bluuebunny/crossref_metadata_2025_split huggingface dataset:
7503 Light Composition Alters Feline Stress in a Shelter Environment
Authors: Yaw Alexandra M , Gardella Mary E , Jacobs Jacquelyn , Hoffmann Hanne Mette 
Published: October 2024

Abstract
Disclosure: A.M. Yaw: None. M.E. Gardella: None. J. Jacobs: None. H.M. Hoffmann: None.
Millions of cats enter animal shelters each year. Unfortunately, due to high numbers of cats entering shelters and limited physical housing space, over 50% of healthy and adoptable cats with extended shelter stays are euthanized yearly. While animal shelters are essential for keeping cats safe from unfit living conditions, they are a stressful environment. High stress in cats increases health risks and undesirable behaviors and is associated with reduced adoptions. Given the role of light in regulating hormonal stress responses and behavior, we partnered with a Midwestern animal control and shelter to evaluate how light intensity and light composition impact feline behavior and urinary cortisol levels in 123 domestic cats (Felis catus; 65 male and 58 female). The impact of three lighting conditions, white, dim, and orange (blue-depleted) light, were evaluated for the first 5-6 days following admittance into the shelter. Individually housed adults (8 months-10 years) were outfitted with PetPace Smart Collars to evaluate locomotor activity, and cat stress was evaluated daily through urine samples and a behavioral approach test. All data were analyzed by experimenters who were blind to the groups and tested via one or two-way ANOVA or repeated measures mixed-effects model with Geisser-Greenhouse correction. Urinary cortisol levels were dependent on both light quality and day in shelter, where cats under orange light had reduced cortisol on days 4-5 in the shelter compared to cats in standard lighting. Light quality also altered cat hiding behavior, such that the percentage of cats hiding was increased on dim light compared to both standard and orange light. A novel behavioral approach task found reduced cat stress on days 4-5 in standard and orange light; however, dim light increased cat stress on day 5 in shelter. All cats exhibited circadian rhythms in locomotor activity with periods ranging from 21.33-35.67h independent of light condition and day in shelter, and locomotor activity increased on days 3-4 compared to day 2 in the shelter, with no effect of light condition. There were no sex differences in in hiding, PetPace activity, or cat stress scores under any light condition; however, females displayed increased urinary cortisol levels compared to males in standard, but not dim or orange, light. This shows for the first time that room light manipulation can help shelters enact easy and inexpensive changes that make the adjustment period shorter and less stressful for incoming cats which will improve animal wellbeing.
Presentation: 6/1/2024
8110 Lymphocytic Hypophysitis secondary to a ruptured Rathke’s Cleft Cyst complicated by post surgical recurrence: A rare phenomenon
Authors: Maharaul M S , Thelmo F , Ahmed I 
Published: October 2024

Abstract
Disclosure: M.S. Maharaul: None. F. Thelmo: None. I. Ahmed: None.
Introduction: Lymphocytic hypophysitis secondary to ruptured Rathke’s cleft cyst (RCC) is a rare entity. Rathke’s cleft cysts are benign fluid-filled intra-sellar cysts that originate from the remnants of Rathke’s pouch and contain mucoid material. Most are asymptomatic; some may get symptomatic during cyst expansion and rupture releasing liquid content and trigger local inflammation. Surgical resection followed by glucocorticoids is usually curative. Case: A 42-year-old female presented to the hospital with one week history of right sided frontal headache associated with blurred vision in right eye. MRI Brain showed a 15 mm complex cystic lesion in the sella with suprasellar extension associated with peripheral calcifications. On admission, endocrine laboratory investigations including pregnancy test were normal. Ophthalmic testing did not reveal any acute abnormalities. Transsphenoidal surgery was performed for tumor resection. Pathology examination revealed infiltration of massive lymphocytes, macrophages, plasma cells, and eosinophils that were diagnostic of lymphocytic hypophysitis in the anterior pituitary lobe. She was started on glucocorticoids and discharged home. Rheumatology and Infectious diseases workup were unrevealing. On follow up 3 weeks later, she had self-discontinued steroids. The following week, she presented to the emergency room again with a right sided headache and blurred vision. MRI Brain revealed a 16 mm recurrent inflammatory mass lesion in the sella. Endocrine panel demonstrated an 8 am serum cortisol level of 7.4 mcg/dl, ACTH 20 pg/ml, FSH 6.2 mIU/ml, LH 4.9 mIU/ml, free T4 1.1 ng/dl and prolactin 8 ng/ml. She underwent transsphenoidal resection of the mass again and was restarted on glucocorticoids. This time pathology examination revealed an epithelial lined cyst most compatible with Rathke’s cleft cyst. She continued to remain on a glucocorticoid taper during the follow up period. On re-evaluation, her endocrinology laboratory investigations continued to show a deficiency of gonadotropins for which she is following up with OBGYN, but the remaining pituitary hormones were all within normal limits. Conclusion: Rathke’s Cleft Cysts (RCCs) should be in the differential diagnoses for evaluation of hypophysitis. There have only been a handful of cases in the literature of hypophysitis associated with a ruptured RCC, and only one case of recurrence after surgical debulking. This case provides an insight into the clinical behavior, diagnosis, and timely management of lymphocytic hypophysitis due to a ruptured Rathke’s cleft cyst and management post-recurrence.
Presentation: 6/3/2024
8322 Mast Cells: a New Player in Gonadotroph Tumors
Authors: Ilie M D , Lepetit M , Chanal M , Vasiljevic A , Jouanneau E , Gandrillon O , Picard F , Raverot G , Bertolino P 
Published: October 2024

Abstract
Disclosure: M. Ilie: None. M. Lepetit: None. M. Chanal: None. A. Vasiljevic: None. E. Jouanneau: None. O. Gandrillon: None. F. Picard: None. G. Raverot: None. P. Bertolino: None.
Context: While gonadotroph tumors lack both prognostic markers and medical treatment options, the tumor microenvironment (TME) stands as a promising therapeutic and prognostic tool. Aim: Identify new TME players in gonadotroph tumors, gain insight into the mechanisms of tumorigenesis driven by these TME cells, and identify new TME-related prognostic markers and therapeutic targets. Methods: Data analysis of single-cell transcriptomics of 6 gonadotroph tumors and spatial transcriptomics of 3 gonadotroph tumors. Immunohistological validation on a cohort of 50 gonadotroph tumors, including 10 paired recurrent tumors. Results: 24,471 sequenced cells from the 6 tumors were analyzed. As expected, we found all previously TME-reported cell types (including stromal, endothelial, monocytes/macrophages, stem, and T cells) and identified mast cells as a new population in gonadotroph tumors. Tryptase immunostaining and whole slides analysis confirmed the presence of mast cells in all 50 gonadotroph tumors (range 0.01-4.33%). Ligand-receptor networks analysis, done with CellPhoneDB, identified bilateral crosstalk between mast cells and endothelial cells. VEGFA was the top ranked secreted ligand signaling from mast cells towards endothelial cells, suggesting a proangiogenic role for mast cells. Consistent with this hypothesis, the percentage of mast cells was very strongly correlated with the percentage of endothelial cells in the 6 tumors (Spearman’s rho=0.94, p=0.01). Spatial transcriptomics analysis showed that mast cells and endothelial cells were frequently colocalized, which was confirmed by double tryptase/CD34 immunofluorescence. We further found mast cells to express more VEGFA than TNF in the 6 sequenced tumors, which is suggestive of a pro-tumorigenic role. Using a clinical cohort, we confirmed the association of mast cells with a bad prognosis, as tumors progressing/relapsing more rapidly after surgery had more mast cells (p=0.002). In addition, more mast cells were present in the recurrent compared to the initial tumor for a same patient (p=0.007). Finally, bioinformatic analysis using Nichenet pinpointed KITLG (acting via KIT) to be one of the probable drivers of VEGFA expression in mast cells. Interestingly, KITLG-KIT was also the top ranked interaction between endothelial and mast cells. Conclusion: We identified and validated the presence of mast cells in gonadotroph tumors. The phenotype of mast cells was indicative of a bad prognosis, which was confirmed in a clinical cohort of 40 patients. Moreover, bilateral crosstalk between mast cells and endothelial cells was indicative of a mutual potentiation, suggesting that KIT and VEGFA targeting might be beneficial for the treatment of gonadotroph tumors.
Presentation: 6/1/2024
6917 Multiple Red Herrings Complicating the Diagnosis of Cyclic Cushing’s Syndrome
Authors: Grover A , McGlotten R , Nieman L K 
Published: October 2024

Abstract
Disclosure: A. Grover: None. R. McGlotten: None. L.K. Nieman: None.
Introduction: Cyclic Cushing’s syndrome (CCS) is a rare disorder characterized by intermittent hypercortisolemia. It may be caused by pituitary tumor (Cushing disease), ectopic ACTH tumor secretion (EAS), or primary adrenal disease. We present a case of CCS with multiple red herrings complicating the diagnosis. Case: A 57-year-old Cushingoid appearing woman presented elsewhere with weight gain, brain fog, weakness, hypertension, worsening diabetes, and OSA. Screening tests showed more than three episodes of hypercortisolism with interval eucortisolism: salivary and 24-urine cortisol (UFC) ranged from 0.06-0.34 µg/dL (reference range, RR, ≤0.09 µg/dL) and 59.7-137.1 µg/24 h (RR 4-50 µg/24 h) respectively. The patient was symptomatic throughout. Differential diagnosis was CCS vs a physiologic non-neoplastic condition. As she had no clear etiology for the latter, further testing was performed. ACTH was indeterminate (23-27 pg/mL, RR &lt;46). Pituitary MRI showed a left 7 mm lesion. Inferior petrosal sinus sampling (IPSS) with Corticotropin Releasing Hormone (CRH) administration showed peripheral baseline ACTH levels of 9.0 and 10.0 pg/mL, suggesting that she had cycled out of a hypercortisolemic phase. The left petrosal baseline values were low (9 pg/mL,16 pg/mL), suggesting poor catheterization, which was confirmed by a low prolactin-normalized ACTH ratio. The petrosal levels were lower than expected (maximum 767 pg/ml), due to suppression of normal corticotropes vs poor tumor response. However, a central:peripheral step-up was consistent with Cushing's disease (CD) or pseudo-CS. She was referred to us for re-evaluation. A low FSH, LH, low normal TSH, and UFC of 160 µg/24h supported a diagnosis of CS. ACTH was 14.6 pg/mL. Pituitary MRI showed a 1.3 cm x 0.8 cm mass extending into the left cavernous sinus. She did not suppress cortisol during a dexamethasone suppression test (DST). After CRH administration ACTH levels doubled. Based on the macroadenoma and CRH response, CD was established; IPSS was not repeated. After transsphenoidal hypophysectomy, pathology revealed ACTH positive adenoma. Post-operative adrenal insufficiency required hydrocortisone replacement. Conclusion: CCS can pose a diagnostic challenge due to unpredictable duration and frequency of hypercortisolism. Intermittently elevated cortisol levels with CS symptoms should raise suspicion for CCS. In our case, low peripheral ACTH levels further suggested this possibility. DST may give spurious results in CCS owing to spontaneous falls or rises in cortisol at the time of testing. Prolonged hypercortisolism is required in all patients to ensure suppression of normal corticotropes, which if not complete, may confound results in patients with EAS. Finally, inadequate catheterization may affect accuracy of lateralization in any patient with CS and is ideally evaluated both by venography and prolactin measurement.
Presentation: 6/1/2024
7996 Neuroanatomic Characterization of Mouse Kisspeptin Neurons in the Bed Nucleus of the Stria Terminalis
Authors: Zdon Samuel Thomas , Silva Mauro S B , Navarro Victor Manuel 
Published: October 2024

Abstract
Disclosure: S.T. Zdon: None. M.S. Silva: None. V.M. Navarro: None.
Kisspeptin (Kiss1) neurons are essential for reproductive function as they are strong regulators of the hypothalamic-pituitary-gonadal axis (HPG). Mammalian Kiss1 neurons are mainly located in the hypothalamus, controlling gonadotropin-releasing hormone (GnRH) secretion, where the anteroventral periventricular nucleus (AVPV) population is morphologically and functionally sexually differentiated. Kiss1 neurons are also found in limbic areas, such as the bed nucleus of the stria terminalis (BNST). This nucleus is involved in the integration of the HPG axis with sex-dependent social behaviors and metabolic functions. However, it remains unclear whether these populations show sexually dimorphic features. The present study focused on the neuroanatomical characterization of Kiss1BNST neurons in mice on both sexes. A Kiss1cre;salsa6f mouse strain carrying the expression of tdTomato specifically in Kiss1 neurons was used to study the distribution of Kiss1BNST neurons. The BNST is divided into the anterior division of the BNST (aBNST), and a more posterior division called the principal component of the BNST (prBNST). Results indicate that male mice have significantly more Kiss1prBNST neurons than females (Male: 139.4 ± 23.32 vs. Female: 43.70 ± 5.33 neurons; **P &lt; 0.01). This sex-biased distribution was absent in Kiss1aBNST neurons. Additionally, stereotaxically injecting a Cre-dependent recombinant adenovirus carrying the expression of mCherry reporter into the aBNST or prBNST in adult mice was performed to observe neuronal projections. We observed fibers from aBNST-injected Kiss1 neurons projecting widely to areas that include the AVPV, medial preoptic area (MPO), lateral preoptic area (LPO), and periventricular hypothalamic nucleus (PVH). Moreover, fibers and cell bodies from male prBNST-injected Kiss1 neurons projected to dorsal lateral BNST (dlBNST), juxta-periventricular lateral hypothalamic area (JPLH), and the posterolateral stria terminalis (STMPL). This study observed a sexual dimorphic Kiss1 neuronal population in the prBNST, with males having more Kiss1prBNST neurons present and prospective postsynaptic areas in the brain where these neurons project to, helping to aid future studies on characterizing the functional role of these neurons.
Presentation: 6/1/2024
9325 Obesity Alters Pomc And Kisspeptin Neuron Crosstalk Leading To Lower Luteinizing Hormone
Authors: Villa Pedro , Ruggiero-Ruff Rebecca , Jamieson Bradley , Campbell Rebecca , Coss Djurdjica 
Published: October 2024

Abstract
Disclosure: P. Villa: None. R. Ruggiero-Ruff: None. B. Jamieson: None. R. Campbell: None. D. Coss: None.
Obesity is a significant public health concern due to its high prevalence and numerous comorbidities. It is associated with hypogonadism in males, characterized by low testosterone and sperm number. Previous studies determined that these stem from dysregulation of hypothalamic circuitry that regulates reproduction, by unknown mechanisms, since studies are confounded by chronic nature of this condition that leads to synaptic changes and alterations in neuron responsiveness to stimuli. Herein, we used mice fed chronic high-fat diet, that mimics human obesity, to determine mechanisms of impairment at the level of the hypothalamus, in particular gonadotropin-releasing hormone (GnRH) neurons that regulate luteinizing hormone levels (LH), which in turn regulates testosterone synthesis. Consistent with obese humans, we demonstrated lower LH, and lower pulse frequency of LH secretion, but unchanged pituitary responsiveness to GnRH. Pulse frequency of LH is regulated by pulsatile GnRH secretion, which is controlled by kisspeptin. Peripheral and central kisspeptin injections, and DREADD-mediated activation of kisspeptin neurons, demonstrated that kisspeptin neurons were suppressed in obese mice. Thus, we investigated regulators of kisspeptin secretion. We determined that LH response to NMDA was lower in obese mice, corresponding to fewer glutamate receptors in kisspeptin neurons, which may be critical for kisspeptin synchronization. Given that kisspeptin neurons also interact with POMC neurons, which regulate satiety and are particularly affected by obesity, we examined their crosstalk, and determined that LH response to either DREADD-mediated activation of POMC neurons or central injection of αMSH, a product of POMC, is abolished in obese mice. This was accompanied by diminished levels of αMSH receptor, MC4R, in kisspeptin neurons. The reason may be that chronically higher activity of POMC neurons in response to obesity, downregulates αMSH receptors on target neurons, including kisspeptin. This may lead to suppression of kisspeptin neurons, and their inability to regulate pulsatile secretion of GnRH. Together, our studies determined that obesity leads to downregulation of receptors that regulate kisspeptin neurons, which is associated with lower LH pulse frequency, leading to lower LH and hypogonadism.
Presentation: 6/2/2024
7726 Central Adrenal Insufficiency From Inhaled Mometasone Manifesting As Growth Deceleration
Authors: Gurnurkar Shilpa , Ilyssa Cooper Felicia 
Published: October 2024

Abstract
Disclosure: S. Gurnurkar: None. F.I. Cooper: None.
Introduction: While long courses and/or high-doses of oral steroids have been found to cause adrenal suppression and resultant insufficiency, inhaled corticosteroids from asthma management typically do not affect cortisol production. However, in this case, we describe a patient who presented with 3 years of growth deceleration and was found to have adrenal suppression from her inhaled corticosteroid/long-acting beta agonist, Dulera (mometasone furoate and formoterol fumarate). Case Presentation: An 11-year-old female with history of moderate persistent asthma presented to our endocrinology department with growth deceleration and resultant short stature. The parent noted that the child started to decelerate in height percentiles from the 50th percentile at age 8 to the 6th percentile at age 11. BMI gradually rose from the 85th to 95th percentiles. The parent noted that the child started having worsening asthma symptoms around the start of the growth deceleration, requiring a handful of oral steroid courses and the addition of daily inhaled corticosteroid, Dulera. She had remained on the Dulera for the previous three years, with her asthma under good control. She also took cetirizine daily and albuterol as needed. The last course of oral steroids was three months prior to her first endocrinology visit. The patient’s mid-parental target height was at the 50th percentile and she denied fatigue, headache, or abdominal pain. Family history was negative for endocrine conditions and short stature. Puberty began at age 10. Further workup was recommended. A bone age was concordant with chronologic age. Initial labs including a TSH, free T4, IGF-1, IGFBP-3, CBC, ESR, and CMP were within normal limits. A growth hormone stimulation test with arginine and clonidine was performed. Growth hormone peak was 11 ng/mL, but, interestingly, cortisol resulted as &lt;1.0 ug/dl throughout the test. Due to concerns of adrenal insufficiency, she underwent a high dose ACTH stimulation test. Initial ACTH was 6.3 pg/mL (ref 6-48 pg/mL) and cortisol remained at &lt;1.0 ug/dl at 0, 30, and 60 mins. She was diagnosed with central adrenal insufficiency and prescribed 11 mg/m2 BSA/day of hydrocortisone divided three times daily, with stress dosing and emergency hydrocortisone injection instructions. Conclusion: The existing literature suggests that Dulera (mometasone furoate and formoterol fumarate) does not significantly influence adrenal function nor growth velocity. However, we present the case of a child with 3 years of inhaled Dulera use and significant central adrenal insufficiency. This case report is the first of its kind to detail decreased adrenal function with Dulera in particular.
Presentation: 6/2/2024
8138 Pituitary Stalk Interruption Syndrome (PSIS) in a patient with Isolated Hypogonadotropic Hypogonadism
Authors: Thomson A , Osman R 
Published: October 2024

Abstract
Disclosure: A. Thomson: None. R. Osman: None.
Pituitary Stalk Interruption Syndrome in a Patient with Isolated Hypogonadotropic Hypogonadism Pituitary Stalk Interruption syndrome (PSIS) is a rare cause of hypopituitarism, characterized by a radiologic constellation of thin or interrupted pituitary stalk, hypoplasia, or aplasia of the anterior lobe and with the presence of an ectopic posterior pituitary (EPP). It is most commonly associated with isolated growth hormone deficiency (IGHD) and is often diagnosed in childhood. We present one case of a patient with isolated hypogonadotropic hypogonadism in adulthood, subsequently found to have an PSIS on MRI. A 45 year old male patient presented to our clinic with hypogonadism. He gradually started developing decreasing libido, fatigue, and loss of erections. He had normal puberty and childhood growth, and has fathered one child. He denied history of anosmia or visual symptoms. Subsequent hormonal testing showed: morning Total Testosterone: 145 ng/dl (normal 264-916 ng/dl), Free testosterone 1.5 pg/ml (normal 6.8-21.5 pg/ml), LH 1.1 mIU/ml (normal 1.7-8.6 mIU/ml) and FSH of 3.6 mIU/ml (normal 1.5-12.4 mIU/ml). Prolactin was minimally elevated at 21 ng/ml (normal 4.0 - 15.2 ng/ml). Thyroid, IGF-1, cortisol, and ferritin levels were within normal limits. Repeat levels showed similar findings. He denied ever taking any form of exogenous testosterone. His pituitary MRI revealed a small volume of anterior pituitary tissue, measuring 0.2cm x 0.7cm x 0.7cm, without discrete pituitary adenoma, a hypoplastic midline stalk measuring 1.3 mm in AP diameter (nl 2-3 mm), with a T1 hyperintense nodularity measuring 0.6cm x 0.4cm along the posterior aspect of the sella turcica consistent with EPP. No additional structural abnormality or any mass lesions were identified. He was subsequently started on replacement testosterone therapy and his symptoms resolved. PSIS usually presents in childhood with IGHD. Patients may have other pituitary hormone deficiencies and congenital central nervous system defects, although panhypopituitarism is rare. There have been reports in children with delayed puberty and isolated hypogonadotropic hypogonadism who have been found to have PSIS. Only one othercase of an adult female patient exhibiting hypogonadotropic hypogonadism as the only manifestation of PSIS has been documented in the literature. Our case highlights the potential for an adult male to present later in life with hypogonadotropic hypogonadism as a manifestation of PSIS. The marginally elevated prolactin level may be due to lack of inhibition of hypothalamic dopamine on lactotroph cells within the pituitary caused by the EPP, although it is doubtful that this has clinical significance. This is a rare presentation of PSIS, clinicians should be mindful ofthis radiological constellation and the potential for isolated hypogonadotropic hypogonadism presenting unusually in the adulthood.
Presentation: 6/3/2024