bluuebunny/crossref_metadata_2025 huggingface dataset:
9359 Patients’ Perspectives On Telemedicine In Endocrinology
Authors: Pikielny Pnina Rotman , Yoseph Liat Barzilay , Meron Michal Kasher , Rodrig Keren , Shapira Sofia
Published: October 2024

Disclosure: P. Rotman Pikielny: None. L. Barzilay Yoseph: None. M. Kasher Meron: None. K. Rodrig: None. S. Shapira: None.

Background: Telemedicine has emerged as an important and sometimes crucial tool in patient care, particularly during the COVID-19 pandemic. It offers numerous benefits, including time efficiency and improved access to specialized services. However, its adoption by endocrinology is constrained by the traditional emphasis on the physician-patient relationship and physical examinations. Objectives: This study evaluated patients’ perspectives on telemedicine, regarding specific aspects of satisfaction, including communication, wait times, and financial and time burdens. Methods: Surveys were delivered via text messages sent after telephone vs. frontal visits in an outpatient endocrinology clinic in a tertiary referral center. The surveys, sent from Nov 2022 to Dec 2023, investigated various aspects of satisfaction with the appointment and were based on the Telemedicine Satisfaction Questionnaire, a 5-point Likert scale questionnaire. Variations in preference levels across diverse patient groups were also examined. Answers were received via the REDCap application. Patients were told that responses were optional and answering the survey granted informed consent. Results: A total 135 patients completed the questionnaire, 93 who attended telephone and 42 after frontal visits. The groups were similar clinically: 77% were women, with an average age of 63 years. Visits were held mainly due to diabetes (22%), osteoporosis (31%), or obesity 10%), with no statistical differences between groups. 60% were followed more than a year. More patients who had telephone visits (69.9%) had previous experience with telephone visits vs. patients who had frontal visits (40.5%; p<0.004). Patients who had telephone visits reported higher satisfaction with wait time (p=0.002), physicians' explanations (p=0.03) and lower financial and time burdens (p<0.001). However, they were less able to share personal situations with the physician (p<0.001). More patients who experienced telephone visits thought they were preferrable to frontal visits (p<0.001). Notably, individuals with long-term follow-up and non-diabetic endocrine conditions had more interest in telemedicine. Conclusions: Patients report high satisfaction with telemedicine, but constrained in-person interactions remain a notable limitation. Telemedicine may not suit all patient groups or all time-points of patient care, requiring adaptation for broader use. Further research with higher response rate and specifications of different patient populations are essential to generalize these findings.

Presentation: 6/2/2024
7413 Postsurgical Complications In Gender Affirmation Surgery According To Body Mass Index: Case Series
Authors: Tovar Cortes H
Published: October 2024

Disclosure: H. Tovar Cortes: None.

Introduction: Therapeutic approach to gender dysphoria includes surgical interventions as part of the gender affirmation process.To make these procedures safe, it is recommended for the patient to have a normal BMI (body mass index). Obesity can increase the risk of complications during the perioperative period. To date, no studies have been published in Colombia documenting the results, and complications in patients undergoing gender affirmation surgery, and the relation to BMI. Case series A case series of patients diagnosed with gender dysphoria and multidisciplinary treatment is presented. Patients undergoing a gender affirmation surgical procedure, both in the context of transition from man to woman and from woman to man, who presented post-surgical complications are described. An analysis of the anthropometric measurements obtained through bioelectrical impedance analysis (BIA) of each of the patients was carried out; including weight, height, and BMI, with the objective of describing the surgical complications that occurred, as well as the categorization according to BMI range, and its possible correlation. From a database of 121 records of patients brought to a medical-surgical board for approval of gender affirmation procedures, a total of 78 patients were included, of which 33 presented post-surgical complications; 37 patients underwent feminization surgeries and 41 masculinization surgeries. In patients with post-surgical complications, it was found that 3% had a BMI less than 20 kg/m², 47% of the population had a BMI between 20 and 24 kg/m², 28% had a BMI between 25 and 29 kg/m², and 9 % of patients had a BMI grater than 30 kg/m². Most frequent complications were derived from thoracic masculinization surgery, highlighting suture dehiscence (7 cases), pectoral collections (6 cases) and tension hematomas (2 cases). All patients had in common post-surgical complications secondary to thoracic masculinization and BMI within normality. Conclusions Overweight and obesity are associated with an increase in surgical complications. Therefore, it is recommended that patients undergoing gender affirmation interventions should have a normal BMI, with the aim of reducing it, and achieving better surgical results. However, in our study, it was evident that these complications occurred predominantly in patients with BMI within normal range. These results could suggest that obesity is not associated with a significant increase in post-surgical complications. This provides important bases to carry out new studies that allow confirming these findings and bringing them to clinical practice. More evidence will reduce treatment barriers in these patients, allowing comprehensive treatment, and thereby improving the quality of life and biopsychosocial dysfunction of individuals with this condition. Abbreviations Body mass index (BMI), Bioelectrical impedance analysis (BIA)

Presentation: 6/3/2024
7627 Prevalence Of True Endocrinopathies In Patients Presenting To An Endocrine Clinic With Fatigue
Authors: Dimech Christina , Barnett Katherine , Hasan Farhad
Published: October 2024

Disclosure: C. Dimech: None. K. Barnett: None. F. Hasan: None.

Introduction: Fatigue is a common chief complaint, resulting in approximately 7 million physician office visits per year in the US. Fatigue is a non-specific symptom which can be associated with many acute or chronic conditions. In our clinical experience fatigue is a frequent reason for referral to the endocrine clinic, and often assessment does not reveal an endocrine pathology. However, the prevalence of endocrinopathies discovered following endocrinology assessment has not been well studied. Methods: In this retrospective study, we completed chart review of electronic medical records of patients who were evaluated for a chief complaint of fatigue at outpatient endocrinology centers belonging to an integrated health network in the Pittsburgh Metro area. We included patients aged 18-40 years old from 01/01/2019- 12/31/2022. We hypothesized that there is not a significant incidence of endocrinopathies found on evaluation. Results: Extensive clinical and laboratory data were gathered for 226 patients during the study period. 39.9% of patients were self-referred. 60.1% of patients seen were through physician referrals, however 17.9% of these patients had no prior investigations completed. The majority of patients evaluated for fatigue were female (76.5% vs 23.5%). 55.3% of patients were 30-39 years of age. 27% of patients were overweight and 23% were obese with BMI 30 or greater. Nearly half of all patients had a diagnosis of anxiety or depression (51.7% and 48.2% respectively). Of those patients with anxiety, 57.3% were prescribed an SSRI or SNRI. Similarly, 58.7% of patients with depression were prescribed an SSRI/SNRI. Patients most commonly reported other non-specific symptoms such as weight gain, poor sleep and poor mood (51.3%, 38.9%, 25.2% respectively). 54.9% of female patients presenting with fatigue were concerned for thyroid dysfunction whereas 45.3% of male patients were concerned for hypogonadism. 12.3% of patients evaluated never completed the recommended testing. Vitamin D deficiency was notably prevalent in 42.4% of patients tested. One patient was found to have secondary adrenal insufficiency in the setting of chronic exogenous glucocorticoid use for back pain. Of 163 patients tested for thyroid dysfunction, no new diagnoses of thyroid abnormalities were revealed. Conclusion: In this study, laboratory testing from an endocrinology consultation was not useful in detecting newly discovered endocrinopathies as a cause of fatigue.

Presentation: 6/2/2024
8059 An Interesting Case Of Hypogonadism Likely Caused By Cushing's Syndrome
Authors: Ripa Rashelle , Su Jennifer , Patel Ronak
Published: October 2024

Disclosure: R. Ripa: None. J. Su: None. R. Patel: None.

Introduction: Cushing’s Syndrome is a rare endocrine disorder that comprises a multitude of symptoms caused by hypercortisolism. Given non-specific symptoms, the disease can often be overlooked for more common diseases, such as diabetes, obesity, and even hypogonadism. Hypogonadism is a clinical disorder defined by decreased functional activity of the gonads. The diagnosis can often be challenging in developed males, who present with hypogonadotropic hypogonadism without an obvious cause. Here we present a case of a male who presented with hypogonadism symptoms for at least 5 years before being diagnosed with Cushing’s syndrome. Case Presentation: 58-year-old Caucasian male with a medical history of hypertension, cardiomyopathy and a BMI of 23, presented with decreased libido and erectile dysfunction. He was started on testosterone therapy three years prior, however it was discontinued due to heart failure. Without testosterone replacement, lab work was notable for: low free and total testosterone, 21.4 and 50.6 ng/dL, respectively, inappropriately normal findings of LH, FSH (1.0 and 4.9 IU/L, respectively), as well as unremarkable findings of GH, Prolactin, TSH, pituitary MRI and testes ultrasound, leading to a suspicion of hypogonadism. Due to persistent symptoms of hypogonadism and low testosterone, clomiphene was started but later changed to testosterone therapy after cardiology consultation. Shortly after, he began reporting facial flushing, associated with facial roundedness and elevated blood pressure. Upon further work up, hyperaldosteronism and pheochromocytoma testing was negative and his baseline cortisol was 21.9 mcg/dL with a low adrenocorticotropic hormone (ACTH), <5 pg/mL. Further, dexamethasone suppression testing showed suboptimally suppressed cortisol (14.4 mcg/dL). An abdomen MRI with and without contrast revealed a 2.3 cm adrenal adenoma, confirming an adrenal source of Cushing’s syndrome, and he underwent an adrenalectomy. Post-procedure, his cortisol and ACTH levels normalized to 10.5 mcg/dL and 39 pg/mL, respectively, showing a revival of his hypothalamic - pituitary - adrenal axis. Unfortunately, however, his free and total testosterone levels continued to remain low (38.9 and 152 ng/dL, respectively) and he was continued on testosterone therapy. Discussion: Our patient initially presented with decreased libido, and low testosterone levels and was treated for hypogonadism, as he did not have typical Cushing’s symptoms. Due to eventual weight gain and facial edema, it was only then that work up was pursued showing hypercortisolism release, leading to a proper diagnosis of Cushing’s syndrome. Hypercortisolism can affect all parts of the body, including hormones, muscles, joints and bones. When presenting in the initial stages and with mild symptoms, the diagnosis of hypercortisolism is often challenging and can go undetected for many years.

Presentation: 6/2/2024
7053 Sex Differences in Endocrine-Related Pre-existing, COVID-19- and COVID-19 Vaccine-Related Health Conditions and Adverse Events
Authors: Knapp J , Karumanchi R , Fee C , Inslicht S , Bhargava A
Published: October 2024

Disclosure: J. Knapp: Other; Self; Co-founder, Aseesa Inc. R. Karumanchi: None. C. Fee: None. S. Inslicht: None. A. Bhargava: Other; Self; Co-Founder, Aseesa Inc.

COVID-19 illness-related symptoms and outcomes are highly variable, with reported sex differences. mRNA vaccines were deployed for the first-time on a large scale for COVID-19, and the endocrine effects of Pfizer’s and Moderna’s mRNA vaccines, remain to be elucidated. Associations between COVID-19 illness and/or COVID-19 vaccines and reproductive disturbances have been reported based on large nation-wide surveys and targeted studies. Yet, none of the studies have directly ascertained similarities and differences between reproductive adverse outcomes from COVID-19 illness in unvaccinated individuals versus COVID-19 mRNA vaccines in individuals without COVID-19 illness. Here, we report preliminary findings on endocrine systems from a global survey of ∼8,000-10,000 participants collected between February 2022 and October 2023. Approximately 62.5% of the participants were from the United States, and the remaining were international. Nearly 1.49% of respondents reported hospitalization after COVID-19, whereas 5.69% of the respondents reported hospitalization after vaccination in our cohort. SARS-CoV-2-related severe symptoms were reported by ∼9.3% of COVID-19 vaccinated versus 6.7% of unvaccinated individuals (p<0.001). Women reported more vaccine-related adverse events (AEs) than men; 30% of men and 19% of women reported no AEs after any vaccination dose. After the first dose, 60% women and 48% of men reported some AEs, whereas after the second dose, 46% of women and 40% of men reported experiencing several AEs. Sex differences were present in endocrine and autoimmune pre-existing health conditions, including thyroid disease (13%F vs 3%M), osteoporosis (6%F vs 1%M), elevated cholesterol (M>F), and hypertension (M>F). Nearly 5% of women reported pre-existing irregular menstrual cycle irregularities and hormonal changes, whereas only 2% of men reported hormonal irregularities. In unvaccinated individuals, after COVID-19 illness, nearly 6% of women reported experiencing hot flashes, whereas 7.5% reported irregular menstrual cycles. In COVID-19 vaccinated individuals without SARS-CoV-2 infection, 94.6% of men and 62.5% of women respondents reported no reproductive changes. Of those reporting reproductive AEs included hormonal changes in 5% of women and 3.5% men, hot flashes in 8.5% women and 1.9% men, heavy periods and/or dysmenorrhea in 16.7% of women, and irregular periods in17.1% of women. In summary, reproductive AEs in vaccinated individuals without COVID-19 illness were more frequent than in unvaccinated individuals with COVID-19 illness. A detailed and thorough follow-up is needed to better understand if pre-existing health conditions exacerbated vaccine-associated AEs.

Presentation: 6/3/2024
6428 Update on Genetic F6428 actors of Nonalcoholic Fatty Liver Disease
Authors: Heshmati Hassan M
Published: October 2024

Disclosure: H.M. Heshmati: None.

Background: Nonalcoholic fatty liver disease (NAFLD) is a pandemic with a prevalence of 25% among the adult population worldwide. NAFLD is a spectrum of liver disorders ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). NASH can progress to cirrhosis and hepatocellular cancer. The pathogenesis of NAFLD is complex and multifactorial, involving metabolic, epigenetic, and genetic factors. Several medical conditions (e.g., obesity, type 2 diabetes, inflammation, insulin resistance, disrupted gut microbiome, and impaired intestinal barrier function) are important risk factors associated with and/or contributing to NAFLD. This review presents an update on the genetic factors of NAFLD identified by the genome-wide association studies (GWAS). Methods: A systematic search of literature was conducted using the search terms nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, cirrhosis, hepatocellular cancer, obesity, type 2 diabetes, epigenetics, and genetics. Results: Evidence for the contribution of genetic factors to NAFLD is further emphasized by the ethnic differences in the prevalence of NAFLD (e.g., higher prevalence among Hispanic American compared to African American adults). Based on the results of the GWAS, several genetic modifiers are relevant to NAFLD development and progression. They include variations in patatin-like phospholipase domain-containing protein 3 (PNPLA3), transmembrane 6 superfamily 2 (TM6SF2), membrane-bound O-acyltransferase domain-containing protein 7 (MBOAT7), glucokinase regulatory protein (GCKR), programmed cell death protein 1 (PDCD1), and hydroxysteroid 17β-dehydrogenase 13 (HSD17B13) genes (non-exhaustive list). These genetic modifiers interact with the metabolic and epigenetic factors for the development and progression of NAFLD and are responsible for the variability in the severity of NAFLD. The PNPLA3 gene variant (rs738409), which is the first and the best validated genetic modifier, is associated with a high risk of development and progression of NAFLD. The PDCD1 gene variant (rs7421861) is independently associated with hepatocellular cancer development. In contrast, the HSD17B13 gene variant (rs72613567) may have a protective effect for NAFLD risk. Conclusion: NAFLD is a multifactorial condition with a complex pathogenesis involving the interactions between metabolic, epigenetic, and genetic factors. The prevalence and risk of NAFLD differ across populations mainly due to genetic polymorphisms. Genetic factors relevant to NAFLD include variations in PNPLA3, TM6SF2, MBOAT7, GCKR, PDCD1, and HSD17B13 genes. A better understanding of these genetic modifiers and their mechanisms of action should allow a better risk prediction of the development of NAFLD and its progression to cirrhosis and hepatocellular cancer and help the development of new and selected therapies for NAFLD.

Presentation: 6/3/2024
7479 An Uncommon Indolent Form Of Adrenocortical Carcinoma
Authors: Arumugam M , Kim G
Published: October 2024

Disclosure: M. Arumugam: None. G. Kim: None.

Introduction: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy that typically presents with characteristic clinical and biochemical manifestations that are aggressive in nature. We present a case of ACC which was incidentally noted on imaging with no symptoms or signs of hormone excess. Case report: A 62-year-old male was noted to have an adrenal mass during evaluation of 30 lb unintentional weight loss and failure to thrive. The adrenal mass measured 18.3 x 14.4 x 6.8 cm with central necrosis and demonstrated extrinsic mass effect on surrounding structures. He denied any symptoms of hypercortisolism or clinically apparent androgen excess. He quit smoking 31 years ago and occasionally chews tobacco. Overnight dexamethasone suppression test with 2 mg dexamethasone showed an appropriately suppressed cortisol of 1.3. Androgen levels including DHEA-S, androstenedione, testosterone, and 17 hydroxy-progesterone were all within the normal range. PET CT revealed intensely increased radiotracer uptake in a large central necrotic mass in left adrenal gland, suggestive of malignant neoplasm. No other abnormal radiotracer activity was noted to suggest metastasis. The patient underwent left adrenalectomy. Intraoperatively, invasion of left kidney and tail of the pancreas was noted. Left nephrectomy was performed, and the pancreas was dissected off. The pathologist used three different staging systems to characterize the adrenal tumor. The Helsinki scoring system and Reticulin Algorithm were consistent with Adrenocortical Carcinoma. The Lin-Weiss-Bisceglia grading interpreted it as adrenal oncocytic neoplasm of uncertain malignant potential. Given the latter interpretation, the case was sent to Massachusetts General Hospital (MGH) for expert opinion. MGH deemed the tumor to be low-grade adrenocortical carcinoma. Conclusion: This is an uncommon presentation of adrenocortical carcinoma with patient presenting with weight loss and failure to thrive but without biochemical findings such as elevated cortisol or androgens.

Presentation: 6/1/2024
8710 “The Refractory Giant”: Functional FSH-Producing Pituitary Adenoma, A Case Report
Authors: Manolas Melina , Samavedam Janaki Manasa , Stefan Simona , Sapna Fnu
Published: October 2024

Disclosure: M. Manolas: None. J. Samavedam: None. S. Stefan: None.

Introduction: Gonadotroph pituitary adenomas are common but typically hormonally silent. Functioning gonadotroph adenomas (FGAs) are rare, accounting for less than 1% of pituitary adenomas, and pose unique clinical challenges. We report a rare case of a functional FSH-producing pituitary macroadenoma refractory to multiple resections. Clinical Case: A 50-year-old woman with a long history of FSH-producing pituitary macroadenoma, complicated by central adrenal insufficiency and hypothyroidism, was admitted for altered mental status and complete vision loss. Brain MRI revealed a residual pituitary mass over 8cm in size with multi-directional extension. She initially presented at age 35 with menorrhagia and diplopia. She underwent transsphenoidal resection (TSS) in Jamaica with no records of hormonal assessments or pathology available from that procedure. In 2012, brain MRI showed residual invasive 3.2cm tumor compressing the optic chiasm. Laboratory results revealed high FSH of 74.5 mIU/mL (RR: Follicular, days 2-3 - 3.0-14.4; Follicular, midcycle - 5.8-21.0; Luteal - 1.2-9.0), low LH of 2.68 mIU/mL (RR: Follicular, days 2-3 - 1.1-11.6; Follicular, midcycle - 17.0-77.0; Luteal - 1.0-14.7), and significantly elevated Estradiol of 1800 pg/mL (RR: 6.0-490) concerning for a functional, FSH-producing adenoma. Pathology from repeat TSS confirmed isolated FSH immunopositivity. She was started on Bromocriptine but given refractory menorrhagia required total hysterectomy and bilateral salpingo-oophorectomy, after which her Estradiol level was undetectable. Between 2014 and 2020 the tumor grew from 3.8cm to 6.8cm, resulting in ongoing visual field defects necessitating a third TSS. Surprisingly, the tumor consistently demonstrated a Ki-67 index of 3% or less. Despite a low mitotic index, it eventually exceeded 8cm in size, causing hallucinations, seizures, memory deficits, and complete vision loss due to progressive extrasellar extension with mass effect on the right temporal lobe. The family is engaged in discussions to weigh the risks and benefits of further tumor debulking. Conclusion: In premenopausal women, FGAs may present with menstrual irregularities, menorrhagia, or ovarian hyperstimulation syndrome as a consequence of hypothalamic-pituitary-gonadal axis dysregulation. They often go undiagnosed or misdiagnosed until the patient develops symptoms of mass effect. Standard treatment for FGAs is tumor resection. While dopamine agonists can help reduce estradiol levels and ovarian size, they do not appear to decrease pituitary tumor size. Existing literature shows that FSH-producing FGAs typically respond well to surgical resection. However, our case is exceptional due to the unusual size of the tumor, its rapid regrowth, and its resistance to multiple resections despite a low Ki-67 index. This atypical case warrants reporting and further discussion.

Presentation: 6/2/2024
8130 A Case of Cushing’s Disease Presenting with Posterior Reversible Encephalopathy Syndrome
Authors: Chincholi A H , Goldberg M D
Published: October 2024

Disclosure: A.H. Chincholi: None. M.D. Goldberg: None.

Introduction: Posterior reversible encephalopathy syndrome (PRES) is characterized by headaches, altered mental status, vision changes, and seizures, along with characteristic imaging findings of bilateral white matteredema in the posterior cerebral hemispheres. The syndrome often occurs in the context of severe hypertension, and has previously been reported in 6 patients with Cushing’s syndrome (CS) - 4 with ectopic sources of ACTH, 1 with micronodular adrenal hyperplasia and 1 pediatric case with Cushing’s disease. Clinical Case: An 18-year-old-man was admitted to our hospital after experiencing a second seizure at home. His presentation was significant for lethargy, hypertension, facial plethora, acne, proximal muscle weakness,central obesity, extensive purple striae, hyperglycemia, and hypokalemia. Two months prior, a diagnosis of ACTH-dependent CS had been made at an outside facility when he presented with a hypertensive emergency and new-onset diabetes. One month prior, he had been hospitalized with pneumonia complicated by acute kidney injury requiring temporary hemodialysis, and his first seizure. Brain MRI had shown extensive T2/FLAIR hyperintensities in the temporal lobes and cerebellum,consistent with PRES. On this admission, morning serum cortisol was 56.1 mcg/dL, and then 57.9 mcg/dL following 10 mg dexamethasone at night; ACTH was 120 pg/mL, and 24-hour UFC was 2,204 mcg. Ketoconazole and spironolactone were added, with no appreciable improvement in his cortisol levels but normalization of blood pressure. He required up to 150 units of insulin per day to manage his hyperglycemia. PituitaryMRI revealed a 0.6 cm adenoma, along with the T2/FLAIR hyperintensities. Chest CT showed no masses. A 10 mcg IV desmopressin stimulation test resulted in a 248% increase in ACTH and 32% increase in cortisol, and a second MRI with a 3T scanner measured the pituitary adenoma to be 1.0 cm. It was concluded that he had Cushing’s disease, and he underwent transsphenoidal resection of the pituitary adenoma. The surgery was curative, as reflected by postoperative central adrenal insufficiency. The patient was discharged on postoperative day 3 with oral hydrocortisone. Two weeks later, he was euglycemic off insulin and his blood pressure had normalized off spironolactone. Three months later, his muscle weakness and his headaches had completely resolved. Brain MRI showed complete resection of the pituitary adenoma and resolution of the white matter changes. Conclusion: To our knowledge, this is the first report of PRES associated with CS due to an ACTH-secreting pituitary adenoma in an adult. We suspect that this patient’s marked secondary hypertension triggered the reversible encephalopathy. Providers should be aware of this potential complication of hypercortisolism. This case also highlights the utility of desmopressin stimulation test in defining the cause of ACTH-dependent CS.

Presentation: 6/3/2024
8129 A Case of Pituitary Stalk Interruption Syndrome Presenting With Panhypopituitarism
Authors: Salvat Aleida , Sevilla Marla
Published: October 2024

Disclosure: A. Salvat: None. M. Sevilla: None.

Background: Pituitary stalk interruption syndrome (PSIS) is a rare congenital abnormality characterized by the classic triad of a thinned or interrupted pituitary stalk, an ectopic or absent neurohypophysis, and a hypoplastic or absent anterior pituitary gland. Clinical manifestations vary and can include neonatal hypoglycemia, short stature, cryptorchidism, and delayed puberty. Symptoms can present at birth or later in life with variable degrees of hormone deficiency. Clinical case: A 25-year-old male with hypothyroidism (on levothyroxine since age 13) presented for evaluation of hypogonadotropic hypogonadism. At birth, he was diagnosed with bilateral cryptorchidism and had frequent hypoglycemic episodes. During his childhood and early teenage years, his growth paralleled of his peers. However, at age 18, he experienced a growth spurt with unusually long arms and legs. He never developed secondary sexual characteristics. Physical examination showed blood pressure of 109/62 mmHg, height 193 cm, weight 76 kg, Tanner stage 1 pubic hair, microphallus, and nonpalpable testicles. The initial labs were consistent with panhypopituitarism: FSH 0.14 mIU/mL (0.95–11.95 mIU/mL), luteinizing hormone <0.09 mIU/mL (0.57–12.07 mIU/mL), total testosterone <4 ng/dL (240–871 ng/dL), prolactin 30.31 ng/dL (3.46–19.40 ng/dL), AM cortisol <1 ug/dL (3.7–19.4 ug/dL), ACTH 14 pg/mL (6–50 pg/mL ), cortisol levels 60 minutes after consyntropin stimulation test of 3.6 ug/dL (3.7–19.4 ug/dL), IFG-1 <16 ng/mL (63–373 ng/mL), TSH 7.24 uIU/mL (0.35–4.94 uIU/mL), free T4 0.53 ng/dL (0.70–1.48 ng/dL). Karyotype 46, XY, inv (9) (p12q13). The whole exome sequencing testing was negative. Pituitary magnetic resonance imaging showed hypoplasia of the anterior pituitary gland, ectopic location of the posterior pituitary gland at the expected base of the pituitary infundibulum anterior to the mammary bodies, and hypoplastic or absent pituitary infundibulum, findings suggestive of pituitary stalk interruption syndrome. Scrotal ultrasound showed no testicular or epididymal tissue within the scrotum. DEXA scan showed osteoporosis associated with a long history of non-treated testosterone deficiency. The levothyroxine was adjusted, and the patient was started on intramuscular testosterone, calcium, and vitamin D to manage the hypogonadism and improve the bone mineral density. Conclusion: Diagnosis of PSIS is often delayed due to its variable presentation and age of onset. Although this condition is considered rare, it should be in the differential diagnosis of patients presenting with panhypopituitarism. Early identification of deficient hormones, as well as prompt initialization of hormone replacement therapy, is essential to prevent serious complications associated with these deficiencies, such as adrenal crisis, osteoporosis, diminished quality of life, delayed puberty, and infertility.

Presentation: 6/3/2024
8024 A Case of Smoldering Clinically Silent Cushing’s Disease
Authors: Bheeman Chandni , Shafiq Ismat
Published: October 2024

Disclosure: C. Bheeman: None. I. Shafiq: None.

Aggressive pituitary adenomas account for about 10% of all pituitary adenomas. These aggressive tumors are noted to have unusually rapid tumor growth rate despite optimal standard therapies including surgery, medical therapy and radiotherapy. We present a case of a 39-year-old female with no prior past medical history who initially presented with complaint of amenorrhea. She had reported she had not menstruated for the past 6 months. She also endorsed galactorrhea with nipple stimulation. A pituitary dedicated MRI revealed a pituitary adenoma measuring 2.5 x 1.7 x 1.7 cm. Hormonal work-up showed salivary cortisol on two consecutive nights that was 66 ng/dL and 52 ng/dL (reference range: 0 - 99 ng/dL) and a prolactin that was slightly elevated at 44.9 ng/mL (reference range: 4.8-23.3 ng/mL). This elevation in prolactin was thought to be due stalk effect and since her hypothalamus-pituitary-gonadal axis was suppressed, patient had a transsphenoidal resection of what was thought to be a nonfunctioning adenoma. However, the pathology of her tumor was significant for extensive ACTH staining and a Ki-67 of 11 - 15%. Her clinical course proved to be challenging as her tumor reoccurred multiple times and she eventually developed biochemical and clinical evidence of Cushing’s disease and had visual defects due to compression of the tumor on the optic nerves. This tumor was refractory to multiple surgeries, radiation treatment and chemotherapy. Through the presentation of this case, we aim to highlight the factors associated with aggressive pituitary adenomas, the current treatment guidelines and emerging medical therapies.

Presentation: 6/1/2024
6459 A Novel Long-Acting GH Receptor Antagonist Optimizing Therapeutic Efficacy and Duration
Authors: Ku Cheol Ryong , Kang Chan Woo , Hun OH Ju , Wang Eunkyung , Song Hyung Nam , Park Ki Bum , Kim Bum Joon , Kim Kyuwan , You Sun-Ah , Park Soon-Jae , Lee Eun Jig
Published: October 2024

Disclosure: C. Ku: None. C. Kang: None. J. Oh: None. E. Wang: None. H. Song: None. K. Park: None. B. Kim: None. K. Kim: None. S. You: None. S. Park: None. E. Lee: None.

Background: Forty to sixty percent of acromegalic patients undergo medical treatment, utilizing somatostatin analogues, dopamine agonists, and GH receptor (GHR) antagonists. The GHR antagonist, pegvisomant exhibits the most robust efficacy in reducing IGF-1 levels in acromegalic patients. However, pegvisomant faces several clinical limitations, such as poor compliance due to the necessity of daily injections. This study aimed to develop a novel, long-acting fusion GHR antagonist with optimized therapeutic efficacy and duration. Method: Twelve mutant proteins with alterations in the C-terminal and N-terminal regions of GHR were generated to confirm the GHR binding affinity and inhibitory potency compared with pegvisomant, which was evaluated with STAT5b luciferase reporter assay. Several carriers were engineered into selected mutant GHRs to increase the therapeutic duration. For in vivo experiments, single or repetitive injection of GHR antagonists were applied to acromegalic mouse model (somatotroph specific Aip knock out (sAIPKO) mice). Pharmacokinetics (PK) and pharmacodynamics (PD) were evaluated in New Zealand White (NZW) rabbits. Result: Four out of the 12 GHR mutants exhibited higher affinity and stronger inhibitory potency toward human GHR when compared to pegvisomant. Specifically, three GHR mutants significantly reduced serum IGF-1 levels in sAIPKO mice following daily injections of 20 mg/kg for 7 days (52.3±6.0 to 5.9±1.3, 50.3±3.5 to 32.3±2.3, and 49.8±3.7 to 13.9±4.3 ng/mL; all p < 0.05). Among them, S4020N exhibited the lowest EC50 value for GHR binding affinity in in vitro analysis containing human GHR (0.594 nM) and mouse GHR (0.891 nM). Following fusion with each long-acting carrier, S4020N with the Fc carrier protein (ALT-B5) demonstrated the highest binding affinity and the strongest inhibitory potency toward human GHR, surpassing pegvisomant by 14 and 25 times, respectively. Administration of ALT-B5 (80 mg/kg) and pegvisomant (24 mg/kg) at a 3-day interval revealed the superior efficacy of ALT-B5 over pegvisomant (1879±219.4 vs. 3800±355.9 ng*hr/mL IGF-1 AUC for 5 days in ALT-B5 and pegvisomant, respectively; p < 0.01). In PK/PD studies, ALT-B5 was administered at doses of 3 mg/kg and 10 mg/kg in NZW rabbits, and PK/PD parameters were compared with the same molar concentration of pegvisomant. ALT-B5 exhibited the longest therapeutic duration and the highest efficacy compared to pegvisomant. Conclusion: ALT-B5 exhibited the longest duration and highest effectiveness in lowering IGF-1 levels. ALT-B5 emerges as a potential novel therapeutic option for acromegaly.

Presentation: 6/1/2024
8301 A Rare Case of IgG4-Related Hypophysitis
Authors: Kesavan Chary P , Silverstein J M
Published: October 2024

Disclosure: P. Kesavan Chary: None. J.M. Silverstein: None.

Background: IgG4-related disease (IgG4-RD) is an immune-mediated condition that presents as systemic inflammation and fibrosis of tissues, often affecting multiple organs. Isolated IgG4-related Hypophysitis is rare and characterized by lymphoplasmacytic infiltration of the pituitary gland by IgG4-positive plasma cells. A combination of clinical, serologic, radiologic, and histopathologic findings is used for diagnosis of IgG4-RD and approximately two-thirds of all patients have elevated serum IgG4 levels. We report a case of isolated IgG4-related Hypophysitis in a middle-aged woman serologically negative for IgG4-related disease. Case Report: A 52 year old female with history of steroid dependent severe persistent asthma, allergic rhinitis, and chronic sinusitis presented with one month of headache, polyuria, and polydipsia. MRI Brain demonstrated an enlarged, rounded pituitary gland 16 x 11 x 9 mm, with homogeneous enhancement, extension into the suprasellar cistern, and mild thickening of the infundibulum suspected to represent a pituitary adenoma. Lab evaluation revealed mild hyperprolactinemia (prolactin 83.2, normal 4.8-23.3 ng/mL) and secondary adrenal insufficiency based on an abnormal high-dose cosyntropin stimulation test in the setting of a low adrenocorticotrophic hormone (ACTH) level (<2.0 pg/mL). Remaining pituitary hormone levels were normal. Inpatient work-up for polyuria and polydipsia showed a low urine specific gravity of 1.003. An overnight water deprivation test was performed. Baseline urine osmolality (UOsm) was 95 mOsm/kg and serum sodium was 144 mmol/L; after 3 hours of water deprivation, serum Osm increased to 301 mOsm/kg (275-300 mOsm/kg) and UOsm only to 215 mOsm/kg, while her sodium increased to 145 mmol/L. Results were felt to be consistent with AVP deficiency (Central Diabetes Insipidus) and the patient was started on desmopressin. Because of the presence of AVP deficiency, further work-up was done to evaluate for an infiltrative process or malignancy. ANA, RPR, ESR, CRP, CBC, ACE level, T-SPOT, and IgG subclasses were unremarkable. Further imaging studies yielded a negative nuclear bone scan and PET/CT scan. For diagnostic purposes, the patient underwent biopsy via an endoscopic endonasal transsphenoidal approach. Pathology showed the presence of >10 IgG4+ plasma cells in a single high-power field, consistent with a diagnosis of IgG4-related Hypophysitis. Conclusion: Isolated IgG4-related Hypophysitis is the least common clinical presentation of IgG4-RD, which is itself a rare and relatively newly recognized condition. IgG4-related Hypophysitis should be suspected in patients presenting with AVP deficiency and pituitary stalk enlargement with an otherwise negative work up.

Presentation: 6/2/2024
7420 A Role for Glycoprotein Hormone Subunit Alpha 2 in Pituitary Development
Authors: Raetzman Lori Therese , Ge Xiyu , Weis Karen
Published: October 2024

Disclosure: L.T. Raetzman: None. X. Ge: None. K. Weis: None.

Hypopituitarism results when the pituitary gland is not able to make one or more of its hormones. It is estimated that up to 80% of hypopituitarism detected at or near birth has no identifiable cause. We have created a mouse model of congenital hypopituitarism by conditionally deleting the gene Notch2 in the developing pituitary. NOTCH2 is expressed in pituitary stem cells and is necessary for stem cell maintenance, proliferation, and differentiation. However, the pathways NOTCH2 engages to affect pituitary development remain unclear. It is important to determine the mechanism of NOTCH2 action in the pituitary because it might help to reveal novel causes of hypopituitarism. In this study, we hypothesized that glycoprotein hormone subunit A2 (GPHA2), a corneal stem cell factor, is downstream of NOTCH2 signaling in the mouse pituitary. We found Gpha2 is expressed in a subset of quiescent Sox2-expressing pituitary stem cells by RNAscope in situ hybridization and scRNA seq analysis. A scRNA seq study in rats has also localized Gpha2 to Sox2-expressing folliculostellate cells. In Notch2 conditional knockout pituitaries, Gpha2 mRNA is reduced over 75% compared with control littermates. We then investigated the possible functions of GPHA2, hypothesizing it might have a role in stem cell maintenance and quiescence. However, pituitaries treated with a GPHA2 peptide do not have a change in proliferation or stem cell-related gene expression. Another role of GPHA2 may be as a paracrine signal to control lineage restricted cell fate. GPHA2 has been demonstrated to be a ligand for the thyroid stimulating hormone receptor (TSHR) and part of the hormone thyrostimulin. We demonstrated that, in dissociated adult pituitary cells, GPHA2 increased pCREB expression and this induction was reversed by co-treatment with a TSHR inhibitor. Our data show that TSHR is expressed in the rostral tip thyrotropes of the pars tuberalis and in isolated cells in the anterior lobe. These data suggest GPHA2 is a NOTCH2 related stem cell factor that activates TSHR signaling, potentially impacting pituitary development and maintenance as a paracrine signaling molecule.

Presentation: 6/3/2024
8203 A Solitary Fibrous Tumor Mimicking a Non-functional Pituitary Macroadenoma
Authors: Rivera Luisa Bernacet , Omay Sacit , Huttner Anita , Inzucchi Silvio E
Published: October 2024

Disclosure: L. Bernacet Rivera: None. S. Omay: None. A. Huttner: None. S.E. Inzucchi: None.

Background: A solitary fibrous tumor (SFT), also known as hemangiopericytoma (HPC), is a rare subset of soft tissue tumors of mesenchymal origin. This type of tumor tends to have aggressive behavior and a high risk of recurrence. Approximately less than 1% of central nervous system (CNS) tumors have been identified as part of this subtype. Case Presentation: A 73-year-old female with medical history of primary hypothyroidism, myelodysplastic syndrome (MDS), and IgM kappa MGUS initially presented to her primary care physician for evaluation of progressive visual loss over several weeks, accompanied by worsening headaches. Ophthalmologic exam revealed bitemporal hemianopsia which prompted urgent imaging. Pituitary MRI with IV contrast revealed a solid sellar mass with suprasellar extension measuring 1.8 x 1.3 x 1.9 cm. The lesion was noted to superiorly displace the optic chiasm as well as to cause mild impingement of the anterior cerebral arteries. Patient was urgently referred to neurosurgery and endocrinology for further evaluation. Initial neuroendocrine laboratory assessment, performed at 8 am, revealed a cortisol 16.5 ug/dL, free T4 1.2 ng/dL, TSH 0.77 mIU/L, prolactin 9.9 ng/mL, IGF-1 17 ng/mL, the latter value consistent with adult growth hormone deficiency. Her LH and FSH were 4.3 mIU/mL and 12.6 mIU/mL, respectively, lower than expected for a post-menopausal woman. She underwent a transnasal transsphenoidal resection of the sellar lesion. Surgery was difficult due to the fibrous nature of the tumor, for which complete resection was not achieved. Post-operative course was complicated by thrombocytopenia due to MDS. Hormonal workup following surgery was consistent with central adrenal insufficiency, hypogonadotropic hypogonadism, and central hypothyroidism. Pathology showed densely cellular spindle cell neoplasm with a collagenous background consistent with hemangiopericytoma. She underwent fractionated radiotherapy and tumor has since remained stable in size. Her visual symptoms resolved quickly following surgery. Discussion: SFT is an aggressive mesenchymal tumor which rarely appears in the sellar region. There are no identified brain MRI findings that would suggest the nature of this tumor. As a result, endocrinologists should be aware of this rare condition while evaluating pituitary neoplasms.

Presentation: 6/3/2024
12526 Acromegaly Secondary to Sparsely Granulated Adenoma
Authors: John D , Kinaan M , Titus J , Lamar K
Published: October 2024

Disclosure: D. John: None. M. Kinaan: None. J. Titus: None. K. Lamar: None.

The most common pathological finding in acromegaly is a densely granulated adenoma which is composed of large round eosinophilic cells with prominent nucleoli and spherical nuclei that closely resemble a somatotroph cell. Less common finding is a sparsely granulated adenoma that is composed of sheets of poorly cohesive, pleiomorphic nuclei, chromophobic cells. We present a case of a 58-year-old gentleman presenting to our endocrine clinic for evaluation of a pituitary macroadenoma. The patient was hospitalized for nausea, vertigo, headaches, and blurring of vision. CT brain at that time showed a pituitary mass measuring 2.4 x 1.6 x 1.7 cm centered in the right cavernous sinus and inseparable from the pituitary gland. Hormonal work-up in the hospital was remarkable for high GH level. IGF-1 level was not done. Patient was advised to follow-up with neurosurgery as outpatient and no emergent surgery was planned. In the clinic, patient denied symptoms of DI, adrenal insufficiency or hypothyroidism. He has history of hypogonadotropic hypogonadism and was on testosterone therapy, but he stopped it since his hospitalization. On physical examination, he was noted to have macroglossia, deep voice, prominent jawbone, and soft tissue swelling in the hands and feet. Patient did not have any visible joint swelling. He stated he did not notice these changes personally and that he’s always been a “big guy” and always had a deep voice since he was a teenager. Repeat hormonal workup (done at 8 AM) showed: normal CMP, ACTH, cortisol, prolactin, TSH, T4, and T3. Testosterone was low with LH and FSH inappropriately within the normal reference range consistent withhypogonadotropic hypogonadism. IGF-I was elevated at 628ng/mL with a Z score of 3.9. These findings were consistent with acromegaly. He underwent surgery for tumor resection and pathology report showed that about 40% of the cells demonstrated weak immunoreactivity for GH, and rare (less than 1%) prolactin-positive cells were present within the tumor. The specimen was negative for TSH, ACTH, FH, and LH immunostains. Immunostain for CAM5.2 showed predominantly perinuclear dot-like immunoreactivity. The *MIB1 proliferation index is about 1%. The findings were consistent with a sparsely granulated gonadotrophic adenoma, which may demonstrate aggressive behavior. Postoperative MRI showed postoperative changes with residual pituitary tissue (normal gland vs. residual tumor). Postoperative cortisol >16. Postoperative GH dropped from 4.39 to 2.69 after 1 month. After 3 months, patient was doing well with no symptoms. However, IGF1 level (>400) showing that surgery was not curative. Currently he is awaiting gamma knife radiation therapy with possible medical therapy afterwards. Our case will provide an overview of the specific management considerations for these tumor and how they differ from densely-granulated tumors.

Presentation: 6/3/2024
8600 Acute Peripheral Pro-inflammatory Cytokine Injection Results in a Rapid Increase in Microglia Density in the Nucleus of the Solitary Tract
Authors: Castellanos E A , Tobet S A
Published: October 2024

Disclosure: E.A. Castellanos: None. S.A. Tobet: None.

The autonomic nervous system (ANS) is a major integrator of stress responses throughout the body. Physical or psychological stressors lead to neuroendocrine outputs from the hypothalamus and neurotransmitter mediated alterations in circuitry that control peripheral body systems including cardiovascular, pulmonary, and gastrointestinal, among others. Chronic stress can activate immune components, including microglia, leading to increased levels of proinflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-a) in the blood. Increased levels of these cytokines have been associated with several psychiatric disorders including major depressive disorder. In the current study, the impact of pro-inflammatory cytokines was examined in the dorsal vagal complex (DVC), a key brainstem region responsible for integrating autonomic inputs and outputs. The DVC includes the area postrema (AP), a sensory circumventricular organ, the nucleus of the solitary tract (NTS), and the vagal dorsal motor complex. The AP is in the middle of the DVC region, adjacent to cerebrospinal fluid and lacking a blood brain barrier (i.e., fenestrated capillaries). These traits make the AP uniquely located to integrate peripheral and central interactions between circulating cytokines and select immune cells in the DVC. This study concentrated on the effects of a single peripheral injection on microglia quantities in the DVC. TNF-a (50µg/Kg) and IL-6 (50µg/Kg) were administered by intraperitoneal injection and 2h later animals were perfused with 4% paraformaldehyde. Immunoreactive ionized calcium-binding adapter molecule 1 (IBA1) was used to identify microglia in the brainstem. In the area postrema there was a trend towards more immunoreactive IBA1 total area (µm^2; p = 0.08, ns) in mice that were injected with TNF-a and IL-6 compared to controls. By contrast, in the adjacent NTS there was 1.5x’s more immunoreactive IBA1 in mice that were injected with IL-6 and TNF-a (µm^2; p < 0.001) compared to control vehicle injections. Comparing brain regions in the DVC, there is 1.7x more microglia cells in the area postrema per section (50µm) compared to the NTS (p < 0.001), but in the NTS cells are 1.3x larger in size in comparison to the microglia cells in the AP overall (µm^2/ number of cells; p < 0.05). Finally, in the NTS there was a 1.5x larger total area of the IBA1 immunoreactivity following TNF-a injections compared to IL-6 injected mice (µm^2; p < 0.05). These data reveal a rapid effect of peripherally injected pro-inflammatory cytokines on microglial quantities and size in the brainstem. Future investigations will elucidate the role of neural-immune pathways in influencing the ANS during a chronic immune stress response. Supported by ORWH U54-MH118919.

Presentation: 6/3/2024