bluuebunny/crossref_metadata_2025_split huggingface dataset:
THU459 Hypophosphatasia With Normal ALPL Gene Test; A Case Report
Authors: Alkwatli Kenda , Khan Leila Zeinab 
Published: October 2023

Abstract
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

Abstract
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

Abstract
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(&gt;28.9ng/ml), aldosterone 9ng/dl(&lt;/=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

Abstract
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 &lt; 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&lt;0.001). There was also a lower odds of death at 10 years in those who had successful parathyroidectomy (OR 0.29, p&lt;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&lt;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

Abstract
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

Abstract
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

Abstract
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 &lt;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

Abstract
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