bluuebunny/crossref_metadata_2025 huggingface dataset:
FRI038 Differences In Bone Accrual Over One Year In Young Girls With Obesity Compared To Normal Weight Controls
Authors: Kaur Snimarjot , Singhal Vibha , Haidar Lea Abou , Bredella Miriam , Misra Madhusmita
Published: October 2023

Disclosure: S. Kaur: None. V. Singhal: None. L.A. Haidar: None. M. Bredella: None. M. Misra: None.

Introduction: Despite higher bone mineral density (BMD), women with obesity are at an increased risk of fracture compared to normal-weight women. Optimal adolescent bone accrual is critical for normal peak bone mass acquisition and future bone health. Whereas several studies have examined the impact of low body weight on bone accrual in youth, data are lacking regarding the impact of obesity on bone accrual. We aimed to assess changes in areal and volumetric BMD, bone geometry and microarchitecture, and estimates of bone strength over one year in young females with moderate to severe obesity compared to their normal-weight counterparts. Methods: We recruited females between 13-25 years of age with moderate to severe obesity (OB) (n=21) and compared their bone accrual over one year with normal-weight controls (NWC) (n=50). Dual-energy X-ray absorptiometry to assess areal BMD (aBMD), high-resolution peripheral quantitative computed tomography (distal radius and tibia) to assess volumetric BMD (vBMD), bone geometry, and microarchitecture, and micro finite element analysis for estimates of bone strength was used. Analyses were controlled for age and race. Results: The mean age was 18.7 ± 2.7 years. OB and NWC were similar for age, race, height, and physical activity at baseline. OB had higher weight and BMI (p<0.0001 for both) and younger menarchal age (p=0.022) than NWC. Over one year, there was no difference between the groups for change in height, weight, and BMI. However, OB did not demonstrate the increase in total hip BMD observed in NWC (p=0.03) over a year. OB also had lesser increases in percent cortical area, cortical thickness, cortical and total vBMD at the radius over a year than the NWC group (p≤0.037 for all). The groups did not differ for tibial bone accrual. Conclusions: Our study demonstrates that longitudinal bone accrual over one year is impaired at the total hip and radius in adolescents and young adult females with obesity compared to normal-weight controls, while no differences are observed in tibial bone accrual. This raises concerns regarding future bone health in women with obesity, particularly at certain skeletal sites.

Presentation: Friday, June 16, 2023
FRI041 Obesity-associated Diaphragm Weakness Is Not Explained By Defects At The Level Of The Contractile Apparatus
Authors: Verma Romil Kaul , Claflin Dennis , Davis Carol , Converso-Baran Kimber , Michele Daniel , Brooks Susan , Chun Tae-Hwa , Buras Eric Dale
Published: October 2023

Disclosure: R. Kaul Verma: None. D. Claflin: None. C. Davis: None. K. Converso-Baran: None. D. Michele: None. S. Brooks: None. E.D. Buras: None.

Respiratory muscle dysfunction contributes to obesity-associated ventilatory disorders and is epidemiologically linked with diabetes and the metabolic syndrome. Despite its clinical relevance, the pathophysiology of obesity-related respiratory muscle weakness remains unclear. We previously applied non-invasive ultrasound to show that mice subjected to a 6-month diet-induced obesity (DIO) protocol develop diaphragm motion abnormalities. Isometric contractile force—measured ex vivo on isolated diaphragm strips—also declines with 6-month high fat diet (HFD) feeding, demonstrating that overnutrition causes functional impairment intrinsic to the diaphragm muscle. Intra-diaphragmatic adipocyte number and polymerized collagen content both increase with long-term DIO; however, their occupation of muscle cross sectional area (CSA) is insufficient to quantitatively account for force generation deficits. While disruption of tissue architecture secondary to intramuscular adiposity and fibrosis might underlie diaphragm contractile dysfunction, it is also possible that obesity impairs force production in individual myofibers. The functional integrity of the contractile apparatus (ie the sarcomere) can be interrogated in single myofibers. In this approach, muscle samples are subjected to membrane permeabilization, then individual myofibers are mechanically dissected out and affixed to a force transducer apparatus in which isometric contraction is stimulated via calcium administration. An attached camera allows for measurement of fiber CSA, such that specific force (measured force per unit CSA) can be calculated. We measured isometric specific force on both diaphragm strips and permeabilized single myofiber segments isolated from mice fed control diet (CD) or HFD feeding for periods of 6 weeks or 6 months. At the 6-week time point, muscle strip specific force was indistinguishable between groups; however, at 6 months, this parameter was significantly lower in samples from HFD-fed mice—consistent with our previous findings. In contrast, specific force measurements taken from individual myofibers were equivalent between CD and HFD-fed mice at both 6-week and 6-month time points. These data demonstrate that long-term DIO is required to reduce diaphragm contractile force; and that this decline occurs at the level of the tissue rather than the single myofiber contractile apparatus.

Presentation: Friday, June 16, 2023
FRI052 Z-score Of The Log-transformed A Body Shape Index As A Screening Tool For Sarcopenia In Population With Central Obesity
Authors: Chung Hye Soo
Published: October 2023

Disclosure: H. Chung: None.

Background: Sarcopenic obesity is related with a higher risk of cardiovascular disease, metabolic disease, and mortality than obesity alone. Nevertheless, few studies have investigated body shape indices for the assessment of sarcopenia in obese populations. The purpose of this study was to evaluate the accuracy of the Z-score of the log-transformed A Body Shape Index (LBSIZ) to assess sarcopenia in nationally representative populations with central obesity. Methods: Data from Korea NHANES (KNHANES) and the U.S. National Health and Nutrition Examination Survey (U.S. NHANES) were evaluated. Sarcopenia for the Korean population it was defined when appendicular skeletal mass index (ASMI ) < 7 kg/m2 in men or ASMI < 5.4 kg/m2 in women, according to the Asian Working Group for Sarcopenia and for the American population was defined when ASMI < 7 kg/m2 in men or ASMI < 5.5 kg/m2 in women, according to the revised European consensus on definition and diagnosis for sarcopenia. LBSIZ cut-off value was defined as that with the highest score of the Youden’s index. Changes in odds ratios (OR) for sarcopenia were investigated using restricted cubic spline (RCS) plots. Results: This study was conducted for population with central obesity in 4,855 Koreans and 8,010 Americans. Among these, 330 Koreans and 373 Americans were accompanied with sarcopenia. The cut-off values for the LBSIZ were 1.15 (sensitivity, 78%; specificity, 77%) for Korean men, 0.95 (sensitivity, 74%; specificity, 69%) for Korean women, 1.05 (sensitivity, 88%; specificity, 82%) for American men, and 0.45 (sensitivity, 77%; specificity, 71%) for American women in the development groups. Comparable results were verified in validation groups. The RCS plot indicated that ORs for sarcopenia rapidly increased with an increase in the LBSIZ cut-off value. Conclusion: The LBSIZ index is a powerful and reliable indicator of sarcopenia in adults with central obesity.

Presentation: Friday, June 16, 2023
SAT135 Prospective Analysis For Improvement For Glycemic Control Using A Patient Portal And Automated Messages
Authors: Cristancho Cagney C , Brandao Marjorie , Morocho Alexandra Lema , Amorim Talmas
Published: October 2023

Disclosure: C.C. Cristancho: None. M. Brandao: None. A. Lema Morocho: None. T. Amorim: None.

Background: Type II diabetes is a complex metabolic disorder which is influenced in part by patient dietary choices, medication adherence, and environmental factors. Behavioral health interventions offer an opportunity to potentially affect patient outcomes in a cost-effective manner. Purpose: To study whether automated clinical messaging via the electronic medical chart would be associated with improvement in diabetes-related health measures. Methods: We created an automated clinical messaging system (January 2020) via our electronic medical record. Patients who opted-in for this service received bi-weekly messages which included reminders about diabetes medication adherence as well as exercise and dietary recommendations. We then performed a retrospective longitudinal analysis of patients followed in our diabetes clinic, comparing those who opted-in for messing vs those who did not, and assessed diabetes-related biomarkers including baseline and follow-up hemoglobin A1c, lipid markers, and BMI using linear mixed-effects regression models. Results: 69 patients who had at least 2 measures of hemoglobin A1c were followed longitudinally, of whom 37 (54%) had opted to receive automated messaging. Patients who opted-in were younger (53±12 vs 62±11 years old, p<0.1), but not different in terms of sex (60% F vs 61% F), BMI (31±6 vs 30±7, p=0.84), or A1c (9.4±2.3 vs 8.8±2.7, p=0.34). In the group that received messages, we did not find any significant pre-post differences in A1c, LDL, or BMI over time. In the opt-in group, mean change (over average follow-up of 256 days) in HgbA1c was -0.4 (p=0.42) compared to a change of 0.0 in the non-opt-in group (p=0.99). Discussion: Patients who opted-in to electronic messaging were younger on average. We did not observe any significant longitudinal change in diabetes-related biomarkers within or between groups as related to an automated clinical messaging service, although there was a directional trend toward improvement. Given the cost-effectiveness and ease of this program, consideration should be given toward a trial with a larger sample size and longer follow-up.

Presentation: Saturday, June 17, 2023
SAT155 Insulin Receptor Autoantibody Syndrome (Iras): A Rare Occurrence In Lymphoproliferative Disease
Authors: Santos Claudia Villatoro , Oral Elif A
Published: October 2023

Disclosure: C. Villatoro Santos: None. E.A. Oral: None.

Insulin receptor antibody syndrome (IRAS) may present as fasting hypoglycemia, high serum insulin, and serum autoantibodies to insulin receptor at low titers. We present a case of a patient with multiple myeloma (MM) who developed hypoglycemia suspected to be related to insulin receptor antibodies. The patient is a 60-year-old male with history of prediabetes, MM, anemia, and thrombocytopenia treated with carfilzomib, dexamethasone 20 mg weekly, and prior radiation to the right pelvis, who presented to the hospital for increased right hip pain and cough. Patient reported 4 days of markedly decreased appetite with poor intake. He noted increased chronic right hip and low back pain. On exam, he was cachectic, had hyperpigmentation under bilateral eyes, and muscle wasting. Hypoglycemia as low as 38 mg/dL (70-180 mg/dL) was noted. MM studies on hospital day 4 showed increased kappa-M protein and kappa-free light chains with worsening anemia and thrombocytopenia, concerning for progression of his disease. He later developed recurrent hypoglycemia; endocrinology was consulted on hospital day 6. He also had hyponatremia and borderline low blood pressure. Cortisol on hospital day 7 at 9:00 am was 15.4 μg/dL (5.3-22.5 μg/dL) in the setting of normoglycemia. On hospital day 9, hematology started dexamethasone 40 mg daily for 3 days for MM relapse, which resulted in marked improvement in his mental status, appetite, and resolution of hypoglycemia. On hospital day 11, he started weekly cyclophosphamide, bortezomib, plus dexamethasone for 3 weeks. Results for hypoglycemia workup returned on hospital day 12 from samples of Day 7: glucose 53 mg/dL (70-180 mg/dL), C-peptide 0.2 ng/mL (1-5.2 ng/mL), insulin 14.6 μU/mL (1-21 μU/mL), insulin antibodies undetectable, negative serum screen for oral hypoglycemic agents. His course was complicated by sepsis with gram-negative bacteremia treated with antibiotics and stress dose hydrocortisone. He was discharged to rehab on hospital day 34 on dexamethasone 4 mg daily. Glucose, c-peptide and insulin levels could be consistent with exogenous hyperinsulinemic hypoglycemia but may also represent delayed insulin clearance due to insulin receptor antibodies and autocrine suppression of pancreatic insulin production in a patient with no access to insulin. Therefore, the most likely diagnosis was IRAS. The insulin antibody radioactive essay was negative for native IgG and IgM antibodies; testing for insulin receptor antibodies is in progress as a clinical test is unavailable. Treatment is common with high doses of steroids. IRAs can be seen in patients with lymphoproliferative disorders and would respond to steroid treatment for hospital management. Definitive treatment should be tailored with oncology guidance. There is a need for an accessible clinical test for IRAS in the US.

Presentation: Saturday, June 17, 2023
THU017 Severe Hypercortisolemia- A Biological Time Bomb
Authors: Munasinghe Uthpala , Pittampalli Shanti , Das Dhriti , Pattan Vishwanath
Published: October 2023

Disclosure: U. Munasinghe: None. S. Pittampalli: None. D. Das: None. V. Pattan: None.

Cushing's disease, the most common cause of endogenous Cushing syndrome, is usually insidious and has less severe hypercortisolemia than ectopic Cushing's. 73 yr.old female with hypertension, hyperlipidemia, T2DM, and OSA on anticoagulation for recent pulmonary embolism, presented with recurrent hypokalemia and proximal muscle weakness of 3 months duration. She denied visual symptoms and headaches. BP was 158/90 mmHg, HR 92 bpm, and BMI 34.9. She had a round face with ruddy complexion, extensive bruising on her upper extremities and proximal muscle weakness. Laboratory tests showed serum bicarbonate 26 mmol/l (22-29), sodium 140 mmol/L (136-145), potassium 2.0 mom/L (3.4- 5.1), chloride 106 mmol/L (98-107), glucose 164 mg/dl. Hemoglobin A1c 9.6 %, random cortisol 46.2mcg/dL, ACTH 72.4 pg/ml (7.2-63.3), late-night salivary cortisol sample was inadequate to assess, 24-hour urine cortisol 1802 ug/24 hr (6-42). Prolactin level was 14.6 ng/ml(4.7-23.3), IGF-1 62 ng/dl (48-191), GH 0.12 ng/ml (0-3.61), FSH< 0.3 mU/ml (25.8-134.8), TSH 0.193 u/ml (0.27-4.2), Ft4 1.1 ng/dl (0.93-1.7), alpha subunit <0.15 ng/ml (<3.56). She had non-suppressed cortisol of 44.3 mcg/dL and ACTH of 113 pg/mL after overnight 8mg dexamethasone suppression test. CT angiogram chest did not reveal any pathology. MRI pituitary revealed pituitary adenoma measuring 9 x 8 mm. IPSS with desmopressin stimulation showed IPSS to peripheral prolactin ratio was greater than 1.8 verifying successful catheterization. Her central to peripheral ACTH gradient was >2 before stimulation confirming pituitary source. Her ACTH concentration gradient >1.4 between 2 sinuses lateralizing the lesion to the right. The patient was started on Osilodrostat 2mg bid for control of hypercortisolemia and subsequently treated with transsphenoidal resection of the pituitary adenoma. Surgical pathology was consistent with densely granulated corticotrophin adenoma. Initial presentation of recurrent hypokalemia, proximal muscle weakness, pulmonary embolism and severe hypercortisolemia was suspicious for ectopic Cushing’s but after initial chest imaging was negative for ectopic pathology, MRI and subsequent IPSS helped with timely diagnoses and management. Severe hypercortisolemia is an endocrine emergency carrying high mortality. Expedited diagnoses, control of hypercortisolemia, anticoagulation and antibiotic prophylaxis can be life saving before definitive treatment can be done.

Presentation: Thursday, June 15, 2023
FRI317 Simultaneous Occurrence Of A Pineal Germ Cell Tumor And Pituitary Macroprolactinoma In A Young Male
Authors: Monsour Elio Paul , Badour Sanaa , Munoz Pena Juan Manuel , Donahoo William Troy
Published: October 2023

Disclosure: E.P. Monsour: None. S. Badour: None. J.M. Munoz Pena: None. W.T. Donahoo: None.

Background: Germ Cell Tumors (GCTs) are a group of heterogeneous tumors that derive from pluripotent germ cells and originate in the yolk sac of the embryo in early gestation. They account for 10% of all central nervous system (CNS) GCTs, primarily occurring in the pediatric and adolescent populations. The co-existence of macroprolactinoma and a mixed CNS GCT is extremely rare, with an unknown worldwide prevalence. Here we report a case of a pituitary macroprolactinoma occurring with a separate primary CNS mixed GCT. Clinical Case: A 19-year-old male presented with a 2-month history of headaches associated with nausea and vomiting. Relevant physical exam findings included decreased visual acuity, absent facial and axillary hair, and prominence of the left testis. Brain MRI demonstrated a pituitary adenoma measuring 3.5 x 2.3 x 3.2 cm extending into the cavernous sinus and an enhancing necrotic lesion in the third ventricle measuring 5.0 x 3.7 x 4.9 cm. Testicular ultrasound revealed two sub-centimeter ill-defined masses in the left testis. Pre-operative labs showed intact thyroid, adrenal, and growth hormone axis. He had a low total testosterone [14.2 ng/dl, reference range (RR): 230-800 ng/dL] with inappropriately normal gonadotrophins and markedly elevated prolactin (PRL) level (2,517 ng/mL, RR <14 ng/mL). Testicular tumor marker, alpha-fetoprotein, was elevated (15.3 ng/dL, RR <9 ng/dL). He was started on glucocorticoids for vasogenic edema and cabergoline twice weekly. He underwent left orchiectomy and subsequent pineal tumor resection. Testicular tumor pathology was consistent with teratoma and a well-differential neuroendocrine tumor with negative margins. Pineal tumor pathology was diagnostic of a mixed GCT. Despite optimal medical therapy, the patient ultimately opted to pursue transsphenoidal tumor resection. Pituitary mass pathology was compatible with a pituitary adenoma, immunoreactive for PRL. Post-operative PRL levels decreased to 6 ng/dL. He achieved a surgical cure without the need to restart dopamine agonist therapy. Conclusion: Simultaneous occurrence of primary brain tumors with different pathologies is estimated to be ∼0.9% of all brain tumors. To our knowledge, only one other case report described an adolescent with a craniopharyngioma and intracranial GCT. This is the first report in the literature of a pituitary macroprolactinoma synchronous with a mixed CNS GCT, and testicular well-differential neuroendocrine tumor with teratoma.

Presentation: Friday, June 16, 2023
FRI318 A Case Of Mixed Growth Hormone And Prolactin-secreting Giant Pituitary Macroadenoma
Authors: Khan Aysha , Alpertunga Ipek , Kantorovich Vitaly
Published: October 2023

Disclosure: A. Khan: None. I. Alpertunga: None. V. Kantorovich: None.

Introduction Co-secretion of prolactin (PRL) and growth hormone (GH) from a single pituitary adenoma is an established entity in the medical literature and present in about 5% of the cases. Guidelines recommend to obtain an insulin-like growth factor-1 (IGF-1) in patients with prolactinoma at the time of initial diagnosis. Our case describes the management of a giant pituitary macroadenoma co-secreting PRL and GH. Case A 20-year-old male with history significant for schizophrenia presented with visual disturbances and discharge from his left nipple. His prolactin level (PRL) was noted to be elevated at 12,396 (4.0-15.2) ng/ml on work-up during recent prior investigation. On physical exam, he had bilateral temporal visual field deficit as well as dysfunction in upward gaze of left eye. Head imaging showed a 7.5 x 6.2 x 5 cm associated with remodeling of the sella turcica and expanding into the suprasellar space and significant mass-effect on the adjacent frontal lobes bilaterally, mild mass-effect on the adjacent optic chiasm with significant surrounding vasogenic edema and compressing the bilateral anterior cerebral arteries. Patient was started on low dose cabergoline in caution of prevention of possibility of rapid response-related significant volume contraction of the tumor with possibility of reactive edema. The dose of cabergoline was rapidly titrated up to 3 mg bi-weekly with minimal prolactin fluctuation of PRL between 12,000 and 16,000 ng/ml. Because of mild atypical acromegalic facial features, patient had GH axis assessment. IGF-1 level came back elevated at 529 (83-456) ng/ml with a high IGF Binding Protein- 3 of 8.9 (2.9-7.2) mg/l. He was started on octreotide titrated up to a dose of 150 mcg three times daily. Repeat MRI brain did not show tumor shrinkage. Subsequently, patient underwent bifrontal craniotomy for resection/debulking of parasellar tumor. PRL dropped to 931 ng/ml immediately after surgery. At the time of writing, pathology of the tumor and repeat IGF-1 level is pending. Patient was monitored closely in the ICU with a steroid taper postoperatively. Discussion Dopamine agonists are the first-line therapy for medical treatment of hyperprolactinemia but can also suppress GH and IGF-1 levels. However, in acromegaly, cabergoline is utilized mostly for small adenomas with mild elevation of IGF-1. In our case, we decided to use a combination of cabergoline and somatostatin receptor analog, octreotide. However, given the giant adenoma with very high PRL and IGF-1 levels, patient showed a poor response to medical therapy, and given the impending threat to patient’s vision, he underwent surgical debulking. Our case highlights the management of a giant, mixed hormone-secreting pituitary adenoma.

Presentation: Friday, June 16, 2023
THU147 Peritoneal Dialysis To Improve Hyperglycemic Hyperosmolar State In Child With Renal Failure
Authors: Choudhari Pooja , Mootha Sudha
Published: October 2023

Disclosure: P. Choudhari: None. S. Mootha: None.

Background: Hyperglycemic hyperosmolar state (HHS) without ketosis is rare in children. While the crux of management of HHS is extensive hydration followed by insulin, this management can be difficult for children with kidney failure. Clinical Case: A 6-year-old female with complex medical history including Jeune syndrome (asphyxiating thoracic dystrophy), end stage renal disease status post kidney transplant, currently with rejection, now on peritoneal dialysis (PD), and history of steroid induced hyperglycemia was admitted for altered mental status. Several days prior to the current admission, she was admitted for an upper respiratory infection and found to have hyponatremia, which improved with fluid restriction and sodium supplementation. Subsequent worsening of hyponatremia led to adjustments in her PD to include higher amounts of dextrose in the dialysate (1.5% to 2.5%). At the current admission, she was found to have a blood glucose of 2096 mg/dL, uncorrected sodium of 121 mg/dL, corrected to 153 mg/dL, serum osmolality of 406 mOsm/kg, and hemoglobin A1c of 11.3%. She had mild acidemia and beta-hydroxybutyrate of 0.5 mmol/L. She was transferred to the Pediatric Intensive Care Unit (PICU) and intubated given her waxing and waning mental status and complex history. Since she was anuric, fluid resuscitation was carefully managed. She received a total of 14 mL/kg normal saline boluses, which lowered blood glucose by about 240 mg/dL. Multidisciplinary conversations between PICU, Endocrinology, and Nephrology culminated with a plan to attempt to slowly reduce blood glucose levels via PD prior to using regular insulin infusion. 24-hour PD was restarted with lower dextrose in the dialysate (1.5%). Due to persistent hypotension, she required norepinephrine infusion and stress dose hydrocortisone. With PD, blood glucose levels decreased by 20-30 mL/kg/hr in the first day. Regular insulin infusion was started, while continuing 24-hour PD, after blood glucoses stagnated at 1400-1500 mg/dL. After 4-5 days of PD and insulin infusion, the child’s blood glucoses decreased to 300-400 mg/dL. After tolerating her g-tube feeds, she was transitioned to an insulin pump as she was requiring high doses of insulin (1.8 units/kg/hr). Conclusion: We present a child with complex medical history, including history of steroid induced hyperglycemia, end stage renal disease status post renal transplant, anuria, currently on PD, who developed hyperglycemic hyperosmolar state (HHS). PD helped to lower her significant hyperglycemia, initially without insulin. There are few case reports on the use of PD or hemodialysis to improve hyperglycemia or hypernatremia in children with renal failure. This case demonstrates dialysis can be an effective strategy to attempt for children in a hyperosmolar state in whom aggressive fluid management can be detrimental.

Presentation: Thursday, June 15, 2023
THU189 Complex Treatment Of Recurrent Gynecomastia In An Affirmed Male With 46XX Ovotesticular Difference Of Sexual Differentiation (DSD).
Authors: Jumani Sanjay , Shimy Kim , Casella Daniel , Long Jessica , Gomez-Lobo Veronica
Published: October 2023

Disclosure: S. Jumani: None. K. Shimy: None. D. Casella: None. J. Long: None. V. Gomez-Lobo: None.

Introduction: Identifying gonads with ovarian and testicular components (ovotestis) can be difficult, despite multimodal imaging, biopsy, and surgical visualization. Here, we describe an unexpected identification of an ovotestis following the initiation of tamoxifen in a patient with 46XX Ovotesticular Difference of Sexual Differentiation (DSD). Case: A 14YO affirmed male with 46XX Ovotesticular DSD presented to our clinic for management of recurrent gynecomastia. At birth, he had ambiguous genitalia consistent with a under-virilized phallus, dorsally hooded foreskin, bifid scrotum, proximal hypospadias, palpable left gonad and non-palpable right gonad. He had a “normal” testosterone (i.e. presumably in male range for mini-puberty, though specific values predate available records). Limited genetic testing showed a karyotype of 46XX and negative SRY. He underwent a laparoscopy during which a right ovary, Müllerian tissue, and a small amount of vaginal tissue were identified and removed. A biopsy of the left gonad showed Sertoli cells without germinal epithelium. In adolescence, he developed progressive gynecomastia, with tanner 3 breasts by 12y6m. Treatment with anastrozole was unsuccessful, and he underwent a reduction mammaplasty at 13y6m. Unfortunately, the gynecomastia recurred shortly thereafter, and he was referred to our institution. At 14y7m bloodwork revealed a robust testosterone (543ng/dL), elevated estradiol (106 pg/mL, ref: 10-36), and estrone (71pg/mL, ref: 15-45). A trial of 20 mg tamoxifen daily was initiated. After 1 month, he developed scrotal pain suspicious for torsion and was taken to the operating room. Scrotal exploration revealed a hemorrhagic cyst at the superior pole of the gonad and an external appearance consistent with an ovo-testis. The hemorrhagic cyst was drained, and the remainder of the gonad left in situ. His pain resolved post-operatively however he returned 3 weeks later with scrotal pain and a recurrent hemorrhagic cyst on ultrasound. Tamoxifen was discontinued, and treatment with a Gonadotropin Releasing Hormone agonist (GnRHa) and concomitant testosterone replacement was initiated. This medication change led to resolution of the gonadal cysts. Conclusion: Initiation of tamoxifen as treatment for gynecomastia resulted in recurrent hemorrhagic cysts and the identification of ovarian tissue in a descended gonad which was presumed to be a biopsy proven testis. Recurrent hemorrhagic cysts in the ovotestis were likely due to physiologic stimulation and tamoxifen1 as well as elevated estradiol. Treatment with a GnRHa and testosterone offered a reversible, non-surgical method to suppress endogenous sex hormones contributing to gynecomastia while continuing male pubertal development. 1.PMID: 16254040.

Presentation: Thursday, June 15, 2023
THU619 Atypical Clinical Presentation Of Adrenal Hemorrhage
Authors: Madsen-Barbosa Thayse Lozovoy , Antoni Fidini Hayati , Ghazi Adline
Published: October 2023

Disclosure: T.L. Madsen-Barbosa: None. F.H. Antoni: None. A. Ghazi: None.

Introduction: Adrenal hemorrhage (AH) is an uncommon condition that is challenging to diagnose due to its nonspecific findings. We illustrate a case of AH that presented with acute clinical deterioration and had catecholamine overproduction. Case: A 58-year-old woman with a history of migraine headaches and prediabetes presented to the emergency department for “the worst headache of her life” and palpitations of 4 hours duration. On admission, her blood pressure was 224/139 mmHg and heart rate was 102 bpm. Her physical examination was significant for diaphoresis and active vomiting. Initial laboratory tests showed hyperglycemia and leukocytosis. Her ECG, non-contrast CT scan of the head and CT angiography of the head and neck were unremarkable. Her hospital course was complicated by recurrent hypertensive episodes, arrhythmias including Torsades de pointes, and left flank pain. A CT chest, abdomen, and pelvis revealed a large left retroperitoneal hemorrhagic collection which seemed to arise from the inferior aspect of the left adrenal gland. She subsequently underwent successful IR embolization of the left inferior suprarenal artery. Further workup showed elevated urinary fractionated metanephrine and normetanephrine levels, as well as elevated levels of plasma free metanephrine and normetanephrine. Given concern for pheochromocytoma, phenoxybenzamine was started. A repeat CT abdomen after six days demonstrated shrinkage in hematoma and a 7 mm hypoattenuating nodule arising from the medial limb of the left adrenal gland. Outpatient follow-up CT abdomen showed left adrenal thickening with a 2.3 cm nodular area with 78.9 Hounsfield units and absolute washout of 60.9% suggestive of adenoma. After one month, repeat catecholamine levels normalized. Discussion: The clinical manifestation of AH varies widely. Acute adrenal insufficiency is seen if bilateral glands and 90% of the cortices are compromised. However, unilateral AH is most often asymptomatic - found incidentally on imaging. Having elevated catecholamines is described in 30% of patients in one case series. Differentiating spontaneous AH from hemorrhagic adrenal tumors is also a dilemma. Among the hemorrhagic adrenal masses, pheochromocytoma is the most common. Conclusion: This case highlights that clinicians should be aware of clinical manifestations of catecholamine excess when evaluating patients with AH. A catecholamine producing adrenal mass (pheochromocytoma) should also be ruled out in these situations. Reference:1- Elhassan YS, Ronchi C, Wijewickrama P, Balvedeweg SE. Approach to the patient with adrenal hemorrhage. J Clin Endocrinol Metab. 2023, 108 (4):995-1006.2- Karwacka IM, Obolonczyk L, Sworczak K. Adrenal hemorrhage: a single center experience and literature review. Adv Clin Exp Med. 2018; 27 (5): 681-687.

Presentation: Thursday, June 15, 2023
FRI601 Unique Considerations For Workup And Management Of An 11 Year Old Male With Concern For A Neuroendocrine Tumor
Authors: Gunaratne Naiomi C , Deplewski Dianne
Published: October 2023

Disclosure: N.C. Gunaratne: None. D. Deplewski: None.

Background: Pheochromocytoma/paragangliomas are very rare in children. In patients who are undergoing work up for paragangliomas and pheochromocytomas, special considerations need to be made to distinguish neuroendocrine tumor findings from medication and other symptoms. Clinical Case: An 11 yo male with past medical history of migraines presented with new onset seizure, hypertension and tachycardia. Initial exam was remarkable for severe lower back pain, which eventually progressed to generalized pain. His tachycardia and hypertension were initially thought to be related to his pain, but were not improved with escalating pain and intermittent anti-hypertensive medications – leading to admission to the intensive care unit. He was started on lisinopril and metoprolol, but continued to have persistent tachycardia and hypertension.Initial work up included an echocardiogram revealing concentric left ventricular hypertrophy suggesting long-standing hypertension, MRI brain significant for Posterior Reversible Encephalopathy Syndrome, MRI abdomen and spine with no significant findings, and elevated urine metanephrines. Urine and serum catecholamines and serum metanephrines were also elevated, but not at levels typical of neuroendocrine tumors. Due to concern for possible pheochromocytoma/paraganglioma, patient was started on alpha-blocker phenoxybenzamine, and had marked improvement in hypertension. Patient was also started on scheduled gabapentin one day after initiation of phenoxybenzamine and noted to have some improvement in pain – making cause of acute improvement in blood pressure less clear. Patient underwent Ga-68 DOTATATE imaging that was significant for “mild to moderately increased activity within the left adrenal gland,” but no distinct lesion was appreciated on scan. After discussion with endocrine surgery, plan was made to monitor the patient in outpatient setting with serial plasma free metanephrines and chromogranin A while continuing phenoxybenzamine. Conclusion: Pheochromocytoma/paragangliomas are very rare in children. In patients who are undergoing work up for paragangliomas and pheochromocytomas, special considerations need to be made when patient has concomitant pain or is on beta-blockers. Ability to interpret urine/plasma metanephrines and catecholamine levels while on beta-blockers and other pharmacologic agents is difficult due to known iatrogenic alterations of these levels. Management for patients with elevated metanephrines without a localized neuroendocrine tumor can consist of pharmacologic intervention with alpha-blockers and close monitoring with serial labs.

Presentation: Friday, June 16, 2023
OR15-06 Measuring Hepatic Steatosis With Transient Elastography In Adolescents With Obesity
Authors: Sundararajan Divya , Lo Jaclyn S , Morelli Nazeen , Garcia-Reyes Yesenia , Ware Meredith A , Rahat Haseeb , Sundaram Shikha , Severn Cameron , Pyle Laura L , Tas Emir , Cree Melanie G
Published: October 2023

Disclosure: D. Sundararajan: None. J.S. Lo: None. N. Morelli: None. Y. Garcia-Reyes: None. M.A. Ware: None. H. Rahat: None. S. Sundaram: None. C. Severn: None. L.L. Pyle: None. E. Tas: None. M.G. Cree: Consulting Fee; Self; Pollie, Inc. Research Investigator; Self; Amino Corp.

Obesity affects nearly 20% of adolescents in the United States. Nonalcoholic fatty liver disease (NAFLD) is a common comorbidity, affecting between 40-70% of youth with obesity, thus approximately 10% of United States youth. Traditional diagnostic methods for NAFLD are expensive or invasive, and recently, transient elastography has been used to diagnose hepatic steatosis (HS). We sought to determine if transient elastography accurately diagnosed HS as compared to MRI in adolescents with obesity. Baseline data from adolescents (age 12-18 years) with obesity studied in 3 clinical trials were included (NCT03919929, NCT03717935, NCT04342390). Liver fat was assessed with 2 methods: MRI proton density fat fraction and transient elastography controlled attenuation parameter (CAP) score. Demographics, anthropometrics, liver scans and fasting serum laboratory measures were collected. HS was defined as MRI fat fraction ≥ 5.0%. Group data means, standard deviation, and ranges were calculated, and CAP for those with and without HS by MRI were compared with Mann Whitney U tests. Receiver operator curves (ROC) for CAP were generated based on MRI-determined HS. Data from 84 adolescents (age 15.6 ± 1.4 years, BMI 36.5 ± 5.96 kg/m2, 81% female) were included. Fifty-one had HS by MRI, with liver fat % different by HS status [9.3 (6.7, 14.0)% HS vs 3.1 (2.2, 3.9); p < 0.001]. CAP scores were different by MRI based on HS status [293 (267, 325) HS vs 267 (248, 282); p = 0.012]. With the recommended CAP cutoff for HS of 241, there was only a 59% concordance of HS status between the MRI and CAP. For CAP, ROC for HS was significant (r = 0.66, p = 0.012) and the Youden index had a sensitivity of 70.0% (56.3-80.9) and a specificity of 62% (42.3-74.5) at a CAP score of > 270. Additionally, BMI was not significantly related to hepatic fat (by MRI), AUC (0.44, 0.69, p-value = 0.323), or to CAP-determined HS, AUC 0.613 (0.425-0.802, p-value = 0.2686). In adolescents with significant obesity, the transient elastography CAP is not an accurate measure of HS compared to MRI. A CAP score of 270 to identify HS is higher than previously described in pediatrics, but may be needed in youth with obesity to improve accuracy.

Presentation: Friday, June 16, 2023
THU649 PCOS Phenotype In Unselected Populations (P-PUP) Study: Defining And Comparing Hirsutism Across Various Ethnic Groups In Unselected Populations
Authors: Kiconco Sylvia , Joham Anju Elizabeth , Suturina Larisa V , Zhao Xiaomiao , Gambineri Alessandra , Tehrani Fahimeh Ramezani , Yildiz Bulent Okan , Kim Jinju , Teede Helena Jane , Azziz Ricardo
Published: October 2023

Disclosure: S. Kiconco: None. A.E. Joham: None. L.V. Suturina: None. X. Zhao: None. A. Gambineri: None. F.R. Tehrani: None. B.O. Yildiz: None. J. Kim: None. H.J. Teede: None. R. Azziz: None.

Introduction Hirsutism is defined as the male pattern distribution of terminal hair in a female. It is one of the diagnostic features of polycystic ovary syndrome (PCOS), reflecting clinical hyperandrogenism, as measured by the modified Ferriman-Gallwey score (mFG). However, whether the mFG scores and the normative cut-off varies by ethnicity is unclear. We aimed to describe and compare the distribution of mFG score in different ethnic groups from eight countries using data from unselected (medically unbiased) populations to determine and compare the normative cut-off values between the different ethnic groups and the prevalence of hirsutism thereby defined. Methods We utilised data of 10,919 participants aged 15 to 80 years. Data were obtained from epidemiologic studies assessing unselected women conducted in different countries including China, Iran, Italy, Nigeria, Russia, South Korea, Turkey, and the United States of America. The distribution of mFG between ethnic groups was determined descriptively as medians. Cluster analysis (k means, k=2) and the receiver operating characteristics curve were used to determine the normative cut-offs for the mFG score. All medians, cut-offs and percentile values were compared between ethnic groups using the Kruskal-Wallis test at a 95% level of significance. Results Our data consisted of 11 ethnic groups from 8 countries. The Persian (4.8±4.7) and Italian (4.8±4.7) populations had higher median mFG scores than the rest of the ethnic groups, whilst Asian populations (Chinese, Korean and Buryat) had the lowest scores. Overall, the median distribution of mFG differed significantly by ethnicity. Using cluster analysis, the mFG cut offs range from 4 to 9, with the Persian ethnic group having the highest, followed by the Italian group, with cut-offs differing by ethnicity overall; however cut offs are similar for Black American, Turkish, Asian and Russian groups. Conclusion The distribution and normal cut off values for hirsutism differ significantly by ethnicity, with the Persian population having the highest cut offs. Ethnicity needs to be considered when assessing women for clinical hyperandrogenism.

Presentation: Thursday, June 15, 2023
FRI374 Immunomodulatory Effects Of Progesterone And Glucocorticoids In Pregnancy Immunity
Authors: Yasuda Atsushi , Seki Toshiro , Kashiwagi Hirofumi , Kitajima Natsumi , Kametani Yoshie
Published: October 2023

Disclosure: A. Yasuda: None. T. Seki: None. H. Kashiwagi: None. N. Kitajima: None. Y. Kametani: None.

Immune tolerance to a semi-allogeneic fetus is crucial for a successful pregnancy. However, the mechanisms of tolerance to semi-allografts in the co-existence with normal defenses against cancer and pathogens is not clear. During pregnancy, levels of pregnancy-related proteins and hormones such as progesterone (P4), estrogen, testosterone, and glucocorticoids (GC) increase. We hypothesized that the most abundant pregnancy related hormone in the placenta, P4, might play an important role in the local tolerance in the placenta. Thus, we aimed to compare the effects of P4 and cortisol (COR) on human lymphocytes in vivo, to clarify their role in the systemic regulation of immunity during pregnancy. Healthy donor peripheral blood mononuclear cells (PBMCs) were treated with P4 or COR for 6 h. These PBMCs were washed and transplanted intravenously into 8- to 9-week-old NOG-hIL-4-Tg (formal name, NOD.Cg-PrkdcscidIl2rgtm1Sug/Tg(CMV-IL4)/Jic) mice. Human epidermal growth factor receptor-2 (HER2) peptide was emulsified in complete Freund's adjuvant and administered intraperitoneally to these PBMC-NOG-hIL-4-Tg mice at the same day. As a negative control, an equal volume of PBS was added to the culture and transplanted into NOG-hIL-4-Tg mice. Boosters were administered using incomplete Freund's adjuvant 2 weeks after the primary immunization. Peripheral blood was collected 4 weeks after transplantation and 2 weeks after booster administration. T and B cell profiles were analyzed using FCM 28 days later. The results revealed that significantly higher numbers of human CD45+ cells engrafted in the spleens of P4-treated mice compared to COR-treated mice 4 weeks post-transplantation. Transplanted human CD45+ cells included T and B cells, and CD8+ T cells were significantly higher in P4-treated mice compared to both control and COR-treated mice. Moreover, antigen-specific IgG production was maintained in the P4-treated mice, suggesting that the T cell/B cell function was maintained in the mice. Compared to control and P4-treated mice, COR-treated mice tended to engraft fewer human CD45+ cells. Moreover, B cell engraftment tended to be lower in COR-treated mice than in control mice. Antigen-specific IgG production was not maintained. There results suggest that lymphocytes which experienced a high P4 environment maintain engraftment and function of human lymphocytes in the NOG-hIL-4-Tg mice, while high COR environment rather dampens the engraftment and function of them. The high-P4 environment limited in the placenta may support pregnant immunity to protect the semi-allogeneic fetus from pathogen-induced infectious disease or cancer.

Presentation: Friday, June 16, 2023
FRI430 A Case Of Elevated Sex Hormone-binding Globulin Secondary To Variegate Porphyria In A Patient With Hypogonadotropic Hypogonadism
Authors: Law Jocelyn , Yip Churn-Ern
Published: October 2023

Disclosure: J. Law: None. C. Yip: Research Investigator; Self; Eli Lilly & Company.

Background: Acute porphyria is a group of disorders characterized by enzymatic defects in the heme biosynthetic pathway. The liver is the source of both acute intermittent porphyria (AIP) and variegate porphyria. AIP is known to cause an elevation in sex hormone-binding globulin (SHBG) levels, likely secondary to impaired hepatic function and hepatocyte abnormalities1.

We describe a case of elevated SHBG secondary to variegate porphyria, in a male with hypogonadotropic hypogonadism.

Case Report: A 44-year-old male presented with an elevated SHBG and symptoms of hypogonadism with low libido, weakness, and fatigue. Fasting morning bloodwork revealed an elevated SHBG at 89 nmol/l (13.5- 71.0), a normal total testosterone level at 12.95 nmol/l (8-32), and a low bioavailable testosterone at 0.82 nmol/l (2.5-10), with confirmatory repeat blood work.

His history was significant for longstanding variegate porphyria, manifesting as frequent attacks of abdominal pain. He was on opioids for greater then 10 years for his chronic pain, as well as metoclopramide.

On assessment of causes for his elevated SHBG, his TSH was normal at 1.49 mIU/L (0.35-4.30). He did not have cirrhosis, hepatitis, hereditary hemochromatosis, and was not on anticonvulsants. No other cause was found, and his elevated SHBG was deemed secondary to his variegate porphyria.

His normal total testosterone level was due to his elevated SHBG, but as mentioned, his bioavailable testosterone was low. His LH and FSH were both inappropriately normal, with his LH being 4.67 IU/L (0.6-12.0) and his FSH 4.7 IU/L (1.0-12.0), in keeping with hypogonadotropic hypogonadism. He went through normal pubertal development and had no anosmia. Workup revealed an elevated prolactin level of 73.8 ug/l (3.5-19.4). He had no galactorrhea or gynecomastia and an MRI sella revealed a normal pituitary gland. His elevated prolactin level was determined to be secondary to his opioid medication and/or metoclopramide use. His hypogonadotropic hypogonadism was deemed secondary to his opioid medications and/or hyperprolactinemia.

Conclusion: This case demonstrated variegate porphyria as a likely cause of elevated SHBG, similar to AIP. In patients with variegate porphyria and symptoms of hypogonadism, the SHBG should be measured and if it is elevated, the bioavailable or free testosterone levels should be used in assess instead of relying on the total testosterone levels. As has been previously shown, this case also illustrated the use of opioid medications as a cause of hypogonadotropic hypogonadism.

References: (1) Herrick AL, McColl KE, Wallace AM, Moore MR, Goldberg A. Elevation of hormone-binding globulins in acute intermittent porphyria. Clin Chim Acta. 1990 Feb 28;187(2):141-8. doi: 10.1016/0009-8981(90)90340-x. PMID: 2107988.

Presentation: Friday, June 16, 2023
SAT366 Expression of Amyloid-related Proteins Associated With Dementia in Polycystic Ovary Syndrome Compared to a Control Population
Authors: Butler Alexandra E , Moin Abu Saleh Md , Sathyapalan Thozhukat , Atkin Stephen Lawrence
Published: October 2023

Disclosure: A.E. Butler: None. A.S. Moin: None. T. Sathyapalan: None. S.L. Atkin: None.

Objective: Several risk factors in polycystic ovary syndrome (PCOS) are associated with increased risk for Alzheimer’s disease (AD). We hypothesized that circulatory levels of amyloid-related proteins would be elevated in PCOS but that these would potentially be mitigated by elevated levels of proteins associated with protection from AD. Methods: Somascan proteomic analysis of amyloid-related proteins was undertaken in a well validated PCOS database of 143 women with PCOS and 97 control women. Results: Amyloid-precursor protein (APP) (p<0.05), amyloid P-component (APCS) (p<0.001), apolipoprotein E (apoE) (p<0.01) and apoE3 (p<0.05) were elevated in PCOS, whilst alpha-synuclein (SNCA) (p<0.05) was reduced in PCOS, all features associated with increased AD risk. Correlation analyses of the AD-related proteins with protective heat shock proteins (HSPs) showed that SNCA positively correlated with HSP90 (p<0.01) and with HSP60 (p<0.0001). Correlations with markers of inflammation showed APCS positively correlated with interleukin-6 (IL6) (p<0.05) whilst ApoE and ApoE3 correlated positively with tumor necrosis factor-alpha (TNF-alpha) (p<0.05). Conclusion: The AD-associated protein pattern found in PCOS, with basal elevated APP and reduced SNCA, parallels what has been reported in patients type 2 diabetes. This dysregulated AD-related protein expression in PCOS is likely exacerbated by obesity and insulin resistance-related inflammation and may be modulated by protective HSP mechanisms.

Reference: Moin ASM, Al-Qaissi A, Sathyapalan T, Atkin SL, Butler AE. Hypoglycaemia in type 2 diabetes exacerbates amyloid-related proteins associated with dementia. Diabetes Obes Metab. 2021 Feb;23(2):338-349. doi: 10.1111/dom.14220. Epub 2020 Oct 25. PMID: 33026133.

Presentation Date: Saturday, June 17, 2023