bluuebunny/crossref_metadata_2025_split huggingface dataset:
7027 A Rare And Multifactorial Etiology Of Severe Parathyroid Hormone Independent Hypercalcemia In An Adult Female With Rett Syndrome
Authors: Foo Madeline I , Thompson Michael 
Published: October 2024

Abstract
Disclosure: M.I. Foo: None. M. Thompson: None.
Background: Symptomatic hypercalcemia is a rare, but potentially life-threatening disorder. Although dehydration is an unusual cause of severe hypercalcemia, in the appropriate clinical setting dehydration may amplify underlying mild or moderate hypercalcemia to dangerous levels.Case: A 46-year-old non-verbal, non-mobile Caucasian female with Rett Syndrome (RS) with Stage III Chronic Kidney Disease (CKD3) who is dependent on percutaneous endoscopic gastrostomy (PEG) tube for nutrition and known PTH independent hypercalcemia of unknown etiology presented to the hospital with intractable vomiting and constipation, an outpatient serum calcium level of 16.0 mg/dL, and serum creatinine 4.03 mg/dL (baseline 1.2 mg/dL). Initial laboratory assessment revealed elevated corrected serum calcium levels (15.7 mg/dL), with appropriately suppressed PTH levels (12.5 pg/mL) and hypernatremia (146 mmol/L). Thyroid function tests, both Vitamin D 1,25(OH)2D and D 25(OH)D levels and PTH-RP were normal. Computed tomography of the abdomen and pelvis revealed bilateral nephrolithiasis and moderate stool burden, but no evidence of malignancy or granulomatous disease. Skeletal scintigraphy was also without evidence of osseous metastatic disease or Paget’s disease of bone. An in-depth interview with the patient’s caregiver uncovered that the patient had a relative intolerance to enteral hydration and had been receiving minimal water flushes prior to admission, contributing to severe dehydration. Hypercalcemia was ultimately ascribed to prolonged immobilization due to RS compounded by inadequate fluid intake and auto-diuresis secondary to hypercalciuria in the setting of CKD (prior baseline eGFR 45 mL/min/1.73m2).Outcome: The patient's hypercalcemia improved after a multidisciplinary and multi-directed approach involving intravenous and enteral fluid resuscitation, calcitonin, furosemide, and ultimately zoledronic acid following improvement in creatinine with fluid resuscitation. The dietary service employed a strategy of 24-hour enteral feeding, increasing both the frequency and amount of enteral water, which the patient tolerated well, and provided her with a new pump for home use. Education on monitoring tube feed tolerance and providing adequate enteral hydration was provided to both the caregiver and group home. On discharge, eGFR stabilized at 33 mL/min/1.73m2 and corrected calcium stabilized at 10.0–10.4 mg/dl. She was provided with an endocrinology follow-up to continue bisphosphonate therapy.Discussion: Hypercalcemia of immobility should remain a differential diagnosis in severe hypercalcemia, especially PEG tube dependent patients with underlying kidney disease. This case highlights the importance of thorough history taking and a multidisciplinary strategy to guarantee optimal care and mitigate potential adverse outcomes in medically complex patients.
Presentation: 6/2/2024
7331 A Rare Case Of Familial Hypoparathyroidism
Authors: Sekhon Navharsh , Zin Win Kyaw 
Published: October 2024

Abstract
Disclosure: N. Sekhon: None. K.Z. Win: None.
Background: Autosomal dominant hypoparathyroidism disorders are very rare and mostly asymptomatic. We present an interesting case of autosomal hypoparathyroidism with a new variant of gene defect on genetic analysis. Case: A 66-year-old female was referred to the endocrinology clinic for familial hypoparathyroidism and calcium oxalate nephrolithiasis. She had onset of seizures at age 16. She was diagnosed with hypocalcemia and hypoparathyroidism at age 30 when she had her first episode of nephrolithiasis. She had recurrent nephrolithiasis and lithotripsies, ultimately developing chronic kidney impairment that was at stage 3b at the time of evaluation. Renal Ultrasound revealed bilateral nephrolithiasis, and nephrocalcinosis. There was a history of hypoparathyroidism in her father, paternal uncle, and son. Her medications included calcium carbonate-vitamin D3 600-400 mg-unit oral 2 tablets daily and calcitriol 0.5 mcg daily. The pertinent physical examination finding was a short stature with height 4’11” and calluses in fingers. Her recent serum chemistry showed calcium 8.8 mg/dL (reference range 8.3 - 10.6 mg/dL), PTH &lt; 6.3 pg/mL (reference range 18.4 - 80.1 pg/ mL), and phosphorus 3.3 mg/dL (reference range 2.4 - 5.5 mg/dL). 24 hr urine calcium was 96 mg (reference range 50-300 mg/24h). She was treated with hydrochlorothiazide for nephrolithiasis but was discontinued due to hypokalemia. We performed genetic testing that resulted positive for CASR NM_001178065.1 with heterozygosity and damaging missense predictions inherited as autosomal dominant or recessive. Discussion: The calcium-sensing receptor (CaSR) has an important role in calcium homeostasis by regulating parathyroid hormone (PTH) secretion and urinary calcium excretion. Familial hypoparathyroidism disorders are divided into Autosomal dominant hypocalcemia (ADH) type 1 and Autosomal dominant hypocalcemia (ADH) type 2. ADH1 is caused by an activating mutation of calcium-sensing receptor (CASR). The estimated prevalence of ADH1 ranges from 1 per 70,000 to 3.9 per 100,000. It is characterized by mild to moderate hypocalcemia, hyperphosphatemia, hypercalciuria, and inappropriately low but detectable PTH levels. It can be associated with Bartter syndrome Type 5. ADH2 is due to mutations in the alpha subunit of the G protein G11 (Gα11). Our patient had classic symptoms of hypocalcemia including short stature, seizures, kidney stones and its sequelae. Her 24-hour urine analysis showed inappropriately normal urine calcium with low normal serum calcium, undetectable serum PTH, and normal phosphorus. Our patient’s genetic analysis revealed a heterozygous defect in gene CASR with DNA variants c.2564G&gt;A with damaging missense predictions. There is no such variant reported or listed in the ClinVar database. To our knowledge, this is the first such case of an autosomal dominant hypoparathyroidism with this gene defect.
Presentation: 6/1/2024
6874 A Rare Case Of Hereditary 1,25 (OH)2D Resistant Rickets
Authors: Umarji G , Thelmo F , Jabbour S A 
Published: October 2024

Abstract
Disclosure: G. Umarji: None. F. Thelmo: None. S.A. Jabbour: None.
Vitamin D-dependent rickets type 2A (VDDR2A) also known as hereditary 1,25 (OH)2D resistant rickets is due to biallelic loss-of-function mutations in the gene encoding vitamin D receptor on chromosome 12q13.11, thus, it represents a true form of tissue resistance to vitamin D. It is a scarce form of rickets with approximately only 120 cases reported. A 37-year-old male was referred to endocrinology by neurosurgery for evaluation of metabolic bone disease. Seven years ago, he was in a car accident which resulted in a lumbar spine injury causing radiculopathy and severe low back pain leading to lumbar spine decompression/fusion. However, he suffered from nonunion of bones and had to undergo another surgery a year later with recurrent postoperative nonunion of bones. During the operation, the surgeon noticed that his spine seemed demineralized. He had a history of multiple minor fractures in childhood, decreased hearing in left ear for two years, fragile teeth for many years, and some hair loss since age 30. Physical exam showed a height of 1.82 m, weight 89.3 kg with body mass index of 26 kg/m2, broken teeth, no leg bowing and normal stance. Laboratory results showed normal renal function, thyroid function tests and testosterone level, corrected calcium 8.3 mg/dL (8.7-10.2), 25-OH-vitamin D 54 ng/mL (30-100), phosphorus 2.8 mg/dL (2.8-4.1), intact parathyroid hormone 65 pg/mL (15-65), bone-specific alkaline phosphatase 21 mcg/L (4-27), 24-hour urine calcium 156 mg/day (100-300), 24-hour urine phosphorus 1,752 mg/day (390-1,425), FGF-23: 93 RU/mL (44-215) and 1,25 (OH)2D 92 pg/mL (24-81.5). Dual absorptiometry of the lumbar spine and hip showed osteopenia with Z scores of -2.2 and -1.2 respectively. Genetic testing for metabolic bone disease panel showed heterozygous mutation in VDR gene at nucleotide position c.146+9dup associated with autosomal recessive VDDR2A. We present a very rare form of vitamin D resistant rickets. As many patients with VDDR2A are unable to respond to any form of vitamin D, it is suggested that VDDR2 be more appropriately described as hereditary 1,25 (OH)2D resistant rickets (HVDRR), hereditary resistance to 1,25 (OH)2D, or even pseudovitamin D-deficiency type IIA (PDDR IIA). Clinical features include severe rickets, bone pain, hypotonia, dental caries and alopecia. Biochemical features include hypocalcemia, hypophosphatemia, normal to elevated alkaline phosphatase, normal 25(OH)D and importantly, elevated 1,25-(OH)2D levels. Management is with high doses of calcium and vitamin D therapy. While rare, this disease highlights the need for a comprehensive evaluation of metabolic bone diseases and a thorough understanding of calcium and vitamin D metabolism.
Presentation: 6/2/2024
12372 A Rare Case Of Silicon Granulomatosis Induced Hypercalcemia In A Transgender Female
Authors: Aluko Oluwatomisin A , Singh Ishita 
Published: October 2024

Abstract
Disclosure: O.A. Aluko: None. I. Singh: None.
Introduction: Hypercalcemia has been described in patients with most granulomatous disorders, of which sarcoidosis and tuberculosis are the most common. Granuloma formation is a rare, however well known complication of silicon implants and injections. We present a case of silicon granulomatosis induced hypercalcemia in a transgender female. Case Report 60-year-old transgender female, with past medical history of HIV on HAART was referred to Endocrinology for evaluation of hypercalcemia. She Bloodwork done a few weeks prior revealed elevated calcium 12.3 and low PTH of 9. Reported symptoms include worsening abdominal pain similar to prior gastritis flare, insomnia and significant weight loss. Denied any constipation, joint pain, mood changes, no history of bone fractures or kidney stones. Admitted to significant dairy intake - half a gallon of milk within 3 days and daily yogurt consumption. Endorsed inadequate daily fluid intake and she was not taking oral calcium or Vitamin D supplementation. Quit tobacco 9 years ago. Vitals were significant for tachycardia with HR 120/min, BP stable. Patient was referred to the ER for IV hydration and further evaluation with initial suspicion of malignancy. Repeat corrected calcium was 14.7, ionized calcium 6.8, PTHrP undetectable &lt;2, borderline high 1,25 dihydroxyvitamin D 74.5, low vitamin D 17.9 and normal free T4 1.5. ACE, SPEP, UPEP levels within normal limits. Vitamin A low. CT chest/abdomen/pelvis revealed innumerable soft tissue foci in the subcutaneous adipose tissue of the flanks and lateral gluteal areas; nodular liver, suspected cirrhosis and portal hypertension. Imaging findings prompted further discussion regarding prior procedures. She endorsed history of silicone fillers in hips and breast implants 30 years ago. Images reviewed with radiology confirmed calcification around bilateral breast implants, with intracapsular rupture. Calcium improved with IV Fluids, bisphosphonates and steroids. The most probable cause of hypercalcemia was believed to be secondary to silicone granulomatosis. Innumerable granulomas were deemed irresectable, removal of the breast implants considered however not performed. She was later diagnosed with hepatitis B, cirrhosis and succumbed to sepsis and multiorgan failure. Conclusion Eliciting a detailed history, physical exam and correlating with imaging findings is imperative to establishing an uncommon diagnosis. PTHrP was low and there were no bony metastases making the possibility of malignancy related hypercalcemia less likely. FDG-PET if performed would reveal hypermetabolic nodules, often an initial indication to the underlying etiology.
Presentation: 6/2/2024
7154 Adult Hypophosphatasia With Heterozygous Missense Mutations In ALPL Gene
Authors: Chaugule Akshata S , Cervelo Yeset , Dhillon Shabnam , Tuncay Delibasi 
Published: October 2024

Abstract
Disclosure: A.S. Chaugule: None. Y. Cervelo: None. S. Dhillon: None. D. Tuncay: None.
We present a case of a male in his third decade of life discovered to be a carrier of the genetic mutation associated with hypophosphatasia during routine pre-conception genetic screening. Genetic analysis revealed a heterozygous pathogenic missense variant which is c.979TC, p.F327L in the ALPL gene. A retrospective chart review after genetic diagnosis revealed that he had an alkaline phosphatase (ALP) level at 35 Units/Liter (U/L) which was considered normal as the reference range of the lab test was 31-120 U/L in 2019. The patient also had a childhood history of severely weakened enamel, dental cavities, and renal stones. After the genetic diagnosis, he was referred for a bone density scan which revealed osteoporosis of the lumbar spine. On review of symptoms, he complained of diffuse musculoskeletal pain. Current investigations revealed a low alkaline phosphatase level of 32 (U/L) and high 24-urine calcium excretion. He was started on vitamin D3 supplements and hydrochlorothiazide which led to improvement in his 24-urine calcium excretion. As an adopted individual, no family history was available. Based on laboratory and clinical findings he qualified for starting therapy with Asfotase Alfa. Hypophosphatasia is a rare and highly heterogeneous disease condition with varied mutations in the ALPL gene resulting in multiple phenotypes. Numerous studies have studied the importance of diagnosing hypophosphatasia based on clinical features, laboratory testing, radiographic findings, and family history. Fragility fractures along with age and sex-adjusted serum total ALP levels are important clinical and laboratory features respectively, promptly leading to a clue in the diagnosis of adult hypophosphatasia. ALP levels should always be corrected to the age and sex of the patient and levels less than 40 U/L should prompt a workup for hypophosphatasia. The diagnosis of hypophosphatasia for our patient was delayed due to the absence of a history of fractures, a previously recorded normal ALP and an unknown family medical history. Diagnostic criteria have been formulated to help aid the diagnosis of hypophosphatasia in childhood and include various childhood clinical manifestations and laboratory features. Diagnosis can often be missed given the wide range of clinical features. This case underscores the importance of genetic screening in symptomatic children with frequent dental problems for identifying carriers of hypophosphatasia, especially in the case of an unknown family history. Timely diagnosis and management can help improve a patient’s quality of life.
Presentation: 6/2/2024
8106 An Uncommon Cause Of Hyperparathyroidism: A Case Report
Authors: Calderon Andres , Aguilera Maria C , Kansara Abhishek 
Published: October 2024

Abstract
Disclosure: A. Calderon: None. M.C. Aguilera: None. A. Kansara: None.
Introduction: Parathyroid adenomas are the most common cause of primary hyperparathyroidism. Imaging techniques to locate parathyroid adenomas and hyperplasia include U/S (Sensitivity: 72%-89%), Sestamibi Tc-99 (Sensitivity of 68-95%), and 4D CT scan (Sensitivity of 80%). Combined imaging modalities increase sensitivity to 95%. We describe a case of symptomatic primary hyperparathyroidism with rapid development of hypercalcemia, and conflicting imaging findings. The final diagnosis was made after surgery and pathology review. Case presentation: A 76-year-old man with a history of hypertension, Parkinson’s disease, and prostate cancer was admitted due to a calcium level of 13 mg/dL (8.0 - 10.2 mg/dl) on routine blood tests. He had complained of progressive fatigue and constipation, attributed to Parkinson’s Disease. Five months prior his calcium was 9.7 mg/dL. Hydrochlorothiazide was discontinued due to hypotension after two months. Blood tests in the hospital showed a corrected calcium of 12.5 mg/dL, phosphorus of 1.7 (2.4 - 4.5 mg/dl), PTH of 195 (15 - 65 pg/ml), with normal vitamin D and undetectable PTHrP. A U/S of the neck showed a 0.4 x 0.5 cm cystic mass in the right-inferior pole of the thyroid. A 4D CT scan of the neck showed a non-enhancing 0.9 x 7 x 1 mm mass in the same location, and a 7 x 4.7 x 4.8 mm mildly enhancing mass in the left lower pole of the thyroid. A parathyroid nuclear scan did not identify a parathyroid adenoma. He underwent minimally invasive parathyroidectomy and was found to have a 3.2 cm enlarged and cystic right inferior parathyroid gland weighing 792 mg. Frozen section showed hypercellular parathyroid with cystic and fibrotic changes. The PTH level dropped 59% after removal of the right cystic mass. The left inferior mass identified on CT scan was identified as normal thyroid tissue. Conclusions: Parathyroid cysts are uncommon neck masses and represent less than 5% of causes of all neck masses. They can be divided into functional and non-functional. Large retrospective studies have shown that about 5% of patients manifest as classic hyperparathyroidism, whereas the most common presentation was neck mass (40%). Identification of parathyroid cysts through imaging can be challenging. In our case, the patient presented with symptomatic and rapidly progressive primary hyperparathyroidism, and imaging findings that were discordant among ultrasound, 4DCT scan and Sestamibi Tc-99 scan. The final surgical and pathology reports identified a large parathyroid cyst. This case emphasizes the variable clinical and imaging behavior of parathyroid cysts, imposing a puzzling medical challenge.
Presentation: 6/3/2024
7293 An Unusual Case Of Adult-Onset Heterozygous HHRH In A Male With Normal Phosphorus And Severe Osteoporosis
Authors: El Najjar Mayssam , Sabet Amin , Willard Devina 
Published: October 2024

Abstract
Disclosure: M. El Najjar: None. A. Sabet: None. D. Willard: None.
Introduction: Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare genetic disorder characterized by renal phosphate wasting, which can affect bone metabolism. Although onset is typically in childhood, adult-onset forms have been described, and the manifestation depends on the zygosity of each patient. Most commonly, adults with HHRH demonstrate markedly reduced bone density and multiple fractures. Heterozygotes have milder presentations with mild hypophosphatemia, hypercalciuria, and nephrolithiasis, usually without bone disease; however, it is less well characterized. Case report: A 73-year-old man suffered an L1 vertebral compression fracture while playing golf. Bone mineral density testing revealed T-scores of -0.9 at the lumbar spine and -3.4 at the femoral neck (Z-score -2.6). He started alendronate 70 mg weekly for osteoporosis treatment. A year later, the patient sustained an L3 vertebral compression fracture while on treatment with no improvement in his bone density. His family history was remarkable for osteoporosis in his mother but no nephrolithiasis or hypercalcemia. Physical examination was unremarkable. Laboratory evaluation was notable for a 1,25-dihydroxyvitamin D of 87 pg/mL (18-72 pg/mL) , a 24-hour urine calcium of 240 mg/g Cr (30-210 mg/g),a serum PTH of 9 pg/mL (16-77 pg/ml) , but otherwise a normal serum calcium level of 9.4 mg/dL (8.6-10.3 mg/dL) and serum phosphate level of 2.2 mg/dl (2.1-4.3 mg/dl). Genetic testing revealed heterozygosity for SLC34A3 mutation, which is associated with HHRH. The patient discontinued alendronate and started 250 mg phosphorus supplementation 4 times daily. At 6 months follow up, he reported improvement in his body aches, and biochemical testing showed normalization of his 24-hour urine calcium to 171 mg/g Cr and serum PTH to 21 pg/mL. Repeat bone density scan after 1 year of phosphorus supplementation showed T-scores of -0.3 at the lumbar spine (5.8% increase) and -2.6 at the femoral neck (15.5% increase). Clinical Lesson: HHRH is an autosomal recessive hypophosphatemic rickets associated with mutations of the SLC34A3 sodium-phosphate cotransporter, where it is believed that selective phosphate wasting leads to increased calcitriol, in contrast to other forms of hypophosphatemic rickets, causing increased intestinal calcium absorption and resulting hypercalciuria. Adult-onset forms of HHRH have been described in heterozygous carriers of the SLC34A3 mutation and usually present with low to low-normal phosphate levels, hypercalciuria, and nephrolithiasis but without bone disease. However, clinical variations of heterozygous carriers have also been recognized, and therefore are likely underdiagnosed. Our patient’s serum phosphorus level was within the normal range, and hypophosphatemic rickets could have been missed if a more extensive laboratory evaluation had not been performed.
Presentation: 6/1/2024
12460 Bilateral Parietal Thinning: A Rare Condition Of Unclear Etiology
Authors: Madsen-Barbosa Thayse L , Cheikh Malek , Marcano Isabel 
Published: October 2024

Abstract
Disclosure: T.L. Madsen-Barbosa: None. M. Cheikh: None. I. Marcano: None.
Background: Bilateral parietal bone thinning (BPT) is an infrequent and often underdiagnosed condition characterized by the external thinning of the skull's parietal bone. The pathophysiology is unclear, but some studies suggest a link to osteoporosis. We present a case of osteoporosis diagnosed on evaluation of BPT. Case Description: A 77-year-old woman with a history of chronic kidney disease (CKD stage IV) and type 2 diabetes was referred to the Bone Health Clinic for evaluation of low bone density. She initially presented to Neurosurgery clinic for evaluation of head indentations. A dual energy x-ray absorptiometry (DEXA) scan showed values in osteopenia range (left total hip bone mineral density (BMD) 0.678 and T-score of -2.2, left femoral neck BMD 0.272 and T-score of -1.6, and left 33% radius BMD 0.577 and T-score of -2.0), leading to the referral. The patient reported painless indentations in the parietal bones that had been progressing for four years, with no history of head trauma, inflammatory disease, or prolonged steroid use. A head computed tomography (CT) scan showed symmetric thinning of the skull’s parietal bones, with an average thickness of 2.34 mm (compared to 5.1 mm four years earlier). Review of prior images also revealed a T11 compression fracture on spine X-ray from 2019. Laboratory tests showed elevated parathyroid hormone (PTH) 155 pg/mL (reference range 15-65 pg/mL), low vitamin D 25-OH 10.6 ng/mL (reference range 30-100 ng/mL), elevated alkaline phosphatase 142 units/L (reference range 46-116 units/L), and high creatinine level 2.7 mg/dL (reference range 0.5-0.8 mg/dL), other laboratory tests were normal. After discussion with the patient and Nephrology, Denosumab therapy along with Calcium and Vitamin D supplementation were started in November 2023. The patient continues the treatment with antiresorptive medication every 6 months and head CT scan to monitor the skull thinning changes. Discussion: BPT is rare, with only approximately 150 cases reported. Crucial aspects such as its etiology, pathophysiology, treatment, and prognosis remain unknown. It can result from various conditions like trauma, systemic mastocytosis, diabetes mellitus, hereditary diseases, or idiopathic causes and mainly affects women of advanced age. Osteoporosis is suggested as a possible cause based on histological findings on prior studies that propose BPT may result from osteoporosis-induced decreased bone formation rather than increased bone destruction. The reason for excessive bone resorption in the skull of osteoporotic patients remains unclear. Our case highlights progressive and symmetric BPT possibly related to systemic conditions like osteoporosis, with a focus on treatment options. Conclusion: This case sheds light on the clinical presentation, imaging findings, pathogenesis, and treatment options for the rare condition of bilateral parietal bone thinning.
Presentation: 6/3/2024