bluuebunny/crossref_metadata_2025 huggingface dataset:
THU013 A Rare Case of Ectopic Cushing’s Syndrome Caused By Metastatic Parotid Gland Carcinoma
Authors: Punni Emma , Goyal Itivrita
Published: October 2023

Disclosure: E. Punni: None. I. Goyal: None.

Introduction: Ectopic Cushing’s Syndrome (ECS) is a rare condition that accounts for only a small percentage of all Cushing’s syndrome cases. Although rare, the typical tumors associated with ECS are small cell lung carcinomas, bronchial carcinoids, pancreatic neuroendocrine tumors, medullary thyroid carcinomas, thymic carcinoids and pheochromocytomas. Metastatic acinic cell carcinoma (ACC) of the parotid gland has very rarely been associated with ectopic Cushing’s syndrome. Case Presentation: A 67-year-old Caucasian male with a known diagnosis of high grade metastatic ACC of the parotid gland presented to the hospital with progressively worsening proximal muscle weakness and bilateral lower extremity edema of 6 weeks duration. A month prior to presentation, he developed persistent hypokalemia requiring potassium supplementation and was diagnosed with new onset type 2 diabetes mellitus. Laboratory results on admission were remarkable for low potassium at 2.5 mEq/L (N: 3.5-5.3 meq/L), a random cortisol level of 107 mcg/dL (N: 6 - 30 mcg/dL), and an ACTH level of 485 pg/mL (N: 7.2 - 63.3 pg/mL). Subsequently, a 24-hour urine cortisol was > 1600 ug/24 hours (N 5-64 ug/24 hours). A 1 mg dexamethasone suppression test failed to suppress an 8 a.m. cortisol with level of 110.8 mcg/dl (N < 1.8 mcg/dl). Following, an 8 mg dexamethasone suppression test also failed to suppress 8 a.m. cortisol with a value of 100.8 mcg/dl. A MRI of the pituitary with and without contrast showed mild diffuse enlargement of the pituitary gland concerning for pituitary hyperplasia. At the time, ECS was highly suspected given the rapid course of patient’s presentation, known metastatic malignancy, and failed 8 mg dexamethasone suppression test. An inferior petrosal sinus sampling (IPSS) could not be performed given the patient’s guarded condition. Instead, a PET/CT Ga-68 DOTA-TATE scan obtained showed widespread DOTA-TATE avid malignancy concerning for neuroendocrine type tumor. Patient was a poor surgical candidate, therefore bilateral adrenalectomy could not be performed for the rapid treatment of ECS. Patient was started on a steroidogenesis inhibitor ketoconazole. However, he elected to undergo hospice care and passed away shortly after. Conclusion: This case is particularly interesting given that metastatic ACC of the parotid gland causing ECS is rare with only a few cases reported in the literature. This case highlights the importance of maintaining a high degree of suspicion for diagnosing ECS especially when patients present with rapid onset of signs and symptoms of Cushing’s syndrome and a known underlying malignancy. Recognizing less common causes of ECS may prompt early diagnosis and intervention.

Presentation: Thursday, June 15, 2023
THU014 Post-surgical Remission After Resection Of Solitary Mediastinal Lymph Node In A Metastatic Occult Ectopic ACTH Syndrome Patient
Authors: de Magalhães Isabelle P A , Oliveira Caroline P F , Lins Lais P , Andrade Natália X S , Lima Marcos S , Siqueira Sheila A C , Fonini Jaqueline S , Assis Filho Eudes C , Mariani Alessandro W , Machado Marcio Carlos
Published: October 2023

Disclosure: I.P. de Magalhães: None. C.P. Oliveira: None. L.P. Lins: None. N.X. Andrade: None. M.S. Lima: None. S.A. Siqueira: None. J.S. Fonini: None. E.C. Assis Filho: None. A.W. Mariani: None. M.C. Machado: None.

BACKGROUND: The prevalence of occult cases has been increasing in the most recent series of Ectopic ACTH syndrome (EAS) maybe due to the small size of pulmonary neuroendocrine tumors. We present an atypical and very rare case of EAS with initial presentation of a single metastatic mediastinal lymph node that evolved with remission after your resection with no defined primary tumor. CASE REPORT: A 15-year-old female patient presented a clinical feature of Cushing’s syndrome (CS) with a 1-year evolution. Hormonal evaluation confirmed ACTH-dependent CS: urinary free cortisol of 819 µg/24h (3-43), late night salivary cortisol of 409 ng/dL (<274) and ACTH of 105 pg/mL (<63.3). Noninvasive methods for differential diagnosis of ACTH-dependent CS did not clarify the etiology (conflicting results): pituitary MRI negative, suppression of 59.6% of cortisol after high dose dexamethasone suppression test, positive response of ACTH and cortisol at desmopressin test, suppression of 81% of ACTH at acute octreotide SC test, negative serum tumor markers (gastrin, calcitonin, CEA, CA125, alpha-fetoprotein, CA19.9 and bhCG), negative cervical and pelvic ultrasound, negative computed tomography of thorax and negative abdominal MRI. Bilateral and simultaneous petrosal inferior sinus sampling with desmopressin confirmed EAS due to negative central to peripheral ACTH gradient, even after normalized PRL/ACTH gradients. Finally, PET/CT with Ga68-DOTATATE revealed a single infracarinal nodule of 1.5x0.6 cm with high capture of radioligand, SUVmax of 23.2, suggestive of affected mediastinal lymph node. The patient was submitted to thoracic surgery and the infracarinal lymph node was dissected and removed. Anatomopathological and immunohistochemical analyses disclosed a lymph node metastatic of a well-differentiated grade neuroendocrine tumor ACTH positive, Ki-67 2%. After surgery, the patient exhibited CS improvement and impressive drop of hormones at 5th postsurgical day (serum cortisol <1.0 µg/dL and ACTH of 2.2 pg/mL) confirming remission of CS. CONCLUSION: To our knowledge, approximately 36 cases of EAS due to neuroendocrine tumor of unknown primary origin were reported. However, previous cases commonly exhibited no remission after only removal of metastasis. Our case presented initial remission even with no primary tumor identified (occult primary tumor non-functioning?). Follow up with clinical, hormonal and imaging methods are necessary due to recurrence risk.

Presentation: Thursday, June 15, 2023
THU022 A Case Of Delayed Diagnosis Of Acromegaly
Authors: Blanchard Kayla , Musurakis Clio , Havrylyan Andriy
Published: October 2023

Disclosure: K. Blanchard: None. C. Musurakis: None. A. Havrylyan: None.

A 57-year-old hispanic female with hypertension, prediabetes, hyperlipidemia, and uterine leiomyomata with hysterectomy one year ago presented to our emergency department with sensations of numbness, tingling, and pressure on the top of her head for 12 days’ duration and left eye blurred vision with photosensitivity for 3 days’ duration. Physical exam was significant for evident enlarged facial features including macroglossia, macrognathia, separation of teeth, enlarged lips, enlarged ears and increased size of hands and feet with thickening of the skin on the fingers and toes. Many skin tags were noted on the neck and chest. She reported noticing these changes gradually over the past five years, as well as noticing an increase in shoe size and ring size. Admission labs were significant for IGF-1 965 ng/mL (47-236), Glucagon 172 ng/mL (0.05-8.00), AM cortisol 24 ug/dL (6.7-22.6), ACTH 29.6 pg/mL (7.2-63.3), FSH 13.22 mIU/mL (16.74-113.59), LH 3.79 mIU/mL (10.87-58.64), and Prolactin 24.3 ng/mL (2.74-19.64). Hemoglobin A1c was 5.8% (<5.7) and lipid profile was significant for triglycerides of 202 mg/dL (<150). TSH was within normal limits. A chest x-ray showed no cardiomegaly. An echocardiogram showed no cardiomyopathy. A CT scan of the brain showed a hyperdense sellar/suprasellar mass measuring 2.1 x 0.7 x 2.4 cm with mass effect on the optic chiasm and intracranial optic nerve not excluded. An MRI brain confirmed a large pituitary macroadenoma measuring 2.7 x 2.5 x 2.2 cm with mass effect on the optic chiasm and pituitary stalk. In addition to the above workup, we recommended Neurosurgery evaluation for symptomatic macroadenoma with optic chiasm mass effect, Ophthalmology evaluation for visual fields testing, and referral to a tertiary care center for evaluation and treatment of acromegaly. The patient was discharged with Neurosurgery and Endocrinology outpatient follow-up, but unfortunately did not attend her appointments. Acromegaly is a rare condition with a prevalence of 60 cases per million. While the mean age of occurrence is 32 years, the mean age of diagnosis is 40 to 45 years, highlighting a persisting delay in the diagnosis. The changes associated with acromegaly occur slowly and therefore can be overlooked by the patient, their family members, and even physicians. Left untreated, continued exposure to increased levels of growth hormone and IGF-1 leads to development of comorbidities including Cushing’s disease, cardiovascular disease, diabetes, arthralgias, decreased bone mineral density, sleep apnea, and uterine leiomyomata, as well as increased mortality and decreased quality of life. This case highlights the importance of physicians in all specialties being familiarized with the symptoms and physical features of acromegaly to aid in timely diagnosis.

Presentation: Thursday, June 15, 2023
THU049 Growth Hormone Treatment Reverses Deficits In POU1F1 Gene Mutation
Authors: Al-Samerria Sarmed , Phelan Joseph , Xu Huiting , Negron Ariel , Wondisford Fredric , Radovick Sally
Published: October 2023

Disclosure: S. Al-Samerria: None. J. Phelan: None. H. Xu: None. A. Negron: None. F. Wondisford: None. S. Radovick: None.

Mutations in the Pit 1 gene, also known as POU1F1, have been linked to the deficient development of somatotrophs and the synthesis of growth hormone (GH) in the anterior pituitary gland. In a previous study, we reported a point mutation in the PIT1 gene caused by a substitution of a lysine (K) with a glutamic acid (E) at position 216 (K216E) on one allele in a patient presenting with combined pituitary hormone deficiency (CPHD). This patient had undetectable levels of GH, TSH, very low PRL, and severe mental retardation associated with short stature (SS). To study the effects of GH treatment on growth and metabolism in CPHD, we created a unique mouse model with the K216E mutation in the PIT1 gene using the CRISPR/Cas9 genome editing system. In this study, 4-week-old male and female homozygous mice were randomly divided into two groups. The treatment group received subcutaneous injections of GH (5 mg/g/day) for 5 consecutive days per week for 4 weeks, while the control group received saline injections on the same schedule. GH treatment significantly improved the growth and body composition of male and female mice bearing the K216E. GH treatment also increased metabolism as measured by oxygen consumption, carbon dioxide production, and energy expenditure. These effects were observed both during treatment and 4 weeks post-treatment, although some reversal of the changes in body composition was observed 4 weeks post-treatment. Our findings demonstrate the utility of this mouse model in studying the effects of GH deficiency and treatment on growth and metabolism. This model holds great promise in advancing our understanding of the underlying mechanisms of hypopituitarism and CPHD, potentially serving as a valuable tool in identifying metabolic biomarkers for these conditions.

Presentation: Thursday, June 15, 2023
THU079 Danio Rerio (Zebrafish): A New Model Of AIP Loss Of Function
Authors: Wang Xian , Leggieri Adele , Anagianni Sofia , Brennan Caroline H , Korbonits Marta
Published: October 2023

Disclosure: X. Wang: None. A. Leggieri: None. S. Anagianni: None. C.H. Brennan: None. M. Korbonits: None.

Background: Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene account for 10% of cases with familial isolated pituitary adenoma (FIPA). The main features of patients carrying heterozygous AIP mutations include young-onset, large and invasive growth hormone and/or prolactin-secreting pituitary tumours, although a milder spectrum of presentation has been also described. In several animal models (mouse, fruit fly, round worm), homozygous deletion of AIP results in embryonic mortality. In mice abnormal cardiac development has been observed. Objective: The aim of this study was to generate a zebrafish loss-of-function model to explore the cellular biological processes affected by heterozygous or homozygous aip mutations. Methods: Zebrafish homologue of human AIP was identified by EMBOSS Needle program. We used CRISPR/Cas9 to generate a line of fish carrying loss-of-function mutations targeting zebrafish aip exon 2. aip RNA expression was examined using in situ hybridisation. The growth rate and cardiac function were assessed using a stereo microscope with an integrated camera. The videos and pictures were analysed in ImageJ. Antisense in situ hybridisation with probes to growth hormone 1 (gh1), prolactin (prl) and proopiomelanocortin a (pomca) was used to assess pituitary phenotypes. Results: Zebrafish aip shows 78.8% of homology to human AIP. aip mRNA is expressed throughout the developing zebrafish embryo until 28 hours post fertilisation (hpf) stage when it becomes more strongly expressed in the head. We generated a 29 bp deletion in exon 2 of the zebrafish aip gene. These mutant animals showed reduced aip expression. No significant gross morphology differences were observed at 3 to 7 days post fertilisation (dpf) between wildtype (WT) and heterozygote (Het) animals. At 5dpf, WTs showed an increased heart rate than Hets (P=0.033). Conclusion: We have generated an aip loss of function zebrafish line that provides an ideal opportunity to analyse the role of aip in development.

Presentation: Thursday, June 15, 2023
THU084 Corticotroph Tumor Type Influences Clinical Presentation In Patients With Nonfunctioning Pituitary Neuroendocrine Tumors
Authors: Al-Shamkhi Nasrin , Engström Britt Edén , Gudjonsson Olafur , Wikström Johan , Casar-Borota Olivera , Rask Eva
Published: October 2023

Disclosure: N. Al-Shamkhi: None. B. Edén Engström: None. O. Gudjonsson: None. J. Wikström: None. O. Casar-Borota: None. E. Rask: None.

Introduction: According to the current World Health Organization classification of endocrine tumors the classification of non-functioning pituitary neuroendocrine tumors (NF-PitNET) is based on pituitary cell lineages, defined by immunohistochemical expression of anterior pituitary hormones and pituitary specific transcription factors. The second most common NF-PitNET type, after silent gonadotroph tumors, are silent corticotroph tumors that are regarded as a potentially more aggressive type. If there is indication for treatment, the first-line treatment is transsphenoidal surgery. Some, but not all studies have shown a higher degree of preoperative pituitary failure or more frequent postoperative pituitary failure in patients with silent corticotroph tumors compared to the other NF-PitNET. Objectives: We compared patients with silent corticotroph and silent gonadotroph tumors, and explored whether tumor type and radiological findings were associated with pre- or postoperative pituitary failure. Design and method: One hundred patients who underwent surgery for NF-PitNET at the same tertiary center were included. Data regarding age at surgery, sex, pre- and postoperative pituitary function and tumor type, were collected after chart review. Preoperative MRI examinations were revised regarding tumor volume and Knosp classification. Results: The majority, 72% (72/100) were classified as silent gonadotroph tumors followed by 18% (18/100) silent corticotroph tumors. Patients with silent corticotroph tumors were younger at surgery, P=0.003. There were no differences regarding sex, preoperative tumor volume, invasive growth on MRI, defined as Knosp grade > 3, pituitary failure or prolactin elevation between the two tumor types. Binary logistic regression showed that having a silent corticotroph tumor, P=0.04, odds ratio 5.7 (CI: 1.06-30.71), higher age at surgery, P=0.003, odds ratio 1.07 (CI: 1.02-1.13), and a larger preoperative tumor volume, P=0.01, odds ratio 1.18 (CI: 1.04-1.33), were all factors associated with an increased likelihood of having postoperative pituitary failure. Sex, invasive growth and preoperative prolactin elevation were not significant predictors of postoperative pituitary failure in the binary logistic regression. Conclusion: The results indicate that silent corticotroph tumors influence the clinical presentation of NF-PitNET. Patients with silent corticotroph tumors were significantly younger at surgery, and demonstrated an increased likelihood of postoperative pituitary failure.

Presentation: Thursday, June 15, 2023
THU122 Effects Of A GLP-1 Agonist On Consumption Of Alcohol In Patients Treated For Smoking Cessation
Authors: Probst Leila Sofia , Monnerat Sophie , Lengsfeld Sophia , Bathelt Cemile , Meienberg Andrea , Burkard Thilo , Christ-crain Mirjam , Winzeler Bettina Felicitas
Published: October 2023

Disclosure: L.S. Probst: None. S. Monnerat: None. S. Lengsfeld: None. C. Bathelt: None. A. Meienberg: None. T. Burkard: None. M. Christ-crain: None. B.F. Winzeler: None.

Introduction: Alcohol use disorder causes high socio-economic costs and has a detrimental impact on health globally, being considered a key factor contributing to non-communicable diseases. In Switzerland four substances are currently approved for treatment of alcohol use disorder with only limited to moderate effects. Thus, the need for new treatment options in alcohol and substance use disorder is evident. Recent research has shed light on a new potential target for treatment of addiction: a body of preclinical studies provide evidence for the attenuating effects of GLP-1 agonists on addictive behavior in rodents and non-human primates. A few studies have shown a link between GLP-1 receptors and reward related processes in humans, and a trial from denmark examined the effect of exenatide in patients treated for alcohol use disorder, however clinical data are scarce and results remain inconclusive. Methods: This is a secondary analysis of the SKIP study, a double-blind, randomized, placebo-controlled trial to evaluate treatment with the GLP-1 agonist dulaglutide (Trulicy®) as a new therapy for smoking cessation. In the present analysis, the primary objective was to assess differences in alcohol consumption after 12 weeks of treatment with dulaglutide compared to placebo in alcohol-consuming smokers willing to quit smoking. We selected patients out of the cohort (n=255) who consumed alcohol at baseline and completed 12 weeks of treatment (n= 151). The independent effect of dulaglutide on alcohol consumption was analysed by fitting a multivariate generalized linear regression model with quasipoisson distribution and adjustment for baseline alcohol consumption. Preliminary Results: One hundred and fifty-one patients (placebo n=75, dulaglutide n=76) were included in the primary analysis. Baseline patient characteristics were well balanced between groups. The median age was 42 [IQR 33, 53] years with 61% (n=92) females. At baseline, patients in both treatment groups consumed 3 [IQR 2, 7] standard glasses of alcohol per week on average. At week 12, patients in the dulaglutide group drank an estimated 29% (IRR = 0.71; 95% CI 0.52, 0.97; p=0.04) less compared to the placebo group. For each additional glass consumed at baseline, alcohol consumption at week 12 increased by 6% (95% CI 5, 7; p<0.001). Conclusion: These preliminary findings suggest that in patients who drink, alcohol intake tends to increase during smoking cessation. In the present analysis we were able to show that this increase was attenuated by the addition of a 12-week treatment with dulaglutide to standard smoking cessation therapy.

Presentation: Thursday, June 15, 2023
THU123 Knockout Of Renal Glut2 Gene Activates The Hypothalamic-pituitary-adrenal Axis To Increase Glucose Production In Mice
Authors: Faniyan Tumininu S , Robles Jorge , Zhang Xinyi , Bathina Siresha , Brookes Paul S , Perry Rachel J , Chhabra Kavaljit H
Published: October 2023

Disclosure: T.S. Faniyan: None. J. Robles: None. X. Zhang: None. S. Bathina: None. P.S. Brookes: None. R.J. Perry: None. K.H. Chhabra: None.

We recently reported the contribution of renal GLUT2 (glucose transporter 2) to systemic glucose homeostasis using a mouse model in which we can knockout renal Glut2 gene at a desired time. Renal Glut2 knockout mice have improved glucose tolerance and are protected from high-fat diet or streptozocin-induced diabetes because they excrete excess blood glucose in urine. Interestingly, despite the profound loss of glucose in urine, renal Glut2 knockout mice have normal fasting blood glucose levels. These findings indicate that an increase in endogenous glucose production may be compensating for the loss of glucose in urine. To determine the mechanisms responsible for evoking the increase in endogenous glucose production, we focused on studying the hypothalamic-pituitary-adrenal (HPA) axis because of its established role in elevating blood glucose levels. We used ELISA to measure circulating adrenocorticotrophic hormone (ACTH) and corticosterone, which are major hormones of the HPA axis. Moreover, we used fluorescence in situ hybridization to assess the expression of hypothalamic corticotropin releasing hormone gene (Crh). We also performed in vitro metabolomics analysis of the mouse liver using mass spectrometry. Finally, we measured glucose production from pyruvate in vivo in the liver and kidney using mass isotopomer distribution analysis. Renal Glut2 knockout mice had increased (p<0.05) levels of hypothalamic Crh (100 ±13 vs 142 ±9 %, control vs experimental), circulating ACTH (120 ±8 vs 213 ±12 pg/ml), and corticosterone (30.4 ±5.5 vs 115 ±15.2 ng/ml). In addition, we found that metabolites such as hepatic glucose-6-phosphate (19.2 ±1.5 vs 15 ±1 arbitrary unit, control vs experimental), glucose-1-phosphate (20 ±1.5 vs 15.5 ±1), and fructose-6-phosphate (16 ±1.2 vs 12.4 ±0.8) were decreased in renal Glut2 knockout mice. We further observed that glucose production was increased in both the liver (15.1 ±0.4 vs 18.4 ±0.5 mg/kg/min) and kidney (1.7 ±0.2 vs 2.6 ±0.3 mg/kg/min) in renal Glut2 knockout mice. Our results demonstrate that loss of renal Glut2 causes hyperactivation of the HPA axis coupled with decrease in hepatic glucose metabolism and increase in hepatic as well as renal glucose production. These findings may explain how the renal Glut2 knockout mice prevent hypoglycemia despite massive glycosuria. Altogether, our study identifies a novel crosstalk between the kidneys, hypothalamus, and adrenal glands to regulate systemic glucose homeostasis. This information may be useful in either optimizing the efficacy of drugs that enhance glycosuria to treat diabetes or addressing the side effects of such drugs on the HPA axis.

Presentation: Thursday, June 15, 2023
FRI288 Single-Cell Transcriptomics Identifies Pituitary Gland Cell Type Population Changes In Diet Induced Obesity
Authors: Ruggiero-Ruff Rebecca Elizabeth , Le Brandon , Lainez Nancy , Coss Djurdjica
Published: October 2023

Disclosure: R.E. Ruggiero-Ruff: None. B. Le: None. N. Lainez: None. D. Coss: None.

Obesity is a worldwide growing public health concern, with a current prevalence of 43% in the United States and projected future increase. Obesity is associated with type 2 diabetes, cardiovascular disease, stroke, and endocrine abnormalities. The pituitary gland is the master gland that responds to metabolic perturbations and regulates homeostasis via hormone secretion. Thyrotrophic, gonadotropic, somatotropic, lactotropic and corticotropic dysfunctions may occur as a consequence of obesity and perpetuate pathophysiologic conditions since pituitary hormones regulate metabolic function in return. Previous work from our lab determined that mice fed high fat diet have reduced levels of gonadotropin hormones, indicating that diet-induced obesity may play a role in pituitary hormone production. We postulate that diet-induced obesity alters the pituitary transcriptome and/or select population changes. To determine the effect of diet-induced obesity on pituitary gland population plasticity, we performed single-cell RNA-sequencing (scRNA-seq) of pituitary glands from control and high-fat diet-fed mice and characterized population changes and gene expression changes in each population. While gonadotrope population changes levels of gene expression that results in the lower gonadotropin levels, somatotrope and lactotrope populations, on the other hand, change at the population level with alterations in the cell numbers that result in altered levels of growth hormone and prolactin in the circulation. In summary, we defined diet-induced changes in pituitary hormone production and population shifts that may play a role in altered hormone production in obese patients and consequently dysregulation of homeostasis.

Presentation: Friday, June 16, 2023
FRI298 Serum Prolactin To Tumor Size Ratio As An Effective Parameter To Accurately Distinguish Prolactinoma From NFPT
Authors: Mishra Ipsita , Pradhan Amrita , Baliarsinha Anoj Kumar
Published: October 2023

Disclosure: I. Mishra: None. A. Pradhan: None. A.K. Baliarsinha: None.

Preoperative diagnosis of prolactinomas is critical because dopamine agonists therapy have been regarded as a primary treatment. Multiple studies have compared serum prolactin levels in clinically nonfunctioning (NF) tumors and prolactinomas to identify cutoffs that may distinguish primary tumoral secretion from stalk effect. Prolactin levels are correlated with the size of prolactinomas but are not associated with tumor size in non prolactin-secreting lesions or the degree of stalk deviation and compression. By using the tumor size, we investigated an effective parameter for the discrimination between prolactinoma and NFPT. 33 patients with pituitary lesion of histological diagnosis were retrospectively recruited for this study. The data obtained was entered into Microsoft Excel Worksheet and analysed using Statistical Package for Social Sciences (SPSS, IBM Corp. Released 2020. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp.).The Prolactinoma group (n=16) showed higher serum prolactin (mean=418 ng/mL) than those in the NFPT group (n=17) (mean=33.34 ng/mL, p-values < 0.001).Using receiver operating curve analyses, we compared diagnostic performances of serum prolactin (PRL)/ tumor volume ratio in both groups. Unlike NFPT, serum prolactin values significantly correlated with tumor volume in Prolactinoma group. At a cut off of 12.2ng/ml/cm3,serum PRL/tumor volume was found to have a sensitivity of75.8% in diagnosing prolactinomas. However the specificity was 24.2%. Burke et al and Wright et al studied significantly smaller groups of patients and reported a linear relationship between prolactin levels and prolactinoma volume as estimated by a simplified ellipsoid volume equation. Our study demonstrates that the assessment of prolactin secretory density, based on a calculation of serum prolactin per unit tumor volume, can be used as a potential method to distinguish prolactinomas from hyperprolactinemia secondary to stalk effect and could be valuable in guiding patient management in equivocal or challenging patient cases wherein the etiology of hyperprolactinemia is uncertain.

Reference: (1) Burke WT, Penn DL, Castlen JP, et al. Prolactinomas and nonfunctioning adenomas: preoperative diagnosis of tumor type using serum prolactin and tumor size. J Neurosurg. 2019:1e8.(2) Wright K, Lee M, Escobar N, et al. Tumor volume improves preoperative differentiation of prolactinomas and nonfunctioning pituitary adenomas.Endocrine.2021;74(1):138e145

Presentation: Friday, June 16, 2023
FRI301 Prolactin And Obesity: Analysis Off Weight Oscillation In The Follow-up Of Macroprolactinomas
Authors: Oliveira Miriam C , Côrtes Aguiar Diego Paixão , Brand Corso Eduardo R , Rech Carolina G S L , Pereira Lima Julia F S
Published: October 2023

Disclosure: M.C. Oliveira: None. D. Paixão Côrtes Aguiar: None. E.R. Corso: None. C.G. Rech: None. J.F. Lima: None.

Introduction: Prolactin can be a modulator of body composition and weight and has been associated with obesity. However, the data, especially regarding weight behavior when normalizing hyperprolactinemia, are controversial. Methods: We retrospectively reviewed our data on a large sample of patients with treated macroprolactinomas, with or without normalization of PRL levels. Results: The sample consisted of 73 patients, 35 F, 38 M, and 15 to 86 years. In 42 cases (57.5%), the MRI showed suprasellar extension of the tumor, and in 37 (50.6%) some sort of invasion. In the presentation, the patients' weight varied between 49 and 156 kg, and the BMI (n=69) was between 18 and 52. Obesity was present in 39 patients (56.5%) and overweight in 19 (27.5%). Obesity was classified as class 1 in 19 cases (48.7% of obese patients), class 2 in 7 (17.9%), and class 3 in 13 cases (33.3%). The occurrence of obesity showed no significant difference between gender (p= 0,627) or the presence of suprasellar tumor extension. Of the patients with invasion (38/68), 92% were obese or overweight, with a significant association between both (p= 0,05). The obesity/overweight did not show an association (p= 0.716) with hypopituitarism or with specific deficiencies: GH, ACTH, and TSH, all with p= 1,000, and hypogonadism, p= 0,649. There was no correlation between initial weight and PRL levels (r= -0.033; p= 0.783). The follow-up ranged from 6 and 202 months. All patients used, at some point, bromocriptine or cabergoline. In 51 cases (69.9%) the PRL normalized. Of those who did not normalize, 19 had a reduction in the PRL level superior to 50%, in 14 cases in a percentage greater than 90%. There was a correlation between the initial weight and the percentage reduction in PRL at the last visit: higher initial weights correlated with smaller reductions in PRL (r= -0.470; p= 0.042). The last weight (n 64) was 89 ± 23,8 kg and the last BMI was 31,4 ± 6,9. In 36 cases (56.3%) the weight decreased: 18 of them with significant loss (reduction >5% of initial weight). Another 27 patients (42.2%) had weight gain: 18 of them with significant gain (>5% of the initial). In 12 patients, there was a class change in weight rating, 5 cases for a better classification and 7 for a worse. Significant weight loss was not associated with PRL normalization, p= 0.149. Conclusion: The prevalence of obesity and overweight in patients with macroprolactinomas far exceeds that found in the general population. In one-third of the cases, obesity is class 3. A meaningful association between obesity and tumor invasion was observed. There was no correlation between initial weight and PRL levels, and significant weight loss was also not associated with PRL normalization.

Presentation: Friday, June 16, 2023
FRI302 Umar Durrani
Authors: Durrani Umar Safwaan , Paracha Awais , Vasireddy Satvik , Waheed Fatima , Thomure Michael
Published: October 2023

Disclosure: U.S. Durrani: None. A. Paracha: None. S. Vasireddy: None. F. Waheed: None. M. Thomure: None.

Prolactinomas are tumors of the pituitary gland that induce hyperprolactinemia. Symptoms at presentation can include growth delay, infertility, neurologic deficits and bothersome galactorrhea. Dopamine suppresses prolactin production; therefore, dopamine agonists are first-line treatment for prolactinomas. However, hyperdopaminergia is also associated with psychiatric disorders. The dopamine hypothesis states that cerebral hyperdopaminergia can contribute to symptoms of schizophrenia. Thus, psychiatric disorders are commonly treated with dopamine antagonists. Almost 1 in 8 people in the world have a psychiatric condition. It is almost inevitable that the medical system will have to treat patients with both a psychiatric condition and a prolactinoma; thus, it is essential to identify treatment regimens for these patients. In order to identify potential treatments, we conducted a PubMed literature search focusing on patients with prolactinomas and co-existing psychiatric diagnoses. Our inclusion criteria helped us focus on patients who presented with concurrent prolactinoma and psychiatric condition which were confirmed by brain imaging, serologic prolactin levels, and reports of psychiatric conditions/episodes in their medical history (or chart). Our search yielded 30 studies representing a total of 54 patients with both conditions. We found that four key themes emerged from the literature: 1) discontinuing risperidone in exchange for other atypical antipsychotics such as aripiprazole, olanzapine or ziprasidone, 2) discontinuing thioridazine, thiothixene and remoxipride in exchange for clozapine, 3) dopamine agonist therapy cessation to abate psychiatric symptoms, and 4) surgery and/or radiation after pharmacotherapy. In conclusion, we would recommend focusing on specific antipsychotics (aripiprazole, olanzapine, ziprasidone, or clozapine) while shying away from (risperidone, thioridazine, thiothixene, and remoxipride). We would also recommend ceasing dopamine agonist therapy at least until symptoms improve. If these two methods are not yielding sufficient results, then pursuing surgical options or radiation therapy may be considered.

Presentation: Friday, June 16, 2023
SAT678 Metabolic Disorders In Thalidomide Embryopathy
Authors: Tanabe Akiyo
Published: October 2023

Disclosure: A. Tanabe: None.

Thalidomide embryopathy (TE) is a disease that develops in neonates born from women who have taken thalidomide during early pregnancy. Most cases of TE are characterized by developmental abnormalities of the limbs and/or auditory organs. In Japan, thalidomide was marketed as an agent for sleep-induce and digestive ulcers from 1958 to 1962. Up to now, 309 patients have been certified and are supported by the government as drug-induced disease. Currently, many of the victims are in their late 50s, and in addition to congenital disabilities, various health issues such as lifestyle-related diseases can be developed. We investigated their metabolic condition using data of medical health checkup between 2017 and 2019. Sixty-five Japanese cases of TE (33 men and 32 women) were included in this study. The mean age was 56.3±1.5 years in men and 56.1±1.2 years in women. The prevalence of upper limb deformities was 70% in men and 72% in women. The mean body mass index (BMI) was 22.7±2.1 in men and 22.5±4.0 in women. Twelve percent of men and 9% of women had a BMI between 25-30, while 9% of women and no men had a BMI of 30 or greater. Liver dysfunction was seen in 67% of men and 19% of women. The mean low-density lipoprotein cholesterol level was 61±19 mg/dL in men and 69±22 mg/dL in women. The mean high-density lipoprotein (LDL) cholesterol level was 116±29 mg/dL in men and 142±35 mg/dL in women, with 21% of men and 56% of women had LDL level of 140 mg/dL or greater. The mean triglyceride (TG) level was 137±82 mg/dL in men and 121±70 mg/dL in women, with 39% of men and 22% of women had a level of 150 mg/dL or greater. The mean fasting blood glucose level was 114±31 mg/dL in men and 102±17 mg/dL in women. The mean HbA1c level was 5.9±0.9% in men and 5.9±0.4% in women. The prevalence of impaired glucose tolerance was 19% in men and 9% in women. Fatty liver evaluated by ultrasonography or CT scan was 56% in men and 41% in women. The patients with fatty liver showed significantly high BMI, body fat percentage and TGs in men, high alanine aminotransferase and TGs in women, respectively, compared to the patients without fatty liver. There was no significant difference in with or without the upper limb abnormalities in both groups. This is the second report of metabolic disorders in TE, following one from our research group in 2015. Although without obvious overweight, thirty percent of the patients had dyslipidemia and 50% of the patients had the fatty liver. Because there was no association between limb abnormalities and metabolic disorders, other factors could be involved in the development of metabolic disorders. The results of this study provide valuable information for future health management in thalidomide embryopathy. (This study was conducted by a research grant from the National Center for Global Health and Medicine, Japan: 21A1015 and a Grant-in-Aid from the Ministry of Health, Labour, and Welfare, Japan: 20KC2005, 23KC2017).

Presentation: Saturday, June 17, 2023
FRI326 Hypophysitis: A Formidable Diagnostic Challenge
Authors: Pandey Shanta , Houston Caroline
Published: October 2023

Disclosure: S. Pandey: None. C. Houston: None.

Background: Hypophysitis, defined as inflammation of the pituitary gland, may pose a formidable diagnostic challenge due to its protean clinical manifestations and growing spectrum of potential causes. We present a case of a young man with presumed hypophysitis in whom the etiology remains unknown. Case Summary: A previously healthy 20-year-old male with bilateral gynecomastia was referred to the endocrinology clinic. He reported a 1-year history of worsening fatigue, weight gain, intermittent headaches, bilateral breast enlargement, lack of morning erections, polydipsia, and polyuria. His childhood growth and pubertal development were reportedly normal. He denied prior head or testicular trauma, major systemic illnesses, and chronic opiate or glucocorticoid use. His physical exam was remarkable only for scant facial hair and bilateral nontender gynecomastia. His visual fields were normal, and sense of smell was intact. Laboratory evaluation at 8am revealed low total and free testosterone of 32 ng/dL (240-950) and 0.98 ng/dL (5.25-20.7), respectively, with LH of 1.4 mIU/mL (1.0-12.0) and FSH of 1.9 mIU/mL (1.0-12.0). Free T4, prolactin, IGF-1, and serum sodium were all within normal ranges. Serum cortisol was modestly elevated at 22.3 ug/dL (3.7-19.4) with normal ACTH of 49 pg/mL (7.2-63.0). Pituitary MRI showed diffuse thickening and enhancement of the pituitary stalk, compatible with infundibular hypophysitis, without evidence of mass effect upon the native gland or surrounding structures. Additional testing showed normal levels of serum calcium, iron, ferritin, ESR, and antinuclear antibodies. After overnight water deprivation, his serum sodium was elevated at 156 mmol/L (134-144) with low urine osmolality of 121 mOsmol/kg (300-900). He was started on desmopressin and testosterone, and close clinical monitoring was enacted. Conclusion: The diagnosis of hypophysitis poses multiple challenges. Its clinical manifestations can vary widely, including symptoms related to mass effect and/or symptoms of pituitary dysfunction. Diagnosis is often presumptive based on history and exam, biochemical evaluation, and neuroimaging. The spectrum of potential causes is broad and growing, including infiltrative, infectious, neoplastic, immunoglobulin G4-related, immunotherapy-induced, other autoimmune, and paraneoplastic causes. It is often a humbling experience for clinicians to narrow this exhaustive differential. Pituitary biopsy is the gold standard for diagnosis but poses significant risks, so is reserved for cases when the diagnosis remains uncertain or malignancy is suspected. Close clinical monitoring and re-evaluation is an acceptable alternative in select cases.

Presentation: Friday, June 16, 2023
FRI327 Lymphocytic Hypophysitis Presenting As Hypoprolactinemia In A Post-partum Female
Authors: John Jessica , Graybill Sky
Published: October 2023

Disclosure: J. John: None. S. Graybill: None.

Lymphocytic hypophysitis is the most common presentation of primary pituitary gland inflammation. It typically presents with headache, vision changes, and sequelae of hypopituitarism, including central diabetes insipidus, anterior pituitary dysfunction, and hyperprolactinemia. Lymphocytic hypophysitis has a propensity to affect women in association with pregnancy due to an unknown underlying mechanism. A 38-year-old female presented with intractable headache and peripheral vision changes 3 weeks after giving birth to twin boys. Her post-partum course was complicated by preeclampsia with severe features. She also began experiencing blurry vision during this period. Seventeen days after delivery, she developed an acute onset headache and peripheral vision loss. She also noted sudden cessation of lactation with the onset of her headache. Initial CT head demonstrated a 1.6 centimeter enhancing pituitary mass suspicious for macroadenoma, and subsequent MRI sella revealed a 2.0 x 1.7 x 1.5 cm heterogeneously enhancing mass arising from the pituitary adenohypophysis extending to the undersurface of the optic chiasm. Initial laboratory evaluation demonstrated central hypothyroidism and inappropriately normal prolactin for a recently post-partum female. Given the patient’s impending vision loss, she was taken to the operating room for resection of suspected pituitary macroadenoma. Upon gross dissection, the abnormal appearance of the suspected mass prompted biopsy and immediate frozen section evaluation demonstrated significant lymphocytic infiltration. The resection was subsequently aborted. The patient was placed on levothyroxine and prednisone 80 milligrams daily for suspected lymphocytic hypophysitis, which was confirmed on tissue pathology. The patient’s headache and vision changes improved and after six days, she was discharged on a prednisone taper. Following three months of prednisone therapy, a repeat MRI sella demonstrated a reduction in the overall size of the pituitary gland to 1.7 x 1.2 x 1.1 cm. The patient was maintained on physiologic hydrocortisone and levothyroxine while monitoring for potential pituitary function recovery. Twelve months following her initial diagnosis, the patient did not demonstrate normalization of anterior pituitary function and required ongoing treatment for hypopituitarism. While hypoprolactinemia is atypical of hypophysitis, it is imperative to consider alternative pituitary pathology such as lymphocytic hypophysitis in the post-partum female when the clinical history is suspicious.

Presentation: Friday, June 16, 2023
FRI328 Granulomatous Hypophysitis With Magnificent Response To Glucocorticoids
Authors: Rodriguez Caballero Maria Galiana , Romero Fabiola , Escurra Clara , Rodriguez Roque , Rolon Roger , Valinotti Elizabeth , Ayala Alejandro
Published: October 2023

Disclosure: M. Rodriguez Caballero: None. F. Romero: None. C. Escurra: None. R. Rodriguez: None. R. Rolon: None. E. Valinotti: None. A. Ayala: None.

Granulomatous hypophysitis corresponds to 1% of sellar lesions. It maybe primary or secondary to tuberculosis, Pneumocystis carinii, Toxoplasma gondii, Cytomegalovirus or parasitic infections. Non-infectious etiologies include sarcoidosis, vasculitis, dendritic cell disorders, ruptured Rathke cysts or Crohn's disease. A 59-year-old immunocompetent woman was evaluated for decreased visual acuity, diplopia, and palsy of the 6th cranial nerve. Asellar MRI confirmed an 18 x 14 x 12 mm pituitary lesion with chiasmatic compression and visual field involvement. Hormonal evaluation revealed a TSH 0.03 mIU/L, FT4 0.44 ng/dL, random of GH 5.64 ng/mL, FSH 55.2 IU/mL, LH33.1 mIU/mL, and cortisol of 16 ng/dl. There was no evidence of diabetes insipidus. Transsphenoidal resection resulted in visual field improvement with a noticeable residual tumor of 12 x 9 x5 mm within the sellar space on the postoperative MRI. The patient developed panhypopituitarism. Pathology revealed non-caseous granulomatosis, with histiocytic aggregates of giant cells forming granulomas, with negative immunohistochemistry for mycobacteria. Tuberculin test, VDRL, blood cultures, ANA, Anti-DNA, ANCA C and P were negative. Tomography images and PET scan ruled out systemic involvement. The patient was treated with high doses of glucocorticoids under a presumptive diagnosis of isolated pituitary sarcoidosis vs. primary hypophysitis, resulting in complete disappearance of the lesion. Conclusion: Granulomatous hypophysitis is the second most common cause of chronic inflammation of the pituitary gland mimicking pituitary adenomas. Surgical removal and glucocorticoids are often utilized although there is no consensus regarding the treatment. Our case illustrates the importance of considering this diagnosis when confronted with incidental sellar lesions. Pharmacotherapy resulted in symptomatic improvement and complete involution of the pituitary lesion confirming the utility of empiric high-dose glucocorticoid as a therapeutic strategy for granulomatous hypophysitis.

Presentation: Friday, June 16, 2023
FRI366 “Carotid Body Tumor” Is A Misnomer For Head And Neck Paraganglioma
Authors: Rabiei Samaneh , Kantorovich Vitaly
Published: October 2023

Disclosure: S. Rabiei: None. V. Kantorovich: None.

Introduction: Glomus tumors are often treated as benign, hormonally inactive tumors through simple surgical resection. In many cases, full endocrine work-up and post-resection surveillance are overlooked. Endocrine consultation is currently underutilized in patients with glomus tumors because features of paragangliomas (PGs) such as multiple tumors are not always clinically evident at the time of initial presentation. It is important to be aware that carotid body and glomus tumors should be considered a variant of head and neck paraganglioms (HNPGs) and endocrinology consultation should be requested early on to optimize patients’ outcome. Case Presentation: Patient is a 52-year-old female who presented with back pain and difficulty walking. Imaging obtained for back pain work-up revealed a 6.2 x 4.4 x 4.2 cm right paraspinal soft tissue mass at T9 level on MRI with local invasion and cortical destruction of the T9 vertebra and involvement of the spinal canal. She was also found to have a 0.2 cm solid pulmonary nodule within the right lower lobe on chest CT. The history was also significant for resection of a jugular glomus tumor 12 years prior at the age of 40. Pathology findings at the time were consistent with glomus tumor. She also reported history of glomus tumor in her sister. However, the patient did not undergo genetic study at the time of diagnosis of her primary tumor.The patient subsequently underwent T9 corpectomy. Pathology report revealed a 5-cm tumor with characteristic histologic appearance of PG with epithelioid foci growing in distinctive small nests (Zellballen pattern), separated by prominent fibrovascular stroma with moderate cellularity and with slightly elevated (approximately 5%) Ki-67. Genetic study revealed a carrier state for a pathogenic variant of SDHD (c.112C>T; p.Arg38*). Gallium-68 DOTATATE PET/CT demonstrated intense focal DOTATATE uptake at the site of previous left-sided jugular glomus tumor resection as well as small foci of uptake bilaterally in upper and mid neck. Intense DOTATATE avidity was also identified at T8, T9, and T10 levels. Serum metanephrine, catecholamine, and PTH levels were within normal range. Chromogranin A is pending at this time. Discussion: We presented a case of glomus tumor in a young patient with a positive family history for glomus tumor who did not receive genetic study upon initial diagnosis of her primary tumor. The patient presented 12 years later with metastatic thoracic PG. Considering high mortality and morbidity of PGs, it is recommended to request endocrinology consultation at the time of diagnosis of carotid body or glomus tumors to prevent negative effects of disease recurrence.

Presentation: Friday, June 16, 2023