bluuebunny/crossref_metadata_2025_split huggingface dataset:
FRI272 Sex-Specific Role Of ProkR2 Neurons Of The Posterior Amygdala In The Integration Of Odors And Neuroendocrine Responses
Authors: Cisneros-Larios Brenda , Elias Carol F 
Published: October 2023

Abstract
Disclosure: B. Cisneros-Larios: None. C.F. Elias: None.
Kallmann Syndrome (KS) is characterized by abnormal development of the reproductive axis and olfactory bulb dysgenesis. Genetic studies have revealed that Kallmann Syndrome is caused by loss-of-function mutations in several genes including the prokineticin receptor 2 (PROKR2) gene. Prokr2 null mice exhibit the same phenotype of KS patients. While the role of PROKR2 during development has been linked with GnRH neuron migration, limited data exists on PROKR2 neurons in adult reproduction. PROKR2 mRNA are highly expressed in reproductive control sites. Furthermore, our lab previously found sexually dimorphic expression of PROKR2 mRNA and Prokr2-Cre GFP+ cells in several reproductive control sites. The posterior amygdala had higher PROKR2 expression in males compared to female mice. More recently, we identified expression of sex steroid receptors in PROKR2 expressing cells of the PA. The amygdala is an important site of socio-sexual inputs and reproductive neuroendocrine responses in rodents and primates, including humans. We hypothesize Prokr2-Cre neurons in the PA have a role in male reproductive function. Using genetic tracing techniques, we mapped PA Prokr2-Cre neuronal projections in male mice and found dense innervation to reproductive control sites such as the medial preoptic area and the ventral premammillary nucleus. We found activation of these neurons, via fos expression, after opposite sex soiled bedding exposure (olfactory cues). Lastly, selective activation, using chemogenetic technology DREADDs, of PA Prokr2-Cre cells in males can induce a rise in circulating luteinizing hormone. These data suggest PA Prokr2-Cre cells have a role in pathways integrating olfactory cues and reproductive endocrine responses (e.g., aggression, mating behavior). We expect our studies will contribute to the understanding of the role of PROKR2 neurons in adult reproduction and reproductive deficits associated with PROKR2 mutations.
Presentation: Friday, June 16, 2023
FRI291 Musashi1 And Musashi2 Mark Distinct Pituitary Stem Cell Populations
Authors: Rahmatallah Yasir , Banik Jewel , Bronson Katherine , MacNicol Melanie C 
Published: October 2023

Abstract
Disclosure: Y. Rahmatallah: None. J. Banik: None. K. Bronson: None. M.C. MacNicol: None.
The cell plastic state of the pituitary is required to meet the changing demands upon pituitary function and may also result in these cells being more vulnerable to malignant transformation. The mechanisms that control pituitary cell plasticity are unknown. The RNA binding protein Musashi (MSI) is expressed in embryonic stem cells, and in cancer stem cells, where MSI functions to promote stem cell plasticity and to oppose premature cell maturation. MSI is also expressed at high levels in adult gonad and adult pituitary. The function of MSI in adult tissues is not fully understood, and the mechanisms that control the pro-proliferative and pro-malignant aspects of MSI function in adult tissues are not known. The two evolutionarily conserved MSI proteins, Musashi1 (MSI1) and Musashi2 (MSI2), are predicted to function redundantly, however, regulatory distinctions have been reported for MSI1 and MSI2. Towards a characterization of MSI1 and MSI2 in pituitary, we analyzed transcriptomics data from public datasets of single-nucleus and single-cell and bulk-tissue gene expression data from physiological and pathophysiological human pituitary tissue. We performed bioinformatics analysis utilizing the single-cell genomics analysis tool, Seurat in R and the pseudotime trajectory analysis tool Monocle and additional genomics and statistics analyses tools in R. We identify the MSI1-expressing pituitary cell population as immature stem cells and the distinct MSI2-expressing pituitary cell population as more mature, committed progenitor cells. Pituitary from human fetal tissue contains multiple distinct MSI1-expressing cell populations while, in contrast, pituitary from human adult tissue contains multiple distinct MSI2-expressing cell populations. Pituitary from human pediatric tissue demonstrates an intermediate state with both distinct MSI1-expressing and distinct MSI2-expressing cell populations. We identify increased MSI1 expression but not increased MSI2 expression in adult pituitary adenoma, and a high level of variation in the MSI1 to MSI2 expression ratio between distinct pituitary adenomas. Based upon this re-analysis of reposited datasets from other pituitary investigators, we hypothesize that the increase that we observe, in MSI1 to MSI2 expression ratio in adult pituitary tumors is consistent with a reversion of mature cells to an earlier immature state. Adult pituitary may contain the mechanisms that regulate MSI2 function but may not be equipped to properly control high levels of re-expressed MSI1. An understanding of the physiological functions and mechanisms of regulation of the distinct MSI proteins in pituitary may provide insight into potential mechanisms that could be recruited to increase physiological pituitary cell growth and differentiation in regenerative therapy and to oppose pathological cell growth in pituitary tumor.
Presentation: Friday, June 16, 2023
FRI292 Asymptomatic TSH Secreting Pituitary Macroadenoma
Authors: Gautam Bharat , Hossain Md Shajjad , Liao Huijuan , Mandal Kaushik , Rosenthal David S , Kumar Salini Chellappan 
Published: October 2023

Abstract
Disclosure: B. Gautam: None. M.S. Hossain: None. H. liao: None. K. Mandal: None. D.S. Rosenthal: None. S.C. Kumar: None.
Introduction: TSH-producing adenoma is a rare disorder accounting for 0.5-2% of all pituitary adenomas with prevalence of 1-2 cases/million, often diagnosed at the stage of invasive macroadenoma hence challenging to manage. Case Presentation: A 36 years old male with no PMH referred to endocrine clinic for the evaluation of insomnia with abnormal thyroid panel for last 4 years. He denied skin or hair changes, diaphoresis, tremor, change in appetite, weight or bowel habits, cold/heat intolerance, palpitations, recent use of biotin or x-ray contrast exposure. Patient denied headache, visual or hearing impairment, galactorrhea, sexual dysfunction, change in facial appearance or size of gloves & shoes. Patient also denied childhood history of developmental delay, learning disability and family history of thyroid disorder. Unremarkable physical exam with normal vitals. Thyroid was normal without palpable nodule. No thyroid bruit. Normal visual field by confrontation. No tremors, gynecomastia or galactorrhea noted. Laboratory results showed normal CBC, CMP, TSH 5.2 (0.55-4.78 uIU/ml) with FT4 2.1 (0.8-1.8 ng/dl), FT3 5.4 (2.3-4.2 pg/ml), FT4 by dialysis 3.1 (0.9-2.2 ng/dl), FT3 by dialysis 433 pg/dl, Thyroglobulin ab &lt;1 (&lt;1 IU/ml), TPO ab 3 (&lt;9 IU/ml), TSI &lt;89 (&lt;140%), TBII &lt;1 (&lt;2 IU/L), HAMA &lt;6 (&lt;74 ng/ml). Normal ACTH 17 (6-50 pg/ml), serum cortisol level 10.5 (5.2-22.4 ug/dl), prolactin 9.2 (2-18 ng/dl), GH 0.1 (&lt;7.1 ng/ml), IGF-1 183 (53-331 ng/ml), LH 4.7 (1.5-9.3 mIU/ml), FSH 5.9 (1.6-8 mIU/ml), free testosterone 120 (35-155 pg/ml) and total testosterone 1100 (250-1100 ng/dl), SHBG 82 (10-50 nmol/L), alpha-subunit 0.8 (0.1-0.5 ng/ml) & alpha/TSH molar ratio 1.5. MRI brain with pituitary protocol showed an expansile round enhancing soft tissue mass filling the sellar cavity measuring 1.5 x 1.5 x 1.3 cm tenting the optic chiasm without cavernous sinus involvement. Patient was diagnosed with TSH secreting pituitary adenoma and referred to Neurosurgery. Patient had successful trans-sphenoidal adenectomy. Post-surgery TFTs: TSH 2.18 (0.55-4.78 uIU/ml), FT4 1.2 (0.8-1.8 ng/dl). Pathology report showed pituitary adenoma, IM stains positive for FSH, GH patchy and TSH (patchy and weak), negative for prolactin and ACTH. Rare tumor cells positive for LH Discussion: Our case highlights the importance of early diagnosis and appropriate treatment of TSH secreting adenoma to prevent complications such as hyperthyroidism, visual field defect and pan-hypopituitarism. Diagnosis in our case was particularly challenging as the patient was completely asymptomatic, therefore emphasize the importance of correlating TSH level with FT4 and early evaluation of central cause in the presence of biochemical evidence suggesting central thyroid disorder.
Presentation: Friday, June 16, 2023
FRI293 Phoenixin As A Novel Autocrine/Paracrine Factor Mediating Prolactin Regulation By Functional Interaction Of LH And IGF-I/-II In Carp Pituitary Cells
Authors: Ye Cheng , Qin Xiangfeng , He Mulan , Wong Anderson On-Lam 
Published: October 2023

Abstract
Disclosure: C. Ye: None. X. Qin: None. M. He: None. A.O. Wong: None.
Phoenixin (PNX), a novel peptide identified by bioinformatics, is known to have pleiotropic functions mediated by its receptor GPR173. At present, very little is known for PNX regulation and the intracellular signaling for PNX expression is still unclear. Recently, PNX and GPR173 were cloned in grass carp and found to be co-expressed in carp lactotrophs. In carp pituitary cells, PNX was also confirmed to be a novel autocrine/paracrine factor maintaining/stimulating prolactin (PRL) synthesis & secretion. To unveil the functional role of PNX in PRL regulation, a systematic screening of &gt;40 neuroendocrine factors/local growth factors was conducted in the same cell model to look for regulators with modulatory functions for both PNX and PRL in carp pituitary. Based on our study, IGF-I & -II were shown to elevate PNX mRNA level with parallel rise in PRL gene expression in carp pituitary cells whereas the opposite was true for the functional agonist of LH, namely hCG. In parallel experiment, PRL mRNA expression induced by IGF-I was negated by removing endogenous PNX using immunoneutralization with PNX antiserum. Besides, hCG inhibition on PNX & PRL gene expression could be mimicked by parallel treatment of LH but not FSH, whereas removal of endogenous LH by LH antiserum immunoneutralization could lead to the opposite effects. Of note, hCG co-treatment not only attenuated the PNX and PRL responses induced by IGF-I but also triggered notable suppression of IGF-I receptor (IGF1R) gene expression at pituitary cell level. In our study, IGF1R & insulin receptor (InsR) expressed in carp pituitary cells were both activated by IGF-I treatment, but IGF-I induced PNX and PRL mRNA expression could be blocked only by the inactivators for IGF1R but not InsR. Using a pharmacological approach, the gene expression of PNX and PRL induced by IGF-I was confirmed to be mediated through the PI3K/Akt and MEK1/2/ERK1/2 but not P38MAPK pathways. Our findings, as a whole, suggest that (i) IGF signals can induce PRL gene expression in carp pituitary via IGF1R coupled to PI3K/Akt & MAPK cascades and this stimulatory effect is mediated via local production of PNX, and (ii) LH released in the pituitary can act locally to inhibit both basal & IGF-induced PRL expression and these inhibitory actions are mediated by blocking pituitary expression of PNX & IGF1R.
Presentation: Friday, June 16, 2023
SAT676 Severe Recurrent Pancreatitis In A Familial Partial Lipodystrophy Patient On Metreleptin
Authors: Sargin Pinar , Vinicky Mark , Biglione Alejandro 
Published: October 2023

Abstract
Disclosure: P. Sargin: None. M. Vinicky: None. A. Biglione: None.
Lipodystrophy syndromes are congenital or acquired disorders characterized by either total or partial lipoatrophy and often unrecognized by clinicians due to their rarity. Patients with lipodystrophy may demonstrate severe complications of metabolic syndrome since lipids are deposited in non-adipose organs where they induce lipotoxicity resulting in insulin resistance, diabetes mellitus, hypertriglyceridemia, and hepatic steatosis. Familial Partial Lipodystrophy (FPLD) syndromes are one of the four major subtypes of lipodystrophy syndromes. These are heterogeneous, mostly autosomal dominant, and characterized by site-specific subcutaneous adipose tissue loss. The management of patients with FPLD can be challenging with life-threatening complications, heavy dependence on lifestyle modifications, limited treatment options and medication availability. One of the important complications seen in these patients is pancreatitis, related to high triglyceride levels. It can be recurrent and the episodes can be more severe compared to the general patient population. Metreleptin, the human leptin analogue, is the only disease-specific treatment for lipodystrophy syndromes and it has been shown to reduce the complications of leptin deficiency, but it is not currently approved for FPLD in the USA. Previous studies showed improvement of the complications of FPLD with its use. Our case is a 29-year-old woman who has Dunnigan type FPLD with a history of numerous bouts of pancreatitis while on fenofibrate, statin and omega-3-acid ethyl esters, later was on metreleptin for almost 3 years, presented to our hospital with typical symptoms of acute pancreatitis incited by severe hypertriglyceridemia (&gt;1,500 mg/dL). Lipase levels were high at 27,501. Patient was treated with vigorous intravenous hydration, insulin and home metreleptin was continued at the hospital. Despite the initial improvement of the symptoms, on the 6th day of hospitalization, she developed worsening abdominal pain, nausea, and vomiting. CT angiogram of the abdomen showed 2.0 cm splenic artery pseudoaneurysm. Coiled embolization of the superior segmental branch of the splenic artery performed by interventional radiologist which was further complicated by splenic infarction. Her condition improved eventually, she was able to be discharged home. Importance of adherence to medications and special diet was discussed with the patient in length. This case report aims to bring attention to this rare disease and urgent need for further treatment options for these patients to prevent serious complications in this young patient population. Metreleptin is a daily injection which could be challenging to adherence and the consequence can be relapse of pancreatitis. Lack of other treatment options, treatment availability, physician awareness are barriers to optimize the treatment for these complex patients.
Presentation: Saturday, June 17, 2023
FRI307 Gigantism Due To Transcriptional Activation Of GHRH: The First Case Of Hormone-encoding Gene Overexpression Underlying A Congenital Disorder
Authors: Hattori Atsushi , Katoh-Fukui Yuko , Zhang Ruogu , Terao Miho , Takada Shuji , Nakabayashi Kazuhiko , Hata Kenichiro , Yamada Yutaka , Matsuura Nobuo , Fukami Maki 
Published: October 2023

Abstract
Disclosure: A. Hattori: None. Y. Katoh-Fukui: None. R. Zhang: None. M. Terao: None. S. Takada: None. K. Nakabayashi: None. K. Hata: None. Y. Yamada: None. N. Matsuura: None. M. Fukami: None.
Background: Pituitary gigantism is characterized by tall stature due to GH overproduction. To date, known genetic causes of pituitary gigantism are invariably associated with predispositions to tumors producing GH or GHRH. Clinical and genetic findings of the patient: The patient was a Japanese woman who was born mildly large for gestational age. Her overgrowth started in her first year of life. Despite radiation and pharmacotherapy starting at age three years, she reached an adult height of 197 cm (+7.4 SD). She developed panhypopituitarism associated with empty sella in adulthood and was deceased during sleep at age 53 years. Exome sequencing identified no pathogenic variant causing acromegaly or gigantism. Chromosomal microarray analysis detected a 752-kb deletion upstream of GHRH. This deletion was predicted to create a chimeric gene consisting of the 5´-UTR of TTI1, a ubiquitously expressed gene, and the coding region of GHRH. Reverse transcription PCR (RT-PCR) using mRNA of immortalized lymphoblastoid cells detected the chimeric transcript. Analysis of model mice: We established a mouse model harboring a 676-kb deletion upstream of Ghrh using the CRISPR/Cas9 system. RT-PCR detected a chimeric transcript consisting of the 5´-UTR of Tti1 and the coding region of Ghrh, which mimicked the patient’s chimeric transcript. Mutant mice started to overgrow at two weeks of age and showed high serum GH levels and long tibia at 12-13 weeks of age. Quantitative RT-PCR showed that the median level of Ghrh expression in the hypothalamus of the mutant mice was three-fold higher than that of the wildtype mice. Furthermore, the mutant mice had ectopic Ghrh expression in all analyzed tissues (the pituitary, thymus, heart, liver, and gonad). Discussion: Our findings propose a novel etiology of gigantism. In the present case, the GHRH gene obtained a constitutively active promoter through germline genomic microdeletion. The newly acquired promoter likely led to the constant expression of GHRH in various tissues including the hypothalamus. Possible explanations for GH overproduction in the present case include (1) GHRH overproduction in the hypothalamus, (2) paracrine and autocrine effects of GHRH secreted from the pituitary, and (3) endocrine effects of GHRH produced outside the hypothalamic-pituitary unit. The patient’s clinical course suggests that prenatal GHRH overproduction only mildly affects human growth. More importantly, this is the first case in which transcriptional activation of a hormone-encoding gene caused a human congenital disorder.
Presentation: Friday, June 16, 2023
FRI314 Prolactinoma And Macroprolactin; A Diagnostic Dilemma
Authors: Farooqi Aneeba , Dewan Sandesh , Jun John 
Published: October 2023

Abstract
Disclosure: A. Farooqi: None. S. Dewan: None. J. Jun: None.
Prolactin is a 199 amino acid, 23 (Kilo Dalton) kDa protein secreted by pituitary lactotroph cells. The two other major forms of prolactin present in circulation are big prolactin, the dimeric 40-60 kDa prolactin and big-big prolactin or macroprolactin, 100-150 kDa complexes of 23 kDa prolactin and IgG autoantibodies. Hypothalamic dopamine is the primary regulator of prolactin secretion through its inhibitory effect. Prolactinoma accounts for ∼40% of pituitary tumors with clinical presentations of hypogonadotropic hypogonadism and tumor-related mass effects.  A 77-year-old female with a past medical history of hypertension and hyperlipidemia was admitted after a mechanical fall. She underwent a computed tomography (CT) of the brain which incidentally showed a pituitary mass. Magnetic resonance imaging (MRI) of pituitary showed a homogenously enhanced 3.0 x 3.5 x 2.8 cm mass centered in the Sella turcica, invading the supra-seller cistern, left cavernous sinus, and orbital apex abutting the optic chiasm and optic tracts. The patient did not report headache, nausea, vomiting, visual changes, or abnormal milky nipple discharge. Physical examination was unremarkable without any neurologic deficit. Formal ophthalmology evaluation showed intact extra ocular movements, visual field-testing using octopus 24-2 and Humphrey test showed few missed points, though not suggestive of pituitary related loss. Serum prolactin was measured at 1432 ng/ml (reference range, 0-25). The presence of macroprolactin was considered due to the absence of clinical features of hyperprolactinemia. The monomeric prolactin was found to be 68.7% (&lt;40%) at 867.5 ng/ml of the total prolactin at 1259.7 ng/ml with 31.3 % of other prolactin forms are present. Evaluation for other pituitary functions was unremarkable with thyroid stimulating hormone (TSH) of 0.72 uIU/ml (0.49-4.76l), morning serum cortisol of 52.9 ug/dl (6.7-22.4), and insulin like growth factor (IGF-1) 73 ng/ml (20-214). Cabergoline 0.5 mg twice weekly was prescribed. This case illustrates a menopausal state as a probable explanation for lack of clinical features of hyperprolactinemia with macro adenoma while macroprolactin should be considered.
Presentation: Friday, June 16, 2023
FRI321 Aggressive Prolactinoma Empirically Treated With Cabergoline Leading To Rapid CSF Leak
Authors: Yau Alice , Reisman Tamar 
Published: October 2023

Abstract
Disclosure: A. Yau: None. T. Reisman: None.
Over two-thirds of pituitary tumors are prolactinomas. These are discovered as a result of symptoms of hypogonadism, menstrual irregularities, infertility or galactorrhea, as well as symptoms of mass effects including visual field deficit or acute severe headaches.1 A more rare subgroup, aggressive prolactinomas, in which the tumors are radiographically invasive and show resistance to dopamine agonist treatment as well as surgery, account for 10% of all hypophyseal neoplasia. 2 During medical treatment of prolactinomas, there is a known rare complication of CSF rhinorrhea; recorded time of onset of leak following treatment ranges from 14 days to 5 years.3 We present a case in which a patient with an aggressive prolactinoma rapidly developed a CSF leak within 48 hours of starting cabergoline treatment. Case: A 36-year-old male with type 2 diabetes, erectile dysfunction and infertility presents to Endocrine clinic after initial evaluation by Urology revealed elevated prolactin. He reported headaches, gynecomastia associated with liquid discharge from nipples, and minor issues with peripheral vision. He was started empirically on cabergoline for probable prolactinoma and within 48 hours developed worsening frontal headache, cough and clear fluid leakage from his right nostril. Labs revealed prolactin over 2600 ng/ml. MRI pituitary showed evidence of pituitary adenoma as well as likely CSF leak. Cabergoline was stopped and the patient was sent to the emergency room. The patient was underwent urgent neurosurgical transsphenoidal endoscopic surgery and CSF leak repair with resolution of rhinorrhea and cough. Post-operative MRI was consistent with minimal residual tumor. He was monitored in the NICU with no obvious post-operative pituitary hormone imbalance, diabetes insipidus, adrenal insufficiency or syndrome of inappropriate ADH. Months after discharge, the patient’s prolactin remained elevated to the 600’s ng/ml and repeat MRI showed a mass occupying the entire sella and suprasellar cistern, compressing the optic chiasm. Conclusion: In this case of a patient with the subtype of aggressive prolactinoma, there seems to be a more rapid presentation of complications. When treating these rare subtypes, physicians need to stay vigilant of developing complications or even consider nonstandard therapies as first-line management. 1. Molitch ME, Drummond J, Korbonits M. Prolactinoma Management. In: Feingold KR, Anawalt B, Boyce A, et al., eds. Endotext. South Dartmouth (MA): MDText.com, Inc.; January 6, 2022.2. Lasolle H, Ilie MD, Raverot G. Aggressive prolactinomas: how to manage?. Pituitary. 2020;23(1):70-77. doi:10.1007/s11102-019-01000-73. Arimappamagan A, Sadashiva N, Kandregula S, Shukla D, Somanna S. CSF Rhinorrhea Following Medical Treatment for Prolactinoma: Management and Challenges. J Neurol Surg B Skull Base. 2019;80(6):620-625. doi:10.1055/s-0039-1677686
Presentation: Friday, June 16, 2023