bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Challenging Case of Phosphaturic Mesenchymal Tumor With Primary Hyperparathyroidism
Authors: Salim Michael , Barengolts Elena 
Published: May 2021

Abstract
Background: Localization of tumor-induced osteomalacia (TIO) is often challenging. Primary hyperparathyroidism (HPT) following curative surgery for TIO is rarely reported. Clinical Case: A 49-year-old man presented with fragility rib fractures, generalized bone pain, and muscle weakness worsening over the past 3 years. Rheumatologic workup was negative. Initial tests showed elevated levels of parathyroid hormone (PTH) 114.1 pg/mL (14–72 pg/mL) and alkaline phosphatase (ALP) 283 IU/L (44–174 IU/L), reduced levels of 25(OH)D 16 ng/mL (30–100 ng/mL), 1,25(OH)2D 9 pg/mL (18–72 pg/mL), and phosphorus 1.6 mg/dL (2.5–4.9 mg/dL), calcium levels of 9.2 mg/dL (8.5–10.1 mg/dL), and eGFR 58 mL/min/1.73 m2. A sestamibi scan showed normal parathyroid uptake. The diagnosis was secondary HPT due to chronic kidney disease and vitamin D deficiency. The patient was treated with D3 and phosphate. During a 2-year follow-up, the patient reported improvement of pain and weakness with no additional fractures. Further investigations showed persistent hypophosphatemia with elevated urinary fractional phosphate excretion (44%, ref. &lt;20%), indicating renal phosphate wasting. Fibroblast Growth Factor 23 (FGF23) was high, 291 RU/mL (0–180 RU/mL). DXA results were consistent with osteopenia. TIO was suspected. At a 3-year follow-up, investigations included three whole-body 18F-FDG PET-CT scans revealing several areas suspicious for tumor presence. However, multiple MRIs were inconclusive. Laboratory tests showed persistent hypophosphatemia (despite D3 and phosphate treatment), elevated FGF23 (1330 RU/mL) and PTH (274.4 pg/mL), and normal calcium, 25(OH)D, and 1,25(OH)2D. The patient subsequently underwent 68Ga DOTATATE PET-CT, which revealed a somatostatin receptor-positive lesion involving the left upper lobe of the lung. The mass was resected without complications. Histopathology was compatible with a phosphaturic mesenchymal tumor. At a 6-month postoperative follow-up, the patient reported dramatically improved symptoms with decreased weakness and pain, normal phosphate, calcium, ALP, and FGF23 (160 RU/mL) levels, while DXA results were significantly improved. Phosphorus supplementation was discontinued. At follow-up 3 years post-surgery, the patient had slowly rising PTH (126.3 pg/mL) and calcium (10.1–10.6 mg/dL) levels with normal phosphate, 25(OH)D, and FGF23 (174 RU/mL) levels. A diagnosis of primary HPT was made. Further evaluation was deemed unnecessary since the patient did not meet the criteria for surgical treatment. The development of primary HPT was considered mechanistically related to long-standing hypophosphatemia and hypovitaminosis D stimulating PTH production. Conclusion: This case report highlights the pitfalls contributing to delayed diagnosis of TIO and alerts clinicians to the potential development of primary HPT after curative surgery for TIO.
Autosomal Dominant Hypocalcemia Due to a GNA11 Variant: The First Case in Japan
Authors: Yamauchi Ichiro , Ueda Yohei , Sugawa Taku , Hakata Takuro , Fujita Haruka , Okamoto Kentaro , Ohno Youichi , Fujii Toshihito , Taura Daisuke , Inagaki Nobuya 
Published: May 2021

Abstract
Background: Autosomal dominant hypocalcemia (ADH) is characterized by hypocalcemia and hyperphosphatemia due to hypoparathyroidism. ADH type 1 is caused by gain-of-function variants in CASR gene coding the calcium-sensing receptor. Recently, ADH type 2 caused by gain-of-function variants in GNA11 gene coding G-protein subunit α11 has been recognized.
Case: A 32-year-old female patient visited our hospital because she suffered from hyperhidrosis, exertional dyspnea, and palpitations. She had a past medical history of paroxysmal kinesigenic dyskinesia confirmed by genetic analysis of PRRT2. Although her sister has unspecified epilepsy, no members of her kindred have episodes of tetany. Her height was 155.7 cm and weight was 64.1 kg. She had goiter with tremor and tachycardia and was diagnosed as Graves’ disease (fT3 &gt;32.55 pg/mL, fT4 &gt;7.77 ng/dL, TSH &lt;0.005 µIU/mL, and TRAb 36.9 IU/L). Thiamazole therapy ameliorated her hyperthyroidism, while serum calcium level was low (7.5 mg/dL) and serum phosphate level was slight high (5.1 mg/dL). Hypoparathyroidism was confirmed because intact-PTH was relatively low (20 pg/mL) under the hypocalcemia. Her episode of tetany that she could not sit on her heels from childhood and her basal ganglia calcification in head CT scan suggest the long disease duration. Germline whole exome sequence detected a rare variant in GNA11 gene; c.1023C&gt;A resulted in p.Phe341Leu. There were no relevant pathogenic variants in other candidate genes such as CASR, PTH, and GCM2. Treatment with 2 µg/day of alfacalcidol and 1200 mg/day of calcium aspartate could not normalize serum calcium level (7.0 mg/dL) and serum phosphate level (5.3 mg/dL) even after 1 year.
Conclusions: The pathogenicity of the variant, p.Phe341Leu, in GNA11 gene was previously confirmed [1]. ADH type 2 is extremely rare as our literature review found only four previous reports; 17 patients in 5 families [1–4]. Phenotypes of the present case are mild and skeletal growth is normal. Meanwhile, we are having difficulty in management of her hypocalcemia, even though Graves’ disease might affect her bone metabolism. Optimal therapy for ADH type 2 needs further investigation.
References: [1] Nesbit et al. Mutations Affecting G-protein Subunit α11 in Hypercalcemia and Hypocalcemia. N Engl J Med. 2013; 368: 2476–2486. [2] Li et al. Autosomal Dominant Hypoparathyroidism Caused by Germline Mutation in GNA11: Phenotypic and Molecular Characterization. J Clin Endocrinol Metab. 2014; 99: 1774–83. [3] Piret et al. Identification of a G-Protein Subunit-α11 Gain-of-Function Mutation, Val340Met, in a Family With Autosomal Dominant Hypocalcemia Type 2 (ADH2). J Bone Miner Res. 2016; 31: 1207–14. [4] Tenhola et al. Impaired Growth and Intracranial Calcifications in Autosomal Dominant Hypocalcemia Caused by a GNA11 Mutation. Eur J Endocrinol. 2016; 175: 211–8.
Denosumab Induced Severe Hypocalcemia in a Patient With Metastatic Prostate Cancer
Authors: Naher Kamrun , Thrupthi Komandur , Samsuddoha Kazi , Galiveeti Sneha , Leung Vivien 
Published: May 2021

Abstract
Background: Denosumab can lead to severe hypocalcemia in patients with underlying risk factors such as vitamin D deficiency, low PTH, hypomagnesemia, and CKD. Denosumab is a monoclonal antibody against RANKL, reducing the activity of osteoclasts and thus reducing the release of calcium in the bloodstream causing hypocalcemia. Hypocalcemia can range from mild to severe symptoms requiring prolonged hospitalization. Medications such as zoledronic acid and Denosumab are known to reduce the occurrence of Skeletal related events (pathological fracture, spinal cord compression, and radiation to bone). For metastatic prostate cancer, about 90% can develop bone metastasis with significant morbidity and mortality [1]. Our patient presented with severe hypocalcemia after denosumab use without any above risk factors. Clinical Case: A 66-year-old male with a medical history of Prostate cancer with Metastasis to chest and bone presented to ER with syncope. Patient-reported poor oral intake, nausea, and vomiting for the last few days. In the ER, the patient was found afebrile, bp 116/76, HR 92, saturating 100% on room air. On examination, the patient was found lethargic, malnourished, foley in place due to chronic urinary retention. The abdomen was soft and non-tender. Laboratory findings were significant for Hb 9.1, Na 133, K3.6, bicarb 21, total calcium (Ca) 4.2, ionized Ca 0.63 and corrected Ca 5.4, magnesium 1.6, phosphorus 2.1, albumin 3.3, ALT 218, AST 229, ALP 1607. Lipase 82, Total bilirubin 1.5, direct bilirubin 0.8. Spot Urinary Ca 0.7, Vitamin D 25 OH 36.9, serum PTH 225 pg/mL. Serum cortisol AM 20.9, BUN 16, and serum Creatinine 1.0. The patient was started on 11g calcium gluconate in 1L dextrose @ 50c/hr and calcitriol 0.25mcg twice daily. Serum Ca level was monitored every 6 hours and reached 6.7. Later was started on Ca carbonate 1250 TID with meals. Finally, after electrolyte correction, the patient clinically improved and was discharged with the plan to follow Calcium at the outpatient clinic. On review of previous labs at the oncology clinic, the patient received Denosumab at his oncologist’s clinic 10 days before this hospital admission, last Ca level from 6 months ago 8.6, the patient was not any vitamin D or Ca supplement. Conclusion: Many case reports have been published on severe hypocalcemia after denosumab usage. Several patients had underlying risk factors such as vitamin D deficiency, osteoblastic lesion, and AKI leading to an additional cause of hypocalcemia. We emphasize careful monitoring of serum Ca levels particularly in the first few weeks of treatment even without significant risk factors for hypocalcemia. References: [1] Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients. Bubendorf L, Schöpfer A, Wagner U, Sauter G, Moch H, Willi N, Gasser TC, Mihatsch MJ. . Hum Pathol. 2000 May; 31(5):578–83
Hypercalcemia With Non Suppressed Parathyroid Hormone in a Young Female- A Rare Case of Calcium Sensing Receptor Gene Related Familial Hypocalciuric Hypercalcemia-1
Authors: Shanaz Fazeena , Bachman Kristine Kay 
Published: May 2021

Abstract
Background: Familial Hypocalciuric Hypercalcemia (FHH) is a rare disorder, associated with hypercalcemia and hypocalciuria and inherited in an autosomal dominant manner. Its true prevalence is unknown, and is estimated to be around 1 in 78,000 as compared to primary hyperparathyroidism (PHPT) which is around 1 in 1000. There are 3 mutations known to cause FHH. FHH-1 is caused by inactivating mutation in the calcium sensing receptor (CaSR) gene. Mutations associated with FHH-2 and FHH-3 are GNA11 and AP2S1 respectively. Case Presentation: 38-year-old female presented to endocrinology, for evaluation of hypercalcemia (10.8 mg/dL, with normal albumin). She was not on any calcium supplements or any other medications which can cause hypercalcemia. She did not have any prior fracture or nephrolithiasis or renal insufficiency. Her father reported to have hypercalcemia; no further evaluations of her father were available. Examination revealed an obese female with no skeletal or dental or other physical abnormalities. Laboratory evaluations: PTH= 37 pg/ml (15–65), 25 OH vitamin=D-30 pg/ml, Mg=2 mg/dL (1.5–2.6), phosphorus=3.1 mg/dl (2.5–4.8), 24 hour urine calcium=0.151 g/24 hours-with 24 hour urine calcium clearance of 0.008. Therefore, evaluations were highly suggestive of FHH. Subsequently, she had genetic evaluation which confirmed heterozygous CaSR mutation, confirming FHH-1. Her mother had genetic testing and was not found to have the mutation. So, it was concluded that the patient likely inherited the gene from her father, who also had hypercalcemia. She is being monitored clinically and with serial laboratory evaluations to monitor her calcium levels. Discussion: CaSR is expressed in parathyroid glands and kidneys which plays a key role in calcium regulation. CaSR inactivating mutation (seen in FHH-1) leads to hypocalciuria and hypercalcemia. 24 hour urine calcium clearance (urine Ca x serum Cr/ serum Ca x urine Cr) of &lt;0.01 is highly suggestive of FHH. Furthermore, higher concentration of calcium is required to suppress PTH release leading to high or nonsuppressed PTH. This finding can mislead towards the diagnosis of PHPT and unnecessary parathyroid surgery, if the diagnosis of FHH is missed. FHH is usually a benign disorder; subtotal parathyroidectomy does not cure the disease. FHH, rarely can cause atypical complications such as pancreatitis and total parathyroidectomy may be indicated to prevent further episodes of pancreatitis. Conclusions: This is a rare case presentation of hypercalcemia due to CaSR inactivating mutation related FHH. FHH and PHPT are competing diagnoses, when a patient presents with hypercalcemia and has nonsuppressed PTH. FHH is rare, however needs to be suspected in a young patient with family history of hypercalcemia, to avoid misdiagnosis of PHPT and unnecessary surgical intervention.
Osteitis Fibrosa Cystica: An Unusual but Still Prevalent Manifestation of Uncontrolled Secondary Hyperparathyroidism
Authors: Luzuriaga Maria Gracia , Diez-Cardona Elsie , Lagari-Libhaber Violet S 
Published: May 2021

Abstract
Background: Osteitis fibrosa cystica is an uncommon complication of untreated secondary hyperparathyroidism in patients with end-stage renal disease. The characteristic bony lesions that are seen in this condition very rarely can regress after medical treatment or parathyroidectomy. Clinical Case: A 65-year-old male with PMH of Systemic Lupus Erythematous (SLE) resulting in End-Stage Renal Disease (ESRD) on peritoneal dialysis (PD) and HTN, presented to his primary care physician for evaluation of a painful, enlarging lesion in his left forearm. The patient reported no history of trauma and denied having systemic symptoms. An X-Ray of his left forearm showed a lytic lesion within the proximal neck of the ulna, with erosion of the adjacent cortex. CT of the forearm showed a very vascular soft tissue mass causing significant erosive changes of the anterior cortex in the proximal ulna. Due to the characteristics of the lesion, an underlying malignancy was suspected as a possible diagnosis. The patient had a whole-body PET CT which showed multiple scattered hypermetabolic lytic osseous lesions throughout the axial and appendicular skeleton, including a large left proximal ulnar lesion. The patient had a bone biopsy from the lesion in his left ulna which showed a giant cell proliferation in a background of fibrosis and hemosiderin, suggestive of Osteitis Fibrosa Cystica (brown tumor of hyperparathyroidism). His laboratory workup around the time of the symptoms showed a normal serum calcium (9 mg/dl), associated with a high serum phosphorus (6.2 mg/dl), low vitamin D (20 ng/ml), and an elevated PTH (900 pg/ml). The patient was started on Cinacalcet, an increased dose of phosphate binders, as well as Calcitriol and the lesions and pain disappeared. Follow up lab work showed a normal Vitamin D (34 mg/dl), normal Phosphorus (4 mg/dl), and a PTH of 199 mg/dl, with a normal serum Calcium. A surveillance PET was performed 6 months after the initial one when the lesions clinically had disappeared and it showed again the presence of the bony lesions described prior, including the one in the left ulna, but with decreased FDG uptake, as well as new lesions in the spine. To date, the patient is asymptomatic and has not noted any new painful lesions. Conclusions: Osteitis fibrosa cystica remains a rare manifestation of secondary hyperparathyroidism, which may lead to an initial impression of malignancy. This patient exhibited clinical resolution of the painful symptoms associated with osteitis fibrosa cystica following medical management, though the lytic lesions involving the axial and appendicular skeleton persisted on surveillance imaging. This case serves as a reminder of the severe manifestations of a skeletal disease that has become rare given advances in early detection of and appropriate medical management of hyperparathyroidism.
Prolonged Hypercalcemia After Recovery From Severe Rhabdomyolysis and Acute Renal Failure
Authors: Mody Tanvisha , Mullally Jamie 
Published: May 2021

Abstract
Introduction: Rhabdomyolysis is characterized by elevated creatine kinase, electrolyte abnormalities and acute renal failure. After the initial hypocalcemic phase, serum calcium levels can normalize or become significantly elevated during the recovery phase. We report a case of persistent hypercalcemia during the recovery phase of rhabdomyolysis-induced acute renal failure. Case Description: A 26-year old woman with Cornelia de Lange syndrome initially presented with septic shock, complicated by severe rhabdomyolysis and acute renal failure requiring hemodialysis. On admission, creatine kinase level was &gt;30,500 U/L [29–168], BUN 95 mg/dL [6–22], Creatinine 3.39 mg/dL [0.57–1.11], and Corrected Calcium 7.1 mg/dL [8.6–10.2]. Approximately 1 month after admission, the patient developed hypercalcemia with corrected calcium values ranging from 10.4 to 14.5 mg/dL with PTH 10.5 pg/mL [8.7–77.1] and 1,25-Dihydroxyvitamin D and 25-OH Vitamin D levels &lt;8.0 pg/dL [18–78] and 21.20 ng/mL [30–80], respectively. Her renal function improved and dialysis was discontinued seven weeks after initial presentation, although her GFR remained impaired (22 mL/min/BSA). She remained hypercalcemic and was treated with intermittent doses of Calcitonin when the level rose above 12.0 mg/dL. Spot urinary calcium to creatinine ratio was low at 0.13. Improvement in her calcium was seen with a level of 10.8 mg/dL eleven weeks after she was initially noted to be hypercalcemic and she was able to be discharged. Two weeks after discharge, an outpatient calcium improved further to 10.4 mg/dL.
Discussion: Rhabdomyolysis is a clinical syndrome that results from severe muscle damage with release of the breakdown products from injured muscle cells leading to acute renal failure and electrolyte abnormalities. The initial hypocalcemic phase is due to entry of calcium into damaged myocytes and deposition of calcium salts in damaged muscle. After recovery, most patients have normalization of calcium levels. However, in up to one-third of patients, a rebound hypercalcemia can ensue. The proposed mechanism is massive muscle calcium release during renal recovery. In the cases reported, the hypercalcemia phase resolves by an average of 8 days with the longest reported recovery being 3.5 months. We report a case of prolonged hypercalcemia in the setting of continued renal impairment. It appears that the patient’s low GFR impaired urinary calcium excretion resulting in persistent hypercalcemia which eventually resolved over time with some improvement in renal function. Other case reports have described treatment with IV fluids, Calcitonin, Pamidronate and hemodialysis, although the efficacy of these interventions is unclear. Rhabdomyolysis is an under-recognized cause of hypercalcemia. Our case highlights the potential for prolonged hypercalcemia after recovery from rhabdomyolysis in the setting of renal impairment.
Prolonged Hypocalcemia After a Single Dose of Denosumab in Chronic Kidney Disease
Authors: Puar Akshan , Saeed Zeb Ijaz 
Published: May 2021

Abstract
Introduction: Denosumab, a monoclonal antibody that inhibits RANK L (receptor activator nuclear factor-kappa beta ligand), is one of the few medications that can be used to treat osteoporosis in patients with chronic kidney disease (CKD). However, its use is associated with a much higher incidence of hypocalcemia in this patient population. What remains unclear is the duration of hypocalcemia after denosumab use. We describe a case of prolonged hypocalcemia of 9 months in a patient with CKD after a single dose of denosumab.
Case: A 64-year-old Caucasian man with a history of bilateral lung transplant for interstitial pulmonary fibrosis and CKD Stage IV was referred to the Endocrinology clinic for evaluation of steroid-induced osteoporosis. Bone density scan was consistent with osteoporosis with the lowest T-score of -2.8 at the left femoral neck, which showed a 25.3% decline from a previous one two years prior. His labs upon initial visit: 25 hydroxy Vitamin D: 36.5 ng/mL (30–100), 1, 25 hydroxy vitamin D 32 pg/ml (19.9–79.3), corrected Serum Calcium 8.9 mg/dL (8.5–10.5), Serum Cr 4.38 mg/dL (0.6–1.4), PTH 157 pg/mL (10–65), Serum Alkaline Phosphatase 61 Units/L (25–125), Urine NTX 39 nM BCE/mM creatinine (21–83). After discussing risks and benefits, he was given a dose of subcutaneous denosumab 60 mg. He had been started on Calcium/Vitamin D (600 mg/400 IU BID) prior to receiving his dose. Keeping in mind the increased risk of hypocalcemia given his history of CKD, his corrected serum calcium was checked one week later, and it was 6.5 mg/dL. The patient was asymptomatic. However, given the severity of his hypocalcemia, he was started on calcitriol 0.25 mcg oral BID and calcium carbonate 1200 mg daily. He did show mild improvement in three days to a corrected calcium of 7.0 mg/dL. His calcitriol was briefly increased to 0.5 mcg BID and calcium carbonate was increased to 1800 mg daily. The regimen was weaned to calcitriol 0.25 mcg daily and previous calcium/Vitamin D dosing later that month. Thereafter, his labs were monitored regularly and there were several unsuccessful attempts made to decrease the calcitriol/calcium carbonate. Given persistent hypocalcemia, other bloodwork including a bone specific alkaline phosphatase and celiac screen were checked which were unremarkable. Finally, nine months after his denosumab dose, calcitriol was discontinued safely. Serum calcium levels have remained stable thereafter. Given prolonged hypocalcemia, it was decided not to administer another dose of denosumab.
Conclusion: Patients with CKD who receive denosumab are not only at risk for developing severe, but also prolonged hypocalcemia. Therefore, it is imperative to monitor serum calcium levels, not only immediately after receiving a dose, but serially.