bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-LB48 Increased Mortality in Acromegaly Is Mainly Due to Vascular and Respiratory Disease and Is Normalized by Control of Growth Hormone Hypersecretion
Authors: Orme Stephen Michael , McNally Richard , Peter James , plummer Zoe , Archer Natasha , Wass John A H , Trainer Peter James 
Published: May 2020

Abstract
Introduction: Epidemiological studies in acromegaly have shown increased mortality rates from vascular, respiratory and malignant diseases. We aimed to use a large national cohort of subjects with acromegaly to determine mortality rates due to the above disease categories and to determine whether suppressing post treatment growth hormone (GH) levels to &lt; 1 ng/ml improved survival compared with GH levels of 1-2.5 ng/ml.Methods: We identified 1845 cases from the UK Acromegaly database diagnosed 1970-2016 (31,768 person-yrs.), determined population mortality rates (for the period in question, age and sex of the study population) based on historic data, and death certification data for the study population from NHS digital. We were then able to determine standardized mortality rates (SMR) for the above conditions and determine whether they were associated with with age at diagnosis, duration of disease, post treatment (last recorded random or mean of profile) and mean GH levels (day weighted average of all GH measurements). Data presented as SMR, 95% CI and P value.Results: Overall standardised mortality rate (SMR) was increased, Observed 556 vs. Expected 412.74, 1.35 (1.24 -1.46, P &lt;0.001), with increased deaths from cardiovascular 1.38 (1.16-1.63, P&lt;0.0001), cerebrovascular 1.49 (1.10-1.97, P &lt;0.006) and respiratory disease 1.55 (1.22-1.93, P&lt; 0.001), but not malignancy 0.94 (0.78-1.11, P=0.786).We found no increase in mortality from breast 0.62 (0.25-1.27, P=0.936), lung 0.87(0.58-1.26, P=0.789) or colon cancer 1.26(0.63-2.25, P= 0.265).There was no relationship between age at diagnosis and SMR, however, there was a declining relationship between duration of acromegaly and all-cause SMR &lt;5 yrs. 6.02 (4.59-7.75) 5-10 yrs. 2.42 (1.9-3.03) &gt;10yrs.1.13 (1.03-1.25) P &lt;0.001.Lowering post-treatment GH levels lead to a significant reduction in all-cause SMR &lt;2.5 ng/ml 1.15 (1.03-1.28) 2.5- 9.9 ng/ml 1.73 (1.47-2.02) ≥10 ng/ml 2.27 (1.72-2.95) P&lt;0.001 and SMR in all disease categories. A similar relationship between mean GH levels and SMR was found for all disease categories and all-cause SMR &lt; 2.5 ng/ml 1.00 (0.89-1.18) 2.5- 9.9 ng/ml 1.50 (1.33-1.69) ≥ 10 ng/ml 2.28 (1.85-2.79) P&lt;0.001.Lowering post-treatment GH levels to less than 1 ng/ml appeared to have an additional beneficial effect for all-cause SMR, &lt;1ng/ml 1.03 (0.89-1.18) 1-2.5 ng/ml 1.38 (1.16-1.62) P&lt;0.001. A similar relationship was shown in cardiovascular, respiratory and malignant disease, but not cerebrovascular disease.Conclusion: Acromegaly is associated with an increased mortality from vascular, respiratory, but not malignant disease. The highest risk is within the first 5 years following diagnosis and the risk is abrogated by lowering GH levels to &lt;1.0 ng/ml.On behalf of UK Acromegaly Register Study Group 2020
SAT-LB14 Anthropometry and Vertebral Abnormality in Children With Transfusion-Dependent Thalassemia in Phramongkutklao Hospital, Bangkok, Thailand
Authors: Lertvivatpong Nawachai , Phatarakijnirund Voraluck 
Published: May 2020

Abstract
Anthropometry and vertebral abnormality in Children with Transfusion-dependent Thalassemia in Phramongkutklao HospitalBackgrounds: Thalassemia is an untreatable inherited hematologic disorder, unless stem cell transplantation, characterized by anemia from decreased hemoglobin production. Growth failure is one of the most common endocrine dysfunction in children with transfusion-dependent thalassemia (TDT) Objective: To evaluate the prevalence and associated factors of anthropometry and vertebral abnormality in transfusion-dependent thalassemia (TDT) children in a single tertiary center. Method: A cross-sectional study was conducted in transfusion dependent thalassemia patients who had visited in pediatric hematology clinic during 1st January 2018 to 31st December 2019. Collaborators had examined by history taking, physical examinations, laboratory and radiology reviewed. Results: Eighty-one collaborators were enrolled. Mean age was 13.7 ± 6.4 years and 46 of them (56.8%) were male. Pre-transfusion Hb and serum ferritin were 8.0 ± 1.0 g/dL and 1,562 + 1,394 ng/mL, respectively. Twenty-one (25.9%) had short stature determined by predicted adult height (PAH) below target adult height (TAH), 27(33.3%) had decreased upper-lower segment ratio for and 21 (26%) had BMI z-score below -2SD for age. Delay puberty was found in 13.2% of patients. Radiological examinations revealed delayed bone age of 4.9% and osteopenia of 25.9% whereas no vertebral fracture was documented. In multivariate logistic regression analysis (backward Wald), Serum ALP (p=0.009), mean pre-transfusion hemoglobin &lt;9 g/dL (p&lt;0.001), osteopenia (p=0.05) and delay bone age (p=0.019) were associated with PAH below TAH. Duration of chelation (p=0.013) and osteopenia (p=0.015) were associated with decreased upper-lower segment ratio. Low serum calcium (p=0.009), high serum phosphate (p=0.04) and impaired fasting glucose (p=0.004) were associated with BMI z-score below -2SD for age. Conclusions: Anthropometry abnormalities, including short stature, abnormal upper-lower segment ratio and low BMI, are common in TDT children. However, no vertebral abnormality was found in this study. Routine screening program by multidisciplinary team approach should be applied in thalassemia children.Keywords: Thalassemia major, endocrinopathies, growth failure, short stature, body disproportion
SUN-LB130 Identification of IGSF1 Ligands
Authors: Smith Courtney L , Bayne Andrew N , Trempe Jean-François , Bernard Daniel J 
Published: May 2020

Abstract
Immunoglobulin superfamily, member 1 (IGSF1), is an X-linked, type 1 transmembrane glycoprotein that is highly expressed in the anterior pituitary gland and testes. Mutations in the IGSF1 gene cause congenital central hypothyroidism, variable hypoprolactinemia, growth hormone dysregulation, and macroorchidism. Igsf1 knockout mice exhibit reduced pituitary TRH receptor (Trhr1) expression with an associated impairment in TRH-stimulated TSH secretion. The mechanism through which IGSF1 loss leads to reductions in Trhr1 levels is unresolved, at least in part because IGSF1’s cellular functions are unknown. The mature form of the IGSF1 protein consists of seven extracellular Ig loops, a single transmembrane domain containing a positively charged arginine, and a short intracellular carboxy-tail devoid of known functional motifs. Recently, IGSF1 was argued to be a member of the leukocyte receptor cluster (LRC) family. LRC proteins act as cell surface receptors for soluble or membrane-bound proteins. We therefore hypothesized that IGSF1 is a cell surface receptor for a presently undescribed ligand that regulates Trhr1 expression in pituitary thyrotrope cells. To identify candidate IGSF1 ligands, we implemented a new ligand trapping method, Ecto-Fc MS. We fused the extracellular (Ecto) domain of IGSF1 to the fragment crystallizable (Fc) region of human IgG, creating an Ecto-Fc fusion protein. Secreted IGSF1-Fc was purified and used as a ligand trap for bait proteins extracted from rat testes. The protein complexes were affinity purified with protein A beads, trypsin digested into peptides, subjected to orthogonal high-pH fractionation, and identified by tandem LC-MS/MS. More than 700 proteins were enriched in IGSF1-Fc preparations compared to an Fc-only negative control. Several secreted ligands and plasma-membrane proteins were identified, many of which are also expressed in pituitary thyrotrope cells. Identifying the ligand or ligands will enable us to determine IGSF1 function, and may lead to the discovery of novel causes of central hypothyroidism and macroorchidism.
SUN-LB45 Identifying a Role for Lactogenic Hormones in Maternal Motivation
Authors: Swart Judith M , Ladyman Sharon Rachel , Grattan David Ross , Brown Rosemary Shanon Eileen 
Published: May 2020

Abstract
The onset of appropriate maternal behaviour is essential for the survival of dependent offspring in mammals. Lactogenic hormones, including prolactin and placental lactogen, play an important role in the regulation of this behaviour, mediated through prolactin receptor expression in the medial preoptic area (MPOA) of the hypothalamus1. However, it is unclear how lactogenic action in this region induces the display of maternal behaviour. It has been shown that activation of neuronal projections from the MPOA to the ventral tegmental area (VTA) is necessary for maternal behaviour2, with reward circuitry activated in order to motivate a mother to invest in time- and resource-costly care for her young. We aimed to investigate whether lactogenic hormones play a role in the activation of reward circuitry for maternal behaviour. First, we characterised specific aspects of motivation and reward behaviour in wildtype female C57BL/6 mice of different reproductive states, using three behavioural testing paradigms. We showed that virgin and pregnant mice develop a preference for contexts associated with the presence of foster pups in a conditioned place preference test (p&lt;0.01, n=9 per group), an aspect of reward behaviour that was not observed in lactating females (p=0.14, n=8). However, in a novel T maze and when a climbable barrier was placed in the home cage, virgin and pregnant mice showed low motivation for pup retrieval compared to lactating mice (p&lt;0.05, n≤6 per group). These data demonstrate that reproductive state differentially affects passive reward learning and active motivation for maternal care in wildtype mice. Moreover, we can differentiate between maternal and non-maternal states of pup-related reward behaviour with the use of the T maze and barrier climbing paradigms. Next, we tested mice with a conditional deletion of prolactin receptors in Gamma-Aminobutyric Acid (GABA) neurons (Prlr flox/VGat Cre) in the T maze during lactation. Knockout mice showed incomplete retrieval behaviour, and latencies for pup retrieval were significantly longer than in controls (p&lt;0.01, n≤6 per group). The behavioural impairments observed in Prlr flox/VGat Cre knockout mice in the T maze imply that the action of lactogenic hormones on GABA neurons is required for full maternal motivation.
1.Brown RSE, et al. Prolactin action in the medial preoptic area is necessary for postpartum maternal nursing behavior. Proc Natl Acad Sci U S A114, 10779-10784 (2017). 2.Fang YY, Yamaguchi T, Song SC, Tritsch NX, Lin D. A Hypothalamic Midbrain Pathway Essential for Driving Maternal Behaviors. Neuron98, 192-207 e110 (2018).
SUN-LB8 Cross Sex Hormone Therapy and Breast Cancer in Transgender Male to Female
Authors: Eldin Randa Sharag , Zia Aleena , Pethe Gauri , Nabil Nur , Charkviani Mariam , Ibrahim Mohamed , Babiker Mohamed Abubakr Hassab Elrasoul 
Published: May 2020

Abstract
Case Presentation: We are presenting a 53-year-old Male to Female transgender patient who has been receiving estradiol valerate injections every 14 days for 13 years and had no gender surgical reassignment procedures or breast implants. Her past medical history was significant for HIV on Highly Active Anti-retroviral therapy (HAART). No family history of breast cancer. She presented with severe bilateral left elbow, lower back and bilateral chest pain for 3 days. Chest CT done to exclude pulmonary embolism showed an incidental 4 cm right breast mass. Enlarged lymph nodes in the right axilla, scattered lytic lesions in the axial skeleton and the left humeral head were also noted. Breast exam was not performed until the significant findings were seen in CT chest and it showed a palpable hard-circumscribed subareolar right breast mass without skin changes. Ultrasound guided biopsy of the breast mass confirmed invasive ductal carcinoma of the breast. The patient had no previous mammogram testing. Oncology work-up was positive for estrogen and progesterone receptors but negative for human epidermal growth factor-2 receptor. The patient opted to return home in another state to seek treatment and further oncological workup but subsequently lost follow up. Discussion: Male to female breast cancer was first recognized in 1968. However, risk factors for this condition remain unclear. In our patient, long-term use of Cross-sex Hormone Therapy (CHT) represented a major risk factor for breast cancer. In a Dutch study, the risk of breast cancer increased during a relatively short duration of CHT and the cancer characteristics reassembled female pattern. As theoretically implicated, increased estrogen exposure in males may have a role in the proliferation of neoplastic breast epithelium. There are growing evidence to support increasing rates of breast cancer in HIV-positive population, making it a potential risk factor as well. Loss of CXCR-4 protective effect promoted by HIV virus may explain the increase in the breast cancer incidence after the introduction of HAART. In general, routine screening for breast cancer in MTF transgender population remains controversial. The Endocrine Society Clinical Practice guidelines suggest that MTF transsexual individuals who have no known increased risk of breast cancer should follow screening guidelines for biological women. While the Canadian Cancer Society recommends screening mammography every two years for MTF individuals taking CHT for more than 5 years and those between the ages of 50 and 69 years.
Conclusion:Breast cancer in MTF transgender patients is associated with receiving CHT and represents diagnostic and treatment challenge. More research is need to comment on routine breast cancer screening in this population. However, physicians should remember performing a regular breast exam in MTF individuals looking for a possible mass.
MON-LB72 Multicentric Carpotarsal Osteolysis Syndrome (MCTO) Has a Generalized High Turnover Bone Phenotype, High S RANKL and Responds to Denosumab
Authors: Regev Ravit , Laxer Ronal , Whitney-Mahoney Kristi , Elia Yesmino , Noone Damien , Shammas Amer , Reza Vali , Sochett Etienne B 
Published: May 2020

Abstract
Background:MCTO is a rare disorder, caused by mutations in the MABF gene, a negative regulator of RANKL. Manifestations include carpal tarsal osteolysis and subsequent renal failure in some. Pathophysiology is poorly understood, and no effective treatment is available. Clinical case:A 5y old boy presented (2011) with R wrist pain and diffuse swelling. MRI showed pan-carpal synovitis with joint effusion. He did not respond to different anti-inflammatory medications. Plain films showed central loss of the proximal row of carpal bones. His mother was followed as an adolescent with presumed juvenile rheumatoid arthritis. Genetic testing confirmed MAFB gene mutation (c.206C&gt;T,p.Ser69Leu) in both patient and mother.At 7y, skeletal survey showed diffuse osteopenia and mild height loss in T1. DXA (L1-4) Z-score was -0.7. Calcium phosphate metabolism indices were within reference ranges. Bone Specific Alk Pi was modestly increased and C-telopeptide markedly increased.He received Denosumab (0.5-0.75 mg/Kg) 4-monthly for two years and experienced less pain and increased daily activities with improved R wrist function. Osteolysis stabilized and none was noted in the L wrist or ankles. BMD Z-score was -0.2. A year following treatment (2016) he received two more injections of Denosumab following pain and movement restriction of R elbow, R knee and L ankle. In 2019 (13y) he fell and radiology showed, R knee osteopenia, R wrist almost complete destruction of the carpal bones. Neither ankle nor L wrist showed osteolysis. R upper limb musculature was wasted when compared with the left. Shoulder and elbow strength were preserved. BMD Z-score was -1.2. Serum calcium, 25(OH)Vitamin D and PTH were normal. Bone specific alkaline phosphatase and C-Telopeptide were elevated. Serum creatinine was normal, eGFR 150 ml/min/1.73m2, ACR (6.6 [normal&lt; 3.5] mg/mmol)) with no hypercalciuria or nephrocalcinosis. He was normotensive.High resolution peripheral quantitative computerized tomography (HRpQCT) of the L distal radius and distal tibia compared with 7 age-matched healthy males showed reduced total volumetric BMD (186.4;198.2-306.4), normal trabecular volumetric BMD and markedly reduced cortical volumetric BMD (320.4;636.5-792.5). Cortical thickness was below the expected range. HRpQCT measurements of the R wrist and tibia were similar. sRANKL, 6 weeks after Denosumab were markedly increased in both undiluted (35.4 pmol/L) and averaged diluted samples (83.73 pmol/L) when compared with healthy age-matched children (0.21-0.41pmol/L).
Conclusions/Clinical Lessons:MCTO (MAFB, mutation c.206C&gt;T,p.Ser69Leu), has a generalized high turnover skeletal phenotype (osteoporosis), likely driven by very high levels of sRANKL. Denosumab is a targeted treatment for the osteoporosis, which may help stabilize the osteolysis.
SAT-LB46 Depression as an Atypical Presentation of Cushing’s Disease
Authors: Pahwa Dhivya , Shanik Michael Howard 
Published: May 2020

Abstract
Introduction: Cushing’s disease is an abnormal secretion of ACTH from the pituitary that causes an increase in cortisol production from the adrenal glands. Resultant manifestations from this excess in cortisol include multiple metabolic as well as psychiatric disturbances which can lead to significant morbidity and mortality.
Case: The patient is a 29 year old woman who presented with fatigue, decreased energy, poor memory and insomnia for 3 months. She noted irregular menses for 4 months. She was referred from her primary doctor for elevated salivary cortisol and DHEA levels. Evaluation revealed BP: 104/76, HR 78, RR 12, BMI 22.7. She was a thin woman without striae, moon face, buffalo hump or bruising. 24 hour urine free cortisol was 90.3 mcg/24hr. One mg dexamethasone suppression test resulted in an AM cortisol of 17.6 ug/dL and ACTH 25 pg/mL. An 8 mg dexamethasone suppression test showed a cortisol level of 1.2 ug/dL with an ACTH &lt;5 pg/mL. The combined results were suggestive of Cushing’s disease. The patient went for MRI of the pituitary which showed a 4 mm hypoenhancing region on the right side of the gland suspicious for a microadenoma. The patient was followed closely and continued to report fatigue and insomnia. Inferior petrosal sinus sampling was performed. Venous blood sampling of ACTH from the periphery at 0 min, 5 min and 15 min were: &lt;5 pg/mL, &lt;5 pg/mL, and &lt;5 pg/mL respectively. On the right at 0 min, 1 min, 5 min, 15 min ACTH levels were: 12 pg/mL, 14 pg/mL, 16 pg/mL, 14 pg/mL. On the left at 5 min and 15 min ACTH measured 8 pg/mL and 7 pg/mL. These findings confirmed the suspicion of a right-sided ACTH-secreting pituitary adenoma. She was referred to a neurosurgeon to evaluate for resection of the adenoma. Due to the ongoing symptoms, the neurosurgical removal of the lesion was expedited and scheduled within several weeks. While awaiting removal the patient sadly took her own life.
Conclusion: Aside from the more commonly associated metabolic manifestations of elevated cortisol levels, psychiatric symptoms can be the initial complaint of patients with Cushing’s disease. Symptoms can include fatigue, depressive symptoms, insomnia, and sleep dysregulation. Currently the Endocrine Society Guideline for Cushing’s syndrome does not have any specific recommendations regarding depression screening. Psychiatric complications are a known manifestation of Cushing’s disease. Close follow up and urgent psychiatric referral with the onset of signs of depression or anxiety should be included as part of Cushing’s disease evaluation. Symptoms of mental health disturbances may be subtle and thus all patients with Cushing’s disease should be screened and monitored for underlying psychiatric illnesses.
Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5152600/pdf/JMedLife-09-12.pdf
SUN-LB50 Increased In Vivo Pulsatile LH Secretion and Hypothalamic Kisspeptin, NKB, and Dynorphin RNA Levels in a PCOS-Like Mouse Model
Authors: Esparza Lourdes , Schafer Danielle , Ho Bryan , Thackray Varykina G , Kauffman Alexander S 
Published: May 2020

Abstract
Polycystic ovary syndrome (PCOS) is a reproductive disorder in women characterized by hyperandrogenemia, anovulation, cystic ovaries, and LH hyper-pulsatility, but the mechanisms causing the pathophysiology remain incompletely understood. We recently reported a novel mouse model that recapitulates the majority of PCOS phenotypes in adulthood. Females given constant, long-term letrozole to reduce aromatase activity demonstrate PCOS-like phenotypes, including polycystic ovaries, anovulation, elevated circulating testosterone, and increased LH. In vivo LH pulsatile secretion, which is greatly elevated in PCOS women, was not previously studied, nor were possible changes in reproductive neurons known to control GnRH/LH secretion. Here, we used recent technical advances in the field to examine in vivo LH pulse dynamics of freely-moving LET female mice versus control and ovariectomized (OVX) mice. We also studied whether hypothalamic gene expression of several important reproductive regulators, kisspeptin, neurokinin B (NKB), and dynorphin, is altered in LET females. Compared to controls, LET females exhibited very rapid, elevated in vivo LH pulsatility, with increased pulse frequency, amplitude, and basal levels, similar to PCOS women. LET mice also had markedly elevated Kiss1, Tac2, and Pdyn expression along with increased Kiss1 neuron activation in the hypothalamic arcuate nucleus. Although elevated, most hyperactive LH pulse parameters and increased arcuate mRNA measures of LET mice were significantly lower than in OVX littermates. Our findings demonstrate that LET mice, like PCOS women, have markedly elevated LH pulsatility which likely drives increased ovarian androgen secretion. Increased arcuate kisspeptin and NKB levels may be fundamental contributors to the enhanced stimulation of LH pulse secretion in this PCOS-like condition, and perhaps, in some PCOS women.