bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Testing in a Patient With Suspected Hyperparathyroidism- Jaw Tumor Syndrome (HPT-JT)
Authors: Kazi Fatima M , Sadiq Sobia 
Published: May 2021

Abstract
Introduction: Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare autosomal dominant disorder characterized by parathyroid tumors in association with fibro-osseous jaw tumors, uterine tumors and renal lesions. We present a case of suspected HPT-JT. Clinical Case: A 50-year-old female with suspected HPT-JT was referred for treatment of osteoporosis. Patient was initially diagnosed with osteosarcoma in 1980 at age 10, and underwent resection with leg amputation and chemotherapy. Around 1995, she was found to have primary hyperparathyroidism secondary to a parathyroid adenoma and underwent one gland parathyroidectomy. At age 30, she was then found to have multiple uterine tumors requiring hysterectomy. In 2017, she underwent CT abdomen for suspected appendicitis, which revealed multiple renal cysts and hepatic hemangiomas. In 2019, patient was found to have recurrent parathyroid adenoma and underwent revision parathyroidectomy. Pathology revealed hypercellular parathyroid gland consistent with adenoma. Based on constellation of symptoms, HPT-JS was suspected. Patient was referred to genetic counselor. Detailed family history revealed multiple family members affected by malignancies including melanoma, breast cancer, prostate cancer, liver cancer and two cousins with suspected MEN1. She underwent testing for hereditary hyperparathyroidism and melanoma including CDC73 gene. All genetic testing was surprisingly unrevealing. Discussion: CDC73 gene (also known as HRPT2 gene) is responsible for the pathogenesis of HPT-JT. While HPT-JT itself is a rare condition, 60% of patients affected by it, harbor the HRPT2 gene mutation. About 10–15% of these individuals are affected by parathyroid carcinoma. HRPT2 mutated parathyroid adenomas also seem to have some malignant potential. The autosomal dominant inheritance of HPT-JT makes gene testing important since it has implications for other family members and carries weight in clinical management of genetic carriers. Therefore patients with extensive personal or family history of malignancy should be followed closely. Endocrinologists should have a low threshold to refer such patients for genetic counseling and testing. However genetic testing also has its limitations and can only explain 50–75% of cases of HPT-JT syndrome. Hence, even though our patient has a negative genetic screen, the possibility of HPT-JT is not complete ruled out.
Hypercalcemia Due to Immobilization
Authors: Ahamed Irshad , Jauhar Niyati 
Published: May 2021

Abstract
Background: Hypercalcemia associated with immobilization is an infrequent diagnosis. It is usually associated with prolonged immobility due to traumatic brain injury or spinal cord injuries. It results from rapid bone turnover. Diagnosis requires workup to rule out other causes of hypercalcemia. Keywords: Hypercalcemia; immobilizationCASE REPORT: We report a case of a 49 year old woman with severe traumatic brain injury and paraplegia following an electric-scooter accident. She had an extended stay in hospital and was noted to be hypercalcemic after six months’ in-patient. Laboratory investigations showed increased calcium level at 3.34 mmol/l (ref. 2.15–2.50 mmol/l) with diminished parathyroid hormone (PTH) level of 0.2 pmol/l (ref. 1.6–6.9 pmol/l), low 25-hydroxyvitamin D at 26.7 ug/l (toxicity &gt;100 ug/l) and low 1,25-dihydroxyvitamin D at 13 pg/l (ref. 18–78 pg/l) with increased 24-H urinary calcium at 11.74 mmol/day (ref. 2.50 – 7.50 mmol/day). There was no clinical or biochemical evidence of other endocrinopathies such as hyperthyroidism or adrenal insufficiency. There was also no underlying malignancy to explain the hypercalcemia. In the context of recent prolonged immobility, a diagnosis of immobilisation hypercalcemia (IH) was made. The pathophysiology of IH is unclear. It is said that muscle activity transmits signal for bone formation through osteocytes and with immobility, mechanical stimulation is reduced, causing unopposed resorption. Another cause may be increased acidic environment due to low blood flow which impairs bone mineralization. There is also increased osteoclastic resorption, leading to loss of calcium from bones and hypercalciuria. Hypercalcemia occurs when calcium efflux from bone exceeds renal calcium excretion. For our patient, hydration therapy was initiated with no improvement in calcium. SC calcitonin was added and IV pamidronate given. Two weeks after treatment serum calcium improved to 2.38 mmol/L and remained normal on subsequent monitoring. Conclusion: IH is a known but uncommonly recognized complication in immobile patients. If not treated properly patients may develop typical complications of hypercalcemia including dehydration, confusion and renal impairment. Mobilization by using weight bearing exercises where possible is a cornerstone of long term management. In conclusion, our case serves as an important reminder of this differential and illustrates the management of IH.
Hypercalcemia in a Patient Treated With Abaloparatide
Authors: Sherpa Chheki , Shrestha Bishow Chandra , Nallala Deepika , Gabriely Ilan 
Published: May 2021

Abstract
Introduction: The antifracture efficacy of newer agents like PTHrP analogues is promising but knowledge about the mechanism of action and safety profile is needed in order to use these agents effectively. The reported incidence of hypercalcemia defined as albumin-adjusted serum calcium ≥10.7mg/dL was 3.4% in Abaloparitide. Case Presentation: A 59 year-old female with past medical history significant for diabetes mellitus type 2, hypothyroidism, necrotizing autoimmune myositis, osteoporosis and renal stones presented with complaints of generalized body aches and pains with swelling and redness of the left leg. The patient was diagnosed with osteoporosis based on atraumatic L4 compressive injury involving superior end plate. Her only DXA scan was 8 years ago which showed osteopenia, with the lowest T score of -1.2 at lumbar spine. Subsequent evaluation with DXA scan was unable to be performed due to physical disabilities. She was intolerant to oral bisphosphonates and was started on abaloparatide subcutaneous injections 2 weeks prior to her current admission. Her physical examination was positive for obesity, proximal muscle weakness and bilateral leg edema with bruises and left leg erythema. Laboratory findings showed hypercalcemia with corrected calcium levels of 12.48 mg/dl, suppressed intact PTH 4 pg/ml. Evaluations for secondary causes of hypercalcemia were negative. Her last dose of abaloparatide injection was the morning prior to her presentation to the emergency room. The patient was treated with IV fluids and her calcium level improved within 24 hours with normalization of intact PTH level in 72hrs. Abaloparatide injection was suspended on admission. Hypercalcemia with suppressed PTH was most likely secondary to abaloparatide given the timing of the hypercalcemia after the injection and resolution of hypercalcemia and normalization of PTH. Conclusions: Abaloparatide is a peptide that selectively binds to the RG conformation of the parathyroid hormone type 1 receptor. Abaloparatide is increasingly used following the results from the ACTIVE and ACTIVExtend trials which demonstrate significant increase in bone mineral density and risk reduction of vertebral, nonvertebral, clinical, and major osteoporotic fractures. Hypercalcemia was reported as a side effect, but there is no guidance on further evaluation or management of these patients. The incidence of hypercalcemia defined as albumin-adjusted serum calcium ≥10.7mg/dL is 3.4 % and risk is increased in patients with renal impairment. As in our case, transient hypercalcemia and PTH suppression may be associated with abaloparatide. Efficacy of abaloparatide and impact on bone density with delay or interrupted treatment are not available. Further studies are needed to guide monitoring and treatment of clinically symptomatic transient hypercalcemia in patients taking abaloparatide.
Hypercalcemia in Disseminated Coccidioidomycosis
Authors: Ryu Christina , Kirkeby Kjersti Meyer 
Published: May 2021

Abstract
Introduction: Hypercalcemia is associated with various granulomatous diseases, most commonly sarcoidosis and tuberculosis, less frequently fungal disease. We present a rare case of hypercalcemia associated with disseminated coccidioidomycosis.
Clinical Case: A 44-year-old man with ESRD s/p DDRT on immunosuppression presented with fever and cough. His physical exam was significant for tender scattered cutaneous nodules. His labs revealed non-PTH mediated hypercalcemia: calcium 12 mg/dL (normal 8.5–10.1 mg/dL), albumin 2.2 g/dL (normal 3.6–5.1 g/dL) and PTH 41 pg/mL (normal 14–72 pg/mL). Further hypercalcemia work-up was unremarkable: PTHrP 16 pg/mL (normal 14–27 pg/mL); 25-hydroxyvitamin D 33 ng/mL (normal 30–100 ng/mL); 1,25-hydroxyvitamin D 62 pg/mL (normal 20–79 pg/mL); serum electrophoresis was indeterminate; and immunofixation did not detect monoclonal proteins. His highest calcium level was 12.8 mg/dL with albumin 1.9 g/dL. He underwent additional tests that explained his presentation: sputum culture grew Coccidioides immitis; CT scan showed miliary pulmonary nodules, and bilateral deep cervical and mediastinal lymph node enlargement; lumbar puncture revealed elevated protein and cell counts; and a biopsy of a nodule on his thigh revealed Coccidioides immitis. He was treated with amphotericin for disseminated coccidioidomycosis with pulmonary, cutaneous and possible CSF involvement. He received IV fluids, furosemide and pamidronate for treatment of hypercalcemia. Based on his presentation, evaluation and complete resolution without recurrence of hypercalcemia after treatment of disseminated coccidioidomycosis, the most likely cause of hypercalcemia was disseminated coccidioidomycosis.
Hypercalcemia is associated with various granulomatous diseases. It is a rare complication of disseminated coccidioidomycosis that is important to recognize as Coccidioides is endemic in the United States. The pathology of the disease is pyogenic granuloma. In contrast to sarcoidosis, our case and previous case studies of hypercalcemia in coccidioidomycosis did not show an elevation of 1,25 dihydroxyvitamin D. Various potential inducers have been implicated including PTHrP, lipopolysaccharide, prostaglandin E, interleukin 1 and transforming growth factor β. It has been demonstrated that granulomas produce PTHrP; however, not all patients with granulomas develop hypercalcemia. One theory is that hypercalcemia may be a sequelae in cases with a greater number and extent of lesions making PTHrP as seen in disseminated disease.
Conclusion: Hypercalcemia is a rare complication of disseminated coccidioidomycosis that is important to recognize as coccidioidomycosis is endemic in the United States. The mechanism of hypercalcemia is poorly understood; in contrast to other granulomatous disease, it appears to be unrelated to 1,25-hydroxyvitamin D.
Hypercalcemia: A Metabolic Complication of an AIDS-Defining Illness
Authors: Bennett Dorothy E , Riachy Ruba , Blanton Lucas S , Belalcazar L Maria 
Published: May 2021

Abstract
Background: Hypercalcemia may result from the activation of macrophages in granulomatous diseases with increased production of 1,25 dihydroxyvitamin D/calcitriol. Its occurrence in patients with human immunodeficiency virus-1 (HIV-1) infection may be atypical and signal major changes in immune status. We report on a patient with acquired immunodeficiency syndrome (AIDS) presenting with new-onset hypercalcemia after months of treatment for mycobacterium avium complex (MAC) infection and normal calcitriol levels. Clinical Case: A 37-year-old man on treatment for HIV-1 and disseminated MAC infection presented to the hospital 6 months after initial diagnosis with worsening headache, cough, and abdominal pain. On arrival he was afebrile and without palpable lymphadenopathy. He was found to have a high serum calcium (13.4 mg/dL, n 8.6–10.6 mg/dL) and acute kidney injury (AKI) (creatinine 4 mg/dL, n 0.6–1.25 mg/dL). His CD4 count had increased from 24 at time of diagnosis to 162 cells/μL (n 410–1,590 cells/μL); his HIV viral load was undetectable. Workup for hypercalcemia revealed an elevated phosphorus (5.2 mg/dL, n 2.5–5.0 mg/dL), low 25-OH vitamin D level (&lt;13 ng/mL, n 25–80 ng/dL), low PTH (4.8 pg/mL, n 12–88 pg/mL), and calcitriol level of 31.4 pg/mL, n 19.9–73.3 pg/mL). Additional tests, including serum electrophoresis, thyroid stimulating hormone, and parathyroid hormone-related peptide levels, were unremarkable. The patient was diagnosed with hypercalcemia secondary to dysregulated calcitriol production in the setting of disseminated MAC and possible immune reconstitution. Hypercalcemia resolved with hydration and prednisone 20 mg daily. Patient was discharged with an 8-day prednisone taper, but readmitted to the hospital 3 weeks later with recurrent hypercalcemia (13.8 mg/dL) and AKI. Urine calcium was found to be elevated (484 mg/24 hours, n100-300 mg/24 hours) and repeat calcitriol was 53.6 pg/ml. Patient was restarted on prednisone 40 mg daily with normalization of calcium within 5 days (calcium 10.3 mg/dL). Conclusion: Hypercalcemia due to increased calcitriol production in the setting of MAC infection, an AIDS-defining illness, may occur months after initiation of effective antibiotic and antiviral therapy and could represent a manifestation of immune reconstitution. The deleterious effects of excess calcitriol may be present even in patients with chronic vitamin D deficiency and a calcitriol level that inappropriately remains within the normal range.
Hyperparathyroidism-Jaw Tumor Syndrome in a Patient With Colon Cancer: A Case Report
Authors: Alexandre Maria Inês , Marçalo José , Gomes Ana , Domingues Rita , Silva Ana Luisa , Bugalho Maria Joao 
Published: May 2021

Abstract
Background: Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare autosomal dominant disease, caused by mutations in the CDC73 gene, characterized by parathyroid tumors in association with fibro-osseous lesions of the mandible or maxilla. The occurrence of renal cysts or tumors, uterine and thyroid tumors has been reported. The association with other neoplastic lesions has been described, but its meaning and frequency are not well established. Clinical Case: A 48-year-old Roma woman was admitted to our hospital due to severe abdominal pain and constipation. She had a past history of kidney stones with several episodes of acute renal colic and had been recently diagnosed with colon cancer. Her family history was positive for colon cancer. Disease staging suggested the presence of liver metastases and multiple lytic lesions of the axial skeleton, pelvis and femurs. Laboratory investigation disclosed high calcium levels (15 mg/dL) and cancer associated hypercalcemia was suspected. However, PTH was markedly elevated (2979 pg/mL), in favor of a parathormone dependent cause. Further imaging procedures showed a heterogeneous mass, posterior to the right thyroid lobe and bone lesions on the left mandible, likely to correspond to brown tumors. Once the hypercalcemia was controlled, she was submitted to parathyroidectomy and right thyroid lobectomy plus sigmoidectomy and liver biopsy. The histology revealed an atypical parathyroid adenoma with 3,5 cm and papillary thyroid cancer with 1,2 cm, as well as colon adenocarcinoma metastatic to the liver. Postoperatively, the patient developed a hungry bone syndrome needing adequate treatment. Two months after surgery, the patient initiated chemotherapy for colon cancer. Screening for germline mutations in the CDC73 gene (formerly HRPT2) was positive for a deletion (c.765_766delTG/p.Val256LysX10). Conclusions: Hypercalcemia in a patient with malignant disease may be independent of malignancy. In the patient presented herein her past history of kidney stones and the involvement of the mandible were highly suggestive of HPT-JT. Missing the diagnosis would negatively impact in the patient′s prognosis and in the management of her family. Further clinical and genetic studies are ongoing trying to clarify whether the patient has two inherited conditions or a phenotype of HPT-JT including colon cancer.
Hypervitaminosis A: A Rare Cause of Hypercalcemia
Authors: Patel Chandani , Anbari Raghda Al , Lomonaco Mayra Romina 
Published: May 2021

Abstract
Introduction: Hypercalcemia is a rather common clinical problem and a majority of cases are found to be secondary to primary hyperparathyroidism and malignancy. A rare cause of hypercalcemia is associated with high levels of vitamin A and thought to be secondary to the effect of vitamin A on bone to stimulate osteoclastic resorption or inhibit osteoblastic formation. Clinical Case: A 54 year-old male with a past medical history of CKD stage 3 secondary to medullary sponge kidney presented for hypercalcemia. He complained of chronic constipation, joint pain, mood changes and recurrent kidney stones. Reported multivitamin use (including 1000mcg of vitamin A) for years but was discontinued one year prior to visit. Lab work showed calcium of 11.5 mg/dL (8.7–10.2mg/dL), albumin 4.9 g/dL (3.8–4.9g/dL), elevated 24h urine calcium, eGFR 40 mL/min/1.73, parathyroid hormone 5 pg/mL (15-65pg/mL,) normal 1,25-OH vit D and 25-OH vit D, PTHrP &lt;2.0 pmol/L, serum protein electrophoresis unremarkable. His vitamin A level was elevated to 103 ug/dL (20.1–62.0ug/dL). CT chest showed no findings concerning for sarcoidosis. Bone density scan showed normal bone mineral density. Patient diagnosed with hypercalcemia secondary to elevated vitamin A levels. Current limited literature shows stopping the vitamin A supplement will normalize vitamin A levels and correct the hypercalcemia. This patient had discontinued his multivitamin 1 year prior and vitamin A remained elevated, thought to be due to his poor kidney function. Treatment was targeted at improving his hypercalcemia and reducing his symptoms. He was prescribed a one-week course of prednisone 40 mg daily. His calcium level improved to 10.5 mg/dL. Prednisone was reduced to 20 mg daily with normalization of calcium to 10.3 mg/dL (8.7–10.2mg/dL). Conclusion: Hypercalcemia is a rare but known complication of vitamin D toxicity. The liver, kidney and adrenal glands store vitamin A and it is excreted in the urine. Liver and kidney disease pose higher risk of vitamin A toxicity. We present a unique case of Hypercalcemia secondary to elevated vitamin A levels in a patient with moderate chronic kidney disease who was not taking excessive amounts of vitamin A and whose calcium and vitamin A did not normalize once vitamin A supplements were discontinued. The CKD 3 may have reduced vitamin A clearance and increased its toxicity. Hypercalcemia is not the only concern regarding vitamin A toxicity, the increasing use of dietary supplements and over the counter medications may pose significant risks for osteoporosis and bone fractures. A high clinical suspicion and thorough workup to exclude other causes of hypercalcemia is warranted to diagnose hypervitaminosis A as the etiology. Steroids can reduce gastrointestinal absorption of calcium, however, its role in vitamin A toxicity remains unclear. Further research is needed to investigate the appropriate treatment for these patients.
Hypocalcemia in a 15 Year Old With New Onset Type 2 Diabetes Mellitus
Authors: Becerril Romero Carlos C , Aguirre Rebecca Schneider , Imel Erik Allen , DiMeglio Linda A , Gohil Anisha 
Published: May 2021

Abstract
Background: Diabetic ketoacidosis and significant hyperglycemia are associated with known electrolyte derangements in sodium, potassium, and phosphorus. Hypocalcemia and hypoparathyroidism occurring in uncontrolled diabetes are rare. We present a case of new-onset diabetes with severe hypocalcemia.
Case: A 15-year-old obese Caucasian male with ADHD and autism presented to the Emergency room due to hyperglycemia found on laboratory evaluation for hypertension. Serum glucose was 563 mg/dL, serum bicarbonate 24 meq/L (21 - 31 meq/L), and HgbA1C 11.4% (4.0 - 5.6%). He was admitted to initiate insulin and for diabetes education. On admission, hypocalcemia was noted: serum calcium 6.6 mg/dL (8.5 - 10.5 mg/dL), alkaline phosphatase 352 units/L (48 - 277 units/L), and albumin 4.6 g/dL (3.5 - 5.0 g/dL). Repeat testing revealed serum calcium 5.1 mg/dL, phosphorus 4.3 mg/dL (2.5 - 4.5 mg/dL), and magnesium 1.7 mg/dL (1.6 - 2.9 mg/dL). He endorsed a 2 month history of tetany, paresthesia, and muscle weakness. Due to food aversions, his dietary intake of calcium and vitamin D was minimal. He had limited sun exposure. Subsequent PTH was 40 pg/mL (10 - 65 pg/mL) with concurrent serum calcium of 6.5 mg/dL. QTc was prolonged [529 msec (&lt;440 msec)], prompting transfer to the intensive care unit for telemetry, intravenous calcium gluconate, and regular calcium monitoring. Treatment was commenced with cholecalciferol 2000 international units daily and oral calcium carbonate (50 mg elemental calcium/kg/day) in divided doses for presumed Vitamin D deficiency. After several intravenous calcium gluconate doses over 24 hours, the patient’s QTc and ionized calcium normalized. At discharge, calcium was 8.5 mg/dL. He was discharged on the above regimen of calcium and cholecalciferol, and basal and bolus insulin. After discharge, laboratory results returned indicating negative diabetes autoantibodies (GAD 65, Insulin, IA-2) and 25-OH Vitamin D &lt;10 ng/mL (30 - 100ng/mL). Two days after discharge, calcium was 7.3 mg/dL. Two weeks later, labs were: 25-OH Vitamin D 11.3 ng/mL, PTH 10.4 pg/mL, and calcium 9.6 mg/dL.
Conclusion: This teen presented with new-onset type 2 diabetes and symptomatic hypocalcemia, an atypical feature of new-onset diabetes. This patient’s hypocalcemia was likely due to both vitamin D deficiency and hypoparathyroidism. He had a low vitamin D level and poor calcium intake with elevated alkaline phosphatase; however, his high normal serum phosphorus and inappropriately normal PTH (instead of elevated in the setting of severe hypocalcemia) indicated a component of hypoparathyroidism. Calcium normalized with detectable 25-OH Vitamin D levels but PTH remained low. Our case highlights the importance of recognizing both that electrolyte abnormalities at diabetes onset may not be directly attributable to diabetes/hyperglycemia and that vitamin D deficiency and hypoparathyroidism may co-exist.