Hypercalcemia Research Articles

ODP552 Hypercalcemic Crisis Due to PTH Secretion From a Poorly Differentiated Esophageal Neuroendocrine Tumor

Abstract Background Paraneoplastic secretion of PTH is described in a number of solid organ tumors. Hypercalcemia occurs in up to 30% of patients with malignancy. The most common cause of this phenomenon is PTHrP production. We present a rare case of PTH mediated hypercalcemic crisis from a tumor of presumed esophageal lineage. Clinical Case A 54-year-old man presented with several days of fatigue, lethargy and polyuria. Initial calcium was markedly elevated at 18.4 (8.3-10.1mg/dL). Past medical history included Barrett's esophagus, history of gastric bypass, and prior alcohol abuse. He also had progressive dysphagia and 30lb weight loss over the prior month. On examination, he had tachycardia, cachexia, and encephalopathy. Laboratory testing revealed an elevated PTH of 281 (nl 18.4-80.1pg/mL), creatinine 1.34mg/dL, and low phosphorus at 2.8 (nl 2.7-4.5mg/mL). Hypercalcemia was treated with IV fluids, calcitonin, and pamidronate. The calcium normalized but PTH remained 210pg/mL. Subsequent PTHrP and 1,25 di-hydroxy vitamin D levels were normal. Esophagogastroduodenoscopy (EGD) revealed a friable esophageal mass and biopsy identified a poorly differentiated carcinoma with neuroendocrine features, immunoreactive to synaptophysin and high Ki-67 index of 90%. Immunostains for chromogranin and PTH were negative. A CT of the chest, abdomen, and pelvis revealed diffuse metastases in the liver, lungs, and enlarged mediastinal lymph nodes. The source of primary tumor could not be fully identified from pathology but suspected to be esophageal. Parathyroid scan showed a subtle persistent uptake posterior to right side of trachea suspicious for a parathyroid adenoma, but that could not account for the severity of PTH elevation. He was readmitted in 1 month with recurrent symptomatic severe hypercalcemia to 18mg/dL and PTH to 619.4pg/mL. Again, he received IV fluids, calcitonin, and zoledronic acid. He received 3 cycles of platinum and etoposide based chemotherapy. After chemotherapy, PTH decreased to 123pg/mL and calcium to 9.7mg/dL but he continued to have rapid disease progression including jaundice, pathological bone fractures and orbital metastases. He elected hospice care and passed away in about 4 months from initial diagnosis. Final PTH was 916.8pg/mL. Conclusion PTH is a normally secreted by parathyroid gland chief cells, which are part of the embryonic neural crest cells found in various neuroendocrine tissues. It is plausible that malignancies with neuroendocrine features may secrete neuropeptides including PTHrP and PTH. Few case reports exist describing PTH secretion by neuroendocrine tumors, though most common are tumors of gastroenteropancreatic origin. PTH stain and focal chromogranin tends to be negative with poorly differentiated neuroendocrine tumors. PTH gene is usually intact and upregulation of the regulator sequence of PTH gene promotor is suspected to be the mechanism of elevated PTH levels and hypercalcemia. This case demonstrates the potential for poorly differentiated neuroendocrine malignancies to cause hypercalcemic crises from paraneoplastic secretion of PTH. Presentation: No date and time listed

Hypercalcemic Crisis as a Presentation of Parathyroid Adenoma: An Atypical Clinical Case Study

Hypercalcemic Crisis as a Presentation of Parathyroid Adenoma: An Atypical Clinical Case Study

ODP564 Hypercalcemia in the Setting of HTLV-1 Infection and Normal PTHrP Levels

Abstract A 53 year old male with history of HTLV-1 infection associated myelopathy but with unknown mode of transmission, presented with acute on chronic bilateral lower extremity weakness and numbness with no other deficits. Examination revealed decreased strength (grade 1/5) in lower extremities with normal bulk, tone and sensations. Initial blood work revealed hypercalcemia with corrected Calcium of 16.2mg/dl(8.5-11.5), Phosphorus of 2.7mg/dl (2.5- 4.5) and Alkaline Phosphatase of 126mg/dl(20-140). Workup for hypercalcemia revealed Parathyroid hormone (PTH) level of 14pg/ml (10-65), 25 hydroxy vitamin D at 19.6 ng/ml(30-100), 1,25 dihydroxy vitamin D at 6.7pg/ml(19.9-79.3) and TSH of 1.265 microIU/ml(0.5-5). The Parathyroid hormone related protein(PTHrP) level was low at < 2pmol/L while Lactate Dehydrogenase (LDH) was 433U/L(100-220). Urine calcium creatinine ratio was 0.388. Reverse Transcriptase PCR was positive for HTLV-1 but negative for HTLV-2. Smudge cells and atypical lymphocytes were noted on peripheral smear. Imaging revealed generalized lymphadenopathy with splenomegaly but no spinal cord compression. Flow cytometry showed 7.8% atypical helper T cells, positive for CD3, CD4, CD5 and CD45. Clonal T cell receptor gene rearrangements were found, suggesting an underlying T cell neoplasm. Lymph node biopsy confirmed ATLL. He received treatment with fluids, Calcitonin and Denosumab after which serum Calcium levels fell (nadir 7.7mg/dl) and then normalized. He developed another episode of hypercalcemia 5 weeks later which was treated similarly. Discussion Human T cell Lymphotropic Virus-1 (HTLV-1) is a retrovirus causing asymptomatic infections, symptomatic systemic disorders and adult T cell Leukemia and lymphoma(ATLL). HTLV-1 infections, whether in asymptomatic or symptomatic patients, and ATLL are rare but important causes of hypercalcemia and hypercalcemic crises. Individuals with ATLL have the highest incidence of hypercalcemia(50-70%) among all hematologic malignancies. Hypercalcemia is a poor prognostic factor and predicts lower overall survival. It is caused by increased bone resorption, mediated by various factors with the largest role being played by Receptor Activator of Nuclear Factor Kappa B ligand (RANKL), followed by PTHrP, Interleukins, Macrophage Inflammatory Protein 1 alpha and gp 46. RANKL expression is increased upon transactivation by the viral TAX gene product and mediates conversion of osteoclast precursors to mature osteoclasts engaging in bone resorption. PTHrP expression is variable among patients, relating to levels of the TAX gene product that transactivates the PTHrP gene promoter. Thus, a low level, like in our patient, does not rule out HTLV infection as the cause of hypercalcemia. Management of hypercalcemia is in keeping with guidelines for management of other causes of hypercalcemia but may be better responsive to monoclonal antibodies against RANKL than bisphosphonates given the role of the ligand in mediating hypercalcemia in these cases. It can also be used in the setting of poor renal function, which is commonly encountered in hypercalcemic patients. Presentation: No date and time listed

ODP084 Denosumab as a therapuetic modality in management of primary hyperparathyroidism induced severe hypercalcemia

Abstract Background Primary Hyperparathyroidism(due to parathyroid adenoma) is usually associated with smoldering clinical course due to effects of chronic hypercalcemia whereas malignancy related hypercalcemia is often associated with life threatening severe hypercalcemia. However in rare instances, hypercalcemic crisis may be sole presenting feature of primary hyperparathyroidism. The role and utility of denosumab therapy in such clinical settings is less well studied. Case Report: A 53 year old male patient was referred for evaluation of severe hypercalcemia. He presented with symptoms of nausea, vomiting and constipation for last two weeks. He did not give any history of abdominal pain, polyuria, polydipsia, nephrolithiasis, bony fractures, acid peptic disease or cognitive impairment in past. He was a known case of type 2 diabetes mellitus for last 2 years and was on oral anti diabetic drugs with fairly good glycemic control. On evaluation, the patient was conscious, oriented and lethargic. His vitals were stable and systemic examination was grossly normal. Abdominal imaging including upper gastrointestinal endoscopy for his above complaints revealed no gross abnormality. Significant positive findings from biochemical evaluation included: severe hypercalcemia(serum calcium level-20.45 mg/dl, normal: 8.6-10.3mg/dl), serum phosphorous-2. 09mg/dl(normal: 2.7-4.5mg/dl), serum albumin-4.26g/dl(normal: 3.4-4.4g/dl) and serum creatinine-3.1mg/dl(normal: 0.8-1.5mg/dl). A kidney function test done during periodic health screening two months ago was absolutely normal(serum creatinine: 0.9 mg/dl). PTH levels were found to be significantly elevated (1383.6pg/ml, normal: 15-65pg/ml). A presumptive diagnosis of primary hyperparathyroidism induced severe hypercalcemia with acute kidney injury was made. He was initially managed with saline rehydration followed by diuretic therapy and subcutaneous calcitonin administration. However, no significant response was seen. In view of his deteriorating renal function and severe hypercalcemia, immediate hemodialysis was planned in consultation with nephrologist. Despite three sessions of hemodialysis, his serum calcium and creatinine levels were lowered to 17.69mg/dl and 2.1mg/dl respectively. Owing to refractory and persistent hypercalcemia, injection denosumab(60 mg sc) was subsequently administered. Following denoumab therapy, serum calcium continued to show a declining trend and it came down to 10.8mg/dl by end of fourth day. In the meantime, localization studies including neck ultrasonography and Technetium 99m sestamibi scan confirmed presence of right inferior parathyroid adenoma. The patient subsequently underwent successful focused parathyroidectomy with rapid improvement in his health status. Following surgery, he was managed with calcium and calcitriol supplementation to maintain normocalcemia. Histopathological examination of excised tumor confirmed presence of parathyroid adenoma. Conclusion Hypercalcemic crisis can be a rare presenting feature of primary hyperparathyroidism. Denosumab therapy can play a pivotal role in managing such patients(especially when other therapeutic modalities fail to control underlying severe hypercalcemic state) and act as beneficial bridging therapy till definitive surgery can be undertaken. Presentation: No date and time listed

PSUN377 Use of Novel Therapy in Management of Metastatic Parathyroid Cancer

Abstract Introduction Parathyroid cancer (PC) is a rare malignant tumor which represents <1% of patients with primary hyperparathyroidism (PHPT). With less than 1000 reported cases, PC is the rarest endocrine cancer. Complicating its rarity, is the known resistance to radiation and chemotherapy, and complete surgical resection is the only curative treatment available. Genomic sequencing targeted therapy has shown encouraging results. We hereby present a case where Pembrolizumab was used in treatment of metastatic PC. Case A 50 year old lady with a history of nephrolithiasis, hypercalcemia(HC) presented for evaluation of neck mass. She had a recent admission to outside hospital for HC, dehydration, bone pain, polyuria, constipation and workup was suggestive of PHPT with Calcium(Ca) 13.2mg/dL and PTH 1,500pg/ml. Neck ultrasound demonstrated a 3 cm nodule in the left thyroid and fine needle aspiration was suspicious for malignancy. She underwent left hemithyroidectomy, and left parathyroidectomy. PTH levels pre-, intra- and postoperatively were 680, 220, 20 pg/ml respectively with normalization of Serum Ca. Histopathology revealed high grade PC with lymphovascular and perineural invasion. Postoperatively she received adjuvant radiotherapy. Ten months later CT Neck surveillance revealed a 4cm Left prevertebral(PV) mass with recurrence of bone pain, PTH 110pg/ml, and Ca-11.2mg/dL. Parathyroid scan showed Left PV mass and Left level 2 lymph node. PET/CT later revealed fluorodeoxyglucose avidity of the recurrent mass, as well as bilateral lung, right ventricle, and pelvic lesions. Incisional biopsy confirmed carcinoma consistent with PC. Her neck lesions were deemed unresectable. Germline mutation testing confirmed Next Generation Sequencing: PDL1 5% by CPS, TMB 10 mut/Mb, IDH2, JAK1, KMT2C, NF1, PIK3RI. On the basis of TMB >10 mut/Mb Pembrolizumab was then initiated with good response, noting improvement in symptoms, and normalization of Ca 8.7mg/dL and PTH 35pg/ml. Within 4 months of therapy Surveillance CT showed an approximate 40% reduction in tumor burden noting decrease in size of neck mass and lesions in lungs, right ventricle, and pelvis. Discussion Approximately 10%-30% of PCs have metastasis at presentation, most commonly to the lung, bone, or liver. However they can often develop local recurrence and or distant metastases despite early intervention. Surgical resection remains the mainstay of treatment, and is often used to decrease tumor burden which has been shown to improve morbidity. However when surgical resection is not an option, newer approaches using gene sequence targeted therapy may be an attractive option in the future as was demonstrated in this patient. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

ODP589 Acute Hypercalcemic Crisis in an Elderly with Granulomatous Disease

Abstract We present here a case of an 81 year old female who developed changes in neurologic status due to elevated serum calcium levels in the setting of an elevated Vitamin D and low-normal parathyroid hormone level. Upon evaluation of PTH-independent causes of hypercalcemia, she was noted to have Tuberculosis. Anti-Koch's and steroids were initiated on top of vigorous hydration and diuresis which lead to improvement in the patient's serum calcium levels and clinical status. Tuberculosis rarely leads to clinically significant hypercalcemia. However, elderly patients remain predisposed due to advanced age, multiple comorbidities and polypharmacy. Hypercalcemia is a life threatening condition, but with prompt diagnosis and management it portends excellent outcomes. Presentation: No date and time listed

Bones, Groans, and Thyroid Hormones: A Rare Case of Hyperthyroidism Induced Hypercalcemic Crisis

Bones, Groans, and Thyroid Hormones: A Rare Case of Hyperthyroidism Induced Hypercalcemic Crisis

ODP133 Rare Case of Primary Hyperparathyroidism Causing Hypercalcemic crisis in Systemic Lupus Erythematosus (SLE)

Abstract Introduction Hyperparathyroid crisis is a rare endocrine emergency with a high mortality. Primary hyperparathyroidism (PHP) can present as severe hypercalcemia. There are very few cases documented in literature of patients with concomitant SLE and PHP. We present a case of hypercalcemic crisis in a patient with untreated primary hyperparathyroidism with a history of SLE. Case description A 46 year old woman was found to have hypercalcemia of 12.9 mg/dl on routine lab work. Her medical history is significant for SLE (diagnosed 9 years prior) and osteoarthritis. She had no physical complaints. Further workup confirmed primary hyperparathyroidism with PTH of 322.8 pg/ml and findings consistent with parathyroid adenoma on Sestamibi scintigraphy. Parathyroidectomy was strongly recommended however the patient refused. She was then offered medical management but did not show up for any follow up appointments. Two years later, she presented to the emergency department with altered mentation, lethargy, poor oral intake and abdominal pain for 2 days. She was found to have severe hypercalcemia with a serum calcium of > 24.8 mg/dl and was in acute renal failure. On admission, EKG changes suggestive of pseudoinfarct pattern from severe hypercalcemia were present. She was managed in the intensive care unit with intravenous hydration, calcitonin, zoledronic acid and hemodialysis. Shortly after initiation of hemodialysis, the patient succumbed to a cardiac arrest. Conclusion Hyperparathyroid crisis when untreated has a 100% mortality rate. Early management with surgical intervention is the only confirmed cure for PHP. There are only 18 cases reported in literature of hypercalcemia in SLE. Mechanisms involved are believed to be stimulatory PTH antibodies, PTHrP and osteoclastic activity due to inflammatory cytokines. To our best knowledge this is the 6th case report of a patient with concomitant SLE and PHP. A prospective study by Norman et. al 1 done in 10000 PHP patients demonstrated a Gaussian distribution with the average calcium concentration being 10.9 ± 0.6 mg/dL and the average parathyroid hormone concentration being 105.8 ± 48 pg/ml . Her baseline calcium at diagnosis was 13mg/dl and intact PTH was 322.8 pg/ml which is higher than seen in the normograms as per the study. In our patient, we believe SLE could have exacerbated the hypercalcemia caused by PHP. It is important to perform further studies to identify if any association exists between the two conditions. Physicians must recognize their concomitant occurrence as prompt management of hypercalcemia becomes even more crucial in these cases.

PSAT215 Hypercalcemic Crisis Complicating a First Trimester Pregnancy Caused by a Giant Parathyroid Adenoma Masquerading as a Thyroid Nodule

Abstract Background Primary hyperparathyroidism (PHP) during pregnancy is rare with a reported incidence of 1%, although the true incidence is unknown. It is associated with increased morbidity and mortality for both mother and fetus. Most reported cases of PHP during pregnancy are due to small adenomas causing mild hyperparathyroidism. Surgical management is recommended if the calcium level is >11mg/dL (2.75mmol/L) or the patient has symptomatic hypercalcemia. It is generally recommended that surgery be performed in the second trimester due to the risk of miscarriage in the first trimester, and preterm labor in the third trimester. Case A 29-year-old woman presented to our emergency department at 10 weeks’ gestation with nausea and vomiting. She also reported constipation and fatigue. On examination, she was euvolemic, awake and alert, with no neurological symptoms or signs. The suspected diagnosis was hyperemesis gravidarum until her laboratory evaluation revealed marked hypercalcemia [15.6mg/d (3.9mmol/L)]. Further labs revealed hypophosphatemia [1.2mg/dL (0.39mmol/L)], hypokalemia [3.3mEq/L], hypomagnesemia [1.4mEq/L], low 25-hydroxy vitamin D [16.2ng/mL (40.44pmol/L)], and elevated intact parathyroid hormone (iPTH) [573pg/mL], 1,25-dihydroxy vitamin D [251.1pg/mL (626.75pmol/L)], and 24 hour urinary calcium [448mg/24 hours (11.2mmol/24 hours]. On cardiac evaluation, her QTc was normal. The patient was given intravenous hydration with normal saline, which reduced the calcium to 13.6mg/dL (3.4mmol/L) after 48 hours. She remained symptomatic and severely hypercalcemic, so calcitonin 4 IU/kg every 12 hours was added, while a neck ultrasound was performed to localize the parathyroid adenoma. Her calcium level decreased to 10.7mg/dL (2.7mmol/L) after calcitonin, but rapidly rebounded to 13.3mg/dL (3.3mmol/L) along with hypophosphatemia and hypokalemia. Intravenous potassium phosphate was initiated and her calcium decreased to 11.8mg/dL (2.95mmol/L). The neck ultrasound did not identify a parathyroid adenoma, but identified a 2.5×1.5×3.3 cm right mixed cystic/ solid thyroid nodule. An MRI of the neck revealed two right thyroid nodules. The decision was made to perform a neck dissection given the persistent severe hypercalcemia after a multidisciplinary team evaluation, and extensive discussion with the patient. The surgical exploration of the right neck identified a giant parathyroid adenoma that weighed 11.3g. The intraoperative PTH levels reduced from 804pg/mL to 60.7pg/mL. Her calcium normalized immediately postoperatively and she was discharged home without complication. At the time of last follow up, she was 18 weeks’ gestation and a fetal ultrasound was normal. Discussion This case had three unusual features: PHP causing severe hypercalcemia during pregnancy; a giant parathyroid adenoma; and parathyroid adenoma masquerading as a thyroid nodule on imaging. This case highlights the importance of a multidisciplinary team approach in optimizing the care of such complicated patients, along with the need for definitive surgical intervention. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Primary hyperparathyroidism, presenting with acute kidney injury in the first trimester of pregnancy; a case report

Primary hyperparathyroidism (PHPT) is the leading cause of hypercalcemia. Total serum calcium level >3.5 mmol/L is associated with a high risk of a hypercalcemic crisis, manifesting with nausea, vomiting, dehydration, myalgia’s, abdominal pain, acute pancreatitis, acute kidney injury (AKI), cardiac rhythm disorders and disturbances of consciousness. We report here a case of PHPT, manifested with hypercalcemic crisis during pregnancy. A 30-year-old woman in the first trimester of pregnancy admitted complaining on loss of appetite, nausea, vomiting, lower abdomen pain, weakness, and leg pain during the last 10 days. She had a history of two uncomplicated pregnancies, and two episodes of renal colic, her kidney function was normal 2 weeks prior to admission. Work-up showed hypochloremia, hypokalemia, hyponatremia, total serum calcium was 5.34 mmol/L, and serum creatinine 226 µmol/L, and she underwent urgent hemodialysis (HD). Her parathyroid hormone (PTH) was 948 pg/mL, and imaging revealed missed miscarriage 9-10 weeks, soft tissue mass 30x20x33mm near the lower pole of the left lobe of the thyroid gland, small stones in renal calices, and polysegmental pneumonia. She received antibiotics, calcimimetics, and every-day hemodiafiltration (HDF), and underwent vacuum aspiration of uterine cavity and surgical removal of the parathyroidoma. Her PTH shortly returned to the reference level, and serum creatinine dropped to 140 µmol/L after kidney replacement therapy (KRT) secession. Pathology confirmed the diagnosis of parathyroid adenoma. PHPT should be included in the diagnostic algorithm of AKI in pregnancy along with vomiting of pregnant, sepsis, pre-eclampsia and other causes. Successful management of PHPT complications in pregnancy demands multidisciplinary team.

Hypercalcemia in the setting of HTLV-1 infection and a normal PTHrP level

SummaryHuman T-cell lymphotropic virus-1 (HTLV-1) causes adult T-cell leukemia and lymphoma (ATLL) and is a rare but important cause of hypercalcemia. A 53-year-old male with HTLV-1-associated myelopathy presented with acute on chronic bilateral lower extremity weakness and numbness. Initial blood work revealed hypercalcemia with corrected calcium of 16.2 mg/dL (8.5–11.5) with normal levels of phosphorus and alkaline phosphatase. Workup for hypercalcemia revealed parathyroid hormone (PTH) of 14 pg/mL (10–65), 25 hydroxy vitamin D at 19.6 ng/mL (30–100), 1,25 dihydroxy vitamin D at 6.7 pg/mL (19.9–79.3), thyroid-stimulating hormone of 1.265 μIU/mL (0.5–5), undetectable PTH-related protein (PTHrP) and lactate dehydrogenase of 433 U/L (100–220). The urine calcium creatinine ratio was 0.388. Reverse transcriptase PCR was positive for HTLV-1 and negative for HTLV-2. Peripheral blood flow cytometry and lymph node biopsy confirmed ATLL. He received treatment with fluids, calcitonin and denosumab after which serum calcium levels fell (nadir: 7.7 mg/dL) and then normalized. Humoral hypercalcemia in this setting is mediated by receptor activator of nuclear factor-kappa B ligand (RANKL), PTHrP and other cytokines. PTHrP levels depend on levels of the TAX gene product, cell type and lymphocyte-specific factors. Thus, a low level, like in our patient, does not rule out HTLV-1 infection/ATLL as the cause of hypercalcemia. Hypercalcemia is known to be responsive to monoclonal antibodies against RANKL given the compound’s role in mediating hypercalcemia in these cases.Learning pointsHuman T-cell lymphotropic virus-1 infection and adult T-cell leukemia and lymphoma are associated with high rates of hypercalcemia and hypercalcemic crises.Hypercalcemia in these cases is mediated by osteoclastic bone resorption carried out by several agents including receptor activator of nuclear factor-kappa B ligand, parathyroid hormone-related protein (PTHrP), macrophage inflammatory protein 1 alpha, interleukins, etc. A normal PTHRrP does not rule out humoral hypercalcemia of malignancy in this setting, as indicated by this case.Hypercalcemia in such settings is highly responsive to monoclonal antibodies against RANKL given the role the ligand plays in resorptive hypercalcemia.

Dihydrotachysterol: a bad choice in the treatment of chronic hypoparathyroidism

Hypoparathyroidism is an endocrine disease caused by damage of the parathyroid glands and characterized by underproduction of parathyroid hormone. This can lead to severe hypocalcemia and its associated complications. The chronic hypoparathyroidism requires lifelong therapy including calcium and vitamin D analogues. The goal of treatment is to maintain the target parameters of phosphorus-calcium metabolism. At the same time, there is a risk of iatrogenic hypercalcemia on the standard therapy, up to the hypercalcemic crisis, often complicated by the acute renal failure. Moreover, chronic hypercalcemia acts as a predisposing factor for nephrolithiasis, nephrocalcinosis, chronic renal failure including pre- and dialysis stages.Dihydrotachysterol is a synthetic analogue of vitamin D, which was previously widely prescribed for hypocalcaemic hypoparathyroidism. In accordance with modern Russian and international guidelines, this drug should not be used in the treatment of chronic hypoparathyroidism. The main features in the metabolism of dihydrotachysterol (long elimination period, lack of feedback regulation of the active metabolites, high biological activity) and a narrow therapeutic window cause the frequent development of hypercalcemia and associated disorders.We present several clinical cases of patients with hypoparathyroidism treated with dihydrotachysterol, which was complicated by severe hypercalcemia and acute renal failure.

Acute hypercalcemic crisis in an elderly with granulomatous disease

Acute hypercalcemic crisis in an elderly with granulomatous disease

Abstract #1182278: Hyperthyroidism-induced hypercalcemia: Timing of response to treatment in the acute setting

Hyperthyroidism is an uncommon cause of hypercalcemia (HYPERCA). There is little information to guide the clinician on calcium (CA) response in relation to thyroid hormone control. This knowledge may be important when HYPERCA needs to be quickly treated due to its severity or to underlying patient co-morbidities. We describe a patient with HYPERCA of moderate severity due to Graves’ disease (GD) hyperthyroidism in whom normalization of CA level was a priority. Changes in CA levels in response to improvement in thyroid function and the role of anti-resorptive agents in this setting are discussed.

Primary hyperparathyroidism: optimize the detection and monitoring (organizational aspects)

Background. The relevance of the study is due to the fact that undiagnosed primary hyperparathyroidism (PHPT) significantly increases the risk of osteoporosis and fractures, nephrolithiasis and renal failure, reducing the quality of life of patients. All this necessitates the improvement of the organizational system of disease detection and monitoring. The purpose of the study was to assess the incidence of hypercalcemia (HCa) in patients with endocrine disorders and to determine the sex and age composition in the subgroup with HA. Materials and methods. The frequency of HCa (by total calcium and ionized calcium levels) in 107 patients with endocrine pathology examined in endocrine clinic during November and December 2021 was determined, gender and age characteristics, the nature of endocrine pathology in the subgroup with HCa were characterized. The level of total calcium was determined by photocolorimetric method using a photometer ”Solar PM 2111“, set ”SpL“ (Ukraine), the level of ionized calcium was determined by a calculated method depending on the concentration of albumin. Results. Among patients with endocrine pathology, HCa occurs in approximately 30 % of cases. The ratio between men and women is similar in the subgroups with normo- and hypercalcemia. The presence of endocrine comorbidity in patients increases the risk of HCa. The obtained results show that the existing organization of work in Ukraine to identify and monitor patients with HCa needs to be optimized. As a sample, we can use the conceptual model of action of a primary care physician developed by American authors, aimed at optimizing the work on the detection and monitoring of PHPT. Conclusions. For Ukraine, the problem of improving the organizational system for detection and monitoring of HCa, which should include deadlines for monitoring blood calcium levels, periodicity of research, further monitoring of people with HCa, provide communications to primary and specialized physicians.

Hypercalcaemic crisis due to parathyroid adenoma of atypical location.

Not required for Clinical Vignette.

BRAF Mutations and Inflammatory Gene Expression in Myeloma Cells from Patients with Renal Dysfunction

BRAF Mutations and Inflammatory Gene Expression in Myeloma Cells from Patients with Renal Dysfunction

A 40-year-old Woman with Hypercalcemia Crisis Caused by Bone Metastasis in Stage IV Breast Cancer

Breast cancer is still global burden especially for woman with 2.3 million cases every year dan 15% mortality among cancer diseases. In developing countries, most of the cases are diagnosed at terminal stage when metastasis already found. Bone metastasis is the highest among other metastasis sites such as: lung, liver and brain. Bone metastasis will cause hypercalcemia and bone pain as complications. Both will gradually decrease patient’s quality of life. Comprehensive and holistic management for these complications will reduce deterioration and hopefully increase patient’s quality of life even they were at terminal stage. We describe a 40-year-old woman who got hypercalcemia crisis. Hypercalcemia usually manifest as a consequence of other diseases. Epidemiologically, majority come from metastasis, but can be other diseases, such as multiple myeloma. Interestingly, during medical investigation through her medical history, and physical examination, and laboratory examinations, we conclude that her hypercalcemia crisis was caused by bone metastasis from breast cancer.

Total Calcium and Ionized Calcium (pH = 7.4) Tests Are Equal When Screening Patients for Hypercalcemia at Admission in the Emergency Department: A Retrospective Descriptive Study

Background: Ionized calcium (pH = 7.4) (CaI) is a laborious test compared to tests for total calcium (CaT). However, CaI is the biologically active part of calcium in the blood and is therefore often considered the most relevant measure of calcium status. In this study, CaI and CaT tests were compared by identifying clinically relevant hypercalcemia (HC) in unselected patients acutely admitted to an emergency department (ED). Methods: CaI and CaT were measured in all medical patients admitted to the ED at a single Danish Hospital (N = 13,400) between January 2018 and May 2019. The majority (97%) of the patients were admitted 1 - 3 times summing up to a total of 17,838 admissions. As limits for clinically relevant HC, 1.45 mmol/L for CaI and 2.77 mmol/L for CaT were used. Mismatches were defined as one test being equal to or above the limit while the other test was within or below its reference interval. In cases of mismatch, the medical record was reviewed. Results: Seventeen mismatches with CaI ? 1.45 mmol/L were observed in 16 patients, of whom eight were known with diseases with risk of HC. Five patients had HC with no clinical relevance, one had HC of unknown relevance, and only two patients were discovered as having a prior unknown calcium metabolic disease. Three mismatches were observed in admissions with CaT ? 2.77 mmol/L. Mismatches did in none of these cases have any clinical consequences. Conclusion: By using CaT as a screening method for HC instead of CaI, only two patients with prior unrecognized HC would have been missed and it did not result in a large number of patients with false HC. We therefore find that CaT is an acceptable test when screening for HC in the ED. J Endocrinol Metab. 2021;11(5):108-114 doi: https://doi.org/10.14740/jem757

POST TRAUMATIC CAROTID CAVERNOUS FISTULA PRESENTING AS PARATHYROID CRISIS

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: This is a case of two rare entities causing non-specific symptoms. Carotid-cavernous sinus fistula (CCF) arises from miscommunication of carotid arterial flow and the cavernous sinus. Post traumatic CCF presents bilaterally are uncommon, only 1-2% of patients. While already a rare diagnosis, our patient presented in an acute parathyroid crisis defined by symptomatology caused by markedly elevated calcium and parathyroid hormone, which may have masked our diagnosis of CCF. CASE PRESENTATION: A 57-year-old Colombian female presented with dizziness, anorexia, nausea, and vomiting. She also endorsed intermittent diplopia in the left eye. Physical exam revealed left sided ptosis. She reports a remote history of head trauma a month prior. Serum calcium on presentation was 13.6 mg/dL, ionized calcium of 6.8 mg/dL, and parathyroid hormone (PTH) was 219.8 pg/mL. Subsequently, a Technetium 99m sestamibi scan showed increased radioisotope along the right lower pole of the thyroid gland confirming primary hyperparathyroidism. She was resuscitated with normal saline fluid and started on Cinacalcet for hypercalcemia. Attempts to lower serum calcium can be achieved using bisphosphonates and may be effective within the first 24 hours. In our patient, Cinacalcet did not achieve sufficient calcium lowering thus, Zoledronic acid was used due to its potency with small doses. Nausea, vomiting, and positional dizziness resolved. Despite resolution of symptoms, she continued with ptosis; thus prompting further work up. Magnetic resonance angiography and venography revealed extensive time of flight enhancement throughout the bilateral cavernous sinuses. A cervical and cerebral angiography revealed bilateral carotid cavernous fistulas with ophthalmic vein arterialization. The next day, she underwent left cavernous sinus embolization with coiling. Parathyroidectomy was delayed due to recurrence of ptosis and need for a second embolization for persistent diplopia that resulted in resolution of symptoms. DISCUSSION: Each of these diagnoses are rare and both require timely evaluation and treatment. The patient's symptoms are classically seen in a parathyroid crisis, with nausea, vomiting, and anorexia being the most common symptoms in up to 48% of parathyroid crises. Like the aforementioned, CCF symptomatology also includes non-specific symptoms; however, may pose more of a challenge during diagnosis as symptoms wax and wane depending on the hemodynamic flow within the fistula. CONCLUSIONS: This case highlights the necessity of a thorough physical exam and further as a reminder that a clinician must be vigilant in ruling out alternative pathologies supported by the objective findings no matter how rare or unlikely. REFERENCE #1: Churojana A, Chawalaparit O, Chiewwit P, Suthipongchai S. Spontaneous occlusion of a bilateral post traumatic carotid cavernous fistula. Interv Neuroradiol. 2001;7(3):245-252. doi:10.1177/159101990100700311 REFERENCE #2: Singh DN, Gupta SK, Kumari N, et al. Primary hyperparathyroidism presenting as hypercalcemic crisis: Twenty-year experience. Indian J Endocrinol Metab. 2015;19(1):100-105. doi:10.4103/2230-8210.131763 REFERENCE #3: Lowell AJ, Bushman NM, Wang X, et al. Assessing the risk of hypercalcemic crisis in patients with primary hyperparathyroidism. J Surg Res. 2017;217:252-257. doi:10.1016/j.jss.2017.06.041 DISCLOSURES: No relevant relationships by Roman Bernstein, source=Web Response No relevant relationships by Ariol Labrada, source=Web Response No relevant relationships by Tram Nguyen, source=Web Response No relevant relationships by Elena Tellez, source=Web Response No relevant relationships by Yaswanraj Yuvaraj, source=Web Response