bluuebunny/crossref_metadata_2025 huggingface dataset:
SUN-493 A “Curve Ball” in the Management of an Infertile Hyperthyroid Patient
Authors: Lessard Kimberly K , Miller Jeffrey L , Arzeno Luis
Published: May 2020

Introduction: We present the case of a young female patient referred for hyperthyroidism with persistently detectable TSH despite elevated free thyroxine (FT4) levels which, interestingly, failed to normalize following anti-thyroidal treatment. Further testing elucidated the underlying causation for detectable TSH in presence of hyperthyroxinemia to be due to interfering substances in the thyroid function assays.

Case: A 35-year-old female is evaluated for hyperthyroidism discovered in preparation for embryo transfer. History includes transient hyperthyroidism two years ago while undergoing in vitro fertilization. Prior workup included negative antibodies and nuclear uptake scan revealing a right-sided autonomously functioning thyroid nodule with 24-hour uptake of 40.7%. She was briefly treated with PTU in first trimester and lost to follow-up. While once again undergoing fertility treatment with clomiphene, the patient developed tremor and heat intolerance. She was found to have TSH 0.3 (0.45-4.12 mU/L) and analog FT4 of 6.4 (0.8-1.8 ng/dL). She denied use of OTC supplements. PTU 50 mg twice daily was initiated with minimal improvement with TSH 0.7 mU/L, FT4 3.7 ng/dL. On evaluation, slight tremor and mild thyroid enlargement were noted. Our differential expanded to include TSH-secreting pituitary adenoma, thyroid hormone resistance (no family history), and assay interference. Both MRI pituitary and an alpha-subunit level (0.36) were normal. Symptoms improved gradually with repeat TSH 1.79 mU/L, FT4 2.4 ng/DL by standard analog methods. We suspected ‘assay interference’ for which FT4 via direct equilibrium dialysis was obtained and was indeed normal at 0.76 ng/dL. Further lab testing verified interference in both in the standard TSH and FT4 assays presumed secondary to heterophile antibodies.

Discussion: Interpretation of thyroid studies discordant with the clinical picture or incongruent with each other requires understanding of thyroid physiology and the intricacies of commonly utilized assays. The differential of elevated thyroxine levels with detectable/normal TSH rests between thyroid hormone resistance syndromes, TSH secreting pituitary tumors and interfering substances in the assay. Most commercially available TSH assays are based on a ‘sandwich’ assay which is notoriously interfered with by heterophile antibodies and excess biotin. Determination of FT4 is also challenging as the assay must detect very low concentrations of free hormone relative to excess of protein-bound analyte. When in question, it is important consider utilization of laboratory expertise and retesting by alternative assays.
OR15-03 High Prevalence of Gene Variants in Boys of Prepubertal Age with Clinical Suspicion of Central Hypogonadism and Low AMH
Authors: Brunello Franco , Sansó E Gabriela , Scaglia Paula , Azcoiti María Esnaola , Berenstein Ariel , Izquierdo Agustín , Bedecarrás Patricia , Martí Marcelo , Ropelato M Gabriela , Rey Rodolfo Alberto , Grinspon Romina , Freire Analía
Published: May 2020

Introduction: In boys of prepubertal age, the diagnosis of central hypogonadism may be difficult to ascertain since gonadotropins and testosterone are normally low. Sertoli cell markers, like AMH and inhibin B, may be useful. In recent years, with the development of next generation sequencing (NGS) technology, the number of genes associated with central hypogonadism has had an exponential increase. However, even with these advanced techniques, the gene variants with potential pathogenicity can be found at present in only 30-50% of the patients. Hypothesis of the study: Low serum AMH is an appropriate screening biomarker to select patients for NGS, in order to make a genetic diagnosis in boys of prepubertal age with suspected central hypogonadism. Patients and methods: All patients aged 1-10 yr referred between 2001 and 2018 with clinical suspicion of central hypogonadism (micropenis and cryptorchidism and/or microorchidism), with low serum AMH (<10th centile) were included. Serum AMH was determined by ELISA (Beckman-Coulter), and LH, FSH and testosterone (T) by ECLIA (Roche). NGS was performed with the TruSight™ One Sequencing Panel in a NextSeq® 500 sequencer (Illumina). Results are expressed as medians (range). Results: 13 patients were included. Age at first visit was 4.4 (0.1-9.2) yr. Cryptorchidism was present in all of them, micropenis in 10 and microorchidism in 11. Orchiopexy was required in 11 boys and the other 2 responded to hCG treatment. 4 patients had olfactory disturbances, 1 had sensory deafness and 1 had piebaldism. 2 patients had a family history of olfactory disturbances and/or central hypogonadism. 7 patients could be followed up to pubertal age, and the diagnosis of central hypogonadism was clinically confirmed. At age 6.1 yr (1.2-10), AMH was 159 pmol/L (65-363), LH was <0.1 IU/L in all, FSH was 0.61 IU/L (<0.1-1.9). 17 variants in 9 genes associated with central hypogonadism were found in 10 of 13 patients. 5 boys had 1 gene variant, while 4 had 2 gene variants and 1 had 3 gene variants indicating probable oligogenicity, in the following genes: FGFR1 (n:4), CHD7 (n:3), PROKR2 (n:2), SOX10 (n:2), AXL (n:2), HS6ST1 (n:1), AMHR2 (n:1), NSMF (n:1), DCC (n:1). Conclusion: A high prevalence of gene variants was found in boys of prepubertal age with a suspicion of central hypogonadism based on micropenis and cryptorchidism and/or microorchidism with low serum AMH.
OR29-01 Long-Term Safety in Adults with X-Linked Hypophosphatemia (XLH) Treated with Burosumab, a Fully Human Monoclonal Antibody Against FGF23: Final Results of a Phase 3 Trial
Authors: Perwad Farzana , Portale Anthony A , Carpenter Thomas O , Briot Karine , Imel Erik Allen , Kamenicky Peter , Weber Thomas Joseph , Pitukcheewanont Pisit , Cheong Hae Il , De Beur Suzanne Marie Jan , Imanishi Yasuo , Ito Nobuaki , Lachmann Robin , Tanaka Hiroyuki , Zhang Lin , Skrinar Alison , Rees Linda , Insogna Karl Leonard
Published: May 2020

Burosumab, a fully human IgG1 monoclonal antibody to FGF23, is approved in Canada and Brazil to treat XLH in patients ≥1 year of age and in the US to treat XLH in patients ≥6 months of age. Burosumab has also received conditional marketing authorization in Europe to treat XLH with radiographic evidence of bone disease in children ≥1 year of age and in adolescents with growing skeletons. Burosumab significantly improved serum phosphorus, fracture/pseudofracture healing, stiffness, and physical functioning in a phase 3, double-blind, multicenter study (CL303, NCT02526160). In this trial, subjects were randomized 1:1 to receive burosumab or placebo subcutaneously every 4 weeks. At Week 24, subjects in the placebo group crossed over to receive burosumab (total duration ≥96 weeks). Here, we report final long-term safety results from this trial. Most (119/134, 89%) subjects completed 96 weeks and received 1 mg/kg burosumab; protocol-specified dose reductions were required for 11/134 (8.2%) subjects to effectively manage hyperphosphatemia (all mild [Grade 1]). Mean (±SE) baseline serum phosphorus was 1.98 (±0.03) mg/dL and was 2.97 (±0.05) mg/dL at Week 94 (midpoint of dose interval). Mean (±SE) iPTH level was 96 (±3.8) pg/mL at baseline and progressively declined to 79 (±3.3) pg/mL at Week 96. Nephrocalcinosis score at Week 96 changed by 0 in 101 subjects, -1 in 9 subjects, +1 in 10 subjects (14 subjects not available). There were no meaningful changes in ectopic mineralization. There were no neutralizing antibodies. No treatment-emergent adverse events led to study or treatment withdrawal. Serum phosphorus was maintained with long-term burosumab treatment, with no evidence of loss of effect in adults with XLH. Burosumab dose reductions effectively managed mild hyperphosphatemia. Frequency, severity, and types of AEs reported were consistent with previous burosumab trials.
SAT-384 Identification of Heterozygous LRP5 Mutation and a TGFβ-1 Variant of Unknown Significance in a Patient with Hearing Loss, High Bone Mass, and Oropharyngeal Exostoses
Authors: Cheng Cheng , Avery James , Gottesman Gary , Mumm Steven , Whyte Michael P
Published: May 2020

Background: Manifestations of the high bone mass (HBM) disorders not only include strong bones, but also excessive bones causing cranial nerve palsies and oropharyngeal exostoses. Due to overlap of clinical phenotype in dense bone diseases, one or more distinct genes may be involved. Up-regulation in bone formation can result from gain of function mutation of the low-density lipoprotein receptor-related protein 5 (LRP5), which mediates activation of the canonical Wnt pathway via co-binding with the frizzled protein, but may also be a consequence of activating mutations in the transforming growth factor β1 (TGFβ-1) gene that associate with stimulated osteogenesis. Clinical Case: Here we report a 41 year-old woman referred for incidentally found dense bones on screening dual-energy X-ray absorptiometry (DXA) that led to subsequent revelation of several family members sharing similar histories including inability to float in water, strong bones on skeletal surgery, and presence of palatal exostoses. Her childhood history included mandibular pain developing at age 15 years due to bony overgrowth of her lower jaw requiring multiple drilling for removal. At age 33, she manifested trigeminal neuralgia initially responsive to medical management but eventually needed microvascular decompression for unremitting pain. Preoperative brain magnetic resonance imaging (MRI) noted significant hyperostosis of the skull as well as mild narrowing of internal auditory canals, for which auditory testing showing mild mixed hearing loss in her right ear. Skeletal survey revealed diffuse thickening of axial and appendicular skeleton with characteristic endosteal hyperostosis. DXA demonstrated Z scores of +8.3 and +5.3 in the lumbar spine and total hip, respectively. Torus palatinus was also identified on exam. Mutational analysis disclosed a heterozygous LRP5 missense mutation, c.844A>G, p.Met282Val, together with a variant of unknown significance in TGFβ-1 (c.887G>A, p.Arg296Gln) possibly linked to Camurati-Engelmann disease (progressive diaphyseal dysplasia). As transmission in both conditions follows an autosomal dominant pattern, multigenerational family history was elicited from patient that her mother, who underwent knee replacement in her 80’s, was described by the surgeon as “having bones of a 30-year old man,” and that her deceased maternal grandmother possibly had “thickened” bones. Half of patient’s 18 siblings reportedly also carry features suggestive of high bone mass phenotype. Genetic testing of family members is planned. Conclusion: While HBM disorders protect against fractures, it is important to recognize that these relatively benign conditions may present with neurological and oropharyngeal complications prompting the need for their surveillance and surgical precautions during orthopedic procedures.
SAT-202 Hypoglycemia Following Unilateral Pheochromocytoma Resection in the Immediate Post-Surgical Period
Authors: Ghosh Raisa , Dalwadi Sanketkumar , Luo Hongxiu
Published: May 2020

Introduction

Hypoglycemia in the immediate post-resection period of unilateral pheochromocytoma is a potential complication but not very well recognized.

Clinical Case

A 47 year old female with past medical history of Hypertension, coronary artery disease, Myocardial infarction, Depression, Systemic lupus erythematosus presented to the hospital initially for elective robotic assisted Left adrenalectomy. CT scan showed a big left adrenal mass with normal right adrenal gland. It was clinically diagnosed as Pheochromocytoma as outpatient by primary internist. Biochemical studies showed elevated serum metanephrines and normetanephrines, and urine normetanephrine.

Post-surgery (< 24 hours) patient had episodes of fasting hypoglycemia with blood glucose levels as low as 68 mg/dl, accompanied with neuroglycopenic symptoms like tremors, sweating and palpitations.

High dose ACTH stimulation test was performed. Serum cortisol levels were tested as 5.1, 11.7 and 14.4 mcg/dl within 0, 30 minutes and 60 minutes of Cosyntropin 250 mcg IV injection.

The patient was started on Prednisone 5 mg daily to prevent any further episodes, which was successful, and was stopped by the patient one week after discharge, without any more hypoglycemia episodes. Further endocrinology work up could not be done as the patient did not follow up.

Post-surgical pathology showed a 7x 5.5 x4 cm mass, which was confirmed as pheochromocytoma histopathologically and immunohistochemically by positive chromogranin, synaptophysin and BCl2 and negative for calretinin and S100.

Discussion and Conclusion

The etiology of hypoglycemia after resection of unilateral pheochromocytoma can be explained by impaired glucagon secretion and decreased gluconeogenesis due to the suppression from higher catecholamine levels in the blood pre-operatively. The second mechanism is rebound insulin secretion from the pancreas due to sudden withdrawal of catecholamines.

In our patient, the transient hypocortisolemia could be another reason. The lack of immunohistochemical evidence in post-surgical pathology report excluded cortisol- secreting tumor. Another rare situation, ACTH-secreting pheochromocytoma, has been reported but was not checked in the case.

In a word, hypoglycemia is common after surgical removal of unilateral pheochromocytoma. Careful monitoring of patients’ glucose level in immediate post-resection period is essential to prevent transient hypoglycemia

References

1.Akiba M, Kodaba T, Ito Y, Obara T, Fujimoto Y. Hypoglycemia induced by excessive rebound secretion of insulin after removal of pheochromocytoma. World J Surg; 14(3):317-24

2.Chen Y, Hodin RA, Pandolfi C, Ruan DT, McKenzie TJ. Hypoglycemia after resection of pheochromocytoma.Surgery;156(6): 1404-09
MON-446 Anaplastic Thyroid Cancer Presenting with Brain Metastasis: 17-Year Progression Free Survival
Authors: Howard Kathryn Kay , Lapkus Morta , Johnson Natalie , Nagar Sapna , Czako Peter
Published: May 2020

Background: Anaplastic Thyroid Cancer is the most aggressive thyroid cancer with a median survival of just five months. Long term survival has been reported in locally aggressive cases, but has yet to be reported in metastatic disease.

Case Information: A 34-year-old male presented with symptoms of dizziness, confusion, intermittent headaches, and erratic behavior for two weeks. CT of the head revealed a 1 cm ring enhancing lesion in the left parietal lobe with surrounding vasogenic edema. He was taken to the operating room for a left parietal craniotomy and a vascular, solid mass was removed. Initial pathology suggested papillary thyroid origin due to positive staining for thyroid transcription factor (TTF) and thyroglobulin (Tg). On exam, he had a palpable 3 cm mass in the right thyroid lobe with no associated adenopathy. He underwent thyroidectomy to optimize post-operative radioactive iodine treatment. Intraoperative frozen section revealed anaplastic thyroid cancer and final pathology revealed anaplastic carcinoma identical to the brain lesion. The tumor pathology showed extension through the thyroid capsule with lymphovascular invasion and one of two positive lymph nodes. Post-operatively, he underwent 15 cycles of whole brain radiation therapy for a total of 35 Gy. Two additional brain lesions were identified after thyroidectomy and a third was identified after whole brain radiation. He underwent stereotactic radiosurgery of these three lesions less than two months after thyroidectomy. The patient went on to receive modified mantle field irradiation (46 cycles, total 55.2 Gy) to the neck, thyroid bed, and the upper mediastinum. Additionally, he received chemotherapy with doxorubicin 6-8 weeks and temozolomide for 2 years. Thyroid uptake studies showed minimal residual iodine-avid disease and, in the setting of chemotherapy-induced cytopenias, radioactive iodine treatment was not administered. The patient has currently survived 17 years post-treatment. His persistent, but stable, brain lesions are being followed with serial imaging. He remains clinically and neurologically asymptomatic.

Conclusions: This is the first case presenting with long-term survival in a patient with metastatic anaplastic thyroid carcinoma. A multidisciplinary course with early aggressive surgical removal, adjuvant treatment with chemotherapy and radiation, and long term imaging follow up may be an acceptable treatment plan for stable patients.

References:

Smallridge RC, Ain KB, Asa SL, Bible KC, Brierley JD, Burman KD, et al. American Thyroid Association guidelines for management of patients with anaplastic thyroid cancer. Thyroid. 2012;22(11):1104-39.
MON-122 Introduction of an Ambulatory Curriculum in Endocrinology Diabetes and Metabolism for Internal Medicine Trainees
Authors: White Caitlin A , Cardillo Serena
Published: May 2020

Internal Medicine (IM) training programs are disproportionately weighted to inpatient learning opportunities. IM residents‘ exposure to outpatient internal medicine subspecialties, such as Endocrinology, Diabetes and Metabolism (EDM), is limited. This may contribute to gaps in medical knowledge in these content areas in spite of the frequent occurrence of EDM disorders. Further, reduced exposure during training may adversely impact interest in pursuing fellowship training in these fields, in spite of increased societal need.

In July 2015 the IM residency program at the University of Pennsylvania switched to a “6 + 2” training model. In this training module, trainees are grouped into four cohorts, each of which have 6 weeks of inpatient rotations, followed by 2 weeks of an ambulatory experience. This model allowed the introduction of an organized ambulatory curriculum during the 2-week outpatient blocks, which was named the Interactive Learning Module (ILM). This creates the opportunity to deliver a standardized curriculum to all residents. Through this module we coordinate an immersive experience in five distinct outpatient themes: General Internal Medicine, Infectious Disease, EDM, Nephrology, and Rheumatology. The EDM ILM is co-led by a core faculty member and senior endocrinology fellow with interest in pursuing a career in medical education.

During the EDM ILM, IM interns receive 12 hours of interactive didactics in high yield content areas including: Diabetes Workshop, Adrenal and Pituitary Diseases, Osteoporosis, Thyroid Diseases, Women’s Health, Calcium Disorders, Obesity and Endocrine Emergencies.

Interns are given 3-4 opportunities to work with an EDM faculty member in the outpatient setting. Interns are also asked to read and review three publications within the field, which are discussed as a group.

The EDM ILM has been consistently praised by IM interns, and feedback for the curriculum has been overwhelmingly positive. 97% of interns agreed the breadth of content was comprehensive and 94% agreed that the content was applicable to their delivery of ambulatory primary care. The quality of the teaching was rated high among 96% of interns. 89% reported improved understanding of EDM. Four years after the institution of the curriculum, we have not yet noted an increase in graduating IM residents choosing fellowship in EDM. However, all three of our IM residents who have matched into EDM fellowship over the past four years have chosen to stay at our institution.

Faculty have thrived with these teaching opportunities: their consistently high evaluations have been an important criterion for academic promotion.

Co-leading this course has been an important opportunity for senior EDM fellows to build expertise in medical education; three out of four participating fellows accepted academic positions with GME support.
SUN-004 Case Study: A 17-year-old Girl with HAIR-AN Syndrome, T2DM and Primary Amenorrhea
Authors: Alsaeed Abdulghani Habib , Harthi Hayat Al
Published: May 2020

Introduction: HAIR-AN syndrome is a sub-type of polycystic ovarian syndrome which consists of virilization, insulin resistance and acanthosis nigricans. It may be associated with menstrual irregularity, and hyperandrogenic features such as hirsutism and masculinization. Aim: We report an adolescent girl with HAIR-AN syndrome, T2DM, a very high testosterone level (male range) and primary amenorrhea Case report: A 17-year-old female who had been investigated by pediatric endocrinology since the age of 13 because of hyperpigmentation which was proven to be acanthosis nigricans on skin biopsy. The patient was found to have insulin resistance with initially normal glucose level. She has hirsutism and hypertrichosis. There is no similar condition in her family, she has three siblings all are well. She developed T2DM with at the age of 14. She was started on Metformin 2 gram daily and them pioglitazone 30 mg was added when she was 16 years. She never had menarche. The clinical examination revealed an adolescent girl with normal BP 106/68 mmHg, and BMI 19.6kg/m2. She scored 24 onFerriman-Gallwey hirsutism scoring system. She had severe acanthosis nigricans on both axillae. She also had back and upper limbs hyperpigmentation.Lab tests revealed normal thyroid function tests, prolactin, cortisol, DHEA-S, and 17 hydroxy progesterone. Fasting glucose 7.2, insulin 123 μU/ml (2.6-24.9), c-peptide 964, HbA1c 8.2%. Total testosterone 24.61 nmol/L (0.069-2.715), SHBG 184.9 nmol/L, and Free testosterone index 13.31 (0.51-6.53). Her LH 8.9 and FSH 4.7.Radiological investigations revealed polycystic ovaries on pelvic ultrasound. MRI abdomen showed normal adrenals, and mildly enlarged ovaries with peripherally located follicles consistent with polycystic ovarian syndrome. The patient was started in Diane-35 (cyproterone acetate and ethinyl estradiol) oral pills. She started to have menarche three months after using Diane-35. Her Total testosterone had dropped from 24.61 to 1.69 nmol/L (0.069-2.715), SHBG 579 nmol/L, and Free testosterone index 0.29 (0.51-6.53). She reported that the hirsutism is getting less than before starting the treatment.Conclusion: Primary amenorrhea might be a manifestation of in HAIR-AN syndrome due to sever hyperandrogenism. The management of such condition is challenging. In addition to controlling the metabolic parameters, combined oral pills with antiandrogen effect might be effective.
SAT-217 Paraganglioma in Two Unrelated Kinyarwanda-Speaking Patients in Anatomically Distinct Sites
Authors: Ejaz Sadia , Nandam Neeharika , Styner Maya
Published: May 2020

Introduction: Capable of generating excess catecholamines, untreated extra-adrenal paragangliomas (PGL) result in severe cardiovascular morbidity and mortality. Increasingly, a hereditary basis can be identified to underlie PGLs, though such data is largely absent in non-Caucasian populations.

Case 1: A 43 yr. old Kinyarwanda-speaking woman from DR Congo presented with left lower extremity edema and hypertension, with blood pressure of 154/86 while on spironolactone, HCTZ and furosemide. Ultrasound was negative for a DVT; abdominal CT revealed a 3 cm necrotic mass, inferior to the duodenum and abutting the IVC and aorta, as well as 2 bladder wall lesions. EUS-guided FNA revealed a keratin-negative neuroendocrine tumor. Urinary 24hr norepinephrine (NE) was high at 185 mcg [15–80]. Urinary 24hr normetanephrine (NM) was high at 1404 mcg [119-451; hypertensive <900]. MIBG scan confirmed avidity in the aortocaval mass. Despite lack of bladder uptake on MIBG, pathology similarly pointed to PGL. Surgery included excision of bladder, pelvic nodes, uterus, and aortocaval tumor. Post-op, urinary 24hr NE was 18 mcg and NM was 297 mcg, both normal. One year later, MIBG/SPECT and CT of the abdomen were negative for recurrence. A GeneDx panel of 12 PGL/PCC mutations was negative.

Case 2: An unrelated 41 yr. old Kinyarwanda-speaking woman from Rwanda, with prior history of preeclampsia and multiple miscarriages, presented with palpitations, headaches and hypertension. Echo showed a 4 cm mass posterior to the left atrium; the mass was18F-FDG PET-avid. Video-assisted thoracoscopy was performed yet the tumor’s vascularity precluded a biopsy. Biopsy of mediastinal mass after performing thoracotomy was consistent with PGL. Plasma NM was high at 7.1 nmol/l (<0.90), consistent with PGL and she underwent complete removal of the tumor. Testing for SDHB mutation was negative. Symptoms resolved and antihypertensives were discontinued. Follow-up plasma NM was 0.55 nmol/l 1-year post op and remained normal for six years of follow-up.

Discussion: Less than 10% of PGLs are known to involve the mediastinum or bladder (1). In familial PGL, the most commonly identified non-syndromic mutations involve SDHD, SDHAF2, SDHB, SDHD, SDHC, VHL, and MAX. Tumorigenesis in a sizable fraction of PGLs is not well understood.

Conclusion: We present two cases of extra-adrenal PGL, both exhibiting similar age, sex and geographic ancestry. Our cases raise questions that require active investigation regarding additional environmental and/ or genetic factors which might predispose to PGLs in uncommon anatomic sites.

References: (1) Erickson D et al. J Clin Endocrinol Metab, 2001 (2) Martins et al. Int J of Endocrinol, 2014
OR27-03 Duration of Testosterone-Induced Acyclicity Influences Corpora Lutea Formation and Stromal Changes in a Transgender Mouse Model
Authors: Kinnear Hadrian M , Hashim Prianka H , Rubenstein Gillian , Brunette Margaret A , Padmanabhan Vasantha , Shikanov Ariella , Moravek Molly B
Published: May 2020

The impact and reversibility of long-term gender-affirming testosterone (T) therapy on the reproductive axis of transgender men has not been well-established. Little is known about outcomes for transgender men interested in pausing T therapy to harvest oocytes or get pregnant. We previously established a translational mouse model to investigate T-induced acyclicity and ovarian perturbations. We hypothesized that the duration of T-induced acyclicity would impact the reversibility of cyclic and ovarian changes. To test this hypothesis, T-treated mice were assigned to two groups: (SHORT) 6 weeks of T therapy with immediate reversibility (1.5 mg T propionate pellet implant/removal, n = 5) and (LONG) 6 weeks of T therapy with a prolonged T washout phase (subcutaneous oil injections of T enanthate at 0.9 mg once weekly, n = 5). Control groups (placebo pellets n = 5, sesame oil vehicle injections n = 5) were run in parallel. Estrous cycles were monitored using daily vaginal cytology. Following cessation of T therapy, mice were sacrificed in diestrus after resumption of cyclicity for 4 cycles and ovarian histology examined. Data were analyzed in GraphPad Prism using Welch’s t-test or Mann-Whitney where appropriate. T therapy led to persistent diestrus within a week after T administration for all T-treated mice and none of the controls. The total duration of acyclicity was 6±1 weeks for the SHORT group, which was significantly shorter than the 11±2 weeks for the LONG group (mean ± s.d., p = 0.0079). With resumption of cyclicity, both the SHORT and LONG groups had a significantly lower percentage of days in estrus and higher percentage of days in metestrus as compared to their parallel age-matched controls. Ovarian histology for the SHORT group all showed regular corpora lutea and minimal stromal changes, however, 3/5 mice in the LONG group lacked corpora lutea and 4/5 revealed marked stromal cell hypertrophy. Similar stromal cell changes were not seen in control mice. In conclusion, the length of time of T-induced acyclicity appears to impact the development of stromal cell hypertrophy and formation of corpora lutea even after resumption of cyclicity with similar alterations to the estrous cycles. These findings may have clinical relevance for transgender men interested in fertility, based on duration of gender-affirming T therapy. Future work will aim to separate out the respective contributions of T exposure and acyclicity to the stromal phenotype.
SAT-367 A Case Series: Discovery of Parathyroid Carcinoma During Parathyroidectomy for Primary Hyperparathyroidism
Authors: Gazda Chellse , Abramowitz Jessica , Abreu Marconi
Published: May 2020

Introduction: Parathyroid carcinoma is rare and represents <1% of patients diagnosed with hyperparathyroidism (1).

Clinical Cases: We present two cases of incidentally diagnosed parathyroid carcinoma during parathyroidectomy for primary hyperparathyroidism.

A 69-year-old female was referred for hypercalcemia of 10.7 mg/dL (normal range 8.4-10.2). She had bone pain, fatigue, and mild depression. She was taking triamterene-hydrochlorothiazide, vitamin D 2000 international units daily, and 1 caltrate daily. Her thiazide diuretic was discontinued, and a repeat calcium was 9.5 mg/dL with a PTH of 79 pg/mL (normal range 14-64). Vitamin D and renal function were normal. A 24 hour urine calcium was elevated at 706 mg/24 hours (normal range 100-321). A bone density revealed osteopenia.

Based on the high urine calcium, a thyroid ultrasound was completed and showed an enlarged right parathyroid gland. Intraoperatively, the surgeon found a superior parathyroid gland adherent to the local soft tissues with recurrent laryngeal nerve entrapment. The right superior parathyroid and right thyroid lobe were resected. Pathology demonstrated an infiltrating parathyroid carcinoma. Postoperative monitoring has included: calcium, creatinine, PTH and neck ultrasound every six months without evidence of recurrence.

A 79-year-old man was referred for an approximate 18-month history of hypercalcemia. He had a prior kidney stone and constipation. He was not on calcium supplementations or thiazides. On lab testing calcium was 11.0 mg/dl with prior levels of 11.7 mg/dl. PTH was 246 pg/ml and vitamin D was 20.1 ng/ml (normal range 30-80). Imaging was obtained for parathyroid localization. A neck ultrasound and nuclear medicine study showed a right inferior parathyroid adenoma. A bone density revealed osteoporosis. Intraoperatively, the surgeon found a bilobed parathyroid extending intrathyroidal and adherent to the recurrent laryngeal nerve. The right inferior parathyroid, right thyroid lobe, and isthmus were resected. Pathology was consistent with parathyroid carcinoma. The patient had recurrent laryngeal nerve damage with persistent hoarseness postoperatively.

Clinical Lessons: Patients with parathyroid carcinoma typically present with symptomatic hypercalcemia with mean levels of 13.5-14 mg/dL and mean PTH values 8.7 times the upper limit of normal (1). Given the rarity of the condition, there are no guidelines for surveillance (1). These cases highlight atypical, mild, and early presentations of an unusual and typically aggressive disease and serve as an example of how to monitor for recurrence.

Reference: 1- Stack BC, Bodenner DL. Medical and Surgical Treatment of Parathyroid Diseases An Evidence-Based Approach. Switzerland: Springer, Cham; 2017.http://link.springer.com/chapter/10.10

07/978-3-319-26794-4_31#enumeration. Accessed November 3, 2019.
SUN-063 Usefulness of a LHRH Test with Low Dose of Triptorelin Pamoate in the Diagnosis of Precocious Puberty in Girls
Authors: Llano Juan Pablo , Llano Mauricio Javier , Katherine Pineda , Picon Teresa Ortiz , Laverde Gladys , Castro Sonia
Published: May 2020

Objective : to determine diagnosis value of a new LHRH test for diagnosis or precocious puberty (PP) correlated with clinical and paraclinical pubertal changes. Methods:79 girls under age 10 years old were referred to our laboratory with diagnosis of precocious puberty went thought a physical exam and bone age /pelvic US review to classify them clinically in probably PP or unlikely PP. A LHRH test was performed with measurement of at least 3 times including baseline measurement of gonadotrophins (LH / FSH) and estradiol 0-24 hours after a dose of 100 mcg/m2 (max 100 mcg) of Triptorelin Pamoate. The results for LH greater than 8 uUI / L and estradiol of 80 pg / ml were considered positive - Results: From 79 girls, mean age 8,02 years old (+/- 2,2) 41 were classified as likely PP (group 1) and 38 unikely PP (group 2) On group 1, 39 patients (95,1 %) had results of LH above 8 uUI/L. In this group, 5 patients (12.1%) had estradiol results below 80 pg / ml. Of the positive test, 3 patients (7,6%) %) had LH peak time 60 min, 4 patients (10,2%) had LH peak time 90 min, 31 (79,4%) had LH peak at time 180 minutes. In group 2, 3 patients (7,89 %) had values of estradiol above 80 pg/ml and 1 patient had values above 8 uUI/ml. Sensitivity was 95,1% specificity 97,4%, predicted positive value 97,5% and negative predicted value 95%. Conclusion: Low dose LHRH test for precocious puberty with 100 mcg/m2 of Pamoate Triptorelin is a useful tool in the diagnosis of precocious puberty in girls, with high sensitivity and specificity and with lower cost than other diagnostic tools.
SUN-115 Distinct DNA Methylation Signature in Neuroendocrine Tumors of Different Primary Sites and Hereditary Predisposition
Authors: Tirosh Amit , Killian Jonathan Keith , David Petersen , Zhu Yuelin Jack , Blau Jenny , Nilubol Naris , Patel Dhaval T , Agarwal Sunita Kishore , Weinstein Lee Scott , Meltzer Paul , Kebebew Electron
Published: May 2020

Objective

There is scant data of the genome-wide methylome alterations in neuroendocrine tumors (NET). Thus, the goal of this study was to compare the DNA methylation signature of NETs with respect to various primary sites and inherited genetic predisposition syndromes including von Hippel-Lindau (VHL) and multiple endocrine neoplasia type 1 (MEN1).

Methods

Genome-wide DNA methylation analysis of 96 NETs (primary and metastatic) was performed by using the Illumina Infinium EPIC Array. Principal component analysis (PCA) and unsupervised clustering analyses were performed to identify distinct methylome signatures. The methylation status of genetic drivers such as APC were assessed by primary site.

Results

A total of 835,424 CpGs methylation sites were quantified. Hypermethylated CpG sites were detected more frequently in sporadic vs. MEN1-related vs. VHL-related NETs, respectively (p < 0.001 for all comparisons), while hypomethylated CpGs sites were more common in VHL-related NETs vs. sporadic and MEN1-related NETs (p<0.001 for both comparisons).

Small-intestinal NETs (SINETs) had the most differences at CpGs with the highest number of hyper- and hypomethylated CpG sites, followed by duodenal NETs (DNETs) and pancreatic NETs (PNETs, p<0.001 for all comparisons). PCA showed distinct clustering of SINETs and three NETs of unknown primary. Sporadic, VHL-related and MEN1-related PNETs formed distinct groups on PCA. VHL-related NETs clustered separately showing pronounced CpG hypomethylation, while sporadic and MEN1-related NETs clustered together showing relative CpG hypermethylation. In a subgroup analysis, MEN1-related SINETs, DNETs and gastric NETs had distinct methylome signatures, respectively, with complete separation by PCA and unsupervised hierarchical clustering. Furthermore, we found CpG hypermethylation in the APC (adenomatous polyposis coli) gene, specifically in the 1A promoter, with higher methylation levels in gastric- and DNETs vs. SINETs, PNETs and NETs of unknown primary (p < 0.001 for all comparisons).

Conclusion

Various primary NET sites and genetically predisposed MEN1-related NETs have distinct DNA CpG methylation signatures. The methylome signatures identified in this study may be useful for non-invasive molecular characterization of NETs, through DNA methylation profiling of biopsy samples or circulating tumor DNA.
SAT-291 SIX3 Is Essential for Hypothalamic and Pituitary Development
Authors: Bando Hironori , Brinkmeier Michelle L , Castinetti Frederic , Gergics Peter , Mortensen Amanda H , Ozel Ayse Bilge , Ma Qianyi , Li Jun Z , Brue Thierry , Camper Sally A
Published: May 2020

The genetic basis for congenital hypopituitarism and related disorders is beginning to emerge, and over causal 30 genes have been identified, including six in the SHH signaling pathway. Mutations in some of these genes can also cause holoprosencephaly (HPE) or septo-optic dysplasia. SIX3 is a homeodomain protein expressed in the developing brain, pituitary gland, and eye. It activates SHH signaling and represses BMP signaling. Heterozygous mutations in SIX3 cause variable HPE in humans and mice. We identified a rare, heterozygous variant in SIX3 in two children with neonatal GH and TSH deficiency and stalk interruption, p.P74R. Using transient transfection in 3T3 cells, we demonstrated that the variant reduced the ability of SIX3 to transactivate the SHH enhancer and promoter of FOXG1, suggesting that the variant could be deleterious. To understand the role of SIX3 in hypothalamic and pituitary development we used Nkx2.1-cre and Prop1-cre to delete Six3 in mice. The Nkx2.1-cre, Six3flox/flox embryos had no evidence of infundibulum evagination or expression of Fgf10 or Tcf7l2 at e11.5. The oral ectoderm invaginated in mutants, but no definitive Rathke’s pouch formed. There was no evidence of Lhx3 expression and only trace amounts of Pitx1, indicating that pituitary induction failed due to the lack of Six3 in the developing hypothalamus. Similarly, disruption of Six3 expression in Rathke’s pouch using Prop1-cre ablated pituitary development. Together, these data reveal essential roles of Six3 in both the neural and oral ectoderm for hypothalamic and pituitary development, respectively. Heterozygous loss of function variants in SIX3 could be a contributor to multiple pituitary hormone deficiencies in children, especially if there are associated craniofacial abnormalities.
MON-449 Thyroid Microcarcinoma Histopathology Relevance
Authors: Sandoval Letícia A M , Diniz Bruna Dellatorre , Coelho Juliano , Jesus Gabriel de , Azevedo Monalisa F , Vianna Leonora M S
Published: May 2020

INTRODUCTION: Thyroid carcinoma is the most common endocrine neoplasia. The predominant histological variant is the papillary subtype. Tumors with 1 centimeter diameter or less are defined as papillary thyroid microcarcinoma (PTMC). The clinical diagnosis of PTMC is challenging. The evaluation of the gland includes mostly image methods and fine-needle aspiration (FNA). Nevertheless, the sensibility of these techniques, when compared to total thyroid histology, is less than desired. AIM OF THE STUDY: Recognize the real prevalence of papillary thyroid microcarcinoma (PTMC) based on histological evaluation of the total gland among a group of adults in Brasilia, Brazil, and compare the data with the clinical suspicion of PTMC established by FNA and ultrasonography (USG). PATIENTS AND METHODS: Retrospective cohort study based on medical records of 76 patients who underwent surgical thyroidectomy treatment for several types of thyroid diseases at the University Hospital of Brasilia - Brazil, from 2005 to 2015. A full inclusion of the surgical specimen was made and stained with hematoxylin and eosin. All of the preparations were evaluated by an expert pathologist. The histopathological report was compared to the previous clinical diagnosis, which was based on FNA and USG of the gland. In addition, the exams results were stratified by the Bethesda criteria. RESULTS: Seventy-six individuals with the histopathology diagnosis of PTMC were included (68 were females). A total of 65 FNA and 57 USG results were evaluated, 6 patients had only the histopathologic diagnosis of PTMC. A total of 52 patients had both USG and FNA of the thyroid. All of the patients that had USG records had at least one thyroid nodule, 52,6% of them had multiple nodules. Regarding the FNA results, only 9,2% were classified as Bethesda I; 21,5% as Bethesda II; 7,7% Bethesda III; 7,7% Bethesda IV; 10,8% Bethesda V; 43,1% Bethesda VI. At this cohort, 19 patients were false negatives. The sensibility of FNA for diagnosis of PTMC was 67,79%. CONCLUSION: Despite careful evaluation of the patients, there might have false negatives results. Total thyroid total inclusion of surgical specimen is not a routine diagnostic tool, making less invasive new diagnosis methods desirable.
SAT-225 A Rare Cause of Cardiogenic Shock
Authors: Wahab Azni Lihawa Abdul
Published: May 2020

Background: Rare cases of pheochromocytoma are associated with stress induced Takotsubo cardiomyopathy, occurring in approximately 3% of secreting pheoochromocytoma and paraganglioma (PPGL). Case: A 39-year-old female with a history of hypertension and anxiety disorder, re-presented to the ED within 24 hours with headache, vomiting and severe hypertension (BP 205/70 mmHg). She rapidly developed acute pulmonary oedema and cardiogenic shock. ECG revealed dynamic ST-segment abnormalities and troponin rise peaked at 38,000 ng/L (N < 16ng/L). The coronary angiography excluded any coronary artery lesion. Echocardiography revealed severe global hypokinesis with an ejection fraction of 5% and evidence of apical ballooning. A bedside abdominal ultrasound revealed 7cm left adrenal mass confirmed by computed tomography (CT). Investigations revealed a metanephrine level of > 13,760 pmol/L (N < 900 pmol/L) and normetanephrine of > 60,780 pmol/L (N < 500 pmol/L). Her clinical status deteriorated despite on diuretics, inotropes and mechanical ventilation. Extra-corporeal membrane oxygenation (ECMO) was implanted. Alpha adrenergic blockades were initiated followed by beta blockers, during which control of blood pressure was achieved. Her haemodynamic status improved and ECMO removed 8 days post-implantation. Two weeks after discharge from hospital, she underwent uncomplicated open adrenalectomy; histologic examination of the mass confirmed the pheochromocytoma diagnosis. Reference 1. Gagnon N, Mansour S, Bitton Y et al. Takotsubo-like cardiomyopathy in a large cohort of patients with pheoochromocytoma and paraganglioma. Endocrine Practice.2017;10: 1178-1192
MON-456 Clinical Profile of Thyroid Papillary Microcarcinoma in Brazil
Authors: Diniz Bruna Dellatorre , Sandoval Letícia Assad Maia , Coelho Juliano Ferreira , de Jesus Gabriel Caetano , Azevedo Monalisa Ferreira , Vianna Leonora M S
Published: May 2020

INTRODUCTION: The thyroid papillary microcarcinoma (TPMC) is defined as a tumor ≤ 1 centimeter. This variant of thyroid papillary carcinoma is generally characterized by slow progression and minimal invasion. Although the TPMC subtype usually has good prognosis, itʼs early recognition has clinical relevance because it may present with regional lymph node metastasis, as well as increased risk of recurrence. AIM OF THE STUDY: The aim of the study is to identify the epidemiologic profile of the population diagnosed with TPMC, as well as the signs and symptoms observed in these patients. This study intends to guide early clinical suspicion of thyroid tumors; in order to propose assertive forms of management and prevention of undesirable outcomes. PATIENTS AND METHODS: Retrospective cohort study based on medical records of patients diagnosed with TPMC at University Hospital of Brasilia-Brasil, from 1999 to 2017. The clinical aspects analysed were: gender; race; age of the patient when the diagnosis was made; symptoms reported by the patients regarding the pathology and comorbidities. RESULTS: Fifty-eight patients who underwent thyroidectomy for variable thyroid criteria were included in this study. 87,93% were women, (seven fold higher female prevalence of the TPMC). Mean age of diagnosis was 42, 94 ± 11,4. Regarding the race, the majority of the patients had self-entitled as mixed race, which corresponds to 39,65% of the sample. Symptoms reported included dysphagia (29,31%), dyspnea (17,24%) and feeling of neck compression (13,79%). Even though these aspects of the clinical approach are significant diagnosis tools, only 26,5% of the patients in this sample attested those kinds of signs/symptoms. Considering that actual clinical manifestation is relatively rare, total inclusion of the anatomic specimen is useful in this unsettling scenarios. Among the most commonly reported comorbidities, benign thyroid affections were the most prominent, such as multinodular goiter and hypothyroidism. CONCLUSION: Analysis of the data endorses that the TPMC does not have a well defined clinic presentation. Nonetheless, dysphagia is the most reported symptom. Analysis of the data pointed to a higher prevalence of the pathology in women in their 40s, which can be used as parameter of investigation on patients that have symptoms that cannot be explained by other pathologies. Although TPMC usually presents with good prognosis, the non incidental groups may present with aggressive behavior and should be treated as papillary thyroid carcinoma. Despite that, fine needle aspiration and ultrassonografy are the preferable methods in the evaluation of thyroid tumors.
MON-237 Primary Pituitary Lymphoma - an Unusual Guest in the Sella!
Authors: Harjanto Sumitro , Lim Dawn Shao Ting
Published: May 2020

Background

Primary Pituitary Lymphoma (PPL) is a rare differential diagnosis for a sellar / suprasellar lesion. Less than 40 cases have been reported.

Case presentation

A 75-year old Chinese lady with known subclinical hypothyroidism presented with 3-day history of dull frontal headache, giddiness and diplopia. Incomplete left cranial nerve (CN) III palsy was noted with no other neurological deficit or hemodynamic instability. MRI brain and pituitary showed a T1- and T2 isointense, 2.0 x 1.1 x 1.3 cm enhancing mass arising from the left sellar region, extending to the left sphenoid and cavernous sinuses, displacing the pituitary stalk towards the right, with no optic chiasm compression. There was no imaging evidence of apoplexy.

Evaluation of anterior pituitary hormones revealed hypocortisolism (peak cortisol post 1mcg Synacthen 344 nmol/L, ACTH 3.5 ng/L [10 - 60]), subclinical hypothyroidism (free T4 9.6 pmol/L [8.8 - 14.4], TSH 7.19 mU/L [0.65 - 3.70]), normal prolactin 7.4 ug/L [5.0-27.7], mildly elevated IGF-1 193.7 mcg/L [67.0 - 189.0] with normal GH 1.0 ng/ml, and elevated FSH appropriate for menopause. Glucocorticoid replacement was started.

Though the clinical presentation was not typical of a pituitary macroadenoma, in view of symptomatic improvement and neurological stability, she was conservatively managed with plans for early repeat imaging outpatient.

Patient was readmitted 1 month later for headache and decreased left-sided visual acuity. A complete CN III palsy, and new CN II, IV and VI deficits were noted (orbital apex syndrome). Repeat MRI showed increase in the size of the sellar lesion to 2.6 x 2.1 x 1.3 cm, surrounding the optic nerve and with left cavernous and sphenoid sinus invasion. Again, there was no suggestion of apoplexy. Biopsy of the lesion was performed, and histology was consistent with Diffuse Large B-cell Lymphoma and Grade 3A Follicular Lymphoma with high proliferative index (Ki67 70%). Immunohistochemistry excluded carcinoma, meningioma and pituitary tumor. PET-CT and bone marrow aspirate confirmed the diagnosis of PPL without metastasis.

After 3 cycles of chemotherapy (Methotrexate, Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone), significant decrease in the size of the lesion was noted on repeat MRI. Only mild asymmetric soft tissue thickening remained noticeable over the left sella and cavernous sinus. Cranial nerve deficits had since completely resolved. Glucocorticoid replacement was continued in the meantime while awaiting the completion of chemotherapy.

Conclusion

PPL may present in a similar manner as pituitary apoplexy. Absence of typical imaging characteristics of apoplexy in patients with rapid symptom progression and CN involvement should alert clinicians to consider alternative diagnosis including aggressive neoplastic, inflammatory and infective lesions.