bluuebunny/crossref_metadata_2025 huggingface dataset:
5131 Vanishing Act: Uncommon Case Of Pheochromocytoma With Positive Biochemical Work-up With Absence Of Tumor And Medullary Tissue
Authors: Chan Nicole , Kaufman Ronald , Farhat Nada , Kim Grace Y
Published: October 2024

Disclosure: N. Chan: None. R. Kaufman: None. N. Farhat: None. G.Y. Kim: None.

Pheochromocytomas are rare neuroendocrine tumors derived from adrenal chromaffin cells that result in hyperactivity of the sympathetic nervous system. In the United States, they occur in about 0.05% to 0.1% patients with sustained hypertension. We are presenting a case of a patient with biochemical evidence of pheochromocytoma, but surgical pathology revealed absence of tumor and residual normal medulla.80-year-old female with a history of follicular lymphoma and hypertension presented for evaluation of an incidental right-sided adrenal nodule noted on a PET-CT. She had a history of hypertension managed on lisinopril 40 mg, amlodipine 10 mg and atenolol 100 mg daily. She denied a history of weakness, dizziness, headaches, palpitations, or easy bruising. Workup was negative for primary aldosteronism and Cushing’s Syndrome. Plasma normetanephrines was high at 675.7 pg/mL (0-285.2 pg/mL). 24-hour urinary normetanephrine was also elevated at 562 ug/g (0-400 ug/g). CT abdomen and pelvis with and without contrast revealed a 1.4 cm right adrenal nodule approximately 16 Hounsfield units. These findings were suggestive of pheochromocytoma. She was pre-treated with alpha blockade and subsequently had a robotically assisted laparoscopic right adrenalectomy. Postoperatively, the patient was hypotensive and required vasopressors. She was eventually weaned off vasopressors and discharged on lisinopril 20 mg daily. Soon after discharge, the patient was complaining of hypotension and this dose was halved. 4 weeks postoperatively, laboratory evaluation showed normalization of plasma normetanephrines to 0.83 nmol/L (0-0.89 nmol/L). Surgical pathology revealed an infarcted benign adrenal cortical proliferative lesion with background of cortical hyperplasia, fibrotic adrenal medullary region, and hemosiderin deposition. There was no identifiable medullary neoplasm and no residual medulla.Pheochromocytomas are highly vascular tumors as angiogenesis is a critical step in tumor growth, which can lead to frequent infarcts. This case shows classic biochemical evidence of pheochromocytoma. Interestingly, the resulting clinical examination displayed obliteration of the medullary tissue. Complete disappearance of both tumor and residual normal medulla is extraordinarily rare. The pre-operative hormonal levels in association with findings of complete absence of neoplastic and nonneoplastic medullary tissue cannot be explained.

Presentation: 6/1/2024
8740 Visceral Adipose Tissue Assessment in Patients With Mild Autonomous Cortisol Secretion Using Dual-Energy X-Ray Absorptiometry: A Cross-Sectional Study
Authors: Saini Jasmine , Zhang Catherine D , Fell Vanessa , Atkinson Elizabeth , Achenbach Sara , Bancos Irina
Published: October 2024

Disclosure: J. Saini: None. C.D. Zhang: None. V. Fell: None. E. Atkinson: None. S. Achenbach: None. I. Bancos: None.

Background: Several studies employing computed tomography (CT) scans for body composition measurements have reported lower muscle mass and a higher proportion of visceral fat in patients with mild autonomous cortisol secretion (MACS) compared to referent subjects. While a CT scan assesses visceral adipose tissue (VAT) at a single slice level (L3), no studies have evaluated the overall VAT in patients with MACS using Dual-Energy X-ray absorptiometry (DXA). Objective: To determine the impact of MACS on VAT using DXA scan as compared to referent subjects. Methods: We conducted a single-center cross-sectional study of adults with 75 MACS and 75 referent subjects. MACS was defined as serum cortisol>1.8 mcg/dL after 1 mg dexamethasone suppression test in patients with adrenal adenomas and no features of overt hypercortisolism. Referent subjects were included if they had abdominal imaging and had no adrenal disorders. All the participants underwent a full body DXA scan between 04/2019 and 07/2022. We applied the CoreScan software to estimate the (1) total lean and fat mass (2) visceral fat mass and volume (3) lean android, fat android, and android mass, and compared measurements of patients and referent subjects using linear regression models adjusted for sex and BMI. Results: A total of 75 patients with MACS (median age 57.0 years, IQR 47.8-65.6, 67% women) and 75 referent subjects (median age 57.6 years, IQR 49.1-65.8, 67% women) were included. Patients had a higher BMI compared to referent subjects (median 31.7 kg/m2, IQR 27.4-37.9 vs 28.7, IQR, 25.4-33.8, P=0.004). The median post-DST cortisol in patients was 3.1 mcg/dL (IQR, 2.2-5.2). When compared to referent subjects, and after adjustment for sex and BMI, patients had a similar total body fat (estimate=846, p-value=0.28) and lean mass (estimate=-201, p-value=0.83), similar android fat mass (estimate=59, p-value=0.64) but lower gynoid fat mass (estimate=400, 0.007). Notably, sex and BMI-adjusted analysis also showed that patients had a higher VAT fat mass (estimate= -225, p-value=0.084) and a higher VAT fat mass/total mass ratio (estimate= -0.007, p-value=0.026). Conclusions: When adjusted for BMI and sex, patients with MACS do not demonstrate differences in overall fat and lean mass. However, we showed that MACS is associated with increased visceral adiposity, a known cardiovascular risk factor. Body composition assessment by DXA could be a safer and less expensive alternative in the evaluation and follow-up of patients with MACS.

Presentation: 6/2/2024
8695 What Comes Fast, Goes Fast: Acute Megestrol Acetate Induced Adrenal Insufficiency
Authors: Kabir Purnima N , Bantu Sravani S , Bril Fernando
Published: October 2024

Disclosure: P.N. Kabir: None. S.S. Bantu: None. F. Bril: Other; Self; Novo Nordisk.

Megestrol acetate (MA; Megace®) is oftentimes used in the treatment of anorexia, cachexia, or unexplained weight loss in the setting of acquired immunodeficiency syndrome or disseminated carcinomatosis. MA is a synthetic progestin which has partial cross affinity to the glucocorticoid receptor. Its use can affect the pituitary-adrenal axis in a wide range of ways, from adrenal insufficiency (AI) to Cushing’s syndrome. We present a patient with advanced heart failure who developed acute AI after starting MA, which showed clinical and biochemical resolution after discontinuation of the medication.A 26-year-old male with a history of non-ischemic cardiomyopathy, heart failure with reduced ejection fraction, left ventricular thrombus, and CVA, who was admitted for management of heart failure exacerbation. Patient had a prolonged and complicated hospital course due to oliguric acute kidney injury requiring hemodialysis. He was subsequently diagnosed with protein calorie malnutrition. Oral calorie intake was poor and nutrition via tube feeds was insufficient, and the patient was started on MA 400 mg daily. Subsequently he developed hypotension, but after appropriate work-up, it was thought to be unrelated to cardiac etiology or infection, prompting further work up. Other causes of hypotension were ruled out, and an initial 6 am cortisol was 2.1 μg/dL. Repeat 8 am cortisol was 4.0 μg/dL, and an ACTH level was inappropriately normal at 14 pg/mL. Endocrinology service was consulted, and the recommendation was to discontinue MA. Repeat cosyntropin test results 1 week later were: cortisol at baseline 4.8μg/dL, at 30 minutes it was 19.2 μg/dL, and at 60 minutes it was 22.1μg/dL. Upon MA discontinuation, episodes of hypotension/orthostatism resolved, and the patient was discharged shortly afterwards. AI could be easily overlooked in patients taking MA due to confounding symptoms of cachexia. Moreover, because of the partial agonism of glucocorticoid receptor, many of the symptoms of MA-induced AI may be mild. Indeed, MA has been frequently associated with Cushing’s syndrome or AI upon discontinuation of the drug. Our case illustrates a patient that presented with acute MA-induced AI, which resolved quickly after MA discontinuation. Literature review mentions use of MA for weeks prior to development of AI usually seen with doses more than 400 mg/day. There is limited data regarding the timeline for resolution of AI, although it has been reported that symptoms usually resolve within days to months off the MA. Early recognition and prompt diagnosis of AI in patients initiating MA can prevent severe complications, such as adrenal crisis, as early discontinuation of MA can result in reversal of AI symptoms, avoiding the use of steroids to treat these individuals.

Presentation: 6/2/2024
7984 A Challenging Case Of Hyperphosphatemic Familial Tumoral Calcinosis
Authors: de Souza Tamara Gizelle , Joseph Weber Thomas
Published: October 2024

Disclosure: T.G. de Souza: None. T.J. Weber: None.

Introduction: Hyperphosphatemic Familial Tumoral Calcinosis (hFTC) is a rare, autosomal recessive metabolic disorder characterized by elevated serum phosphate levels and the accumulation of calcium phosphate deposits in soft tissues. There are fewer that 150 genetically confirmed cases in the literature. There are no consensus guidelines; therapeutic approaches are guided by case reports or series. This case serves to heighten awareness of therapeutic strategies including global health considerations for the disabled adult with a rare bone disorder. Case: A 32-year-old African-American woman presented to establish care for hFTC, for which she takes ibuprofen for disabling bilateral hip pain. hFTC was diagnosed in early childhood and managed at a large children’s hospital. Therapeutic modalities relied on operative resection of skin lesions on eruption. She describes cosanguinous parentage, consignment to foster care as a child and homelessness as an adult. She has not had adult endocrine care for her hFTC. Her medical comorbidities include major depressive disorder, PTSD and suicide attempt. She reports one uncle with hFTC noting that his phenotype was not significantly disabling and apparent recession of his lesions with age. Her parents did not have symptoms of hFTC. Radiographically, she had amorphous calcium deposits over both hips (her primary sites of severe pain), upper back (site of painless spontaneous eruptions), and left elbow without pain or skin penetration, as well as hyperostosis of the ilium bilaterally. She noticed waxing and waning of her eruptions with her menstrual cycle, such that lesions worsen in the luteal phase. Megestrol acetate also induced new eruptions. Examination shows brown staining to all teeth with several missing teeth. She had a marked lower extremity limb length discrepancy with severe restriction of hip abduction. Blood chemistries were grossly normal, including renal function, calcium, uric acid and PTH. Serum phosphorous was elevated at 5.2 (2.3 - 4.5 mg/dL). CT showed bilateral nephrocalcinosis. We instituted treatment with a low phosphorous diet, sevelamer to reduce intestinal phosphate absorption and acetazolamide to increase urinary phosphate excretion. For her pain and functional disability, we recommended continued NSAIDs, physical therapy and social work consultation to facilitate continued access to care. Conclusions: This case uniquely describes hFTC symptom fluctuation with the menstrual cycle, worsening with increased progesterone, suggesting a possible role of gonadal hormones on FGF-23 biology. It also highlights the socioeconomic burdens that can accompany rare bone disease, which become more pronounced as the patient achieves adulthood. Successful transition of care from pediatric to adult endocrinologist, in addition to engaging multi-disciplinary support, is essential in optimizing life-long care in hFTC.

Presentation: 6/1/2024
7200 A Unique Case Of Hypercalcemia From Primary Hyperparathyroidism With Thymoma And Concurrent Pulmonary Tuberculosis
Authors: Hang Randy Soh Jing , Huiling Liew
Published: October 2024

Disclosure: S. Jing Hang Randy: None. L. Huiling: None.

Background: Several case reports have reported the rare association of thymoma with primary hyperparathyroidism. We describe a unique case of hypercalcemia with such association but was also found to have concurrent pulmonary tuberculosis. Clinical Case: A 50-year-old Indian female with a significant history of anterior mediastinal mass underwent median sternotomy with mass resection and was found to have peri-operative hypercalcemia. Her only complaint was chronic cough. Initial investigations showed high adjusted calcium 2.78 mmol/L (2.15– 2.50 mmol/L), normal phosphate 1.1 mmol/L (0.8– 1.4 mmol/L) and high PTH 24.7 pmol/L (1.6– 6.9 pmol/L). Apart from the mediastinal mass, a whole-body CT scan showed multiple prominent mediastinal lymph nodes with non-specific subcentimetre lung nodules. The post-operative finding was a Type AB thymoma with necrotizing granulomatous inflammation in adjacent station I lymph node. Differentials for patient’s hypercalcemia included primary hyperparathyroidism, malignancies such as lymphomas and infectious causes in particular tuberculosis. Her 25-OH Vitamin D was low at 9 ug/L (30 - 100 ug/L), 1,25-dihydroxyvitamin D was elevated at 205 pg/mL (18-64 pg/mL) while creatinine, ALP, serum ACE and PTHrP were unremarkable. She was subsequently admitted for worsening hypercalcemia, fever and left pleural effusion with generalized lymphadenopathy where she underwent an Endobronchial Ultrasound-guided Transbronchial Needle Aspirate of station IV lymph nodes before being started on tuberculosis treatment. The AFB culture showed Mycobacterium Tuberculosis Complex thereafter. Parathyroid sonography revealed a 2.2cm x 0.9cm x 0.8cm lobulated hypoechoic lesion posterior to the inferior pole of left thyroid lobe. However, a confirmatory sestamibi scan could only be done 6 weeks post-thymectomy given the raw surgical bed, with a possibility of false-negative result for cervical parathyroid adenoma given a recent thymectomy. It subsequently showed a hyperfunctioning left inferior parathyroid nodule with no other suspicious focal uptake in the neck or mediastinum. Patient underwent a focused left parathyroidectomy. Histology showed features consistent with parathyroid adenoma. A stepwise trajectory of her calcium normalization was observed with hydration, intravenous zoledronic acid for her osteoporosis, tuberculosis treatment, adjuvant radiation therapy for her thymoma with margins involvement, and parathyroidectomy. Conclusion: This case illustrates the challenges faced while considering localizing scans for primary hyperparathyroidism with recent thymectomy given the common embryological origin of inferior parathyroid and thymus. It also demonstrates the possible co-existence of separate pathologies in hypercalcemia and the need to exercise prudent clinical judgement to further evaluate for these various etiologies.

Presentation: 6/2/2024
7216 Absence Of Weight Gain In C57Bl/67 Female Mice On A High-Fat Diet Protects The Skeleton From Bone Loss
Authors: McAndrews Casey , Chlebek Carolyn , Costa Samantha , Rosen Clifford J
Published: October 2024

Disclosure: C. McAndrews: None. C. Chlebek: None. S. Costa: None. C.J. Rosen: None.

Background: Obesity is associated with both systemic metabolic changes that increase the risk of comorbidities and reduced bone quality that increases the risk of fracture. The effects of high-fat diet consumption have been well studied in preclinical models where high-fat diet-feeding induces obesity, but there have been no studies to investigate the effects of high-fat diet-feeding in animals that do not become obese. Therefore, we characterized components of systemic metabolism and bone mineral content in non-obese C57Bl/6J mice that were fed a high-fat diet. Methods: Female C57Bl/6J mice aged 8 weeks received either a high-fat (60% kcal fat, n = 31) or control (10% kcal fat, n = 17) diet for 12 weeks. Body composition, areal bone mineral density (BMD) and bone mineral composition (BMC) were assessed after the feeding period using dual energy x-ray absorptiometry (Faxitron UltraFocus-DXA). Glucose (GTT) and insulin (ITT) tolerance testing were performed at the conclusion of the study. Changes in body weight were calculated as the difference between baseline and experiment end. High-fat diet-fed animals were classified as obese (HFD-O, n = 24) if they weighed more than 25 g or had greater than 25% body fat as evaluated via DXA, and were otherwise considered non-obese (HFD-NO, n = 7). In a small subset of animals, subcutaneous inguinal fat pads were harvested and weighed (n=5-7/group). Differences between groups were assessed with one-way ANOVAs and Tukey post-hoc analyses. Results: HFD-O mice weighed more than HFD-NO and control animals, whereas the body weights of HFD-NO mice were not significantly different from control (p < 0.001). Fat percent was increased in HFD-O mice compared to HFD-NO and control animals (p < 0.001). Subcutaneous inguinal fat mass was increased in both HFD-O and HFD-NO mice compared to control (p < 0.001). Fasting blood glucose did not significantly differ between groups. Glucose tolerance was worsened in both HFD-O and HFD-NO mice compared to control (p < 0.001), but there were no significant differences in insulin tolerance between groups. BMD was decreased in HFD-O mice compared to HFD-NO and control animals (p < 0.001). DISCUSSION: The consumption of a high-fat diet in mice induces deleterious metabolic changes irrespective of weight gain. However, high-fat diet-induced bone loss does not occur in the absence of weight gain. These findings suggest that certain adipokines derived from larger adipose depots may drive high-fat diet-induced bone loss and warrant further investigation. Acknowledgements: This work was supported by the 2023 Endocrine Society Research Experiences for Graduate and Medical Students (REGMS) Program.

Presentation: 6/1/2024
8643 Acute Anterior Uveitis Complicating Zoledronic Acid Infusion
Authors: Belal H F , Gandhi G Y
Published: October 2024

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

Background: Zolendronic acid is a nitrogen-containing, third-generation intravenous bisphosphonate commonly used to treat osteoporosis, Paget’s disease, and solid tumor bone metastasis due to its antiresorptive properties. Well-recognized side effects of bisphosphoantes include acute phase flu-like symptoms, hypocalcemia, renal toxicity, and jaw osteonecrosis. Acute anterior uveitis is a rare but serious side effect of bisphosphonates that has been reported in 0.8-1.1% of patients. Clinical Case: A 75-year-old female with a history of malignant melanoma (s/p wide resection) and current tobacco use presented for evaluation of osteoporosis. She had premature menopause that had not been treated with estrogen. She had pronounced kyphosis and an antalgic gait. Laboratory workup revealed normal serum calcium, thyroid function, renal function, and vitamin D level. CT imaging revealed T5, T7, T11, and T12 vertebral compression fractures with up to 50% loss of height. DEXA scan was notable for a femur neck T score of -3.2. She was started on oral alendronate 70 mg once weekly. However, she discontinued it after one dose due to fatigue. She then received one dose of intravenous zolendronate 5 mg. Three days later, she developed fatigue, nausea, decreased appetite, severe bilateral eye pain, blurry vision and photophobia. She was urgently evaluated by ophthalmology and found to have severe bilateral acute anterior uveitis. She was treated with high-dose oral prednisone with the resolution of uveitis. Conclusion: The mechanism of bisphosphonate-associated ocular reactions is thought to be activation of T cells producing inflammatory cytokines and macrophages. Manifestations include ocular pain, blurred vision, photosensitivity with flares, hyperemia, ciliary spasms, and synechiae. The most common eye-related side effect is conjunctivitis. However, uveitis and scleritis are the most severe eye reactions which require discontinuation of bisphosphonate use. Onset is usually 2 to 4 days after infusion but can occur up to 7 days later. Uveitis and scleritis have fulfilled the WHO Causality Guide of Suspected Adverse Reactions criteria and are deemed certain side effects of bisphosphonates. Recommended treatments include ocular corticosteroids and cycloplegics. Systemic corticosteroids have been used in severe cases. Symptoms typically improve over four weeks of treatment with corticosteroids without long-term sequelae. Rates of complications are also higher when bisphosphonates are used for malignancy compared to osteoporosis. Intravenous forms, such as pamidronate and zoledronate, tend to have higher rates and faster onset of ocular inflammation. Clinicians should be aware of and counsel patients with risk factors for uveitis (i.e., rheumatological inflammatory disorders, smoking) of this rare side effect and instruct them to seek immediate ophthalmological care.

Presentation: 6/3/2024
7254 An Unusual Case Of Hypercalcemia
Authors: Shushtarian Sara , Balogun Mojolaoluwa , Kaur Tarandeep
Published: October 2024

Disclosure: S. Shushtarian: None. M. Balogun: None. T. Kaur: None.

Hypercalcemia varies depending on severity. Higher serum calcium levels and more severe symptoms may indicate primary hyperparathyroidism or a malignant cancer. This is a case of a 32 year old female who presented with recurrent history of nephrolithiasis, found to have hypercalcemia of 13.4 mg/dL and parathyroid hormone of 1928.9 pg/mL, with phosphorus of 1.5 mg/dL. Ultrasound of her thyroid revealed a complex nodule arising from the right parathyroid gland measuring 2.2 X 2.0 cm. CT chest revealed diffuse osseous sclerosis secondary to metabolic disorder. Sestamibi scan did not localize any parathyroid adenoma. MRI of the thoracic and lumbar spine showed multiple small enhancing lesions throughout the pelvis and in the left rib, likely brown tumors related to hyperparathyroidism. X-ray of bony prominence on the patient’s left knee revealed a large lytic lesion of the proximal tibial diaphysis measuring 5.1 X 1.9 cm, concerning for aggressive neoplasm. Subsequent left tibial bone biopsy revealed giant cell rich lesions consistent with brown tumor of hyperparathyroidism. Due to our patient’s high calcium levels and large nodule size, she was referred to a tertiary center as the concern for parathyroid carcinoma and post-op hungry bone syndrome was high. Pre-op PTH level was 1408 pg/mL and post-op PTH was 96 pg/mL. The tumor removed was 2.1 cm. Post surgical pathology was consistent with atypical parathyroid adenoma. Patient was referred for genetic testing. An atypical parathyroid adenoma (APA) only accounts for 1.2 to 1.3% of cases of primary hyperparathyroidism. 80-85% of primary hyperparathyroidism is due to typical adenoma, and 10 to 15% of cases are due to hyperplasia or multiple gland disease. APA can often be confused with parathyroid carcinoma (PC), as they both have a 1:1 male to female ratio, high serum calcium levels, symptomatic hypercalcemia, high PTH levels, and fragility fractures. There are studies showing that both APA and PC have loss of nuclear parafibromin immunoreactivity. In addition, neither APA nor PC have any correlation with menopause, hormones, or gene deletions, unlike typical adenomas. Biopsy is necessary for diagnosis as the histological and immunohistochemical differences can differentiate APA vs PC. Histological features include pseudo-capsular invasion, bands of fibrosis, pronounced trabecular growth, nuclear atypia, and prominent nucleoli. Also, APA has a strong membranous staining pattern of E-cadherin, whereas PC has a loss of membranous staining. These differences are essential as although APA and PC clinically present similarly, APA lacks the invasive growth and possibility for metastatic disease that PC has. The likelihood for relapse of APA is low. Presence of malignancy criteria are indicative that a mass is actually PC and not APA. Despite this, APA is still considered a tumor of uncertain malignant potential and requires follow up.

Presentation: 6/3/2024
6714 Bone And Radiologic Findings In Congenital Generalized Lipodystrophy: A Systematic Review
Authors: Tuska R M , Brush M , Livinski A A , Brown R J
Published: October 2024

Disclosure: R.M. Tuska: None. M. Brush: None. A.A. Livinski: None. R.J. Brown: None.

Congenital Generalized Lipodystrophy (CGL) is characterized by a near-total loss of subcutaneous adipose tissue, leading to severe metabolic and systemic comorbidities. CGL is most commonly caused by mutations in AGPAT2 (CGL1) and BSCL2 (CGL2) genes. Skeletal abnormalities such as diffuse sclerosis, lytic bone lesions, and high bone mineral density (BMD) have been recognized in many patients with CGL, but the radiologic and clinical features of these bone phenotypes remain ill-defined. The aim of this systematic review was to evaluate the bone manifestations and radiologic findings associated with CGL1 and CGL2. We searched 6 databases: CINAHL Plus, Embase, Global Index Medicus (WHO), PubMed, Scopus, and Web of Science: Core. We screened articles utilizing a dual reviewer process in Covidence. Included publications reported primary bone and radiologic findings in patients with CGL1 or CGL2. Exclusions comprised publications without full text, duplicate publications, those lacking bone measures, and review articles. Two reviewers extracted data using RedCap and assessed risk of bias. 270 records were screened and 37 records reporting 179 cases of CGL were included for data extraction. Among the 79 patients assessed for bone cysts, 49 (62%) exhibited lytic appearing lesions. Of these 49, 14 (29%) patients presented with symptomatic lesions, primarily manifesting as bone pain at the lesion site (n=6), or pathologic fracture at the lesion site (n=9). Bone biopsy (n=7) revealed thin trabeculae and extensive vascular proliferation at the lesion site. Bone marrow biopsies (n=2) and imaging (n=20) revealed normal hematopoietic marrow with a marked reduction in marrow fat. 12 patients underwent serial bone imaging revealing diffuse osteosclerosis and the absence of lytic lesions in early childhood. During adolescence, lytic lesions appeared and progressed throughout the proximal and distal ends of the long bones in the appendicular skeleton sparing the axial skeleton. Markers of bone turnover were within normal limits except for sclerostin, which was elevated in a cohort of 11 patients. High BMD (n= 65), advanced skeletal maturation (n= 49), diffuse osteosclerosis (n=30), scoliosis (n=8), pseudo-osteopoikilosis (n=6), coxa valga (n=5), enlarged epiphyses (n=7), and coarse trabeculae (n=8) were also reported. While leptin replacement therapy improved metabolic parameters in many patients, it did not reverse the high bone mineral density or significantly alter markers of bone turnover. Individuals with CGL exhibit a spectrum of skeletal abnormalities including lytic-appearing lesions, osteosclerosis, high bone mineral density, advanced skeletal maturation, and pseudo-osteopoikilosis. Further long-term follow-up is needed to comprehensively assess the progression of these lesions over the life course and to elucidate the mechanisms contributing to their development.

Presentation: 6/2/2024
9336 Bone Pain Caused By Computer Cleaners Huffing
Authors: Sokrab M , Rao V S , Shah P , Shaker J L
Published: October 2024

Disclosure: M. Sokrab: None. V.S. Rao: None. P. Shah: None. J.L. Shaker: None.

A 47 year-old woman was evaluated 2/2024 for bone pain especially in the forearms and lower legs. The symptoms were worse since about 4/2023. Initial evaluation 11/2023 revealed elevated alkaline phosphatase levels and markers of bone remodeling (P1NP 396 ug/dl, normal; 20-101 and C-telopeptide 4389, normal; 177-1015. The plasma fluoride level was 17.1 mcmol/L (normal; < 4.1). There was no history of excess exposure to fluoride from dental products. She did not drink powdered iced tea or use green tea capsules. There was no industrial fluoride exposure and she consumed city water. She used inhaled fluticasone twice weekly but was not taking other fluoride containing medications, particularly voriconazole. She reported huffing computer cleaner containing difluoroethane between mid 2023 and early 2024. On examination, she had diffuse skeletal tenderness especially over her forearms and lower legs. Lab data revealed calcium 9.2 mg/dl (normal, 8.6-10.2), albumin 4 g/dl, phosphorus 3.6 mg/dl (normal, 2.5-4.5), creatinine 1.08 mg/dl (normal, 0.5-1.1), ionized calcium 1.33 mmol/l (normal, 1.18-1.33), pH normalized ionized calcium 1.25 mmol/l (normal, 1.18-1.33), PTH 126 pg/ml (normal, 15-72), 25(OH)vitamin D 29.5 ng/ml (normal, 20-50), and alkaline phosphatase 287 u/l (normal, 40-120) with a predominant elevation of the bone isoenzyme. The bone specific alkaline phosphatase was 93.4 mcg/l (normal, 7.0-22.4). The SPEP revealed a biclonal IgG Kappa monoclonal protein too small to quantify. The repeat fluoride level was 1.2 mg/l (normal, <0.05). Imaging included diffuse uptake on bone scan as well as periostitis/periosteal thickening involving legs, arms, and hands. There was axial osteosclerosis. Our patient appears to have skeletal fluorosis. Although the time-line of reported huffing and symptoms is not completely consistent, we could find no other exposure to fluoride and speculate she may have been huffing before she recalls. Skeletal fluorosis (SF) is endemic in some countries generally related to drinking water or tea that is high in fluoride, In the US, SF is caused by abnormal use of fluoride-containing dental products, excessive consumption of powdered iced tea containing fluoride, chronic use of the antifungal agent voriconazole and now more often huffing abuse of computer cleaners containing difluoroethane. The number of reported cases of huffing-related SF appears to be increasing and greater awareness of this problem is needed.

Presentation: 6/1/2024
8476 Case of Zoledronic Acid Induced Acute Anterior Uveitis In A 63-Year-Old Woman
Authors: Halstrom R , Perez J Sanchez , Lobo-Chan A M , Reutrakul S
Published: October 2024

Disclosure: R. Halstrom: None. J. Sanchez Perez: None. A. Lobo-Chan: None. S. Reutrakul: None.

Background: Bisphosphonates used for osteoporosis treatment are commonly known for their adverse gastrointestinal side effects and jaw osteonecrosis. Here, we document a case of anterior uveitis and scleritis post intravenous zoledronic acid infusion. Clinical case: A 63-year-old woman with osteoporosis, Graves disease complicated by thyroid eye disease s/p thyroidectomy, gastroesophageal reflux disease, positive antinuclear antibody and cataracts presented for a follow up of osteoporosis. She previously took alendronate 70 mg weekly for four years given a multi-bone arm fracture after a fall from standing height. On follow up 2 years after treatment, bone mineral density (BMD) by dual-energy absorptiometry had improved in the right femoral neck (T score from -3.3 to -1.8). A repeat BMD while on drug holiday showed T-score at left femoral neck of -2.4, with a calculated fracture risk assessment tool (FRAX) score of 18% and 4.8% for major and hip osteoporotic fractures, respectively. A zoledronic acid infusion was given due to elevated FRAX score, fracture history, and severe acid reflux. Nine days post-infusion, she presented to the emergency room with 2 days of right eye pain with blurry vision, eyelid swelling, photophobia, and tearing. Physical examination showed conjunctival and scleral injection, punctate epithelial erosions on corneal staining, and anterior chamber with anterior chamber cell. Labs were notable for weak positive RNP 29 (<19u). The following autoantibodies and levels were within normal limits: TSH 2.08 (0.35-4.0 mciu/ml), freeT4 1.0 (0.6-1.7 ng/dl), C3 152 (90-180 mg/dl), C4 33 (12-47 mg/dl), ESR 9 (<20 mm/hr), CRP 7 (<19u), SSA 0 (<29AU/ml), SSB 0 (<29AU/ml), dsDNA 4 (<24IU), Rh Factor (<10IU/ml), CCP 7 (<19U), and ANA. The patient was started on prednisolone acetate 1% 4 times daily, cyclopentolate twice daily with naproxen added 3 days later for additional anti-inflammatory treatment for the mild scleritis component. Therapy led to significant improvement on follow up 3 weeks later and topical corticosteroids and oral NSAIDs were tapered and discontinued. Conclusion: The onset of ocular symptoms and negative inflammatory workup raised concern for bisphosphonate induced anterior uveitis and scleritis. This case displays a rare side effect of bisphosphonate induced ocular inflammation with an approximate incidence of 0.046%-1% (1). We present this case in a patient with autoimmune disease and prior tolerance to oral bisphosphonate to shed light on a lesser-known side effect of bisphosphonates to promote prompt recognition and treatment. Reference: (1) Chartrand, Nicholas A., et al. “Ocular Side Effects of Bisphosphonates: A Review of Literature.” Journal of Ocular Pharmacology and Therapeutics, 39;1;2023, 3-16.

Presentation: 6/3/2024
7192 Description Of Patients With Post-surgical Hypoparathyroidism In Clinical Follow-up In Brazil
Authors: Dos Santos Lívia Marcela , Oliveira Martins Graziela , Costa Figueiredo Luis Felipe , de Lemos Manuela Nascimento , Viana Lima Jose , Azevedo Alvares Leonardo , Naomi Sakane Eliane , Maria Scalissi Nilza
Published: October 2024

Disclosure: L.D. Santos: None. G. Oliveira Martins: None. L. Costa Figueiredo: None. M. Nascimento de Lemos: None. J.V. Lima: None. L.A. Alvares: None. E.N. Sakane: None. N. Scalissi: None.

Post-surgical hypoparathyroidism is an event that may occur, especially after extensive procedures in the cervical region. There are few long-term follow-up studies on individuals who develop permanent post-surgical hypoparathyroidism and its long-term complications. Objective: This study aims to assess the clinical and laboratory characteristics of patients diagnosed with permanent hypoparathyroidism at a tertiary care center in Brazil. Methods: We conducted a retrospective analysis of medical records. Results: We evaluated 27 patients with permanent hypoparathyroidism, with an average age of 53 years (SD=10), where 15% were alcohol and tobacco consumers, and 88% were female. The average time of permanent hypoparathyroidism diagnosis was 9 years and 3 months. Regarding the surgical indication, 35% were due to Graves' disease, 25% for thyroid goiter, 25% for thyroid cancer, and 15% for glottic cancer. Only 15% had a description of the parathyroid glands in the pathology report. As for medications, all patients were using calcium carbonate, with an average dose of 1700 mg daily per individual. 90% of the patients were using calcitriol, with an average dose of 0.64 mcg daily, and 55% were using cholecalciferol, with an average weekly dose of 9700 IU. Hydrochlorothiazide was used by 35% of the patients, with an average daily dose of 34 mg. Regarding postoperative exams 24 hours after surgery, only half had the parathyroid hormone (PTH) test requested or available, with only one patient having PTH >10 pg/mL. Regarding chronic complications, 15% presented with nephrolithiasis, 5% with subcapsular cataract, 5% with prophylaxis for seizures, 15% with a diagnosis of depression, and 10% with arrhythmias. Conclusion: Individuals with permanent hypoparathyroidism require attention due to chronic complications, and proper treatment aims to reduce the chance of developing other diseases associated with permanent post-surgical hypoparathyroidism.

Presentation: 6/2/2024
9198 Dimeric [Cys25]PTH(1-34) Induces Differential Transcriptional Responses Versus Monomeric PTH(1-34)
Authors: Noh Minsoo , Jieun Kim Hani , Kim Jinseok , Kang Mikyung , Young Lee Soo , Lee Hunsang , Lee Sihoon
Published: October 2024

Disclosure: M. Noh: None. H.J. Kim: None. J. Kim: None. M. Kang: None. S. Lee: None. H. Lee: None. S. Lee: None.

Introduction: Patients with hypoparathyroidism caused by the homozygous mutation that changes arginine to cysteine at position 25 in parathyroid hormone (PTH) exhibit high bone densities, which suggests a potential influence of the mutant hormone on bone formation. We also have found that [Cys25]PTH forms homodimers, and that the dimeric peptide exhibits altered functionality versus monomeric PTH. Dimeric [Cys25]PTH(1-34) (Dimer) thus displays selective binding to the G protein-coupled PTH1R conformation (RG) in vitro and markedly diminished cAMP-inducing capability in vivo. Despite these alterations, Dimer induced bone anabolic effects in both calvarial injection assays and after injection in ovariectomized osteoporotic mice, closely mimicking the effects of PTH(1-34) (wtPTH). Our current objective is to explore the downstream signaling pathways activated by Dimer vs wtPTH to help elucidate the bone anabolic effects of the Dimeric analog and its therapeutic potential. Methods: A phospho-protein antibody array assay developed for G protein-coupled receptor (GPCR) downstream target proteins was employed in HEK293/hPTH1R (GP-2.3) cells following treatment with chemically synthesized wtPTH or Dimer. We further conducted RNA-seq analysis of transcriptome changes in primary cells collected from calvarial bones of mice treated with wtPTH or Dimer at 6, 12, and 24-hours post-injection. Finally, we used quantitative reverse transcription PCR (qRT-PCR) to analyze changes in specific marker genes in tibiae and kidney isolated from mice after treatment with Dimer vs. wtPTH. Results: The number of phosphorylated proteins significantly regulated by PTH1R upon exposure to Dimer was remarkably enhanced, relative to the number regulated upon exposure to wtPTH. RNA-seq analysis revealed that the early effects of wtPTH and Dimer on transcriptional regulation were similar, whereas marked differences in expression levels became apparent over time. qRT-PCR analyses of RNA expression levels in kidneys versus tibiae from mice treated with wtPTH or Dimer revealed in bone that the expression of genes associated with bone catabolism, particularly RANKL, was significantly lower in response to Dimer as compared to wtPTH treatment, while in kidney there was an overall reduced response to Dimer as compared to wtPTH. Conclusions: Our study supports the hypothesis that as compared to PTH(1-34), dimeric [Cys25]PTH (1-34) induces altered signaling responses in vivo and has a lower effect on bone catabolism. Dimeric [Cys25]PTH(1-34) thus holds interest as a potential bone anabolic agent that utilizes a distinct mechanism of action.

Presentation: 6/3/2024
12466 Dual Bone Defect In Patients With Charge Syndrome
Authors: Reyes N , Santen R J , Jan De Beur S M , Balasubramanian R
Published: October 2024

Disclosure: N. Reyes: None. R.J. Santen: None. S.M. Jan De Beur: None. R. Balasubramanian: None.

Chromodomain Helicase DNA-binding protein 7 (Chd7) is an ATP-dependent chromatin modifier that mediates nucleosome remodeling. Chd7 mutations result in CHARGE syndrome characterized by coloboma, heart defects, choanal atresia, growth/developmental delay, ear abnormalities, and hypogonadotropic hypogonadism/Kallmann syndrome (IHH/KS). Testosterone has direct and indirect effects (through estrogen), to increase bone formation and decrease bone resorption. Untreated hypogonadism is associated with decreased bone density and fractures. Reports of fractures and low bone density in CHARGE syndrome patients have been attributed to sex hormone deficiency associated with hypogonadism. However, recent data from a Chd7 mouse knockout model suggests an intrinsic Chd7-related bone defect. In wild-type mice, Chd7 promotes osteogenic differentiation of mesenchymal stem cells. Chd7 deficient mice show markedly reduced osteoblasts. Thus, we propose, a dual bone defect in CHARGE syndrome resulting from impaired osteogenesis from CHD7 and sex steroid deficiency; and increased bone resorption due to lack of sex steroids. Here we present two individuals with CHARGE syndrome with markedly low bone density and literature review supporting the dual bone defect concept. Case 1 is a 30 yo male with a pathogenic CHD7 mutation, multiple congenital anomalies of CHARGE syndrome and hypogonadotropic hypogonadism. He had multiple fractures in his teen age years and a bone density Z score of -5.2 at the lumbar spine and -3.3 at the left femoral neck. Because he did not tolerate androgen therapy, a single infusion of zoledronic acid was administered with no further fractures for eight years following infusion. Case 2 is a male evaluated for IHH/KS and ultimately diagnosed with CHARGE Syndrome based on a pathogenic CHD7 mutation. Despite 7 years of testosterone therapy with full virilization, his bone density remained low at Z-score of -1.9 at the spine and -2.6 at the total hip. Results: Both patients had low bone density, one while untreated and the other after full virilization with exogenous androgens. This raises the question whether the bone defects were related to the CHD7 mutation, to androgen deficiency or both. To answer this question, a literature search examined bone density data in untreated patients with CHARGE syndrome versus IHH/KS. We found substantially lower bone density in untreated CHARGE patients Z score -3.46±0.36 (SEM) (n=13) versus IHH/KS -2.16 ±1.0 (n=4). Furthermore, the bone density was also lower in treated CHARGE patients -2.46±0.28 (n=6) versus IHH/KS -0.94±0.26 (n=140). Conclusion: These data, taken together, provide direct human evidence to support the concept that the CHD7-related CHARGE syndrome patients have a defect in both osteogenesis as well as an effect of sex steroid deficiency on bone.

Presentation: 6/3/2024
6986 Efficacy and Safety of Weekly Liquid Alendronate Sodium Trihydrate in Korean Postmenopausal Women with Osteoporosis: A 12-Month, Multi-Center, Randomized Trial
Authors: Rhee Y , Ahn S , Hong N , Seo D , Hong S
Published: October 2024

Disclosure: Y. Rhee: None. S. Ahn: None. N. Hong: None. D. Seo: None. S. Hong: None.

Background: Although alendronate is the most prescribed oral bisphosphonate for osteoporosis treatment, it can lead to gastrointestinal problems, impacting treatment compliance and efficacy. This study aimed to assess the efficacy and safety of once-weekly alendronate sodium trihydrate (ALN-S), an oral solution, compared to once-weekly alendronate sodium (ALN-T), an oral tablet, in Korean postmenopausal women with osteoporosis. Methods: Conducted as a 12-month, multi-center, prospective, randomized, open-labeled, parallel trial at two hospitals in Korea, 170 postmenopausal women were randomized to ALN-S (N=85) or ALN-T (N=85). Bone mineral density (BMD) at the lumbar spine (LS), femoral neck (FN), and total hip (TH) was measured at baseline and after 12 months. Bone turnover markers, including C-telopeptide (CTX) and procollagen type 1 amino-terminal propeptide (P1NP), were assessed at baseline, 6 months, and 12 months. The primary outcome was the percentage change in LS BMD, evaluated for non-inferiority. Results: After 12 months, both ALN-S and ALN-T groups exhibited a significant increase in LS, FN, and TH BMD, with no significant intergroup differences (ALN-S: LS 5.0 ± 0.6%, FN 1.8 ± 0.6%, TH 2.2 ± 0.5%; ALN-T: LS 5.2 ± 0.6%, FN 1.6 ± 0.6%, TH 1.8 ± 0.5%). ALN-S was found to be non-inferior to ALN-T for BMD change at LS (treatment difference: -0.22%, 95% CI: -1.84 to 1.40%), excluding the predefined non-inferiority margin of -2.29%. Changes in both CTX and P1NP over time did not significantly differ between the groups. There was no significant difference in the frequency of adverse events between the groups. Conclusion: Weekly liquid alendronate sodium trihydrate demonstrated non-inferiority to weekly tablet alendronate sodium in increasing LS BMD in Korean postmenopausal women with osteoporosis.

Presentation: 6/2/2024
6424 From Hyperparathyroidism To Neurologic Crisis: A Tale Of Brown Tumor And Spinal Cord Compression
Authors: Kormanis Aryn , Anderson Matthew , McKnight Miya , Darapu Hima
Published: October 2024

Disclosure: A. Kormanis: None. M. Anderson: None. M. McKnight: None. H. Darapu: None.

Background/Objective: In this case, we present a rare and severe consequence of secondary hyperparathyroidism, a Brown tumor leading to spinal cord compression, in a young adult with end-stage renal disease. Case Report: A 26-year-old male with a medical history of polycystic kidney disease and IgA Nephropathy complicated by ESRD, history of brown cell tumors (s/p surgery) was admitted for hospitalization due to hypocalcemia after presenting to the Emergency Department with right lower extremity weakness. Examination revealed right hip flexor weakness and right foot clonus. Lab results showed serum calcium of 10.4 mg/dL . MRI displayed a 2.5cm X 3.7 cm soft tissue mass with circumferential encroachment of the epidural space leading to severe spinal canal stenosis of T4-T5 at the site of prior Brown tumor resection. Ultimately, the patient underwent subtotal parathyroidectomy with left cervical thymectomy, leading to an intra-operative PTH drop from >3500 to 247 pg/mL. Discussion: In the context of treating vertebral brown tumors, the consensus suggests that parathyroidectomy plays a crucial role in achieving both clinical and radiographical amelioration of the tumor. However, in cases like ours where paresis is present, surgical decompression of the tumor becomes imperative. Conclusion: The development of Brown tumors is a severe and rare long-term complication for hyperparathyroidism, and the location of a Brown tumor in the thoracic spine causing symptomatic cord compression is even more rare.

Presentation: 6/2/2024