bluuebunny/crossref_metadata_2025_split huggingface dataset:
Post-Traumatic Heterotopic Ossification With Incidental Hyperparathyroidism
Authors: Wootton Elizabeth , Balcerek Matthew , Lazarus Syndia , Duncan Emma L 
Published: May 2021

Abstract
Background: Heterotopic ossification (HO) is a rare disease characterised by abnormal bone growth in non-osseous tissues, causing pain, immobility and impaired quality of life. Although still being elucidated, the underlying pathophysiology may relate to local macrophage-driven inflammation in response to trauma1.
Case: A 35-year-old man involved in a motor vehicle accident (MVA) fractured over twenty bones (multiple vertebrae, ribs and complex open book pelvic fracture with shattered left acetabulum) with extensive soft tissue injuries requiring multiple surgeries. Past medical history included a renal calculus three years earlier. His serum corrected calcium on admission was elevated at 2.87mmol/L (2.10-2.60mmol/L). Peri-operative fluid over-resuscitation necessitated boluses of intravenous furosemide, and serum calcium transiently normalised before rapidly incrementing and peaking at 3.04 mmol/L. Serum parathyroid hormone post-operatively was inappropriately high at 9.4pmol/L (1.0–7.0pmol/L) and 25-hydroxyvitamin D low at 24nmol/L (50-150nmol/L). Oral vitamin D replacement was commenced and he received intravenous pamidronate (3x60mg infusions) which briefly restored normocalcaemia. Neck ultrasound and sestamibi scintigraphy demonstrated a left parathyroid adenoma, and he underwent parathyroidectomy. Histology revealed a single parathyroid adenoma. He has been normocalcaemic since surgery. Despite excellent overall recovery, mobility at the left hip remained restricted in all planes of movement. He could not perform simple activities such as putting on his shoe. Plain radiographs showed HO lateral to the left acetabulum, femoral head and neck, with bony bridging to the left ilium on computed tomography. Bone turnover markers (BTMs) measured eleven months post-MVA (and pamidronate) were elevated, with CTX of 750ng/L (100-600ng/L) and P1NP of 207ug/L (15-80ug/L). BTMs gradually reduced over time, plateauing two years post-MVA (CTX 480ng/L and P1NP 103ug/L). Surgery with pre-operative radiotherapy to remove the left hip HO is now planned.
Discussion: This man had multiple recognised risk factors for HO, including male sex, trauma followed by immobilisation and pelvic fracture. His hyperparathyroidism may have predisposed HO development through excess calcium-phosphate product promoting soft tissue calcification. Bisphosphonates may also increase the risk2. Elevated BTMs have been demonstrated in the early phase of HO; further research may elucidate whether BTMs can guide timing of surgical intervention relative to the pathophysiological processes driving HO.
References:
1 Meyers C et al. Heterotopic Ossification: A Comprehensive Review. JBMR Plus 2019, 3: e10172
2 Genêt F et al. Neurological heterotopic ossification following spinal cord injury is triggered by macrophage-mediated inflammation in muscle 2015. J Pathol. 236(2):229–40
Prednisone-Responsive Hypercalcemia in a Patient With IgG4 Disease and Elevated Serum PTHrP Levels
Authors: Cohen Melissa , Sanchez Julienne , Toft Daniel Joseph , Eisenberg Yuval , Kukreja Subhash C 
Published: May 2021

Abstract
Background: Ninety percent of hypercalcemia cases are related to either primary hyperparathyroidism or malignancy (1). This case presents one of the atypical etiologies of hypercalcemia.
Clinical Case: A 53-year-old man with past medical history of nephrectomy was admitted for acute respiratory distress syndrome secondary to SARS-CoV-2. Hospital stay was complicated by septic shock and acute kidney injury requiring hemodialysis. Three months post hospital admission, the patient developed non-parathyroid (PTH) mediated hypercalcemia. Lab work results showed elevated serum calcium of 12.7 mg/dl (8.6–10.6), ionized calcium 6.8 mg/dl (4.2–5.4), albumin 2.6 g/dl (3.4–5.4), serum creatinine of 3.5 mg/dl (0.5–1.5), eGFR of 18.4 ml/min, and a PTH of 4 pg/ml (12–88). Liver profile - total bilirubin of 10.5 mg/dl (0–1.2), direct bilirubin of 5.9 mg/dl (0–0.2), GGTP 2055 U/L (6–60), alkaline phosphatase of 936 u/L (40–125), bone fractionated alkaline phosphatase 216 u/L (0–55), 25-OH Vitamin D of 11 ng/nl (20–80), 1,25 OH vitamin D of &lt;5 pg/ml (19–79), TSH of 3.56 mciu/mL (0.35–4.0), CPK of 20 u/L (21–232) and a normal SPEP and immune-electrophoresisTreatment for hypercalcemia was initiated with calcitonin and oral steroids (prednisone 40mg/day for 4 days, 20mg/day for 1 day, and 10mg/day for 2 days), resulting in normalization of serum calcium. Patient received tube feedings that contained 2192 mcg retinol activity equivalents of vitamin A daily, which is associated with vitamin A intoxication in the presence of renal insufficiency. Vitamin A returned 0.78 mg/L (0.3–1.2). Serum Parathyroid hormone-related peptide (PTHrP) was elevated at 12.4 pmol/L (0.0–2.0). There was no obvious malignancy on various imaging studies. A magnetic resonance cholangiopancreatography (MRCP) showed biliary stricturing suggestive of primary sclerosing cholangitis (PSC), however, liver biopsy was not consistent with PSC. Serum IgG4 level was found to be elevated to 142 mg/dl (range: 1–123) which raised suspicion for autoimmune cholangiopathy.
Discussion: Patient presented with non-PTH mediated hypercalcemia with low serum 1,25 OHD levels and elevated serum PTHrP level. Although most cases of elevated PTHrP associated with hypercalcemia are due to solid tumors, increased PTHrP levels have been seen in hypercalcemic patients with hematological malignancies and rare benign causes such as pneumonia (5). Association of elevated hypercalcemia with elevated IgG4 levels and PTHrP levels has not been previously reported. MRCP findings and abnormal morphology detailed in liver biopsy are suggestive of IgG4-related disease (IgG4RD) (3). The responsiveness in hypercalcemia to prednisone also supports this diagnosis. IgG4RD is associated with multi-organ autoimmune involvement. This case report highlights another complication of IgG4RD (i.e. hypercalcemia) associated with elevated PTHrP levels.
Rare Case of Severe Hypocalcemia Due to PTH Resistance Related to Diet Pill
Authors: Katkar Rujuta Baban , Madam Narasa 
Published: May 2021

Abstract
Introduction: The production of parathyroid hormone (PTH) is essential for calcium the maintenance of normal mineral metabolism. Parathyroid cells have cell-surface calciumsensing receptors, even small changes in extracellular Ca induce rapid changes in PTH secretion. Hypocalcaemia is a well-recognized manifestation of magnesium deficiency. We present rare case of severe hypocalcemia due to PTH resistance caused by hypomagnesemia related to diet pill. Case Report: 61 year old Hispanic obese female with chronic gastritis on omeprazole 20 mg daily, no other significant past medical and surgical history, not taking any prescribed medications presents to ED with complaints of tingling and numbness around the mouth, abdominal cramps, chest pain, shortness of breath and anxiety. On arrival calcium was found to be 6.0mg/dl(8.2–10.2mg/dl) with ionized calcium of 0.60mmol/l(1.13-1.32mmol/l) and EGFR&gt;90ml/min, Albumin-4.0g/l, Magnesium-1.1mg/dl(1.6–2.3mg/dl), Phosphorus-6.1mg/dl(2.4–4.5mg/dl),rest of the electrolytes were normal. Patient was given IV calcium gluconate 2g and magnesium which helped improving her symptoms. PTH was 1700pg/ml(23-73pg/ml), low Vitamin D 25-hydroxy 20ng/dl(30-100ng/dl). Urinary calcium was &lt;1mg/dl(2.0–17.5mg/dl). Vitamin D1,25- dihydroxy 34pg/ml(18-78pg/ml), PTH-like peptide levels 0.6pmol/l(&lt;4.2pmol/l). EKG was normal no QT interval changes. For 4 weekspatient was taking weight loss medication was given to her by her brother called nucific-bio-x4. Patient had lost 4 pounds while taking the medication and had suppression of appetite. Physical features of pseudohypoparathyroidism were not seen. Patient had poor dietary intake of calcium, denied taking vitamin D supplements. Patient was given calcium acetate 2001 mg TID with meals, calcitriol 0.5mcg daily and calcium gluconate 2g IV intermittently was given. That improved her calcium levels to 6.8mg/dl with ionized calcium-0.90mmol/l. Magnesium was replaced IV and discharged on magnesium oxide 400mg BID to maintain magnesium the normal range. The patient was given loading dose of ergocalciferol 50,000 IUfor 8 weeks. At the time of discharge repeat PTH levels were 1600 pg/ml and calcium levels were 8.2mg/dl. 3D CT of the neck did not parathyroid mass. After discharge patient continued on oral calcium and magnesium to maintain calcium levels between 8.4–10.2mg/dl. After discharge calcium levels were 8.6mg/dl, vitamin D 25-hydroxy levels were 32ng/dl and maintenance dose of vitamin D3 2000 IU daily also continued. Nucific-bio-x4 pill was discontinued. Conclusion: In conclusion, severe life threatening hypocalcemia can occur with unsupervised weight lossmedications due to malabsorption of magnesium in patient with likely mutation in magnesium receptors causing PTH resistance. Vitamin D deficiency worsens hypocalcemia resulting into secondary hyperparathyroidism.
Severe Hypocalcemia and Vitamin D Deficiency in Adolescence - A Case Series
Authors: Rothstein Rachel , Allen Natalie 
Published: May 2021

Abstract
Background: Hypocalcemia due to vitamin D (vit D) deficiency is uncommon among adolescents in the US. Only 3% to 6% of those ages 12- to 19-years-old have a vit D level &lt;12 ng/ml.1 We present three cases of severe hypocalcemia secondary to vit D deficiency in non-obese adolescents with restricted diets and limited sun exposure.
Clinical Cases: A 14-year-old Ethiopian male with history of absence seizures presented with bloody stool. Incidentally, labs revealed: Ca 5.6 (8.4–10.2) mg/dL, iCal 0.71 (1.2–1.38) mmol/L, PTH 295.1 (10.0–65.0) pg/mL, 25(OH)D &lt;4 (20–100) ng/mL, Mg 1.9 (1.7–2.2) mg/dL, PO4 3.8 (2.5–4.5) mg/dL. He endorsed weight loss and knee pain, but denied paresthesias, tetany and seizures. He was a vegetarian and had minimal sun exposure. EKG and femur X-ray were unremarkable. He was started on IV calcium gluconate initially. Oral calcium carbonate and cholecalciferol were started on days three and four. He was discharged on day ten with iCal 0.84 on oral calcium carbonate and calcitriol.
A 16-year-old male with history of autism, ADHD and bipolar disorder presented with a seizure. Labs revealed: Ca 5.7, iCal 0.62, PTH 372, 25(OH)D &lt;4, Mg 1.9, PO4 3.5. Exam showed tetany, carpopedal spasms and positive Trousseau and Chvostek signs. EKG revealed prolonged QTc of 480 (&lt;450) ms. He had a restricted diet and minimal sun exposure. His mother described his gait as “waddling” for the past two years. X-ray revealed bilateral femoral head fractures and evidence of rickets. He underwent bilateral surgical repair. He was started on IV calcium gluconate initially. Oral calcium carbonate and cholecalciferol were started on days two and four. He was discharged on day 14 with iCal 1.01 on oral calcium carbonate and cholecalciferol.
A 16-year-old male with history of severe food allergies and restricted diet presented with a seizure. He visited urgent care three months prior for perioral tingling, muscle cramps and chest pain. He started a multivitamin for “low Ca” and “prolonged QTc.” The ED labs revealed: Ca 4.8, PTH 414.8, 25(OH)D 11, Mg 1.9, PO4 5.0, Alk Phos 539 (44–147) IU/L. Exam showed upper extremity twitching and QTc was 543 ms. He received 2 g calcium gluconate IV, then began oral calcium carbonate and cholecalciferol and continued supplementation following discharge on day six.
Conclusions: Vit D deficiency among adolescents is re-emerging, likely due to decreasing sun exposure, unbalanced diets and increasing obesity.2 Adolescents with restricted diets due to allergy or behavioral disorders may be at higher risk of vit D deficiency. Increased screening of high-risk adolescents may lead to early identification of cases.
References: 1) Palacios, C., et al. Is vitamin D deficiency a major global public health problem? J Steroid Biochem Mol Biol. 2013;144PA;138-145 2) Antonucci, R., et al. Vitamin D deficiency in childhood: old lessons and current challenges. J Pediatr Endocrinol Metab. 2018;31(3);247–260.
Short-Term Treatment With Teriparatide Restores Independent Ambulation in a Patient With Glucocorticoid-Induced Osteonecrosis of the Knees and Ankles
Authors: Chen Xin , Mimoto Mizuho 
Published: May 2021

Abstract
Teriparatide is a well-established treatment for osteoporosis. It is emerging as a promising treatment for osteonecrosis of the jaw and may be superior to alendronate for treating glucocorticoid-induced osteonecrosis of the femoral head and reduce collapse progression. However, few studies have investigated its efficacy in treating steroid-induced osteonecrosis affecting other sites such as the knee and ankle. Osteonecrosis treatment at these sites in early stages is limited to protected weight bearing and pain management. Surgical management is required for advanced stages. This case describes an unusual presentation of steroid-induced osteonecrosis in the bilateral lower extremities and illustrates the potential benefit of teriparatide as an alternative to surgery in managing this debilitating condition. A 25-year-old male with a history of a heart transplant for viral myocarditis was admitted to the hospital for severe bilateral lower extremity pain. His post-transplant course was complicated by giant cell myocarditis, treated with a prednisone taper from 80 mg to 7.5 mg daily over the course of one year. MRI showed diffuse osteonecrosis in the distal femora, medial femoral condyles, bilateral proximal tibias, left distal tibia, and bilateral ankles. A bone density test showed only mildly low bone mass with Z-scores of -0.8 at the right femur, -1.3 at the left femur and -1.3 at the lumbar spine. Due to progressive osteonecrosis on imaging and a decline in functional status over the next two months, following a discussion of risks, benefits and alternatives, he was started on daily teriparatide injections. Prior to therapy, he was using a walker and had difficulty ambulating more than a few feet. Within a month of teriparatide initiation, he reported improvement in both pain and mobility, and was able to walk independently into clinic. MRI two months later demonstrated no new lesions and significant improvement in previously necrotic areas. Our case highlights the importance of considering osteonecrosis at atypical locations in patients on chronic glucocorticoid therapy. It also demonstrates a promising role for teriparatide in treating steroid-induced osteonecrosis atypical sites and without concurrent osteoporosis.
Successful Parathyroidectomy May Not Resolve Hypercalciuria in Patients With Primary Hyperparathyroidism
Authors: Izkhakov Neriy , Prasad Heranmaye , Vernetti Nicholas John , Nakhle Samer 
Published: May 2021

Abstract
Background: Hypercalciuria, with twenty-four-hour urinary calcium of &gt;400 mg/day, is one of the indications for parathyroidectomy in patients with primary hyperparathyroidism. We report five cases where hypercalciuria is not resolved following a successful parathyroidectomy (normalization of serum calcium) in such patients. Here resolution of hypercalciuria is defined as twenty-four-hour urinary calcium of less than 200 mg/day. Clinical Case: This is a case series of five patients who remained hypercalciuric at 6 to 19 months after successful parathyroidectomy. Pre-parathyroidectomy, average PTH was 95 pg/dL (Min 69 pg/dL, Max 120 pg/dL), average serum calcium was 11.0 mg/dL (min 10.3 mg/dL, max 12.0 mg/dL), and average twenty-four-hour urinary calcium was 455 mg/day (min 386 mg/day, max 551 mg/day). Calcium levels were corrected to normal range post-parathyroidectomy and remained in normal range. However, hypercalciuria did not resolve. Post-parathyroidectomy, average PTH was 44 pg/dL (min 25 pg/dL, max 69 pg/dL), average serum calcium was 9.6 mg/dL (min 9.3 mg/dL, max 9.8 mg/dL), and average twenty-four-hour urinary calcium was 284 mg/day (min 201 mg/day, max 376 mg/day). Two patients who had history of nephrolithiasis prior to parathyroidectomy continued to develop nephrolithiasis at six and sixteen months after successful parathyroidectomy. Conclusions: This case series showed that hypercalciuria may not resolve following a successful parathyroidectomy in patients with primary hyperparathyroidism and elevated twenty-four-hour urinary calcium at 6 to 19 months after surgery. Further observations to evaluate long term effects of parathyroidectomy on hypercalciuria is needed.
The Importance of Interpreting Urine Calcium:Creatinine Ratio in PHPT Within Ethnic Context
Authors: Abdel-Malek Mariana , Zaman Shamaila , Tharakan George , Mills Edouard G , Buckley Adam John , Todd Jeannie , Behary Preeshila , Cox Jeremy Philip , Comninos Alexander N 
Published: May 2021

Abstract
A 56-year-old Afro-Caribbean lady was found to have incidental hypercalcaemia on routine GP investigations. Tiredness was the only elicitable hypercalcaemic symptom and aside from early menopause at age 40, she had no significant past medical or family history. Examination was unremarkable. Blood results showed a raised adjusted calcium 2.68mmol/L (2.2–2.6), normal phosphate 1.06mmol/L (0.80–1.50), raised parathyroid hormone (PTH) 14.1pmol/L (1.6–7.2) and low 25-hydroxyvitamin D 28.1nmol/L (70–150).
She had osteopaenia of the femora and left radius on DEXA scan but no nephrocalcinosis on renal ultrasound. On initial investigation, her urinary calcium output was low at 1.55mmol/day resulting in a 24h calcium:creatinine ratio (UCCR) of 0.0065. Although suggestive of Familial Hypocalciuric Hypercalcaemia (FHH), her notable Vitamin D deficiency was considered to contribute to the observed hypocalciuria. After Vitamin D repletion, a repeat UCCR improved to 0.012, however, remained in the indeterminate range. No known pathogenic variant was identified on genetic analysis for FHH.
Her PTH and Calcium levels remained persistently high within 9.7–17.1pmol/L and 2.65-2.82mmol/L respectively, suggestive of Primary Hyperparathyroidism (PHPT) given the end organ damage and negative genetic studies. Based on her symptom of fatigue, osteopaenia at a young age and hypercalcaemia, localisation studies were arranged which showed no definitive evidence of a parathyroid adenoma and explorative surgery was planned.
The negative genetic testing, PTH level 17.1pmol/L, osteopaenia, low-normal magnesium and phosphate level collectively support a diagnosis of PHPT in this case, despite a low UCCR which however is observed in some PHPT patients. Indeed, a lower UCCR ratio has been reported in the healthy Afro-Carribean population across all age groups, as well as in Afro-Carribean patients with PHPT [1]. The underlying mechanism for this is yet to be determined but may be due to increased renal sensitivity to PTH or altered activity of the tubular calcium reabsorptive pathways. One can further speculate regarding an evolutionary reason behind a protective homeostatic system favouring renal calcium reabsorption over excretion in this frequently vitamin D deficient population.
Clinical practice relies heavily on the use of UCCR in aiding the biochemical differentiation of PHPT and FHH. However, as this case highlights, its use can be misleading in Afro-Carribean patients and therefore should be interpreted within an ethnic context.
References: Taha W., Singh N., Flack J. M., Abou-Samra A. B. Low urine calcium excretion in African American patients with Primary Hyperparathyroidism. Endocr Pract. 2011; 17: 867–872
Vitamin D Supplements: Over-the-Counter Accessibility... It Is Safe?
Authors: Figueroa-Cruz Alegyari , Villarrubia-Ocasio Lisselle M , Madera-Marin Luis N , Ortiz-Torres Yineli , Vazquez-Roura Francis , Garcia-Mateo Jose M 
Published: May 2021

Abstract
Calcium is the fifth most abundant element in earth and human body. It has multiple functions within our system such bone mineralization, neuromuscular excitability regulation, hemostasis, membrane transport, release of hormones and neurotransmitters, among others. For duodenal absorption of calcium, we need vitamin D, reason for which supplementation of both components is important to maintain adequate calcium homeostasis. However, it is entirely beneficial or can be harmful? As we know everything in excess has its consequences, as we describe below.
72 y/o male is brought to the ED after relative find him lethargic, she reports noticing generalized weakness that has been progressing over weeks, prominent in upper extremities with associated increased in urinary frequency. Patient past medical history is relevant for CAD, hypothyroidism, dyslipidemia, and DMT2. On physical examination patient is found hypoactive, but arousable to verbal stimuli, without distress, focal neurologic deficit, thyromegaly nor lymphadenopathy. Presents with Ca+: 18.8mg/dL (n:8.0–10.5mg/dL), that could explain patient clinical presentation for which workup for hypercalcemia is done finding PTH suppress: 14.57pg/mL (n:15-65pg/mL). Patient now with non-PTH related hypercalcemia is further evaluated and found with negative UPEP and SPEP ruling out multiple myeloma and PTH-rp &lt;2.0pmol/L (negative). While etiology of severe hypercalcemia is being study, patient complications of it are being managed such as AKI stage 3 as he presents with Cr: 3.85mg/dL, BUN: 62.5, CrCl:18ml/min and GFR: 15ml/min. Aggressive IV hydration and bisphosphonate therapy failed to decrease calcium and renal function continues worsens, for which hemodialysis is required for calcium clearance. Patient then found with vitamin D25-OH levels: 210.4ng/mL (n:30-100ng/mL), upon questioning he reports taking multivitamins and supplements equivalent for a daily ingestion of 50,700IU of Vitamin D3 and 334mg of calcium carbonate. Patient calcium levels normalize after dialysis but develops renal failure for which he has to be discharged on permanent hemodialysis.
Although prevalence is unknown, hypercalcemia due to vitamin D intoxication is relatively uncommon in comparison to hyperparathyroidism and malignancy. An exact dose intake that leads to intoxication has not yet being stablished but supplementation besides dosage is also dependent on duration of therapy. This case has a lot to teach us, starting with detrimental effects of hypercalcemia, follow by the consequences of lack of counseling and close follow-up of patient over-the-counter supplementation. As physicians we should inquire more about OTC medications and supplements our patients are taking not only for intoxication concerns, but also for drugs interactions. Counseling must be the cornerstone of our practice to avoid life changing consequences as in this case.