bluuebunny/crossref_metadata_2025_split huggingface dataset:
THU036 68Ga-DOTATOC PET/CT In Localization Of ACTH-producing Pituitary Tumors In Patients With Cushing Disease
Authors: Kim Kyungwon 
Published: October 2023

Abstract
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 &gt;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
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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 (&lt;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&lt;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

Abstract
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