Cause Of Hypercalcemia Research Articles

SAT-502 Bisphosphonates for Treatment of Calcitriol-Induced Hypercalcemia

Calcitriol excess is a less common cause of hypercalcemia than hyperparathyroidism. While its primary mechanism is thought to be increased intestinal calcium absorption, accelerated bone resorption contributes as well. The mechanism is presumably through a molecular interaction between the receptor activator of NF-κB ligand/osteoprotegerin ligand on marrow stromal cells and receptor activator of NF-κB on osteoclast precursors. It is this component of increased bone resorprtion that is addressed by bisphosphonates. A 77 year old woman with remote history of non-small cell lung cancer status post left lower lobe lobectomy presented with dry mouth, polyuria, 11 pound weight loss in 6 months, fatigue and calcium of 14.7. Examination was unremarkable. Laboratory evaluation included creatinine of 1.4 mg/dl, parathyroid hormone low at 19 pg/ml, 25 hydroxyvitamin D normal at 47 ng/ml, normal kappa/lambda and serum and urine protein electrophoresis, parathyroid hormone-related protein normal at 15 pg/ml, and 1,25 dihydroxyvitamin D was high at 89 pg/ml. A search commenced for the source, during which time hypercalcemia recurred despite strict low-calcium diet and IVF. PET-CT showed innumerable foci of increased uptake in the skeleton and lymph node biopsy revealed grade 3A follicular lymphoma. She received Zoledronic acid 5 mg IV and normocalcemia was maintained thereafter, without any diagnosis-specific treatment for >3 months. She was subsequently started on Rituxan and Bendamustine.This case demonstrates a patient with calcitriol-induced recurrent hypercalcemia from a follicular lymphoma who achieved normalization and subsequent stabilization of serum calcium levels following administration of bisphosphonate. Hypercalcemia due to calcitriol excess is usually managed acutely with intravenous fluid administration and dietary calcium restriction. Second-line agents such as steroids and ketoconazole can also be used, but these interventions alone have side effects and were contraindicated in our case, while the patient was being evaluated for causes of calcitriol excess which would have been masked by the steroids. There is evidence supporting the role of bone resorption in the genesis of hypercalcaemia in vitamin D intoxication and the rapid response of hypercalcaemia to treatment with bisphosphonates. The first choice for calcitriol-induced hypercalcemia is treating the underlying cause. Bisphosphonates are, however, useful until a diagnosis is made, as they may be safer than steroids and can provide rapid relief even with a single treatment, with minimal side effects.

SAT-505 A Rare Case of Teriparatide Induced Persistent Hypercalcemia

INTRODUCTION Teriparatide is a recombinant endogenous parathyroid hormone. It is an anabolic medication which is FDA approved for treating Osteoporosis in postmenopausal women, men with primary or hypogonadal osteoporosis and Glucocorticoid-induced osteoporosis. Transient hypercalcemia with Teriparatide is reported in 1-3% of patients, 4-6 hours after the dose administration and lasts for 24 hours. It is thought to be through the increased renal production of 1,25-dihydroxy vitamin D, increased intestinal calcium absorption and inhibition of renal calcium excretion. We report a case of persistent hypercalcemia with Teriparatide use. CASE REPORT: A 74-year-old Caucasian female presented to the hospital with mental status changes, generalized bone pain, weight loss, and poor oral intake. Her past medical history includes Rheumatoid arthritis, Sjogren syndrome, osteoporosis with compression fractures and osteoarthritis of multiple joints. Patient’s medications include Prednisone 5 mg daily, calcitonin nasal spray, vitamin D and calcium supplements. She had previously failed bisphosphonate therapy for osteoporosis. She developed new compression fracture of L4 vertebra while being treated with Denosumab. Hence Teriparatide was started 4 months prior and she received the last dose 3 days prior to the presentation On presentation, she was noted to have severe hypercalcemia with total calcium of 17.3 mg/dL, ionized calcium of 9.4 mg/dL, albumin of 3.2 g/dL and a suppressed PTH of 3ng/L. Laboratory workup including renal function, phosphorus level, 25-hydroxyvitamin D level, 1,25-dihydroxy vitamin D, Parathyroid hormone-related peptide, Thyroid stimulating hormone, serum, and urine protein electrophoresis was unremarkable. CT scan of the neck, chest, abdomen, and pelvis showed no mass lesions or lymphadenopathy. An extensive evaluation failed to identify other causes of hypercalcemia except for immobilization. She was treated as a new onset Non-PTH dependent severe Hypercalcemia case. The patient had multiple admissions with recurrent hypercalcemia since then despite discontinuation of Teriparatide. Her calcium level normalized transiently with Intravenous fluids, an Intravenous bisphosphonate, and calcitonin. However, such treatment failed to maintain normal calcium level for more than 3-4 weeks.DISCUSSION Recurrent severe hypercalcemia with Teriparatide use is rarely reported. Although immobilization can precipitate hypercalcemia, immobilization is rarely a sole etiology of severe hypercalcemia. Our case report suggests that severe recurrent hypercalcemia can be associated with teriparatide use especially in the setting of immobilization. As far as we are aware, this is the fourth reported case of persistent hypercalcemia with Teriparatide use. This case highlights the importance of monitoring calcium levels periodically when Teriparatide is used.

SAT-503 A Rare Case of Hypercalcemia Due to PTH Secreting Lung Adenocarcinoma

Introduction: Hypercalcemia can be present in up to 20% of malignancies. The majority are caused by humoral hypercalcemia of malignancy, mediated by secretion of PTHrP, typically by squamous cell carcinomas. Other etiologies of hypercalcemia in malignancy include local osteolysis, and increased production of 1,25(OH)2D. In rare cases, hypercalcemia can be caused by secretion of PTH by tumors. Clinical Case: A 60-year-old man with metastatic lung adenocarcinoma presented with altered mental status and was noted to have hypercalcemia to 19.2 mg/dL (reference range, 8.5-10.1). Imaging revealed a 12.0 cm right mediastinal soft tissue mass. He was initially treated with isotonic saline, calcitonin, and zolendronic acid. PTH was elevated to 594 pg/mL (reference range, 14-72), 25OHD was low at 13.2 ng/mL (reference range, 30-100), and PTHrP was normal at 22 pg/mL (reference range, 14-27). Serum calcium reached a nadir of 9.3 mg/dL (reference range, 8.5-10.1). During the course of hospitalization, serum calcium began to rise despite repeated infusions of zolendronic acid. Given inappropriately elevated PTH, hypercalcemia, and normal PTHrP, it was assessed that primary hyperparathyroidism may be the cause of hypercalcemia, and potentially treatable with parathyroid surgery. Endocrine surgery was consulted, and recommended a sestamibi scan, which failed to reveal parathyroid adenomas; however, there was significant uptake over the right upper lung region, left axillary region and bony structures, spatially concordant with the known malignancy. Calcium continued to rise, at which time the health care proxy decided against any further interventions. The patient expired on day 30. Conclusion: PTHrP causes hypercalcemia via similar mechanisms to PTH. In this patient, primary hyperparathyroidism was considered unlikely as the sestamibi scan did not reveal any evidence of parathyroid adenomas; instead, there was increased uptake over the patient’s lung mass, axillary lymph nodes, and metastatic bone lesions. There are known case reports of PTH secreting tumors, which were demonstrated on both sestamibi and immunohistochemistry for intact PTH on tumor tissue. PTH secreting tumors, whilst rare, should be considered in patients with elevated PTH, normal PTHrP levels, and no evidence of primary hyperparathyroidism. Sestamibi scan should be considered as a modality to help diagnose PTH secreting tumors if suspected.

SAT-501 A Rare and Potentially Fatal Etiology of Hypercalcemia in an Infant

Background: Increased 1alpha-hydroxylase activity in granulomatous diseases is a well-defined cause of hypercalcemia. Disseminated fungal infections are a rare cause of granulomatous diseases in immunocompetent children. Clinical Case: A 7-month-old female presented with failure to thrive and vomiting for 2 months. Initial tests showed Hgb 10.9 g/dL, WBC 4.2k/uL (37% Neutrophil), total Ca 17.9 mg/dL, iCa 2.43 mmol/L, Mg 2.4 mg/dL, Phos 4.8 mg/dL, AST 102 IU/L, ALT 115 IU/L, albumin 4.4 g/dL, PTH 5.3 pg/mL (RR 10-65), 25-OHD 61.3 ng/mL, 1,25-(OH)2D 146 pg/mL (RR 19-79). Abdominal US showed an enlarged, heterogeneous liver parenchyma and splenomegaly. Calcium level did not respond to calcitonin. She received pamidronate IV 0.5 mg/kg total over 2 days. Initial workup for infectious, hematologic, oncologic and immunologic etiologies was negative. She had a G-tube and was discharged after achieving adequate weight gain and normal Ca (9.5 mg/dL). Three weeks later she returned with vomiting and hypercalcemia (13.5 mg/dL). She started prednisolone PO 1 mg/kg/day for hypercalcemia. Clinical and biochemical markers improved and she was discharged home on steroid. Six-weeks later, while on prednisolone, she presented with fever and hypotension. A stat CBC showed pancytopenia (Hgb 8 g/dL, WBC 2.4k/uL, Plt 23k/uL) and fungal elements in peripheral smear. Admitted to ICU for anti-fungal and supportive treatment. Serum Histoplasma antigen was mildly positive at 2.4 U/mL (negative <2). Bone marrow aspirate showed phagocytic histiocytes. Liver biopsy demonstrated lobular histiocytic infiltrate with rare granulomas and increased portal/periportal and pericellular fibrosis with bridging confirming the granulomatous disease. Extensive immunological tests did not identify any underlying immunodeficiency. She had a normal SNP microarray but a heterozygous mutation in the UNC13D gene, this was classified as a variant of unknown significance. No deletion or duplication was found in HLH gene panel. After one month of amphotericin B IV treatment, her clinical status improved and discharged home. She took itraconazole PO treatment for 9 months and made full recovery. Serum and urine Histoplasma antigens remained negative during and after completion of antifungal therapy. Steroid slowly tapered while Ca and vitamin D levels remained normal. Conclusion: Hypercalcemia can be the presenting sign of a potentially fatal disseminated fungal infection even in immunocompetent children. Although prednisolone has corrected hypercalcemia in this case, it has likely contributed to the dissemination of the unmasked fungemia. Extra caution should be used before considering steroid treatment for hypercalcemia and ideally, it should be delayed until after anti-fungal treatment begins once the correct diagnosis is reached.

SAT-492 Intact PTH Secretion from Hepatocellular Carcinoma in a Patient Presenting with Hypercalcemia

Background Hypercalcemia of malignancy is typically associated with bony metastases or production of PTHrP. However, rarely, it can be due to intact PTH (iPTH) secretion from solid tumors1. Clinical Case A 61 year old man with chronic kidney disease and hepatitis C cirrhosis complicated by hepatocellular carcinoma (HCC) presented with abdominal pain and was found to have hypercalcemia and a new 5 cm mesenteric mass. Admission labs showed PTH-mediated hypercalcemia: calcium 12.7 mg/dl (8.5-10.1 mg/dl), albumin 3.1 g/dl (3.5-4.8 g/dl), serum creatinine 2.4 mg/dl (0.6-1.4 mg/dl), PTH 397.4 pg/ml (18.4-88 pg/ml), PTHrP 16 (14-27 pg/ml), 25-OH Vitamin D 12.9 ng/ml (30-100 ng/dl), and 1,25-OH Vitamin D 12 (18-72 pg/ml). SPEP and UPEP were normal. Prior to presentation, his baseline calcium was normal and PTH had ranged 150-180 pg/ml with similar renal function as on admission. A parathyroid ultrasound and sestamibi scan were negative for a parathyroid adenoma. A nuclear bone scan was negative for bony metastases. An octreotide scan was also negative. A PET-CT scan showed an FDG-avid mesenteric mass and new FDG-avid hepatic lesions. A biopsy of the mesenteric mass was consistent with metastatic HCC and stained positive for PTH, which suggested iPTH secretion from the HCC. The patient was given IV fluid, calcitonin and cinacalcet with minimal improvement in his hypercalcemia. He later received pamidronte and also underwent embolization to one of the larger hepatic HCC lesions. The mesenteric HCC lesion was not resectable, nor was it amendable to embolization. His calcium normalized after treatment, though his PTH remained very elevated, indicating this improvement was from the pamidronate and not the embolization. Hypercalcemia in other reported cases of iPTH secretion from HCC did improve after embolization2,3, though in these cases, the HCC had not metastasized. The patient had several recurrent admissions for hypercalcemia with increasingly poor response to bisphosphonates. His PTH had climbed to 1275 pg/ml. Denosumab therapy was considered, but he had transitioned to hospice care and died 3 months after his initial presentation. Conclusion Intact PTH secretion from HCC is a rare cause of hypercalcemia

SUN-327 Hypercalcemia and Hypoglycemia Due To EBV-Associated Lymphoma

Background: Hypercalcemia is uncommon in HIV infection but can occur in the setting of lymphoma. We describe a patient with HIV with hypercalcemia and hypoglycemia due to an initially undetected EBV-associated lymphoma. Clinical Case: A 32-year old Caucasian male with recent diagnosis of HIV was admitted for HIV arthropathy and sepsis, and found to have hypercalcemia (Ca 10.7mg/dL, n 8.9-10.2mg/dL; ionized Ca 6.1mg/dL, n 4.6-5.7mg/dL). PTH was suppressed (<10pg/mL, n 12-72pg/mL). PTH-independent causes of hypercalcemia were unremarkable for humoral hypercalcemia of malignancy (PTHrP 0.2pmol/L, n <2.0pmol/L), vitamin D toxicity (24-hydroxyvitamin D 41ng/mL, n 30-80ng/mL), granulomatous disorders (1,25-dihydroxyvitamin D 24.8pg/mL, n 19.9-79.3pg/mL; quantiferon negative), hyperthyroidism, and adrenal insufficiency. Renal function was normal and there was no thiazide, lithium, calcium, or vitamin A use. Serum protein electrophoresis (PEP) showed hypogammaglobinemia consistent with immunodeficiency. Urine PEP was negative for immunoglobulin light chains. Hypercalcemia was initially attributed to HIV with immobilization and calcium level was expected to normalize with antiretroviral therapy. Workup for infectious etiology was negative, his arthralgia and overall clinical status improved, and he was discharged. Three days later, he was readmitted for altered mental status and anemia. He was hypoglycemic, which was new on readmission, and required dextrose-containing IV fluids in addition to tube feeds to keep his serum glucose within normal range. Work up was negative for insulinoma (C peptide 0.48ng/mL, n 0.81-5.3ng/mL; glucose 31mg/dL) but IGF-2 to IGF-1 ratio was elevated at 4.57 which was suggestive of IGF-2-mediated tumor-associated hypoglycemia. Persistent leukocytosis and type B lactic acidosis also suggested an underlying malignancy. Bronchoscopy, bone marrow biopsy, and CSF cytology were negative for malignancy. CSF was positive for EBV (77,100 copies/mL). CT imaging showed liver lesions and biopsy led to the diagnosis of high-grade B-cell lymphoma. He was started on chemotherapy. Hypoglycemia resolved 10 days later, as did the lactic acidosis. Hypercalcemia was treated with pamidronate with return to normal levels. Conclusion: Hypercalcemia in an HIV patient warrants diligent workup. Hypercalcemia in lymphomas are often attributed to elevated 1,25-dihydroxyvitamin D. A possible explanation for normal 1,25-dihydroxyvitamin D observed in our patient is the effect of antiretroviral therapy on accelerated catabolism of vitamin D. Hypoglycemia may be due to IGF-2 production by tumor and malignancy-related glucose consumption via glycolytic pathway with lactic acid production. Literature on concurrent hypercalcemia and hypoglycemia with B-cell lymphoma is sparse and, to our knowledge, occurrence in the setting of HIV has not been reported.

Biological secondary contributors to osteoporosis in fractured patients, is an early systematic assay relevant?

To evaluate the prevalence of biological abnormalities leading to secondary osteoporosis in recently fractured patients. Adults older than 50, hospitalized for a non-vertebral fracture from July 2015 to October 2016, were assessed for bone fragility contributors in the orthopedics department. Bone mineral density (BMD) measurements and vertebral fracture assessment (VFA) were performed within 3 months. We assessed the prevalence of biological abnormalities in all the patients with recent fracture and in subgroups. Among 439 hospitalized patients for non-vertebral low trauma fracture, 372 had biological tests (285 women, mean age 77.5 ± 13 years) and 353 (94.6%) had at least ≥ 1 biological abnormality, most frequently vitamin D insufficiency (< 75 nmol/L) (80%). Hypercalcemia was found in 22 (7.7%) patients, explained by possible primary hyperparathyroidism in 6 cases, and by the other causes of hypercalcemia including postoperative low albumin. A high PTH level was observed in 64 (20.8%) patients. We found 3 monoclonal bands. Results were similar in patients with and without vertebral fracture or osteoporosis. Finally, many biological abnormalities can be explained by the postoperative context (low TSH, hypogammaglobulinemia, low albumin, low alkaline phosphatase) and need a control. This study performed in patient with recent low trauma non-vertebral fractures showed that 94.6% of patients had at least one contributor to bone fragility, which was the vitamin D insufficiency in most of cases. We found a high proportion of biological abnormalities which require additional explorations but most of them can be explained by the postoperative context.

Primary Hyperparathyroidism: Redefining Cure

Primary hyperparathyroidism is the most common cause of hypercalcemia. Follow-up can be resource-intensive and costly. The aim of this study was to determine if there is a subset of patients who can be defined cured earlier than six months. This was a retrospective study of patients who underwent parathyroidectomy between January 2012 and March 2014. Patients with a history of multiple endocrine neoplasia syndrome, and secondary or tertiary hyperparathyroidism were excluded. Patients with normal preoperative calcium and parathyroid hormone (PTH) and those without six months follow-up were excluded. Patients were divided into two groups: cured and not cured. Data analysis was performed between the two groups. A total of 509 patients were screened, and 214 met our inclusion criteria: 202 in the cured category and 12 in the not cured category (94% cure rate). There was no significant difference between age, gland weight, or preoperative PTH. There was a statistically significant difference between final intraoperative PTH (IOPTH) (37 vs 55, P = 0.008) and per cent PTH decrease (69 vs 43%, P < 0.0001). There was a significant difference between intraoperative cure rate (P < 0.0006), imaging concordance (P = 0.0115), and solitary versus multiglandular disease (P = 0.0151). Subgroup analysis in patients with concordant imaging, solitary parathyroid adenoma, and IOPTH decrease by 50 per cent to normal or near-normal correlated with a six-month cure rate of 97 per cent. Patients with primary hyperparathyroidism with concordant imaging, single-adenoma pathology, and IOPTH decrease by 50 per cent to normal or near-normal levels (15-65 pg/mL) can be considered cured and may need less frequent follow-up.

Hungry bone syndrome: biochemical and clinical risk factors

Primary hyperparathyroidismremains the first cause of hypercalcaemia. Parathyroid surgery is the most efficient treatment of primary hyperparathyroidism, however surgery entails risk of development of a Hungry Bone Syndrome (HBS) – rapid, profound, and prolonged hypocalcaemia. The risk factors of HBS are significantly elevated calcium and PTH concentration in plasma, large tumor mass, previously diagnosed osteoporosis and age over 61 years old before surgery. Pre-surgery supplementation of vitamin D3 and long-term therapy with bisphosphonate allows for more efficient control of hypocalcemia and bone metabolism after surgery.

Silicone-Induced Granulomatous Reaction Causing Severe Hypercalcemia: Case Report and Literature Review

A 67-year-old woman presented to the hospital with complaints of abdominal pain. Physical exam was significant for signs of severe dehydration, mild epigastric tenderness and multiple non-tender hard nodules over her arms and thighs. Incidental finding of severe hypercalcemia led to negative workups for hyperparathyroidism, vitamin D intoxication, and malignancy. However, elevated levels of 1,25-hydroxy vitamin D raised the possibility of granulomatous diseases. Imaging and patient report revealed silicone-induced foreign body granulomatous reaction as the cause of hypercalcemia. Use of silicone for cosmetic enhancement of body contours can result in siliconomas, severe hypercalcemia, and complications. Treatment is unestablished for this condition. Increasing prevalence of cosmetic enhancement should prompt vigilance for this rare disease entity. Providers should counsel and educate individuals undergoing such procedures.

Daily oral dosing of vitamin D3 using 5000 TO 50,000 international units a day in long-term hospitalized patients: Insights from a seven year experience

Vitamin D3 is a secosteroid hormone produced in the skin in amounts estimated up to 25,000 international units (IUs) a day by the action of UVB radiation on 7-dehydrocholesterol. Vitamin D deficiency is common due to both lack of adequate sun exposure to the skin, and because vitamin D is present in very few food sources. Deficiency is strongly linked to increased risk for a multitude of diseases, several of which have historically been shown to improve dramatically with either adequate UVB exposure to the skin, or to oral or topical supplementation with vitamin D. These diseases include asthma, psoriasis, rheumatoid arthritis, rickets and tuberculosis. All patients in our hospital have been routinely screened on admission for vitamin D deficiency since July 2011, and offered supplementation to either correct or prevent deficiency. During this time, we have admitted over 4700 patients, the vast majority of whom agreed to supplementation with either 5000 or 10,000 IUs/day. Due to disease concerns, a few agreed to larger amounts, ranging from 20,000 to 50,000 IUs/day. There have been no cases of vitamin D3 induced hypercalcemia or any adverse events attributable to vitamin D3 supplementation in any patient. Three patients with psoriasis showed marked clinical improvement in their skin using 20,000 to 50,000 IUs/day. Analysis of 777 recently tested patients (new and long-term) not on D3 revealed 28.7% with 25-hydroxyvitaminD3 (25OHD3) blood levels < 20 ng/ml, 64.1% < 30 ng/ml, a mean 25OHD3 level of 27.1 ng/ml, with a range from 4.9 to 74.8 ng/ml. Analysis of 418 inpatients on D3 long enough to develop 25OHD3 blood levels > 74.4 ng/ml showed a mean 25OHD3 level of 118.9 ng/ml, with a range from 74.4 to 384.8 ng/ml. The average serum calcium level in these 2 groups was 9.5 (no D3) vs 9.6 (D3), with ranges of 8.4 to 10.7 (no D3) vs 8.6 to 10.7 mg/dl (D3), after excluding patients with other causes of hypercalcemia. The average intact parathyroid hormone levels were 24.2 pg/ml (D3) vs. 30.2 pg/ml (no D3). In summary, long-term supplementation with vitamin D3 in doses ranging from 5000 to 50,000 IUs/day appears to be safe.

Vitamin D Toxicity: A Prospective Study from a Tertiary Care Centre in Kashmir Valley.

Background:Vitamin D toxicity (VDT), a “not uncommon” cause of hypercalcemia, can be life-threatening and cause substantial morbidity, if not treated promptly.Aims:To describe presentation, management, and outcome in 32 patients with VDT diagnosed over 3 years.Materials and Methods:Patients presenting with VDT at a tertiary care centre in Srinagar Kashmir India were included. Evaluation included detailed history and biochemical tests including serum calcium, phosphate, creatinine, intact parathyroid hormone (iPTH), 25-hydroxy Vitamin D (25-OHD), and 24-hour urinary calcium.Results:The clinical manifestations of the 32 patients (median age 65; range 3–77 years) included gastrointestinal symptoms (constipation and vomiting), polyuria/polydipsia, altered sensorium, pancreatitis, acute kidney injury, and nephrocalcinosis. The median total serum calcium level was 13.95 (range 11.10-17.20) mg/dl and median 25-OHD level was 306 (range 105–2800) ng/ml. All patients had suppressed or low normal iPTH and hypercalciuria and 78% had azotemia. All patients had received multiple intramuscular injections of vitamin D3. The median cumulative dose was 4,200,000 (range, 1,800,000-30,000,000) IU. The median time to resolution of hypercalcemia was 7 months (range 4–18 months).Conclusion:We conclude that VDT is an increasingly common cause of symptomatic hypercalcemia. VDT needs prolonged follow up as it takes months to abate its toxicity. Enhancing awareness among general practitioners regarding the toxicity resulting from high doses of vitamin D is the key to prevent VDT. We suggest that VDT be considered in patients, especially the elderly, presenting with polyuria, polydispsia, vomiting, azotemia, or encephalopathy.

Preoperative Localization Studies in Primary Hyperparathyroidism.

Primary hyperparathyroidism (pHPT) is the third most frequently seen endocrine disease and it is the most common cause of hypercalcemia seen in ambulatory patients. PHPT is most often (80%-85%) caused by a single parathyroid adenoma, followed by double adenoma (4%-5%), multiple gland hyperplasia (10%-15%), and parathyroid carcinoma (<1%). The diagnosis of pHPT is biochemically established and the only curative treatment is surgery. Since the cause of pHPT is typically single-gland disease, it is possible to determine the majority of pathological glands with preoperative localization methods and use the minimally invasive parathyroidectomy (MIP) approach. MIP has become the standard treatment for pHPT in selected patients. There are both noninvasive and invasive preoperative localization methods. Noninvasive methods currently used include ultrasonography (US), parathyroid scintigraphy, 4-dimensional computed tomography (CT), magnetic resonance imaging, and positron emission tomography-CT with 18F-fluoroquinolone and 11C-methionine. Preoperative invasive localization methods include parathyroid hormone (PTH) measurement with fine-needle aspiration biopsy, lateralization with PTH measurement via bilateral jugular vein sampling, selective venous sampling, and parathyroid arteriography. The aim of this study was to evaluate preoperative localization studies used in cases of pHPT.

Acute hypercalcemia and hypervitaminosis D associated with pulmonary tuberculosis in an elderly patient : A case report and review of the literature.

An 80-year-old man was referred to our hospital for further examination of fever, cough and left pleural effusion. The laboratory findings showed acute inflammation, and the elevation of albumin-corrected serum calcium and 1,25-dihydroxyvitamin D3. A chest CT revealed centrilobular particulate opacity in the bilateral lung fields and left pleural effusion, indicating acute hypercalcemia and hypervitaminosis D associated with pulmonary tuberculosis. By the confirmation of Mycobacterium tuberculosis on polymerase chain reaction and cultures of the sputum and pleural effusion, a diagnosis of pulmonary tuberculosis was made. The patient successfully completed a 9-month course of the anti-tuberculosis treatment, and bilateral infiltrative shadows and left pleural effusion in chest X-ray disappeared. Symptoms progressively improved and serum level of albumin-corrected calcium and 1,25-dihydroxyvitamin D3 eventually normalized. While pulmonary tuberculosis is an infrequent cause of hypercalcemia, it should be considered in patients with hypercalcemia and elevated serum level of 1,25-dihydroxyvitamin D3. J. Med. Invest. 66 : 351-354, August, 2019.

Milk Alkali Syndrome

Milk-alkali syndrome consists of the triad of hypercalcemia, metabolic alkalosis, and renal insufficiency associated with the ingestion of large amounts of calcium and absorbable alkali. There has been a resurgence of this disorder, as it now accounts for up to 12 percent of cases, making it the third leading cause of hypercalcemia behind primary hyperparathyroidism and malignancy. We present a case report of a 38-year-old male with ingestion of large amounts of calcium carbonate resulting into milk-alkali syndrome and its complications. Avoid excessive amounts of calcium carbonate ingestion.

Clinical and surgical approach to parathyroid adenomas: A single-center experience

Aim: Primary hyperparathyroidism is a clinical condition caused by excessive parathyroid secretion of the parathyroid glands and related hypercalsemia. Hyperparathyroidism is a common cause of hypercalcemia. In this study, we aimed to present the results of patients operated on due to parathyroidadenoma in our clinic.Material and Methods: IPatients who underwent surgery for parathyroid adenoma in our clinic between January 2007 and January 2019 were included in the study. Clinical characteristics, biochemical data, treatment methods and results of the patients were analyzed retrospectively.Results: 156 patients with a mean age of 50.8 years participated in the study. Female sex was 76.2%. Preoperative calcium level was found as 11.2+1.02 mg/dl, Parathormone level was found as 114.7+109.5 pg / ml. The most common clinical presentation was asymptomatic hypercalcemia (48.7%). While 89.7% of the patients had only parathoridectomy, 3.2% had total thyroidectomy and 7.1% had lobectomy due to associated thyroid pathology (10.3%). Intraoperative rapid parathormone was used in 54.4% of the patients. Frozen examination was performed in all patients. The most common localization was inferior left 39.7%. The most common ectopic localization was intratymic at 2.6%. The mean duration of postoperative hospital stay was 3.81+2.69 days. Three patients (1.9%) had persistent hyperparathyroidism and 6 patients (3.8%) had recurrent hyperparathyroidism. The mean follow-up was 57.2+39.5 months. Conclusion: Proper preoperative evaluation, careful exploration, frozen examination and rapid parathormone test increase the success of parathyroid adenoma surgery.

Nonparathyroid Hypercalcemia.

Primary hyperparathyroidism is among the most common causes of hypercalcemia. However, ingestion of medication, including hydrochlorathiazide, lithium, and foscarnet, excessive vitamin A ingestion, endocrinopathies such as hyperthyroidism, adrenal insufficiency, and acromegaly, abnormal nutrient intake such as parenteral nutrition in preterm infants and milk-alkali syndrome, and prolonged immobilization have all been associated with hypercalcemia. The most common cause of nonparathyroid hypercalcemia is neoplasia. Hypercalcemia is generally due to the secretion of parathyroid hormone (PTH)-related peptide (PTHrP) by a wide variety of nonmetastatic solid tumors, including squamous cell tumors but also hematologic tumors. PTHrP, although encoded by a distinct gene, shares amino acid sequence homology with PTH in the amino-terminal domain, which allows it to cross-react at a common G protein receptor, the type 1 PTH/PTHrP receptor (PTHR1), resulting in similar skeletal effects and effects on calcium and phosphorus metabolism. Increased PTHrP action with hypercalcemia may be seen in the benign disease Jansen's metaphyseal chondrodysplasia due to a gain-of-function mutation in PTHR1. Another humoral factor, 1,25-dihyroxyvitamin D [1,25(OH)2D] may be produced by lymphomas, but also by benign granulomatous disorders and may also cause hypercalcemia when its metabolism is genetically impaired. Vitamin D intoxication may cause hypercalcemia due to overproduction of the metabolite, 25 hydroxyvitamin D, apparently in the absence of conversion to 1,25(OH)2D. Malignancies metastatic to bone or arising in bone (such as multiple myeloma) may produce a variety of growth factors and cytokines, in addition to PTHrP, which can contribute to tumor growth as well as osteolysis and hypercalcemia.

Case report: lady with bone pains for 5\xa0years\u2014parathyroid carcinoma

BackgroundParathyroid cancer is a rare cause of primary hyperparathyroidism. It presents a diagnostic and therapeutic challenge that may not be recognized preoperatively, and is often not conclusively identified during the operation. We present the case of a lady with backache and hypercalcemia, but with inadequate work-up for her condition for several years.Case presentationA middle aged lady of Asian descent presented with backache. Initial work up revealed mild hypercalcemia, negative work up for multiple myeloma, negative sestamibi scan for parathyroid pathology. A phenomenally elevated parathormone (PTH) level—2105 pg/mL (16–87 pg/mL), and rising serum calcium, 15.1 mg/dL, (8.6–10.5 mg/dL), ordered years later prompted a repeat sestamibi scan and ultrasonography of neck. Based on these investigations, a diagnosis of primary hyperparathyroidism, with high suspicion of parathyroid cancer was made. The patient underwent surgical tumour resection, with subsequent histopathological confirmation of diagnosis.ConclusionIn the setting of hypercalcemia, PTH level assessment is a must. This helps to differentiate between the parathyroid dependant and independent causes of high serum calcium, thereby encouraging a comprehensive pathway to the work up of the cause of hypercalcemia. The parathyroid cancer is a very rare cause of hypercalcemia, which needs to be considered in the differentials of primary hyperparathyroidism, particularly in the setting of high PTH levels.

Severe hypercalcemia from multiple myeloma as an acquired cause of short QT

An otherwise healthy 64-year-old man with recently diagnosed multiple myeloma was admitted to hospital with hypercalcemia and renal failure. Despite his electrocardiogram showing short QT/QTc intervals, he was admitted without cardiac monitoring. He died suddenly a few hours later, likely from a fatal arrhythmia. This case illustrates that pronounced QT shortening from hypercalcemia is an underappreciated malignant finding that can portend a significant risk for arrhythmia and sudden cardiac death. In addition, we also discuss the causes of hypercalcemia associated short QT/QTc intervals and its ECG features.

Primary Hyperparathyroidism.

Primary hyperparathyroidism (PHPT), the most common cause of hypercalcemia, is most often identified in postmenopausal women. The clinical presentation of PHPT has evolved over the past 40 years to include three distinct clinical phenotypes, each of which has been studied in detail and has led to evolving concepts about target organ involvement, natural history, and management. In the present review, I provide an evidence-based summary of this disorder as it has been studied worldwide, citing key concepts and data that have helped to shape our concepts about this disease. PHPT is now recognized to include three clinical phenotypes: overt target organ involvement, mild asymptomatic hypercalcemia, and high PTH levels with persistently normal albumin-corrected and ionized serum calcium values. The factors that determine which of these clinical presentations is more likely to predominate in a given country include the extent to which biochemical screening is used, vitamin D deficiency is present, and whether parathyroid hormone levels are routinely measured in the evaluation of low bone density or frank osteoporosis. Guidelines for parathyroidectomy apply to all three clinical forms of the disease. If surgical guidelines are not met, parathyroidectomy can also be an appropriate option if no medical contraindications are present. If either the serum calcium or bone mineral density is of concern and surgery is not an option, pharmacological approaches are available and effective. Advances in our knowledge of PHPT have guided new concepts in diagnosis and management.