bluuebunny/crossref_metadata_2025_split huggingface dataset:
OR29-04 TGFβ Regulates Bone Perilacunar/Canalicular Remodeling in a Sexually Dimorphic Manner
Authors: Dole Neha , Alliston Tamara 
Published: May 2020

Abstract
Sexual dimorphism in the material properties of bone extracellular matrix (ECM) and geometry, which are parameters of bone quality have been recognized (Alswat, 2017; Nieves et al., 2005). However, the molecular mechanisms responsible for dimorphic bone quality remain unclear, limiting our ability to therapeutically target fragility, which is determined by bone quality. Recently, using male mice, we found that systemic or osteocyte-intrinsic inhibition of TGFβ signaling (TβRIIocy-/-), suppresses perilacunar/canalicular remodeling (PLR) and compromises bone quality (Dole et al., 2017). Since we previously demonstrated that female bone mass is more sensitive to TGFβ (Mohammad et al., 2009), we hypothesized that loss of osteocytic TGFβ in females will lead to more severe deterioration of PLR and bone quality.
Analysis of female bones, however, surprisingly revealed sexual dimorphism in the TGFβ regulation of osteocyte function. While the male TβRIIocy-/- mice demonstrated reduced trabecular bone mass and repression in expression of requisite PLR genes, including matrix metalloproteinases (Mmp2, Mmp13, and Mmp14), cathepsin K (Ctsk), and tartrate-resistant acid phosphatase (Acp5/TRAP) (Qing et al., 2012), the female TβRIIocy-/- bones were intact. With absence of osteocytic TGFβ signaling, the canaliculi of male TβRIIocy-/- osteocytes were truncated and a severe deterioration of lacuno-canalicular network (LCN) was observed. Unlike the male TβRIIocy-/- mice that exhibited poor bone quality, female TβRIIocy-/- bones were completely protected from bone quality defects and macromechanical bone fragility. Thus, TGFβ-dependent regulation PLR and bone quality is sexually dimorphic.
Since, lactation is a potent PLR agonist, we also evaluated the lactation-induced PLR response of TβRIIocy-/- female mice. Compared to WT, lactation-induced bone loss and upregulation of PLR genes was significantly attenuated in the TβRIIocy-/- female mice. Lactation-mediated increases in osteocyte lacunar volume were suppressed in TβRIIocy-/- bones as well. This mitigation in PLR of lactating TβRIIocy-/- mice was analogous to that observed in mice with osteocyte-specific ablation of parathyroid hormone type I receptor (PTHR1) (Qing et al., 2012). Remarkably, lactation-inducible PTHR1 expression was also diminished in TβRIIocy-/- osteocytes. Therefore, osteocyte-intrinsic TGFβ signaling is critical for the maximal induction of PLR during lactation, and TGFβ is an upstream regulator of PTHR1-dependent activation of osteocytic PLR. Indeed, we also found sexual dimorphism in the regulation of osteocytic PTHR1 expression by TGFβ, such that male, but not female, TβRIIocy-/- mice had reduced PTHR1 compared to WT.
In summary, we identify a novel PTH-dependent mechanism that protects female bone against the severe bone fragility that results from suppressed TGFβ signaling in osteocytes.
SAT-LB76 Impact of Glucocorticoid Cosecretion in Primary Aldosteronism on Thyroid Autoantibody Titers During the Course of Disease
Authors: Handgriff Laura , Adolf Christian , Heinrich Daniel , Braun Leah , Ladurner Roland , Ricke Jens , Seidensticker Max , Bidlingmaier Martin , Reincke Martin 
Published: May 2020

Abstract
Context: Excess aldosterone is associated with the increased risk of cardio- and cerebrovascular events as well as metabolic comorbidities not only due to its hypertensive effect but also due to its proinflammatory action. Autonomous cortisol secretion (ACS) in the setting of primary aldosteronism (PA) is known to worsen cardiovascular outcome and potentially exhibit immunosuppressive effects.The aim of this study was to determine the impact of ACS status in patients with PA on kinetics of thyroid autoantibodies (anti-TPO, anti-TG) pre and post therapy initiation.
Patients and Methods: 97 PA patients (43 with unilateral, 54 with bilateral PA) from the database of the German Conn’s Registry were included. Anti-TPO and anti-TG levels were measured pre and 6 to 12 months post therapeutic intervention. Patients were assessed for ACS according to their 24h urinary cortisol excretion, late night salivary cortisol and low-dose dexamethason suppression test.
Results: Abnormal test results in line with ACS were identified in 74.2% of patients. Significant increases in anti-TPO levels were observed in adrenalectomized patients with at least one abnormal test (p = 0.049), adrenalectomized patients with at least two pathological ACS tests (p = 0.015) and adrenalectomized patients with pathologic dexamethasone suppression tests (p = 0.018). No antibody increases were observed in unilateral PA patients without ACS and in patients with bilateral PA receiving mineralocorticoid antagonist therapy.
Conclusion: ACS appears to be a relevant factor in PA affecting thyroid autoimmune disease. The biochemical and clinical course maybe be exacerbated after resolution of hypercortisolism by adrenalectomy in PA.
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

Abstract
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 &gt;200 ng/ml and 16,610 ng/ml after dilution (male &lt;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

Abstract
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

Abstract
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

Abstract
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 (&gt;0.05)
MON-LB46 Thyrotropinoma and Pregnancy
Authors: Namboodiri Divya , Ng Hui Yi , Davidson Andrew , Champion Bernard , Preda Veronica Angela 
Published: May 2020

Abstract
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

Abstract
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

Abstract
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.