bluuebunny/crossref_metadata_2025 huggingface dataset:
THU452 Polyostotic Fibrous Dysplasia Complicated By Aneurysmal Bone Cyst In A Patient With McCune-Albright Syndrome
Authors: Milazzo Eliana , Hermayer Kathie Lynn
Published: October 2023

Disclosure: E. Milazzo: None. K.L. Hermayer: None.

Introduction: McCune-Albright Syndrome (MAS) is a rare mosaic disorder with GNAS mutations, encoding the alpha-subunit of the Gs G-coupled protein receptor, activating it, and inappropriately producing cAMP. The hyperfunctioning endocrinopathies associated with MAS are due to signaling through the TSH, LH, FSH, GHRH, and ACTH receptors. MAS clinical presentation occurs with café-au-lait skin macules, precocious puberty, and fibrous dysplasia (FD) of the bone. FD is a benign tumor that leads to increased rates of bone fractures and if it causes facial deformities, can be complicated with orbital neuropathies. An aneurysmal bone cyst (ABC) is a blood-filled cyst that can be a primary or secondary lesion due to co-existing lesions. ABC is a rare complication of FD. We report a rare case of ABC in a MAS patient who presented with acute visual disturbance and enlargement of the forehead and was successfully treated with surgery. Clinical Case: A 20-year-old female diagnosed with MAS at the age of 2 who had precocious puberty by the 3rd year of life and developed polyostotic FD in the right arm, left femur, cranial, and skull bones with multiple long bone fractures by the age of 5-6 and required numerous orthopedic surgeries. She presented with the characteristic café-au-lait skin macules on the back and right arm. In 2018, a slow decline of left eye vision required left cranial decompression of the optic nerve, with pathology showing fibrous tissue compatible with FD. In 2021, she complained of acute right forehead enlargement, compressing her right eye with blurry vision. An MRI showed FD involving the facial and skull bones with a new expansible lesion in the right frontal bone with internal layering fluid, exerting a mild mass effect on the frontal lobe and extending superiorly to the orbit with inferior displacement of the globe. These findings were consistent with an ABC. Right frontal craniectomy and cranioplasty were performed in 12/2021, with pathology showing a fibrous pseudocyst wall with associated lymphoplasmacytic inflammation and evidence of prior hemorrhage with Ki-67 in the cyst wall at 15%. Lab work showed chronic alkaline phosphatase elevation at 567IU/L (42-106IU/L), normal calcium at 9.2mg/dl (8.4-10.3mg/dl), phosphate at 3.3mg/dl (3.3-5.1mg/dl), and PTH at 26pg/ml (15-65mg/dl), with Vitamin D insufficiency at 25.1ng/ml (30-100ng/ml). Endocrinology workup was negative for thyroid, adrenal, gonadotrophic, and GH dysfunction. 5 months post-surgery, the patient demonstrated complete recovery, and MRI showed no recurrence of the ABC. Conclusion: ABC is a benign solitary tumor generally arising from the metaphysis of long bones and rarely involves the cranium. ABC associated with FD has only been reported in a few cases. The treatment is surgical excision, with radiation and cryotherapy used in nonorbital cases.

Presentation: Thursday, June 15, 2023
THU457 Variable Presentations Of Hypophosphatasia In Two Patients In The Outpatient Setting
Authors: Elmaaz Ahmed , Batool Syeda Sabeeka , Dandona Paresh
Published: October 2023

Disclosure: A. Elmaaz: None. S. Batool: None. P. Dandona: None.

Introduction: Hypophosphatasia is a rare disorder characterized by defective mineralization of bone and teeth which is caused by an autosomal inherited mutation in the tissue nonspecific alkaline phosphatase (ALP) encoding genes. Here we present two cases of multiple dental and bony defects secondary to low ALP enzyme activity due to hypophosphatasia. Case 1: A 27-year-old female with history of mitochondrial disease, gastroparesis, malabsorption syndrome, and autonomic dysfunction was referred to Endocrinology clinic because of persistently low serum ALP levels associated with recurrent muscle, joint, and bone pain since the age of 13. She had history of multiple tooth extractions because of dental developmental abnormalities and fractures. She also reported history of fractures of three of her fingers in both hands during her childhood and teenage years. The patient was adopted and was unaware of any biological family history. Physical examination was remarkable for short-statured female, 4'8". Notably, the middle phalanges in little fingers bilaterally were shorter than the other fingers. Workup showed vitamin D level of 21 (30-80) ng/ml, despite being on 50,000 IU twice a week for 6 months with normal PTH and ionized calcium levels. The repeated serum level of ALP was 24 (31-125) U/L with bone and liver isoenzymes levels of 42% and 58 % respectively. Vitamin B6 level was 13.2 (2.1-21.7) ng/ml. Bone mineral density was unremarkable. Case 2: A 53-year-old female with history of congenital left hip dysplasia, hypertension, and dyslipidemia was seen by Endocrinology service for evaluation of decreased ALP levels. She denied any history of falls or fractures. However, she reported chronic bone pain, especially in bilateral hip joints with history of multiple surgeries in her left hip joint. She had required teeth braces and multiple dental surgeries during her childhood due to dental maldevelopment. Her height was 4'8". Laboratory workup was remarkable for low serum ALP level of 30 U/L with bone isoenzyme of 24 %. Vitamin B6 level was 206.7 (2.1-21.7) ng/ml. She had elevated serum phosphorus levels with normal calcium, PTH, and vitamin D levels. Pyridoxal-5- Phosphate level was high. Bone mineral density revealed osteopenia. Conclusion: Hypophosphatasia is a rare disease, hence it could be easily missed due to high variability in clinical presentations and severity of symptoms. Low serum levels of ALP with history of bone pain, recurrent fractures, premature loss of deciduous teeth, or loss of adult dentition should raise the suspicion of hypophosphatasia. Resistance to vitamin D supplementation is another clue to the diagnosis. A multidisciplinary approach is required for appropriate management.

Presentation: Thursday, June 15, 2023
THU458 Demineralization Zebras: A Rare Case Of Hypophosphatasia In An Adult Presenting With Osteopenia
Authors: Ramchandani Bhanvi Prakash , Khan Aysha , Aftab Hassaan
Published: October 2023

Disclosure: B.P. Ramchandani: None. A. Khan: None. H. Aftab: None.

Introduction: Hypophosphatasia (HPP) is a rare genetic bone disease with only 500-600 cases reported in the United States. It is characterized by mutations in the tissue non-specific alkaline phosphatase (TNSALP) gene, leading to impaired bone mineralization. HPP presenting in the perinatal period is fatal. During infancy, rachitic deformities develop by age 6 months. Children present with early loss of deciduous teeth and delayed milestones while in adulthood, HPP is characterized by recurrent fractures, osteoporosis, and muscle weakness. We describe a case of HPP diagnosed in a patient after low ALP was discovered on laboratory testing. Case: A 69-year-old female presented for the evaluation of osteopenia. She had a history of fracture of the right knee as well as fracture of the base of the right 5th metatarsal and lateral aspect cuboid, which healed well with conservative management. Dental history was significant for 5 implants over the last 15 years. She was on vitamin D supplements and had also taken risedronate for osteopenia for 14 years which was discontinued at her first visit with us. Family history was significant for osteoporosis in her mother. Initial lab studies were significant for an ALP of 29 U/L (ref range 39-113 U/L), phosphate of 4.9 mg/d (ref range 2.4-4.8 mg/dl), pyridoxal 5’-phosphate level (vitamin B6) of 308 nmol/L (ref range 20-125 nmol/l), a vitamin D 25-OH level of 20 ng/mL (ref range >30 ng/ml) and PTH of 49 pg/dl (ref range 15-88 pg/ml). Repeat lab testing done 6 months after stopping risedronate showed consistent similar results with an ALP of 32 U/L, phosphate level of 5.1 mg/dl, vitamin B6 level of 349 nmol/L, and vitamin D 25OH level of 26 ng/mL. Bone density scan revealed a lumbar spine BMD of 1.503 g/cm2 (T-score 2.5) and a mean total hip BMD of -0.3 consistent with osteoporosis of spine and osteopenia of hip. Genetic testing and counseling were offered to the patient, however she declined. Discussion: Our patient presented with recurrent fractures and loss of dentition requiring multiple dental implants in the background of osteopenia. Given persistently low serum ALP and elevated serum vitamin B6 levels her presentation suggested a diagnosis of HPP. Management includes supportive treatment with prompt treatment of fractures, and routine dental care. Although there is no approved medication for adults, enzyme therapy replacement with asfotase-alfa (a recombinant human ALP) is FDA-approved for pediatric-onset HPP which improves bone mineralization and muscle strength, however discontinuation of therapy leads to reappearance of bone hypomineralization. Once the diagnosis is made, genetic testing and counseling should be offered to prevent complications in future pregnancies.

Presentation: Thursday, June 15, 2023
THU459 Hypophosphatasia With Normal ALPL Gene Test; A Case Report
Authors: Alkwatli Kenda , Khan Leila Zeinab
Published: October 2023

Disclosure: K. Alkwatli: None. L.Z. Khan: None.

Introduction: Hypophosphatasia is a rare hereditary disorder caused by loss of tissue nonspecific alkaline phosphatase activity, an essential enzyme in phosphate metabolism. Severe cases present perinatally and in early childhood. Mild cases can present in adulthood and can be misdiagnosed. We present an interesting patient who was clinically diagnosed with hypophosphatasia despite negative molecular genetic testing. Case presentation: 40 years-old female with a history of fibromyalgia and multiple bone fractures presented to the clinic with a long-standing history of multiple cavities, severe fatigue, headaches, muscle cramps, and arthralgia. The patient had numerous fractures throughout her life that started at age five without significant trauma, including wrist, forearm, and metatarsal bones. Her family history was negative. Laboratory testing showed low alkaline phosphatase levels on multiple occasions, 28,29,30 U/L (reference range 34-123). Her vitamin B6 was elevated at 309 nmol/L (20-125). Her zinc, calcium, vitamin D, and liver function tests were all within normal limits. Bone density scan showed a Z score of -1.0 at the lumbar spine and a Z score of -0.3 at the left femoral neck. Molecular genetic testing of the ALPL gene was negative. Hypophosphatasia was diagnosed based on her clinical and lab assessments, and she is being treated with Asfotase alfa. Her clinical course is yet to be determined. Discussion: ALPL gene is responsible for encoding the tissue nonspecific alkaline phosphatase (TNALP), the main enzyme affected in patients with hypophosphatasia. TNALP degrades inorganic pyrophosphate (PPi) to inorganic phosphate (Pi), an essential element for bone mineralization. It also facilitates vitamin B6 to cross the cell membranes. Therefore, loss of function mutations of the ALPL gene cause accumulation of PPi, which impairs the calcium-phosphate hemostasis and causes damage to multiple organs. In addition, the accumulation of the active form of vitamin B6 extracellularly can result in neurological damage.Patients present with a broad spectrum of musculoskeletal, renal, dental, and neurological symptoms. The variability of the phenotypic magnitudes is thought to be due to heterogeneity in the ALPL gene mutations. Over 400s of ALPL gene mutations have been identified in patients with hypophosphatasia. Novel variants are increasingly being reported.Negative genetic testing of the ALPL gene can still be seen in patients with hypophosphatasia due to either a variant that is undetectable by current testing methodology or if the causative gene/s are not on the ALPL gene panel. Conclusion: Genetic testing is helpful in confirming the disease and providing genetic counseling; however, treatment should still be considered if patients have sufficient clinical and laboratory findings.

Presentation: Thursday, June 15, 2023
THU460 A Case Series Of Hypophosphatasia: Presentation And Response To Asfotase Alfa
Authors: Alsarraf Farah , Ali Dalal S , Almonaei Khulod , Al-Alwani Hatim , Brandi Maria Luisa , Khan Aliya Aziz
Published: October 2023

Disclosure: F. Alsarraf: None. D.S. Ali: None. K. Almonaei: None. H. Al-Alwani: None. M. Brandi: Consulting Fee; Self; Aboca, Alexion Pharmaceuticals, Inc., Amolyt, Bruno Farmaceutici, Calcilytix, Kyowa Kirin, UCB. Grant Recipient; Self; Abiogen, Alexion Pharmaceuticals, Inc., Amgen Inc, Bruno Farmaceutici, Echolight, Eli Lilly & Company, Kyowa Kirin, SPA, Theramex, UCB. Speaker; Self; Abiogen, Alexion Pharmaceuticals, Inc., Amgen Inc, Bruno Farmaceutici, Calcilytix, Echolight, Eli Lilly & Company, Kyowa Kirin, SPA, Theramex, UCB. A.A. Khan: Advisory Board Member; Self; Amgen Inc, Amolyt, Takeda. Consulting Fee; Self; Amgen Inc. Grant Recipient; Self; Alexion Pharmaceuticals, Inc., Amgen Inc, Ascendis, Chugai, Radius Health, Inc, Takeda, Ultragenyx. Research Investigator; Self; Amgen Inc, Radius Health, Inc. Speaker; Self; Alexion Pharmaceuticals, Inc., Amgen Inc.

Introduction: Hypophosphatasia (HPP) is a rare inherited metabolic bone disorder characterized by a deficiency in the tissue non-specific alkaline phosphatase (TNSALP) due to loss of function mutation in the ALPL gene. HPP is associated with impaired skeletal mineralization due to elevations in inorganic pyrophosphate and altered phosphate: pyrophosphate ratio. Asfotase alfa (AA) was approved for treatment of HPP in 2015. We present a case series of 7 patients with HPP, 5 with pediatric-onset and 2 with adult-onset, who have been treated with AA and describe the efficacy and safety in these patients. Case presentation: 7 patients (4 females, 3 males) aged 19-68 years with HPP were included in this case series. Diagnosis of HPP was confirmed by DNA analysis. AA was administered in doses of 6mg/kg/week with a mean follow-up of 6 months (SD= 5). Management outcome: Improvement in muscle strength, muscle pain, walking ability and walking distance with a reduction in the use of gait aids was seen. Muscle strength and pain improved by up to 70% from baseline as quantified subjectively by patients. Walking distance improved by up to 100%. Patients also reported improved cognition, mood and energy levels, with up to 90% improvement in mood and 75% improvement in energy levels. 4 out of 6 patients first noted clinical signs of improvement after 3 months of being on therapy. 1 out of the 7 patients sustained a toe fracture 10 months from being on AA. AA was well-tolerated with injection site reactions being the most commonly reported adverse effect. Discussion: HPP treatment with AA in individuals with both pediatric and adult-onset forms resulted in significant improvement in musculoskeletal and cognitive manifestations in addition to patients’ quality of life. It was well tolerated in 6 patients. 1 patient discontinued therapy because of minor adverse effects with myalgias.

Presentation: Thursday, June 15, 2023
THU474 Primary Hyperaldosteronism As A Cause Of PTH Elevation After Parathyroid Surgery
Authors: Thi Wai Phyo , Rao Ambika
Published: October 2023

Disclosure: W. Thi: None. A. Rao: None.

Background: Primary hyperaldosteronism can cause hypercalciuria, parathyroid hormone (PTH) elevation due to secondary hyperparathyroidism, and reduce bone mineral density. Screening for primary hyperaldosteronism can be done with serum aldosterone-renin ratio (ARR). We report a case of recurrent hyperparathyroidism after parathyroid surgery. Workup identified primary hyperaldosteronism as the cause of recurrent hyperparathyroidism. Treatment with spironolactone normalized PTH levels. Case Presentation: A 59-year-old African-American female in the Columbia VA Health Care System presented with hypertension, hypokalemia, bone density loss, and elevated PTH with normal calcium, one year after resection of a right inferior parathyroid adenoma to treat primary hyperparathyroidism. The patient had uncontrolled hypertension with hypokalemia while on losartan and amlodipine. Serum calcium was 9.4mg/dl(8.4-10.2mg/dl), PTH 89.4 pg/ml(29.2-79.9pg/ml), albumin 3.8g/dl(3.5-5G/dl), vitamin D 34 ng/ml(>28.9ng/ml), aldosterone 9ng/dl(</=28ng/dl), plasma renin activity 0.28ng/ml/h(0.25-5.82ng/ml/h), ARR 32. Treatment of the patient with potassium supplements corrected the hypokalemia to 3.7mmol/L (5-5.1mm/l), and ARR was 94 with aldosterone 17 ng/dl and PRA 0.18 ng/ml/h and 24-hour urine calcium 304mg/24h(35-250mg/24h). Based on the laboratory values, and the absence of adrenal nodules during a CT scan, a diagnosis of primary hyperaldosteronism due to idiopathic hyperplasia of the adrenal was made. Spironolactone was started and PTH levels dropped down to 64.8pg/ml and serum calcium remained normal 5 months after treatment was initiated. Discussion: Primary Hyperaldosteronism causes extravascular fluid volume expansion with a reduction in proximal tubular sodium and calcium reabsorption. Increased calcium and sodium delivery to distal segments of the nephron leads to sodium reabsorption by mineralocorticoids without reabsorbing calcium, resulting in hypocalcemia with concomitant secondary hyperparathyroidism. Bone loss results from direct mineralocorticoid receptor-mediated effects of aldosterone on osteoblasts and osteoclasts and indirectly from high PTH levels to promote bone resorption. Treatment of primary hyperaldosteronism can reverse bone loss and reduce fracture risk rate within 18-36 months. This case suggests that primary hyperaldosteronism be considered a cause of secondary hyperparathyroidism and successfully treated with mineralocorticoid receptor antagonists.

Presentation: Thursday, June 15, 2023
FRI700 Adverse Events In Patients With Primary Hyperparathyroidism With And Without Successful Parathyroidectomy - A Propensity-matched Comparison
Authors: Min Han Ji , Yuan Ye , Hu Jiangnan , Ghosh Chandrayee , Kebebew Electron
Published: October 2023

Disclosure: J. Han: None. Y. Yuan: None. J. Hu: None. C. Ghosh: None. E. Kebebew: None.

Objective: The aim of the study was to evaluate the impact of successful parathyroidectomy on renal, skeletal and cardiovascular adverse events in patients with primary hyperparathyroidism (PHPT). Background: PHPT may be associated with renal, skeletal and cardiovascular diseases. In some but not all studies, successful parathyroidectomy has been reported to be associated with reduced risks of renal, skeletal or cardiovascular adverse events. To date, there has not been a comprehensive study with granular data looking at the impact of parathyroidectomy on all adverse events that have been associated with PHPT. Methods: A health system cohort study was performed in 3,048 patients with PHPT as defined by ICD10 or ICD9 codes who had successful parathyroidectomy defined by CPT codes (n=1,105) and no parathyroidectomy (n=1943). Comparison of cardiovascular (arrhythmias, myocardial infarction, congestive heart failure, cardiac admission, hypertension, diabetes mellitus), renal (kidney stone, end-stage renal disease requiring dialysis, GFR < 30 mL/min) and skeletal (all fractures, fragility fractures (hip/pelvis and spinal fractures), diagnosis of osteoporosis or osteopenia) adverse events by parathyroidectomy status (successful vs. no parathyroidectomy) in unmatched and basic matched analyses, and propensity score (PS) matched analysis at 10 years of follow up. Results: The mean age was higher in the no parathyroidectomy arm. The comorbidity score was higher (4.1 vs 3.6) in patients who did not have parathyroidectomy with higher rates of congestive heart failure and myocardial infarction at baseline. Patients who had parathyroidectomy had a lower rate of subsequent diagnosis of cardiovascular adverse events at 10 years of follow up (OR 0.57, p<0.001). There was also a lower odds of death at 10 years in those who had successful parathyroidectomy (OR 0.29, p<0.001). These differences were significant in the unmatched and basic matched analyses, but were not significant after PS matching. There was no significant difference in 10 years rates of any fractures , fragility fractures, or renal adverse events. The odds of diagnosis of osteoporosis or osteopenia at 10 years of follow up was significantly lower in patients who had successful parathyroidectomy in all 3 analyses (PS-matching: OR 0.507, p<0.001). Conclusions: Compared to patients who did not have parathyroidectomy for PHPT, patients who had successful parathyroidectomy have lower 10 years rates of osteoporosis/osteopenia diagnoses. Cardiovascular adverse events were lower in patients who had successful parathyroidectomy but this may be due to higher baseline comorbidities in those who did not have parathyroidectomy.

Presentation: Friday, June 16, 2023
SAT185 Parathyroid Adenoma Localized By Cytogenetic Testing
Authors: Khadija Sairah , Rao Ambika
Published: October 2023

Disclosure: S. Khadija: None. A. Rao: None.

Introduction: Primary hyperparathyroidism can be caused by a parathyroid adenoma, hyperplasia or rarely by parathyroid carcinoma. Most patients have few or no symptoms. Diagnosis of primary hyperparathyroidism can be challenging in the setting of secondary/tertiary hyperparathyroidism. Correct diagnosis can be reached by clinical evaluation, biochemical and radiological tests. We describe a case that was diagnosed by cytogenetic testing of the biopsy specimen. Case Report: We report a case of a 64-year-old man. He was referred to the endocrine clinic for an incidental thyroid nodule on CT scan. He had hypothyroidism after I-131 treatment for Graves’ disease 15 years back. He had a long history of hypertension with renal failure. He had a renal transplant in 2017 and had hypercalcemia intermittently with elevated PTH since 2012. Ultrasound of thyroid reported a 1.6 x 1.7 x 2.0 cm nodule in the left thyroid lobe. He denied any compressive symptoms and was euthyroid on levothyroxine. An ultrasound guided FNA of the left thyroid nodule was reported as Bethesda III FLUS and sent to Veracyte for Affirma, which indicated a parathyroid adenoma. A sestamibi scan indicated a left lower parathyroid adenoma. He had surgery and intraoperative parathyroid hormone (PTH) dropped from 122pg/ml to 35.8pg/ml(29.1-79.7 pg/ml). Pathology confirmed parathyroid adenoma 3.8 grams in weight. Postoperatively calcium normalized with drop in PTH to 36.1pg/ml. After 2 weeks his calcium remained normal. Discussion: Parathyroid adenoma is a relatively rare condition and causes a majority of cases of primary hyperparathyroidism. A few cases are due to hyperplasia, more common in secondary hyperparathyroidism due to renal disease. Parathyroid adenoma is difficult to diagnose in patients with underlying hyperplasia due to chronic renal disease. Sonography and 99mTc preoperative sestamibi (MIBI) scan are the primary imaging modalities utilized for the visualization of diseased glands. MIBI scan is approximately 90% sensitive for localizing a parathyroid adenoma. Ultrasonography is the first-line imaging modality and parathyroid adenomas are nearly always homogeneously hypoechoic to the overlying thyroid gland and are commonly detected using gray-scale imaging alone when they are larger than 1 cm in diameter. Nodular goiter or enlarged lymph nodes are causes of false-positive results. Biopsy is very rarely used to diagnose a parathyroid adenoma with cytogenetic testing. Conclusion: Parathyroidectomy is the main stay in management of primary hyperparathyroidism due to parathyroid adenoma. Cervical sonography and sestamibi imaging are used for prediction of adenoma location. Both are limited by increased thyroid volume. Biopsy with cytogenetic testing can help in diagnosis in difficult patients.

Presentation: Saturday, June 17, 2023
SAT188 Atypical Parathyroid Adenoma: A Diagnostic Challenge Of Primary Hyperparathyroidism
Authors: Bendaram Snigdha Reddy , Dulipsingh Latha
Published: October 2023

Disclosure: S. Bendaram: None. L. Dulipsingh: None.

Introduction: Atypical parathyroid adenomas(APA) are parathyroid neoplasms with some atypical histological features and of indeterminate malignant potential. They may occur sporadically or as a part of hereditary syndromes and contribute to 1.2-1.3% cases of Primary Hyperparathyroidism (PHPT). Here, we present an interesting case of hypercalcemia secondary to PHPT due to an underlying APA. Case Presentation: 28 year old white female with no known significant past medical history presented to ED with symptoms of nausea, vomiting and dizziness on standing. Physical examination was unremarkable except for dry mucous membranes and decreased bowel sounds. Initial labs revealed a total calcium of 19.6 mg/dl (8.4-10.2), PTH of 1161pg/ml (10-65), creatinine 1.2mg/dl (0.5-1.0), albumin 5.0 g/dl (3.5-5.0), ionized calcium 2.37 mmol/L (1.19-1.35), phosphorus 3.4 mg/dl (2.5-4.5), magnesium 1.6 mg/dl (1.7-2.8) TSH 0.51 uIU/ml (0.35-5.5), 25-hydroxy Vitamin D 24 ng/ml (30-100),1,25-dihydroxy Vitamin D 68 pg/ml (20-79) and PTHrP 19 pg/ml (11-20). Family history was negative for hypercalcemia, hyperparathyroidism, fragility fractures, pancreatic disease or any genetic syndromes. Inpatient treatment included IV fluids, 2 doses of calcitonin and Pamidronate 60 mg IV. Subsequently, over the hospital course, calcium improved to 11.9 mg/dl with improvement in her symptoms and she was discharged home. 24-hour urine calcium checked on an outpatient visit, after vitamin D replacement, revealed low urine calcium of 31 mg/24 hr. Ultrasound Thyroid demonstrated a 3.7 cm mass inferior to the right hemithyroid, suspicious for parathyroid adenoma versus abnormal lymph node. CT Parathyroid with and without contrast revealed normal thyroid and bilateral inferior parathyroid adenomas, right larger than left. She underwent en-bloc resection of right thyroid and right inferior parathyroid gland with final pathology showing atypical parathyroid adenoma, without evidence for obvious parathyroid carcinoma or metastatic disease. Genetic testing for a total of 53 genes including MEN, BRCA1, BRCA2 were negative. PTH levels normalized post-surgery. Conclusion: Atypical Parathyroid Adenomas have a clinical and biochemical profile more severe that the typical adenomas and, to some extent, similar but less severe to that of patients with parathyroid carcinoma, creating an overall diagnostic challenge. The molecular mechanisms are unclear, with germline CDC73 mutations appearing to be the most common defect. Due to uncertain malignant potential, a close and careful monitoring is recommended for these patients.

Presentation: Saturday, June 17, 2023
SAT230 A Case Of Pseudohypoparathyroidism Without Any Hereditary Features
Authors: Haque Ikram , Alejandra Robles Lydia
Published: October 2023

Disclosure: I. Haque: None. L.A. Robles: None.

Background: Pseudohypoparathyroidism (PHP) refers to a heterogeneous group of disorders characterized by resistance to parathyroid hormone. PHP type Ib is characterized clinically by isolated renal PTH resistance manifesting as hypocalcemia, hyperphosphatemia, and increased serum PTH. About 60-70% of patients also present with elevated TSH levels due to TSH resistance. We present a unique case of adult onset PHP. Clinical Case: A 30-year-old woman admitted to the hospital for recent onset recurrent hypocalcemia with symptoms of weakness, muscle spasm and cramps. Until recently she was in a normal state of health. Admission labs revealed ionized calcium 0.78 (1.15 - 1.30 MM/L) , serum Ca 6.2 (Albumin 4.3). PTH elevated to 364. Creatinine 0.54 mg/dl, GFR 131 ml/min. Vit D level 35, Bone ALP 49.3 (premenopausal female :4.5-16.9 UG/L), Mag 1.9 , Ph 6.6. A 24-hour urine collection for Ca showed a value of 14 mg/24hr (50 - 400 MG/24H). Additionally, she was found to have a TSH <0.01 and Free T4 1.1. These labs confirmed PTH-resistant hypocalcemia and hyperphosphatemia with concurrent hyperthyroidism. Thyroid Ultrasound demonstrated a possible parathyroid adenoma on the left measuring 0.8x0.4x0.7 cm, which we suspect was a result of hyperplasia from PTH hypersecretion secondary to PTH resistance. TSI and TRAB antibodies were later found to be positive confirming grave’s hyperthyroidism. She had a similar presentation about 3 months earlier with symptomatic hypocalcemia and was discharged on Calcitriol, Ca CO3, and Cholecalciferol. Prior to this including through childhood, patient denies symptoms or lab abnormalities. Patients’ physical exam shows a height of 5ft 4-inch, weight 78kg, BMI 29.7. She had no abnormal facial features or skeletal/digit abnormalities. Patient reached all physical and cognitive milestones at expected times through childhood. Her calcium supplementation was adjusted to calcium carbonate 2000 mg every 8 hours, calcitriol 1 mcg twice daily, cholecalciferol 1000 units daily. Her total calcium improved to 7.4, ionized calcium improved to 0.93, phosphorus remained elevated at 6.1. Patient was discharged at her will due to personal social commitment. She was also started on Methimazole 5mg daily on discharge. Follow up labs showed Ca remained stable and eventually normalized on the above Ca supplementation 6 months after discharge. Conclusion: Unlike PHP Ia, patients with PHP Ib usually lack the physical characteristics of Albright hereditary osteodystrophy (round facies, short stature, short metacarpal bones (especially III-V), obesity, subcutaneous calcifications, and developmental delay), and typically show no other endocrine abnormalities, although our patient presented with subclinical hyperthyroidism. Typically, PTH-resistance disorders present as symptomatic hypocalcemia in childhood, however our patient presented in adulthood.

Presentation: Saturday, June 17, 2023
SAT243 A Rare Triad
Authors: Liaqat Hassan , Pasha Fajar , Chavez Luis
Published: October 2023

Disclosure: H. Liaqat: None. F. Pasha: None. L. Chavez: None.

Introduction: Hypercalcemia contributing to and directly causing pancreatitis is a well-known etiology in literature. Possible mechanisms identified include increased intrapancreatic conversion from trypsinogen to trypsin leading to damage of the pancreas and deposition of calcium in the pancreatic duct followed by pancreatic duct obstruction. The etiology of hypercalcemia-induced acute pancreatitis is usually hypercalcemia of malignancy. Less than ten cases of sarcoid-induced hypercalcemia leading to acute pancreatitis have been reported in the literature. Case Report: We present a case of a 39-year-old male who presented with complaints of generalized fatigue 60, pound weight loss, severe abdominal pain and sensation of lumps in his groin and neck. Examination revealed cervical and inguinal lymphadenopathy and a palpable spleen. Blood work revealed elevated lipase, creatinine, and hypercalcemia up to 14.8 mg/dl. Initial imaging revealed massive hepatosplenomegaly, hilar adenopathy and bilaterally miliary nodules in the lungs. Further workup of hypercalcemia revealed suppressed PTH, normal levels of PTHrP, and 25 hydroxyvitamin but elevated ACE levels and 1,25 dihydroxy vitamin D. Presentation and workup was concerning for sarcoidosis, and diagnosis was confirmed with a liver biopsy. The patient was treated initially with IV fluids, calcitonin, and steroids with resolution of his hypercalcemia and eventually pancreatitis symptoms. Case Discussion: Less than ten cases of sarcoid-induced hypercalcemia leading to acute pancreatitis have been reported in the literature, making this an extremely rare triad. The mechanism remains similar to other causes of hypercalcemia that lead to pancreatitis. Despite steroids not being recommended during an acute pancreatitis episode, this is one of the uncommon instances where steroids would be the preferred approach to tackle sarcoid-induced hypercalcemia. Other calcium-lowering therapies can be used short term like calcitonin and zoledronic acid.

Presentation: Saturday, June 17, 2023
SAT245 Hips Don’t Lie: A Case Of Peri-Prosthetic Pseudotumor Leading To Hypercalcemia After Total Hip Replacement.
Authors: Sotomayor Fiorella , Whitlatch Hilary
Published: October 2023

Disclosure: F. Sotomayor: None. H. Whitlatch: None.

Background: Peri-prosthetic pseudotumors are well described, yet rare complications of total hip replacement. They can present as destructive or granulomatous lesions. We present the first documented case of 1,25 vitamin D-mediated severe hypercalcemia caused by a periprosthetic granuloma. Case: A 62-year-old man with a history of osteoporosis, ankylosing spondylitis presented with hypercalcemia (calcium 12.2 mg/dL) on routine laboratory testing. He had a history of bilateral cement hip arthroplasty in 1981 followed by multiple bilateral revisions - three revisions of left hip arthroplasty, one revision of right hip arthropasty. Biochemical evaluation included PTH 5 pg/mL (8 - 54 pg/mL), PTHrP 2.7 pmol/L (0.0 - 2.3 pmol/L), vitamin D-25 59 ng/mL (20-80 ng/mL), a negative Quantiferon TB Gold, and normal serum protein electrophoresis. 1,25 Vitamin D was elevated at 280.5 pg/mL (19.9-79.3 pg/mL). During investigation of 1,25 vitamin D-mediated hypercalcemia, he received a dose of zoledronic acid with transient improvement in hypercalcemia. ACE was negative and CT chest and abdomen was without evidence of granulomatous disease. A whole-body PET scan showed increased metabolic activity surrounding the right femoral and acetabular components with a broad zone of osteolysis in the proximal femur and increased metabolic activity surrounding the left greater trochanter. These findings were concerning for inflammatory granuloma formation. He was prescribed prednisone 30 mg daily with rapid normalization of serum calcium. Prednisone was gradually tapered to 10 mg daily with maintenance of normocalcemia. Discussion: Pseudotumors are an uncommon complication of total hip arthroplasty. These are described as non-infectious and non-neoplastic adverse soft tissue reactions to implants. They manifest as destructive or granulomatous periprosthetic lesion. They cause osteolysis, erosions, pathological fractures, and dislocations. Their formation is due to foreign body reaction to polyethylene, methylmethacrylate, cement or metal adjacent to the joint implant. Associated inflammation leads to macrophage activation, prostaglandin release, and osteolysis. Histologically, they are characterized by the presence of macrophages, extensive coagulation necrosis, lymphocytes, eosinophilic infiltration and granulomatous reaction. While non-malignant, they can cause extensive bony destruction and may require complex revision surgery. To date, this is the first reported case of hypercalcemia due to excess 1,25 vitamin D caused by a periprosthetic granuloma. Conclusion: Hypercalcemia is a well-described complication of granulomatous diseases, including sarcoidosis, mycobacterium infection, and lymphoma. In patients with a history of arthroplasty, we recommend adding peri-prosthetic pseudotumors to the differential diagnosis of 1,25 vitamin D mediated hypercalcemia.

Presentation: Saturday, June 17, 2023
SAT249 Femur Lysis Calcium Crisis
Authors: Gupta Gunjan , Idriss Setana , Barua Nabonita , Hodge Jordesha , Jamal Issra
Published: October 2023

Disclosure: G. Gupta: None. S. Idriss: None. N. Barua: None. J. Hodge: None. I. Jamal: None.

Introduction: Primary hyperparathyroidism usually presents with symptoms of bone pain, fatigue, polyuria, constipation, and nephrolithiasis. Here we describe a 27-year-old female with a femoral neck fracture and found to have a parathyroid mass. Case: 27 y/o female with autism spectrum, presented to the ED for evaluation of a mechanical fall and was found to have a left femur and pubic ramus fracture. On arrival she was vitally stable, labs were significant for parathyroid hormone-related hypercalcemia corrected Ca 14.8 mg/dL, PTH 911 peaked to 2884 pg/mL, vit D level of 12.7 ng/mL, phosphorus of 2.3 mg/dL. Trauma workup revealed numerous osseous lytic lesions lower extremities. Review of system was negative except for localized pain at fracture site. Family history negative for hypercalcemia or hyperparathyroidism. She was managed with IV fluids, IV Zoledronic Acid 4 mg, SC calcitonin 240 units, and 50K IU D3. During hospitalization, she needed re-dozing with Zoledronic acid and Cinacalcet due to recurrence of significant hypercalcemia, warranting further imaging. CT neck showed mandibular and maxillary bone lesions raising suspicion of hyperparathyroidism jaw tumor syndrome (HPT-JT) vs brown tumors, 3.1 cm lobular mass inferior to the right thyroid lobe suspicious for large parathyroid adenoma vs carcinoma, and other multiple enlarged parathyroids. She underwent left femur cephalomedullary nailing and prophylactic nailing for the impending right femur fracture. Bone pathology showed fragmented bone, adipose, and skeletal muscle with fibrinous debris. She underwent subtotal parathyroidectomy (4-1/2 glands) and intraoperative PTH level declined from 1537 to 75 pg/mL 15 minutes after removal. Pathology showed tissue consistent with multi glandular parathyroid disease without evidence of malignancy. Postop her course was complicated with hungry bone syndrome requiring a few weeks on IV calcium. Discussion: Pathologic conditions in primary hyperparathyroidism include single adenomas (80-90% of the time), multiglandular hyperplasia multiple-gland (three or more glands) accounting for approximately 6%, and parathyroid carcinomas account for 1-2% of cases. Other conditions as with primary hyperparathyroidism include Familial hyperparathyroidism such as MEN 1 & 2A, Familial isolated hyperparathyroidism, and Familial HPT-JT syndrome, previously termed familial cystic parathyroid adenomatosis. Interestingly our pt had multiglandular hyperplasia which is a less common cause, she also demonstrated jaw lesions but didn’t fulfill the criteria for HPT-JT. Conclusion: Our patient had an unusual presentation of large bone fracture and multiple lytic lesions likely representing a brown tumor of the bone due to primary hyperparathyroidism. Most patients with lytic lesions have malignancy, however, endocrine pathologies should also be considered.

Presentation: Saturday, June 17, 2023
THU600 Coronary Calcium Scores In Medical Group Versus Individualized Dietitian-led Visits Group In An Inner-city Setting
Authors: Friedman Theodore C , Duran Petra , Budoff Matthew J , Shaheen Magda
Published: October 2023

Disclosure: T.C. Friedman: None. P. Duran: None. M.J. Budoff: None. M. Shaheen: None.

Obesity is highly prevalent in the U.S., particularly among ethnic minority groups. The purpose was using a randomized trial of 12-months to evaluate if coronary artery calcium (CAC) scores will decline in the medical arm compared to the dietitian-led arm and the control arm. Adult patients were recruited from LAC-DHS and randomized to medical group visit (n=58), dietitian individual visit (n=18) and control (n=50) groups. We measured the total CAC score and left anterior descending [LAD] scores using cardiac computed tomography to quantify CAC. We analyzed data for the change from baseline in the CAC scores between groups using the Kruskal Wallis test. We categorized the total CAC scores into 0-100 (no/mild risk); 101-400 (moderate risk); and > 400 (severe risk) and the LAD score into 0-99 (no/mild risk); 100-300 (moderate risk); and >300 (severe risk) and compared the groups using chi square or fisher exact test. P-value <0.05 was statistically significant. No statistical difference was found between the study groups in the change of the total CAC score. The mean, median and IQR of the change in total CAC score were -26.4, 0.0,3.0 in the dietitian group; 21.6, 0.0, 10.0 in the medical group; 44.6, 3.0, 23.0 in the control group (p=0.10). At baseline and post-intervention, no significant differences were found between the study groups in the total CAC risk (p=0.22). The mean, median and inter-quartile range (IQR) of the change in LAD score were -23.6, 0.0, 2.0 in the dietitian group; 4.7, 0.0, 2.0 in the medical group; 12.5, 1.0, 9.8 in the control group (p=0.036). Significant improvements were found between the dietitian group and control group (p=0.039) and the medical group and control group (p=0.027). For LAD risk groups at baseline, 10%, 11.1% and 10.3% of the control, dietitian, and medical groups, respectively, had moderate risk; and 10.0%, 5.6%, and 1.7%, respectively, had severe risk (p=0.069). Post intervention, there was a reduction in the percent with moderate risk in the dietitian (-5.5%) and the medical (-1.7%) groups relative to control group (2.0%). For the severe risk, there was a reduction of 5.6% in the dietitian group, with no change in the medical group relative to 2% increase in the control group (p=0.013). Our study showed significant improvement in the LAD score and its risk groups in the dietitian group relative to the control and medical groups indicating that the dietitian intervention was able to attenuate the progression of atherosclerosis. The implications of our study is that lifestyle obesity interventions have the potential to reduce cardiovascular disease.

Presentation: Thursday, June 15, 2023
FRI094 Case Report: Treatment Of Sitosterolemia With Ezetimibe - 17 Years Of Follow-up
Authors: Vieira Coutinho Jean Gabriel , Santos Costa Ana Carolina , Moura Issa Milka Maria , Pereira Paim Neiva , Quedas Elisangela P S , Sutti Nunes Valeria , Lima Jorge Alexander Augusto , Regina Nakandakare Edna , Faria Carrilho Alexandre Jose
Published: October 2023

Disclosure: J.V. Coutinho: None. A.S. Costa: None. M.M. Issa: None. N.P. Paim: None. E.P. Quedas: None. V.S. Nunes: None. A.L. Jorge: None. E.R. Nakandakare: None. A.F. Carrilho: None.

Background: Sitosterolemia is a rare autosomal recessive disease caused by inactivating mutations in the ABCG5 or ABCG8 genes. It is characterized by the accumulation of plant sterols in tissues in the form of xanthomas and vascular atheroma. Ezetimibe has been used to decrease serum sterol levels, but its role in xanthomas and arterial atherosclerosis progression remains undetermined. We present a patient diagnosed with sitosterolemia done at age 23 years and followed for 17 years on treatment with ezetimibe 20 mg daily. Clinical case: A 23-year-old man showed typical xanthomas on the extensor surfaces of his hands and Achilles tendons, in addition to splenomegaly and thrombocytopenia. Serum cholesterol and triglyceride levels were normal and sitosterolemia was suspected by a tendon biopsy. The diagnosis was confirmed by high serum concentrations of β-sitosterol and campesterol, and the patient was advised to follow a low plant-sterol diet and to take ezetimibe 20 mg daily. Seven years later, there was no change in xanthoma size, abdominal ultrasound showed normal spleen, and plasma lipid levels were: total cholesterol (TC) 147 mg/dL, HDL cholesterol (HDL) 44 mg/dL, LDL cholesterol (LDL) 61 mg/dL, triglycerides (Tg) 206 mg/dL, desmosterol 0. 137 µg/mL (n < 1.6 µg/mL), lanosterol 0.368 µg/mL (n < 2.2 µg/mL), campesterol 39.65 µg/mL (n < 5.5 µg/mL), β-sitosterol 87.53 µg/mL (n < 1.7 µg/mL) and platelet count 109,000/mL. Seventeen years after diagnosis, at age 40, there was no significant change in xanthoma size and the patient remained without cardiovascular symptoms (normal echocardiography and exercise stress test), however ultrasound showed bilateral carotid-intimal-medial thickening (0.1 on the right and 0.17 on the left, n < 0.1) and serum lipid concentrations were: TC 203 mg/dL, LDL 130 mg/dL, HDL 46 mg/dL, Tg 145 mg/dL, campesterol 21.34 µg/mL (n < 5.5 µg/mL) and β-sitosterol 65.13 µg/mL (n < 1.7 µg/mL). Then, atorvastatin 20 mg daily was added to ezetimibe. In addition, genomic DNA sequencing revealed a compound heterozygous mutation of the ABCG5 gene (NM_022436:exon1:c.64C>T:p.Q22* and NM_022436:exon9:c.1217G>A:p.R406Q). Conclusion: treatment with ezetimibe prevented the growth of xanthomas, however it was not able to normalize plasma levels of campesterol and β-sitosterol. Furthermore, the small carotid intimal-medial thickening found raised the question about the role of plant sterols in atherosclerosis.

Presentation: Friday, June 16, 2023
FRI096 Efficacy Of Pemafibrate In Patients With Dyslipidemia: A Systematic Review And Meta - Analysis Of Randomized Controlled Trials
Authors: Caroline Cristine Almeida Balieiro , Romero Nakajima Noah , Mizuhira Gobbo Marcela , Assunes Gonçalves Beatriz Polachini , Amaral Peixoto Natália Araujo do , Teixeira Sirena Eduardo Cesar , Barbosa Moreira Matheus José
Published: October 2023

Disclosure: C.A. Balieiro: None. N.R. Nakajima: None. M.M. Gobbo: None. B.A. Gonçalves: None. N.D. Peixoto: None. E.T. Sirena: None. M.B. Moreira: None.

In individuals with dyslipidemia, which is a well-known risk factor for cardiovascular events, pemafibrate may improve lipid abnormalities. We aimed to perform a systematic review and meta-analysis of randomized clinical trials (RCT) comparing pemafibrate to either placebo or fenofibrate in patients with hypertriglyceridemia. The PubMed, Cochrane, and Embase databases were searched for RCTs only. Data were extracted from published reports, and quality assessment was performed according to PRISMA guidelines. We used a random-effects model to calculate the mean difference (MD) and the 95% confidence interval (CI). The primary endpoints of interest were percent changes in triglycerides (TG) and non-HDL cholesterol. The review protocol is registered at PROSPERO, under the number CRD42022374852. Nine studies involving 12,644 patients were included. Of all participants, 6,699 (53%) received the intervention. There was a higher percentage of decrease in serum TG in the pemafibrate group at the dose of 0.4 mg/day (MD −48.29 [−61.45, −35.13], 95% CI; P < 0.0001, I2 = 93%), in comparison to placebo. In addition, non-HDL levels were significantly lower in patients treated with pemafibrate at the dose of 0.4 mg/day when compared to placebo (MD - 6.35, [−10.62, −2.08], 95% CI; P < 0.0001, I2 = 82%). There was no significant percent change in TG between patients treated with pemafibrate 0.2 mg/day compared when compared to fenofibrate 200 mg/day (MD −2.90 [−12.90, 7.11], 95% CI; P = 0.003, I2 = 83%), neither in the pemafibrate groups at the doses of 0.1 mg/day (MD 43.72 [-53.51, -33.93], 95% CI; P = 0.06, I2 = 60%) and 0.2 mg/day (MD −47.30 [−53.99, −40.60] , 95% CI; P = 0.11, I2 = 47%) when compared to placebo. Decrease of non-HDL levels were not significantly different when comparing pemafibrate and placebo, neither at the dose of 0.1 mg/day (MD -7.11 [−10.71, - 3.50], 95% CI; P = 0.26, I2 = 25%) nor 0.2 mg/day (MD - 7.70 [-10.66, −4.74], 95% CI; P = 0.20, I2 = 33%). Our meta-analysis demonstrates that pemafibrate is effective in lowering triglycerides and non-HDL levels in patients with dyslipidemia compared to placebo. Furthermore, the difference in reduction between pemafibrate and fenofibrate was not statistically significant. This study represents the most current evidence. Keywords: Dyslipidemia, Pemafibrate, Triglycerides

Presentation: Friday, June 16, 2023