bluuebunny/crossref_metadata_2025 huggingface dataset:
FRI208 Treating Pheochromocytoma For Glycemic And Blood Pressure Control
Authors: Santiago Carrion Ada Marie , Gonzalez Bossolo Alex N
Published: October 2023

Disclosure: A.M. Santiago Carrion: None. A.N. Gonzalez Bossolo: None.

Pheochromocytomas are catecholamine-secreting tumors of the adrenal medulla chromaffin cells. They account for 0.2-0.6% of hypertension (HTN) in patients of general outpatient clinics. In addition, is known that this excess of catecholamine production is associated with impaired insulin release from pancreatic beta-cells leading to hyperglycemia. However, pheochromocytoma as a cause of diabetes and HTN is frequently overlooked. A 60-year-old woman with medical history of arterial HTN and type 2 diabetes mellitus since 10 years ago was referred to the Endocrine clinic by Nephrology for glycemic control. Her medical regimen consisted of linagliptin 5mg daily, metformin 1000mg twice daily, insulin glargine 40 units daily, losartan 50mg twice daily, amlodipine 10mg daily and hydrochlorothiazide 25mg daily. Physical examination was unremarkable, including adequate vital signs with blood pressure 110/64 mmHg and heart rate 93/min. Laboratories were notable for glycated hemoglobin 8.7%, fasting blood glucose 118 mg/dL, and urine albumin-creatinine ratio (UACR) 4622 mg/g with adequate glomerular filtration rate. Upon further investigation of nephrotic-range proteinuria, patient was incidentally found with a right adrenal mass on ultrasound, which was confirmed to have absent signal dropout on MRI and measured 5 cm. On retrospective, patient revealed feeling episodic palpitations, diaphoresis, and occasional headaches which she attributed to menopausal symptoms. Plasma free metanephrines were negative, but free normetanephrines were elevated at 2160 pg/mL (range <148 pg/mL). Patient underwent successful right adrenalectomy and pathology confirmed a right 5 cm pheochromocytoma with negative margins. Unfortunately, she wished to defer genetic testing. Four weeks after surgery, plasma normetanephrines fell to normal levels 141.8 pg/mL. Furthermore, patient was able to wean off basal insulin completely and HTN remained controlled with losartan monotherapy. Glycated hemoglobin improved to 6.7%. Additionally, UACR improved to 1352.94 mg/g and empagliflozin was added to avoid diabetic kidney progression. In this case we presented a patient with common comorbidities encountered in the clinic, but with an unusual etiology. Moreover, this patient presented with nephrotic-range proteinuria that has significantly improved after removal of the tumor, which has only been seen in case reports. Some authors propose a possible immunological pathogenesis or glomerular hyperfiltration. Detection of resistant HTN should had prompted earlier detection of pheochromocytoma in this patient. As physicians, we should be aware of endocrine causes of diabetes and HTN, such as Cushing syndrome, Acromegaly, Primary Aldosteronism, and Pheochromocytoma and Paraganglioma, as treating these may lead to better quality of life, and less disease-related complications and polypharmacy.

Presentation: Friday, June 16, 2023
SAT565 Is Firefighting An Occupational Risk For Papillary Thyroid Cancer? A Case Report
Authors: Diamond-Rossi Samantha Anne , Lee Patty , Thomas Cheddhi , Stanislawski Rita , Kim Jina
Published: October 2023

Disclosure: S.A. Diamond-Rossi: None. P. Lee: None. C. Thomas: None. R. Stanislawski: None. J. Kim: None.

Background: Papillary thyroid cancer (PTC) is the most prevalent histologic type of thyroid cancer. The toxic exposures associated with firefighting from both protective gear and combustion products have brought to question whether this population is at an increased risk of developing certain malignancies, including thyroid cancer. The objective of this case report is to raise awareness of the possible association between firefighting and thyroid cancer.

Case Presentation: A 46-year-old asymptomatic male career firefighter presented to our clinic following a mobile screening thyroid ultrasound which revealed bilateral suspicious nodules. FNAs of a 1.0 cm right nodule and 1.2 cm left nodule were consistent with papillary thyroid cancer. Lymph node mapping revealed bilateral suspicious lymph nodes in levels 3 and 4 with FNAs confirming metastatic PTC. He underwent total thyroidectomy with bilateral central and lateral lymph node dissections confirming multifocal disease, which included numerous submillimeter foci of PTC. 21 of 68 lymph nodes had metastatic disease. He is now scheduled for adjuvant radioactive iodine therapy.

Discussion: Compared to the general population, firefighters have a higher incidence of thyroid cancer. In 2022, the International Agency for Research on Cancer (IARC) announced that occupational exposure as a firefighter would be considered a Group 1 carcinogen, designating this exposure as having sufficient evidence for carcinogenicity in humans. In recognition of this risk, our local fire department, the Fairfax County Fire & Rescue, has implemented a cancer screening protocol offered to firefighters which includes a mobile thyroid ultrasound. Our patient had extensive disease with bilateral lymph node involvement requiring radioactive iodine after surgical resection. Without a screening ultrasound, it can be presumed that our patient would have presented later and perhaps with even more advanced disease. Firefighters are exposed to carcinogens and possible endocrine disrupting chemicals as part of their work, either via their protective equipment or products of the fire itself. More research is needed to determine if the higher incidence of thyroid cancer can be attributed to this occupational exposure versus surveillance bias due to increased screening of this population in recent years.

Presentation: Saturday, June 17, 2023
SAT573 Incidental Discovery Of CHEK2 Mutation With Papillary Thyroid Cancer
Authors: Thelmo Franklin L , Mehrab Amina , Jabbour Serge A
Published: October 2023

Disclosure: F.L. Thelmo: None. A. Mehrab: None. S.A. Jabbour: None.

A 66-year-old white male had been following steadily with our practice for greater than a decade where we were managing his post-ablative hypothyroidism from toxic multinodular goiter 20 years prior. Many years later, the patient developed hypercalcemia and was found to have asymptomatic primary hyperparathyroidism. He did not meet any indication for parathyroidectomy. In early January 2021, the patient was referred to a clinical geneticist at the behest of his wife as she was concerned that he had a very high rate of cancer in his family. The patient had a total of 11 relatives who either currently had or previously died from a malignancy, of which only one of them was on his maternal side. The patient’s father had a personal history of breast cancer, prostate cancer, and bone cancer at the time he passed away. The patient underwent a full panel of genetic testing and was found to be positive for a CHEK2 (Checkpoint Kinase 2) mutation. Around this time, the patient’s hypercalcemia escalated up to 13mg/dL without evidence of hypoalbuminemia. Decision was made to pursue surgery. In order to localize the parathyroid adenoma, a technetium sestamibi scan and a neck ultrasound were obtained. Sestamibi scan showed increased parathyroid adenomatous activity in the left lower portion of the thyroid bed and ultrasound confirmed the left lower pole parathyroid adenoma with a dominant hypoechoic 2.5cm TI-RADS 5 thyroid nodule which on biopsy was suspicious for papillary thyroid carcinoma. The patient underwent a total thyroidectomy in addition to the parathyroidectomy. Pathological evaluation confirmed a parathyroid adenoma and a classic variant of papillary thyroid carcinoma without angioinvasion and minimal extrathyroidal invasion classified as Stage 1 T2N0M0. The patient did not meet criteria for treatment with radioactive iodine and at the time of this writing is doing well, on levothyroxine with low-normal TSH and undetectable thyroglobulin with normal serum calcium. He has no other signs of malignancy at this time. However, given his CHEK2 mutation, he will require ongoing multi-disciplinary cancer surveillance. We would like to draw attention to this not uncommon oncogenic mutation that due to its incomplete penetrance does not always present such a staggering family history of cancer and thus may go undetected. CHEK2 mutations occur in roughly 1% of all individuals who undergo genetic evaluation for cancer. The mutation moderately increases the patient and their family’s risk for multiple malignancies including: breast, thyroid, prostate, stomach, kidney, and plasma cell malignancies. Individuals with this mutation should be screened thoroughly by a multi-disciplinary team based on the severity of their inherited mutation. These individuals should also receive counseling on family planning if conception is desired.

Presentation: Saturday, June 17, 2023
SAT313 Therapeutic Dosing Of Steroids In Patients On Mitotane
Authors: Pham Christopher , Cannon Sophie M , Lopresti Jonathan S
Published: October 2023

Disclosure: C. Pham: None. S.M. Cannon: None. J.S. Lopresti: None.

Introduction: Mitotane is a known inhibitor of steroidogenesis with some patients requiring supraphysiologic dosing for steroid replacement. Clinical Case: A 43-year-old female with a history of adrenal cell carcinoma (ACC) on multiagent chemotherapy and mitotane presents with a pruritic rash. Three weeks prior, she had received her first dose of pembrolizumab. Her other home medications included mitotane 500mg QID and hydrocortisone 180mg (40mg-40mg-30mg -20mg QID). Labs on admission were notable for an ALT of 458 (ref 10-35 U/L), AST of 272 (ref 10-35 U/L), and normal alkaline phosphatase and bilirubin with otherwise normal electrolytes. Due to the temporal relation of her transaminitis and rash to recent pembrolizumab infusion with an otherwise negative work-up, the patient was diagnosed with immune-mediated liver injury from checkpoint inhibitors (ILICI). Per National Comprehensive Cancer Network (NCCN) guidelines, high dose methylprednisolone was initiated (1mg/kg) equivalent to approximately 525 mg hydrocortisone total daily. Over five days, the patient’s transaminases continued to rise and methylprednisolone was increased to 3mg/kg/day to account for the known effects of mitotane on steroid metabolism. The patient’s rash subsequently resolved followed by slow improvement of her transaminitis with steroid taper. Mitotane level obtained one week after discontinuation of mitotane was noted to be 21mcg/mL demonstrating persistent therapeutic levels (14-20mcg/mL).

Mitotane has a profound inhibitory effect on steroidogenesis through multiple mechanisms, inhibiting glucocorticoid production by the adrenal and increasing hepatic disposal of glucocorticoids leading to subtherapeutic doses1, Furthermore, mitotane can persist in the body for a prolonged period, with a half-life between 18-154 days. As such, patients who develop adrenal insufficiency on mitotane typically require higher doses for physiologic replacement up to three times standard physiologic dose1. In this case, only when the patient’s methylprednisolone dose was tripled did her ILICI begin to improve. Conclusion: This is one of the first cases to describe ILICI in a patient with ACC highlighting unique clinical considerations in management. Higher doses of corticosteroids may be required to overcome the effects of mitotane on steroid metabolism in patients with adverse effects from immune checkpoint inhibitor therapy.

1.)Puglisi, S., Calabrese, A., Basile, V., Pia, A., Reimondo, G., Perotti, P., & Terzolo, M. (2020). New perspectives for mitotane treatment of adrenocortical carcinoma. Best Practice & Research Clinical Endocrinology & Metabolism, 34(3), 101415. https://doi.org/10.1016/j.beem.2020.101415

Presentation: Saturday, June 17, 2023
SAT316 Severe Cushing’s Syndrome Due To Ectopic ACTH In Newly Diagnosed Small Cell Lung Cancer: The Pivotal Role Of Etomidate In Acute Treatment
Authors: Belal Heiba , Gandhi Gunjan Yogendra
Published: October 2023

Disclosure: H. Belal: None. G.Y. Gandhi: None.

Introduction: Ectopic ACTH syndrome can present as an endocrine emergency. Etomidate, the only parenteral steroidogenesis inhibitor, can rapidly treat critically ill patients with Cushing’s syndrome (CS) and concurrent significant metabolic derangements, severe hypertension, or psychosis. Case Description: A 66-year-old female presented with abdominal pain, vomiting, proximal muscle weakness, and confusion for 6 months. Physical exam revealed hypertension, bilateral supraclavicular fat pads, and abdominal distention, while laboratory evaluation uncovered severe hypokalemia <1.5 mmol/L, metabolic alkalosis, and elevated proBNP. A hilar soft tissue mass with mediastinal lymphadenopathy and bilaterally enlarged adrenal glands were seen on CT imaging. Serum cortisol was high at 114 mcg/dL. ACTH was inappropriately elevated at 111 pg/mL. MRI revealed a normal pituitary gland. She developed hypertensive emergency and status epilepticus, requiring intubation. Due to her life-threatening presentation, a guideline-based hypercortisolism workup was forgone for emergent treatment with continuous etomidate infusion. Serum cortisol normalized after 4 days of etomidate therapy. Due to concerns of reduced seizure threshold with etomidate therapy, it was weaned off after 14 days and replaced by ketoconazole. She subsequently developed recurrent hypercortisolism (serum cortisol 92 mcg/dL). After 14 days of etomidate, 9 days of ketoconazole, and 3 days of chemotherapy for biopsy-proven small-cell lung carcinoma, serum cortisol reached a trough of 22 mcg/dL. At this point, hydrocortisone therapy was initiated (block-and-replace). Recurrent clinical hypercortisolism then developed, and hydrocortisone was discontinued. Hypercortisolism comorbidities were treated appropriately: trimethoprim-sulfamethoxazole for pneumocystis pneumonia prophylaxis, anticoagulation for DVT prophylaxis, antibiotics for acute diverticulitis, and insulin for hyperglycemia. Despite treatment, her condition worsened; she was transitioned to comfort care one month after admission and died 4 days later. Discussion: Etomidate inhibits steroidogenesis through 11 beta-hydroxylate blockade and works rapidly (within 12-24 hours) to decrease cortisol levels versus ketoconazole (several days) and has a reduced risk of hepatic injury. Side effects of etomidate include respiratory depression, myoclonus, and reduced seizure threshold. Several experts have suggested a block-and-replace strategy in severe CS treatment. While effective, this strategy poses risks of etomidate toxicity and makes serum cortisol interpretation unreliable. Etomidate analogs are on the horizon that retain the potent adrenostatic action of etomidate without its sedative-hypnotic activity, offering an alternative treatment option for treating patients with severe CS in non-ICU hospital settings.

Presentation: Saturday, June 17, 2023
SAT329 Case Series Of Patients With FGFR-1 Related Pheochromocytoma With A Focus On Biochemical And Imaging Signatures
Authors: Jhawar Sakshi , Del Rivero Jaydira , Pacak Karel
Published: October 2023

Disclosure: S. Jhawar: None. J. Del Rivero: None. K. Pacak: None.

Introduction: Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine tumors arising from chromaffin cells of adrenal gland and neural crest, respectively. 40% of cases are associated with germline mutations and 30-40% somatic driver mutations. Here, we present two patients with PCC who were found to have somatic FGFR1 mutation. FGFR signaling is involved in regulation of tissue repair, angiogenesis, and inflammation. Patient 1: A 70-year-old female with a history of resistant hypertension, episodic palpitations and sweating presented with diffuse abdominal pain and chest tightness. She was noted to have a blood pressure of 220/160 mm Hg. CT scan showed a 4.2 x 3.9 cm left adrenal mass, suspicious for malignancy and a <1 cm retroperitoneal mass. Blood work revealed elevated plasma normetanephrine (NM) 3543 pg/mL (normal 0- 145) and metanephrine (MN) 871 pg/mL (normal 0-62). 18F-FDG PET/CT showed a left adrenal mass without abnormal FDG activity. 68Ga-DOTATATE PET/CT was compatible with left PCC (SUVmax 28). 18F-DOPA PET/CT showed left PCC and a small retroperitoneal PGL. Two weeks after initiating phenoxybenzamine, she underwent total left adrenalectomy. Pathology was consistent with PCC. Molecular testing revealed FGFR1 pathogenic somatic mutation (c.1638C>G p.Asn546Lys). Patient 2: A 73-year-old male with known left renal cell carcinoma presented to our institution for management of recurrent right PCC. He was found to have a 3.8 cm right adrenal incidentaloma eight years ago and elevated plasma NM 6.3 nmol/L (normal <0.9), MN 1.5 nmol/L (normal <0.5). He underwent total right adrenalectomy, and the diagnosis of PCC was confirmed on histopathology. Two years later, he developed a 5.1 x 4.7 cm nodular mass in the right adrenal fossa and a <1 cm liver lesion on CT scan. The adrenal lesion showed intense avidity on 68Ga-DOTATATE PET/CT and 18F-DOPA PET/CT and mild avidity on 18FDG-PET/CT. 18F-DOPA PET/CT also showed avidity towards the liver lesion. He was started on doxazosin and underwent laparoscopic right adrenalectomy. Pathology demonstrated PCC. Whole exome sequencing of the tumor showed pathogenic FGFR1 mutation (c.1638C>G, p.Asn546Lys). Discussion: Activating FGFR1 mutations are associated with sporadic PCC. The biochemical phenotype of our patients showed higher levels of NM than MN. The imaging profile revealed that 18F-DOPA PET/CT was more sensitive than 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT as it showed avidity towards other extra-adrenal lesions. Further studies in larger cohorts are needed to enhance understanding of pathogenesis, biochemical and imaging phenotype, which will help tailor the treatment and potential development of novel targeted therapies.

Presentation: Saturday, June 17, 2023
SAT336 A Successful Ovulation Induction And Embryo Generation In A Woman With P450-oxidoreductase Deficiency From Mutation G539R, Which Preferentially Impairs 17,20-lyase Activity
Authors: Charoensri Suranut , Thakur Mili , Auchus Richard J
Published: October 2023

Disclosure: S. Charoensri: None. M. Thakur: None. R.J. Auchus: None.

Introduction: Cytochrome P450 oxidoreductase (POR) deficiency is an autosomal recessive disorder causing decreased activity of several P450 enzymes, including CYP21A2, CYP17A1, and CYP19A1 that are essential for steroidogenesis in the adrenals and gonads. Female POR deficiency patients are typically manifested with genital ambiguity, abnormal menstruation, and infertility. Very few pregnancies have been documented from these patients.

Case presentation: During an evaluation for infertility, a 35-year-old woman with late menarche, irregular cycles, and unruptured ovarian follicles was diagnosed with POR deficiency due to compound heterozygous pathogenic variant c.1615G>C (G539R) and a large deletion c.1669+5_1669+32del in the POR gene. Because mutation G539R preferentially impairs the 17,20-lyase activity of CYP17A1, she underwent in-vitro fertilization (IVF) with the protocol that has been used successfully to achieve pregnancy in incomplete 17-hydroxylase deficiency. Oral dexamethasone of 0.5 mg/day was given to suppress the adrenal-derived progesterone. After one menstrual cycle induced with estradiol and progesterone priming, leuprolide acetate was used to down-regulate endogenous gonadotropin secretion, then the oocyte maturation was induced with recombinant follicle-stimulating hormone (rFSH) and highly purified menotrophin. In the first cycle, 6 eggs were retrieved, 2 that were mature and fertilized with intracytoplasmic sperm injection (ICSI); however, none advanced to the blastocyst stage. She underwent the same protocol in a second IVF cycle with higher rFSH dosing. Despite increasing dexamethasone to 1.5 mg/day, progesterone rose to 4.9 ng/mL, while estradiol peaked at 120 pg/mL, consistent with progesterone accumulation in the developing ovarian follicles due to POR deficiency. From 6 eggs retrieved, 5 eggs were mature and all fertilized, and 3 developed past day 3. On day 6, one embryo (grading 5BB) was biopsied for preimplantation genetic testing and frozen. The second phase of the treatment plan is to lower adrenal-derived progesterone with a combination of hydrocortisone and prednisolone, prepare the endometrium with estradiol followed by progesterone, and perform embryo transfer. Conclusions: Very few examples of pregnancy in women with POR deficiency have been reported, and we describe the first example of successful ovulation induction and embryo generation in a woman with POR deficiency caused by the G539R mutation, which preferentially impairs 17,20-lyase activity. The complex array of steroid excess and deficiencies, from both adrenal and ovarian origin, must be systematically managed during assisted reproduction treatment for these women.

Presentation: Saturday, June 17, 2023
THU418 Steroid Profiles And Its Implication In Bone Mass And Quality In Premenopausal Women With Adrenal Tumors With Autonomous Cortisol Secretion
Authors: Nakao Hiroshi , Nakatani Kohta , Yokomoto-Umakoshi Maki , Umakoshi Hironobu , Kaneko Hiroki , Iwahashi Norifusa , Ogata Masatoshi , Fukumoto Tazuru , Masamichi Fujita , Tatsuki Ogasawara , Matsuda Yayoi , Sakamoto Ryuichi , Izumi Yoshihiro , Bamba Takeshi , Ogawa Yoshihiro
Published: October 2023

Disclosure: H. Nakao: None. K. Nakatani: None. M. Yokomoto-Umakoshi: None. H. Umakoshi: None. H. Kaneko: None. N. Iwahashi: None. M. Ogata: None. T. Fukumoto: None. F. Masamichi: None. O. Tatsuki: None. Y. Matsuda: None. R. Sakamoto: None. Y. Izumi: None. T. Bamba: None. Y. Ogawa: None.

Context: Osteoporosis is a major complication in adrenal tumors with autonomous cortisol secretion (ACS). We conducted steroid profiling to elucidate how steroid metabolites affect bone mass and quality in patient with ACS. Methods: Ninety patients with ACS and 91 with non-functioning adrenal tumors (NFAT) were included, of whom 73 ACS (18 pre-, 26 postmenopausal women, and 29 men) and 85 NFAT (12 pre-, 34 postmenopausal women, and 39 men) were evaluated for 21 plasma steroid metabolites using liquid chromatography-tandem mass spectrometry. Results: Premenopausal women with ACS had lower lumbar spine (LS)-bone mineral density (BMD) and trabecular bone score (TBS) than those with NFAT. The discriminant and principal component analyses clearly separated ACS from NFAT in premenopausal women, but not in men and postmenopausal women. In premenopausal women, 8 steroid metabolites differed between ACS and NFAT, with 11-deoxycorticosterone having the largest effect size (Cohen’s d=1.600, false discovery rate (FDR)=1e-04). In premenopausal women with ACS, 11-deoxycorticosterone showed a negative correlation with LS-BMD Z-score (r=-0.603, FDR=0.064), and DHEA-S and androsterone-glucuronide showed a positive correlation with TBS (DHEA-S, r=0.647, FDR=0.019; androsterone-glucuronide r=0.681, FDR=0.020). The correlation of 11-deoxycorticosterone with LS-BMD Z-score and that of androsterone-glucuronide with TBS remained significant after adjustment for confounders. In men and postmenopausal women with ACS, no steroid metabolites evaluated were significantly correlated with BMD and TBS. Conclusion: This study provides the evidence for distinct steroid profiles in premenopausal women with ACS, suggesting that elevated 11-deoxycorticosterone, a mineralocorticoid metabolite, induces bone loss, and decreased androsterone-glucuronide, an androgen metabolite, deteriorates bone quality.

Presentation: Thursday, June 15, 2023
THU423 Recognizing Secondary Contributors Of Osteoporosis In A Hip Fracture Cohort In Singapore
Authors: Tay Wei Lin , Kwang Donovan Tay Yu
Published: October 2023

Disclosure: W. Tay: None. T.Y. Donovan: None.

Osteoporotic fractures pose a considerable burden on a country’s healthcare system. Identifying and managing secondary contributors is essential in optimizing the response to osteoporosis treatment. The reported prevalence of secondary osteoporosis is heterogeneous and maybe country-specific and recommendations on screening for these contributors in guidelines are variable. Knowing the frequency of underlying disorders can facilitate development of suitable and cost-effective recommendations specific to a population. We aimed to examine the prevalence of secondary contributors of osteoporosis in a multi-ethnic cohort of Singaporean women and men presenting with hip fracture and to also identify the extent of treatment gap. A retrospective cohort study of 493 consecutive adult patients admitted to a regional hospital in Singapore for a hip fracture were evaluated for secondary contributors. All patients were enrolled in a standard electronic hip fracture clinical pathway. Laboratory investigations were standardised. Deidentified data was extracted from the electronic health intelligence system (eHINTS) using the Oracle Business Intelligence and Enterprise Edition (OBIEE) software. The eHINTS is a data repository that consolidates healthcare, operational and finance data from multiple healthcare system uploaded on the web-based business intelligence software. Demographics, clinical data and laboratory investigations, bone mineral density and current medication were extracted. Approval was obtained from the centralized institutional board of our institution.

The mean age of the cohort was 78 ±11 years. The majority (67.3%) of the cohort were female. Mean BMI was 22.3± 9.2 kg/m2. The mean T score at the lumbar spine was -1.87± 1.55; total hip -2.32±1.42; femoral neck -2.50 ± 1.28. 45.2% of the cohort had at least a secondary contributor of osteoporosis. 30.6% had vitamin deficiency (25OHD <20µg/L). 12.2% were on at least 1 medication implicated in the pathogenesis of osteoporosis such as aromatase inhibitors, glucocorticoids, anti-epileptics, levothyroxine, anti-depressants, warfarin, gonadotropin-releasing hormone (GnRH) therapy. 6.9% had primary hyperparathyroidism. 2.6% had primary hyperthyroidism. In male patients, 2.5% had hypogonadism. 1 patient had hypercalciuria. 13.6% had a BMD done prior to the hip fracture admission and only 11.8% of patients were on osteoporosis treatment prior to admission.

Secondary contributors to osteoporosis are common and this should be considered in the evaluation of patients presenting with hip fractures. A significant treatment gap still exists and future studies should address the reasons behind the treatment inertia.

Presentation: Thursday, June 15, 2023
THU424 A Diagnostic Predictive Model For Secondary Osteoporosis In Patients With Fragility Fracture: A Retrospective Cohort Study In A Tertiary Care Hospital
Authors: Phudphong Pitchaporn , Phimphilai Mattabhorn , Manosroi Worapaka , Adulkasem Nath , Kaewchur Tawika
Published: October 2023

Disclosure: P. Phudphong: None. M. Phimphilai: None. W. Manosroi: None. N. Adulkasem: None. T. Kaewchur: None.

Introduction: Although primary osteoporosis is the leading etiology of osteoporosis in asymptomatic elderly presenting with fragility fractures, secondary osteoporosis can be accounted for one-third of patients. Establishing whether a fragility fracture is secondary to a specific cause of osteoporosis is crucial for treatment outcomes. This study aimed to develop a simple screening tool for secondary osteoporosis in the elderly who are presented with fragility fractures. Methods: A retrospective cohort study of 456 patients diagnosed with non-traumatic hip and clinical vertebral fractures between January 2017 and July 2022 was conducted. Demographic, clinical, biochemical, and final diagnostic data were retrieved. Potential predictors for secondary osteoporosis were identified via multivariate logistic regression analysis. Subsequently, we developed a predictive model for secondary osteoporosis using the identified potential predictors. Results: This study included 343 females and 113 males with a mean age of 76.9±11.0 years. One hundred and twenty-one patients (26.5%) were diagnosed with secondary osteoporosis. Vitamin D deficiency (71.9%) was the most common cause of secondary osteoporosis, followed by glucocorticoid-induced osteoporosis (23.9%) and primary hyperparathyroidism (9.9%). The developed prediction model for secondary osteoporosis demonstrated an acceptable discriminative ability with an AuROC of 0.75 (95%CI 0.69 to 0.81) using the patient’s age, body mass index (BMI), corrected serum calcium, serum phosphate, thyroid stimulating hormone (TSH) level, and BMI-based FRAX score. With a cut-off level of 0.22, the proposed predictive model revealed a sensitivity of 74.4% and a specificity of 65.8%. Finally, the developed prediction model was derived into a web-based screening tool available at: https://www.calconic.com/calculator-widgets/secondary-osteoporosis-screening-tool/62f7c112d5da86001f8e3a25?layouts=true. Conclusion: A predictive model for screening secondary osteoporosis was constructed using simple clinical and biochemical parameters. This newly developed predictive model may provide clinicians with guidance to perform further advanced investigations for secondary causes of osteoporosis.

Presentation: Thursday, June 15, 2023
THU427 The Benefits Of Oral Bisphosphonates For Elderly Patients With A History Of Long Term Aromatase Inhibitor Use
Authors: Dominguez Lorena D , Acosta Sebastian Everett , Alejandro Angel Rodolfo
Published: October 2023

Disclosure: L.D. Dominguez: None. S.E. Acosta: None. A.R. Alejandro: None.

Aromatase Inhibitors (AI) are commonly used to treat estrogen receptor-positive breast cancer as they reduce the risk of recurrence and mortality. The AIs, however, can lead to a decrease in bone mineral density (BMD), resulting in fractures. According to the Journal of Bone Oncology (JBO), postmenopausal women on AIs with two or more risk factors for fractures should be placed on antiresorptive treatment (1). Our objective was to compare the BMD of at-risk patients that have been treated with antiresorptive treatment versus the BMD of patients not treated. An EMR chart review was conducted from 6/14/2022-8/20/2022, in which 295 patients were analyzed by the medications prescribed and their BMD. Our sample size was limited to 90 patients that had obtained DXA scores from the same GE Hologic densitometer. We hypothesized that patients on AIs and antiresorptive treatment would show more improvement in BMD than patients on AIs and not on treatment. Patients were analyzed in the comparison of their BMD. Of the 65 patients on AIs, only 17 were placed on antiresorptive treatment (26%). 94% of these patients showed improved BMD. The increase in BMD for the spine was significant (.030) as it exceeds the least significant change (LSC) of .027 g/cm^2. The improvement of .012 in the hip was not significant (.022 g/cm^2 LSC). 68.75% of patients on AI’s and not on treatment worsened by .025 in the hip (.022 g/cm^2 LSC) and by .017 in the spine (.027 g/cm^2 LSC). Alendronate (76%), Zoledronic acid (18%) and Ibandronate (6%) were commonly prescribed. The patients on Alendronate and Ibandronate, improved by .015 in the hip (.022 g/cm^2 LSC) and improved significantly by .028 in the spine (.027 g/cm^2 LSC). Patients on intravenous(IV) treatment improved significantly in the spine by .041(.027 g/cm^2 LSC) but only improved by .006 in the hip (.022 g/cm^2). Although IV administration of treatment is recommended for patients starting treatment (2), most patients showed a trend of improvement on oral bisphosphonates. Hence, to improve the care offered to at-risk patients who cannot obtain IV bisphosphonates, we can advocate for the use of oral bisphosphonate treatment.

References:

(1)Hadji, Peyman, et al. “Manage of Aromat.” JBO, 2017,doi:10.1016/j.jbo.2017.03.001

(2)”Mottaghi P. Intrav bisphos.” Res Med. 2010 May;1515(3):175-84

Presentation: Thursday, June 15, 2023
THU428 Association Of Bone Turnover Markers Monitoring With Osteoporosis Medication Adherence In Korea: A Nationwide Cohort Study
Authors: Ahn Seong Hee , Park So Young , Kwak Mi Kyung , Kim Se Hwa , Kim Tae-Young , Kim Ha Young , Hong Seongbin
Published: October 2023

Disclosure: S. Ahn: None. S. Park: None. M. Kwak: None. S. Kim: None. T. Kim: None. H. Kim: None. S. Hong: None.

Objective: Bone turnover markers (BTMs) are non-invasive and useful biomarkers for predicting the risk of fractures and monitoring the adherence and response to medical treatment in patients with osteoporosis. However, the contribution of BTMs in the improvement of osteoporosis medication adherence has not been well studied. Therefore, we investigated the association of BTMs monitoring with medication adherence in Korean osteoporosis patients. Methods: We used data from the Korean National Health Insurance Service. Among 1,440,538 osteoporosis patients ≥50 years who started with medical treatment during 2010-2014, we selected 118,598 patients who monitored BTMs at least once during 2 years of follow up (BTM group) and 362,794 age-, sex-, and medication initiation year-matched controls who never measured BTMs (NO-BTM group). Adherence to medical treatment was defined as medication possession ratio ≥80%. Multivariable logistic regression analysis was used to determine the association of BTMs monitoring with adherence at 2 year follow up. Results: Among BTM group, 92.5% and 87.1% patients monitored bone resorption or formation markers at least once during 2 years of follow up, respectively. However, only 36.0% of patients monitored BTMs more than twice. MPRs at 2 year follow up were higher in BTM group than in NO-BTM group (41.4% vs. 26.5%, P<0.001). Among BTM group, MPRs were higher in patients who monitored bone resorption markers than in patients who never monitored them (41.7% vs. 36.1%, P<0.001) and in patients who monitored BTMs more than twice than in patients who monitored them only once (55.6% vs. 32.9%, P<0.001). BTMs monitoring showed positive association with MPRs at 2 year follow up (β = 3.055, SE = 0.137, P<0.001) after adjusting for confounders. BTMs monitoring was associated with increased OR (1.17, 95% CI 1.15-1.20, P<0.001) for better adherence to medical treatment at 2 year follow up after adjusting for confounders. Conclusion: In this retrospective study, monitoring of BTMs was associated with better adherence to medical treatment in Korean patients with osteoporosis.

Presentation: Thursday, June 15, 2023
THU301 Natural History Of Pregnancy And Pregnancy Outcomes In Subjects With Lipodystrophy
Authors: Neal Trinity J , Startzell Megan S , Cochran Elaine , Lightbourne Marissa , Brown Rebecca J
Published: October 2023

Disclosure: T.J. Neal: None. M.S. Startzell: None. E. Cochran: None. M. Lightbourne: None. R.J. Brown: None.

Lipodystrophy syndromes are a group of rare heterogenous disorders characterized by deficiency of adipose tissue in a regional distribution (Partial Lipodystrophy, PL) or all of the body (Generalized Lipodystrophy, GL), leading to severe insulin resistance, diabetes, hypertriglyceridemia, non-alcoholic steatohepatitis, and polycystic ovarian syndrome. During pregnancy in patients with lipodystrophy, insulin resistance worsens during late gestation, leading to pregnancy complications that may threaten the lives of the fetus and mother. Case reports have suggested increased risk of pregnancy complications such as pre-eclampsia in patients with lipodystrophy. We sought to systematically examine pregnancy complications and offspring outcomes in lipodystrophy through a prospective study involving structured interviews with patients with known lipodystrophy and past pregnancy.

Data were collected in 7 patients with PL (2 LMNA, PPARG, 4 unknown genetic cause) and 1 with GL (AGPAT2). These 7 patients had 21 pregnancies (mean 2.6), including 19 singleton and 2 twin gestations. 14 pregnancies (67%) were spontaneous and 7 (33%) required fertility treatment. 10 pregnancies (48%) in 6 patients resulted in 12 live births (7 term, 3 preterm; 3 vaginal and 8 C-section delivery) and 11 (52%) resulted in miscarriage (9 first trimester, 2 second trimester in 1 patient due to cervical insufficiency). There were no episodes of acute pancreatitis during pregnancy. Among the 10 pregnancies resulting in live birth, 100% were complicated by diabetes. 5 (50%) had pre-gestational diabetes and 5 (50%) had gestational diabetes that resolved after delivery. 8 (80%) required insulin during pregnancy (of whom none required insulin pre-pregnancy). 5 (50%) of these pregnancies were complicated by pre-eclampsia. Among all 21 pregnancies, metformin was used in 8 (38%), insulin in 8 (38%), metreleptin in 4 (19%) pregnancies (all 4 of which were in 1 patient with GL), and fenofibrate in 2 (9.5%). Among 12 offspring, 1 (8%) was small for gestational age (GA), 8 (67%) were appropriate for GA and 3 (25%) were large for GA. 6 (50%) had neonatal hypoglycemia.

In summary, pregnancies in women with lipodystrophy showed high complication rates, including very high rates of miscarriage, diabetes, and pre-eclampsia. Larger studies are needed to determine how management of these patients during pregnancy, including with newer treatments such as metreleptin for GL, affects pregnancy and offspring outcomes.

Presentation: Thursday, June 15, 2023
FRI652 Type 2 Diabetes Management: More GLP1 Agonists And Less Metformin?
Authors: Lopez Maldonado Francisco J , Cota Rene A
Published: October 2023

Disclosure: F.J. Lopez Maldonado: None. R.A. Cota: None.

Case presentation: A 41-year-old male patient with family history of T2DM in both parents and brother, personal history of mild alcohol consumption and a sedentary job (public accountant), and obesity since age 30 presented to the endocrinology clinic due to failure to lose weight after 1 year of treatment with a nutritionist. During his first visit, the was asymptomatic and had acanthosis nigricans, his blood pressure was measured at 142/92 mmHg, weight was 100.8 kg, waist circumference was 128 cm, and serum glucose was at 280 mg/dL with an HbA1c of 11.9%. Further laboratory tests showed elevated levels of triglycerides (310 mg/dL), LDL (139 mg/dL), AST (96 U/L), and ALT (65 U/L). Two days later, glucose and HbA1c were repeated with similar results. A liver ultrasound was ordered which revealed diffuse hyperechogenicity of the liver and severe fatty liver disease. The ASCVD risk score was 5.4%. The patient was diagnosed with T2DM, obesity, mixed dyslipidemia, and fatty liver disease. The patient received education, nutrition support, exercise, and pharmacotherapy management with stepped-dose oral semaglutide without metformin. The dose was increased monthly starting at 3 mg and reaching the target dose of 14 mg QD. After three months, the patient demonstrated significant improvements in various parameters such as blood pressure (−10/−8 mmHg), weight (−9.8 kg), waist circumference (−25 cm), serum glucose (−179 mg/dL), HbA1C (−5.7%), triglycerides (−154 mg/dL), LDL (−18 mg/dL), AST (−60 U/L), and ALT (−38 U/L), along with an increase in HDL (+6 mg/dL). After approximately 4 months on the target dose the patient showed further improvements in several parameters including ASCVD risk score (2.1%), blood pressure (−20/12 mmHg), weight (−14.8 kg), waist circumference (−30 cm), serum glucose (−183 mg/dL), HbA1C (−6%), LDL (−25 mg/dL), AST (−63 U/L), and ALT (−40 U/L), and HDL (+10 mg/dL), except for triglyceride levels (−130 mg/dL). Follow-up liver ultrasound showed significant improvement in fatty liver disease. Real-world experiences with newly introduced drugs should be reported, as they may have beneficial effects beyond the ones studied. Oral semaglutide, the first oral GLP-1 analog, has been shown to be non-inferior to other subcutaneous GLP-1 analogs. In this case, improvements were observed in glycemic control, weight loss, lipid levels, and a reduction in cardiovascular risk, as well as an improvement in fatty liver disease.

Presentation: Friday, June 16, 2023
FRI663 A Rare Case Of Igf-2 Induced Hypoglycemia Associated With Metastatic Colon Cancer
Authors: Mohd Mari Anwar Alshaakh , Varshney Aarushi , Sidhu Ashlee , Matos Moises , Kinaan Mustafa
Published: October 2023

Disclosure: A. Alshaakh Mohd Mari: None. A. Varshney: None. A. Sidhu: None. M. Matos: None. M. Kinaan: None.

Introduction: The diagnosis of hypoglycemia in patients without diabetes is uncommon and nonislet cell tumor hypoglycemia (NICTH) represent a minority of these cases. The most common mechanism is related to IGF-2 production from tumor cells. Case description: A 66-year-old man with a history of stage IV colon cancer presented to the hospital due to breathlessness while receiving chemotherapy (Bevacizumab plus FOLFOX4). He had partial colectomy and chemotherapy 3 years earlier but was recently found to have metastatic disease to the liver. A CT abdomen during hospitalization showed a 15 cm hepatic mass occupying the entire right hepatic lobe. Endocrinology was consulted due to persistent postprandial and fasting hypoglycemia despite dextrose infusion. He had no history of diabetes and denied taking any diabetes medications. Plasma blood glucose (BG) was noted to be 74 mg/dl (74-106) while on dextrose. An 8AM cortisol was checked to exclude adrenal insufficiency and was 8.08 mcg/dL (4.30-22.40). A 72 hour fast was done but discontinued at 8 hours when plasma BG dropped to 48 and patient became symptomatic. At the time C-peptide and Insulin levels were low <0.05 ng/mL (0.48-5.05) and <1.0 mU/L (3.0-25) respectively, with normal Beta-hydroxybutyrate (BHB) 1.1 mg/dL (0.2-2.8). At the end of the fast 1 mg of glucagon was administered and his BG increased to 112 mg/dl in 2 hrs. IGF-1 levels were undetectable <15 ng/mL and IGF-2 levels were found to be 175 ng/mL. The IGF2:IG1 ratio was at 11 confirming IGF-2 mediated NICTH. Dexamethasone 10 mg daily was started, and BG were maintained > 70mg/dl without dextrose infusion. Discussion: In approximately 50% of NICTH, the tumor is identified prior to the onset of hypoglycemia, but up to 50% of these patients may be asymptomatic despite hypoglycemia. Our patient had a known hepatic lesion and was minimally symptomatic despite very low BG. The mechanism for NICTH can include insulin secretion from the tumor, replacement of hepatic tissue and increased glucose utilization by the tumor, or most commonly, IGF-2 secretion. In the case of IGF-2 mediated hypoglycemia insulin, proinsulin, C-peptide, and β-hydroxybutyrate levels are low. An elevated IGF-2:IGF-1 ratio (>10) confirms the diagnosis. The primary treatment is through surgical removal or debulking of the tumor. Neoadjuvant therapies such as radiation and chemotherapy may reduce occurrences of hypoglycemia, but only temporarily. Glucocorticoids may be used when the underlying malignancy cannot be treated.

Presentation: Friday, June 16, 2023
FRI664 The Impact Of Prediabetes Diagnosis On The Prevalence Of Postbariatric Hypoglycemia
Authors: Reshma Shariff Julia Rose , Funk Luke , Zaveri Aayush , Belt Davis Dawn
Published: October 2023

Disclosure: J.R. Shariff: None. L. Funk: None. A. Zaveri: None. D.B. Davis: None.

Bariatric surgery is not only a mainstay of obesity treatment, but it can result in remission of metabolic conditions, such as Type 2 diabetes. Post-operatively however, patients can develop postbariatric hypoglycemia (PBH), which is thought to be due to changes in insulin sensitivity and hypersecretion after eating. It has been suggested that prior type 2 diabetes can protect against PBH as decreased β-cell function prevents hyperinsulinemia. Patients with prediabetes may not have deterioration of β-cell function resulting in increased insulin production in response to glycemic excursion and subsequent hypoglycemia. The study aimed to assess the prevalence and severity of PBH in patients with prediabetes compared to those without prediabetes prior to bariatric surgery. We conducted a retrospective cohort study of patients 18 years and older who underwent either Roux-en-Y gastric bypass or sleeve gastrectomy between 2014 and 2021 and did not have a history of type 1 or type 2 diabetes mellitus at a single academic medical center. A history of PBH (hypoglycemia reported or documented after eating, symptoms of hypoglycemia, and resolution of symptoms after eating) and prediabetes (defined as A1c 5.7-6.4%, fasting glucose of 100-125mg/dL, or oral glucose tolerance testing with 2-hour glucose 140-199mg/dL) was determined based on medical record review. 14 patients developed PBH out of 539 (2.6%). 110 patients had prediabetes (20.4%). Of these 110 patients, 4 had PBH (3.6%). Of the 429 patients without prediabetes, 10 patients had PBH (2.3%). There was a greater post-operative weight loss, on average, in patients with PBH (19.5%) than in those without PBH (15.9%), although it should be noted that all PBH patients had Roux en Y gastric bypass. Interestingly, only 15% of the PBH population appeared to be on pharmacologic treatment, despite 21.5% being hospitalized or in the emergency room for hypoglycemic events. Most PBH patients (64.3%) developed symptoms between 1 to 3 years post-operatively, which is consistent with other studies on this topic. There was no association between prediabetes and PBH in our dataset (p=0.46), however our data set was quite small and it may be difficult to draw significant conclusions. A larger scale study done in a prospective manner would be useful for further research.

Presentation: Friday, June 16, 2023