bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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

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 <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

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 < 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

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

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 <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 <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

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
8380 Pituitary Stalk Interruption Syndrome, A Rare Cause of Panhypopituitarism
Authors: Abdulkarim Faridat , Alshdifat Esra’a , Feliz Pamela Henriquez , Vargas-Jerez Julia , Zahra Tasneem
Published: October 2024

Disclosure: F. Abdulkarim: None. E. Alshdifat: None. P. Henriquez Feliz: None. J. Vargas-Jerez: None. T. Zahra: None.

Pituitary Stalk Interruption Syndrome, A Rare Cause of Panhypopituitarism Faridat Abdulkarim, MD. Esra’a Alshdifat, MD. Pamela Henriquez Feliz, MD. Julia Vargas- Jerez, MD. and Tasneem Zahra, MD. Introduction: Pituitary stalk interruption syndrome (PSIS) is a rare congenital pituitary anatomical abnormality with reported incidence of 0.5 per 100,000 live births. It is characterized by the triad of thin or interrupted pituitary stalk, absent or ectopic posterior lobe and hypoplastic or aplastic anterior lobe seen on MRI. The anterior pituitary function is usually impaired however the posterior pituitary is usually intact and normal. We report a case of a Now 34-year-old Female who presented to the endocrine clinic with underdeveloped sexual characteristics. MRI done was consistent with PSIS. This is the second case of PSIS we report from our Institution. Case Presentation: A Now 34-year -old Hispanic American Female presented to our endocrine clinic with underdeveloped secondary sexual characteristics. She had panhypopituitarism, including Growth hormone deficiency and was treated with growth hormone from early childhood until age 13-14 years. She re-presented to our clinic at the age of 28 years after being lost to follow up for many years. On physical examination, she was 175cm tall, weighed 89.4kg and BMI 29.1kg/m2Patient has pre-pubertal breast, tanner stage 1, no axillary hair, small external genitalia with scanty pubic hair. Hormonal analysis revealed Estradiol <5 pg/mL (low), FSH 0.4 IU/L (low), LH <0.3 IU/L (low), Progesterone 0.1ng/mL (Low), Testosterone <2.5 ng/dL (8.4- 48.1ng/dl) Prolactin 22.3ng/mL (3.4-24.1 ng/ml), TSH 0.88uIU/mL (0.27-4.20), Free T4 0.5ng/dl (0.9-1.8) , ACTH 7.7pg/mL (7.2-63.3), Baseline AM Cortisol 0.7ug/dL (6.0-18.4) and 5.5 ug/dL after Cosyntropin test, IGF-1 17ng/mL (83-280). Urinalysis revealed normal specific gravity. Chromosome analysis with Normal Karyotype 46XX. Pelvic US revealed Markedly diminutive uterus and ovaries. MRI of the pituitary was highly suggestive of PSIS. She is currently being treated with levothyroxine and hydrocortisone Conclusion: PSIS is a rare congenital abnormality. Fortunately has good prognosis, however if left undiagnosed/untreated has high mortality mainly from Adrenal insufficiency and Myxedema coma. The patient discussed above, has underdeveloped sexual characteristics and primary amenorrheaLaboratory finding consistent with Panhypopituitarism with Normal prolactin which is the case in most patient with PSIS. Imaging revealed atrophic uterus and ovaries, and MRI revealed Findings which are highly suggestive of PSISShe previously had problems with outpatient clinic visits and medication compliance. However, she is currently compliant with hormonal replacement therapy which is the mainstay of treatment.

Presentation: 6/3/2024
7170 Plasticity of the Hypothalamic Tuberoinfundibular Dopaminergic Neuronal Network in Lactating Rats
Authors: Papaioannou P , Georgescu T , Grattan D R , Bunn S , Yip S
Published: October 2024

Disclosure: P. Papaioannou: None. T. Georgescu: None. D.R. Grattan: None. S. Bunn: None. S. Yip: None.

The tuberoinfundibular dopaminergic (TIDA) neurons play a crucial role in regulating prolactin secretion. Their synchronized network activity with slow but highly rhythmic firing pattern is important for dopamine release in rats[1]. While this unique TIDA network activity is vital for prolactin negative feedback in non-lactating conditions, its behaviour during lactation, when prolactin demand is high, remains unknown. Our hypothesis posited that the TIDA neuronal network in lactating rats becomes desynchronized, disrupting the negative feedback loop. To test this, we utilized ex-vivo Ca2+ imaging to simultaneously monitor population-wide TIDA neuron activity in non-lactating (NL; n=13) and lactating (L; n=10) rats injected with a cre-inducible adeno-associated virus (AAV) containing the Ca2+ indicator, GCaMP6s, into their arcuate nucleus. Analysis of neuronal network synchronicity revealed significant desynchronization in the TIDA network during lactation, as indicated by a markedly lower mean correlation coefficient matrix (CM) compared to non-lactating conditions (NL: 0.87±0.02, n= 26 sections vs L: 0.22±0.03, n=29 sections; p<0.001, Student’s t-test). Furthermore, the oscillatory activity patterns of these desynchronized TIDA neurons displayed a significantly lower cell rhythmicity index (RI) in lactating animals compared to non-lactating ones (NL: 0.17±0.01, n=186 cells vs L: 0.70±0.02, n=77 cells; p<0.001, Student’s t-test). Interestingly, within these low rhythmic neurons, some exhibited higher while others showed lower firing frequencies compared to non-lactating TIDA neurons. After 7 days post-weaning (n=4 animals), the TIDA network activity returned to non-lactating behaviour (CM = 0.85 ± 0.04, n=6 sections and RI = 0.17±0.01; n=47 cells). In summary, our findings demonstrate a reversible reconfiguration of the TIDA neuronal networks during lactation, characterized by low rhythmic oscillations and individual unique firing patterns, leading to diminished intercellular synchrony that may impede dopamine release, ultimately facilitating prolactin release to support lactation. Once weaned, the TIDA neuronal network reset to NL state to allow a new reproductive cycle. [1] Lyons, D. J., Horjales-Araujo, E. & Broberger, C. Synchronized network oscillations in rat tuberoinfundibular dopamine neurons: switch to tonic discharge by thyrotropin-releasing hormone. Neuron 65, 217-229, doi:10.1016/j.neuron.2009.12.024 (2010).

Presentation: 6/2/2024
8363 Prevalence and risk factors related to venous thromboembolism events in a large cohort of Cushing disease patients
Authors: Pereira Ana Julia Garcia , Cunha-Neto Malebranche Berardo Carneiro , Batista Rafael Loch , Cescato Valter Angelo Sperling , da Silva Gilberto Ochman , Villares Fragoso Maria Candida Barisson , Glezer Andrea , Machado Marcio Carlos
Published: October 2024

Disclosure: A.J. Pereira: None. M.B. Cunha-Neto: None. V.A. Cescato: None. G.O. Silva: None. M.C. Fragoso: None. A. Glezer: None. M.C. Machado: None.

Background: Cushing’s syndrome (CS) is associated with a hypercoagulation state with an increased risk of venous thromboembolism (VTE) events, regardless of conditions associated with a higher incidence of cardiovascular events. However, the exact risk profile of CS patients who develop VTE events and the prophylactic anticoagulation strategy are heterogeneous in the literature. Objective: To identify the prevalence and risk factors related to VTE events in a large cohort of Cushing’s disease (CD) patients. Patients and Methods: A single-tertiary referral center retrospective study was conducted. Four hundred and eight confirmed CD patients were included, 79% female, median age of 32 years (ranged of 8-71), 73% harbored microadenomas (n=298), evaluated between 1990 to 2022. Most CD patients were submitted to pituitary surgery as the first treatment option. Detailed retrospective data analyses of medical records (physical and electronic) were used to identify and describe the VTE events (VTE group). Numerous clinical, hormonal, radiological and post-surgical parameters were evaluated in VTE group and compared to CD patients without events. Data from both groups were compared using a multivariate logistic regression study aiming to identify the risk profile of VTE events. As a control group, 323 patients with clinically non-functioning pituitary adenomas (NFPA) were evaluated, 51.1% male, median age of 53 years, all with pituitary macroadenomas, submitted to pituitary surgery in the same conditions and Institution. Results: Thirty-five VTE events (8.6%), mainly deep vein thrombosis (60%), were found in CD patients in comparison to only one VTE event in NFPA patient (0.3%). Most events occurred in the preoperative period (54%) and in a hypercortisolism state (71%). After statistical analysis, higher risk factors for VTE events were associated with age >24 years-old, obesity, filling of supraclavicular fossae, purple striae, mood disorders, serum morning cortisol >40 μg/dL, urinary cortisol >3,500 μg/24-h, and in a presence of postoperative complications (cerebrospinal fluid fistula, transient diabetes insipidus, infections). Conclusions: Active Cushing’s disease was associated with a higher rate of VTE events compared to the NFPA control group, especially in those cases with severe hypercortisolism, older patients and with post-surgical complications. In this profile of cases, a prophylactic anticoagulation can be instituted to reduce the morbid mortality.

Presentation: 6/3/2024
7486 Pulmonary Embolism following Transsphenoidal Surgery in a Patient with Cushing’s Disease
Authors: Davis Adam N , Elshimy Ghada , Vender John
Published: October 2024

Disclosure: A.N. Davis: None. G. Elshimy: None. J. Vender: None.

Introduction: Cushing’s Disease (CD) is associated with increased risk of venous thromboembolism (VTE), especially in the perioperative period. There is no standard of practice for thromboprophylaxis for CD patients. We present a patient with CD who had a pulmonary embolism (PE) postoperatively. Case: Patient is a 42-year-old female with no known history of pituitary adenoma who presented on 11/7/22 as transfer from outside hospital after presenting with left ptosis, diplopia, and headache with CT head showing sellar mass. Vital signs were stable. Physical exam revealed left eye ptosis with inability to abduct the right eye. ACTH level at 12:28 AM was 102pg/mL. Dexamethasone 10mg IV was given at 1:18 AM and then continued at 4mg IV q6 hours. Cortisol at 8:38 AM was 79.73mcg/dL. Calcium was 12.3mg/dL and PTH 741pg/mL, consistent with primary hyperparathyroidism. MRI brain pituitary protocol 11/8/22 revealed a peripherally enhancing 2.1 x 4.2 x 3.6 cm sellar mass extending into both cavernous sinuses, suspicious for apoplexy. Transsphenoidal surgery was performed 11/8/22 for debulking. Pathology was consistent with pituitary adenoma staining positive for ACTH. Postoperative labs included cortisol 16.45mcg/dL on 11/10/23 at 3:34PM while still on dexamethasone 4mg IV q6 hours. Inpatient rehab was recommended by PT, however patient declined. She was discharged home on 11/29/22 on hydrocortisone 20mg PO QAM and 10mg PO early afternoon and desmopressin 0.1mg PO QHS for central diabetes insipidus. Of note, she received thromboprophylaxis with Lovenox 60mg SQ the night of 11/7/22 followed by heparin 7500u q8h SQ until discharge. No thromboprophylaxis was continued at discharge. She was readmitted 12/12/22 after presenting with shortness of breath, and she was found to have a large saddle PE with right heart strain for which she was given tPA. She was discharged on apixaban 3 days later. She had parathyroidectomy 2/22/23 with removal of left inferior parathyroid adenoma with evidence of biochemical cure. Genetic testing was negative for MEN1. Unfortunately, three months later, the patient was admitted for moderate volume subarachnoid hemorrhage and was discharged to a rehabilitation facility after which she was lost to follow up. Discussion: CD is associated with increased risk of VTE, especially in the perioperative period, and this has been attributed to changes in the coagulation cascade. Our patient had increased risk of VTE in the setting of poor functional status and CD with evidence of persistent disease postoperatively. Primary hyperparathyroidism may also be associated with increased risk of VTE, likely due to the effect of hypercalcemia on the coagulation cascade. It is unclear whether continued thromboprophylaxis after discharge may have prevented her PE. There is a need for clear consensus guidelines on patient selection for thromboprophylaxis and duration of thromboprophylaxis.

Presentation: 6/1/2024
8221 Rare and Debilitating Endocrine Complications Post Craniopharyngioma Resection in a 29-year-old Male
Authors: Sargin Pinar , Montoya Jacqueline
Published: October 2024

Disclosure: P. Sargin: None. J. Montoya: None.

Several complications have been reported during the postoperative phase following craniopharyngioma resection, with electrolyte disturbances and hormonal imbalances as two of the most common during the early postoperative period. Central diabetes insipidus (DI) occurs commonly in these patients. In rare cases, patients lose their thirst response to hyperosmolarity, resulting in adipsic diabetes insipidus (ADI). Patients with ADI may develop permanent DI that is often difficult to manage even with proper treatment, leading to multiple hospitalizations, numerous comorbidities including severe hypernatremia and deep vein thrombosis (DVT), high morbidity and mortality. Panhypopituitarism is another common post-operative complication of any suprasellar mass. It is associated with multiple systemic, often life-threatening comorbidities; some are poorly understood. The intricate interplay of hormones in the pituitary gland and their diverse effects on various body systems has hindered our complete comprehension of their synergistic effects and the resulting complications. An otherwise healthy 29-year-old man with craniopharyngioma underwent resection 4 months ago at another facility. His postoperative course was complicated with central DI and panhypopituitarism and he was discharged with desmopressin, levothyroxine, and steroids. He also had a pacemaker placed due to unexplained sick sinus syndrome (SSS) that developed following surgery. He was admitted with lethargy and altered mental status, then was diagnosed with hypovolemic shock in the setting of DI with possible contributing adrenal insufficiency. Laboratory work-up showed hypernatremia (156mEq/L), thrombocytopenia (92k/uL), and macrocytic anemia (7.0g/dL) with normal coagulation factors. Further studies showed extensive occlusive DVT in both legs. A comprehensive work-up was unable to identify the source of cytopenias. After appropriate management, he was discharged home in stable condition. Two weeks later, he presented for the third time with unresponsiveness and worsening severe hypernatremia (170mEq/L). Per the family, he was refusing to drink anything at home. During this admission, the hospital course was prolonged with widely fluctuating Na levels. The diagnosis was concluded as ADI. Eventually, his Na level stabilized, family was educated on adequate water intake. In this complex case with multiple comorbidities, we are highlighting the relationship between panhypopituitarism and its association with SSS and cytopenias with no other identifiable cause. Although it is difficult to prove the causation in our case, some case reports have reported the association between ADI and DVT. The case presented highlights the complex challenges in managing these complications, emphasizing the need for comprehensive care and continuous patient education to mitigate potential adverse outcomes.

Presentation: 6/1/2024
6553 Remission of Cushing’s Disease on Day 6 Post Transsphenoidal Surgery
Authors: Abdou M N , Alhumaidi H
Published: October 2024

Disclosure: M.N. Abdou: None. H. Alhumaidi: None.

Background: Current recommendations for steroids replacement in the immediate post-operative (post op) period after transsphenoidal surgery (TSS) for patients with Cushing’s Disease (CD) are heterogenous and can be misleading. Monitoring daily morning cortisol for 72 hours post TSS with replacing steroids only after detecting low morning cortisol or signs of adrenal insufficiency (AI) has been mentioned in several studies. While some studies recommend either empiric steroids replacement on discharge regardless of status of remission or longer hospital stay for closer cortisol monitoring, others recommended monitoring for 3-4 days and starting steroids on discharge only if morning cortisol was < 415 nmol/L. Case: 60 years old female with a history of type 2 diabetes mellitus, hypertension and dyslipidemia was referred for an evaluation of a pituitary macroadenoma. She had an incidental finding of a pituitary mass measuring 25 mm on a CT brain obtained after a fall 3 months prior to her current visit. MRI pituitary gland revealed a 25x23x22 mm suprasellar mass with cavernous sinus invasion. She reported weight gain and worsening of diabetes control over the 2 years prior to her presentation. On exam, weight was 80 kg, BMI 32.5, BP 110/69, vital signs were otherwise normal. She had central obesity, facial plethora, and frontal hair thinning. Hormonal workup showed elevated 1 mg dexamethasone suppression test: 341 nmol/L (<55). 24h UFC was also high 233 nmol/24 hours (38-208). Morning cortisol 15.5 mcg/dl (6-18) with ACTH 228 pg/ml (7.2-63.3). Prolactin 581 mIU/L (58-418). FSH and LH were at the premenopausal range. TSH, FT4, and IGF-1 were normal. HBA1C 8%. Results were consistent with CD with central hypogonadism and mild elevation of prolactin likely due to stalk effect. Patient was admitted to the hospital for TSS. She had no surgical complications, and no steroids were used to monitor remission. Daily morning cortisol was measured after the surgery, readings were (1631, 668, 469, 224, 318, 110 nmol/l) day 1-6 (D1-D6) post op. She was started on oral Hydrocortisone (HC) 15 mg in the morning and 10 mg in the afternoon on D6 post op after documentation of cortisol level of 110 nmol/l. She was vitally stable and had no signs of AI before starting steroids. 1 day after starting oral HC she developed hypotension and hyponatremia. IV HC 100 mg was given immediately followed by 50 mg every 6 hours. Blood pressure improved with stress dose steroids. She was discharged home on HC 20 mg three times daily, tapered to reach 15, 10 over a period of 2 weeks. Conclusion: We present a case of CD that had a nadir morning cortisol on D6 post op in whom a diagnosis of fatal AI would have been missed if recommendations from some studies were followed. This case highlights the importance of prolonged monitoring for adrenal insufficiency if steroids were not used after surgery for CD.

Presentation: 6/1/2024
8412 Resolution of Central Hypothyroidism shortly after Transsphenoidal Surgery For Cushing’s Disease
Authors: Esper L , Ibrahim A , El Asmar N
Published: October 2024

Disclosure: L. Esper: None. A. Ibrahim: None. N. El Asmar: None.

Background: Cushing's disease is a rare endocrine disorder characterized by excessive cortisol production, resulting in various metabolic disturbances. Hypercortisolism is known to cause central hypothyroidism. The mechanism is complex and involves hypercortisolism mediated decreased TRH and TSH secretion in addition to inhibition of peripheral deiodination. This case details the successful management and recovery of a patient with Cushing's disease and reversal of central hypothyroidism after pituitary surgery.Case:A 43-year-old man was evaluated for central hypogonadism, 20 pound weight gain with central weight distribution, and the development of purple abdominal striae for the past year. He had a normal thyroid exam and appeared euthyroid. He was alsodiagnosed with hypertension and prediabetes in the past yearrequiring medical therapy.A low dose dexamethasone suppression test (DST) resulted in AM cortisol of 12.9 mcg/dl. Two adequate 24hr Urinary cortisol measurements showed elevated cortisol excretion at 458 and 378mcg/24. Lab evaluation revealed elevated cortisol levels along with elevated adrenocorticotropic hormone (ACTH) levels(ACTH of 172 pg/ml with a cortisol level of 23.9 mcg/dl). A high dose DST demonstrated suppression of cortisol to 3.4 mcg/dl. MRI pituitary was performed which showed a clearright sided 7mm pituitary adenoma.Thyroid function tests performed were consistent with central hypothyroidism, with low levels of free thyroxine (FT4) at 0.67ng/dl along with an inappropriately low normal thyroidstimulating hormone (TSH) at 0.596 uIU/ml. Total T4 was low at 4 ug/dl in addition to a low total T3 of 66 ng/dl. Remaining labs revealed central hypogonadism along with slightly elevated prolactin of 16 ng/ml. He was not started on thyroid hormone.He then underwent transsphenoidal surgery for tumor removal. He developed post-operative adrenal insufficiency (cortisol 2.12 mcg/dl) 16 hours post-op after which he was started on hydrocortisone replacement, indicating remission. 12 hours post-op, his TSH was 0.656 uIU/ml with a free t4 of 0.79 ng/dl, both in the normal range. 36 hours post-op, TSH was 0.524 uIU/ml and free t4 was 1.15 ng/dl. Histopathological examination confirmed the diagnosis of an ACTH-secreting pituitary adenoma.At 4 weeks post-op, thyroid labs showed normal FT4 (1.07ng/dl) and TSH (2.06uIU/ml). Conclusion: Hypercortisolism causes a global inhibition of the thyroid axis, with decreased levels of TSH, T4, and T3 (1). Previous studies suggest the monitoring of thyroid function at 6 and 12 months after surgical cure of hypercortisolism. Our case suggests that the resolution of hypothyroidism occurs shortly after surgery for Cushing’s disease and the need for earlier monitoring.

Presentation: 6/3/2024
8533 Salt on the Kidneys A case of DDAVP induced arginine vasopressin resistance
Authors: Jordan M M , Islam J R , Hassan R
Published: October 2024

Disclosure: M.M. Jordan: None. J.R. Islam: None. R. Hassan: None.

A 63-year old female with a history of head trauma complicated by polyuria and excessive fatigue diagnosed with central DI and started on treatment with oral Desmopressin. She had no other known pertinent medical history. Patient was lost to follow-up with an eventual visit to the emergency department with complaints of bilateral leg cramps, nausea and persistent headaches. She was noted to have been initiated intranasal desmopressin in addition to oral DDAVP. On initial lab work, Sodium was 114 along with acute kidney injury. She was admitted to ICU and treated with hypertonic saline. DDAVP was withheld until sodium normalized and stabilization of renal functions. GFR still remained impaired on discharge at 40 mL/min/1.73m*2. She was then discharged on DDAVP with reestablished follow up in the endocrinology clinic with complaints of persistent polyuria. Once more, she was sent to the emergency room and was admitted for acute renal injury secondary to dehydration in the setting of polyuria and altered mentation. Upon review of her medications, the patient continued both oral and inhaled DDAVP. No other medications or supplements were reported. During this subsequent hospitalization, sodium remained between 131-135 with urine output 4.5L/ day despite increasing doses of oral DDAVP and oral sodium supplementation. At which point, suspicion for mixed DI was hypothesized (central DI and arginine vasopressin resistance). Other causes of polyuria were ruled out. Labs for persistent AKI revealed gross proteinuria. Renal biopsy was performed during hospitalization which showed acute to chronic vascular thrombotic microangiopathy and focal segmental glomerulosclerosis with collapsing features. Extensive workup for chronic infections, autoimmune conditions and hematological malignancies were negative. This showed concerns for possible DDAVP induced renal injury.

Presentation: 6/2/2024
8686 scRNA-seq of pituitary from letrozole-induced PCOS mouse model reveals abnormal prolactin secretion
Authors: De Robles G , Ujagar N , Del Mundo Z , Nicholas D
Published: October 2024

Disclosure: G. De Robles: None. N. Ujagar: None. Z. Del Mundo: None. D. Nicholas: None.

Polycystic ovary syndrome (PCOS) has a complex pathophysiology and is the most common endocrine disorder among reproductive-aged women. Ovarian hormonal dynamics are regulated via the secretion of the gonadotropin-releasing hormone (GnRH), which stimulates the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary gland. High serum levels of LH in PCOS patients indicate an increase in GnRH levels, but the mechanisms within the anterior pituitary at a cellular level are unclear. We performed single-cell mRNA sequencing (scRNA-seq) on the pituitaries of the letrozole-induced (LET) mouse model of PCOS to profile the functional genomics of endocrine cell populations relative to serum hormone levels. The population percentage of lactotropes significantly decreased; in contrast, two gonadotrope populations significantly increased in the LET mice compared to the placebo-treated mice. Consistent with these changes, an increasing trend of serum LH levels and a decreasing trend of serum prolactin (PRL) levels were observed in the LET mice, while no change occurred in serum growth hormone levels. A gene set enrichment analysis (GSEA) on the differentially expressed genes (DEGs) from the lactotropes revealed an association with negative regulation of protein kinase activity. These DEGs included Hspb1, Park7, Pcp4, and Ppia, which all share the function of mediating stress-induced apoptosis. A GSEA on the DEGs between the two gonadotrope clusters in the LET mice also confirmed a variation in biological pathways linked to ribosomal subunits, transcription regulation, and the regulation of steroid metabolic processes. Based on the scRNA-seq results of the anterior pituitaries of LET mice, alterations in the proportions of hormone-secreting cells may be a response to hyperandrogenism, in which functionally diverse gonadotropes could contribute to heterogeneity in reproductive phenotypes. Changes in the lactotrope population and PRL serum levels also support further research on the lactation hormone and its role in PCOS. PRL is involved in metabolic homeostasis and reproduction, and understanding its dysregulations may provide additional insight into the pathophysiology of PCOS.

Presentation: 6/3/2024
6622 Severe Primary Hypothyroidism in a Child Presented as a Pituitary Tumour; a case Report
Authors: Awadalla S S
Published: October 2024

Disclosure: S.S. Awadalla: None.

A 9-year-old patient showed up to the emergency department due to a headache that had been going on for a month without other symptoms and no neurological alterations. Complete blood count and glycemia were normal. A Cerebral MRI was requested and showed a pituitary adenoma. The patient was initially evaluated by neurosurgeons and referred to a pediatric endocrinologist. TSH, free T4, IGFI, and cortisol were evaluated, TSH was found to be high at 936 (normal, 0.4-4.2), free T4 < 0.4; suggestive of severe primary hypothyroidism. The case was analysed with the neurosurgery department, and a joint decision to start therapy with LT4 was taken, whilst monitoring the evolution of the pituitary adenoma. TSH and Free T4 were normal, and the MRI of Sella Turcica three months later showed complete pituitary normality. The presentation of this case is of relevance as the primary modality of treatment is thyroid hormone supply and not surgery. Interprofessional team integration is recommended for the treatment of patients with this condition.

Presentation: 6/1/2024