bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT319 Megestrol-induced Adrenal Insufficiency
Authors: Alcorn Chris , Subarajan Prathayini , Ghaith Sarah , Jordan Kim
Published: October 2023

Disclosure: C. Alcorn: None. P. Subarajan: None. S. Ghaith: None. K. Jordan: None.

Introduction: Megestrol, a progestin derivative, is a common drug used for anorexia or cachexia. Chronic use of megestrol can lead to suppression of the pituitary-adrenal axis, causing secondary adrenal insufficiency (SAI). Case: A 93-year-old female with a history of dementia presented with one-week history of confusion and weakness. She was found to have hyponatremia with a sodium of 134meq, consistent with her baseline. CT head and infectious workup were negative. She received 600cc of normal saline and repeat sodium decreased to 124meq/l. Nephrology was consulted due to concern for SIADH. She remained altered and was given a short course of hypertonic saline, 25cc for 4 hours. Repeat sodium after hypertonic saline was 118meq/l. TSH was normal but 8 am cortisol was 1.3 mcg/dL and ACTH level was <1.5 pg/ml. Endocrinology was consulted for evaluation of adrenal insufficiency. Cosyntropin stimulation test was performed with inadequate response, consistent with secondary adrenal insufficiency (SAI). The patient was subsequently given 50mg IV hydrocortisone with improvement in sodium to 125meq/l. The patient had been prescribed megestrol 200mg at home for cachexia. Upon discussion with her family, she was receiving multiple extra doses of megestrol per day for further appetite stimulation. She was only started on 200mg daily dose on admission. It was determined the patient had SAI secondary to megestrol use. This medication was discontinued, and she was initiated on hydrocortisone therapy with endocrinology follow-up. Conclusion: SAI is defined by deficiency of ACTH in setting of hypocortisolemia. SAI is often associated with prolonged glucocorticoid use but can also be seen in patients with pituitary tumors, pituitary surgery, or granulomatous disease. SAI can cause hyponatremia, hypoglycemia, and fatigue but is not typically associated with hypotension or hyperkalemia as the mineralocorticoid function of the adrenals remains intact. Though rare, there have been case reports of patients developing SAI while taking megestrol. Megestrol acts as a progestin and is used for appetite stimulation in patients with cachexia. Megestrol is believed to have cross-affinity for glucocorticoid receptors which leads to suppression of the pituitary-adrenal axis. This suppression leads to decreased ACTH production, inducing SAI. In this case, the patient was receiving higher than prescribed doses of megestrol at home. When her dose was reduced on admission it precipitated her adrenal insufficiency, accounting for the worsening of her hyponatremia. Identification of SAI in patients taking megestrol is imperative as early recognition and diagnosis can prevent severe complications such as adrenal crisis. These patients should have megestrol discontinued and be placed on appropriate hydrocortisone therapy. Close follow-up is required as it can take 2-3 months for pituitary-adrenal axis recovery.

Presentation: Saturday, June 17, 2023
SAT321 Ectopic ACTH Cushing's Syndrome Caused By A Large-cell Neuroendocrine Lung Carcinoma Responding To Desmopressin
Authors: Larose Stephanie , Rioux Dany , Albadine Roula , Lacroix André
Published: October 2023

Disclosure: S. Larose: None. D. Rioux: None. R. Albadine: None. A. Lacroix: None.

Background: Ectopic ACTH secretion (EAS) is a less frequent cause of ACTH-dependent Cushing’s syndrome (CS), most often caused by a thoracic neuroendocrine tumor (NET). Large-cell neuroendocrine carcinomas (LCNEC) with EAS are rare and usually present a more severe phenotype of ACTH secretion and hypercortisolism. Clinical Case: We report the case of a 44-yo non-smoking man, who presented clinical and biochemical evidence of ACTH-dependent severe CS complicated by pulmonary emboli. In the context of an initial equivocal pituitary MRI, desmopressin and CRH stimulation tests were performed. Desmopressin produced a 157% increase in ACTH (basal: 59.0 pmol/L to peak: 151.9 pmol/L) and a 25% increase in cortisol from baseline; there was no stimulation of ACTH or cortisol during a CRH test and no suppression with high dose dexamethasone tests. Repeat pituitary MRI identified a 5 mm lesion, but inferior petrosal venous sinus sampling (IPSS) under desmopressin did not identify a central ACTH source. Thorax and abdominal imaging including Indium-111 octreoscan identified a left lung 3 mm micronodule which became more evident when pulmonary emboli resolved. In this context of probable ectopic ACTH secretion, the patient was treated with left inferior lung lobectomy for a suspected NET. Pathological studies confirmed a lung LCNEC with morphologic features of carcinoid tumor and strongly positive ACTH immunohistochemistry (IHC) in the primary lesion and lymph node metastasis. The patient was in CS remission after surgery and adjuvant chemotherapy, but developed a CS recurrence 9.5 years later, with a morning

ACTH of 56.9 pmol/L, (N <11.0 pmol/L), a non-suppressed AM cortisol of 633 nmol/L after 1mg of dexamethasone overnight and urinary free cortisol of 1717 nmol/24 hours (N:< 789). Imaging showed signs of recurrence, with a hypermetabolic, 14 x 11 mm left hilar lymph node lesion on a TEP-DOTATATE scan in the left lung, near the surgical suture. An endobronchial ultrasound-guided biopsy confirmed the recurrence of the LCNEC. Surgery was performed and demonstrated again positive ACTH IHC of the lesion. The patient achieved remission of CS with secondary adrenal insufficiency, treated with hydrocortisone. Six months later, there was no response of ACTH or cortisol to a desmopressin test. Conclusion: This is the first report of LCNEC with morphologic feature of carcinoid tumor of the lung with ectopic ACTH secretion stimulated by desmopressin. Long delay prior to metastatic recurrence indicates relatively indolent NET. This case report indicates that response to desmopressin can occur in malignant LCNEC. Combining the desmopressin test with other dynamic tests, sellar MRI, IPSS and thoraco-abdominal functional imaging improves diagnostic accuracy of ectopic ACTH source.

Presentation: Saturday, June 17, 2023
OR30-06 Hospitalisation, Intensive Care And Death Due To COVID-19 In Swedish Patients With Adrenal Insufficiency
Authors: Bergthorsdottir Ragnhildur , Esposito Daniela , Johannsson Gudmundur , Ragnarsson Oskar , Dahlqvist Per , Bensing Sophie , Nåtman Jonatan , Nyberg Fredrik
Published: October 2023

Disclosure: R. Bergthorsdottir: None. D. Esposito: None. G. Johannsson: None. O. Ragnarsson: None. P. Dahlqvist: None. S. Bensing: None. J. Nåtman: None. F. Nyberg: None.

Background: Patients with adrenal insufficiency (AI) have increased risk for morbidity and mortality related to infectious disorders. Whether patients with AI have an increased risk for infection with Coronavirus disease 2019 (COVID-19), need of hospitalisation, intensive care or death in COVID-19 disease is still unknown. Methods: Swedish national register-based cohort study. Patients with primary and secondary AI were identified in linked Swedish national healthcare registers and followed from 2020-01-01 until 2021-02-28, and were compared to controls from the general population, matched 10:1 for age and sex. The following COVID-19 outcomes were studied: hospitalisation, intensive care and death. Findings: We identified 5430 patients with AI, and 54300 controls; 47.6% females, with a mean (±SD) age of 57.1 (±18.1) years. The prevalence of positive COVID-19 testing and diagnosis were similar in patients with AI and controls. The rate of hospitalisation (2.1% vs 0.8%), intensive care (0.3% vs 0.1%) and death (0.8% vs 0.2%) for COVID-19 were higher in AI patients than controls, respectively. After adjustment for socioeconomic factors and comorbidities, the hazard ratio (95% confidence interval) for hospitalisation was 1.96 (1.59-2.43), for intensive care admission it was 2.76 (1.49-5.09) and for death 2.29 (1.60-3.28). Interpretation: Patients with AI have an increased risk for severe and fatal COVID-19 infection and should therefore be prioritised for vaccination, early antiviral and supportive treatment to prevent hospitalisation and death.

Presentation: Sunday, June 18, 2023
THU404 Classical Symptoms Masquerading As A Surprising Clinical Picture
Authors: Syal Arshi , Arya Yajur , Teja Sathi Sri Ram , Prater Janna
Published: October 2023

Disclosure: A. Syal: None. Y. Arya: None. S. Teja Sathi: None. J. Prater: None.

Introduction: Primary hyperparathyroidism commonly presents in the setting of a parathyroid adenoma or hyperplasia, although it can rarely be caused parathyroid carcinoma, often accounting for <1% of cases. Markedly elevated PTH levels, along with predominant uniglandular involvement should increase the suspicion of an underlying parathyroid carcinoma, given that multiglandular involvement is rarely encountered. Surgical resection with histopathological confirmation remains the mainstay of diagnosis. Case presentation: We describe the case of a female in her late 50s who was brought to the emergency department by her family with complaints of altered mental status, hallucinations, delusions, anxiety, increased urination, constipation, and decreased appetite for the past month. Her laboratory evaluation was significant for hypercalcemia with a corrected calcium of 13.4 mg/dL. She was started on intravenous fluids and calcitonin, with improvement in her clinical condition. Further workup for her hypercalcemia revealed that the serum parathyroid hormone (PTH) was significantly elevated at 1846.4 pg/mL (normal low: 9, normal high: 73). Her serum phosphorus was low, and 25-hydroxy vitamin D was high-normal. This was consistent with a picture of primary hyperparathyroidism. The severely elevated PTH raised concern for parathyroid carcinoma, a rare clinical entity. The patient underwent a nuclear medicine parathyroid scan (technetium 99m sestamibi), which revealed abnormal focal uptake in the inferior right thyroid bed. Ultrasound of the neck revealed a hypoechoic avascular nodule inferior to the right thyroid lobe corresponding to the area of increased sestamibi activity on nuclear medicine scan. After much discussion with the patient’s family, surgical intervention was deferred to a later date, with a focus on stabilization in the acute setting. The patient was started on cinacalcet for her hypercalcemia. Bisphosphonates were initially held in anticipation for surgery but were eventually started. Discussion: Parathyroid carcinoma is a rare malignancy, which can occur both sporadically and as part of the hereditary hyperparathyroidism-jaw tumor syndrome. In clinical practice, subtle clues which increase the suspicion for a parathyroid carcinoma include severely elevated PTH, sometimes up to 10 times the upper limit of normal, increasing adenoma size, and a presentation outside of the commonly inherited MEN-1 syndromes.[1] We rely solely on post-operative pathology to establish the diagnosis of parathyroid carcinoma, given that there are no well-defined features or criteria that can establish the diagnosis on imaging.

References: 1.Singh Ospina N, Sebo TJ, Thompson GB, et al. Prevalence of parathyroid carcinoma in 348 patients with multiple endocrine neoplasia type 1 - case report and review of the literature. Clin Endocrinol (Oxf). 2016;84(2):244-249.

Presentation: Thursday, June 15, 2023
THU409 Relationship Between Bone Loss And Oral Health Among Post-menopausal Women With And Without Diabetes
Authors: Ahmad Sophie , Nauman Rafae , Batra Kavita , Gupta Ashok , Izuora Kenneth E
Published: October 2023

Disclosure: S. Ahmad: None. R. Nauman: None. K. Batra: None. A. Gupta: None. K.E. Izuora: Research Investigator; Self; Novo Nordisk.

Background: There is a high prevalence of periodontal disease (PD) and bone loss (osteopenia and osteoporosis) among patients with diabetes. Understanding the relationship between these conditions in the context of type 2 diabetes (T2DM) as a risk factor will help better understand their pathophysiology and provide guidance for more appropriate care. Methods: This was a cross-sectional study that enrolled post-menopausal women presenting for routine bone density evaluation. Following informed consent, we obtained information about their demographics, diabetes status, and dental history using an investigator-administered questionnaire. We measured their height and weight with a stadiometer and inspected their oral cavity for teeth loss and PD. We then obtained their bone density assessment after interpretation by the radiologist. Data were analyzed using chi-square and logistic regression tests with the significance level set at 5%. Results: Among 66 eligible participants, the mean age and body mass index (BMI) were 67.67 ± 8.1 years and 29.76 ± 5.45 kg/m2 respectively. Twelve participants (18.2%) had T2DM, 19 (28.8%) had < 20 natural teeth and 17 (25.8%) had normal bone mineral density. Using a binary logistic regression, significant predictors of bone loss included age (OR 1.217, p=0.008), BMI (OR 0.827, p=0.04), and a diagnosis of T2DM (OR 0.056, p=0.033). The number of natural teeth, number of broken or decayed teeth, and presence of periodontal disease were not associated with bone loss. Conclusion: Among our population of post-menopausal women, clinical variables associated with bone loss included older age and lower BMI. Having T2DM was associated with a higher bone mineral density which does not translate to stronger bones according to previous reports. Oral health outcomes were not associated with bone loss and may reflect the similarity in the risk factors for the two conditions.

Presentation: Thursday, June 15, 2023
THU414 Asthma And Cardiometabolic Diseases As Major Risk Factors For Fractures In Women With Osteopenia: Nationwide Cohort Study
Authors: Kong Sung Hye , Jo Ae Jeong , Park Chan Mi , Park Kyun Ik , Yun Ji Eun , Kim Jung Hee , Kim Sang Wan , Shin Chan Soo
Published: October 2023

Disclosure: S. Kong: None. A. Jo: None. C. Park: None. K. Park: None. J. Yun: None. J. Kim: None. S. Kim: None. C. Shin: None.

Background: The study aimed to demonstrate the risk factors for fractures and to develop prediction models for major osteoporotic and hip fractures in osteopenic patients using the nationwide cohort study in South Korea. Methods: The study was a retrospective nationwide study using the national screening program for transitional ages from the National Health Insurance Services database in Korea from 2008 to 2019. Primary outcomes were incident fracture events of major osteoporotic and hip fractures. Major osteoporotic and hip fracture events were defined as diagnostic and procedural codes. Patients were followed until the fragility fractures, death, or 2019, whichever came first. Results: All participants were 66-year-old females, with a mean body mass index was 25.0±3.1 kg/m2. During a median follow-up of 10.5 years, 26.9% and 6.7% of participants experienced major osteoporotic and hip fractures. In multivariate analysis, a history of fracture, asthma/chronic obstructive pulmonary disease (COPD), falls, diabetes mellitus and cerebrovascular diseases were significant risk factors for major osteoporotic (hazard ratio [HR] 2.35 for a history of fracture; 1.17 for asthma/COPD; 1.10 for falls; 1.12 for diabetes mellitus; 1.11 for cerebrovascular disease) and hip fractures (HR 1.75 for a history of fracture; 1.54 for diabetes mellitus; 1.27 for cerebrovascular disease; 1.17 for fall; 1.15 for asthma/COPD). The performances of the prediction models were area under the receiver operating curve of 0.73 and 0.75 for major osteoporotic and hip fractures. Conclusion: The study presented prediction models of major osteoporotic and hip fractures for osteopenia patients using simple clinical features, and showed that asthma and cardiometabolic diseases are major risk factors for fractures in women with osteopenia.

Presentation: Thursday, June 15, 2023
THU431 An Interesting Case Of Severe Osteoporosis In A Young Male
Authors: Bilbatua Martha , Deshmukh Mrunalini
Published: October 2023

Disclosure: M. Bilbatua: None. M. Deshmukh: None.

Background: Systemic Mastocytosis is a rare disorder in which Osteoporosis is seen in about 24% of cases. We describe a rare case of Secondary Osteoporosis in a young man caused by Systemic Mastocytosis. Case presentation: A 32-year-old male with no significant medical history was seen by Endocrinology for evaluation of Osteoporosis. Symptoms started after two episodes of falls which caused persistent pain. A CT scan of thoracic spine revealed chronic anterior wedge compression fracture of T5, T7 and T10 with approximately 5-10% loss of height. DEXA scan demonstrated T-score of -4.2 at L1-L4, T-score of -2.3 at left hip suggestive of severe Osteoporosis. The patient admitted to generalized flushing and itching after taking hot showers as well as intermittent episodes of palpitations. The patient was started on Calcitonin nasal spray daily for pain related to vertebral fracture. Testing for secondary causes of Osteoporosis showed a Total testosterone 410 ng/dL (250-1,100 ng/dL), PTH 16 pg/mL (16 - 77 pg/mL), TSH 1.88 mIU/L (0.40 - 4.50 mIU/L), Phosphorus 4.1 mg/dL (2.5 - 4.5 mg/dL), Magnesium 2 mg/dL (1.5 - 2.5 mg/dL), Alkaline phosphatase 66 U/L (36 - 130 U/L), Vitamin D 25 ng/mL (30 - 100 ng/mL), Calcium 9.3 mg/dL (8.6 - 10.3 mg/dL), Tryptase 64 mcg/L (<11.0 mcg/L), 5-HIAA 24H Ur mg/24H 3 (<=6.0 mg/24 h). Based on this, the patient was seen by Hematology/Oncology for evaluation on elevated tryptase levels. Bone marrow biopsy and aspirate was performed, demonstrating 20% Mast cells positive for CD 117, CD 25, patient was diagnosed with Mastocytosis and treatment with Midostaurin 100 mg PO twice daily and Zometa every 12 weeks was initiated. Improvement of Tryptase was noted within two months of treatment. Discussion: Systemic Mastocytosis is a rare disease often complicated by Osteoporosis of which around 37% of the patients will develop Osteoporotic fractures where Bisphosphonates are effective and have a role in the associated refractory bone pain. The pathophysiological mechanisms leading to osteoporosis in Systemic Mastocytosis are not well understood. Although rare, back pain secondary to osteoporotic vertebral fractures is often the major presenting symptom of Mastocytosis and it should be included in the differential diagnosis of idiopathic osteoporosis due to its significant morbidity.

Presentation: Thursday, June 15, 2023
THU437 Oral Ulcers As A Clue To Bone Fragility
Authors: Sridhar Sushrutha , Krug Esther Irina
Published: October 2023

Disclosure: S. Sridhar: None. E.I. Krug: None.

Introduction: Metabolic bone disease is common in celiac disease (CD) and can occur in patients without gastrointestinal symptoms. Successful treatment of malabsorption is associated with amelioration of bone loss. Recurrent aphthous stomatitis (RAS) may be the sole manifestation of CD (1). According to American College of Gastroenterology Guidelines, tissue transglutaminase (tTG)-IgA antibody and total IgA level is the single preferred test for detection of CD in adults due to reported sensitivity of 90-98% and specificity of 95-97%. No additional testing is typically recommended for patients without IgA deficiency (2). Case: The patient is a 58 year old woman with past medical history of RAS treated with prednisone, 5 mg daily for 10 years, facial and ocular rosacea, menopause at age 49, asthma, chronic back and neck pain, history of spontaneous rib fracture and L4 compression fractures during chiropractic manipulation, who had progressive bone loss despite ongoing treatment with oral bisphosphonates, calcium and vitamin D supplementation for 4 years with good adherence, and was referred for endocrine evaluation. Laboratory studies revealed TSH 1.94 mIU/L (0.4-4.5), 25(OH)vit D 41 ng/mL (30-100 ng/mL), PTH 31 pg/mL (14-64), Ca 9. mg/dL (8.6-10.4), albumin 4.1 mg/dL (3.6-5.1), Mg 2.1 mg/dL (1.5-2.5), tTG-IgA 1 U/mL (<4), total IgA 190 mg/dL (47-310), Gliadin deamidated peptide IgA Ab 11 Units (<20), Gliadin deamidated peptide IgG Ab (DGP-IgG) 44 Units (<20). Duodenal biopsy revealed diffuse increase in intraepithelial lymphocytes, acute and chronic inflammation of lamina propria, focally marked villous blunting consistent with CD. The patient reported complete resolution of RAS and rosacea symptoms within one month of starting a strict gluten free diet. She also noted marked improvement in neck and back pain. After 6 months repeat DGP-IgG was 13 Units. Treatment with teriparatide of 12 months duration resulted in 12.1% and 5.4% gain in bone density of lumbar spine and total hip respectively. Conclusion: CD should be suspected in patients with osteoporosis and extraintestinal conditions including RAS and, possibly, rosacea. CD has been reported in 2.83% of 247 patients with RAS screened for (tTG)-IgA and anti-endomysial IgA Abs (2). Rosacea has also been linked to CD in one study (3). Our case suggests that patients presenting with RAS may need to be tested for DGP-IgG reported to have a sensitivity of 92% and specificity of 100%, regardless of total IgA level. References:

Shakeri R et al. Gluten sensitivity enteropathy in patients with RAS. BMC Gastroenterol. 2009;9:44.

Rubio-Tapia A et al. American College of Gastroenterology. ACG clinical guidelines: diagnosis and management of CD. Am J Gastroenterol. 2013;108(5):656.  

Egeberg A et al. Rosacea and gastrointestinal disorders: a population-based cohort study. Br. J. Dermatol. 2017;176:100-106.

Presentation: Thursday, June 15, 2023
THU444 A Case Of Zoledronic-Acid Induced Acute Anterior Uveitis, Episcleritis, And Synovitis
Authors: Au Xiu Ying , Dorin Richard I , Aguirre Lina E
Published: October 2023

Disclosure: X. Au: None. R.I. Dorin: None. L.E. Aguirre: None.

Introduction: IV zoledronic acid infusion (ZAI) may result in acute phase reaction associated with self-limited symptoms of pyrexia, myalgia, headache, arthralgia, and pain in extremities. Eye inflammation and joint swelling are less common manifestations of post-ZAI acute phase reaction, but are important to recognize and treat owing to the potential for long-term sequelae. Clinical Case: A 66-year-old female was diagnosed with osteoporosis by DXA. She received her first ZAI (5 mg) and within 24 hours noted onset of moderate-to-severe diffuse musculoskeletal pain and fever up to 102°F. Two days later, the patient noted swelling of her left wrist and bilateral knee and ankle joints. Clinical assessment led to a diagnosis of post-ZAI synovitis, which improved somewhat with IV ketorolac followed and outpatient po acetaminophen and ibuprofen. Six days after ZAI she developed left eye (OS) redness. Ophthalmologic evaluation identified acute episcleritis and acute anterior uveitis with normal visual acuity and intraocular pressures. The patient was managed with a transient (5 day) course of prednisone (40 mg daily) and a 14-day course of topical prednisone, cyclosporine, and lubrication. Posterior synechiae of OS resolved on follow-up exam and topical medications were successfully tapered over three weeks with resolution of visual complaints. Discussion: Acute phase reaction is a common side effect of ZAI, with an incidence of fever (17.2%) and diffuse musculoskeletal pain (15.7%) reported in one study [1]. Eye inflammation and joint swelling have also been reported after ZAI, but at a lower incidence (0.4% each) [1]. Patients with acute episcleritis and uveitis may require systemic steroids. While the prognosis of appropriately treated acute anterior uveitis is good, it may be associated with concomitant orbital inflammation that could lead to permanent vision loss. Risk factors for development of severe acute-phase reactions after ZA infusion have not been identified, though acute phase reactions are more commonly observed after the first dose of ZAI [2]. Conclusion: Physicians should be aware of rare ophthalmic complications of ZAI, as their prompt recognition and treatment may be important in prevention of long-term ocular sequelae. References: 1. Reid IR, Gamble GD, et al. Characterization of and risk factors for the acute-phase response after zoledronic acid. J Clin Endocrinol Metab. 2010 Sep;95(9):4380-7.2. Black DM, Delmas PD, et al. HORIZON Pivotal Fracture Trial. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007 May 3;356(18):1809-22.

Presentation: Thursday, June 15, 2023
THU445 Complicated Course And Management After Denosumab Discontinuation: A Case Report
Authors: Arora Ipsa , Ceglia Lisa
Published: October 2023

Disclosure: I. Arora: None. L. Ceglia: None.

Background: Discontinuation of denosumab (DMAb) can lead to rapid bone loss and sometimes multiple vertebral fractures (VFx). Here we present such a case and related challenges in management. Case: A 56-year-old perimenopausal female presented for management of osteoporosis (OP) complicated by multiple VFx following a missed dose of DMAb in 8/2020. Past bone health history was notable for treatment with alendronate for approximately 11 years as a premenopausal woman. During a drug “holiday” in 2015, she was found to have a decline in bone mineral density (BMD). She was advised to start treatment with DMAb in 8/2016. She was adherent to DMAb injections for 4 years but missed a dose in 8/2020 due to the COVID-19 pandemic. In 1/2021, she developed back pain with no trauma and was diagnosed with VFx of T7, T10 and T12. She underwent vertebroplasty of all 3 vertebrae by 2/2021. DMAb was resumed in 2/2021 and 8/2021. Labs were only notable for hypercalciuria for which hydrochlorothiazide (HCTZ) was initiated. In 11/2021 she presented with new symptomatic VFx of T5, T9 and T11. In 12/2021 (3 weeks post 3 new VFx), serum fasting C-telopeptide (CTX) was 79 pg/mL. Teriparatide or abaloparatide were avoided due to hypercalciuria and potential BMD losses with this transition. Thus in 1/2022, she started romosozumab (ROMO) in an attempt to prevent new VFx. CTX was initially 78 pg/mL and rose rapidly over 3 months to 325 pg/mL with new back pain in 4/2022. No new VFx were detected; however, ROMO was discontinued due to the rise in CTX level. In 5/2022, she received a dose of zoledronic acid (ZOL). It suppressed CTX from 325 to 131 pg/mL by 6/2022. She received another 2 doses of ZOL in 8/2022 and 11/2022 due to rebound rises in CTX. Of note, as she reported ongoing menopausal complaints, transdermal low-dose estradiol therapy was started in 11/2022. She has not had a new VFx in more than 1 year. Hypercalciuria persisted throughout 2022 requiring rising doses of (HCTZ). DXA in 12/2022 was stable vs. 12/2021 without evidence of significant BMD loss. Discussion: This case not only highlights the known risk for multiple VFx in a patient discontinuing long-term DMAb treatment (4 years), but also the risks for such VFx complications in women of younger age during menopausal transition and a history of vertebroplasty. In addition, this report does not support transitioning from long-term DMAb to ROMO in order to prevent a rapid increase in the bone resorption marker, CTX. Rather, treatment with ZOL every 12 weeks based on frequent CTX monitoring successfully maintained BMD stable following long-term DMAb discontinuation.

Presentation: Thursday, June 15, 2023
THU450 Looking Beyond The Usual Suspects: A Rare Case Of Teriparatide Induced Gynecomastia
Authors: Ramchandani Bhanvi Prakash , Mirza Faryal Sardar
Published: October 2023

Disclosure: B.P. Ramchandani: None. F.S. Mirza: None.

Introduction: Teriparatide (TP) is a parathyroid hormone analogue used as anabolic therapy for treatment of osteoporosis. Common side effects include nausea, headache and orthostatic hypotension. We hereby describe the first case of gynecomastia that developed shortly after starting treatment with TP, and resolved a couple of months after discontinuation of therapy. Clinical Case: A 61 year old male physician with severe osteoporosis presented to the endocrinology clinic with bilateral nipple tenderness and a firm lump under the left areolar region four months after starting therapy with TP. There was no associated bleeding or nipple discharge. He denied having any erectile dysfunction or decline in sexual function. His medications included vitamin D, lansoprazole and rosuvastatin. Family history was significant for osteoporosis and ductal carcinoma in situ in mother, and bilateral hip fractures after falls in his father at the age of 80. He denied any alcohol or recreational drug use. He was physically active but denied any recent weight loss. Other than the firm glandular tissue under left lateral areola, no other findings including nipple inversion or lymphadenopathy were noted on exam. Laboratory testing showed normal total and free testosterone level at 360 ng/dl and 68 pg/ml respectively, estradiol 39 pg/ml, LH 1.44 mIU/ml, FSH 4.44 mIU/ml, TSH 1.71 uIU/L, Prolactin 4.54 ng/ml and HCG <2 IU/ml, along with normal creatinine and liver enzymes. Mammogram showed left greater than right flame-shaped focal asymmetry contiguous with the nipple compatible with gynecomastia. Breast ultrasound showed left greater than right retroareolar dendritic slightly hypoechoic soft tissue correlating with the mammographic findings. Due to significant discomfort associated with gynecomastia, a decision was made to stop TP and treatment with risedronate was initiated. Following the discontinuation of the drug, the patient reported that his symptoms gradually improved and the nipple sensitivity and the palpable swelling of the left breast completely resolved at his follow up visit four months later. Conclusion: The temporal association between the initiation of teriparatide treatment and onset of gynecomastia, and improvement of the symptoms and physical findings upon discontinuation of the drug suggests that teriparatide was the likely cause of gynecomastia in our patient.

Presentation: Thursday, June 15, 2023
THU465 Significant Improvement In Bone Mineral Density Following Treatment For Tumor Induced Osteomalacia
Authors: McHan Lara C , Augustine Marilyn
Published: October 2023

Disclosure: L.C. McHan: None. M. Augustine: None.

Background: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by renal phosphate wasting and impaired activation of vitamin D due to excess secretion of FGF23, often from phosphaturic mesenchymal tumors (PMTs). TIO typically presents with months to years of bone pain, muscle weakness, and fractures often leading to functional decline. Given these nonspecific symptoms, diagnosis of TIO can be delayed for years. Removal of the tumor is curative, though it can sometimes be a challenge to localize. For those whose tumors are unable to be localized or removed, medical management with phosphorus and vitamin D is recommended. Patients with TIO have low bone mineral density (BMD) at time of diagnosis. Case Reports: We are presenting two cases of TIO, one managed surgically and one managed medically. Patient 1 is a 45-year-old man with Fabry disease who presented with years of progressive pain, difficulty ambulating, and multiple fractures. Lab workup revealed low serum phosphorus, elevated urinary phosphorus, elevated FGF23, and negative genetic testing for heritable causes of hypophosphatemic osteomalacia. DOTATATE imaging identified a subcutaneous left flank mass, which was excised resulting in improvement in symptoms and resolution of biochemical abnormalities. Additionally, lumbar spine (LS) bone mineral density (BMD) nearly doubled; prior to diagnosis of TIO, LS BMD was 0.601 g/cm2 and 8 months after surgical excision of the tumor, LS BMD was 1.178 g/cm2. Patient 2 is a 55-year-old nonverbal man with autism and intellectual disability who presented with months of progressive difficulty ambulating, presumed pain, functional decline, and multiple fractures. Workup revealed low serum phosphorus, elevated urinary phosphorus, and elevated FGF23 concerning for TIO. He was initiated on phosphorus and vitamin D supplementation, but no culprit tumor has been identified despite multiple scans over the course of years. However, the patient has had a significant improvement in functioning with medical management in addition to a remarkable 48% improvement in LS BMD, from 0.855 g/cm2 prior to diagnosis of TIO and 1.264 g/cm2 following 3 years of medical management. Clinical Lessons: In our review of the literature, there are few case reports and case series documenting the significant improvements in BMD with treatment of TIO. In our experience, two patients who had months to years of debilitating symptoms exhibited remarkable improvements in symptoms and marked improvement in LS BMD following treatment. This emphasizes the importance of recognizing the diagnosis of TIO, as even when the causative tumor is not identified, treatment typically has a significant impact on patient functioning and quality of life.

Presentation: Thursday, June 15, 2023
THU469 Inhalant Use Resulting In Diffuse Osteosclerosis: Case Report And Review Of The Literature
Authors: Hung Chermaine , Jesse Mary , Saxon David
Published: October 2023

Disclosure: C. Hung: None. M. Jesse: None. D. Saxon: None.

Osteosclerosis of the bone can develop from excessive fluoride intake. Fluoride sources range from oral intake of fluorinated water, ingestion of toothpaste, to fluorocarbon inhalation. Skeletal fluorosis can manifest with bony changes ranging from increased striation/granulation to thickened trabeculae, and ligaments and tendons can ossify (1). In the literature patients have presented after noticing joint enlargement, worsening chronic joint pains, immobility, and stiffness. Workup generally includes radiographs and dual x-ray absorptiometry (DXA) can reveal increased bone density (2). We describe a patient with osteosclerosis and the workup for this condition. We review the existing literature on fluorinated inhalant use as a cause of osteosclerosis. The patient is a 49-year-old man with type 2 diabetes, chronic pain in multiple joints, hypogonadism, and osteomyelitis status post right above knee amputation was referred to Endocrinology after he was found to have sclerotic bone lesions while undergoing workup for poor mobility. X-ray, CT and MRI scans over the past 7 years showed diffuse bone sclerosis in the spine, pelvis, knee, tibia, and foot. Labs demonstrated normal calcium, albumin, and alkaline phosphatase. DXA confirmed elevated T-scores of +6.8 (1.985 g/cm2) at left femoral neck, +8.6 (2.097 g/cm2) at left proximal femur and +9.8 (2.406 g/cm2) at lumbar spine. The patient confirmed “huffing” computer cleaner for 1 year while having severe depression and had stopped inhalant use 7 years prior to presentation. On literature review we identified case reports of bone sclerosis related to inhalant use. Long-term outcomes and optimal management were described only in case reports. Osteosclerosis from fluorosis should be considered in patients with diffusely increased bone density at multiple sites.

1. Wang Y, Yin Y, Gilula LA, Wilson AJ. Endemic fluorosis of the skeleton: radiographic features in 127 patients. AJR Am J Roentgenol. 1994;162(1):93-8. Epub 1994/01/01. doi: 10.2214/ajr.162.1.8273699. PubMed PMID: 8273699.2.Tucci JR, Whitford GM, McAlister WH, Novack DV, Mumm S, Keaveny TM, et al. Skeletal Fluorosis Due To Inhalation Abuse of a Difluoroethane-Containing Computer Cleaner. J Bone Miner Res. 2017;32(1):188-95. Epub 2016/07/28. doi: 10.1002/jbmr.2923. PubMed PMID: 27449958; PubMed Central PMCID: PMCPMC5977397.

Presentation: Thursday, June 15, 2023
FRI669 Skeletal Effect Of Cyclic Guanosine Monophosphate Dependent Protein Kinase G Type 2
Authors: Kim Se Min , Shelly Eleanor , Sultana Farhath , Korkmaz Funda , Temple Morgan , Gimenez Judit , Muradova Valeriia , Yuen Tony , Zaidi Mone
Published: October 2023

Disclosure: S. Kim: None. E. Shelly: None. F. Sultana: None. F. Korkmaz: None. M. Temple: None. J. Gimenez: None. V. Muradova: None. T. Yuen: None. M. Zaidi: None.

The nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) pathway plays a significant role in bone remodeling. PKG type 2 (PKG2) is expressed in bone cells [1-2], and mice with osteoblast-specific PKG2 upregulation (Col1a1-Prkg2R242Q) showed increased bone formation and preserved bone in mice with streptozotocin-induced diabetes [3]. In this study, we have crossed Prkg2fl/fl mice with Col2.3-Cre mice and Acp5-Cre mice, respectively, to generate osteoblast-specific and osteoclast-specific Prkg2 knockout mutants. The areal BMD of osteoblast-specific or osteoclast-specific mice were not different from the respective Cre- controls at 4, 6 and 8 months. µCT did not show any difference in fractional bone volume (BV/TV), or trabecular parameters compared with the Cre- controls. However, when mice were put under skeletal insults through glucocorticoid injection (dexamethasone, 10 mg/kg, SQ, daily, 4 month), Col2.3-Cre+;Prkg2fl/+ mice lost more bone compared with Col2.3-Cre−;Prkg2fl/+ mice at the tibia (−23.1% vs. −12.1%, P=0.011). In addition, we observed the osteoblast-specific Prkg2 knockout mice displayed increased body weight (Col2.3-Cre+;Prkg2fl/fl +25.1%**, Col2.3-Cre+;Prkg2fl/+ +19.9%*, Col2.3-Cre−;Prkg2fl/fl +7.3%), increased fat mass (Col2.3-Cre+;Prkg2fl/fl +26.0%*, Col2.3-Cre+;Prkg2fl/+ +21.4%**, Col2.3-Cre−;Prkg2fl/fl −3.3%), and decreased lean mass (Col2.3-Cre+;Prkg2fl/fl −4.3%*, Col2.3-Cre+;Prkg2fl/+ −2.9%, Col2.3-Cre-;Prkg2fl/fl +0.3%) from the baseline (**P < 0.01 and *P < 0.05 vs. Cre- controls). Furthermore, we noted a longer femur length in the osteoblast-specific Prkg2 knockout mutants. At 8 months, the femur length of Col2.3-Cre+;Prkg2fl/fl and Col2.3-Cre+;Prkg2fl/+ were 9.3% (P < 0.01) and 7.5% (P = 0.01), respectively, longer than the Cre- controls. Our findings suggest that PKG2 is necessary for protecting bone from glucocorticoid insults and abolishing PKG2 in osteoblasts might affect the differentiation of mesenchymal stem cell towards adipocytes and chondrocytes at the expense of osteoblasts and myocytes.

[1] Kim et al, Ann N Y Acad Sci, 2021[2] Rangaswami J et al, Biol Chem. 2009[4] Ramdani et al, J Endocrinol 2018

Presentation: Friday, June 16, 2023
FRI672 Bone Mineral Density In Neurofibromatosis Type 1: A Systematic Review And Meta-analysis
Authors: Charoenngam Nipith , Wattanachayakul Phuuwadith , Jaroenlapnopparat Aunchalee , Ungprasert Patompong , Chenbhanich Jirat
Published: October 2023

Disclosure: N. Charoenngam: None. P. Wattanachayakul: None. A. Jaroenlapnopparat: None. P. Ungprasert: None. J. Chenbhanich: None.

Neurofibromatosis type 1 (NF1) is known to be associated with low bone mineral density (BMD) and fragility fractures. However, evidence supporting specific age of early BMD measurement is limited as data on the degree of bone loss in NF1 are lacking. Using systematic review and meta-analysis technique, we aimed to identify all available data to assess BMD in patients with NF1. Potentially eligible studies were identified from Medline and EMBASE databases from inception to February 2023 using search strategy that comprised of terms for “Bone mineral density” and "Neurofibromatosis type 1”. Eligible study must include adult or pediatric patients with NF1. The study must report mean Z-score with variance of total body, lumbar spine, femoral neck or total hip BMD of the studied patients. Point estimates with standard errors were retrieved from each study and were combined using the generic inverse variance method. A total of 1,165 articles were identified. After systematic review, 19 studies were included. The majority of participants in the included studies were children and younger adults with the mean age of participants lower than 50 years old in all but one study. The meta-analysis revealed that patients with NF1 had negative mean Z-scores for total body BMD (pooled mean Z-score -0.808; 95%CI, -1.025 - -0.591) and BMD at lumbar spine (pooled mean Z-score -1.104; 95%CI, -1.376 - -0.833), femoral neck (pooled mean Z-score -0.726; 95%CI, -0.893 - -0.560) and total hip (pooled mean Z-score -1.126; 95%CI, -2.078 - -0.173). The subgroup meta-analysis in pediatric patients aged <18 years revealed that patients with NF1 had negative mean Z-scores for lumbar spine BMD (pooled mean Z-score -0.938; 95%CI, -1.299 - -0.577) and femoral neck BMD (pooled mean Z-score -0.585; 95%CI, -0.872 - -0.298). Based on the results from the meta-analysis, patients with NF1 had low Z-scores. However, the lower limits of the 95% CIs for the pooled mean Z-score for total body and specific site BMD were all higher than the Z-score cut-off of -2 for “low BMD for chronological age” in children and adults aged <50 years old. Therefore, the degree of low BMD may not be of clinical significance. Our results do not support the role of early BMD screening in children and young adults with NF1.

Presentation: Friday, June 16, 2023
FRI673 REMS Technology For The Evaluation Of BMD In Hypothyroidism
Authors: Lombardi Fiorella Anna , Pisani Paola , Quezada Alba Paola , Muratore Maurizio , Di Paola Marco , Casciaro Ernesto , Conversano Francesco , Casciaro Sergio
Published: October 2023

Disclosure: F.A. Lombardi: None. P. Pisani*: None. A.P. Quezada*: None. M. Muratore*: None. M. Di Paola*: None. E. Casciaro*: None. F. Conversano*: None. S. Casciaro: None. *Equal contributors in alphabetical order

Thyroid hormones play a crucial role in skeletal development, adult bone turnover, and bone maintenance, but they can also have detrimental effects on bone formation when there is thyroid dysfunction. Thyrotoxicosis (hyperthyroidism), including subclinical illness, can affect bone metabolism, resulting in decreased Bone Mineral Density (BMD) and increased fractures risk, and is a significant contributor to secondary osteoporosis, especially in postmenopausal women. On the other hand, little is known about the impact of overt or subclinical hypothyroidism on bone metabolism. However, hypothyroidism lessens bone turnover, reducing both osteoclastic bone resorption and osteoblastic activity. Such alterations in bone metabolism could potentially result in an increase in bone mineralization, although data on BMD and the risk of fracture in hypothyroidism are lacking and conflicting. Radiofrequency Echographic Multi-spectrometry (REMS) is a novel radiation-free technology for assessing BMD and fracture risk. In this context, the goal of this study was to assess BMD using REMS in patients with and without hypothyroidism, in order to look a possible correlation between the disease, BMD loss and fracture risk. Methods: A sample of 51 Caucasian females with hypothyroidism was compared to a reference group of healthy women who were matched for gender, ethnicity, age, and body mass index (BMI). Using REMS technology, the BMD was measurement at the lumbar spine in all participants at the study. To determine whether the two groups’ lumbar spine BMD value varied, a t-test was run. Results: Patients with and without hypothyroidism were matched in order to get similar anthropometric parameters. In patient with and without hypothyroidism mean ± standard deviation (SD) for age and BMI are (64.8 ± 10.2, 65.2 ± 9.8) and (25.1 ± 3.6, 25.0 ± 3.7), respectively. Patients with hypothyroidism were shown to have a significative lumbar spine BMD difference (0.801 g/cm2 ± 0.063 vs 0.831 g/cm2 ± 0.071, p=0.03) respect to the healthy subjects. Conclusions: Although just a small number of hypothyroidism patients are included in this investigation, without any indication of the drug therapy and its effect, it has been shown that, as compared to controls, women with hypothyroidism have a net decline in REMS-measured BMD values. Based on this thought, REMS technology, thanks to its precision and diagnostic accuracy, might improve the efficient care and follow-up programmes of these patients.

Presentation: Friday, June 16, 2023
FRI680 Atypical Femoral Fracture In Patients With Hypophosphatasia: A Systematic Review
Authors: Charoenngam Nipith , Thongpiya Jerapas , Yingchoncharoen Pitchaporn , Ponvilawan Ben , Marangoz Mehmet Sercan , Chenbhanich Jirat , Ungprasert Patompong
Published: October 2023

Disclosure: N. Charoenngam: None. J. Thongpiya: None. P. Yingchoncharoen: None. B. Ponvilawan: None. M.S. Marangoz: None. J. Chenbhanich: None. P. Ungprasert: None.

A growing number of case reports and case series have demonstrated that atypical femoral fracture (AFF) can occur in patients with hypophosphatasia (HPP). Due to the lack of summary of the clinical manifestation, risk factors, associated ALPL variants and treatment, we conducted this systematic review with the goal to summarize the characteristics of all reported patients with HPP who sustained AFF. Additionally, we aimed to identify all available evidence to quantify the rate of co-existence between HPP and AFF. Potentially eligible articles were identified from MEDLINE and EMBASE databases from inception to September 2022 using search strategy consisting of terms related to “Hypophosphatasia” and “Atypical femoral fracture”. Eligible articles must report one of the following information: 1.) individual data of patient(s) diagnosed with HPP and AFF, 2.) prevalence of HPP among patients with AFF or 3.) prevalence of AFF among patients of HPP. Characteristics of patients reported in each study were extracted. A total of 148 potentially eligible articles were identified from the databases. After systematic review, 23 articles met the eligibility criteria. A total of 27 patients with AFF and HPP were identified. The mean ± SD age of the reported patients was 53.8 ± 12.7 years and 21 patients (77.8%) were female. Nine patients (33.3%) received antiresorptive medication (bisphosphonate and/or denosumab) and two patients (7.4%) received teriparatide prior to development of AFF. Seven (25.9%) and 17 (63.0%) patients sustained unilateral and bilateral AFF, respectively. Twelve patients (44.4%) had a history of fractures at other sites. Four (14.8%) and six (21.4%) patients received asfotase alfa and teriparatide after sustaining AFF. Two studies that reported the prevalence of AFF among patients with HPP of approximately 10%. One study reported one HPP patient in a cohort of 72 patients with AFF. In summary, based on the limited evidence, AFF occurred in up to 10% of patients with HPP. Based on the 27 case reports, almost two-thirds did not receive antiresorptive treatment, suggesting the HPP itself could potentially be a risk factor for AFF.

Presentation: Friday, June 16, 2023