bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ectopic Intact PTH Secretion Causing Humoral Hypercalcemia of Malignancy
Authors: Rauf Mohammad Talha , Nhan Winnie , Clines Gregory A , Khairi Shafaq 
Published: May 2021

Abstract
Background: Tumor-generated ectopic intact PTH is difficult to diagnose and should be suspected in patients with apparent primary hyperparathyroidism but with normal parathyroid glands.
Clinical Case: A 72-year-old man presented with symptoms of hypercalcemia including generalized weakness, polyuria, and polydipsia. Initial labs were consistent with primary hyperparathyroidism: calcium 12.1 mg/dL (n 8.6–10.3 mg/dL, albumin-corrected 12.5 mg/dL), intact PTH (iPTH) 115.6 pg/mL (n 10–65 pg/mL), low normal 25-OH vitamin D (25 ng/mL, n 25–100 ng/mL), and relatively high normal 1,25 dihydroxyvitamin D (52 pg/mL, n 18–78 pg/mL). 24-hour urine calcium was 381 mg/day (n 100–300 mg/day) and PTHrP was 1.6 pmol/L (n &lt;4.2 pmol/L). Neck ultrasound demonstrated a 0.5 x 1 cm hypoechoic mass near right thyroid inferior pole, though sestamibi SPECT/CT scan did not reveal scintographic evidence of a parathyroid adenoma. He underwent subtotal parathyroidectomy with largest excised gland weighing 0.262 grams. The left inferior parathyroid gland appeared normal intraoperatively, thus was clipped and left in place. PTH decreased from 194 pg/mL to 98 pg/mL postoperatively. Pathological examination revealed three normocellular parathyroid glands with enlargement of only the right superior gland. Venous sampling of the parathyroid vasculature failed to identify the source of autonomous iPTH post operatively. Due to refractory hypercalcemia, cinacalcet was initiated. However, hypercalcemia as high as 12.6 mg/dl and hyperparathyroidism to 672 pg/mL persisted despite dose escalation. He eventually received pamidronate with subsequent transition to denosumab due to declining renal function. A  68Ga DOTATATE scan was performed to locate occult ectopic parathyroid, which reported multiple foci of presumed somatostatin receptor expression involving the liver and intra-abdominal lymph nodes without significant uptake in the neck concerning for metastatic disease. Liver lesion biopsy was consistent with pancreato-biliary adenocarcinoma. Surprisingly, the biopsy was negative for iPTH and neuroendocrine tumor markers on staining/immunohistochemistry. Given his poor prognosis and multiple comorbidities, the patient opted not to pursue any further workup or therapy for his malignancy.
Conclusion: Occult malignancy should be suspected for a patient with persistent hyperparathyroidism after parathyroidectomy. Treatment of the malignancy may lead to an improvement in hypercalcemia and iPTH levels. Employment of iPTH mRNA testing or intra-abdominal venous sampling to prove ectopic iPTH secretion would be ideal, as iPTH staining could be falsely negative. Further testing was not completed as the patient declined further evaluation.
Falsely Positive Parathyroid Scan in a Patient With Medullary Thyroid Cancer
Authors: Khthir Rodhan Abass 
Published: May 2021

Abstract
Background: Technitium 99m sestamibi is a very useful method for preoperative localization in hyperparathyroidism. It have some limitations including false positivity due to thyroid pathology. We present a patient with positive Technitium 99m sestamibi uptake by a medullary thyroid cancer Case Presentation: A 67-year-old female referred to the endocrine clinic for evaluation of medullary thyroid cancer diagnosed by fine needle aspiration of left side thyroid nodule. TSH level was normal with high normal serum calcium and high PTH levels. No family history of medullary thyroid cancer, hyperparathyroidism or pheochromocytoma. Her plasma metanephrines were normal. Preoperative evaluation included a parathyroid scan with oral I-123 and Intravenous Technitium 99m sestamibi. I-123 scan showed a cold nodule in the left thyroid lobe and the subtraction images demonstrated persistent uptake of Technitium 99M sestamibi which was reported by the radiologist as a parathyroid adenoma. Repeated serum calcium was normal and intraoperative evaluation of parathyroid glands demonstrated no abnormal enlargement confirming that parathyroid scan was falsely positive secondary to medullary thyroid cancer. Conclusion: This case highlights the importance of careful interpretation of nuclear parathyroid scan results. False positive results have been reported with both benign and malignant thyroid disease including medullary thyroid cancer.
Glomus Tumor: An Unusual Cause of Hypophosphatemic Osteomalacia
Authors: Raj Rishi , Hasanzadeh Samaneh , Dashtizadeh Mitra , Kalantarhormozi Mohammadreza , Vahdat Katayoun , Dabbaghmanesh Mohammad Hossein , Nabipour Iraj , Ravanbod Mohammdreza , Assadi Majid , Hashemi Basir , Asadipooya Kamyar 
Published: May 2021

Abstract
Background: Tumor-induced osteomalacia (TIO) is a rare condition resulting in hypophosphatemic osteomalacia. We present a rare case of TIO secondary to glomus tumor. Clinical Case: A 39-year-old woman with history of chronic sinusitis presented with progressively worsening generalized body pain and muscle weakness of eight months duration. Examination showed decreased muscle strength in bilateral upper and lower extremities and congenital cleft palate. Laboratory work up revealed elevated alkaline phosphatase 603 U/L (44–147 U/L), low serum phosphorus 1.5 mg/dL (3.5–5.0 mg/dL), normal serum calcium 8.9 mg/dL (8.3–10.4 mg/dL), normal 25-hydroxyvitamin D 32 ng/dL (30–100 ng/dL), elevated 1,25-dihydroxyvitamin D 62 g/mL (20–45 pg/mL), elevated intact PTH level 99.01 pg/mL (8–74 pg/mL), high normal 24 hour urinary phosphate levels 1100 mg/dl, and elevated FGF23 level 128 RU/mL (&lt;108 RU/mL). Fractional excretion of filtered phosphate (FEPO4) [FEPO4 = (Urine phosphate / Serum phosphate) / (Urine creatinine / Serum creatinine) * 100] was 107.54 % (normal range &lt;20%). Tubular reabsorption of phosphate (TRP) [Percentage TRP = 100 * {1- (Urine phosphate / Serum phosphate) / (Urine creatinine / Serum creatinine)}] was -7.54 %. Tubular maximum reabsorption of phosphate to glomerular filtration rate (TmP/GFR) calculated using formula [TmP/GFR = TRP x serum phosphate] was -0.1131 mg /dL (2.8–4.2 mg/dL). Bone densitometry revealed normal bone density and parathyroid scintigraphy was negative for adenoma. Clinical symptoms along with biochemical evidence of phosphate wasting confirmed by low TRP and an unsuppressed FGF23 levels suggested oncogenic osteomalacia as underlying etiology. Whole body bone scan demonstrated increased radiotracer uptake in the elbows, spine, sacroiliac joints, knees, ankles and multiple ribs suggestive of inflammatory process. MRI of paranasal sinuses revealed large soft tissue mass occupying right frontal, ethmoid, maxillary and sphenoid sinuses suggestive of sinonasal polyposis. 99mTc-Octreotide scan confirmed increased uptake in the nasopharynx. The sinonasal mass was resected and pathology revealed the mass to be a glomus tumor confirmed on immune histochemical studies with positive staining for vimentin and SMA and Ki67 of 5–10 %. Postoperatively, phosphorus levels normalized to 3 mg/dl on day 7. Conclusion: Glomus tumor as cause of TIO is extremely rare however localization and surgical resection of tumor can result in complete resolution of biochemical and clinical manifestations. References: 1. Minisola, S., et al., Tumour-induced osteomalacia. Nat Rev Dis Primers, 2017. 3: p. 17044.
Low Bone Mineral Density and Recurrent Fractures During and After Pregnancy: Dilemma of an Overlooked Diagnosis
Authors: Jodeh Wade S , Nachawi Noura , Khan Leila Zeinab 
Published: May 2021

Abstract
Background: Decreased bone mineral density (BMD) during pregnancy and lactation are rarely described in literature. We present this case of multiple compression fractures during and after pregnancy, highlighting the diagnostic and therapeutic dilemma of an overlooked diagnosis.
Clinical Case: A 23-year-old female without significant past medical history, suffers from an acute onset lower back pain in the third trimester of her first pregnancy. On initial evaluation, this back pain was thought to be musculoskeletal and was dismissed by her medical team. No imaging was ordered throughout the duration of pregnancy, despite the pain remaining unrelenting. On her second day post-partum, she heard a “pop” in her back and fell while holding her newborn. Imaging revealed multiple vertebral compression fractures, in different stages of acuity. Due to debilitating pain, the patient quit breastfeeding and ultimately would never hold her baby again. Her simple activities of daily living were stymied, both as a mother and secretary. It wasn’t long before she couldn’t even fax forms in her office and had to leave work with debility. Traumatized by these life events and continuing to be afflicted by this chronic pain, the patient decided against having any future children. Her compression fractures were managed with different types of analgesics in addition to vitamin D and calcium supplements.
At age 53 and 57, BMD scans showed a T-score &gt;1 at both the lumbar spine and total hip. Forearm BMD was not evaluated at these times. At age 58, a CT spine demonstrated new compression fractures at T5-T12 & L1-L5. She subsequently underwent kyphoplasty of T5, T7 and T8. Fortunately, a bone core biopsy of these 3 vertebrae showed no malignant pathology. A follow up CT scan 6 months later showed stable compression fractures, along with multilevel degenerative changes and neural foraminal stenosis. At age 60, the patient would receive L4-L5 trans-foraminal epidural corticosteroid injection and referral to the bone clinic at a tertiary health center. Initial lab work on referral was significant for normal calcium, albumin, parathyroid hormone, vitamin D, kidney function, liver function, serum and urine protein electrophoresis and cross link N-telopeptide. Osteocalcin was low at 3.9 ng/mL (NL 8.8–37.6 ng/mL). Repeat BMD scan showed T-scores of 0.6, 1.1 and -2.6 at her lumbar spine, total hip and distal forearm respectively. Her osteoporosis is currently managed with teriparatide without active issues.
Conclusion: This case highlights the rare development of low BMD in pregnant and breastfeeding women, without prior risk factors, jeopardizing future quality of life. The evidence behind the incidence and pathophysiology underlying these changes remains deficient. There remains a dearth of guidelines for definition and treatment of osteoporosis and low BMD in young peripartum women.
Osteitis Fibrosa Cystica A Rare Presentation of Primary Hyperparathyroidism
Authors: Pierrard Patricia Luengo , Tortolero Giamate Laura M , Guerrero Belén Porrero , Ramírez Joaquín Gómez , Nuñez Jordi Nuñez 
Published: May 2021

Abstract
Introduction: Osteitis fibrosa cystica (OFC) is the most serious bone involvement of primary hyperparathyroidism (PHPT), it is characterized by subperiosteal resorption, lytic lesions and the appearance of brown tumors; this is why, in some cases, this condition can easily be mistaken for a malignant neoplasm. Its prevalence in developed countries is only 5%.
Clinical Case: We present a 58-year-old woman, with no relevant personal history, who came to the emergency room with pain in her right shoulder after an accidental fall on the bus. The humerus radiograph shows a pathological fracture of the right humerus, with significant osteopenia. In the emergency analysis, serum Calcium 13.3 mg / d), Ionic Calcium 7.03 mg / dL, Phosphorus 2.4 mg / dL, Alkaline Phosphatase 248 U / L and normal kidney function stand out. With a diagnosis of severe hypercalcemia, treatment was started in the emergency room with serum therapy (1000 ml of 0.9% physiological saline in 4 hours) and intravenous diuretic treatment (furosemide 40mg) with a decrease in calcemia to 12.8mg / dL. Later, she was admitted to the Internal Medicine hospital ward to perform a differential diagnosis of hypercalcemia secondary to a primary tumor, Multiple Myeloma or Primary Hyperparathyroidism. The study findings are: Calcium metabolism: PTH 660 pg / ml (12 - 65), 25 Hydroxyvitamin D: 14.00. Thyroid ultrasound: Posterocaudal to right thyroid lobe, an area of ​​echogenicity slightly lower than the thyroid is identified, of dimensions not estimated by endothoracic component, which could correspond to a parathyroid adenoma. Body CT: Neck: Heterogeneous nodule dependent on the posterior region of the right thyroid nodule with endothoracic extension. Skeleton: Lytic lesions with a tumor aspect in the humerus, right scapula and bilateral seventh rib and right pubic branch. Skull: Diffuse increase in bone density of the calvaria, showing multiple punctate lytic lesions with a permeative appearance. Bone densitometry: Femur neck: - &lt;1.5, Lumbar spine: - &lt;3.0 With the diagnosis of PHPT causing osteitis fibrosa cystica, surgical intervention was decided. Under general anesthesia, a selective right approach was performed, finding a large parathyroid adenoma weighing 17 grams. PTH fell to 36 pg / ml after surgery. At 9 months after surgery, the patient presented calcium levels of 9 mg / dl and PTH 146 pg / ml with clear radiological improvement.
Discussion: Osteitis fibrosa cystica is rare in our environment, it is often confused with other neoplasms. After parathyroidectomy, patients with PHPT have a marked and sustained recovery from OFC, although in some cases this recovery can only be achieved after several years. We consider this case of interest, since it illustrates the importance of evaluating the study of phospho-calcium metabolism and parathyroid function in all patients with bone lesions to rule out Primary Hyperparathyroidism with OFC.
Osteogenesis Imperfecta With Cerebral Atherosclerosis: A Family Report
Authors: He Junyu , Liao Zhihong 
Published: May 2021

Abstract
Background: Osteogenesis imperfecta (OI) is a rare hereditary connective tissue disease. It is mainly associated with pathogenic variants in COL1A1 or COL1A2. Patients with OI usually have repeated history of bone fractures. Besides, osteogenesis imperfecta is associated with some cardiovascular complications, such as aortic and mitral valve dysfunction, aneurysm and aortic dissection. But the relationship between these diseases has not been well studied.
Case Presentation: A 55-year-old man was admitted to our hospital mainly due to “dizziness for 2 hours”. He had a 4-month history of hypertension and a history of smoking for more than 20 years. He had no history of drinking alcohol. He had hunchback and O-type legs. Besides, the patient and some of his relatives had a history of repeated brittle fractures,which was considered as “osteogenesis imperfecta”. The clinical manifestation of OI in this family varies to a certain extent, from simple tooth disintegration to severe fracture deformity. The most serious patient of his family was unable to walk. CT and MRI revealed multiple systemic arteriosclerosis, including vertebral artery, posterior inferior cerebellar artery, cervical artery, and bilateral cerebellar multiple lacunar cerebral infarction. The blood sample of the patient was tested by whole exome sequencing, and the saliva samples of the patient’s family members were tested by Sanger sequencing. A mutation c.3159 + 2T &gt; A was detected in COL1A2 gene associated with OI, also found in the other affected family members, which had not been reported before. It was a segregating mutation in the family. The clinical severity of the family members was heterogeneous.
Discussion:
This case is worth learning from the following aspects: 1. A pathogenic heterozygous mutation, c.3159 + 2T &gt; A was detected in COL1A2 gene in the patient with OI, which is not reported in previous cases of OI. 2. The clinical manifestation of OI in this family varies to a certain extent, from simple tooth disintegration to severe fracture deformity. The most serious patient of his family was unable to walk. It presented the clinical heterogeneity of OI. Further basic researh on the mutation site of related gene of OI are needed. 3. We found the possibility of developing cerebral atherosclerosis in patients with OI. Therefore, patients with OI should give up smooking, exercise properly and keep on a low fat diet. They should pay attention to control blood pressure and blood lipid so as to reduce the risk of atherosclerosis.
Conclusion: A c.3159 + 2T&gt;A mutation in COL1A2 gene detected by whole exome sequencing was the causing reason of OI, the discovery enriched the gene mutation spectrum of OI. We also found that OI may have relationship with premature atherosclerosis, and the abnormal bones of the cervical spine may lead to vertebrobasilar ischemia.
Osteopetrosis - A Case Series Exploring Complications and Multidisciplinary Management
Authors: Stewart Catherine , Loughrey Paul Benjamin , Lindsay John R 
Published: May 2021

Abstract
Background: Osteopetrosis is a group of rare inherited skeletal dysplasias, with each variant sharing the hallmark of increased bone mineral density (BMD). Abnormal osteoclast activity produces overly dense bone predisposing to fracture and skeletal deformities. Whilst no cure for these disorders exists, endocrinologists play an important role in surveillance and management of complications.
Clinical Cases: A 43-year-old female had findings suggestive of increased BMD on radiographic imaging performed to investigate shoulder and back pain. X-ray of lumbar spine demonstrated a ‘rugger jersey’ spine appearance, while shoulder X-ray revealed mixed lucency and sclerosis of the humeral head. DXA scan showed T-scores of +11 at the hip and +12.5 at the lumbar spine. MRI of head displayed bilateral narrowing and elongation of the internal acoustic meatus and narrowing of the orbital foramina. Genetic assessment confirmed autosomal dominant osteopetrosis with a CLCN7 variant. Oral colecalciferol supplementation was commenced and multi-disciplinary management instigated with referral to ophthalmology and ENT teams. A 25-year-old male presented with a seven-year history of low back pain and prominent bony swelling around the tibial tuberosities and nape of neck. Past medical history included repeated left scaphoid fracture in 2008 and 2018. Recovery from his scaphoid fracture was complicated by non-union requiring bone grafting with open reduction and fixation. Plain X-rays of the spine again demonstrated ‘rugger jersey’ spine. DXA scan was notable for elevated T scores; +2.9 at hip and +5.8 lumbar spine. MRI spine showed vertebral endplate cortical thickening and sclerosis at multiple levels. The patient declined genetic testing and is under clinical review. A 62-year-old male was referred to the bone metabolism service following a DXA scan showing T scores of +11. 7 at the hip and +13 at the lumbar spine. His primary complaint was of neck pain and on MRI there was multi-level nerve root impingement secondary to facet joint hypertrophy. Past medical history was significant for a long history of widespread joint pains; previous X-ray reports described generalized bony sclerosis up to 11 years previously. Clinical and radiological monitoring continues. Conclusion: Individuals with osteopetrosis require a multidisciplinary approach to management. There is no curative treatment and mainstay of therapy is supportive with active surveillance for complications.
Fluoxetine Administration During Lactation Impacts the Bone Health of the Dam and the Offspring in Mice
Authors: Fricke Hannah P , Krajco Chandler J , Sheftel Celeste M , Charles Julia F , Hernandez Laura L 
Published: May 2021

Abstract
Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed class of antidepressants during pregnancy and lactation. SSRIs decrease bone mineral density (BMD) across all ages and sexes. Lactation is also characterized by increased bone resorption to mobilize calcium and achieves this via a serotonin-induced hormonal cascade. This serotonin-mediated bone loss is normally restored after weaning but is persistent when an SSRI is administered during the peripartum period. Our lab has previously shown that administration of the SSRI fluoxetine (FLX) during both gestation and lactation results in compromised bone health of the dam, which is characterized by a decreased bone mineral density (BMD). Along with this, we have also shown a decrease in BMD and femoral length in the offspring of the FLX-treated dams at weaning. We hypothesize that FLX usage during lactation only will impact the bone health of the dam as well as the bone health of her offspring due to exposure to FLX via the dam’s milk. Female C57BL/6 mice were randomized to receive the SSRI fluoxetine hydrochloride (20 mg/kg) or saline daily from the beginning of lactation (D0) through the end of lactation (D21), resulting in the following treatments: FLX dams (n=13) and control dams (n=13). The offspring of the treated dams were then harvested at weaning (3 weeks of age). During the peripartal period, the BMD of the dam was monitored via dual x-ray absorptiometry (DEXA). A baseline scan was taken at 6 weeks of age, at the end of pregnancy (E17.5), the beginning of lactation (D2), peak lactation (D10), and at the end of lactation (D21). There was no significant difference in the BMD of the FLX dams compared to the control dams at 6 weeks of age (p=0.9992), E17.5 (p=0.9995), D2 (p&gt;0.9999), or D10 (p&gt;0.9999). However, at D21, the FLX dams had a decreased BMD compared to the control dams (p=0.0493). Along with the decreased BMD of the FLX dams at weaning, there was a significant decrease in femur length in the pups of the FLX dams (p=0.0040). When the pups were separated by sex, the decreased femur length was observed in both the male (p=0.0413) and female (p=0.0047) offspring. These data suggest that fluoxetine use during lactation only results in a decreased BMD of the treated dams, as well as decreased femur length in the exposed offspring in both sexes.