bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT650 Catecholamine-independent Neural Pathways Drive The Rapid Catabolism Of Metabolically Inert Fat
Authors: Zhang Xiao , Majumdar Anurag , Kleiboeker Brian , Magee Kristann L , Learman Brian S , Thomas Steven A , Lodhi Irfan J , MacDougald Ormond A , Scheller Erica L
Published: October 2023

Disclosure: X. Zhang: None. A. Majumdar: None. B. Kleiboeker: None. K.L. Magee: None. B.S. Learman: None. S.A. Thomas: None. I.J. Lodhi: None. O.A. MacDougald: None. E.L. Scheller: None.

Adipocytes classically store or release energy in response to changes in metabolic status. However, several fat depots throughout the body are resistant to these metabolic cues. Identification of novel mechanisms that drive energy release from metabolically inert adipocytes is needed to inform strategies to deplete stubborn fat and, conversely, to preserve these depots in pathologic settings of wasting and cachexia. To address this question, we focused on the constitutive bone marrow adipose tissue (cBMAT), a well-established site of metabolically inert fat that remains unchanged with fasting, exercise, and cold exposure and is depleted only in certain extreme conditions such as cachexia or starvation. To study this unique depot, we developed a mouse model of rapid, complete depletion of all fat, including cBMAT, within 9 days using central intracerebroventricular (ICV) injection of leptin. Surgical denervation, chemical sympathectomy, or genetic dopamine beta-hydroxylase (DBH) deletion did not prevent the ICV leptin-induced depletion of cBMAT, revealing this process to be independent of catecholamines and the sympathetic nervous system (SNS). Vossicle implantation defined the mediators as transported through the circulation, and BMAT-specific ablation of adipose triglyceride lipase (ATGL) identified dependence on basal lipolysis. Gene expression and a radioisotope-based de novo lipogenesis assay pinpointed a concurrent suppression of lipogenesis, and subcutaneous insulin supplementation prevented leptin-induced cBMAT depletion, but not other depots. Together, this defines the differential regulation of metabolism in metabolically inert fat depots such as cBMAT. Specifically, leptin-responsive circuits in the brain can deplete inert adipocytes by suppressing lipogenesis while maintaining basal lipolysis independent of the SNS.

Presentation: Saturday, June 17, 2023
SAT158 Hypoglycemia After Bariatric Surgery Caused By Insulinoma
Authors: Yaseen Aseel , Lam Han
Published: October 2023

Disclosure: A. Yaseen: None. H. Lam: None.

Introduction: Post bariatric surgery hypoglycemia occurs at least 6 to 12 months after bariatric surgery, presents as postprandial neuroglycopenia with documented blood glucose <54 mg/dl occurring 1 to 3 hours after meals, resolving with carbohydrate intake, and normal fasting glucose. Fasting hypoglycemia or hypoglycemia > 4 hours after caloric intake is not typical of post-bariatric hypoglycemia and should raise concern for other etiologies, specifically insulinoma. Clinical Case: A 62 year old female who had Roux-en-Y gastric bypass (RYGB) surgery 18 years ago presented with confusion and a blood glucose level of 35 mg/dl.She had been having episodic hypoglycemia fasting and nonfasting for 4 years prior to presentation. Initial workup revealed serum insulin 10 uIU/ml, C-peptide 2.3 ng/ml, and serum glucose of 19 mg/dl. A dextrose 20% in water intravenous infusion was started in addition to octreotide injections, acarbose, and diazoxide. Prednisone was added later and acarbose discontinued. Magnetic resonance imaging of the abdomen and magnetic resonance cholangiopancreatography showed a 1.8 x 1.3 cm enhancing lesion within the pancreatic tail. Selective arteriography and intra-arterial calcium stimulation with hepatic venous sampling revealed significant elevation of insulin after calcium gluconate injection into the accessory pancreatic tail artery arising from the superior mesenteric artery which supplies the hypervascular pancreatic tail mass. Patient had an exploratory laparotomy and splenic preserving distal pancreatectomy. Surgical pathology revealed a 2.1 cm grade 1, well-differentiated neuroendocrine tumor that was limited to the pancreas. Hypoglycemia resolved after surgery and she was discharged on glargine insulin and metformin. 1 month after surgery, C-peptide was 0.3 ng/ml, serum glucose was 101 mg/dl and HbA1c was 6.5%. Discussion and Conclusion: The incidence of hypoglycemia after RYGB is uncertain but has been reported to be 0.1 to 0.4% of cases. Only 9 cases of insulinoma in patients with a history of gastric surgery have been reported, 7 of 9 (78%) being female with an average age of 56 years old. Symptoms included fasting and postprandial hypoglycemia occurring 6 months to 20 years after bariatric surgery. CT, MRI, and endoscopic ultrasound have been found to have excellent sensitivity for preoperative localization of insulinoma. Selective arteriography and intra-arterial calcium stimulation with hepatic venous sampling is recommended when non-invasive imaging modalities fail to localize the tumor. Surgical resection remains the mainstay for cure. Dietary modification and pharmacological therapy with diazoxide or somatostatin analogues are used in poor surgical candidates. Insulinoma after RYGB is rare, but needs to be considered in patients with hypoglycemia occurring in the fasting state, as this is atypical for post-bariatric hypoglycemia

Presentation: Saturday, June 17, 2023
SAT166 Elevated Insulin Autoantibody During COVID19 Illness Associated With Significant Hypoglycemia In A Type 1 Diabetic
Authors: Shewmon David A , Preston DeVon C
Published: October 2023

Disclosure: D.A. Shewmon: None. D.C. Preston: None.

Background: Insulin antibodies are a rare cause of hypoglycemia in diabetes mellitus type 1 (DM1). Exacerbation of this phenomenon by COVID-19 has not been previously reported. Clinical Case: A 46 year old, 60 kg female with DM1 of 19 year duration with hypoglycemic unawareness and retinopathy, who was admitted for flu-like symptoms, a blood glucose of 600 mg/dL in the absence of DKA, and COVID-19 by RT-PCR test. Hospitalization was complicated by 48 hours of hypoglycemia in the absence of insulin treatment, requiring continuous 10% dextrose infusion. Four months earlier the patient had been admitted for an undiagnosed non-COVID flu-like illness, with hypoglycemia for 60 hours in the absence of insulin treatment. Her glucose control was stable on 5 units of insulin per day at five and nine days after admission, and 25 units per day at 35 days after admission. At both admissions, the workup included a normal cortrosyn stimulation test, an undetectable C-peptide, a normal IGF-2 level, and a careful investigation to rule out evidence for self-administration of insulin. However insulin antibodies were elevated at 1.17 +/- 0.56 U/mL (n=4, normal <0.4) during the non-COVID illness, and 5.0 U/mL and 5.4 U/mL, during and 35 days after the COVID-19 illness, respectively. Thus insulin antibodies were 13 times the upper limit of normal during COVID-19 illness versus 2.9 times the upper limit of normal during the non-COVID-19 illness. Viral infection is one of the most significant environmental factors that may cause overstimulation of the immune system and has been shown to be associated with autoantibody generation and increase, in addition to autoimmune diseases. Known cytokine profiles on COVID-19 infections include IL-1, IL-6, IL-12, IFN-gamma, and TNF-alpha. The presence of IL-1 and TNF-alpha in particular, are known to be key pro-inflammatory cytokines in myriad autoimmune disorders. In vitro data suggest that IL-1 is also an important effector cytokine in DM1, through a number of direct (i.e., beta cell toxicity) and indirect means (i.e., by marking beta cells for Fas-dependent destruction by autoreactive cytotoxic T-lymphocytes). Conclusion: Our data could represent another example of the exacerbation of autoimmunity associated with COVID-19. The increases in the incidence of both autoantibodies and autoimmune diseases seen with COVID-19 suggest one of the conceptual frameworks for creating hypotheses regarding the nature of the Long COVID syndrome.

Presentation: Saturday, June 17, 2023
SAT442 Increased Prevalence Of Precocious Puberty: What Is The Influence Of Endocrine Disruptors?
Authors: Lopes Bastos Dyrlanne Marcia , Da Cunha Bastos João Gabriel Freira , Da Cunha Bastos Ana Clara Freire
Published: October 2023

Disclosure: D.M. Bastos: None. J.F. Bastos: None. A.F. Bastos: None.

Central precocious puberty (CPP) is defined by the onset of the pubertal process before 8 years old in girls and 9 years old in boys. Its main form is idiopathic, and its etiology is still unknown. Thus, several studies point to possible causative factors, from gestational age at birth to hormonal disruptors. Therefore, this work aims to collect the prevalence for the evaluation of the childrens profile who have this pathology in a private clinic in Brasília. Methodology: This is a retrospective and observational study that aims to evaluate the prevalence and analysis of the medical records of children with precocious puberty in a pediatric endocrinology clinic in the Federal District between 2020 and 2021. The medical records of children with genetic syndromes were excluded. Biological, family, nutritional variables and complementary exams were analyzed. Results: The following main characteristics were identified: higher prevalence in girls (90.6%), 23% had a body weight greater than expected for their age, the majority (80.3%) were diagnosed between 8 and 12 years and a difference of 6.7 centimeters was observed between target height and predicted final height according to bone age. Conclusion: The study concluded that among the patients with CPP, the majority were girls and almost quarter of the childrens were obese or overweight. A difference of almost 7 centimeters was found between the predicted final height and the target height of these patients, showing the need for investigation and early diagnosis of this condition.

Presentation: Saturday, June 17, 2023
THU036 68Ga-DOTATOC PET/CT In Localization Of ACTH-producing Pituitary Tumors In Patients With Cushing Disease
Authors: Kim Kyungwon
Published: October 2023

Disclosure: K. Kim: None.

Localization of adrenocorticotrophic hormone (ACTH) producing pituitary tumors has paramount importance as definitive management mainly involves surgical resection of tumors. High-resolution functional imaging modalities, such as 68Ga-DOTATOC PET/CT, have been recently introduced in clinical practice for the identification of neuroendocrine tumors. In this study, we focused on the performance of 68Ga-DOTATOC PET/CT as a tool for localizing ACTH secreting pituitary tumors compared to pituitary MRI. In a retrospective cohort study, we identified 44 patients with Cushing disease who underwent both 68Ga-DOTATOC PET/CT and pituitary MRI before TSA in Severance Hospital from 2015 to 2019. 30 of 44 patients with pathologically positive ACTH immunoreactivity confirmed under TSA were included in final analysis. We compared the accuracy of the predicted tumor location on 68Ga-DOTATOC PET/CT and MRI based on the tumor location under TSA.Median age was 34(15-68) years and 25 of 30 patients showed detected tumor in 68Ga-DOTATOC PET/CT. Age (25 vs. 51 years), pre-operative ACTH level (62.21 vs. 26.21 pg/ml). pre-operative cortisol level (20.60 vs. 17.90 pg/ml), and tumor size on MRI (7.75 vs. 5.00 mm) were not differ according to the presence or absence of DOTATOC uptake. The sensitivity of 68Ga-DOTATOC PET/CT was comparable to those of MRI (90.9% vs. 100% in microadenomas, 79.0% vs. 94.7% in macroadenomas, all p >0.05). However, it was inferior to lateralize pituitary adenoma compared to MRI (72.0% vs. 75.9%, p=0.03). The tumors were localized successfully in 18 patients by 68Ga-DOTATOC PET/CT and we divided into two groups depending on successful lateralization. Pre-operative ACTH in successfully lateralized group was significantly higher than that in the failing lateralized group (91.64 vs. 48.54 pg/ml, p=0.010). The area under the curve was measured to be 0.778 with cut-off 96.59pg/ml in ACTH level to determine the successful lateralization. Pre-operative ACTH higher than 96.59 pg/ml showed the best diagnostic accuracy (Sensitivity 50%, specificity 100%).68 Ga-DOTATOC PET/CT showed that successful detection rate was comparable to those of MRI, but success rate of lateralization was inferior. Serum ACTH level determines the successful lateralization of ACTH secreting pituitary tumor in Cushing disease.

Presentation: Thursday, June 15, 2023
THU088 Perioperative Management Of Patients With Pituitary Tumors Undergoing Surgery: A Retrospective Review
Authors: Batch Jennifer Tania , Belal Heiba , Gandhi Gunjan Yogendra
Published: October 2023

Disclosure: J.T. Batch: None. H. Belal: None. G.Y. Gandhi: None.

Background: Pituitary tumors account for 10% of brain neoplasms with transsphenoidal resection of these tumors responsible for 20% of all intracranial operations performed for primary brain tumors. Hypothesis: We suspected significant heterogeneity and lack of standardized protocols in the perioperative endocrine evaluation and management of patients undergoing resection of sellar masses. Methods: From June 2016 through November 2022, we identified 46 adult patients (23 females, mean age 52 years, age range 25 to 84 years) who underwent pituitary mass resection (44 transsphenoidal and two transcranial approaches) at our institution. We abstracted information about perioperative endocrine evaluation from their medical records. Results: The vast majority (32 patients) had nonfunctioning pituitary macroadenomas. Other indications for surgery included Cushing’s disease (3), prolactinomas (2), acromegaly (3), pituitary metastasis (1), gonadotroph adenomas (2), Rathke cleft cyst (2), and epidermoid cyst (1). Preoperative cortisol level was not measured in 8 patients. The decision to administer intraoperative corticosteroids was not consistently based on preoperative cortisol levels. 24 patients had cortisol levels <11 mcg/dL; 22 received intraoperative corticosteroids at anesthesia induction. 13 patients had cortisol levels ≥11 mcg/dL, and 11 received intraoperative steroids. Two patients had very large pituitary masses (over 4 cm), and one received intraoperative corticosteroids. Of the two patients with Cushing’s disease, one received intraoperative corticosteroids. Cortisol level was checked in 27 patients in the first four weeks after surgery; in the rest, it was measured between 2 months and three years after surgery. All five patients with confirmed adrenal insufficiency with cortisol levels <3 mcg/dL were treated with corticosteroids. 22 patients had cortisol levels in the equivocal zone (3 to 15 mcg/dL), and 16 were treated with corticosteroids. Nine patients ultimately did not have a follow-up in endocrinology. The long-term permanence of the diagnosis of diabetes insipidus could not be established due to a lack of uniform follow-up testing. Conclusions: Patients with pituitary gland tumors represent a heterogeneous yet commonly encountered neurosurgical population. Successful surgical management is critically dependent on the quality of perioperative care. Understanding preoperative evaluation, intraoperative management, potential complications, their management, and strategies for avoidance are fundamental to reduce morbidity and mortality. High-quality evidence guiding perioperative practices in this population is needed. We have used the information gathered in this study to create a multidisciplinary perioperative protocol with expertise from endocrinologists, neurosurgeons, neuro-ophthalmologists, and neuroradiologists.

Presentation: Thursday, June 15, 2023
THU093 Pituitary Enlargement And Hypopituitarism In Patients Treated With Immune Checkpoint Inhibitors: Two Sides Of The Same Coin?
Authors: Menotti Sara , Chiloiro Sabrina , Giampietro Antonella , Bianchi Antonio , Angelini Flavia , Tartaglione Tommaso , Antonini Cappellini Gian Carlo , De Galitiis Federica , Rossi Ernesto , Schinzari Giovanni , Scoppola Alessandro , Pontecorvi Alfredo , De Marinis Laura , Fleseriu Maria
Published: October 2023

Disclosure: S. Menotti: None. S. Chiloiro: None. A. Giampietro: None. A. Bianchi: None. F. Angelini: None. T. Tartaglione: None. G. Antonini Cappellini: None. F. De Galitiis: None. E. Rossi: None. G. Schinzari: None. A. Scoppola: None. A. Pontecorvi: None. L. De Marinis: None. M. Fleseriu: None.

Introduction: Immune checkpoint inhibitors hypophysitis (IIHs) represents an emerging problem in cancer patients treated with immune checkpoint inhibitors (ICIs). In this study, we aimed to describe the clinical and molecular features, therapeutic management and outcome of a multicentre series of IIHs. Material and Methods: Demographic and clinical features were retrospectively collected for all cases. Patients with new onset of pituitary disfunction during ICI treatment underwent contrasted pituitary magnetic resonance images (MRI). IIH was diagnosed if presence of typical radiological finding of hypophysitis. The immunotherapy induced hypopituitarism was defined as patients without the radiological finding of hypophysitis. Anti-pituitary and anti-hypothalamus autoantibodies were also measured. Results: Nine patients were included; 7 with metastatic melanoma, 1 metastatic lung adenocarcinoma and 1 metastatic kidney adenocarcinoma. Six patients were treated with nivolumab and three with ipilimumab. All patients had new-onset asthenia. Secondary hypoadrenalism was diagnosed in all patients. Pituitary MRI showed pituitary enlargement in 2 cases and no abnormalities in the other 7 cases. APA were positive in 57.1% and AHA in 85.7% of cases. Multidisciplinary treatments were established by neuro-endocrinologist and oncologists: all patients were treated with hydrocortisone replacement; ICI was withdrawn in 2 cases, until the clinical stabilization of the hypoadrenalism. None of the patients were prescribed immunosuppressive high dose glucocorticoids (over 40 mg /day). At follow-up, hypoadrenalism persisted in all cases. Pituitary enlargement (hypophysitis per se) on MRI spontaneously recovered in the two affected patients. We found that the typical features of hypophysitis involved more frequently females in our study and in patients treated with ipilimumab. Conclusion: Although this study did not clarify if autoimmune secondary hypoadrenalism and ICI hypophysitis on brain imaging are two sides of the same disease, our preliminary data underline the need for molecular studies of IIHs and of autoimmune ICIs-related hypopituitarism, especially central hypoadrenalism.

Presentation: Thursday, June 15, 2023
THU098 Gonadotropin Secreting Pituitary Tumor Presenting As Primary Hypogonadism
Authors: Shapiro Joshua Nathan , Lu Tiffany Xin , Eapen Jane , Karam Jocelyne Georges
Published: October 2023

Disclosure: J.N. Shapiro: None. T.X. Lu: None. J. Eapen: None. J.G. Karam: None.

Gonadotroph adenomas are the most common subtype of nonfunctional pituitary adenomas, with 35 percent secreting enough LH or FSH to raise serum gonadotropin levels, but clinical syndromes due to hypersecretion of gonadotropins are rare. A low testosterone level with high FSH or LH can mislead to a diagnosis of concomitant primary hypogonadism rather than a secreting pituitary adenoma. We present a case of a patient with an FSH-secreting pituitary macroadenoma presenting with low testosterone levels. The patient is a 67-year-old man incidentally found to have a pituitary macroadenoma measuring 12 x 13 x 12 millimeters, impinging upon the optic chiasm on MRI of the brain obtained for headaches. Visual field tests revealed abnormalities compatible with glaucoma, but not chiasm compression. He has no symptoms of hormonal excess or deficit, although his wife reported decreased erectile function. Physical examination was unremarkable except for an atrophic left testicle. Pituitary hormone function tests (ACTH, AM cortisol, IGF-1, prolactin, thyroid function tests, and 24-hour urine free cortisol) were within normal range, except for an elevated FSH 14.8-18.1 mIU/mL and decreased testosterone in range of 185-256 ng/dL, with normal LH at 7.0 mIU/mL, for which he was referred for urology for evaluation of primary hypogonadism. The patient underwent transsphenoidal resection of the pituitary adenoma. Postoperative pathology revealed a pituitary adenoma, gonadotroph cell type, with immunohistochemical staining scattered positive FSH, and rare positive LH. Postoperative MRI showed post-surgical changes with no residual nodular enhancement. Following surgery, the patient suffered from severe clinical hypogonadism with episodes of profuse diaphoresis and extreme fatigue. Postoperative laboratory values revealed panhypopituitarism with undetectable testosterone level, and low LH and FSH levels. The patient was successfully treated with hydrocortisone, levothyroxine, and testosterone, with resolution of his symptoms. Our patient presented with a pituitary macroadenoma, low testosterone, and high FSH suggestive initially of primary hypogonadism, but found ultimately to have an FSH-secreting adenoma. He likely had underlying hypogonadism, primary or secondary, and although his adenoma secreted FSH, it was not enough to maintain testosterone level in normal range, possibly in part due to biologically inactive FSH molecules or to primary testicular failure. The extremely low testosterone levels postoperatively suggest that his testicular function was mostly stimulated by the adenoma secreted FSH and was therefore drastically lost after surgery. This case increases awareness to consider a gonadotropin-secreting tumor in the differential diagnosis of a pituitary adenoma with high FSH or LH, even when testosterone level is unexpectedly low.

Presentation: Thursday, June 15, 2023
THU127 Deletion Of VGLUT2 In MCH Neurons Induces Sex-Specific Changes In Metabolic And Reproductive Function
Authors: Beekly Bethany Genelle
Published: October 2023

Disclosure: B.G. Beekly: None.

MCH neurons have a well-established role in metabolism and energy balance. MCH-knockout (“MCH-KO”) mice, which lack the MCH peptide itself, are hyperactive, hypophagic, and lean. However, MCH neurons express numerous genes involved in the synthesis, packaging, and release of the classical neurotransmitters GABA and glutamate, which are the central nervous system’s predominant inhibitory and excitatory neurotransmitters, respectively. These genes are also critical for normal metabolism, as the conditional deletion of glutamatergic signaling from MCH neurons also affects energy balance in ways that both mirror and differ from MCH-KO. When the metabolic phenotypes of MCH neuronal ablation (diphtheria toxin), MCH-KO, and transgenic Pmch-Cre;Slc17a6fl/fl mice (which lack VGLUT2 in MCH neurons) are compared, all three experimental groups exhibit decreased body weight and adiposity, increased locomotor activity, late-onset hypophagia, attenuated weight gain on high-fat diet, and reductions in circulating leptin. These data point to some functional redundancy between MCH and glutamate release from MCH neurons in the context of energy balance. By contrast, specific indicators of glucose sensing and handling differ between groups: MCH neuronal ablation and conditional VGLUT2 deletion in MCH neurons, but not global MCH-KO, result in reduced sucrose preference and improved glucose tolerance. These data suggest a role for MCH peptide in body weight regulation, but also a glutamate-dependent mechanism by which MCH neurons contribute to glucose homeostasis. Given the findings related to MCH peptide action on pancreatic islet cells and its effects on insulin resistance, it appears that MCH and glutamatergic signaling from MCH neurons must work synergistically for optimal regulation of energy balance. Importantly, all research to date on the metabolic effect of VGLUT2 deletion from MCH neurons has been in male mice. This constitutes a significant gap in the field’s understanding of these phenomena, particularly because of documented sex differences in glucose handling and associated metabolic disorders like diabetes. To address these gap, we generated Pmch-Cre;Slc17a6fl/fl mice, which lack functional VGLUT2 in MCH neurons. Body weight was measured from weaning until 20 weeks of age and the mice were subjected to comprehensive metabolic testing including oral glucose tolerance testing. We were able to recapitulate some, but not all, of the published findings in males, a fact which may in large part be due to strain differences in metabolism and glucose handling. Notably, several sexually dimorphic phenotypes were also observed, reaffirming the importance of incorporating biological sex variables into metabolic studies.

Presentation: Thursday, June 15, 2023
FRI274 Dopamine Transporter-Expressing Leptin-Sensitive Neurons In The Ventral Premammillary Nucleus Innervate Kiss1 Neurons
Authors: de Miera Cristina Sáenz , Heikkinen Laura , Broberger Christian , Elias Carol F
Published: October 2023

Disclosure: C. Sáenz de Miera: None. L. Heikkinen: None. C. Broberger: None. C.F. Elias: None.

Pubertal development is tightly regulated by energy balance, and easily disrupted in states of excess or negative energy reserves. This crosstalk between metabolism and reproduction is orchestrated by complex neural networks coordinated by circulating hormones, notably, leptin action in the hypothalamus plays a critical role. The ventral premammillary nucleus (PMv) is rich in leptin receptor (LepRb) neurons, and acts as an essential relay for leptin action on reproduction. Here, we describe a novel subpopulation of leptin sensitive neurons within the PMv that express dopamine transporter (DATPMv). We observed that in both prepubertal and adult females in diestrous, virtually all DATPMv neurons express LepRb mRNA and respond to acute leptin treatment with phosphorylation of the intracellular marker signal transducer and activator of transcription 3 (pSTAT3). Electrophyisological recordings from DAT-CRE;R26tdTomato (DAT-tdTom) mice show that DATPMv cells in adult females have a higher resting membrane potential than those in prepubertal females. DAT mRNA expression in the PMv is higher in prepubertal than in adult females. However, DAT mRNA expression was similar in adult females in diestrous, ovariectomized (OVX), and OVX treated with estradiol, indicating that the age difference observed is not due to the increase in estradiol during pubertal maturation. To trace DATPMv projections, we injected an adenoassociated virus expressing Cre-dependent channelrhodopsin (ChR2-mCherry) in the PMv of adult female DAT-Cre;Kiss1-hrGFP mice, which express GFP driven by kiss1 regulatory elements. ChR2-mCherry projections were observed in the anteroventral periventricular nucleus (AVPV) surrounding Kiss1-hrGFP neurons, a population critical for sexual maturation and positive estrogen feedback in females. No projections were observed near arcuate nucleus Kiss1-hrGFP neurons, in the medial preoptic area (MPOA) or near GnRH neurons. This contrasts with previous observations of dense projections from the overall PMv LepRb population to the MPOA, surrounding GnRH cell bodies suggesting the DATPMv subpopulation has different target areas than the non-DAT LepRb neurons. Using DAT-tdTOM females we observed that overall tdTom projections to the AVPV are denser in adult diestrous than in prepubertal females. Overall, these findings suggest that the DAT expressing LepR subpopulation in the PMv play a role in leptin regulation of sexual maturation via actions on AVPV kisspeptin neurons.

Presentation: Friday, June 16, 2023
FRI304 Prolactinomas In A Pituitary Center From Ecuador: Clinical Presentation With High Prevalence Of Giant Adenomas And Delayed Diagnosis
Authors: Quishpe Lopez Darlyng Patricia , Freire Salazar Gabriela Carolina , Villagomez Estrada Mariela Viviana , Ruiz Urbaez Rossana Massiel , Baquero Contreras Stefany Alexandra , Mino Rodriguez Rodrigo Daniel , Salazar Vega Jorge Luis
Published: October 2023

Disclosure: D.P. Quishpe Lopez: None. G.C. Freire Salazar: None. M.V. Villagomez Estrada: None. R.M. Ruiz Urbaez: None. S.A. Baquero Contreras: None. R.D. Mino Rodriguez: None. J.L. Salazar Vega: None.

Background: Prolactinomas are the most common pituitary neuroendocrine tumors (PitNET) and account for about 50% of cases. Most of them respond favorably to pharmacological treatment (cabergoline). Epidemiological data in our country are scarce and more reports are needed. The aim of this study was to analyze the clinical presentation of patients with prolactinomas in a tertiary center. A cross-sectional study was performed (November 2021 - December 2022) analyzing information from clinical records. Results: Seventy-nine patients were included, mean age at diagnosis 29.5 years (SD 12.09, range 11-65) of which the majority were women (63.3%). Due multiple factors the diagnosis was delay with a mean of 45.63 months (range 2-216). As variables related with the clinical manifestations of prolactinomas, overweight/obesity was recorded in 79.6% of the cases. The predominant reasons of attendance in women were galactorrhea 48%, menstrual alteration 22% and headache 20%. In men, in the other hand, were visual alteration 48.3% and headache 31%. The main components of hypopituitarism identified were hypogonadism 46.8% and central hypothyroidism 27.8%. Serum prolactin levels at diagnosis differed between macroprolactinomas and microprolactinomas from 5617 ng/mL (136-47000) to 140.17 ng/mL (68-278) respectively. We identified 27 (34.2%) microadenomas, 39 (49.4%) macroadenomas and 13 (16.5%) giant adenomas. Giant prolactinomas predominated in men (76.9%). There was a linear correlation between tumor size and hyperprolactinemia (Spearman correlation 0.87). Regarding initial treatment: 94.9% received pharmacological treatment. Only 5.1% underwent surgery (100% macroadenomas). Conclusion: Several factors and limitations in the public health system of Ecuador delay the timely diagnosis and treatment of pituitary tumors, affecting the quality of life of these patients. Being a national referral center, we receive a high percentage of macroprolactinomas and giant prolactinomas (65.9%). Within public health, this study is a reference to motivate future research and the development of a national guideline to optimize the management of prolactinomas.

Presentation: Friday, June 16, 2023
FRI306 Natural History Of Untreated Prolactinoma
Authors: Sadek Maryanne , Sandila Navjot , Clarke David B , Imran Syed Ali
Published: October 2023

Disclosure: M. Sadek: None. N. Sandila: None. D.B. Clarke: None. S.A. Imran: None.

BACKGROUND Prolactinomas (PRLomas) are the most common functioning pituitary tumors, and the majority are microPRLomas (<10 mm in size). Current guidelines do not support treating asymptomatic or minimally symptomatic microPRLomas based on older studies utilizing insensitive imaging and assay techniques, whereas only limited information is available about the natural history of microPRLomas based on new generation assay and advanced imaging modalities. OBJECTIVES This study aims to assess the natural history of medically untreated microPRLomas with regards to long-term trends of serum PRL, tumor growth, clinical symptoms, and their effect on other pituitary function. METHODS We conducted a retrospective review of all patients diagnosed with microPRLoma since 2005 from our comprehensive provincial pituitary registry in Nova Scotia, Canada. Secondary causes of hyperprolactinemia were excluded. Outcomes were extracted at diagnosis and each follow-up visit. PRL, % above upper limit of normal (AULN) and tumor size (mm) were modelled using linear mixed effects models and clinical symptoms were analyzed with McNemar’s Test. Increase in PRL was modeled with exact logistic regression with change in tumor size and symptoms as predictors. RESULTS A total of 28 patients were identified; median age at diagnosis was 37 yrs (IQR 27.5 - 47.5) and median follow-up was 70 months (IQR 41.5 - 123.5). No patient had additional pituitary hormonal abnormality except gonadal dysfunction. Median tumour size at diagnosis was 3 mm (IQR 2 - 4), and median PRL (AULN) was 50% (IQR 15.2 - 113.3). Twenty four (85.7%) had symptoms at diagnosis including: galactorrhea, oligomenorrhea and amenorrhea. At last follow-up, those without symptoms at diagnosis remained asymptomatic and the majority (80%) with symptoms at presentation had complete resolution of symptoms (p<0.01). Only 20% had persistent symptoms, commonest being galactorrhea, but none had worsening of symptoms. There was no evidence of any association between elevated serum prolactin and persistent symptoms. Overall, mean change in tumor size (mm) was -0.9286 (p-value = 0.0138), of which, 2 patients (7%) had an increase since diagnosis (mean increase = 2.5 mm) while the rest (93%) had either no change or a decrease in tumor size. Serum PRL (AULN) when adjusted for change over time (month) over during the entire follow-up period decreased in 20 (71.4%) patients by a median of -0.00793 (IQR -0.01556 - -0.00597) and increased in 8 (28.6%) by a median of 0.00321 (IQR 0.00181 - 0.01549).CONCLUSIONS Although limited by sample size, these findings suggest that when left untreated, the majority of microPRLomas remain stable both in terms of size and PRL values and clinical symptoms resolve in most patients over time.

Presentation: Friday, June 16, 2023
FRI308 A Rare Case Of Plurimorphous Plurihormonal Pituitary Neuroendocrine Tumor With LH Hypersecretion
Authors: Jeevananthan Athavi , Gratian Lauren
Published: October 2023

Disclosure: A. Jeevananthan: None. L. Gratian: None.

Background: Plurimorphous plurihormonal pituitary neuroendocrine tumors (PitNETs) are very rare pituitary tumors that are composed of multiple adenohypophyseal lineages and are associated with high risk of recurrence. Further, gonadotropin excess is exceptionally rare. Here we report a rare case of a plurimorphous plurihormonal PitNET with functional hypersecretion of LH. Clinical Case: A 48-year-old male was incidentally found to have a 13x12x14mm pituitary tumor without evidence of cavernous sinus invasion or mass effect during sinus imaging for workup of chronic sinusitis with polyps. Clinical symptoms at the time were notable for night sweats, hot flashes and 1 year history of erectile dysfunction. Functional testing showed normal prolactin, GH, cortisol, and thyroid hormone production. However, LH was elevated at 10.2 mIU/mL (normal range 1.4-7.77 mIU/mL) and FSH was low at 1.3 mIU/mL (normal range 2.5-17.7 mIU/mL) with normal total testosterone of 565 ng/dL (normal range 240-950 ng/dL) but elevated free testosterone of 22 ng/dL (normal range 4.26-16.4 ng/dL). Interval imaging 17 months later showed an increase in size to 16x16x13mm with deviation of the infundibulum to the left and mild mass effect on the optic chiasm. Thereafter, the patient underwent transsphenoidal surgery with subsequent normalization of FSH to 6.2 mIU/mL and LH to 7.9 mIU/mL. Initial post-operative total testosterone level was low at 29 ng/dL but improved spontaneously to 170 ng/dL six weeks following surgery. Pathology was notable for immunohistochemistry (IHC) that showed SF1 lineage (IHC positive for LH, negative for FSH) and PIT1 lineage (IHC positive for prolactin, rare GH). To our knowledge, this is the first reported case of functional LH hypersecretion due to a plurimorphous plurihormonal PitNET. Conclusion: This case aims to shed light on the first noted case of LH only secreting plurimorphous plurihormonal PitNET. Plurihomonal PitNETs are associated with aggressive course and recurrence. Particularly, this case highlights the need for routine use of immunohistochemical staining for accurate diagnosis of PitNETs to ensure rigorous follow-up.

Presentation: Friday, June 16, 2023
FRI309 Functional Gonadotrophin Secreting Adenoma With Elevated Testosterone—A Rare Entity
Authors: Bulchandani Sheetal , Syal Samriddhi , Sloan Emily A , Sharma Susmeeta Tewari
Published: October 2023

Disclosure: S. Bulchandani: None. S. Syal: None. E. Sloan: None. S.T. Sharma: None.

Introduction: Gonadotroph adenomas are a common type of pituitary neuroendocrine tumor (PitNET). However, most do not lead to elevated sex hormone levels1. Presenting symptoms include headache, visual field deficits, and hypopituitarism.2-3. Gonadotropin-secreting PitNET leading to high circulating testosterone levels are extremely rare. We report a case of a male patient with a gonadotroph PitNET causing hypersecretion of testosterone. Case Report: 53-year-old male with history of hypertension presented for evaluation of dystonia. He also reported fatigue and an episode of diplopia. He had normal libido and sexual function, no mood fluctuations. MRI of the spine performed for evaluation of dystonia revealed a 2.8 cm sellar mass. MRI Pituitary showed a 31 mm in height by 24 mm in width by 19 mm in depth sellar mass suggestive of a pituitary adenoma with compression of the optic chiasm and extension into the left cavernous sinus. Laboratory evaluation revealed an elevated follicle stimulating hormone level (FSH) of 73.6 mIU/ml (1.6-8.0), luteinizing hormone (LH) 13.3mIU/ml (1.5-9.3), elevated total testosterone of 2176 ng/dl (250-1100) and Free testosterone 367.7 pg/mL (35-155), Sex hormone binding globulin of 68 nmol/L, Alpha subunit of 3ng/mL, prolactin 23 ng/ml (4-15.2), no increase with dilution, TSH 2.24 iIU/ml, free thyroxine level 0.9 ng/dL, and AM Cortisol 6.4 mcg/dl. A Cosyntropin stimulation test revealed adrenal insufficiency and treatment with hydrocortisone was initiated. Ophthalmology evaluation revealed left >right asymmetric bitemporal hemianopia. He underwent transsphenoidal resection of the pituitary tumor. Post-operative laboratory evaluation revealed testosterone level of 43.65ng/dL and FSH of 6.6mIU/ml. Pathology showed a gonadotroph PitNet with diffuse nuclear positivity for SF1 and patchy cytoplasmic positivity for FSH with Ki-67 index of 2-3%. Discussion and Conclusion: Most gonadotropinomas are nonfunctional2 and clinically present with hypopituitarism and often low or normal sex hormone levels. We present a rare case of gonadotroph PitNet with elevated testosterone levels not associated with a recognizable clinical syndrome of sex hormone excess. The standard therapy for gonadotropin-secreting macroadenomas is trans-sphenoidal surgery.2-3 Early diagnosis is essential for timely and appropriate management.

Presentation: Friday, June 16, 2023
FRI333 Neurosarcoidosis Induced Panhypopituitarism​
Authors: Alfares Khalid , Han Hye Jeong , Athimulam Shobana
Published: October 2023

Disclosure: K. Alfares: None. H. Jeong Han: None. S. Athimulam: None.

Introduction: We hereby present a rare case of neurosarcoidosis causing panhypopituitarism. According to Martin-Grace et al who conducted a literature search for the timeframe of 2002 to 2014, there were only 8 cases of neurosarcoidosis associated pan hypopituitarism. Case Report: A 35-year-old male with a known diagnosis of sarcoidosis on skin biopsies presented to the hospital for altered mental status, hypernatremia, hypotension and hypothermia. He reported symptoms of polyuria and polydipsia for several weeks prior to admission. MRI of the brain revealed a 3cm mass in the suprasellar region involving the hypothalamus and bilateral optic tracts with mass effect on the anterior third ventricle. No discrete pituitary or stalk lesion was identified. A ventriculostomy tube was placed for developing hydrocephalus. Biopsy of the suprasellar mass revealed non-caseating granuloma, confirming neurosarcoidosis. Laboratory work up revealed elevated serum sodium at 167 mmol/L, high serum osmolality at 381 mOsm/kg and low urine osmolality at 381 mOsm/kg, consistent with diabetes insipidus. Anterior pituitary hormone profile work up revealed low 8am serum cortisol (1.9 mcg/dL) and inappropriately normal ACTH (34 pg/ml), low serum free testosterone (<2.5 ng/dL) and low Luteinizing hormone (0.7 mIU/ml) and low follicular stimulating hormone (< 2.6 mIU/ml), low free T4 at 0.4 ng/dL and inappropriately normal TSH at 2.77 uIU/mL. Serum prolactin was mildly elevated at 86.8ng/mL. Angiotensin converting enzyme level was within normal range at 33 U/L. A diagnosis of panhypopituitarism was made. Treatment was initiated with high dose IV corticosteroids for management of secondary adrenal insufficiency and neurosarcoidosis. He was also started on IV desmopressin and IV levothyroxine for management of his panhypopituitarism. He was transitioned to oral therapy on discharge. Discussion: Panhypopituitarism secondary to neurosarcoidosis is a rare presentation. Panhypopituitarism from sarcoidosis can occur due to infiltration of the pituitary gland or infiltration of the hypothalamus affecting the hypothalamic-pituitary axis. Sarcoidosis should be considered a differential when evaluating patients with symptoms consistent with panhypopituitarism. Prompt diagnosis and initiation of corticosteroids and deficient hormones can be lifesaving.

Presentation: Friday, June 16, 2023
FRI334 A Case Of Delayed Onset Sheehan's Syndrome With Diabetes Insipidus
Authors: Inkollu Sindhura , Estrada Allison
Published: October 2023

Disclosure: S. Inkollu: None. A. Estrada: None.

Introduction: Sheehan's syndrome (SS) is characterized by hypopituitarism that develops due to ischemic pituitary necrosis from severe postpartum hemorrhage. The frequency of SS has declined in developed countries as the result of modern obstetric care. It may present immediately after delivery or many years later with delay up to 32 years after the inciting event.1 SS is characterized by anterior pituitary dysfunction, while diabetes insipidus (DI) is an uncommon complication with an estimated frequency of 5%.2 Here, we present a case of a 58-year-old woman with late onset SS 33 years after delivery, complicated by DI. Clinical Case: A 58-year-old female was referred to endocrine clinic for hypothyroidism with TSH 4.98 mIU/mL (0.27-4.20) and undetectable free T4 (fT4) at <0.1ng/dL (0.8-1.6). Her symptoms included fatigue, dizziness, cold intolerance, dry skin, and hair loss for the past two years. On further questioning, patient reported that she was unable to lactate or menstruate since her last childbirth 33 years ago in Thailand, but never sought evaluation since she had completed her family. She was able to breastfeed her previous 3 children. On examination, she appeared well oriented but lethargic, withdrawn and pale. Axillary and pubic hair was absent. Pituitary hormonal panel demonstrated panhypopituitarism with fT4 <0.1 ng/dL, ACTH 14.2 pg/mL (7.2-63.3), cortisol 0.5 mcg/dL (10-20), prolactin 0.9 ng/mL (4.8-23.3), insulin like growth factor-1 of 10 ng/mL (56-194) and FSH 1.2U/L (25.8-134.8 postmenopausal). MRI of the pituitary showed a partially empty sella turcica. A diagnosis of SS was made and the patient was started on prednisone and levothyroxine. Shortly after starting prednisone, she developed significant polyuria and polydipsia. Given concern for DI unmasked by steroids, she was started on desmopressin 1mcg PO daily. Workup for DI was not done due to financial stressors. She showed marked improvement in general well-being and all her symptoms with hormone replacement. Conclusion: SS is not as rare as assumed in developed countries like USA, likely due to migrant women and unawareness of physicians regarding possibility of late onset SS. DI, though uncommon, still occurs with SS and can be masked by adrenal insufficiency on initial presentation. Clinicians should be aware of this condition as early diagnosis and treatment of SS improves quality of life along with morbidity and mortality to a great extent.

Reference: 1. Otsuka F, Kageyama J, Ogura T, Hattori T, Makino H. Sheehan's syndrome of more than 30 years' duration: an endocrine and MRI study of 6 cases. Endocr J. 1998 Aug;45(4):451-8. doi: 10.1507/endocrj.45.451. PMID: 9881893. 2. Keleştimur F. Sheehan's syndrome. Pituitary. 2003;6(4):181-8. doi: 10.1023/b:pitu.0000023425.20854.8e. PMID: 15237929.

Presentation: Friday, June 16, 2023
FRI345 A Rare Case Of Pituitary Histoplasmosis Presenting With Hypopituitarism
Authors: Jung Andrew , Tan Josenia , Charatz Seth , Azim Salman
Published: October 2023

Disclosure: A. Jung: None. J. Tan: None. S. Charatz: None. S. Azim: None.

A 58-year-old female presented to the endocrine clinic with a history of headache of one year duration. Prior to the visit, she had undergone a right middle lobe lung resection. Histopathology revealed necrotizing granulomas with yeast resembling histoplasmosis on fungal stains. She had no past history to suggest that she was immunocompromised. The patient had completed a three months course of itraconazole. Shortly after, she experienced daily headaches. Pituitary MRI demonstrated an enlarged 1.5cm pituitary gland without compression of the optic chiasm. Laboratory tests showed hypogonadotropic hypogonadism with LH 2.4 mIU/mL (15.9- 54.0), FSH 9.6mIU/mL (23 -116.3), and estradiol 14 pg/mL (<32.2). Free T4 was low 0.7 ng/dL (0.9-1.8) without elevated TSH 1.81 uIU/mL (0.55-4.78). Prolactin was 29.7 ng/mL (2.8-29.2). GH, ACTH, and morning cortisol were normal. Due to the constant headache with hypopituitarism, the decision was made to proceed with transsphenoidal surgery. Pituitary biopsy reported histoplasmosis on Grocott methenamine silver and Periodic acid-Schiff stains. The patient was started on amphotericin B. Repeat MRI confirmed the decrease in size of the pituitary gland after the procedure. Pituitary fungal infections are extremely rare. To our knowledge, this is the first reported case of pituitary histoplasmosis presenting with hypopituitarism. Clinicians should be mindful of the rare etiologies of hypopituitarism when evaluating patients with pituitary enlargement and hypopituitarism.

Presentation: Friday, June 16, 2023