bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management of Pheochromocytoma in a Patient With Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement
Authors: Chopra Karishma A , Banka Ajaz 
Published: May 2021

Abstract
Background: There are few guidelines for the management of patients with both significant cardiac valvular disease and pheochromocytoma. Resection of pheochromocytoma is challenging for surgeons and anesthesiologists due to the potential for sudden releases of catecholamines causing significant hemodynamic effects. The cornerstone of perioperative management of pheochromocytoma involves alpha blockade to prevent the potential for hypertensive crisis from unopposed alpha-adrenergic vasoconstriction. Achieving adequate adrenergic blockade is challenging in patients with aortic stenosis due to the risks of decreased afterload precipitating myocardial ischemia and bradycardia leading to diminished cardiac output [1]. It is difficult to determine whether to proceed first with transcatheter aortic valve replacement or pheochromocytoma resection in patients with both conditions. Clinical Case: An 83-year-old woman with a past medical history of type 2 diabetes, essential hypertension, coronary artery disease, and severe aortic stenosis was found to have a left adrenal mass (10.7 cm) on coronary CTA during pre-operative evaluation for transcatheter aortic valve replacement. She had significantly elevated total urine metanephrines of 16,237 ug/24 hr (n 140–785 ug/24 hr); other hormonal workup was unremarkable. A multi-disciplinary team of interventional cardiology, anesthesiology, and endocrinology specialists determined the safest management plan involved proceeding with transcatheter aortic valve replacement, after adequate alpha and beta blockade and prior to pheochromocytoma resection, to avoid potential for severe heart failure. Due to the potential for unpredictable catecholamine release intra and peri-operatively, the patient was at high risk for hypertensive crisis and mortality. Her home medications of metoprolol 50 mg twice daily, spironolactone 25 mg daily, and verapamil 120 mg daily were continued. She was started on treatment with phenoxybenzamine 10 mg in morning and 10 mg in evening. The phenoxybenzamine dose was titrated to 10 mg in the morning and 20 mg in the evening to achieve a consistent systolic blood pressure of less than 130 mm Hg. She successfully underwent transcatheter aortic valve replacement and remained hemodynamically stable. She was discharged with plan for surgical resection of pheochromocytoma six weeks after her transcatheter aortic valve replacement. Conclusions: This case describes a successful management strategy for achieving alpha blockade in an elderly patient with pheochromocytoma and severe aortic stenosis. Reference: [1] Saran JS, Moalem J, Schoeniger L, Tzimas K. Perioperative Management of Pheochromocytoma Resection in a Patient With Severe Aortic Stenosis. J Cardiothorac Vasc Anesth. 2018 Dec;32(6):2712–2715.
Multifactorial Hyponatremia in a Lung Transplant Recipient: A Case Report of Pseudohyponatremia, SIADH and Secondary Adrenal Insufficiency
Authors: Shayto Rani 
Published: May 2021

Abstract
Background: Lung transplant recipients are prone to developing multifactorial hyponatremia from immunosuppressive therapies and posttransplant lymphoproliferative disorders.
Clinical Case: A 77-year-old male with a history of lung transplantation in 2017 presented for a 3-month history of confusion, decline in executive function and chronic abdominal pain. Vital signs were BP 137/81 mmHg, HR 81 bpm, RR 14 per minute, SPO2 99% and afebrile. The patient was clinically euvolemic with a presenting sodium was 129 mmol/L, and was treated with 2.5L IV 0.9% saline. Home immunosuppression with cyclosporine, azathioprine and prednisone 5 mg/d were continued. Sodium declined to 126 mmol/L on day 4 prompting endocrine consult. Labs prior to fluid administration were consistent with iso-osmolar hyponatremia: sOsm 283 mOsm/kg and uOsm 409 mOsm/kg. Pseudohyponatremia was suspected and electrophoresis and immunofixation revealed a free kappa light chain gammopathy. Evaluation when sodium was 126 mmol/L was now consistent with hypotonic hyponatremia: sOsm 273 mOsm/kg, uOsm 398 mOsm/kg, and urine sodium 56mmol/L. TSH was normal and AM cortisol was 11.9 ug/dL (3.7–19.4 ug/dL), drawn while on maintenance prednisone. Lab findings and improvement of abdominal pain after receiving high dose prednisone for CT contrast-allergy prophylaxis raised our suspicion for SIADH and undertreated secondary AI. Retrospective chart review revealed tacrolimus use after lung transplant before its discontinuation 9 months prior to admission. Chronic hyponatremia was noted a few months post lung transplantation, with a nadir of 120 mmol/L and only mild improvement despite tacrolimus discontinuation and empiric fludrocortisone use. The patient was treated with a 1L fluid restriction, doubling of prednisone to 10 mg/d and cessation of fludrocortisone for lack of concern for primary. Abdominal symptoms resolved, mental status improved, and serum sodium rose to 132 mmol/L over the next few days, later normalizing to 135–140 mmol/L on follow up. The patient was eventually diagnosed with Waldenström macroglobulinemia.
Conclusion: Hyponatremia in lung transplant recipients can be multifactorial. Calcineurin inhibitors and steroids are part of typical immunosuppressive regimens and can lead to hyponatremia through salt wasting nephropathy or SIADH(1), and undertreated secondary AI, respectively. Posttransplant lymphoproliferative disorders occur in up to 9% of cases(2) and must be suspected as an etiology of hyponatremia.
References: 1.Cowan AJ, Johnson CK, Libby EN. Plasma cell diseases and organ transplant: A comprehensive review. Am J Transplant. 2018;18(5):1046–58.2.Aris RM, Maia DM, Neuringer IP, Gott K, Kiley S, Gertis K, et al. Post-transplantation lymphoproliferative disorder in the Epstein-Barr virus-naïve lung transplant recipient. Am J Respir Crit Care Med. 1996;154(6 Pt 1):1712–7.
Non-Fasting Hypoglycemia Secondary to Opioid Induced Adrenal Insufficiency: A Case Report
Authors: Kubbar Alaa , Banerji Maryann 
Published: May 2021

Abstract
Background: A patient on chronic methadone therapy presented following a suicide attempt, was noted to have recurrent episodes of non-fasting symptomatic hypoglycemia and was diagnosed with opioid induced adrenal insufficiency (OIAI). Opioid induced endocrinopathies are underappreciated, particularly in the midst of a growing opioid epidemic in the United States. We believe this is the first reported clinical case of OIAI associated with non-fasting hypoglycemia. Clinical Case: A 33-year-old female with history of depression and heroine abuse on methadone therapy presented after a suicide attempt by methadone overdose. Home medications included 170mg of methadone daily for the past 5 years. She was afebrile, heart rate of 68, blood pressure 102/72, respiratory rate of 10, oxygen saturation 92%. On exam she was lethargic with altered mental status and had pinpoint pupils. Labs showed a normal complete blood count and metabolic panel. Urine toxicology was positive for methadone. Clinical picture improved temporarily after Narcan administration however 1 hour later she was confused again, with a fingerstick glucose of 50mg/dL and she was admitted to ICU for monitoring. In the ICU she continued to be lethargic with dizziness, nausea and headaches. She continued to have approximately 4 spontaneous episodes of hypoglycemia per day, despite having a good appetite and increased parenteral glucose administration. Blood pressure continued to be marginal, ranging from 85–100/50–60. There was no obvious source of infection. Urine sulfonylurea screen was negative. Investigations showed a morning cortisol of 2.23 ug/dL. A 250 µg ACTH stimulation test showed an inadequate response. The am basal plasma cortisol was 2.25 ug/dL with 15.28 ug/dL and 15.13 ug/dL at 30 and 60 minutes respectively (6.20–19.40ug/dL). She was diagnosed with hypoglycemia secondary to OIAI. Given the patient’s critical condition she was initially started on stress dose of hydrocortisone 80mg every 8 hours. Attempts to down titrate the methadone dose were unsuccessful. Patient’s symptoms improved and hypoglycemia subsided. She was discharged home on hydrocortisone 10mg qam & 5 mg qpm and she was continued on Methadone 170mg daily. Conclusion: OIAI is an under-recognized clinical entity with potentially serious adverse outcomes. Currently, 3% to 4% of US adults receive long-term opioid treatment. OIAI is present in 9—29% of individuals on chronic opioids. Opioids act through suppression of the HPA axis, primarily at the level of the hypothalamus, mediated through either delta or kappa receptors leading to a decrease in ACTH and cortisol secretion. Management should include decreasing and ideally discontinue opioids, along with glucocorticoid replacement until documented recovery of the HPA axis. Reference: Reference: (1)Donegan, Diane et al. Opioid-Induced Adrenal Insufficiency. Mayo Clin. Proc. 2018 93(7), 937–944.
A Novel GATA3 Variant Causing Familial Hypoparathyroidism, Renal Agenesis and Sensorineural Deafness Presenting With Atypical Symptoms of Chronic Hypocalcaemia
Authors: Gaur Smriti , Page Suzanne , Khizer Mansoor , Rehman Shoib 
Published: May 2021

Abstract
Introduction: Familial hypoparathyroidism is a rare cause of hypocalcaemia. We report a case of long-standing hypocalcaemia secondary to hypoparathyroidism caused by a novel GATA3 variant resulting in multiple organ involvement. Case: A 20 year old girl was referred to our bone metabolic clinic for hypocalcaemia. Her past medical history included Bechet’s disease, epilepsy and depression. She had bilateral sensorineural hearing loss and encephalitis as a child. She underwent right nephrectomy for an atrophic non-functioning kidney at the age of 16. Current medication included hydroxychloroquine, diazepam, oral calcium and cholecalciferol. It was noted that the hypocalcaemia dated back to 8 years, she denied any typical symptoms of hypocalcaemia but she did report visual and auditory hallucinations, fatigue and had low seizure threshold. She sustained recurrent fractures of her arm, elbow and wrist. Initial investigations: Corrected calcium 1.88 (2.20-2.60mmol/L), Phosphate 1.54 (0.80–1.50mmol/L), PTH 1.2 (1.6–6.9pmol/), 25-OH vitamin D 37 (50-120nmol/L). Myeloma screen, thyroid, renal and liver functions were all within the normal reference range. Other bone markers: Serum Procollagen Type 1 Amino Terminal Peptide was mildly raised at 82 (19-69ug/L), CTX 0.42 (0.1-0.5ug/L), 1,25 OH Vitamin D 29 (55-139pmol/L), 24,25-dihydroxyvitamin D was normal with normal 25:24,25 Dihyroxyvitamin D ratio at 18 normal. Bone density was in the normal range for her age. MRI of the brain was normal with no evidence of calcification. There was a family history of hypocalcemia in her estranged father. Subsequent genetic analysis showed a novel likely pathogenic GATA3 missense variant (c.961T&gt;C p.(Cys321Arg). She was started on alfacalcidol and achieved near normocalcemia with adjusted calcium levels of 2.18nmol/L. Conclusion: Pathogenic variants in the GATA3 gene are responsible for Hypoparathyroidism-deafness-renal dysplasia (HDR) syndrome. In our patient, a novel missense variant in GATA3, p.(Cys321Arg), has been detected. This variant disrupts one of four conserved cysteine residues within a zinc-finger domain, which is involved in DNA binding and is presumed to have a deleterious effect on protein function. Patients may have longstanding asymptomatic hypocalcaemia with atypical features hence genetic testing is recommended in patient with multi-organ involvement. Alfacalcidol successfully restored calcium homeostasis in this case.
Paget’s Disease of Bone Affecting Site With Orthopedic Hardware
Authors: Serrano Santiago Ivan A , Lucier Jessica , Petak Steven Michael 
Published: May 2021

Abstract
Introduction: Paget’s disease of bone is a focal disorder of accelerated bone remodeling which leads to bone hypertrophy, cortical expansion and abnormal bone architecture. Either a single bone (monostotic) or multiple bones (polyostotic) can be affected. Although it has been suggested to be caused by a chronic slow viral infection of the bone, a cause and effect relationship has not been clearly established. Therefore, the etiology of Paget’s disease remains an uncertain and controversial topic of discussion. Case Description: A 62-year-old African American male with a past medical history of a left tibial fracture presented with worsening left leg pain for the past 6 months. He denied any recent traumatic events, falls or strenuous physical activity. Since the pain started, his ambulation had been significantly affected requiring the use of a cane for gait stability. His left tibial fracture occurred over 20 years ago after landing on another person’s foot while playing basketball. It was surgically treated with intramedullary nailing and metal rod insertion into the canal of the tibia. Since then, he remained an active person with no physical limitations or ailments until the recent developments that brought him to clinic. A left leg CT-Scan ordered for evaluation of the tibial hardware revealed cortical thickening, marrow expansion and coarse trabeculae throughout the majority of the tibia consistent with Paget’s disease. The hardware was intact with no peri-hardware lucency to suggest loosening or infection. His laboratory workup showed a normal alkaline phosphatase level (94 U/L; normal range 40 - 115 U/L) and low 25-OH Vitamin D level of 14. A Radionuclide Bone Scan done for evaluation of location and extent of bone disease resulted in diffusely abnormal uptake present in the left tibia with no other locations of suspicious uptake. After his 25-OH Vitamin D levels were replenished, a dose of Zoledronic acid IV infusion was given with significant improvement of pain several months after. Discussion: Paget’s disease of bone is the second most common bone disease after osteoporosis. Affected skeletal sites develop a disorganized mosaic of woven and lamellar bone more susceptible to deformities and fractures than normal bone. It is often asymptomatic, but classical features include bone pain experienced either at rest or with motion, cutaneous erythema and warmth. The goal of medical therapy is to relieve symptoms and to prevent future complications with high potency bisphosphonates. Although it is well known that Paget’s disease increase the risk of fractures, this case brings up an interesting take about the possibility of fractures managed with hardware placement increasing the risk of Paget’s disease in the involved site.
Primary Hyperparathyroidism Presenting With Atrial Fibrillation and Calcified Pericardial Effusion
Authors: Li Francesca , Rogers Rebecca , Rehman Shoib Ur 
Published: May 2021

Abstract
Background: Primary hyperparathyroidism is the most common cause of hypercalcemia and is frequently associated with skeletal and renal complications. It affects the older population and female gender more commonly. Cardiovascular complications due to altered calcium homeostasis are not well recognised or studied but recently cases of calcification of the pericardium, myocardium, valves and dysrhythmias have been reported.
Case: A 47-year old female presented to her GP with atrial fibrillation. Initial blood tests revealed an incidental hypercalcaemia; an adjusted calcium of 2.77 (normal 2.20-2.60mmol/L), raised PTH level of 14.0 (normal 1.6–6.9pmol/L), normal phosphate level and thyroid profile. 25-OH vitamin D level was low 39 (normal 50-120nmol/L). Autoantibody screens and CRP was normal. She was initiated on edoxaban, bisoprolol, and cholecalciferol and treated with a short course doxycycline for a presumed chest infection. There was no history of previous pericarditis but she had long standing hypertension and was obese with BMI of 37kg/m2. Retrospectively patient had sustained a recent wrist fracture and reported classic symptoms of hypercalcemia including fatigue, polydipsia, nocturia, constipation, depression in the endocrinology clinic. Further blood tests found a high C-terminal telopeptide (CTX) level of 0.68 (0.10-0.50ug/L) indicative of high bone turnover.24 urinary calcium/creatinine clearance ratio was 0.0189mmol/mmol (R&gt;0.01 for exclusion of FHH). She was prepped for DC cardioversion and Echocardiogram demonstrated Moderate sized pericardial effusion with some organisation but good biventricular function and dilated LA. Subsequent localisation studies with SPECT CT neck revealed a 9mm parathyroid adenoma along with calcified persistent moderate pericardial effusion putting the patient at risk of pericardial constriction. Patient was referred to the parathyroid surgeon for consideration of urgent parathyroidectomy and will be followed up by the cardiologist to see the impact of normalisation of hypercalcemia on the cardiac complication. It is thought that already established calcification of pericardial effusion is unlikely to resolve but achieving normocalcemia could slow the progression of pericardial calcification and improve bone turnover makers by switching off the excess parathyroid hormone. Patient will be followed up with repeat Echocardiogram post parathyroidectomy to elucidate the effects. Conclusion:Cardiac complications of primary hyperparathyroidism are increasingly becoming more evident with the advent and use of SPECT-CT for localising parathyroid adenomas. Simple screening tests like electrocardiogram may potentially point towards a cardiovascular complication and should be considered routinely in hypercalcaemic patients. Further studies to understand the mechanism of developing cardiac complication in such patients are needed.
Treatment-Resistant Hypercalcemia Secondary to Ectopic PTH Hypersecretion From Disseminated Ovarian Cancer
Authors: Balinski Alexander M , Khatter Neil J , Gold Jeffrey M , Pothugunta Krishna S , Garlapaty Vamshi K , Rankin Steven M , Thorburn Christopher A , Abu-khaled Jamal 
Published: May 2021

Abstract
Background: Hypercalcemia of malignancy (HCM) can present secondary to hypersecretion of parathyroid hormone (PTH)-related protein (PTHrP) from malignant tumors, but rare cases of HCM have also been documented due to inappropriate PTH secretion from ectopic neoplasms. Here, we report an unusual case of HCM due to hypersecretion of PTH from a disseminated mucinous ovarian adenocarcinoma.
Case Presentation: A 45-year-old female presented with confusion, constipation, fatigue, and abdominal pain two weeks after total abdominal hysterectomy with bilateral salpingo-oophorectomy and suboptimal debulking of a newly discovered left ovarian mucinous adenocarcinoma with metastasis to the bladder, parametrium, vagina, right ovary, and rectosigmoid. Subsequent CT revealed numerous bilateral pulmonary nodules, hilar adenopathy, liver lesions, and abdominal adenopathy. On exam, she was tachycardic and hypertensive with diaphoresis, dry mucous membranes, respiratory distress, guarded abdominal tenderness, and altered mental status. Her labs were significant for a serum calcium of 21.7 mg/dL, creatinine of 1.93 mg/dL, ferritin of 2,379 ng/mL, leukocytosis of 21.9 bil/L, PTH of 1,061 pg/mL, and PTHrP of 29 pmol/L. Ectopic PTH secretion was highly suspected after negative parathyroid ultrasound. Pamidronate (60 mg IV), calcitonin (200 U IM), and fluid resuscitation were unable to normalize her serum calcium, resulting in the need for dialysis and subsequent continuous renal replacement therapy. Further intervention with denosumab (120 mg SQ), etelcalcetide (5 mg IV), and cinacalcet (60 mg PO) was also attempted. Serum calcium began to decline, but repeat PTH resulted greater than 2,500 pg/mL. Unfortunately, the patient died just one week into her hospital course from septic shock and multi-organ system failure.
Discussion: Hypercalcemia of malignancy typically arises from tumor secretion of PTHrP, cytokine release from osteolytic metastases, or tumor production of calcitriol. In cases of hypercalcemia due to excess PTH secretion, primary parathyroid etiologies are typically considered while ectopic PTH-secreting tumors are rare. PTH staining of biopsy specimens and total body sestamibi scan may prove useful in the early detection and treatment of these tumors, but HCM offers a poor prognosis with mean survival of 2 to 3 months and in-hospital mortality of 6.8%. Currently, there are only three cases in the reported literature of ectopic PTH-induced hypercalcemia related to ovarian cancer. To our knowledge, this is the fourth reported case.
Conclusion: Ectopic PTH-secreting tumors carry a poor prognosis and should be considered in cancer patients presenting with PTH-associated hypercalcemia. Biopsy staining for PTH and total body sestamibi scan may assist in the early detection of these tumors, but current treatment strategies offer suboptimal outcomes.
The Influence of Vitamin D Status on the Severity of SARS-CoV-2 Respiratory Infection
Authors: Silva José Diogo , Rouxinol-Dias Ana , Rocha Gustavo Melo , Correia Sara , Almeida Lúcia , Alves Helena , Oliveira Maria João 
Published: May 2021

Abstract
Introduction: The high prevalence of vitamin D (vitD) deficiency in the general population is well recognized. Evidence suggests an immunomodulatory role for vitD in pro-inflammatory conditions, but doubt remains on its association with the severity of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) respiratory infection (RI).
Aim: To assess the impact of vitD status on the severity of SARS-CoV-2 RI in adults.
Material and Methods: A cross-sectional study that included adults infected with SARS-CoV-2 until 1/14/2020 was performed. Patients taking calcium, vitD supplementation or antiepileptics, with malabsorptive and/or calcium and phosphate metabolic disorders or stage 4 or 5 chronic kidney disease were excluded. Levels of 25-hydroxyvitamin D (25(OH)D) were obtained at the time of RI diagnosis. The participants were divided into 2 groups, depending on the vitD status (sufficiency and insufficiency [≥20 ng/mL]; deficiency [&lt;20 ng/mL]), and in 3 groups of clinical severity of RI (adapted from the update [14/10/2020] of the standard 004/2020 of the Portuguese Directorate-General for Health): mild/moderate disease (g1); severe disease without bacterial coinfection (g2); severe disease with bacterial coinfection/critical disease (g3). Other factors associated with RI severity were analyzed. A multiple logistic regression model was developed to predict the severity of SARS-CoV-2 RI, considering vitD status as a categorical variable and other variables with statistical significance after univariate analysis.
Results: This study encompassed 71 infected patients with a median age of 68 (p25;p75 = 58;77) years, 40 (56.3%) of which were women. 32 (45.1%) patients integrated g1, 14 (19.7%) g2 and 25 (35.2%) g3. 39 (54.9%) presented vitD deficiency and 32 (45.1%) vitD sufficiency or insufficiency. In the univariate analysis, vitD deficiency, age (&gt;60 years old), male gender, Arterial Hypertension, Diabetes Mellitus, use of angiotensin-II receptor antagonist and reduced levels of ionized serum calcium correlated with the severity of RI. In the multivariate regression model that included these variables, vitD deficiency remained independently correlated with critical/severe disease with bacterial coinfection (g3 vs. g1: OR=9.7; CI95%=[1.7; 56.4]; p=0.011; g3 vs. g2: OR=6.3; CI95%=[1.1–37.0]; p=0.044), with a tendency, albeit not statistically significant, for severe RI without bacterial coinfection (g2 vs g1: OR=1.6; CI95%=[0.3; 7.4]; p=0.581).
Conclusions: An independent association of vitD deficiency with the severity of SARS-CoV-2 RI was found, supporting the anti-inflammatory effects of vitD. It is essential to identify and treat its deficiency in patients prone to adverse outcomes of SARS-CoV-2 RI.