultra-rare, severely disabling genetic disorder characterized by episodic flare-ups and heterotopic ossification (HO) leading to restricted movement, physical disability, and early death. FOP may initially be misdiagnosed in ~90% of individuals leading to unnecessary and often harmful interventions. Patients with FOP are diagnosed and managed by multiple specialties, including endocrinologists.
Data from an ongoing, prospective, longitudinal, global, natural history study (NCT02322255) were used to investigate the progression of FOP, HO formation, and impact on physical functioning over time. We present results from the first 12 months of the 3-year study.
Methods: Males and females with FOP and a documented ACVR1 R206H mutation participated. HO volume was assessed by low-dose whole body computed tomography (WBCT) scan, excluding the head. All imaging was interpreted at a blinded, central laboratory using pre-specified procedures. Functional outcomes were evaluated using the Cumulative Analogue Joint Involvement Scale (CAJIS; for each joint: score=0 represents &lt;10% involvement, score=1 represents 10–90% involvement, and score=2 represents &gt;90% ankylosed across 15 major joints; total score range 0 to 30 [higher scores indicate more severe mobility limitations]) and the FOP Physical Function Questionnaire (FOP-PFQ; percent total score). Changes from Baseline at Month 12 were evaluated for new HO volume, CAJIS, and FOP-PFQ.
Results: Of 114 participants (pts) with Baseline data, 99 (4 to 56 years at enrollment; mean 17 years of age; 56% male) also had a Month 12 assessment. A total of 93 pts had evaluable WBCT scans at Baseline and Month 12 and were included in the HO analysis.
In total, 40% (37/93) of pts had new HO over 12 months; the mean volume of new HO in these pts was 57,706 mm3 (SD=100,079 mm3; median=20,753 mm3; range: 522 to 438,826 mm3). Of the pts with new HO, 65% (24/37) reported at least one flare-up (mean rate of 2.3 flare-ups/year).
Over 12 months, 60% (56/93) of pts did not have new HO; 43% (24/56) of them reported at least one flare-up (mean rate of 1.8 flare-ups/year).
Mean changes from Baseline in CAJIS and FOP-PFQ were minimal: CAJIS: 0.6 (SD=2.4; median=1.0; n=99) and FOP-PFQ: 4.4% (SD=11.2; median=3.7%; n=90); and were similar across pts with or without new HO.
Conclusions: In participants with FOP, although deterioration of physical function is expected over a patient’s lifetime, CAJIS and FOP-PFQ scores did not worsen significantly in the relative short-term of this study. However, HO volume, quantified by WBCT, increased over the course of 12 months. These results show that measuring HO may be a viable way to monitor changes in FOP over short periods of time.
SAT-143 Missed Pituitary Apoplexy in a HIV Patient
Authors: Tsang Tiffany , Raghuwanshi Maya P 
Published: May 2020

Abstract
Background: Pituitary hemorrhage has a prevalence of up to 25% in macroadenomas. In apoplectic hemorrhage, loss of pituitary function is associated with significant mortality. Sudden hemorrhagic enlargement of a preexisting adenoma compresses surrounding structures; ophthalmoplegia, mydriasis and ptosis occur when cranial nerves in the cavernous sinus are affected. The classic clinical syndrome of headache, visual deficits, altered mental status and hypopituitarism, combined with imaging, confirms the diagnosis of pituitary apoplexy.
Clinical Case: A 73 year-old smoker with a history of transsphenoidal surgery 20 years ago for a pituitary adenoma, HIV (CD4 928), hypertension, diabetes, coronary artery disease presented with two days of altered mental status, lethargy and headaches. Patient was febrile to 104.1°F on arrival. Head CT was done prior to a lumbar puncture, which showed a 1.7 x 2.1 x 2.2 cm pituitary mass. CSF analysis was positive for xanthochromia, and revealed 220 RBCs, 275 WBCs, glucose 143 mg/dL, protein 154 mg/dL and an opening pressure of 9 mm H20. Meropenem and vancomycin were started for presumed meningitis. A hypopituitary state was found on labs: prolactin 1.9 ng/mL (4.6–21.4 ng/mL), ACTH 3.2 pg/mL (7.2–63.3 pg/mL), cortisol 3.6 ug/dL, TSH 0.164 uIU/mL (0.27–4.0 uIU/mL), free T4 0.6 ng/dL (0.7–1.5 ng/dL), T3 0.3 ng/mL (0.6–1.6 ng/mL), IGF-1 33 ng/mL (41–179 ng/mL), total testosterone 4 ng/dL (193–740 ng/dL), LH 0.3 mIU/mL and FSH 1.2 mIU/mL. Subsequent MRI showed a 2.2 x 2.4 x 2.9 cm pituitary macroadenoma extending into the suprasellar region with mass effect on the optic chiasm and lateral displacement of the cavernous sinus segment of internal carotid arteries bilaterally. An ophthalmologic exam could not be performed due to altered mentation. Endocrinology recommended cosyntropin testing to assess for adrenal insufficiency. The following day, the patient developed a fixed and dilated right pupil, and was taken to the OR for emergent decompression. IV dexamethasone and levothyroxine were started post-operatively.
Conclusion: Differential diagnoses of pituitary apoplexy include bacterial meningitis and subarachnoid hemorrhage with aneurysmal rupture. A nonpupil-sparing third nerve palsy suggests a mass lesion. Given his symptoms and xanthochromia, this patient likely presented with pituitary apoplexy that was overlooked on initial scans. Hemorrhage that is iso-dense to normal brain tissue would not have the typical “pituitary ring sign”, a radiographic feature of peripheral enhancement around a non-enhancing infarcted center. Predisposing factors include hypertension, diabetes mellitus, pituitary dynamic testing, bromocriptine, estrogens or radiotherapy. This patient had multiple comorbidities. A lumbar puncture possibly worsened preexisting pituitary apoplexy, acutely expanding the area of hemorrhage and causing compressive symptoms.
SAT-072 A Case of Solitary Hyperfunctioning Thyroid Nodule Harboring Papillary Thyroid Carcinoma in a Pediatric Patient
Authors: Burdea Liliana , Calabrese Mary E , Jo Inha , Mantis Stelios 
Published: May 2020

Abstract
Introduction: Thyroid nodules are less common among children than adults but are more likely to be malignant. Among all the thyroid nodules, autonomous functioning thyroid nodules (AFTN) are generally considered to be a benign entity, with malignancy found in less than 1 %. AFTN are very rare in the pediatric population, and the optimal treatment is not well defined. We present a 14-year-old female patient with an AFTN treated with surgical resection and found to contain papillary thyroid carcinoma, despite a previous biopsy which did not demonstrate malignancy. Case presentation: A 14-year-old girl presented with left-sided palpable thyroid lesion for four months. The patient had no symptoms at that time, and the physical exam was notable for a palpable left thyroid nodule measuring 3x 2.2 cm. Thyroid studies were remarkable for a suppressed thyroid-stimulating hormone (TSH) of 0.056uIU/mL (0.350–4.94), normal free thyroxine (FT4): 1.1 ng/dL (0.7–1.5), and positive anti-thyroglobulin antibodies: 9.0 IU/ml (0.0 - 4.1) with negative anti peroxidase antibodies and negative thyroid-stimulating immunoglobulin. Initial ultrasound (US) showed a left complex cystic and solid nodule measuring 3.4 cm x 1.8 cm x 2.3 cm. Fine needle aspiration (FNA) of the nodule revealed a benign aspirate. An I-123 scan revealed a hyperfunctioning nodule with suppression of uptake in surrounding thyroid parenchyma. The patient was then lost to follow up, presenting to our clinic over a year later due to difficulty breathing when supine and increased nodule size. Thyroid studies were notable for a suppressed TSH of 0.005 and slightly elevated FT4:1.8. Thyroid US showed a mixed cystic and solid nodule measuring 4.7 x3 x 4cm, with no calcification. Given the increased size of the lesion, her age, and difficulty breathing when supine, a decision was made to proceed with left hemithyroidectomy for definitive diagnosis and treatment. Pathology of the specimen revealed an encapsulated papillary thyroid carcinoma with focal capsular invasion. Right hemithyroidectomy was performed three weeks later, followed by I-131 ablation one month after surgery. The patient is currently doing well and euthyroid on thyroid hormone replacement therapy, with no evidence of disease. She is undergoing surveillance with ultrasound imaging and laboratory evaluation. Conclusion: This is a rare case of AFTN harboring papillary thyroid carcinoma. Although the majority of cases of AFTN are benign, an FNA was performed and was negative for malignancy. Due to an increase in size, new symptoms and ultrasound changes, surgery was performed and revealed the final diagnosis. The behavior of thyroid nodules in pediatric patients can be different than adult patients. Even though the majority of AFTN are benign, we should still keep malignancy in our differential when the nodule has a growth pattern, new US findings or patient develops worsening symptoms.
SUN-488 A Coexisting of Two Different Thyroid Malignancies: A Collision Phenomenon
Authors: Pishdad Reza , Boutin Regine , Hajjar Richard , Jaloudi Mohammed , Galan Mark , Cespedes Lissette Maria , Raghuwanshi Maya P 
Published: May 2020

Abstract
A Coexisting of Two Different Thyroid Malignancies: A Collision Phenomenon Introduction: Collision tumors are rare clinical entities wherein two histologically distinct tumor types occur at the same anatomic sites. Simultaneous papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) of the same thyroid is a very rare occurrence with limited clinical information. Herein, we report a case of PTC and FTC of the same thyroid lobe. Clinical case: A 79-year-old man presented to the emergency department for evaluation of left hip pain of 2-month duration. Three days before presentation, he sustained a physical trauma to the left side of his body. X-ray imaging of the left femur revealed a lytic bony lesion measuring approximately 5.2 cm x 4.2 cm at the proximal end of left femur as well as a displaced pathologic fracture of its lesser trochanter. Biopsies of the bone lytic lesion suggested metastatic follicular thyroid carcinoma. CT of the neck revealed an enlarged thyroid with a cystic lesion as well as 2 nodules in the left lobe of thyroid gland. Total thyroidectomy was performed. Histopathology revealed 2 separate primary malignancies of PTC and FTC. Following diagnosis, laboratory test results showed TSH 2.6 uIU/mL (reference range, 0.2–4), anti-thyroglobulin antibody (anti Tg) &lt; 1.0 IU/mL (reference range, 0.0–0.9), calcitonin 8.4 pg/mL (reference range, 0–8.4), and CEA 1.1 ng/mL (reference range, 0.0–3.0). The patient was placed on thyroid hormone replacement therapy and was treated with external beam radiation to his bone metastasis. He was scheduled for later further thyroid ablation. In his follow-up visit, three months later, he reported no pain on ambulation. Discussion: For each type of thyroid malignancy, several genes have been identified. However, to date, no common gene mutation responsible for the pathogenesis of the different tumor types has been determined. For instance, point mutations of the RAS oncogene are found in about 40% of thyroid neoplasms (N-RAS, H-RAS, and K-RAS, in order of decreasing frequency) including both PTC and FTC. No single theory can completely explain the pathogenesis of these tumors in all cases, and so, with the present level of understanding of the disease, a combination of theories must be accepted. Management of collision tumors of the thyroid gland is usually complex owing to the presence of dual pathology in the tumor tissues and given the fact that literature on this condition is scarce. Generally, the treatment needs to be individualized. Conclusion: Most likely, a rare phenomenon of simultaneous mutation of different genes can give birth to contemporary different thyroidal neoplasms. References: Zhu Z, Gandhi M, Nikiforova MN, et al. Molecular profile and clinical-pathologic features of the follicular variant of papillary thyroid carcinoma. An unusually high prevalence of ras mutations. Am J Clin Pathol 2003; 120:71.
SAT-282 Hypothalamic Pituitary Adrenal Axis Hyperactivity in Db/db Mice
Authors: Kameda Hiraku , Sekizaki Tomonori , Shibayama Yui , Nomoto Hiroshi , Cho Kyu Yong , Nakamura Akinobu , Miyoshi Hideaki , Atsumi Tatsuya 
Published: May 2020

Abstract
Background: Patients with diabetes present hypercortisolemia, which may exacerbate not only glycemic control but also diabetic complications and fatty liver (1). Blood steroid hormone levels including corticosterone and aldosterone are high in db/db mice (2), although the mechanism is still unclear. Objective: To reveal the mechanism underlying the hypothalamic-pituitary-adrenal (HPA) axis hyperactivity in obese and diabetic condition. Method: Total RNA from hypothalamus, pituitary, and adrenal glands in ten-week-old db/db and db/+ mice were extracted and analyzed with DNA microarray and real-time PCR. Experiments were approved by the Institutional Animal Care and Use Committee. Results: Hypothalamic Crh mRNA expression was not changed in db/db mice, although Avp expression was 2.8-fold higher than db/+ mice. Pituitary Crhr1 and Pomc expression were higher (3.0- and 7.0-fold, respectively), and Nr3c1 expression was lower (0.7-fold) in db/db mice than db/+ mice. Adrenal Mc2r, Nr5a1, Cyp11b1, and Cyp11b2 were higher in db/db mice than db/+ mice (1.7-, 1.7-, 2.2-, 1.3-fold, respectively). Conclusion: Increased expression of tropic hormone receptors and abrogated negative feedback system may be responsible for HPA axis hyperactivity in db/db mice. Reference: (1) Chiodini I et al. Diabetes Care. 2007 Jan;30:83–8. (2) Hofmann A et al. Horm Metab Res. 2017 Jan;49:43–49.
OR15-07 Novel Genes Involved in Sex Differentiation Identified by Whole-Exome Sequencing in a Cohort of Children with Disorders of Sex Development
Authors: Rakover Yardena Tenenbaum , Admoni Osnat , Assad Ghadir Elias , London Shira , Barhoum Marie Noufi , Ludar Hana , Almagor Tal , Bertalan Rita , Bashamboo Anu , McElreavey, Prof Kenneth 
Published: May 2020

Abstract
Background: Disorders of sex development (DSD) are classified as a congenital discrepancy between external genitalia, gonadal and chromosomal sex. Despite extensive laboratory and imaging investigations, the etiology of DSD is unknown in more than 50% of patients and the diagnosis is often delayed to the second decade of life. Our objective was to evaluate the etiology of DSD by whole-exome sequencing (WES) in children in whom hormonal and candidate gene approaches had not identified the etiology. Methods: Nine patients diagnosed with DSD (eight 46,XY and one 46,XX) were enrolled. Patients underwent hormonal evaluation, including ACTH, GnRH and hCG tests. Candidate genes were sequenced in accordance with the hormonal results. WES was performed for the probands and their parents. Results: The eight 46,XY patients presented with micropenis, cryptorchidism and hypospadias at birth and the 46,XX patient with fusion of the labia majora. In six of the nine patients (66%), a pathogenic mutation was identified by WES that explained the phenotype: four known DSD-causing genes—POR, CHD7, HSD17B3 and WT1—and two novel genes—BMP4 and RFXP2. In three patients, variants of unknown significance were found. An 11-y-old boy had a novel de-novo mutation in BMP4. In humans, mutations in this gene, encoding bone morphogenetic protein 4, are associated with autosomal dominant microphthalmia. BMP4 is expressed in the urethral epithelium and has a role in the development of external genitalia and the pituitary. This is the first report of a BMP4 mutation in a child with DSD. A 12-y-old boy had a mutation in RFXP2, encoding insulin-like 3 hormone receptor, which has been previously reported in adult males with cryptorchidism. This is the first case of an RFXP2 mutation in a child with DSD. Conclusions: WES has a crucial role in early diagnosis of the etiology of DSD, making extensive endocrine testing unnecessary, and has important implications for sex of rearing decisions.
SAT-413 Does Dipeptidyl Peptidase-4 Inhibitor Exacerbate Graves’ Disease?
Authors: Sekizaki Tomonori , Kameda Hiraku , Cho Kyu Yong , Akinobu Nakamura , Takahashi Kiyohiko , Wada Norio , Takeuchi Jun , Nagai So , Miyoshi Hideaki , Atsumi Tatsuya 
Published: May 2020

Abstract
Abstract: [Background] Dipeptidyl peptidase-4 (DPP-4) is expressed as CD26 on the surface of immune cells including T cells, suggesting that inhibition of DPP-4 may affect the immune system (1). Actually, DPP-4 inhibitor (DPP-4i)-induced polyarthritis and bullous pemphigoid have been reported (2, 3). It has also been reported that the prevalence of Hashimoto’s thyroiditis was significantly higher in patients on DPP-4i treatment (4). However, relationships between DPP-4i and Graves’ disease has been unclear. [Methods] To investigate the impact of DPP-4i administration on the activity of Graves’ disease, we conducted a multicenter observational trial that included patients with both Graves’ disease and type 2 diabetes mellitus who were administered an oral hypoglycemic agent (OHA) including DPP-4i from December in 2009 to April in 2018. Patients who had systemic diseases affecting thyroid function and those who underwent thyroidectomy or radioiodine treatment within 6 months before or after OHA administration were excluded. Exacerbation of Graves’ disease was defined as an increase in antithyroid drug dose within 6 months after OHA administration. The trial was approved by the institutional review board of Hokkaido University Hospital. [Results] Eighty-three patients were enrolled in the study, and they were divided into an exacerbation group (n = 18) and a non-exacerbation group (n = 65). Comparing baseline characteristics, the percentage of DPP-4i administration was higher in the exacerbation group (83.3%) than in the non-exacerbation group (32.3%) (p = 0.0001). Mean age was also significantly higher in the exacerbation group (p = 0.04), and the duration of Graves’ disease was significantly shorter (p = 0.01). Multivariate logistic regression analysis using factors extracted by comparing baseline characteristics demonstrated a significant association between DPP-4i administration and Graves’ disease exacerbation (odds ratio 5.62, 95% confidence interval 1.16–27.0, p = 0.02). [Conclusion] The current study suggests that DPP-4i administration is associated with exacerbation of Graves’ disease.
Reference: (1) Morimoto C et al., Immunol Rev. 1998 Feb;161:55–70. (2) Yokota K et al., Intern Med. 2012;51(15):2041–4. (3) Yoshiji S et al. J Diabetes Investig. 2018 Mar;9(2):445–447. (4) Kridin K et al. Immunol Res. 2018 Jun;66(3):425–430.