bluuebunny/crossref_metadata_2025_split huggingface dataset:
THU121 Dopamine Regulates Neuroendocrine Cell Expansion In The Developing Lung
Authors: Watanabe Takuya , Stupnikov Maria , Zhou Yizhuo , Ke Xiangyi , Qien Jun , Ozawa Atsushi , Horigome Mitsuaki , Yamada Masanobu , Mori Munemasa , Cardoso Wellington V 
Published: October 2023

Abstract
Disclosure: T. Watanabe: None. M. Stupnikov: None. Y. Zhou: None. X. Ke: None. J. Qien: None. A. Ozawa: None. M. Horigome: None. M. Yamada: None. M. Mori: None. W.V. Cardoso: None.
Pulmonary neuroendocrine cells (PNECs) are rare airway epithelial cells in the lung that have function as neurosensory and endocrine cells. They arise from naive epithelial progenitor cells in mice on embryonic day (E) 12.5, migrate to branch point of proximal airway and rare found as solitary or in clusters of 5 to 20 cells termed neuroepithelial bodies (NEBs). PNECs can be aberrantly increased in a variety of human diseases, including asthma, neuroendocrine hyperplasia of infants (NEHI) and sudden infant death syndrome (SIDS). Ascl1, an Achaete-Scute family bHLH transcriptional factor is the earliest marker and master regulator of PNEC fate specification. No PNECs form in Ascl1 null mice. In an effort to identify Ascl1 downstream targets involved in PNEC specification and expansion, we performed transcriptional analysis of E14.5 lungs from Ascl1 null mouse. Gene Ontology analysis showed a number of genes associated with the catecholamine pathway downregulated in mutants, compared to WT. These included tyrosine hydroxylase (Th) dopa decarboxylase (Ddc), dopamine beta-hydroxylase (Dβh). To gain initial insights into how catecholamine signaling influence PNEC development, we cultured E12.5 lung explants with various inhibitors of the catecholamine biosynthesis pathway and examined the effects on cell differentiation and proliferation. Treatment with Metyrosine (Met) and Benserazide (Benz) which inhibits dopamine production, resulted in a striking increase in PNEC number in NEBs as seen by expansion in Ascl1+ cells, without affecting cell proliferation. By contrast, no effect was observed with Zamicastat (Zami) which inhibits norepinephrine production. To examine whether dopamine regulated PNEC differentiation, we used the D1-like receptor antagonist, SCH-23390 and the D2-like receptor antagonist, Haloperidol in lung explant cultures, as before. Only Haloperidol increased PNECs in cultured lungs. This effect was similarly observed by maternal administration of Haloperidol intraperitoneally from E9.5 to 13.5 and analysis of harvested embryos at E14.5 and 18.5. Current studies mapping expression of other components of the dopamine pathway in the developing airway epithelium suggests a complex interaction of PNECs with neighbor cells in the regulation of the proper number of NEBs and solitary NE cells. These observations may provide a link between catecholamine signaling and aberrant PNEC behavior in the pathogenesis of human conditions affecting these cells.
Presentation: Thursday, June 15, 2023
SAT674 Lipodystrophy: A Hidden Culprit In Uncontrolled Diabetes
Authors: Sayed Farah El , Banka Ajaz 
Published: October 2023

Abstract
Disclosure: F. El Sayed: None. A. Banka: None.
Introduction: Lipodystrophies are rare disorders with selective absence/accumulation of fat tissue. The “common” genetic forms include Congenital Generalized Lipodystrophy or Familial Partial Lipodystrophy (FPLD). Non-genetic factors like autoimmune disorders, chronic infections, or malnutrition can also contribute to a lipodystrophy phenotype. Clinical case: A 49-year-old female with diabetes mellitus, hypertriglyceridemia, gait disturbances, hypertension, hereditary hemorrhagic telangiectasias, asthma, presents with suspected lipodystrophy. She notes truncal obesity as a child, with progression as an adult and subsequent loss of volume from her arms and legs around age 30. Family history is significant for multiple family members with diabetes mellitus. On physical exam, the patient has a BMI of 22.86 kg/m2. She walks with a cane and has abdominal fat deposition, a dorsocervical fat pad, and reduced fat and muscle mass in her lower extremities. Her diabetes is poorly controlled with multiple complications including retinopathy, microalbuminuria, neuropathy, CVA, and CAD. Her medications include metformin, pioglitazone, detemir, aspart, and an insulin sliding scale for diabetes management, and rosuvastatin, fenofibrate, and omega-3-acid ethyl esters for hyperlipidemia. Her last A1C was 12.7%, and urine analysis was positive for glucosuria and ketonuria. Her lipid panel revealed high triglycerides (800s) and low HDL levels. Other pertinent labs include elevated GDF15 at 761 pg/mL. and lactate elevation at 3.4 mml/L. Given suspicion for hypercortisolism, she underwent a dexamethasone suppression test which was negative for Cushing’s disease. She subsequently underwent exome sequencing with mitochondrial deletion testing, which led to the diagnosis of FPLD. Discussion: FPLD results in loss of fat from the extremities starting around puberty, often leading to metabolic complications. Although both sexes are affected, women usually present with more severe disease. Currently, multiple genes are associated with FPLD, most commonly LMNA and PPARG which both follow autosomal dominant inheritance. Conclusion: Presently, there is no cure for lipodystrophy syndromes. However, in patients with diabetes and resistant metabolic syndrome features, a diagnosis of lipodystrophy should be considered. Further evaluation with genetic testing is warranted and has implications for family planning and medical management.
Presentation: Saturday, June 17, 2023
FRI287 Pituitary Gene Signatures Link Chronic Systemic Inflammation To Female Reproductive Physiology
Authors: Garcia Christopher , Velez Leandro , Fox Chelsea , Mark Adam , Fisch Kathleen M , Lawson Mark A , Duleba Antoni , Seldin Marcus M , Nicholas Dequina 
Published: October 2023

Abstract
Disclosure: C. Garcia: None. L. Velez: None. C. Fox: None. A. Mark: None. K.M. Fisch: None. M.A. Lawson: None. A. Duleba: None. M.M. Seldin: None. D. Nicholas: None.
Female reproductive function depends on a perfectly choreographed sequence of hormonal secretion and action, where specific stresses such as inflammation exert profound disruptions. Specifically, LPS-induced inflammation inhibits luteinizing hormone production and secretion from the pituitary, thereby inhibiting downstream production of sex hormones. However, this outcome has only been observed in acute inflammatory stress and little is known about the mechanisms by which chronic inflammation affects reproduction. In this study we seek to understand the chronic effects of LPS on luteinizing hormone secretion and consequent pituitary function. An inflammatory state was induced in female mice using biweekly doses of LPS injections. Surprisingly, luteinizing hormone was not inhibited and instead we found it was increased dose-dependently with LPS treatments. This is consistent with the features of the reproductive disorder polycystic ovary syndrome (PCOS). Here, analysis of bulk RNA-sequencing of mouse pituitary and integration with genetic variation of human pituitary expression profiles revealed pathways that are highly conserved between species. These results provide insights into the impacts of LPS-induced chronic inflammation on reproductive physiology.
Presentation: Friday, June 16, 2023
FRI316 A Rare Case Of Mono-hormonal Silent Prolactinoma
Authors: Esaki Yumiko , Bheeman Chandni , Shafiq Ismat 
Published: October 2023

Abstract
Disclosure: Y. Esaki: None. C. Bheeman: None. I. Shafiq: None.
Introduction: Silent pituitary adenomas secrete one or more anterior pituitary hormones or express their transcriptions factors, but do not secrete hormones at a clinically relevant level. Silent lactotroph adenomas are rare and often encountered as mixed somatotroph-lactotroph adenomas. Mono-hormonal silent lactotroph adenomas are exceedingly rare with the prevalence of 0.6-1.65% with most belonging to the sparsely granulated subtype. Clinical Case: A 32-year-old male presented with right visual problem over the last 7 months. Evaluation by Ophthalmology revealed trace afferent pupil defect of the right eye and bitemporal hemianopsia. MRI head showed an enhancing mass in the sellar and suprasellar regions collectively measured 2.5 x 2.0 x 1.8 cm, which upwardly displaced and distorted the optic chiasm. Biochemical workup showed normal prolactin 8.1 ng/ml (2.6-13.1) and unremarkable other pituitary hormone levels including ACTH 26 pg/ml (7-63), cortisol 16.6 ug/dl (6.7-22.6), growth hormone 0.08 ng/ml (0.00-2.47), LH 4.1 mIU/ml (1.2-8.6), FSH 5.8 mIU/ml (1.3-19.3), estradiol 27.9 pg/ml (15.0 - 31.5), total testosterone 527 ng/dl (240-950), free testosterone 16.1 ng/dl (4.85-19.0), SHBG 23 nmol/L (10-80), TSH 3.34 uIU/ml (0.34-5.60), free T4 0.84 ng/dl (0.58-1.64). He underwent transsphenoidal hypophysectomy. Final pathology showed densely granulated lactotroph, with extensively positive PRL in tumor cells, positive Pit-1 and negative ERa. Patient did well post-operatively. Conclusion: This case illustrates a rare case of a mono-hormonal silent pituitary lactotroph adenoma. The majority of lactotroph adenomas are sparely granulated, so the densely granulated histology shown here makes this case even more rare. Unfortunately, there is no data reported in relation to the association between this histological subtype and the invasiveness of tumor. We need more cases to characterize this subtype of tumor better.
Presentation: Friday, June 16, 2023
FRI325 Pituitary Stalk Interruption Syndrome Presenting As Short Stature: A Case Report
Authors: Ravindra Shruthi , Tirupati Sunanda 
Published: October 2023

Abstract
Disclosure: S. Ravindra: None. S. Tirupati: None.
Background: Pituitary stalk interruption syndrome (PSIS) is a rare congenital pituitary anatomical defect that leads to a variable degree of pituitary hormone deficiency. The classic neuroimaging findings of this condition include thin or interrupted stalk, absent or ectopic posterior pituitary, and hypoplastic anterior pituitary gland. The reported incidence of PSIS is 0.5 per 1,00,000 live births. The exact pathophysiology of this syndrome is not fully understood, but chromosomal microdeletions and perinatal asphyxia have some established roles in the literature as primary miscreants. Here we report a case of an adolescent male child who presented with complaints of short stature and absent secondary sexual characters development, diagnosed with PSIS following an MRI. Clinical Case: A 16-year-old male child was referred to the endocrinology department for the evaluation of short stature and delayed secondary sexual character development. This patient was born out of a non-consanguinous marriage and delivered at term by the vaginal route, with no other significant perinatal or family history. Psychomotor milestones were attained appropriately as per age but had poor linear growth. On examination, he had short stature - height 146cms (-2.7 SDS), weight: 53.5kg BMI: 23.5 Kg/m2 with normal vitals. Head-to-toe examination revealed immature facies, deep-seated eyes, broad nasal bridge, bilateral lipomastia, high-pitched voice, Tanner stage: A1P1, SPL:4cms, the testicular volume of 3cc bilaterally, with rest of the system-wise examinations being normal. Routine laboratory investigations (CBC, RFT, LFT, Electrolytes) were within normal limits. Bone age: 13years. The hormonal assessment showed central hypothyroidism, hypocortisolemia, and GH insufficiency, with pre-pubertal gonadotropin levels- suggestive of pan-hypopituitarism (Table 1). MRI pituitary showed anterior pituitary hypoplasia with interrupted stalk, and ectopic posterior pituitary, with no other brain anomalies which is consistent with the diagnosis of PSIS. The patient was initiated on hormone replacement therapy, currently taking hydrocortisone, growth hormone, levothyroxine, and testosterone. Conclusion: PSIS is a rare condition, that can present with various spectrum of clinical features. Signs and symptoms may not be evident in the neonatal and infancy period, therefore diagnosis is often delayed. Early diagnosis and treatment are crucial for preventing adverse effects of long-term hormonal deficiencies and improving the quality of life.
Presentation: Friday, June 16, 2023
SAT680 Mounjaro: A Side Effect
Authors: Rao Kamini , Nimako Evans Kyei 
Published: October 2023

Abstract
Disclosure: K. Rao: None. E. Kyei Nimako: None.
Mounjaro : A Side Effect Dr K Rao, Dr Evans-Nimako, Internal Medicine, North Alabama Medical Center Introduction: Mounjaro has been heralded as a new miracle drug both in the world of diabetes management and weight loss with its pending FDA approval in the latter category. Although common contraindications are known the wider spectrum and prevalence of side effects including diabetic retinopathy, acute kidney injury and gallbladder disease are still being identified. In this case we present a patient with Mounjaro induced AKI and ileus. Case Presentation: We present the case of a 64year-old diabetic, hypertensive male presenting with a 3-day history of nausea vomiting indigestion and excessive burping one day after taking his first dose of Mounjaro. The Patient was started at a walk-in clinic on 2.5 mg subcutaneously however on the very next day he noticed the onset of cramping abdominal pain with multiple episodes of vomiting and watery diarrhea. The patient has not had any other new foods, sick contacts or preceding illnesses. He had a history of previous hernia surgery, cholecystectomy and exploratory laparotomy some 18 years ago due to concerns for nonresolving small bowel obstruction. On examination he was afebrile but tachycardic and in mild distress. His abdomen was soft and nondistended. Bowel sounds were faint but present. He had generalized tenderness without evidence of rebound or guarding. Initial investigations demonstrated a white cell count of 14.7(10E3/ul), creatinine 1.7mg/dl, potassium 4.5mmol/L, blood glucose 176mg/dl and lactate of 2mmol/L. His urine analysis showed small volume ketones, glucosuria and trace leukocyte esterase with 3-5 white blood cells. CT of the abdomen and pelvis with contrast showed distended small and large bowel loops with fluid air levels but no transition point indicative of underlying ileus. The patient was hospitalized in total for approximately six days post the onset of his symptoms and treated with supportive measures including antiemetics, IV fluids and antacids. He never had any fevers or leukocytosis during his stay. His electrolytes remained within normal limits. Conclusion: Due to the impending widespread use and increasing popularity of Mounjaro this case presentation is aimed at raising awareness of potential side effects and their severity. We also hope to contribute towards further knowledge about specific subset of patients who may be more susceptible to the gastrointestinal side effects of Mounjaro. Particularly those patients who have had previous colonic or multiple abdominal surgeries or history of bowel obstruction. In this case the patient received the medication at a walk-in clinic this also highlights the dangers of lack of established care and monitoring of Mounjaro.
Presentation: Saturday, June 17, 2023
OR17-03 Vasoinhibin Analogs Vi45-51 And Crivi45-51 Lack The Proinflammatory Properties Of Vasoinhibin In Arthritis
Authors: Ortiz Georgina , García Rodrigo José F , Martínez-Díaz Oscar F , Robles Juan P , Zamora Magdalena , Ruiz-Herrera Xarubet , de Los Ríos Ericka A , de la Escalera Gonzalo Martinez , Clapp Carmen 
Published: October 2023

Abstract
Disclosure: G. Ortiz: None. J.F. García Rodrigo: None. O.F. Martínez-Díaz: None. J.P. Robles: None. M. Zamora: None. X. Ruiz-Herrera: None. E.A. de Los Ríos: None. G. Martinez de la Escalera: None. C. Clapp: None.
Vasoinhibin, a fragment of prolactin, has dual actions on inflammatory arthritis. It reduces joint inflammation by the inhibition of pannus vascularization (1) but enhances arthritis by direct proinflammatory effects on synovial fibroblasts (2). Linear (Vi45-51) and cyclic (CRIVi45-51) heptapeptides comprising the 45 to 51 amino acids of vasoinhibin conserve the antiangiogenic effects and potency of whole vasoinhibin, but are easier to produce, stable, and orally active to be developed for clinical use (3). In view of their therapeutic potential in arthritis, we investigated whether Vi45-51 and CRIVi45-51 conserved the proinflammatory effects of vasoinhibin in joint tissues. Synovial fibroblasts (SF) isolated from the knee joint of male C57BL/6 mice were incubated with or without recombinant vasoinhibin of 123 amino acids (positive control), Vi45-51, or CRIVi45-51. As expected, vasoinhibin upregulated the expression of tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) and increased the production of nitric oxide (NO) in SF. However, similar or higher concentrations of Vi45-51 and CRIVi45-51 were inactive. The lack of inflammatory properties suggested improved efficacy of antiangiogenic Vi45-51 and CRIVi45-51 in arthritis. The antigen-induced arthritis (AIA) mouse model was carried out under severe [20 μg of intra-articular administration of methylated serum albumin (mBSA) as antigen] and mild (2.5 μg mBSA) inflammatory conditions to detect the antiangiogenic and proinflammatory effects of vasoinhibin, respectively (2). Consistent with its antiangiogenic properties, intra-peritoneal injection of CRIVi45-51 reduced joint swelling and pannus formation/vascularization in male C57BL/6 mice subjected to severe AIA. Moreover, in agreement with lack of proinflammatory actions, CRIVi45-51 did not elevate joint swelling under mild AIA. We conclude that Vi45-51 and CRIVi45-51 are beneficial in arthritis due to their antiangiogenic properties and lack of proinflammatory actions. Vasoinhibin analogs may be good therapeutic alternatives in inflammatory arthritis, including rheumatoid arthritis. Supported by CONACYT (A1-S-9620B) and UNAM (DGAPA-PAPIIT IN202321).
Reference: (1) Ortiz et al., Lab Invest. 2020 Aug;100(8):1068-79. (2) Ortiz et al., Endocrinology 2022 May;163(5): bqac036. (3) Robles et al., Angiogenesis 2022 Feb;25(1):57-70.
Presentation: Saturday, June 17, 2023
SAT346 Empty Sella Syndrome And Hypopituitarism In A Childhood Cancer Survivor
Authors: Akhter Wajeeha , Gilden Janice L 
Published: October 2023

Abstract
Disclosure: W. Akhter: None. J.L. Gilden: None.
Introduction: It has been reported that 50% of childhood cancer survivors develop an endocrinopathy and require life-long monitoring. Hypopituitarism is common in patients who have been treated with radiotherapy and is progressive and irreversible. We present the case of a young cancer survivor, referred for evaluation of secondary amenorrhea and hyperprolactinemia., who was diagnosed with empty sella syndrome and hypopituitarism. Clinical Case: A 29-year-old female with past history of right maxillary rhabdomyosarcoma at age 15, treated with chemotherapy and radiation, was referred to the endocrinology clinic for evaluation of secondary amenorrhea and hyperprolactinemia. Menarche was at age 13, and stopped when starting chemotherapy and radiation. She had not been treated with hormone replacements or dopamine agonists. Upon evaluation, she had fatigue, lethargy, generalized muscle weakness, but denied headaches, fractures, abdominal pain, galactorrhea, and vaginal dryness. Laboratory revealed hypopituitarism with low estradiol &lt;15 (nl=30-400 pg/ml premenopausal women, &lt;10 pg/ml postmenopausal women) with inappropriately low FSH 0.82 (nl=1.5-12.4 mIU/ml), and low LH 0.22 (nl=5-25 IU/L premenopausal female), high prolactin 41.3 (nl=non-pregnant female &lt;25 ng/mL, pregnant female 80-400 ng/mL), negative HCG, low cortisol 3.4 (nl=5-25 mcg/dL), low ACTH 9.7 (nl= 10-60 pg/mL), normal TSH 2.446 (nl=0.27-4.20 uIU/mL) and Free T4 0.54 (nl=0.5-1.6 ng/dL), negative thyroglobulin &lt;1 (nl=0-4 IU/mL) and thyroid peroxidase AB 0.46(n=0-9 IU/mL), normal HbA1C 5.2(nl&lt;5.7 %). MRI pituitary with contrast done 11 yrs. earlier showed a 1.5 mm focus of relative delayed and nonenhancement between anterior and posterior pituitary gland, as well as an overall volume of the pituitary smaller than expected for age. However, recent repeat MRI of brain and sella revealed a partially empty sella without evidence of macro or microadenoma. Conclusion: Patients with childhood malignancies have a greater chance of survival, as observed in the past 30 years. It is now recognized that disorders of the hypothalamic-pituitary axis can occur at any time in patients who have undergone radiation therapy. We should be aware that empty sella syndrome, which can be caused by radiation, can also be associated with hormonal abnormalities. Studies have reported that 50 % of patients with empty sella syndrome had endocrine dysfunction, with the most common endocrine abnormality being hyperprolactinemia. Therefore, amenorrhea in our patient could be from hypopituitarism caused by radiation and empty sella, as opposed to hyperprolactinemia. When evaluating amenorrhea our focus should not be entirely on hyperprolactinemia, but a diagnosis of empty sella syndrome can be missed, thus delaying appropriate hormonal replacement therapy.
Presentation: Saturday, June 17, 2023