bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT299 Comparison Of Plasma Cortisol-, Salivary Cortisol- And Salivary Cortisone-response To The Short Synacthen Test In Women Using Oral Contraceptives
Authors: Bäcklund Nils , Lundstedt Staffan , Olsson Tommy , Dahlqvist Per Mikael , Brattsand Göran
Published: October 2023

Disclosure: N. Bäcklund: None. S. Lundstedt: None. T. Olsson: None. P.M. Dahlqvist: None. G. Brattsand: None.

Introduction: The short Synacthen test (SST) is a cornerstone in the diagnosis of adrenal insufficiency (AI). However, cortisol levels in serum or plasma may be misleadingly elevated by estrogen containing oral contraceptives (OCs), due to increased levels of cortisol binding protein (CBG). This may falsely declare a woman with AI to be cortisol sufficient. Salivary cortisol and cortisone closely correlate with the unbound fraction of plasma cortisol and is thus less likely to be influenced by variations in CBG levels. Our hypothesis was that the salivary cortisol and cortisone response to SST would be similar in women with and without OC use. Materials and methods: A standard intravenous 250 µg SST was performed in 87 women without known diseases or medications affecting the cortisol axis, 41 using OCs containing ethinylestradiol and 46 controls. Plasma cortisol was analyzed by Roche Elecsys Cortisol II assay and salivary cortisol and cortisone by LC-MS/MS in samples collected at baseline (time 0), and 30 and 60 minutes after Synacthen injection. The effect of OCs upon plasma cortisol, salivary cortisol and salivary cortisone was assessed by a two-way ANOVA with sampling time after SST as repeated measure. Results: There was an overall effect of OCs on plasma cortisol, but not on salivary cortisol or cortisone. Plasma cortisol levels were considerably higher in the OC group vs. controls at all time points; +150% at 0 minutes; +90% at 30 minutes; and +86% at 60 minutes. There was a significant interaction between OC use and sample time point for both salivary cortisol and cortisone. Mean salivary cortisol in women using OCs was 37% higher vs. controls at 0 minutes but was instead lower in the OCs group at 30 and 60 minutes after SST (-13% and -11%, respectively). Similarly, mean salivary cortisone was also slightly higher in the OC group than controls at baseline (+13%) and somewhat lower at 30 and 60 minutes (-6% and -7%). Conclusion: Plasma cortisol levels during an SST were significantly elevated in women using OCs containing estrogen whereas OC effects upon salivary cortisol and cortisone levels were modest, especially for salivary cortisone. Analysis of salivary cortisone is a promising alternative to plasma cortisol for diagnosis of AI in women using OCs.

Presentation: Saturday, June 17, 2023
SAT529 An Uncommon Case Report Of A Paraaortic Paraganglioma
Authors: Askar Esraa , Fredrick Jason Regis , Anantha Sandeep , Reddy Kalpana G
Published: October 2023

Disclosure: E. Askar: None. J.R. Fredrick: None. S. Anantha: None. K.G. Reddy: None.

Background: Extraadrenal pheochromocytomas, also known as paragangliomas are uncommon neuroendocrine tumors that develop from sympathetic ganglia chromaffin cells. These tumors rarely cause hypertension, in less than 0.2% of patients. Although pheochromocytomas are known to be secreting catecholamines, paragangliomas are less likely to be functional. Here we report a rare case of Catecholamine secreting Paraganglioma presenting with hypertension. Clinical Case: A 28 -year-old female with past medical history of Goldenhar syndrome presented to our outpatient institution complaining of headache, palpitations and high blood pressure measurements at home with systolic blood pressure ranging between 160-200 mm Hg for a few months prior to presentation. Her only medication was propranolol for hypertension. At presentation, blood pressure was 126/72 mm Hg, heart rate was 76 beats per minute. Physical examination revealed no significant findings. Abdominal exam did not reveal any palpable masses. The patient denied any history of substance, tobacco, or alcohol abuse. No family history was found for any similar masses or hypertension. Laboratory findings were significant for elevated normetanephrines at 785 pg/mL (18 to 111) with normal metanephrines level. CT abdomen was significant for 2.5 cm enhancing left paraaortic mass separate from kidneys and adrenal glands. The patient was started on doxazosin and propranolol was switched to atenolol. After her blood pressure was adequately controlled with the alpha and beta blockade, she was referred to a tertiary facility for excision of the mass. Robotic excision of the mass was performed successfully without any significant blood pressure variations noted intraoperatively. The diagnosis of a well differentiated extraadrenal pheochromocytoma was confirmed by pathology, and the patient was referred for outpatient genetic testing and endocrinology follow up. Conclusion: This is an extremely rare case of paraganglioma given its presentation and location of the mass. The previously reported paragangliomas usually present as ER visits with severe sympathetic symptoms but it is uncommon to present as an outpatient for secondary hypertension workup. In the literature, we have found case reports of catecholamine secreting paragangliomas which guided the management of this uncommon case as mentioned above. Clinicians must be aware of this rare presentation of paraganglioma in order to properly diagnose and manage the condition.References: https://www.cancer.gov/pediatric-adult-rare-tumor/rare-tumors/rare-endocrine-tumor/paraganglioma

Presentation: Saturday, June 17, 2023
OR30-02 Salivary Cortisol Response To The High Dose ACTH Stimulation Test Provides A Reliable Alternative To Serum Cortisol Measurement In The Evaluation of Suspected Hypoadrenalism, And Is Unaffected By Cortisol-Binding Concentration
Authors: El-Farhan Nadia , Rees Seren , Tennant Sarah , Evans Carol , Rees Aled
Published: October 2023

Disclosure: N. El-Farhan: None. S. Rees: None. S. Tennant: None. C. Evans: None. A. Rees: None.

Context The serum total cortisol response to the ACTH stimulation test is widely used to assess adrenocortical function but is affected in conditions of altered cortisol-binding globulin (CBG) concentration. Salivary cortisol reflects free cortisol concentrations and may offer a reliable alternative. Objectives: 1. To establish the salivary cortisol response to the high dose ACTH stimulation test in healthy volunteers and in patients with altered CBG concentrations. 2. To evaluate the performance of a lower reference limit (LRL) determined in healthy volunteers in patients with suspected hypoadrenalism. Design: A high dose (250 µg) intravenous ACTH stimulation test was undertaken in 139 (60 male, 79 female) healthy volunteers, 24 women taking an oestradiol-containing oral contraceptive pill (OCP females), 10 patients with low serum protein concentration secondary to the nephrotic syndrome or liver cirrhosis (LP patients) and 29 patients with suspected hypoadrenalism (SH patients). Salivary cortisol was measured by liquid chromatography-tandem mass spectrometry. The mean and estimated LRL of the 30-minute salivary cortisol response to ACTH stimulation (mean - 1.96 SD) were derived from log-transformed concentrations. The LRL was subsequently applied as a diagnostic cut-off in SH patients. Results: CBG concentrations were 58 [42-81] mg/L), 64 mg/L [43-95], 41 [28-60] mg/L and116 [84-159] mg/L in male volunteers, female volunteers, LP patients and OCP females, respectively. The mean 30-minute salivary cortisol concentration was 19.3 [2.5th-97.5th percentile 10.3-36.2] nmol/l in healthy volunteers, with no difference between genders. Corresponding values were not different in OCP females (19.7 [9.5-41.2] nmol/l; p=0.59) and LP patients (19.0 [7.7-46.9] nmol/l; p=0.97), in contrast to 30-minute mean serum cortisol responses which differed between healthy female volunteers (555 [421-731] nmol/l) and OCP females (869 [649-1162] nmol/l; p<0.001). Overall diagnostic agreement between 30-minute salivary and serum responses in patients undergoing evaluation for SH was high (79%). Conclusions: Salivary cortisol response to intravenous ACTH stimulation offers a reliable alternative to serum cortisol measurement in the assessment of patients with suspected hypoadrenalism and may be especially useful in conditions of altered CBG concentration.

Presentation: Sunday, June 18, 2023
THU398 Variants In The Vitamin D Receptor, 1alpha-hydroxylase Enzyme Genes In Cholecalciferol Therapy
Authors: Kalinchenko Svetlana , Vorslov Leonid , Shkeleva Tatyana , Kahn Alena , Samburskaya Olga
Published: October 2023

Disclosure: S. Kalinchenko: None. L. Vorslov: None. T. Shkeleva: None. A. Kahn: None. O. Samburskaya: None.

The administration of vitamin D drugs should be done with regard to genetic analysis of polymorphisms in the vitamin D receptor (VDR) and 1alpha-hydroxylase enzyme (CYP27B1) genes to select the required dose, form and activity of the drug. Materials and Methods: In the period from 10.10.2020 to 23.12.2022 there were 936 patients aged from 2 to 77 years on therapy with cholecalciferol, in whom vitamin D status was determined by calcidiol mass spectrometry and parathormone in blood. Patients were genotyped for two markers of susceptibility to vitamin D deficiency: variants in the vitamin D receptor gene (VDR, BsmI Polymorphism, rs1544410) and the 1-alpha hydroxylase enzyme gene (CYP27B1, g.57764205A>G; rs4646536) by direct sequencing. Findings: Patients received therapy with cholecalciferol preparations. As a result, they were divided into 2 groups: the first group in which clinical effects of vitamin D deficiency compensation were achieved against the background of treatment, the second group in which, despite taking adequate selected doses, considering age, weight and degree of deficiency, laboratory criteria of vitamin D sufficiency were achieved, but clinical effects were not achieved. Genetic analysis showed that those patients in whom clinical symptoms of vitamin D deficiency were more severe and those in whom therapy with cholecalciferol did not produce the expected clinical effect had polymorphisms in the genes encoding VDR and/or 1alpha-hydroxylase enzyme. Discussion: In the presence of the CYP27B1 variant, g.57764205A>G; rs4646536 in the gene encoding 1alpha-hydroxylase (86.5% of all patients, n = 809), calcitriol formation is reduced, which explains the lack of effect of cholecalciferol therapy. In the presence of the VDR variant, BsmI Polymorphism, rs1544410 in the gene encoding the vitamin D receptor, sensitivity of the receptor to hormone D is reduced (13% of all patients, n = 122), which explains the lack of clinical effects of therapy with vitamin D drugs in standard therapeutic doses. And the most difficult to treat clinical manifestations of vitamin D deficiency occur in patients with polymorphisms in the two genes encoding both VDR and 1alpha-hydroxylase, which constituted 11.3% (n = 106) according to our study among all those examined. Conclusion: Conflicting literature data and clinical effects in vitamin D therapy are due to variants in the VDR and/or CYP27B1 genes. Knowledge of genetics is the individualized dose, form, and activity of vitamin D medication as the key to success in therapy.

Presentation: Thursday, June 15, 2023
THU403 Fluoxetine Administration During The Peripartal Period And The Effect On Calcium Metabolism And Serotonin Signaling In The Mammary Gland
Authors: Fricke Hannah , Krajco Chandler J , Perry Molly J , Hernandez Laura L
Published: October 2023

Disclosure: H. Fricke: None. C.J. Krajco: None. M.J. Perry: None. L.L. Hernandez: None.

Postpartum depression affects an estimated 10 to 15% of the population. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed class of antidepressants during pregnancy and lactation and are considered safe to use during pregnancy and lactation. During lactation, bone resorption is increased to mobilize calcium via a serotonin-dependent hormonal cascade. In the mammary gland, serotonin acts via the Hedgehog (Hh) signaling pathway to liberate calcium from bone for milk. Previously, our lab has determined that a high dose of the SSRI fluoxetine (FLX) during the peripartal period impacts calcium and serotonin metabolism during lactation. We hypothesize that a low dose of FLX during the peripartal period will upregulate Hh signaling and subsequently modulate calcium and serotonin metabolism during lactation, and that this impact will vary depending on whether FLX was administered during lactation only or throughout gestation and lactation. Female C57BL/6J mice were randomized to receive FLX (2 mg/kg) or saline daily via i.p. injection from parturition to the end of lactation (D21; lactation only), or from P0 to D21 (gestation + lactation), creating the following treatments: lactation saline (LS; n=10), lactation FLX (n=16), gestation + lactation saline (G+LS; n=5), and gestation + lactation FLX (G+LF; n=15). Circulating serotonin and calcium levels were measured in the serum at P0, the beginning of lactation (D2), and D21, and mammary glands were harvested at D21 for gene expression analysis. When normalized to P0 measurements, there were no differences in circulating calcium or serotonin levels between control and FLX groups at D2 or D21 when treated during lactation only, or gestation and lactation. However, G+LF mice tended to have a lower circulating serotonin level than G+LS mice on D21 (p=0.0770). At D21, gene expression of glioblastoma transcription factor 1 (GLI1) and sonic hedgehog (SHH), both members of the Hh signaling pathway, were altered in the G+LF group. There was a tendency for GLI1 expression to be increased in the G+LF dams (p=0.0634) and SHH was significantly increased in the G+LF dams (p=0.0382) when compared to the G+LS dams. These data suggest that a low dose of FLX during lactation only may not have a significant impact on calcium and serotonin metabolism via alterations in Hh signaling in the mammary gland but may be impacted when administered throughout the entire peripartal period.

Presentation: Thursday, June 15, 2023
THU406 24-hydroxylase Deficiency, A Rare Cause Of Hypercalcemia
Authors: Hodge Jordesha , Gortakowski Michele , Barua Nabonita , Jamal Issra , Daniel Shaji , Crosio Stefano
Published: October 2023

Disclosure: J. Hodge: None. M. Gortakowski: None. N. Barua: None.

Background: 24-hydroxylase is encoded by CYP24A1 and functions to convert 1,25 dihydroxyvitamin D and 25-hydroxyvitamin D to their inactive metabolites[1]. 24-hydroxylase deficiency due to CYP24A1 variants is rare and clinical presentation is characterized by hypercalcemia, nephrolithiasis and nephrocalcinosis. Treatment may include thiazide diuretics, sodium cellulose phosphate and ketoconazole.[1] We present a case of hypercalcemia due to 24-hydroxylase deficiency. Clinical Case: A 56-year-old male with chronic kidney disease initially presented with hypercalcemia at age 48 to another institution. He was initially diagnosed with primary hyperparathyroidism in the setting of an inappropriately normal parathyroid hormone (PTH) with hypercalcemia. He subsequently had one parathyroid gland removed a year after diagnosis, then another two years later due to continued hypercalcemia. However, he continued to have persistent hypercalcemia, 10.9-12.7 mg/dL but now in the setting of low PTH. In addition, his 1,25 dihydroxyvitamin D was high normal and 25-hydroxyvitamin D was high off exogenous vitamin D supplementation, which raised the suspicion for 24-hydroxylase deficiency. He presented to our institution eight years later. Initial evaluation revealed, calcium 12.4 (8.6-10.5 mg/dL), phosphorous 2.9 (2.5-4.5 mg/dL), normal albumin, PTH 13 (15-65 pg/mL), 1,25 dihydroxyvitamin D 87.2 (19-79.3 pg/mL) and 25-hydroxyvitamin D 38.3 (20-50 ng/mL), 24hr urine calcium 0.23 (0.05-0.30 g/24hr), fractional excretion calcium 0.02. His 25-hydroxyvitamin D:24,25 dihydroxy vitamin D ratio was unable to be calculated, since 24,25 dihydroxy vitamin D was below the limit of quantification. He also had evidence of nephrocalcinosis on renal ultrasound. Evaluation of other causes of non-PTH mediated hypercalcemia included normal angio converting enzyme, PTHrP level, vitamin A level, SPEP and UPEP. Chest X-ray did not demonstrate any evidence of granulomatous disease. He has been managed conservatively for suspected 24-hydroxylase deficiency. He has been advised to limit calcium and vitamin D intake, as well as sun exposure, with close monitoring of his calcium levels. His calcium levels have ranged from 10.7-12.4 mg/dL and he has had one hospitalization in the setting of heart failure where his calcium levels improved with furosemide to 8.7-9.9 mg/dL. Conclusion: In patients with persistent non-PTH dependent hypercalcemia, 24-hydroxylase deficiency should be a differential diagnosis when other common causes are excluded.

References: 1. Nesterova G, Malicdan MC, Yasuda K, et al. 1,25-(OH)2D-24 hydroxylase (CYP24A1) deficiency as a cause of nephrolithiasis. Clinical Journal of the American Society of Nephrology. 2013;8(4):649-657. doi:10.2215/cjn.05360512

Presentation: Thursday, June 15, 2023
THU410 Retrospective Review Of Adults Patients With Suspected Or Confirmed Hypophosphatasia At The Penn Bone Center
Authors: Tran Richie , Hvisdas Christopher , Riordan Marianne , Novotny Lindsay , Kallish Staci , Patel Kruti , Al Mukaddam Mona
Published: October 2023

Disclosure: R. Tran: None. C. Hvisdas: None. M. Riordan: None. L. Novotny: None. S. Kallish: None. K. Patel: None. M. Al Mukaddam: None.

Abstract: Hypophosphatasia (HPP) is a rare inherited genetic disorder that affects the mineralization of bones and teeth. HPP is the result of a pathogenic variant involving the tissue nonspecific alkaline phosphatase (ALPL) gene. The clinical presentations of HPP greatly vary from serious perinatal manifestations (respiratory failure, seizures, and death) to mild manifestations in adulthood. In adults, hallmark signs and symptoms include early loss of primary or secondary teeth, osteoporosis, osteomalacia, recurring metatarsal stress fractures, and abnormal laboratory values, such as low alkaline phosphatase (ALP), elevated phosphoethanolamine, and elevated vitamin B6.The treatment and follow up of adults with HPP are not clearly described. This retrospective study characterizes 43 patients referred to the Penn Bone Center for suspected HPP. Twelve of the 43 patients had a confirmed HPP diagnosis based on both clinical presentations and evidence of variant in the ALPL gene. The twelve patients consisted of both female and male adults between the ages of 24 to 74. In addition, the patients had abnormal ALP levels, ranging between less than 5 to 38 units per liter (normal range: 38 to 126 U/L). Six of these patients had previous or current use of asfotase alfa with variable treatment response. Two patients decided to stop treatment due to lack of clinical benefit or worsening of symptoms while on asfotase alfa therapy. Biochemical and bone mineral density follow-up while on therapy has not been shown to be helpful in monitoring treatment response. Asfotase alfa is a subcutaneously administered synthetic human alkaline phosphatase that was approved by the Federal Drug Administration (FDA) in 2015 for treatment of perinatal/infantile- and juvenile-onset hypophosphatasia. However, the efficacy of treatment in adults remain unclear at this time. Further research is required to better define the natural progression of mild or adult-onset hypophosphatasia and the patients who would benefit from enzyme therapy.

Presentation: Thursday, June 15, 2023
THU411 Fracture And Osteoporosis In Hereditary Connective Tissue Disorders: A Systematic Review And Meta-analysis
Authors: Charoenngam Nipith , Rittiphairoj Thanitsara , Jaroenlapnopparat Aunchalee , Ponvilawan Ben , Waitayangkoon Palapun , Supakitjanusant Pichatorn , Prasitsumrit Vitchapong , Pongchaiyakul Chatlert , Holick Michael F
Published: October 2023

Disclosure: N. Charoenngam: None. T. Rittiphairoj: None. A. Jaroenlapnopparat: None. B. Ponvilawan: None. P. Waitayangkoon: None. P. Supakitjanusant: None. V. Prasitsumrit: None. C. Pongchaiyakul: None. M.F. Holick: None.

Introduction: Hereditary connective tissue disorders (HCTDs) refer to a constellation of conditions caused by defects in the structure and synthesis of extracellular matrix. It is well-known that bone fragility is the hallmark feature of osteogenesis imperfecta. Interestingly, other HCTDs, including Ehlers-Danlos syndrome (EDS), Marfan’s syndrome (MFS) and Loeys-Dietz syndrome (LDS) are shown to be associated with bone fragility. However, most of the existing studies were small in sample sizes, thereby limiting validity and generalizability. Therefore, we aimed to identify all available data, using systematic review and meta-analysis, to determine the risks of fracture and osteoporosis in patients with HCTDs, including EDS, MFS and LDS. Methods: From inception to June 2022, potentially eligible studies were identified in the Medline and EMBASE databases using search strategy that included terms for “HCTD”, “Fracture” and “Osteoporosis”. Eligible studies must consist of a group of patients with HCTD and report prevalence/incidence of fracture/osteoporosis in their participants, with or without comparison with healthy individuals. Point estimates with standard errors were obtained from each study and combined using the generic inverse variance method. Results: Among the 4,206 articles that were identified, 19 studies fulfilled the eligibility criteria. The pooled prevalence of fracture in patients with EDS, MFS and LDS were 44% (95%CI, 25 - 65%, I2 88%), 17% (95%CI, 11 - 26%, I2 68%), 69% (95%CI, 47 - 85%, I2 83%), respectively. The pooled prevalence of osteoporosis among patients with EDS was 17% (95%CI, 8 - 34%, I2 96%). EDS was associated with fracture [pooled odds ratio 4.90 (95%CI, 1.49 - 16.08, I2 86%)], but not osteoporosis [pooled odds ratio 1.34 (95%CI, 0.28 - 6.36, I2 87%). One study reported a 5% (95%CI, 3 - 8%) prevalence of osteoporosis in MFS, and MFS was associated with fracture [incidence rate ratio 1.35 (95%CI, 1.18 - 1.55)] and osteoporosis [subhazard ratio 3.97 (95%CI, 2.53 - 6.25)]. Conclusion: EDS was associated with fracture, which could be independent of osteoporosis status. MFS had a milder degree of increased risk of fracture and osteoporosis. Despite the lack of data from cohort studies, there was a significantly higher rate of fracture in LDS.

Presentation: Thursday, June 15, 2023
THU412 Role of Glucocorticoid On Bone Metabolism Through AKAP13
Authors: Igarashi Katsushi , Ishida Akiko , Koide Hisashi , Yokote Koutaro
Published: October 2023

Disclosure: K. Igarashi: None. A. Ishida: None. H. Koide: None. K. Yokote: None.

It is not completely clear to what extent glucocorticoids are involved in which stages and sites of bone differentiation, development, and maintenance. we investigated the mechanism of glucocorticoid regulation through the regulation of Rho activation using a regulatory system for the expression of the RhoA activator AKAP13. To examine the effect of glucocorticoids on preosteoblasts, immortalized bone marrow mesenchymal stem cells (imBMSCs) were sown in 6-well plates at a concentration of 2x105/well and treated with various concentrations (0-1000 nM) of dexamethasone (Dex) 24 hr later, and The expression of GILZ, osteoblast and adipocyte-associated markers were evaluated using qRT-PCR. AKAP13 expression vector and AKAP13 siRNA were used to examine the response to Dex. GILZ was induced in a Dex-dependent manner on both day1 and day4. In the differentiation phase, PPARG2 expression was not changed by Dex, but GILZ was induced in a similar Dex-dependent manner. In proliferating imBMSCs, Dex treatment tended to enhance PPARG2 expression in a dose-dependent manner by introducing AKAP13 expression vectors. On the other hand, AKAP13 gene expression was significantly down-regulated in imBMSCs treated with AKAP13 siRNA, and Alp2 mRNA was up-regulated in imBMSCs treated with Dex compared to those not treated with Dex. It has a nuclear receptor binding domain and is known to be involved in osteogenesis. On the other hand, AKAP13 expression was decreased by osteoblast differentiation in an in vitro system, suggesting that AKAP13 may influence the regulation of GC action between the proliferative and differentiation phases of BMSCs.

Presentation: Thursday, June 15, 2023
THU442 A Case Of Early Medication Related Osteonecrosis Of The Jaw In Patient Receiving Intravenous Zoledronate For Treatment Of Osteoporosis
Authors: Ekpe Victor , Au Xiu Ying , Golson Maria , McGuire Lisa E , Aguirre Lina E
Published: October 2023

Disclosure: V. Ekpe: None. X. Au: None. M. Golson: None. L.E. McGuire: None. L.E. Aguirre: None.

Introduction: Medication related Osteonecrosis of the jaw (MRONJ) is a rare side effect in patients receiving nitrogen-containing bisphosphonates intravenously and other anti-bone resorptive agents such as denosumab . The incidence is 0.1% in patients with metabolic bone disease1. Annual infusions of zoledronic acid have been recommended in order to improve patient compliance, optimize therapeutic effects and to minimize side effects in selected patients. Risk factors include history of malignancy, smoking, poor dental health, prior oral surgery, high dose exposure to zoledronic acid and longer duration of treatment with anti-resorptive therapy. Increasing usage of bisphosphonates and other antiresorptive drugs, have led to an increased incidence of MRONJ. Clinical Case: We report the case of a 63-year-old Caucasian female suffering from osteoporosis who developed early stage MRONJ. She has a history of several years of oral bisphosphonate treatment and three annual administrations of zoledronic acid. Patient presented with a new complaint of gum pain and a sore above her tooth. Prior routine dental exams have all been unremarkable. She was promptly referred and evaluated by a dental provider. Dental photographs showed a resorptive defect at the gumline. Patient was diagnosed with medication related osteonecrosis of the jaw (MRONJ) in the gum area above tooth number 9. Our patient was treated with oral amoxicillin 500mg twice daily and chlorhexidine gluconate mouth rinse twice daily. The intravenous zoledronic acid was discontinued. Her gum infection resolved. Discussion: Early detection of MRONJ is possible in patients potentially at risk for this rare complication. Providers should be aware of MRONJ and refer those patients on antiresorptive drugs to the dentist for frequent evaluation and assessment for any drug-related jaw changes.

References: 1. Khosla S, Burr D, Cauley J, Dempster DW, Ebeling PR, Felsenberg D, Gagel RF, Gilsanz V, Guise T, Koka S, McCauley LK, McGowan J, McKee MD, Mohla S, Pendrys DG, Raisz LG, Ruggiero SL, Shafer DM, Shum L, Silverman SL, Van Poznak CH, Watts N, Woo SB, Shane E; American Society for Bone and Mineral Research. Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2007 Oct;22(10):1479-91. doi: 10.1359/jbmr.0707onj. PMID: 17663640. 2. Shoback D, Rosen CJ, Black DM, Cheung AM, Murad MH, Eastell R. Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society Guideline Update. J Clin Endocrinol Metab. 2020 Mar 1;105(3):dgaa048. doi: 10.1210/clinem/dgaa048. PMID: 32068863.

Presentation: Thursday, June 15, 2023
THU468 Finding An Effective Treatment For Osteoporosis In Gaucher Disease
Authors: Lesniak Christopher , Akula Monika Soujanya
Published: October 2023

Disclosure: C. Lesniak: None. M.S. Akula: None.

Background: Gaucher disease is a rare autosomal recessive disorder, leading to a deficiency of the enzyme glucocerebrosidase and accumulation of lipid-laden macrophages and dysfunction of multiple organs. The skeletal system is commonly affected resulting in reduced bone mineral density (BMD), marrow infiltration and bone infarction. Enzyme replacement therapy (ERT) has been a mainstay of treatment, and bisphosphonate therapy has been used to help treat osteoporosis, but newer agents are not well studied in this population. Case Description: The patient is a 62 year old female with a history of Gaucher disease Type 1 (GD1) and osteoporosis, treated with alendronate. She was diagnosed with GD1 in childhood and treated with glucocerebrosidase as ERT. She was diagnosed with osteoporosis in 2018 and started on bisphosphonates after a DXA scan showed a T-score at the lumbar spine of −3.2 and -1.4 at the left hip. She denied bone or back pain and has no history of any osteolytic lesions or osteonecrosis. Workup for secondary causes of osteoporosis was negative. She was taking alendronate 70 mg weekly, calcium 1800 mg daily, and vitamin D 4000 IU daily. Labs showed calcium 9.1 mg/dL, TSH 1.530 uIU/mL, PTH 34 pg/mL, and 25-hydroxy vitamin D 38.7 ng/mL. Repeat DXA scan showed worsening osteoporosis with a T-score at the lumbar spine of −3.4 and left hip of −2.5. As her BMD worsened while on alendronate for 3 years, teriparatide was offered as an alternative treatment. Discussion: Gaucher disease is a rare lysosomal storage disorder affecting multiple organs. Up to 90% of patients with GD1 have bone involvement of some kind. DXA scan should be done soon after diagnosis. Reduced BMD in GD1 is common and is associated with increased fracture risk. ERT has been the main management option to treat bone manifestations with improvement in BMD shown after 3-5 years. After 8 years of treatment with ERT, patients have been shown to reach the BMD of the age and sex matched population. In addition to ERT, calcium and vitamin D3 are recommended to increase BMD. There is no standard of treatment for osteoporosis in Gaucher patients, although bisphosphonates have been shown to improve BMD. Had our patient had early DXA scans, treatment may have been initiated sooner. A single case report showed improvement in BMD with the use of teriparatide after bisphosphonate failure. The efficacy of alternative agents, such as teriparatide and romosumab, in treating osteoporosis in patients with Gaucher disease needs to be further investigated.

Presentation: Thursday, June 15, 2023
FRI691 Intrathyroidal Parathyroid Adenoma With Congenitally Absent Contralateral Thyroid Lobe Treated With Thermal Ablation
Authors: Bilandzic Luka , Bilandzic Luka , Korkusuz Hudayi
Published: October 2023

Disclosure: L. Bilandzic: None. L. Bilandzic: None. H. Korkusuz: None.

We present a rare case of primary hyperthyroidism with ectopic adenoma located in the right thyroid lobe with congenitally absent left thyroid lobe which was treated with thermal ablation. A 60-year-old woman was referred to endocrinology clinic for further evaluation of her elevated total serum calcium of 11.4 mg/dL (reference range 8.5-10.5), elevated parathyroid hormone (PTH) level of 106 (10-60 pg/mL). Bone mineral densitometry showed a total T score of -2.9 in L1-L4. Other results were vitamin D 25-OH 30 ng/mL (ref. range 30 - 100), TSH 3.36 µIU/mL (ref range 0.4-5.0), eGFR 83 (normal > 59 mL/min/ 1.73 m²). She was asymptomatic and had no history of kidney stones. Other causes of hypercalcemia were refuted. Given the osteoporosis in her lumbar spine, parathyroid localization and surgery were suggested. Thyroid and parathyroid sonography demonstrated a solid hypoechoic nodule in the right thyroid lobe, 12x10x11mm, with smooth margins, no calcifications, classified as ACR TI-RADS T4. Left thyroid lobe was not appreciated and was considered to be congenitally absent since the patient did not have a history of a previous thyroid resection. Further localization studies (99mTc Sestamibi parathyroid scintigraphy and 4D-CT of the neck) did not reveal any other possible candidates for parathyroid adenomas. Eventually, a fine needle aspiration of the nodule in the right thyroid lobe was performed. PTH needle wash showed a PTH value of 633 pg/mL whereas the PTH value ≥ 100 pg/mL is suggestive of the presence of PTH secreting tissue. Given the thyroid anatomy found with this patient, a right lobe hemithyroidectomy would result with a permanent substitution dependent hypothyroidism. As an alternative, thermal ablation was presented as a treatment option for which the patient opted. She underwent the procedure in local anesthesia. Sonographic imaging of the adenoma was followed by the percutaneous insertion of the coagulation electrode. The utilized high frequency ablator was used with an output of 9 to 40 W and a frequency of 470 ± 10 kHz. There were no complications developed during or after the procedure. Two weeks after the thermal ablation, PTH level was measured at 55 pg/mL, total serum calcium at 9.5 mg/dL, TSH 1.01 µIU/mL. Sonography showed a hyperechoic nodule at the former location of the parathyroid adenoma, which was evaluated as a scar tissue. Three months after the procedure total calcium was at 9.3 mg/dL, PTH at 58 pg/mL, hence no biochemical evidence of pHPT. This is a rare case of ectopic parathyroid adenoma located in the thyroid gland with hemi agenesis of the contralateral lobe. A minimally invasive thermal ablation was performed with the goal of inactivation of the adenoma and preserving the euthyroid function.

Presentation: Friday, June 16, 2023
OR13-06 Romosozumab After Denosumab Improves Lumbar Spine Bone Mineral Density And Microarchitecture Greater Than Denosumab Continuation In Postmenopausal Women
Authors: Hong Namki , Shin Sungjae , Kim Hyunjae , Rhee Yumie
Published: October 2023

Disclosure: N. Hong: None. S. Shin: None. H. Kim: None. Y. Rhee: None.

Transitioning to romosozumab from antiresorptives can be an effective strategy to improve bone strength. A phase 2 trial and a few observational studies showed improvement of lumbar spine bone mineral density (BMD) with maintained hip bone density by romosozumab after denosumab. However, whether transition to romosozumab after denosumab is associated with greater improvement in BMD and microarchitecture compared to denosumab continuation remains unclear. In this propensity score-matched cohort study, we analyzed data from postmenopausal women who initiated denosumab between 2017 and 2020 (at least two injections; n=696). Individuals who were transited to 12 months of romosozumab after denosumab (n=105) were 1:1 matched to those who continued denosumab (n=591) by propensity score using age (69 years), body mass index, BMD, and numbers of denosumab injection at the time of transition, BMD improvement during denosumab treatment, prior fracture and bisphosphonate use (n=93 for each; denosumab-romosozumab [DR] and denosumab-denosumab [DD]). BMD gain by denosumab in DR and DD groups from denosumab initiation to transition time (to romosozumab or denosumab continuation; median 4 times [range 2 to 8] of denosumab injection) was +4.6% and +2.4% in the lumbar spine (LS, T-score −3.4 to −3.1) and total hip (TH, T-score −2.5 to −2.4), without statistical difference. DR group showed greater LSBMD gain compared to the DD (+7.0% vs. +2.5%, P<0.001) during 12 months after the transition time, yielding greater net LSBMD gain in DR (median 2 years of denosumab followed by 1-year romosozumab) compared to DD (median 3 years of denosumab; +11.6% vs. +7.0%, P<0.001). Differences in LSBMD gain between DR and DD groups remained robust (adjusted difference +4.7% point, P<0.001) after adjustment for covariates. Hip BMD changes did not differ between DR and DD (DR vs. DD; FN, +1.3% vs. +2.0%, p=0.409; TH, -0.9% vs. +0.2%, P=0.132). DR group showed significant improvement in the trabecular bone score during romosozumab use (1.288 to 1.311, p=0.005), whereas denosumab continuation in the DD group did not (1.297 to 1.309, p=0.103). During 12 months, one incident morphometric vertebral fracture (grade 1) and one nonvertebral fracture (patella) were observed in DD, whereas one ankle fracture was observed in the DR group. In summary, romosozumab after denosumab improved lumbar spine BMD and microarchitecture greater than denosumab continuation, with the maintenance of hip BMD.

Presentation: Friday, June 16, 2023
SAT193 Double Trouble: A Case of Ipsilateral Double Parathyroid Adenoma
Authors: Perez Suelto Jeremy Anne , Dimayuga Wassmer Gia
Published: October 2023

Disclosure: J.P. Suelto: None. G.D. Wassmer: None.

Background: Eighty percent of the cases of Primary Hyperparathyroidism is caused by a single adenoma and only about 15% are multiglandular adenoma. Parathyroid imaging like Sestamibi is less sensitive in detecting multiglandular disease. Clinical Case: A 63 year-old female presented with intermittent left lower back pain for 7 years. There was no joint pain, weakness, urinary symptoms, constipation and abdominal pain. In 2019, due to persistence of left back pain, abdominal ultrasound done showed a right non-obstructing nephrolithiasis. Ionized and total calcium were elevated at 1.53 meq/L (NV 1.12-1.32 meq/L) and 11.35 ng/dl (NV 8.42-10.23 ng/dl) respectively with normal creatinine, phosphorus and albumin. PTH was elevated at 116.6 pg/ml (NV 10-65 pg/ml). Primary Hyperparathyroidism probably secondary to parathyroid adenoma was considered. Thyroid ultrasound showed right thyroid cyst but no enlarged parathyroid gland. Parathyroid imaging using Dual Isotope Subtraction Method neither showed evidence of adenoma. Patient was advised parathyroidectomy but did not consent hence started on Cinacalcet. In 2021, ionized calcium was still elevated to 1.58 meq/L with elevated PTH 151 pg/ml and low Vitamin D level 22.76 ng/ml (>30 ng/mL). Patient was given Vitamin D3 2000 IU daily and Cinacalcet was up-titrated to 60mg daily. Sestamibi/SPECT CT showed faint focus of radioactivity in the right thyroidal bed area suspicious for parathyroid adenoma or hyperplasia. She then agreed to have parathyroidectomy. There was no decrease in PTH after removal of the right inferior parathyroid gland (measuring 1.8x0.6x0.6cm, weighs 500mg), hence re-exploration was done. It was only after the removal of the right superior parathyroid gland (measuring 2.8x0.9x0.7cm, weighs 1 gram) when the 5 and 10 minute post excision PTH decreased to 123.91 and 76.01 pg/ml respectively from preincision PTH of 407.19 pg/ml. Histopathology showed Parathyroid adenoma of right inferior and superior parathyroid glands. No further evidence of hypercalcemia was noted at 6-month follow-up. Conclusion: Double adenoma is reported in 2% to 12% of patients with primary hyperparathyroidism. This occurs predominantly as bilateral superior in 45% and on same side of the neck in 18%. Sestamibi scanning is poor in the presence of multiglandular disease. It was observed that the presence of oxyphil cells may cause longer sestamibi retention in parathyroid tissues. Given the same amount of oxyphil cells in ipsilateral adenomas, the tracer may be distributed hence faintly seen on imaging. Addition of SPECT/CT/4D CT may improve the anatomical localization. Another reason for false negative imaging in this patient can be due to use of Cinacalcet which may decrease scintigraphy uptake of parathyroid adenoma. The combination of preoperative imaging localization and intraoperative PTH monitoring permits successful surgical outcome.

Presentation: Saturday, June 17, 2023
SAT199 Intrathyroidal Parathyroid Adenomas: A Case Series
Authors: Bowens Brendan K , LaChance David , Shakir Mohamed K M , Duc Hoang Thanh
Published: October 2023

Disclosure: B.K. Bowens: None. D. LaChance: None. M.K. Shakir: None. T.D. Hoang: None.

Background: Primary hyperparathyroidism (PHPT) is a relatively common condition which affects 1-7 people per 1000. However, intrathyroidal parathyroid adenomas (ITPA) have a prevalence of 1.3% to 6.7%. In this case series, we report 3 cases of ITPA. Case 1: 66-year-old male with a history of PHTP without intervention at initial diagnosis presented to Endocrinology several years after initial diagnosis due to an incidental thyroid nodule on routine CT lung cancer screening. Parathyroid hormone (PTH) level found to be 109.3 from a previous level of 80 (ref 10-55pg/mL) in the setting of mild hypercalcemia and osteopenia. Initial bedside thyroid ultrasound was suggestive of a right ITPA. Parathyroid scan, formal thyroid US and CT gated scan revealed a 1.5cm parathyroid adenoma (PA) posterior to the right superior aspect of the thyroid gland. Fine Needle Aspiration (FNA) was completed with PTH washout of 399.40 pg/mL. Right superior parathyroidectomy confirmed ITPA due to an intrathyroidal parathyroid adenoma Case 2: 44-year-old female presented with 9 months of fatigue and was diagnosed with PHPT. Her PTH level was 167 with a serum calcium of 10.9 (ref 8.5-10.4 mg/dL). CT SPECT with tech-99M sestamibi was positive for a right parathyroid adenoma. Explorative surgery did not localize parathyroid adenoma. Thyroid ultrasound revealed a 9mm hypoechoic lesion in the right inferior lobe with polar artery. FNA of this lesion was completed with PTH washout of 4737 pg/mL. Right hemi-thyroidectomy was completed with resolution of PHTP.

Case 3: 54-year-old male with history of PHPT and carcinoma of the right kidney s/p nephrectomy presented with persistent hypercalcemia. Serum calcium of 10.2-11.0 mg/dL and PTH of 160-186 pg/mL. Thyroid US showed a 1.1cm hyperechoic, cystic nodule in the left inferior thyroid lobe. Sestamibi was consistent with ITPA. FNA of left thyroid mass with PTH washout of 2602 pg/mL. Parathyroidectomy with left thyroid lobectomy was completed with resolution of hypercalcemia. Discussion: PHPT is a common endocrinopathy with 85% of cases due to PAs, 15% due to parathyroid hyperplasia, and <1% due to carcinoma. ITPAs have an incidence of 1.3% to 6.7% and are due to improper embryologic migration. Sestamibi parathyroid scan allows for localization of PA and for minimally invasive procedures. Other imaging modalities include SPECT, US, SPECT-CT, and MRI. PTH washout with more than 101 pg/mL confirms the presence of parathyroid tissue or adenoma. Conclusion: This is a rare presentation of a common endocrinopathy. These patients were noted to have PHTP. Initial exploratory neck dissections did not localize. FNA and US were able to confirm IPTAs and hemi-thyroidectomy was needed for definitive management with resolution of PHTP.

Presentation: Saturday, June 17, 2023
SAT201 A Rare Case Of A Mediastinal Atypical Parathyroid Adenoma Resulting In Severe Hypercalcemia And Brown Tumor
Authors: Aluko Oluwatomisin A , Franey Daniel , Quiros Roderick , Burfeind William , Amori Renee E
Published: October 2023

Disclosure: O.A. Aluko: None. D. Franey: None. R. Quiros: None. W. Burfeind: None. R.E. Amori: None.

Introduction: Primary hyperparathyroidism is most often from parathyroid adenomas located usually in close association to the thyroid gland. Ectopic parathyroid glands result in significant variability in the position of the gland, however rarely in the mediastinum. We report a case of a patient with severe hypercalcemia from a large, ectopic mediastinal parathyroid adenoma. Case Report: A 53-year old male with a past medical history of hypercalcemia and nephrolithiasis was sent to the ER for evaluation of hypercalcemia after he was found to have a corrected calcium of 12.5 mg/dl (n8.4 - 10.2 mg/dl) on routine labs. Repeat blood work at presentation confirmed hypercalcemia with a corrected calcium 11.9 mg/dl and elevated ALP of 211 U/l (n 43 - 122 U/L), elevated initial PTH of799 pg/ml (n 18.4 - 80.1 pg/ml), Vit D 32.7 ng/ml (n 30 - 100 ng/ml), and low phosphorus 2.4 mg/dl (n2.7 - 4.5 mg/dl). Calcium slightly improved to 11.7 mg/dl after IV hydration. Chest CT showed a large mediastinal mass compressing trachea and esophagus, suspicious for parathyroid origin, with a smaller left sided lesion suspicious for parathyroid adenoma. CT also showed multiple bone lesions likely brown tumors. He underwent complete robotic resection of the mediastinal mass. Immediately prior to surgery, PTH was 1002.8 pg/ml, and fell to 131.1 pg/ml and 44.1 pg/ml following removal of the mediastinal mass. Adherence of the mass to surrounding structures made resection challenging, resulting in a right vocal cord paralysis. After surgery, he was empirically started on IV calcium and calcitriol for high clinical concern for hungry bone syndrome, both later discontinued as serum calcium remained within normal limits. Pathologic findings reported as highly suspicious, however not definitive for parathyroid carcinoma with no evidence of perineural or lymphovascular invasion. Given rarity, he was referred to a tertiary cancer center where he was diagnosed with Atypical parathyroid Adenoma (APA). He underwent a right pubic biopsy with pathology diagnosis of brown tumor of hyperparathyroidism. He started on cinacalcet 30 mg daily after surgery. There is a future plan for resection of the smaller left sided parathyroid adenoma. Conclusion: This case highlights two rare entities; a mediastinal ectopic parathyroid and atypical parathyroid adenoma. Atypical Parathyroid Adenoma is a not-well defined entity which could mimic a parathyroid carcinoma as seen in our case. The location of the mass in the superior mediastinum is unusual, making it more difficult to diagnose, and could increase risk of complications during resection. Delayed diagnosis of these entities can lead to severe hypercalcemia and skeletal complications infrequently seen in common primary hyperparathyroidism cases.

Presentation: Saturday, June 17, 2023
SAT202 A Case Of Primary Hyperparathyroidism Secondary To Ectopic Intrathymic Parathyroid Adenoma
Authors: Pandiri Shruti
Published: October 2023

Disclosure: S. Pandiri: None.

Introduction: Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia. Majority of cases are due to a single adenoma. In about 6-16% of cases, the parathyroid adenoma is in an ectopic location. Accurate preoperative imaging is key in localizing ectopic parathyroid adenomas. Clinical Case: 64 year old man with hypercalcemia was referred to endocrinology for further evaluation. His symptoms included fatigue, nausea, polydipsia and polyuria. There was no history of fractures, radiation therapy or family history of hypercalcemia. The patient’s past medical history is significant for nephrolithiasis, thyroid nodules and hypertension. He was started on Cinacalcet 30 mg, twice daily, by his primary care physician about 6 weeks prior to the initial visit. Physical exam was unremarkable. Lab studies were significant for elevated albumin-corrected calcium: 11.2 mg/dl (8.6-10.3 mg/dl), elevated PTH: 578.1 pg/ml (12-88 pg/ml), 25-OH vitamin D: 17 ng/ml (>30 ng/ml), phosphorus: 2 mg/dl (2.5-4.5 mg/dl) TSH: 0.54 mIU/L (0.40-4.50 mIU/L), 24 hr urine calcium: 429 mg (<250 mg/24 hr). The lab findings were consistent with hypercalcemia due to primary hyperparathyroidism. Neck Ultrasound showed bilateral thyroid nodules but no parathyroid adenoma. Tc-99m sestamibi scintigraphy was significant for 2.8 x 1.5 x 3.4 cm mass in the anterior mediastinum but did not show uptake in the neck. CT Neck showed a mass in the anterior mediastinum measuring 1.6 x 2.7 cm. Bone density was significant for osteopenia. He underwent robot assisted mediastinal mass excision two months after the initial evaluation. The pathology was significant for ectopic, intrathymic parathyroid adenoma, watery cell type with nuclear atypia, measuring 3.8 x 3.1 x 1.3 cm. Labs at the follow up visit showed normal albumin-corrected calcium of 8.6 mg/dl, improved PTH of 110.3 pg/ml. His symptoms improved significantly after surgery. Conclusion: This case demonstrates that preoperative localization of an ectopic parathyroid adenoma can prevent recurrent surgeries and persistent hypercalcemia. It is important for physicians to be aware of the various ectopic locations of parathyroid adenomas during the diagnostic workup of PHPT. Reference: Roy M, Mazeh H, Chen H, Sippel RS. Incidence and localization of ectopic parathyroid adenomas in previously unexplored patients. World J Surg. 2013 Jan;37(1):102-6. doi: 10.1007/s00268-012-1773-z. PMID: 22968537.

Presentation: Saturday, June 17, 2023