bluuebunny/crossref_metadata_2025_split huggingface dataset:
Iatrogenic Hypocalcemia With Treatment of Milk-Alkali Syndrome
Authors: Parikh Sharan D , Bhat Geetha K 
Published: May 2021

Abstract
Hypercalcemia is common disorder with the most likely etiology being primary hyperparathyroidism in the outpatient setting and malignancy in the hospitalized. With emergence of proton pump inhibitors and histamine blockers, milk-alkali syndrome has become a rarity. We report a unique case of hypercalcemia secondary to milk-alkali syndrome overtreated with bisphosphate therapy resulting in hypocalcemia.
A 77-year-old woman with a past medical history of hypertension, gastroesophageal reflux disease presented with slurring of speech for 2 days with nausea and vomiting. Labs showed a calcium of 15.4 mg/dL, with an albumin of 4.0 g/dL. Other pertinent labs showed an ionized calcium of greater than 7.3 mg/dL, pH of 7.49, PTH of 15 pg/mL, PTHrP of 9 pg/mL, vitamin D 25-OH of 16 ng/mL, TSH of 2.16 IU/mL and acute kidney injury. Patient was started on intravenous fluids and given both calcitonin and pamidronate on presentation by the admitting team. When seen in consultation, history revealed that patient was consuming more than eight calcium carbonate antacid tablets daily and was also on hydrochlorothiazide. The calcium level decreased to 8.7 mg/dL within 48 hours. There was a concern for potential hypocalcemia due to pamidronate. Patient was advised to restart calcium carbonate 500 mg twice daily upon discharge with close follow up. However, supplementation was not started and repeat calcium was 6.7 mg/dL twelve days later. The calcium normalized within a week after starting temporary calcium supplementation.
A now rare cause of hypercalcemia, milk-alkali syndrome is often overlooked in the differential diagnosis resulting in overtreatment and potentially dangerous hypocalcemia. Emergent management of intravenous hydration and bisphosphonate therapy is often immediately given by clinicians. Bisphosphonate therapy is not immediately effective and demonstrates calcium lowering effects by the second to fourth day. However, patients with milk-alkali syndrome generally improve with intravenous hydration and cessation of the causative agent. This case demonstrates the importance of obtaining a proper history with a complete list of medications and over the counter supplementations prior to treatment.
Lung Transplantation in a Patient With Osteogenesis Imperfecta and Osteoporosis
Authors: Fan Lena , Benvenuto Luke J , Nolan Margaret , DiMango Angela , Shane Elizabeth , Glorieux Francis H , Rubin Mishaela Ruth 
Published: May 2021

Abstract
Background:
Osteogenesis imperfecta (OI) and transplantation (TP) are independently associated with fractures. Yet reports regarding the skeletal effects of organ TP in OI are limited. We report the early skeletal outcomes in an OI patient with osteoporosis who underwent lung TP.
Clinical Case: A 35-year-old man with moderate/severe OI and severe bronchiectasis was admitted for progressive respiratory failure and expedited lung TP evaluation. OI was diagnosed at age 10 after sustaining a hairline coccyx fracture when falling off a stool; scoliosis was diagnosed at age 14; additional fractures included ankle (18 y), toes (28 y) and rib (34 y). He had dentogenesis imperfecta, but no hearing loss, easy bruising or OI family history. Bronchiectasis also began at age 10 and progressed, with multiple drug resistant infections and glucocorticoid (GC) treatments. At admission, he was on 6L oxygen and bed-bound from dyspnea. Notably, he had been rejected twice for TP because of his bone disease. Admission medications included calcium, D3, famotidine, inhaled fluticasone, tobramycin, and tiotropium bromide. His exam was notable for height 5’5”, BMI 16.5 kg/m2, kyphoscoliosis, blue sclera and joint laxity. Labs were notable for (mg/dl): serum calcium 9.4, magnesium 2.4, phosphate 4.4; albumin 4.2 g/dl, alkaline phosphatase 75 U/L, 25(OH)D 34 ng/ml, sCTX 535 pg/ml, urinary calcium 370 mg/24 hr. DXA showed T-scores of -4.7 (lumbar spine), -3.3 (femoral neck), -3.2 (total hip), -2.6 (1/3 radius). Endocrinology was consulted about the skeletal risk of lung transplantation.
Discussion and Follow-up:The patient’s manifestations of OI increased the risk of adverse skeletal outcomes. His high CTX suggested increased bone resorption, often seen with OI; bone formation was not directly measured but in OI is frequently reduced. Notably, his bronchiectasis was likely related to the OI: in addition to restrictive lung disease in OI, the abnormal type 1 collagen likely alters alveolar structure and elasticity. His risk for post-TP fractures was high given that the expected post-TP bone loss would likely be exacerbated by high dose GCs further increasing bone resorption and reducing presumed low bone formation. Nevertheless, because he had never sustained a major fracture even without OI treatment, the decision was made to proceed. He received zoledronate (ZOL) 5 mg IV and underwent an uncomplicated double lung transplant; initial high dose GCs were tapered to prednisone 10 mg/d. Three months later, he has steadily rising lung function, excellent functional status, and is working full time. A current sCTX of 73 pg/ml suggests that bone loss is not increased. Admittedly, the patient remains within the early high-risk fracture window. Yet this case is the first report to our knowledge which suggests that lung TP in an OI patient treated with ZOL did not lead to fracture in the early post-TP period.
Maxillary Brown Tumor as a Rare Complication of Hyperparathyroidism
Authors: Castellano Janet Colón , Ortega Nydia Ivette Burgos , Cordero Nicole Hernandez , Borrero Walter Morales , Nieves Yadiel Rivera , Santini Alberto Javier Grana , Canales Nicolle , Vick Margarita Ramirez , Santiago Milliette Alvarado , Rodriguez Loida Alejandra Gonzalez , Feliciano-Emanuelli Melba 
Published: May 2021

Abstract
Secondary hyperparathyroidism is a common complication of end stage renal disease (ESRD). The inherent impaired phosphorus and calcium metabolism result in altered bone metabolism, which rarely may manifest as osteitis fibrosa cystica with approximately 2% presenting as brown tumors. Brown tumors are areas of excessive bone resorption replaced by giant cells and fibrovascular tissue. Maxillofacial brown tumors are rare and result in increased patient morbidity due to associated nasal bleeding, diffuse pain and focal deformities. Nonetheless, these tumors are treatable and may regress following reduced parathyroid hormone (PTH) levels. Case of a 64-years-old Hispanic male with history of ESRD on hemodialysis for more than 20 years, secondary hyperparathyroidism with fragility fractures of femur status post parathyroidectomy on years 1999 and 2010, coronary artery disease and hypertension, who was consulted to our service for evaluation of a bleeding nasal septum mass suspected of a brown tumor. The patient presented to the emergency room with a massive spontaneous nasal bleeding which was subsequently controlled and evaluated by imaging. Maxillofacial CT scan without contrast showed an expansile soft tissue mass at the right maxillary sinus measuring 3.4 x 3.5 x 3.7 cm with innumerable, similar lesions distributed throughout the cranial, cervical and visualized portions of the shoulder girdle bones. Biochemical evaluation was remarkable for PTH levels 1,229 pg/ml (nl, 18.5 – 88.0 pg/ml), corrected serum calcium 9.0 mg/dl (nl, 8.3 – 10.6 mg/dl), alkaline phosphate levels 391 U/L (nl, 46 – 116 U/L), serum phosphoros 5.5 mg/dl (nl, 2.5 – 4.5 mg/dl), calciferol levels 32.2 ng/ml (nl, 30 – 100 ng/ml) and an estimated glomerular filtration rate at 21 ml/min/1.73 m2 (nl, &gt; 60 ml/min/1.73 m2). An excisional tissue biopsy showed osteoclastic-like multinucleated cells consistent with a brown tumor. These findings are consistent with secondary hyperparathyroidism complicated with osteitis fibrosa cystica. Following histologic diagnosis, a 99mTc-Sestamibi parathyroid scan showed two focal lesions of increased radiotracer uptake in the lower poles of the thyroid confirming parathyroid hyperplasia. Patient’s medical therapy was optimized by increasing cinacalcet dose and adding calcitriol, while continuing Sevelamer. Serum calcium, PTH, and phosphorous levels were closely monitored. Finally, patient was referred for parathyroidectomy. Patients with ESRD are at high risk of developing secondary hyperparathyroidism. Even with prior parathyroidectomy, these patients can develop disease recurrence. Early recognition and management of secondary hyperparathyroidism is crucial to decrease disease complications such as Brown tumors.
Neuroendocrine Tumor Associated Severe Hypercalcemia of Pregnancy
Authors: Deshmukh Shilpa , Coyne Christopher 
Published: May 2021

Abstract
Background: Literature of pregnancy associated neuroendocrine tumors is limited. We report an unusual case of severe hypercalcemia of pregnancy secondary to a neuroendocrine tumor. Clinical Case: A 43-year-old lady presented to our center in her 28th week of pregnancy with complaints of worsening nausea and epigastric pain over few days. She had developed gestational diabetes at 24 weeks for which she was taking insulin. On examination she was tachycardic, mildly confused with a distended abdomen. Serum chemistries revealed serum calcium of 15.9 mg/dL, elevated PTHrP of 64 pg/mL and low PTH of 2 pg/mL consistent with PTHrP mediated hypercalcemia. She had low 25-OH- vitamin D (15 ng/mL) with normal 1–25- OH vitamin D. An abdominal ultrasound showed a solid, heterogenous, soft tissue mass interposed between the left kidney and spleen measuring 11 x 9 x 12 cm. This was confirmed on Abdominal MRI, which also showed multiple large hepatic metastasis. Tumor biopsy with pathology confirmed well differentiated neuroendocrine tumor of gastric or pancreatic origin. Her hypercalcemia was initially treated with infusions of IV normal saline, furosemide diuresis, calcitonin 200 units SC 12 hourly and a single dose of dexamethasone 10 mg IV. Calcitonin and diuresis were discontinued after 5 days once calcium improved to 10 mg/dL. Oncology deferred treatment of the tumor until she had delivered. Patient was discharged with serum calcium of 10.7 mg/dL and counselled for plenty of oral hydration. She was readmitted with nausea, vomiting and serum calcium level of 15.1 mg/dL at 32 weeks gestation. She was again treated with a similar regimen of IV saline and furosemide along with calcitonin 480 units SC 12 hourly and prednisone 10 mg daily, but calcium levels remained high (13.6 mg/dL) despite aggressive treatment. Labor was induced at 33 weeks and she delivered a healthy boy through an uncomplicated vaginal delivery. Remarkably, her serum calcium normalized on day two post-partum and remained so throughout. Her serum calcium remains normal at 2 months post-partum (10.3 mg/dL, PTHrP 36 pg/mL, PTH 7 pg/mL) despite the presence of unresected tumor. She is planned to undergo surgical resection of the tumor and hepatic metastatic lesions. Conclusion: Clinicians must be aware that severe hypercalcemia may be the presenting manifestation of neuroendocrine tumors in pregnancy. In this case, we hypothesize a potential placental contribution to her elevated PThrP given resolution of hypercalcemia post-delivery. However, persistent elevated PThrP post-partum may also be physiologic or related to the abdominal tumor. A placental histopathological could be performed due to logistic reasons.
Rebound-Associated Vertebral Fractures Two Months After a Missed Dose of Denosumab
Authors: Caseja Ahl Jeffrey , Abdullah Najwa , Nakhle Samer 
Published: May 2021

Abstract
Introduction:
Denosumab, an anti-resorptive medication approved for treatment of osteoporosis, increases bone mineral density and reduces fracture risk. Discontinuation of treatment is associated with bone turnover rebound and reduced bone mineral density. We report a case of a woman without prior history of fragility fractures who presented with multiple spontaneous vertebral fractures two months after a missed dose of Denosumab, which is earlier than current available literature.
Clinical Case: A 54-year old female was diagnosed with osteoporosis at the age of 50 with a DXA revealing T-scores of LS -2.9 SD, LFN -0.6 SD, TH -0.5 SD. Ten-year probability of MOF evaluated by FRAX was 6%. Work-up for secondary causes of osteoporosis during the time was unremarkable. She was started on Denosumab 60 mg every 6 months from July 2016 to July 2019, receiving a total of 5 injections. She had missed her dose of Denosumab in January 2020. Two months after the missed dose, she presented to a local hospital with complaints of chest and epigastric pain. A CTA was performed as part of evaluation which was unremarkable aside from an incidental finding of thoracic compression fractures. An MRI of the spine was subsequently done which showed a recent-appearing moderate to severe wedge compression fracture and edema of the T7 and T6 vertebral bodies, and of the upper two-thirds of the T4.
A biological and radiological work-up to exclude other causes of osteoporosis to explain the patient’s vertebral fractures was performed. The patient did not have renal failure, vitamin D deficiency, hyperthyroidism, primary hyperparathyroidism, Cushing’s disease, hypophosphatemia, multiple myeloma, Celiac disease, diabetes mellitus, or prior glucocorticoid treatment. During the time of treatment and discontinuation of Denosumab, the patient was on adequate supplementation of calcium and Vitamin D. The patient’s vertebral fractures were treated with kyphoplasty. To treat osteoporosis and prevent further risk of fractures, she was started on an anabolic agent Abaloparatide.
Conclusion: This case demonstrates rebound vertebral fractures occurring very shortly after discontinuing Denosumab in a relatively young woman with low probability of major osteoporotic fracture. Further investigation must be done to determine pathophysiological process involved of vertebral fractures and treatment regimen after sudden discontinuation of Denosumab.
Severe Hypercalcemia as Rare Manifestation of Acute Lymphoblastic Leukemia in Adolescent
Authors: Fatya Atikah Isna , Annisa Firda , Tahapary Dicky L , Purnamasari Dyah , Yunir Em , Harbuwono Dante Saksono 
Published: May 2021

Abstract
Background: Hypercalcemia is a rare manifestation of acute lymphoblastic leukemia (ALL). Several studies reported that severe hypercalcemia is very uncommon in pediatric ALL, but there is no report regarding ALL in adolescence and young adult (AYA) which comprises distinct entity with diverse prognosis.
Clinical Case: A 18-year-old male presented with prolonged fever, general weakness, fatigue, pale and decrease of body weight for 3 months. He also complained visual disturbances which progressively worsened for 1 month. On admission, systemic examination showed that he was alert, had tachycardia, proptosis of both eyes and splenomegaly. There was neither lymphadenopathy nor thyroid/parathyroid abnormality. Initial laboratory investigation revealed pancytopenia (hemoglobin of 6.8 g/dl, hematocrit of 19.1%, white blood cell count of 3.8 x 109/L with platelets of 58 x 109/L and no blast). There was severe hypercalcemia of 18 mg/dL, hypomagnesemia 1.14 mg/dL, with normal phosphorus level. His serum creatinine level slightly increased to 1.3 mg/dL with filtration rate of 79 ml/min/1.73 m2. Bone marrow evaluation showed blast cells infiltration, consistent with ALL type L3. Leukemia phenotyping revealed B cell-lineage with aberrant exp CD5. CT scan orbita and brain showed bilateral retrobulbar mass and diffuse lytic lesion in skeletal bones due to leukemic cells infiltration. Patient was treated with supplemental oxygen, hydration targeting natriuresis, loop diuretic and steroid. The serum calcium level remained high, thus bisphosphonate was given. There was progressive decline of serum calcium level after therapy. The patient is then prepared to start chemotherapy.
Discussion: Hypercalcemia is associated with both PTH or PTH-independent mechanism, including malignancy. It complicates 5–20% of malignancy, but only 0.6–4.8% reported in leukemia. Hypercalcemia in malignancy may present due to: (1) direct invasion of cancer cells to bone and (2) secretion of humoral PTH-related peptide (PTHrP) which mimics PTH. Severe hypercalcemia without inadequate treatment is fatal. Initial treatment of hypercalcemia includes hydration, loop diuretic, calcitonin and bisphosphonate targeting decline of serum calcium level of 3–9 mg/dL in 24–48 hours. The main treatment of leukemia-related hypercalcemia is chemotherapy. Several cases of pediatric ALL reported normocalcemia after starting induction phase of chemotherapy and exerted good prognosis.
Conclusion: Hypercalcemia should be investigated in leukemia patients and vice versa. The main aim of therapy is to normalize the serum calcium level and treat underlying causes. In adolescent ALL, adequate treatment of hypercalcemia helps achieving better outcome.
Single Dose of Denosumab Effective for Management of Bisphosphonate-Refractory Hypercalcemia of Malignancy Related to Non-Small Cell Lung Cancer
Authors: Dinh Kathryn , Narla Radhika Rao 
Published: May 2021

Abstract
Background: First line therapy for hypercalcemia of malignancy (HCM) includes cancer directed treatment and bisphosphonate therapy. Denosumab is effective in bisphosphonate-refractory HCM (BR-HCM), approved for treatment with dosing schedule at 1, 8, 15, and 29 days and then monthly.
Clinical Case: We present the case of a 64 year-old man with Stage IIIA squamous cell lung carcinoma diagnosed 5/2019 with corrected serum calcium (CSC) of 11.2 mg/dL (8.4–10.2) at presentation. Prior to treatment, he developed symptomatic CSC 14.0 mg/dL, treated with IV pamidronate 90mg and IV fluids (IVF) 6/28/2019 with improvement to CSC 9.7 mg/dL. Hypercalcemia recurred 8/2019 while undergoing radiation therapy with CSC 14.7 mg/dL, phosphorus 2.5 mg/dL (2.7–4.5), PTH 7 pg/mL (15–65), PTHrP 2.2 pmol/L (&lt;2.0), 25-OH vitamin D 30.16 ng/mL (30–100), and 1,25-OH2 vitamin D 98.7 pg/mL (19.9–79.3). He was treated with IVF and 4mg zoledronic acid (ZA) on 8/20 and 8/29/2019. CSC normalized 9/30/2019 and he subsequently received three cycles of pembrolizumab 11/25/2019 to 1/6/2020, discontinued for associated pneumonitis He again developed HCM 6/5/2020 with CSC 12.6 mg/dL. He was treated with ZA 4mg on 6/16 and 6/29/2020 with persistent, symptomatic hypercalcemia to 13.7 mg/dL 7/9/2020 with ongoing confusion, constipation, and lethargy. Endocrinology was consulted 7/9/2020 and initiated IVF, calcitonin SQ 4U/kg q12h for 48 hours, and prednisone 30mg daily for 5 days. Chemotherapy was initiated 7/14/2020. CSC remained stable &lt;11.5 mg/dL until 8/3/2020 with recurrent calcium to 13.0 mg/dL despite cancer-directed therapy. He was then given 120mg SQ denosumab on 8/7/2020. CSC improved to 10.6 mg/dL on 8/11/2020 and has remained &lt;11 mg/dL at 70 days after a single dose of denosumab.
Conclusion: Denosumab was approved for BR-HCM with a complex treatment schedule based on a single-arm study of 33 patients, of whom 39% had treatment-related adverse events.1 We present a case of successful management of BR-HCM with a single dose of 120mg denosumab with CSC &lt;11.5 mg/dL at day 4 after treatment and persistent control of calcium at day 70 without further treatment. Further investigation is warranted to determine the most effective treatment schedule of denosumab for BR-HCM to reduce adverse events including hypocalcemia and overtreatment.
References:
1. Hu MI, Glezerman IG, Leboulleux S, et al. Denosumab for treatment of hypercalcemia of malignancy. J Clin Endocrinol Metab. 2014 Sep;99(9):3144–52
An Observational Study to Assess the Safety and Efficacy on Quality of Life and Patient Satisfaction With Raloxifene/Cholecalciferol Combination Therapy in Postmenopausal Women Requiring Prevention or Treatment for Osteoporosis
Authors: Chung Yoon-Sok , Lee Dong-Yun 
Published: May 2021

Abstract
Background: Preventing bone loss is an important concern for women during post-menopausal period. Menopause significantly speeds bone loss and increases the risk for osteoporosis. The aim of this study was to investigate the effectiveness on quality of life (QOL), patient satisfaction in postmenopausal women receiving raloxifene/cholecalciferol combination therapy. In addition, we analyzed adverse events to assess the safety profile of this drug. Methods: This study is a multicenter, prospective, non-interventional observational study of women receiving raloxifene/cholecalciferol (raloxifene 60 mg + cholecalciferol 800 IU, Rabone D®, Hanmi Pharma, South Korea) combination therapy to treat or prevent postmenopausal osteoporosis. Data have been collected from patients receiving routine clinical practice at 99 hospitals (local clinics and general hospitals) in South Korea. Patients were followed for more than 6 months to evaluate changes in, and QOL (EQ-5D-5L), patient satisfaction with efficacy and convenience (questionnaire), and safety. This study has been approved by Institutional Review Board and is in compliance with clinical research ethics regulations. Results: A total of 3,907 subjects with an average age of 67.68 ± 9.34 (Mean ± SD) were enrolled from November 2017 to July 2020. QOL was significantly improved from 0.77 ± 0.15 to 0.80 ± 0.12, 0.82 ± 0.11 (3 months, 6 months, respectively) after raloxifene/cholecalciferol therapy (p&lt;0.001). Compared to prior drug regimens of all types (bisphosphonates, bisphosphonates with vitamin D, selective estrogen receptor modulators, etc.), QOL after raloxifene/cholecalciferol treatment was significantly improved (p&lt;0.001). Patient satisfaction of efficacy was significantly increased from 37.25% to 67.70% over 6 months (p&lt;0.0001), and patient satisfaction of convenience was significantly increased from 42.75% to 74.07% (p&lt;0.0001). Serious adverse drug reaction (ADR) did not occur. Hot flush as ADR occurred in 12 subjects (0.30%), lower than Caucasian but similar with previous reports in Asians. Conclusion: In postmenopausal women, combination therapy with raloxifene/cholecalciferol significantly improved quality of life, and patient satisfaction with no serious adverse events. This drug regimen has been proven to be suitable therapy for postmenopausal women with osteoporosis in a real-world clinical setting.
References: Kim et al., Expert Opin Drug Safety 2019; 18: 1001–8. Takeuchi et al., Menopause 2015; 22: 1134–7. Xu et al., Osteoporos Int 2011; 22: 559–65.