bluuebunny/crossref_metadata_2025 huggingface dataset:
MON-LB49 Atypical Presentation for a 5.5-cm Macroprolactinoma: Unilateral Visual Loss and Only Partial Hypopituitarism; Asymptomatic Hypogonadism
Authors: panjawatanan panadeekarn , Sekar Vijaykumar , Hughes Joseph
Published: May 2020

Background: Macroprolactinoma is an uncommon pituitary tumor which presents mainly in males. The usual presentation is headache, bitemporal hemianopia, and signs/symptoms of hypogonadism. Ours is a case report of 5.5 –cm macroprolactinoma presented with unilateral optic nerve atrophy and asymptomatic hypogonadism.

Clinical case: A 50-year-old male with past medical history of type 2 diabetes mellitus and essential hypertension presented with progressive blurred vision of the left eye for 6 months. He was able to perceive color but had difficulty reading. There was occasional headache with left periorbital pain. He was seen by an optometrist and was found to have left optic disc atrophy with suspicion of glaucoma. Subsequent visual field test showed entire left and right superior temporal loss. MRI of the pituitary showed 5.5 x 5.6 x 5.3 cm enhancing mass centered in the sellar/suprasellar region. There was significant mass effect with compression of the optic chiasm, temporal lobe and brainstem. The patient reported mood changes, normal libido, but loss of morning erection. He has family history of pituitary macroadenoma with left optic nerve compression. On physical examination, there were left visual field defect and decreased visual acuity. There were no signs of Cushing’s syndrome, hypothyroidism, acromegaly, or hypogonadism. Laboratory tests showed prolactin of >200 ng/ml and 16,610 ng/ml after dilution (male <13), total testosterone 92 ng/dl (240-950) and free testosterone 1.20 mg/dl (4.26-16.40). Surprisingly, other pituitary hormones were normal: AM cortisol 20.3 µg/dl (6-27), GH 0.24 ng/ml (0.01-0.97), IGF-1 58 ng/ml (40-259), FSH 4 IU/l (1-18), LH 3 IU/l (1.3-9.6), TSH 1.38 µIU/ml (0.34-3), and free T4 0.8 ng/dl (0.6-1.6). The patient underwent surgery with partial resection. Pathology revealed lactotroph adenoma. Postoperative prolactin level was 11,900 ng/ml. Medical treatment with cabergoline 0.25 mg twice weekly has been started.

Conclusion: Even though profoundly hypogonadal by labs, the presentation for this 5.5-cm prolactinoma was acute vision loss. The highly elevated prolactin level correlates with the size of macroadenoma. The typical presentation of local mass effect is bitemporal hemianopia, but in our case the patient presented with unilateral optic nerve atrophy. Despite a 5.5-cm lesion, there is partial hypopituitarism; hypogonadism. Based on the size, one would have expected panhypopituitarism. Given a family history of macroadenoma, there might be genetic predisposition. Molecular testing is planned.
MON-285 Clinical Characteristics of Six Patients with Infundibulo-Neurohypophysitis
Authors: Nao Keiko , Fukuda Izumi , Nagamine Tomoko , Hada Mikiko , Kitajima Yuko , Ono Mayo , Shibayama Masayuki , Kobayashi Shunsuke , Tahara Shigeyuki , Sugihara Hitoshi
Published: May 2020

Background: To date, precise pathological studies and the improvement of imaging studies have made it clear that a part of idiopathic diabetes insipidus (DI) could be lymphocytic infundibulo-neurohypophysitis (LINH) caused by autoimmune abnormality. Recently, anti-rabphilin (RPH) 3A antibody was identified and expecting as a useful diagnostic marker of LINH*. Objective: Here, we present the clinical course of 6 patients with central DI (CDI) who were thought to be due to LINH and compared with results of serum anti- RPH3A antibody in each. Patients and methods: Clinical characteristics of 6 patients with CDI regarded as due to LINH (M/F; 3/3, age range; 26–67 years old) were investigated. Clinical course, anterior pituitary functions, MRI findings, complications and results of serum anti-RPH3A antibody were retrospectively analyzed by medical charts. Pituitary biopsy was conducted in 2 patients. Results: On the T1-weighted MR image, one patient (# 3: 67 F) had only a lacking of high signal intensity in the posterior lobe. Thickening of pituitary stalk was seen in other 5 patients. Anti-RPH3A antibody was studied in those 5 patients and positive in 3 and negative in 2. Anterior pituitary function was preserved in 2 patients with positive anti-RPH3A antibody. One patient (#1: 26 F) was diagnosed as LINH by changes in MRI findings over time and the other patient (#5: 41 M) by pituitary biopsy. Impaired anterior pituitary function was observed in 2 of 6 patients. One patient (# 2: 32 F) suffered from CDI since late pregnancy. She had a history of massive bleeding at delivery. Postpartum evaluation revealed that besides CDI, she had TSH, ACTH and GH deficiency. Anti-RPH3A antibody was positive in this patient. A mild low GH response (not severe GHD) to GHRP-2 test was seen in another patient (#4: 37 M). Pituitary biopsy of this patient revealed that infiltration of lymphocytes distributed not only posterior but also anterior pituitary. Anti-RPH3A antibody was negative in this patient. As a complication, Type 2 DM in 2 patients, Graves’ disease and cerebral infarction in one each were observed. Conclusion: Anti-RPH3A antibody was useful as a non-invasive diagnostic marker for LINH. However, among patients who were inferred to have LINH, the clinical course, a degree of extension and severity of inflammation in the pituitary region varied from case to case, suggesting that the clinical features of LINH might be diverse. *: JCEM 100: E 946, 2015
SAT-LB24 Association of Expression of Somatostatin Receptor 2 Subtype in Non-Pituitary Neuroendocrine Tumors With Response to Treatment With Somatostatin Analogues
Authors: Siddiqui Abdullah , Hosseini Alireza , Marandi Roghayeh , Salehian Behrouz , Chang Sue
Published: May 2020

Background: The WHO classification of non-pituitary neuroendocrine tumors (NETs) includes grading (Ki67 proliferation index and mitosis index) and staging, and has been shown to be associated with outcome in this patient population. Neuroendocrine tumors show different somatostatin receptor (SSTR) subtypes expression, but their role has not been considered in tumor progression and prognosis. We hypothesize patients with non-pituitary NET, whose tumor tissues have higher specific SSTR2 expression patterns will experience better outcomes when treated with Somatostatin Analogues (SSA) compared to those with lower or absent SSTR2 expression. Methods and patients: City of Hope patients with non-pituitary NET who received SSA (Octreotide and Lanreotide) for over 1 year as treatment. The progression free survival was based on imaging studies (MRI, CAT scan of index tumor) on RECIST criteria, and expression of SSTR2 on the tumor obtained by surgery at the time of diagnosis. Immunohistochemical staining with a monoclonal antibody to SSTR2 performed at core pathology lab at City of Hope. H-scoring (intensity of immunostaining and percent of SSTR2 expression) was performed by one pathologist, and divided into four categories of 0-4. Pearson Chi-square test was used to assess the correlation between the SSTR2 score and 1-year progression. Outcome Measures: The effect of SSA therapy on 1 year progression-free survival (PFS), among patients with high intensity and percent of SSTR2 expression on the resected tumor tissue was compared to those with low or absent SSTR2 expression. Patient population: Of the 297 patients identified with non-pituitary neuroendocrine tumor, 70 patients satisfied the inclusion criteria and a total of 52 patients had data that was completely available for analysis. Results: Mean age of study subjects was 61+1.8 years. 26 were female and 26 were male. The primary sites for NET were: pancreas 17, jejunum 16, ileum 9; paraganglioma and pheochromocytomas 3, lung and thymus 3, gastric 2, and medullary thyroid carcinoma 1. The one-year progression was not significantly different among those with low and absent SSTR2 compared to high expression of SSTR2. Step wise analysis based on the scoring of the SSRT2 did not show significant 1 year progression. Age was not associated with PFS. However, the need for additional therapy (liver embolization, surgical resection) was signigicantly reduced amongst patients with presence of SSTR2.

Conclusion: In this preliminary study there was no significant association between SSTR2 expression and Progression free survival, however the need for additional therapy in patients on somatostatin analogues were reduced among subjects with presence of SSTR2 expression
SAT-LB5 Prevalence of Hypogonadism in Young Obese Males
Authors: Halappanavar Anup , Pakhetra Rajiv
Published: May 2020

Ageing, obesity, and chronic illness are major factors affecting serum testosterone (T) levels in men.The magnitude of the impact of ageing on serum T levels is well established, for obesity this is less clear. Severe obesity may lead to isolated hypogonadotropic hypogonadism (IHH). Several explanations have been offered to clarify the presence of reduced T levels in obese men. One relates to the technique that is generally employed to measure serum androgen levels, i.e. measurement of total testosterone (TT) instead of free testosterone (FT). TT represents the sum of FT and T bound to albumin and sex hormone binding globulin (SHBG). A profound reduction in SHBG level is commonly found in obese men, and this is a major factor causing a decrease in TT.Measurement of free testosterone levels may provide a more accurate assessment of androgen status than the (usually preferred) measurement of total testosterone in situations where SHBG levels are outside the reference range. However, reference ranges for free testosterone levels are not well established, especially in older men, and some have argued that the measurement of free testosterone levels merely reintroduces age in a covert form. This is a cross sectional study to estimate prevalence of hypogonadism in young obese males. In this study 147 young obese men participated, of which we confirmed low total testosterone (TT) levels in 35.37% of subjects with a p value of 0.06. Since only Total Testosterone was measured for categorizing subjects with or without hypogonadism, Free Testosterone measurement would be a better indicator for the diagnosis of hypogonadism as in cases where the total testosterone is borderline-low or when SHBG concentrations are abnormal. As such, the study is valuable in the context of the ongoing controversy as to whether testosterone treatment should be limited to men with classical hypogonadism, or be considered for appropriately selected men with functional hypogonadism as well. The principal findings are in general agreement with existing literature reporting correlation between levels of testosterone, body mass index and constitutional symptoms. However, this has never been shown before in context of Indian population. The present study was carried out at Armed Forces Medical College and Command Hospital, Pune between October 2017 to August 2019.We studied to see if there is association between testosterone levels and BMI. In our study we found no statistical association as the p value was 0.26 (>0.05)
MON-LB46 Thyrotropinoma and Pregnancy
Authors: Namboodiri Divya , Ng Hui Yi , Davidson Andrew , Champion Bernard , Preda Veronica Angela
Published: May 2020

Thyrotropinomas (TSHomas) are rare pituitary tumours, comprising 1-2% of all pituitary adenomas. Thyrotropinomas in pregnancy are exceedingly rare and management of these in pregnancy can be challenging due to the potential for maternal and foetal harm. We report the case of a 35 year old woman who was found to have a pituitary macroadenoma on imaging whilst being evaluated for headaches and sinusitis. She had felt more stressed than usual but no other overt thyrotoxic symptoms. There were no visual field abnormalities or symptoms to suggest other endocrine hypo or hypersecretion. Pituitary MRI revealed a macroadenoma and biochemistry demonstrated raised free T4 24 pmol/L and free T3 6.8 pmol/L and inappropriately elevated TSH of 4.2 mIU/L, in keeping with secondary hyperthyroidism. She was scheduled for transsphenoidal (TSA) pituitary surgery, however on review she had naturally fallen pregnant. After a multi-disciplinary discussion, it was decided that surgery should be deferred and close observation be undertaken under the care of a multidisciplinary team. During the first half of pregnancy she suffered hyperemesis gravidarum with ongoing thyrotoxicosis but declined carbimazole. Her visual fields were normal throughout pregnancy. She delivered vaginally at 38 weeks, weight 3.395kg and had no malformations. Post birth was complicated by post-partum haemorrhage requiring multiple blood transfusions and intensive care. One week later after recovering, she was able to commence breastfeeding. She went on to TSA at 6months post partum with complete tumour resection. This case demonstrates the complexity of managing TSHomas in pregnancy and the potential cross reactivity of the early hCG rises with the already elevated TSH levels, likely exacerbating her hyperemesis gravidarum.
SUN-LB77 Incidental Anaplastic Thyroid Carcinoma: An Uncommon Entity
Authors: Padmanaban Preethi , Nylen Eric
Published: May 2020

Background:

Anaplastic thyroid cancer is an aggressive thyroid malignancy with a median survival of 3 to 9 months. It is rare and represents 2-5% of all thyroid tumors. Even more uncommonly in about 2%–6% of all ATC cases, it is identified as a small, incidental finding after surgical resection of a predominantly non-anaplastic tumor.

Clinical Case:

We report a case of 67 year old Caucasian male who presented with history of hoarseness of voice for one month. Fine needle aspiration biopsy of right dominant thyroid nodule revealed papillary thyroid cancer. Pre-operative imaging was negative for involvement of surrounding structures or distant metastasis. He underwent total thyroidectomy and final pathology revealed Anaplastic carcinoma arising in papillary carcinoma measuring 3.6cm in greatest dimension. Undifferentiated (Anaplastic) Carcinoma comprised approximately 5% of the tumor. Areas from anaplastic and papillary tumor were dissected separately. DNA separated from these two specimens were analyzed by PCR amplification and both were positive for BRAF mutation. External beam radiation and radioactive iodine therapy were administered after surgery. Given absence of invasion or metastasis adjuvant therapy was not initiated. His positron emission tomography, computed tomography imaging and whole-body scan has been negative for residual/ recurrent or metastatic disease. He remains disease free at 18 months after diagnosis.

Discussion:

Anaplastic thyroid cancer is a rare but highly aggressive tumor. In most cases it develops from a pre-existing well differentiated thyroid cancer. ATC incidence typically peaks at the 6-7th decade of life, predominantly in women. The median survival is between 3 to 9 months with less than 10% of patients alive 3 years after the time of diagnosis. Because of its aggressive behavior, the American Joint Committee on Cancer Staging Manual classifies all Anaplastic thyroid cancer Stage IV tumors. Surgery, chemotherapy and radiotherapy are the conventional therapeutic strategies performed in the attempt to improve survival.

However, incidental anaplastic thyroid cancer is rare variant with very few reported cases. American Thyroid Association (ATA) Guidelines for Management of Patients with ATC do not include specific recommendations for this form of ATC. There is no consensus to define best treatment approach as to whether intrathyroidal incidentally detected ATC is best treated with surgery alone, surgery followed by radiotherapy, or surgery followed by chemotherapy plus radiation therapy.

Conclusion:

Based on review of our case as well as outcomes of similar reported cases, prognosis is favorable for incidental anaplastic thyroid cancer. Hopefully, with more data from similar cases to demonstrate difference in disease free survival we should be able to define the role of chemotherapy and adjuvant therapy for incidental ATC better. The question remains open, as to whether incidental anaplastic thyroid cancer should be considered as a separate entity from aggressive form of ATC.
SUN-LB134 Androgen Receptor Phosphorylated at Serine 815 in Mouse and Human Prostates
Authors: Yokobori Kosuke , Negishi Masahiko
Published: May 2020

Androgen receptor (AR) regulates male sexual development and maintenance. AR forms a homodimer in the cytoplasm and monomerizes following hormonal activation, translocating to the nucleus in Cos-1 cells (Shizu et al. Scientific reports. 2019). Utilizing Ser815 of AR, the conserved phosphorylation residue within the ligand binding domains of steroid hormone receptors (NR3C), whether and how this phosphorylation regulates AR functions was investigated. While, like AR WT, a phosphomimic AR S815D mutant formed a homodimer in the cytoplasm, unlike the WT, this mutant remained as a homodimer in the cytoplasm even after hormone treatment. Apparently, Ser815 phosphorylation disabled AR’s capability to monomerize and nuclear translocate in Cos-1 cells. A phospho-Ser815 peptide antibody was used to detect phosphorylation of endogenous AR in mouse as well as human prostates. Immunohistochemistry showed phosphorylation present in both the cytoplasm and nucleus. Mouse prostates were cell fractionated in cell membrane, mitochondria, endoplasmic reticulum (ER) and cytosolic fractions for subsequent Western blot analysis. While AR was found in all of these fractions, phosphorylated AR was only detected in the ER and cytosolic fractions. A cDNA microarray analysis of PC-3 cells with ectopic expression of AR S815D suggested that phosphorylated AR may regulate ER stress.
SAT-LB13 Clinical Utility of 21-Deoxycortisol in Congenital Adrenal Hyperplasia
Authors: Curtin Bill , Chandler Donald Walt , Holmquist Brett
Published: May 2020

Introduction Congenital Adrenal Hyperplasia (CAH) is most often caused by mutation of the 21-hydroxylase gene (CYP21), which results in underproduction of cortisol with overproduction of precursor steroids and their metabolites by the adrenal glands. Historically the most common biomarker used for detecting CAH in pediatric patients is 17-Hydroxyprogesterone (17OHP). Another less commonly used biomarker for 21-Hydroxylase deficiency is 21-deoxycortisol (21DOF), which increases from very low levels in normal patients to high levels in affected patients as 17OHP rises to very high levels. In this study we performed retrospective analysis of serum 21DOF concentration in specimens that had been genotyped for mutations in the CYP21A2 gene, or had been submitted to our laboratory for provocative adrenocorticotropin (ACTH / Cosyntropin) stimulation testing. Methods: Biochemical testing for 21DOF concentration was measured by LC-MS/MS. Briefly, a TX-4 HPLC system (Thermo-Fisher) with Agilent® 1100 pumps (Agilent Technologies, Inc.) and a Sciex® 5000 (Danaher) triple quadrupole mass spectrometer in positive mode atmospheric pressure chemical ionization (APCI) was used for detection in Multiple Reaction Monitoring (MRM) mode. Genetic testing was performed using the CAHDetx test, which detects the 12 most common small mutations and large gene deletions/conversions in CYP21A2. Genetic Correlations: 21DOF was quantifiable (above the LLOQ of the assay) in 4% (n=24/600) of specimens where no mutation was detected. 21-DOF was quantifiable in 42% (122/292) of specimens with 21-hydroxylase enzyme mutations as determined by the CAHDetx test. Those mutations included In2G, I172N, V281L and others. Some mutations such as Q318X did not result in a detectable increase in 21-deoxycortisol. ACTH Stimulation Response: 21-deoxycortisol was below the quantitation limit in both the baseline and stimulated samples in ~35% (52/148) of submitted samples. The 21-deoxycortisol was quantifiable in only the stimulation sample in ~45% (65/148) of ACTH stimulation submitted, and was quantifiable in both baseline and stimulated samples in the remaining ~20% (30/148) of ACTH stimulation pairings. The extent of 21-deoxycortisol increase ranged from 1.2-fold to 116-fold with a median 14-fold increase. Clinical Significance: The use of 21-deoxycortisol may be beneficial in reducing the rate of false positives in CAH diagnosis when used in concert with other steroid hormones, and may eventually reduce the need for provocative testing to confirm CAH diagnosis.
SUN-LB86 Case Report: Killian-Jamieson Diverticulum Presenting as a Thyroid Nodule
Authors: Ragunanthan Branavan , Salem James K
Published: May 2020

Introduction: Multitudinous endocrine and non-endocrine disorders cause thyroid nodules, thus in an effort to diagnostically exclude various thyroid malignancies, endocrinologists are obligated to perform a thorough investigative workup. A Killian-Jamieson diverticulum (KJD) is a rare form of cervical esophageal diverticulum that results from anterolateral, mucosal protrusion below the cricopharyngeal muscle. Due to the vicinity of the thyroid gland, this lesion can mistakenly present as a thyroid nodule.

Case Description:A 71-year-old female with a past medical history of invasive ductal carcinoma clinical stage 1A, T1a/bN0M0 grade 1 ER+PR+HER2- with treatment composed of radioactive seed localized partial mastectomy and sentinel lymph node biopsy, whole breast radiotherapy, and anastrozole therapy was referred to an endocrinology clinic for evaluation of a left 1.0 cm thyroid nodule incidentally discovered on a CT without contrast scan conducted for bronchitis. Immediate pre-office TSH level collected was normal at 3.28 mIU/L and thyroid ultrasound (US) demonstrated a left lower lobe 2.0 cm AP x 1.7 cm transverse x 2.1cm cephalocaudad heterogenous, solid, well-circumscribed, microcalcified, TI-RADS 4 nodule. In the endocrinology office, the patient’s only symptoms were hoarseness, an improving cough, and neck stiffness. The blood pressure collected was 128/74. Office physical exam demonstrated thyromegaly without nodules. The patient met criteria for a fine-needle aspiration (FNA). A first FNA performed was an uncomplicated biopsy of the lesion, but demonstrated insufficient cellularity on pathology. A second FNA performed was also an uncomplicated biopsy of the lesion, and demonstrated squamous cells, debris material suggestive of vegetable material, and rare benign follicular epithelial cells. Fluoroscopic esophagram was performed subsequently demonstrating a moderate left-sided KJD.

Discussion: While literature exists documenting the etiology, pathogenesis, and medical/surgical treatments for KJDs, only a few case reports exist reporting the resemblance KJDs have with thyroid nodules. This case report hopes to illustrate non-endocrinology pathologies that can mimic thyroid nodules while encouraging current healthcare practitioners to recognize the existence of these conditions so that wasteful diagnostic tests or invasive procedures can be avoided.
SAT-LB102 Obesity Is Associated With Reduced Expression of the Anorexigenic Neuropeptide Nucleobindin-2/Nesfatin-1 in the Human Nucleus of the Solitary Tract
Authors: Psilopanagioti Aristea , Makrygianni Maria , Nikou Sofia , Logotheti Souzana , Chartoumpekis Dionysios , Papadaki Helen
Published: May 2020

Introduction: Feeding is a complex behavior coordinated by interrelated forebrain, hypothalamic, and brainstem neuronal networks. Brainstem neurons constitute an important input for the neural circuitry integrating nutrient signals to control ingestive behavior. Orexigenic and anorexigenic neuropeptides act in concert to regulate energy balance. Data from animal models suggest that altered neuropeptidergic expression contributes to obesity. Nucleobindin-2/nesfatin-1, an appetite-suppressing neuropeptide and negative regulator of body weight, is reduced in the hypothalamus of mouse obesity models. In obese and overweight humans, we have recently reported decreased nucleobindin-2/nesfatin-1 immunoexpression in the lateral hypothalamic area, which is critically involved in appetite and metabolic regulation and has extensive connections with brainstem feeding circuits. Objective: The present study explored nucleobindin-2/nesfatin-1 localization pattern as well as the association between nucleobindin-2/nesfatin-1 protein expression and body weight in human brainstem nuclei. Methods: Sections of 20 human brainstems (13 males, 7 females; 8 normal weight, 6 overweight, 6 obese) were examined by means of immunohistochemistry and double immunofluorescence labeling. Results: Nucleobindin-2/nesfatin-1 widespread distribution was observed in various brainstem areas, including nuclei with well-defined roles in energy homeostasis and in autonomic and behavioral processes, such as the nucleus of the solitary tract, dorsal motor nucleus of vagus, area postrema, inferior olive, raphe nuclei, reticular formation, locus coeruleus, parabrachial nuclei, and pontine nuclei, and in Purkinje cells of the cerebellum. Interestingly, nucleobindin-2/nesfatin-1 immunofluorescence signal extensively localized in neuronal subpopulations expressing neuropeptide Y and cocaine- and amphetamine-regulated transcript (peptides known to exert potent actions on food intake and energy balance) in nucleus of the solitary tract, inferior olive, locus coeruleus, and dorsal raphe nucleus. Of note, nucleobindin-2/nesfatin-1 immunoexpression was significantly lower in obese than normal weight subjects in the nucleus of the solitary tract (p<0.05). Conclusions: These data provide for the first time neuroanatomical support for the potential role of nucleobindin-2/nesfatin-1 in human brainstem circuits controlling energy homeostasis. In nucleus of the solitary tract, a key integrator of nutrient state signals and a neural substrate of food reward-related processes, altered neurochemistry such as nucleobindin-2/nesfatin-1 deficiency may contribute to dysregulation of homeostatic and/or hedonic feeding behavior and ultimately to obesity.
SAT-LB18 A Randomized Controlled Trial of Vosoritide in Children With Achondroplasia
Authors: Savarirayan Ravi , Tofts Louise , Irving Melita , Wilcox William , Bacino Carlos A , Hoover-Fong Julie , Font Rosendo Ullot , Harmatz Paul , Rutsch Frank , Bober Michael B , Polgreen Lynda E , Ginebreda Ignacio , Mohnike Klaus , Charrow Joel , Hoernschmeyer Daniel , Ozono Keiichi , Alanay Yasemin , Arundel Paul , Kagami Shoji , Yasui Natsuo , White Klane , Saal Howard M , Leiva-Gea Antonio , Luna-Gonzáles Felipe , Mochizuki Hiroshi , Basel Donald , Porco Dania M , Jayaram Kala , Fisheleva Elena , Huntsman-Labed Alice , Day Jonathan
Published: May 2020

Background: Achondroplasia is a disorder caused by specific mutations in the gene encoding the fibroblast growth factor receptor 3 (FGFR3) protein. Open-label, phase 2 trials in children with achondroplasia showed that administration of vosoritide, an analogue of C-natriuretic peptide, resulted in sustained increases in annualized growth velocity. Methods: This international, randomized, double-blind, phase 3 trial compared once-daily subcutaneous administration of vosoritide, at a dose of 15 μg per kg of body weight, with placebo in children with achondroplasia aged 5 to <18 years. Eligible patients had participated, for at least 6 months, in an observational growth study in order to calculate their baseline annualized growth velocity. The primary efficacy endpoint was the change from baseline in annualized growth velocity at week 52 of treatment. The primary analysis of the change from baseline in annualized growth velocity was performed using an ANCOVA model. Results: A total of 121 patients were randomized, with 60 assigned to receive vosoritide and 61 to receive placebo. A total of 119 patients completed the 52-week trial. The adjusted mean difference in annualized growth velocity between patients administered vosoritide and those administered placebo was 1.57 cm per year in favor of vosoritide (95% CI: [1.22, 1.93], two-sided p-value <0.001). A total of 119 patients experienced at least one adverse event (vosoritide group, 59 [98.3%], placebo group, 60 [98.4%]). Conclusions: Daily, subcutaneous administration of vosoritide to children with achondroplasia resulted in a significant increase in mean annualized growth velocity and similar incidence of adverse events compared to placebo.
SAT-LB114 Metabolic Profile Changes in Patients With Diabetes Mellitus After Hurricane Maria: A Retrospective Case Series
Authors: Burgos Nydia , Agosto-Mujica Anardi A , Pérez-Cardona Cynthia M , González-Rodríguez Loida A
Published: May 2020

Background: Hurricane María struck Puerto Rico on September 20, 2017. We compared the metabolic profile of patients with diabetes before and after the hurricane.

Methods: A retrospective review of 265 patients with diabetes evaluated at our Endocrinology Clinics 6 months before (March 20, 2017- September 19, 2017) and after the hurricane (October 2, 2017 – September 30, 2018) was performed to compare changes in A1C, fasting blood glucose, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, systolic blood pressure, diastolic blood pressure, body weight, and body mass index.

Results: A total of 374 patients with diabetes were evaluated before the hurricane, of which 71% returned to the clinics after the hurricane. Although there was a significant decrease in body weight, there were no significant changes in the metabolic profile of patients or groups defined by gender, age or diabetes type.

Conclusions: No significant changes were seen in the metabolic profiles of patients with diabetes before and after the hurricane, which might be partially explained by their weight loss. These results differ from similar studies that show a negative health impact on diabetes management after a natural disaster. However, 29% of these patients did not return for evaluation, which may underestimate the full impact of the hurricane. Factors such as death, financial difficulties, lack of transportation, emigration, and access to health care may contribute to this rate of no-return. Further studies that assess these factors are needed.

Acknowledgment: This project is supported by Award Number Grants 5S21MD000242 and 5S21MD000138 from the NCMHD-NIH.
SAT-LB301 Hyperaldosteronism From Adrenal Adenoma in a Young Patient
Authors: Maldonado Francisco Javier Lopez , León Angel Alfonso Mayorga , Gonzalez Alondra Rodriguez , Milán Eduardo Rafael León , Chinchillas Carlos Alfonso Morales , Alvarado Antonio Cruz , Guardado Jesus Alan , Castañeda Jose Fernando Montiel , Bañales Itzel Denisse Ramirez , Peterson Jorge Leo
Published: May 2020

Introduction Primary aldosteronism (PA) is the most common cause of secondary hypertension (HTN) that is often underdiagnosed. Patients with PA have higher cardiovascular morbidity and mortality than age- and sex- matched patients with essential HTN and the same degree of blood pressure elevation. We present a case of a 17-year old male with primary hyperaldosteronism.

Case Report 17-year-old male with no past medical history presented to the emergency department referring bitemporal cephalea, pain in left arm, dyspnea, heart palpitations, a blood pressure (BP) of 220/110 mmHg and a serum potassium of 1.5mmol/L (n. 3.5-5). The patient was admitted to the hospital for better handling of his BP, potassium repositions, monitoring and further management. During hospitalization he referred leg cramps, asthenia, adynamia, nausea, cephalea, and blurred vision. Physical examination demonstrated decreased muscle strength, jugular regurgitation II and hyperreflexia on lower extremities. Thyroid and pulmonary examinations were normal. BP continued elevated despite the concurrent use of 3 antihypertensive drug classes (ARA2, BB, CCB), referred to endocrinologist after being diagnosed with resistant hypertension suspecting of a primary hyperaldosteronism. Lab tests were run obtaining a plasma aldosterone concentration 44ng/dl (n. 4-31), plasma active renin (PRA) 0.05ng/ml/hr (n. 0.2-1.6), aldosterone/PAR ratio 880 (<25 normal). Suprarenal CT scan revealed right suprarenal lesion 2.2 x 2.1 cm, round appearance, hypodense (14 HU) compatible with an adenoma. He underwent unilateral adrenalectomy. Histopathological report from excised adrenal tumor was compatible with a benign adenoma. Patient was discharged with a regularized blood pressure without antihypertensives and normokalemic. No clinical symptoms were reported in follow-up.

ConclusionPrimary aldosteronism (PA) is the most common form of secondary hypertension (HTN) with an estimated prevalence of 4% of hypertensive patients in primary care and around 10% of referred patients. PA is characterized by hypertension, hypokalemia, suppressed plasma renin and increased aldosterone excretion. Aldosterone producing adenomas (APAS) account for around 40% and idiopathic hyperaldosteronism for around 60% of PA cases. The most sensitive screening test for PA is the aldosterone-to-renin ratio. After case confirmation, all patients with PA should undergo adrenal CT as the initial study. Unilateral laparoscopic adrenalectomy is the preferential treatment for patients with APAs, and bilateral hyperplasia should be treated with mineralocorticoid antagonist.
SUN-LB49 Chronic Exposure to Predator Odour Stress Disrupts LH Pulsatility and Delays Puberty While Activation of Amygdala Kisspeptin Advances Puberty
Authors: Ivanova Deyana , Li Xiao Feng , McIntyre Caitlin , O’Byrne Kevin Thomas
Published: May 2020

Chronic exposure to predator odour stress disrupts LH pulsatility and delays puberty whileactivation of amygdala kisspeptin advances pubertyDeyana Ivanova MS1, Xiao Feng Li MD/PhD1, Caitlin Mcintyre BS1, and Kevin O’Byrne PhD1; 1Department of Women and Children’s Health, Faculty of Life Science and Medicine, King’sCollege London, UKPost-traumatic stress (PTSD) is associated with altered pubertal timing and predator odourexposure is a classical rodent PTSD model. Kisspeptin neurones in the posterodorsal sub-nucleus of the medial amygdala (MePD) are thought to modulate pubertal timing and anxiety.We test the hypothesis that psychosocial stress, processed by the MePD, is relayed to theGnRH pulse generator to delay puberty. Female mice were exposed to predator odour, 2,4,5-Trimethylthiazole (TMT), for 14 days from postnatal day (pnd) 21 and pubertal onset wasmonitored. Anxiety was tested using the Elevated Plus Maze (EPM), Light/Dark Box (LDB) andsocial interaction (SI). The effect of TMT on luteinizing hormone (LH) pulses was measured,on pnd 26 and 29. Additionally, kisspeptin-cre mice were bilaterally injected with hM3Dq-DREADD AAV in the MePD at pnd 13. From pnd 21, CNO was administered via drinking waterfor 14 days and pubertal onset was monitored. The TMT-mice showed a significant delay offirst estrous (FE; TMT: 38.1 ± 0.5 vs. control: 33.3 ± 0.6 days; p<0.0001; n=10-14) withoutaffecting body weight (BW; p=0.9; n=10-14). TMT-mice spent less time exploring the openarm of the EPM (TMT: 13 ± 3 vs. control: 32 ± 5 secs; p<0.05; n=10-14) and in the lightcompartment of the LDB (TMT: 117 ± 12 vs. control: 162 ± 15 secs; p<0.05; n=10-14), whileengaging less in SI (TMT: 26.8 ± 2.8 vs. control: 47.7 ± 8.8 secs; p<0.05; n=10-14) during TMT-exposure compared to controls. The TMT group exhibited a reduction in LH pulse frequencyon pnd 26 (TMT: 0.2 ± 0.2 vs. control: 1.7 ± 0.4 pulses/2 h; p<0.05; n=6-9) and 29 (TMT: 0.6 ±0.2 vs. control: 2.6 ± 0.4 pulses/2 h; p<0.001; n=6-9). DREADD activation of kisspeptinneurones in the MePD advances FE (DREADD: 30 ± 1 vs. control 34.67 ± 0.82 days; p<0.05;n=6) without affecting BW (p=0.9; n=6). Predator odour stress reduces GnRH pulse generatorfrequency, delays puberty and enhances anxiety-like behaviour, while selective chemogeneticactivation of kisspeptin neurones in the MePD advances puberty in female mice.
MON-LB68 Dual Pathologic Mutations in SLC12A1 and GALNT3 Lead to Impaired Mineral Homeostasis
Authors: Shi Melody , Page Laura
Published: May 2020

Background

Loss-of-function mutations in SLC12A and GALNT3 individually have effects on calcium and phosphorus metabolism but the combined effect has not been described.Case: A 1-week-old female infant presented with hyponatremia (129 mmol/L), hypokalemia (3.1 mmol/L) and metabolic alkalosis (29 mmol/L). Pregnancy was complicated by polyhydramnios requiring several amnioreduction procedures and parental consanguinity. Urine studies showed sodium, potassium, and chloride loss with hyperreninemia (490 ng/ml/h) and hyperaldosteronism (210 ng/dL). Genetic testing revealed a homozygous mutation in SLC12A1 leading to a diagnosis of severe antenatal Bartter syndrome. The patient was started on sodium and potassium supplements with improvement in electrolytes. A few weeks later, she was found to have mild hypercalcemia (11.1 mg/dL) with elevated PTH (102 pg/mL) and high 1,25(OH)2D levels (224 pg/mL) suggestive of primary hyperparathyroidism. While hypercalcemia and hyperparathyroidism have been described in Bartter syndrome, the infant was also noted to have hyperphosphatemia (8.5 mg/dL), which was not expected. Further review of her chromosomal microarray showed a homozygous mutation in GALNT3, an enzyme that normally protects fibroblast growth factor 23 (FGF23) from proteolytic cleavage through glycosylation. Low FGF23 would subsequently result in hyperphosphatemia as well as elevated 1,25(OH)2D, and could contribute to elevated PTH. She was started on Calcilo formula and sevelamer with improvements in her hypercalcemia and hyperphosphatemia.

Conclusions: To our knowledge, this is the first patient known to have mutations in both SLC12A1 and GALNT3 leading to derangements in mineral homeostasis. Patients with Bartter syndrome typically have hypercalciuria and increased risk of nephrocalcinosis, variable serum calcium levels, and possibly decreased serum phosphate with decreased urine phosphate reabsorption. In contrast, GALNT3 mutations result in hyperphosphatemia and reduced phosphaturia. By approximately 1 month of age, our patient developed hypercalcemia, hyperphosphatemia and elevated PTH. While hypercalcemic, hypercalciuric hyperparathyroidism has been described in Bartter syndrome and could be the driver of increased PTH in our patient, the GALNT3 mutation leading to low FGF23 must also be considered. Thus, patients with dual mutations in SLC12A1 and GALNT3 require close monitoring as symptomatic electrolyte imbalances may present at variable times.
SUN-LB14 Trans and Non-Binary Youth Accessing Gender Affirming Medical Care in Canada: New Research From the Trans Youth CAN!
Authors: Mokashi Arati , Lawson Margaret L , Gotovac Sandra , Bauer Greta R
Published: May 2020

Little is known about youth accessing gender-affirming care in Canada. Trans Youth CAN! is a prospective 24-month cohort study of youth referred for puberty suppression/gender affirming hormones, examining pathways to care, medical, social, and family outcomes. Eligible participants were pubertal, aged <16, naïve to puberty blockers/cross-sex hormones, and recruited at their first endocrine appointment, along with their parent/caregiver (P/C), from clinics in 10 Canadian cities. Baseline sociodemographic, health, and family data were collected from interviewer-assisted youth surveys, self-completed (P/C) surveys, and clinic medical records. Youth data included day-to-day discrimination (InDI-D), depression, (MDS), psychological distress (Kessler-6), gender distress (TYC-GDS), gender positivity (TYC-GPS), and P/C support (self-report by youth and P/C). Pathways to accessing gender-affirming medical care included wait times, prior providers seen, length of time seeking care, and age accessing care. P/C data included parental conflict and consideration/involvement in conversion therapy. Baseline data were collected from 09/2017 to 06/2019 on 174 youth and 160 P/Cs. 78.7% of youth were assigned female at birth. 8.1% of those assigned female at birth, and 8.3% of those assigned male at birth, reported a primarily non-binary identity. 25.7% of youth had one or more immigrant P/Cs; 20.5% were Indigenous; and 15.5% were from rural areas. In the past year, 52.9% of youth reported engaging in self-harm, 32.6% had suicidal ideation, and 13.8% had attempted suicide. Bivariate correlations showed that longer wait times were associated with being older when youth first spoke to someone about their gender, seeing more provider types before first endocrine appointment, P/C report of time spent seeking hormone treatment, and lifetime discrimination. Youth with higher current P/C support were younger at their first appointment. Older youth at first appointment had also been older when they first met with someone outside the family about their gender, and had spent a longer time seeking hormone treatment. These youth also had higher gender distress, lower gender positivity, higher psychological distress, higher depression, experienced higher lifetime and past-year discrimination, and had lower average P/C support. P/Cs reported 8.8% of youth had participated in conversion therapy, while an additional 9.7% had considered having their youth participate. Current or past parental conflict about youths’ gender identity was reported by 40.1%, but was not associated with age of accessing care, types of providers seen, length of time accessing care, or age at first appointment. This research will help fill gaps in knowledge for health care providers about youth accessing gender affirming medical care, enhancing gender-affirming care and support for these youth and their parents/families.
SAT-LB101 Loss of GLP-2R Signaling Activates Hepatic Stellate Cells and Exacerbates Diet-Induced Steatohepatitis in Mice
Authors: Fuchs Shai Z , Yusta Bernardo , Baggio Laurie , Varin Elodie , Matthews Dianne , Drucker Daniel J
Published: May 2020

A GLP-2 analogue is used in individuals with intestinal failure at risk for liver disease, yet the hepatic actions of GLP-2 are not understood. Treatment of high fat diet (HFD)-fed mice with GLP-2 did not modify the development of hepatosteatosis or hepatic inflammation. In contrast, Glp2r-/- mice exhibited increased hepatic lipid accumulation, deterioration in glucose tolerance, and upregulation of biomarkers of hepatic inflammation. Both mouse and human liver expressed the canonical GLP-2R, and hepatic Glp2r expression was upregulated in mice with hepatosteatosis. Cell fractionation localized the Glp2r to hepatic stellate cells (HSC), and markers of HSC activation and fibrosis were increased in livers from Glp2r-/- mice. Moreover, GLP-2 directly modulated gene expression in isolated HSCs ex vivo. Taken together, these findings define an essential role for the GLP-2R in hepatic adaptation to nutrient excess and unveil a gut hormone-HSC axis, linking GLP-2R signaling to control of hepatic stellate cell activation.
MON-LB042 A Rare Case of Adrenocortical Carcinoma Arising From Ectopic Adrenal Tissue in the Mesentery
Authors: George Gemy M , Thumma Soumya P , Menon Lakshmi P
Published: May 2020

Background: ACTH independent Cushing’s syndrome usually arises from benign or malignant tumors of the adrenal gland. Ectopic adrenal tissue can undergo malignant transformation resulting in the development of adrenocortical carcinoma (ACC) with normal adrenal glands. We present a unique case of ACTH independent Cushing’s syndrome from a cortisol and androgen producing ACC arising from the mesentery.

Clinical Case: A 72-year-old woman presented with a 6-month history of progressive weakness, lower extremity edema, worsening hypertension and uncontrolled DM. She had moon facies, hirsutism, multiple bruises, and proximal muscle weakness. Labs revealed hypokalemia (2.6 mmol/L, N 3.5 -5.1 nmol/L), elevated random cortisol (51.3 mcg/dL, Nl- 5-23), suppressed ACTH (<1 pg/mL, Nl-7.2-63.3) abnormal 8 mg dexamethasone suppression test (58.1 mcg/dL, N <1.8 mcg/dL), elevated DHEAS (538mcg/dL, N 10-90 mcg/dL), elevated testosterone (590.2 ng/dL, N <75 ng/dL) and elevated 11-deoxycortisol (4650 ng/dL N-<32 ng/dL). 24 hour urinary free cortisol was 2810mcg/mL (<45mcg/dL). MRI of pituitary was normal. CT scan of abdomen/pelvis showed normal bilateral adrenal glands and innumerable enhancing masses throughout the abdomen with the largest mass near the distal ileum and cecum. Biopsy of right lower abdominal mass revealed adrenocortical morphology with immunohistochemical staining positive for inhibin, synaptophysin and calretinin. Ki-67 index was 10-15%, suggestive of low-grade adrenocortical carcinoma. A CT scan done one and half years prior noted a 4.4 cm soft tissue mass in the right lower mesentery supporting origin of the tumor from the mesentery. Hypercortisolism was controlled with Metyrapone 250 mg BID. Mitotane 1000 mg bid was initiated but patient developed peritoneal carcinomatosis within 1 month. Conclusions: Our case is remarkable for the development of a metastatic ACC from an ectopic adrenal tissue with normal bilateral adrenal glands. Ectopic ACC is very rare with only a handful of cases reported in the literature. This is the first reported case of ACC arising from the mesentery. Ectopic adrenal tissue can be found close to the adrenal glands, along the path from gonads to adrenal glands or in association with the gonads. In the setting of ACTH independent Cushing’s syndrome with normal adrenal glands, physicians should direct their search to a functioning ectopic adrenocortical tissue. Concomitant DHEAS secretion suggests ectopic ACC. If surgery is not an option due to metastatic disease, a multidisciplinary approach should be adopted to control tumor growth and associated symptoms. In such cases, control of the hypercortisolemia can be achieved with adrenolytic medications such as Metyrapone, Ketoconazole or Mitotane. Adjuvant chemotherapy (Mitotane and combination of cytotoxic drugs) might be considered for metastatic ACC treatment.
SAT-LB51 The Unique Etiology and Management of a Third Cranial Nerve Palsy
Authors: Magar Maria
Published: May 2020

Background: Cranial nerve palsies (CNP) in association with a hypophyseal process can be uni/bilateral, single, multiple, with or without visual deficits and pain. It is reported 14-30% of pituitary tumors lead to a palsy. Often the acute cause of palsy is apoplexy (1) but other rare etiologies exist such as abscess or prolactinoma (2, 3).

Clinical Case: A 40 year old woman with no PMH presented to the ED for acute on chronic headaches. Two days prior she started having blurry vision in her R eye. The headache improved with medications and she was sent home. Two days later she returned with new symptoms of the R eye deviating laterally and down, associated ptosis and a 6 mm nonreactive pupil. A stat MRI brain was obtained for her new CN III palsy, showing a 1.4 cm sellar mass with suprasellar extension. Further history revealed that two months prior her regular menses had stopped. Labs were obtained that included a prolactin 127 (nl 4.8-23.3); fT4 1.2 (nl .93-1.7); IGF1 129 (nl 52-328); 9 am cortisol 16.6 (nl 4-22); FSH 5.5 (nl 3.5-12.5); LH 3.8 (nl 2.4-12.6). Neurosurgery (NSGY) was consulted, recommending a trial of medical therapy since her visual fields were intact. Endocrine then advised cabergoline 0.5 mg twice weekly. In NSGY clinic ten days later, her prolactin was 0.2 but her symptoms remained the same. One month later, she was seen in Neuro-ophthalmology clinic where it was noted that her diplopia had subjectively resolved. Her eye exam was documented as normal except for sluggish pupils.

Conclusion: CNP are more common in larger pituitary tumors and often associated with panhypopituitarism and necrosis. About 90% of cases resolve by one year after pituitary surgery. Although our patient had a tumor that was slightly larger than 1 cm, she did not need hormonal replacement, did not have hemorrhage/necrosis, and her symptoms resolved with a dopamine agonist. There is one other case in the literature of medically treated macroprolactinoma with resolution of CN III palsy (3).

References: (1) Hage R, et al. Third, Fourth, and Sixth Cranial Nerve Palsies in Pituitary Apoplexy. World Neurosurgery. 2016; 94:447-452.(2) Wang L, et al. Pituitary abscess resulting in isolated abducens palsy. Journal of the Formosan Medical Association. 2016;115:134-135.(3) Harries A, et al. Resolution of third nerve palsy following treatment of prolactinoma with cabergoline. Acta Neurochir. 2010; 152:1741-1743.