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Sample records for hypercalcemia

  1. Hypercalcemia

    MedlinePlus

    ... work. Hypercalcemia is usually a result of overactive parathyroid glands. These four tiny glands are situated behind the ... isn't enough calcium in your blood, your parathyroid glands secrete a hormone that triggers: Your bones to ...

  2. Hypercalcemia

    MedlinePlus

    ... or health problems such as, Paget's disease and sarcoidosis. An inherited condition that affects the body's ability ... hypercalcemia due to conditions such as cancer or sarcoidosis may not do well. This is most often ...

  3. Paraneoplastic hypercalcemia.

    PubMed

    Bergman, Philip J

    2012-11-01

    Paraneoplastic syndromes (PNSs) are neoplasm-associated alterations in bodily structure or function or both that occur distant to the tumor. They are an extremely diverse group of clinical aberrations that are associated with the noninvasive actions of the tumor. In many situations, the PNS parallels the underlying malignancy, and therefore, successful treatment of the tumor leads to disappearance of the PNS. Alternatively, recurrence of the PNS after successful treatment signals recurrence of the tumor, and the return of the PNS often significantly precedes the detectable recurrence of the tumor. This is often the case with paraneoplastic hypercalcemia, often referred to as hypercalcemia of malignancy (HM). The most common cause of hypercalcemia in dogs is cancer. Neoplasia is diagnosed in approximately two-thirds of dogs with hypercalcemia vs. approximately one-third in cats. A variety of tumors have been associated with HM. Lymphoma is the most common cause of HM, and the most common anatomical site for dogs with lymphoma-associated HM is the cranial mediastinum. Other tumors associated with HM in dogs and cats include anal sac apocrine gland adenocarcinoma, thyroid carcinoma, multiple myeloma, bone tumors, thymoma, squamous cell carcinoma, mammary gland carcinoma/adenocarcinoma, melanoma, primary lung tumors, chronic lymphocytic leukemia, renal angiomyxoma, and parathyroid gland tumors. As HM is a potential medical emergency, the primary goal in cases of HM is the elucidation of the underlying cause and thereby instituting the appropriate specific therapy.

  4. Problems in medicine: hypercalcemia

    SciTech Connect

    Weller, R.E.

    1985-06-01

    The pathophysiologic mechanisms for hypercalcemia are reviewed and a diagnostic approach to determining the cause of hypercalcemia in clinical cases in dogs and cats is recommended. 5 refs., 1 fig., 1 tab. (ACR)

  5. Hypercalcemia in leprosy.

    PubMed

    Ryzen, E; Singer, F R

    1985-07-01

    We report a case of hypercalcemia in a patient with leprosy. Aminoterminal parathyroid hormone and 25-hydroxy-cholecalciferol concentrations were suppressed. Urinary hydroxyproline concentrations were elevated. There was no evidence of malignancy. The hypercalcemia resolved with corticosteroid therapy.

  6. Immobilization induced hypercalcemia

    PubMed Central

    Cano-Torres, Edgar Alonso; González-Cantú, Arnulfo; Hinojosa-Garza, Gabriela; Castilleja-Leal, Fernando

    2016-01-01

    Summary Immobilization hypercalcemia is an uncommon diagnosis associated with increased bone remodeling disorders and conditions associated with limited movement such as medullar lesions or vascular events. Diagnosis requires an extensive evaluation to rule out other causes of hypercalcemia. This is a report of a woman with prolonged immobilization who presented with severe hypercalcemia. This case contributes to identification of severe hypercalcemia as a result of immobility and the description of bone metabolism during this state. PMID:27252745

  7. High Blood Calcium (Hypercalcemia)

    MedlinePlus

    ... as sarcoidosis • Hormone disorders, such as overactive thyroid (hyperthyroidism) • A genetic condition called familial hypocalciuric hypercalcemia • Kidney ... topics: www.hormone.org (search for PHPT, calcium, hyperthyroidism, or osteoporosis) • MedlinePlus (National Institutes of Health-NIH): ...

  8. Hypercalcemia in Children and Adolescents

    PubMed Central

    Lietman, Steven A.; Germain-Lee, Emily L.; Levine, Michael A.

    2010-01-01

    Purpose of the review In this review we define hypercalcemia levels, common etiologies for hypercalcemia in children, and treatment in order to aid the practicing pediatrician. Recent Findings One rare cause of hypercalcemia in the child is Familial hypocalciuric hypercalcemia (FHH) [also termed familial benign hypercalcemia (FBH)]. Mutations that inactivate the Ca2+-sensing receptor gene FHH have been described as an autosomal dominant disorder, but recently milder mutations in the CASR have been shown to cause hypercalcemia when homozygous. Summary Normal serum levels of calcium are maintained through the interplay of parathyroid, renal, and skeletal factors. In this review, we have distinguished the neonate and infant from the older child and adolescent because the causes and clinical features of hypercalcemia can differ in these two age groups. However the initial approach to the medical treatment of severe or symptomatic hypercalcemia is to increase the urinary excretion of calcium in both groups. In most cases, hypercalcemia is due osteoclastic bone resorption, and agents that inhibit or destroy osteoclasts are therefore effective treatments. Parathyroid surgery, the conventional treatment for adults with symptomatic primary hyperparathyroidism, is recommended for all children with primary hyperparathyroidism. PMID:20601885

  9. Hypercalcemia due to talc granulomatosis.

    PubMed

    Woywodt, A; Schneider, W; Goebel, U; Luft, F C

    2000-04-01

    Pulmonary disease due to talc, a group of hydrous magnesium silicates, is almost exclusively encountered after occupational exposure. One form of this rare disorder is talc granulomatosis. In varying degrees, hypercalcemia is typical of granulomatous disease but has not yet been reported in talcosis. We report the case of a former mold maker who presented with hypercalcemia. Laboratory findings indicated extra-renal 1-alpha-hydroxylation of 25-hydroxyvitamin D. Pulmonary infiltrates prompted a lung biopsy that disclosed talc granulomatosis. We suggest that talc granulomatosis should be added to the list of granulomatous disorders capable of causing hypercalcemia due to increased extra-renal 1-alpha-hydroxylation of 25-hydroxyvitamin D.

  10. Acrodysostosis associated with hypercalcemia.

    PubMed

    Kirnap, Mehmet; Calis, Mustafa; Gokce, Cumali; Kurtoglu, Selim; Ozturk, Mustafa; Kelestimur, Fahrettin

    2013-01-01

    An 18-year-old man was admitted to the clinic complaining of deterioration in the function of his hands and feet. The clinical examination revealed that his movements were clumsy and that he had disproportionally short limbs. In addition, he also had facial abnormalities of frontal bossing, hypertelorism, maxillary hypoplasia, broad low nasal bridge, short upturned nose with anteverted nostrils and triangular mouth. All extremities appeared short with stubby fingers and toes and with broad hands and wrinkling of the dorsal skin. Chromosomal analysis showed a normal (46, XY) karyotype. X-ray studies revealed broad, short metacarpals and phalanges with cone-shaped epiphyses and brachycdactyly and a diagnosis of peripheral dysostosis was confirmed by the characteristic radiographic appearance of the hands. Serum calcium and alkaline phosphatase levels were high, parathormone (PTH) was low, but 25 (OH) Vitamin D, albumin, and 24 hour urine calcium levels were in the normal range. Based on these findings, a diagnosis of acrodysostosis associated with hypercalcemia was made. To the best of our knowledge, this represents the first description of this syndrome.

  11. Hypercalcemia due to Primary Hepatic Lymphoma

    PubMed Central

    Gagnier, Michael; Ryer, Elizabeth; Salhab, Mohammed; Rosmarin, Alan G.

    2016-01-01

    A 65-year-old female with a history of mixed connective tissue disease and pulmonary fibrosis on azathioprine, hydroxychloroquine, and prednisone (osteoporosis on teriparatide) presented with a 1-month history of hypercalcemia. After discontinuation of teriparatide, the patient's hypercalcemia persisted. Further evaluation revealed primary hepatic lymphoma as the source of her hypercalcemia. PMID:28116183

  12. Familial hypocalciuric hypercalcemia: review of three cases.

    PubMed

    Olivar Roldán, Juana; Pavón de Paz, Isabel; Iglesias Bolaños, Paloma; Montoya Álvarez, Teresa; Fernández Martínez, Alberto; Monereo Megías, Susana

    2008-06-01

    Familial hypocalciuric hypercalcemia, also denominated familial benign hypercalcemia, is an uncommon cause of hypercalcemia. It is caused by mutations of the calcium-sensing receptor, which are inherited in an autosomal dominant high-penetrance fashion. Generally, patients are asymptomatic, and heterozygote cases are diagnosed in childhood or adulthood, when diagnostic work-up of an incidentally discovered hypercalcemia ensues. This disorder is characterized by moderate hypercalcemia, with normal parathormone levels and low urine calcium excretion. It is very important to diagnose this condition, as it does not require surgical procedures, unlike primary hyperparathyroidism, which needs parathyroidectomy in 50% of cases. We present 3 cases of familial hypocalciuric hypercalcemia belonging to the same family, and provide an updated review on the topic.

  13. Can atorvastatin calcium cause asymptomatic hypercalcemia?

    PubMed

    Ipekçi, Süleyman Hilmi; Baldane, Süleyman; Sözen, Mehmet; Kebapçılar, Levent

    2014-10-01

    The use of statins may have unnatural effects. A 54-year-old woman was admitted to the hospital with an incidental finding of hypercalcemia (10.8 mg/dL). There was no disease other than hyperlipidemia, and the patient had been on a course of atorvastatin calcium 10 mg for 1.5 years. A workup investigation to diagnose the cause of hypercalcemia was completed. The investigation did not reveal any pathological diseases that may have caused the hypercalcemia. The hypercalcemia resolved after atorvastatin-calcium was stopped, and the patient developed hypercalcemia shortly after the initiation of the atorvastatin calcium. Here, we report a clinical case of recurrent hypercalcemia possibly induced by atorvastatin calcium administration.

  14. Hypercalcemia of Malignancy and Colorectal Cancer.

    PubMed

    Galindo, Rodolfo J; Romao, Isabela; Valsamis, Ageliki; Weinerman, Stuart; Harris, Yael Tobi

    2016-02-01

    Our aim is to describe the association between colorectal cancer (CRC) and humoral hypercalcemia of malignancy (HHM). Causes of hypercalcemia of malignancy include parathyroid hormone-related peptide (PTHrP) secretion, local osteolysis, calcitriol production and ectopic parathyroid hormone (PTH) secretion. Hypercalcemia of malignancy in patients with CRCs is a rare scenario. A patient with anal squamous cell carcinoma was admitted with hypercalcemia, suppressed PTH and hypophosphatemia. He was found to have metastatic anal squamous cell carcinoma to the liver. Further evaluation revealed elevated PTHrP and 1,25-dihydroxyvitamin D and low 25-hydroxyvitamin D. Over a 5-month course, the hypercalcemia responded poorly to bisphosphonates, transiently to prednisone, but showed marked improvement with chemotherapy. A review of English language publications in Pubmed and a reference search of retrieved articles revealed 29 cases of CRC causing PTHrP-mediated hypercalcemia. Most patients were middle-aged men (mean ± SD: 56.7 ± 13.4 years), with advanced metastatic cancer (85% with hepatic metastasis) and severe hypercalcemia (mean ± SD: 15.6 ± 1.9 mg/dL, 62% with Ca > 14). This condition is associated with high mortality (79%) and short survival (median 54.5 days, CI: 21 - 168). Despite being uncommon, HHM (PTHrP-mediated) should be considered in patients with metastatic CRC presenting with hypercalcemia. Clinicians should be aware that combined etiologies may be present, particularly in cases of resistant hypercalcemia. Treatment of the underlying malignancy is essential for calcium control.

  15. Hypercalcemia

    MedlinePlus

    ... Other diseases. Certain diseases, such as tuberculosis and sarcoidosis, may raise blood levels of vitamin D, which ... by an underlying problem, such as cancer or sarcoidosis, your doctor might recommend imaging tests of your ...

  16. Hypercalcemia of Malignancy and Colorectal Cancer

    PubMed Central

    Galindo, Rodolfo J.; Romao, Isabela; Valsamis, Ageliki; Weinerman, Stuart; Harris, Yael Tobi

    2016-01-01

    Our aim is to describe the association between colorectal cancer (CRC) and humoral hypercalcemia of malignancy (HHM). Causes of hypercalcemia of malignancy include parathyroid hormone-related peptide (PTHrP) secretion, local osteolysis, calcitriol production and ectopic parathyroid hormone (PTH) secretion. Hypercalcemia of malignancy in patients with CRCs is a rare scenario. A patient with anal squamous cell carcinoma was admitted with hypercalcemia, suppressed PTH and hypophosphatemia. He was found to have metastatic anal squamous cell carcinoma to the liver. Further evaluation revealed elevated PTHrP and 1,25-dihydroxyvitamin D and low 25-hydroxyvitamin D. Over a 5-month course, the hypercalcemia responded poorly to bisphosphonates, transiently to prednisone, but showed marked improvement with chemotherapy. A review of English language publications in Pubmed and a reference search of retrieved articles revealed 29 cases of CRC causing PTHrP-mediated hypercalcemia. Most patients were middle-aged men (mean ± SD: 56.7 ± 13.4 years), with advanced metastatic cancer (85% with hepatic metastasis) and severe hypercalcemia (mean ± SD: 15.6 ± 1.9 mg/dL, 62% with Ca > 14). This condition is associated with high mortality (79%) and short survival (median 54.5 days, CI: 21 - 168). Despite being uncommon, HHM (PTHrP-mediated) should be considered in patients with metastatic CRC presenting with hypercalcemia. Clinicians should be aware that combined etiologies may be present, particularly in cases of resistant hypercalcemia. Treatment of the underlying malignancy is essential for calcium control. PMID:26998187

  17. Hypercalcemia of Malignancy in Thymic Carcinoma: Evolving Mechanisms of Hypercalcemia and Targeted Therapies

    PubMed Central

    2017-01-01

    Here we describe, to our knowledge, the first case where an evolution of mechanisms responsible for hypercalcemia occurred in undifferentiated thymic carcinoma and discuss specific management strategies for hypercalcemia of malignancy (HCM). Case Description. We report a 26-year-old male with newly diagnosed undifferentiated thymic carcinoma associated with HCM. Osteolytic metastasis-related hypercalcemia was presumed to be the etiology of hypercalcemia that responded to intravenous hydration and bisphosphonate therapy. Subsequently, refractory hypercalcemia persisted despite the administration of bisphosphonates and denosumab indicative of refractory hypercalcemia. Elevated 1,25-dihydroxyvitamin D was noted from the second admission with hypercalcemia responding to glucocorticoid administration. A subsequent PTHrP was also elevated, further supporting multiple mechanistic evolution of HCM. The different mechanisms of HCM are summarized with the role of tailoring therapies based on the particular mechanism underlying hypercalcemia discussed. Conclusion. Our case illustrates the importance of a comprehensive initial evaluation and reevaluation of all identifiable mechanisms of HCM, especially in the setting of recurrent and refractory hypercalcemia. Knowledge of the known and possible evolution of the underlying mechanisms for HCM is important for application of specific therapies that target those mechanisms. Specific targeting therapies to the underlying mechanisms for HCM could positively affect patient outcomes. PMID:28168064

  18. Hypercalcemia of Malignancy in Thymic Carcinoma: Evolving Mechanisms of Hypercalcemia and Targeted Therapies.

    PubMed

    Cheng, Cheng; Kuzhively, Jose; Baim, Sanford

    2017-01-01

    Here we describe, to our knowledge, the first case where an evolution of mechanisms responsible for hypercalcemia occurred in undifferentiated thymic carcinoma and discuss specific management strategies for hypercalcemia of malignancy (HCM). Case Description. We report a 26-year-old male with newly diagnosed undifferentiated thymic carcinoma associated with HCM. Osteolytic metastasis-related hypercalcemia was presumed to be the etiology of hypercalcemia that responded to intravenous hydration and bisphosphonate therapy. Subsequently, refractory hypercalcemia persisted despite the administration of bisphosphonates and denosumab indicative of refractory hypercalcemia. Elevated 1,25-dihydroxyvitamin D was noted from the second admission with hypercalcemia responding to glucocorticoid administration. A subsequent PTHrP was also elevated, further supporting multiple mechanistic evolution of HCM. The different mechanisms of HCM are summarized with the role of tailoring therapies based on the particular mechanism underlying hypercalcemia discussed. Conclusion. Our case illustrates the importance of a comprehensive initial evaluation and reevaluation of all identifiable mechanisms of HCM, especially in the setting of recurrent and refractory hypercalcemia. Knowledge of the known and possible evolution of the underlying mechanisms for HCM is important for application of specific therapies that target those mechanisms. Specific targeting therapies to the underlying mechanisms for HCM could positively affect patient outcomes.

  19. [Hypercalcemia revealing sarcoidosis in a child].

    PubMed

    Kinné, M; Filleron, A; Salet, R; Saumet, L; Baron Joly, S; Tran, T A

    2016-05-01

    Sarcoidosis is a systemic granulomatosis disease with a classic triad of presentation: typical clinical and radiological signs, presence of tuberculoid granuloma without caseum in histopathology, and exclusion of other causes of granulomatosis, especially tuberculosis. Sarcoidosis is rare in the general population, and even more so in children. In the literature, few cases of sarcoidosis associated with hypercalcemia have been reported in children. We report here the case of a 14-year-old boy with bone marrow and lymph node sarcoidosis suspected, based on poor general condition with hypercalcemia. The patient was treated with hydration, diuretics, and bisphosphonates with good results. We also performed a literature review of published cases of hypercalcemia since 1990 with a diagnosis of sarcoidosis in children, comparing 23 cases (including ours) on clinical and epidemiological, biological, imaging, and histopathological diagnosis. When hypercalcemia is present in the initial clinical presentation, the diagnosis of sarcoidosis is usually made in younger children. Classical locations of the lesions, including lung, skin, and lymph nodes, were highly suggestive of sarcoidosis. Corticosteroids are commonly used to treat sarcoidosis lesions including hypercalcemia. In conclusion, sarcoidosis in children remains difficult to diagnose because the disease is rare and it is common to have nonspecific symptoms in the clinical picture (with diagnosis delayed between 3 months and several years). The classic triad is not always present. Sarcoidosis should be systematically considered and investigated in case of hypercalcemia of unknown cause in children. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  20. Hypercalcemia complicating an industrial near-drowning.

    PubMed

    Fromm, R E

    1991-06-01

    A 28-year-old man presented with lethargy, solmulence, and polyuria following near-drowning in a vessel of an offshore oil rig. Laboratory evaluation demonstrated severe hypercalcemia that responded to saline diuresis and nasogastric suctioning. Calcium salts are used frequently in the drilling and completion of oil wells, and it is presumed that this patient's hypercalcemia represented acute intoxication from swallowed and aspirated fluid. This case highlights the need to consider the potential constituents of the drowning fluid in victims of near-drowning, particularly if unexplained clinical phenomena are evident.

  1. Hypercalcemia of advanced chronic liver disease: a forgotten clinical entity!

    PubMed

    Kuchay, Mohammad Shafi; Mishra, Sunil Kumar; Farooqui, Khalid Jamal; Bansal, Beena; Wasir, Jasjeet Singh; Mithal, Ambrish

    2016-01-01

    Hypercalcemia caused by advanced chronic liver disease (CLD) without hepatic neoplasia is uncommonly reported and poorly understood condition. We are reporting two cases of advanced CLD who developed hypercalcemia in the course of the disease. This diagnosis of exclusion was made only after meticulous ruling out of all causes of hypercalcemia. The unique feature of this type of hypercalcemia is its transient nature that may or may not require treatment. This clinical condition in patients with CLD should be kept in mind while evaluating the cause of hypercalcemia in them.

  2. Hypercalcemia of advanced chronic liver disease: a forgotten clinical entity!

    PubMed Central

    Kuchay, Mohammad Shafi; Mishra, Sunil Kumar; Farooqui, Khalid Jamal; Bansal, Beena; Wasir, Jasjeet Singh; Mithal, Ambrish

    2016-01-01

    Summary Hypercalcemia caused by advanced chronic liver disease (CLD) without hepatic neoplasia is uncommonly reported and poorly understood condition. We are reporting two cases of advanced CLD who developed hypercalcemia in the course of the disease. This diagnosis of exclusion was made only after meticulous ruling out of all causes of hypercalcemia. The unique feature of this type of hypercalcemia is its transient nature that may or may not require treatment. This clinical condition in patients with CLD should be kept in mind while evaluating the cause of hypercalcemia in them. PMID:27252737

  3. Hypercalcemia of Malignancy: An Update on Pathogenesis and Management

    PubMed Central

    Mirrakhimov, Aibek E.

    2015-01-01

    Hypercalcemia of malignancy is a common finding typically found in patients with advanced stage cancers. We aimed to provide an updated review on the etiology, pathogenesis, clinical presentation, and management of malignancy-related hypercalcemia. We searched PubMed/Medline, Scopus, Embase, and Web of Science for original articles, case reports, and case series articles focused on hypercalcemia of malignancy published from 1950 to December 2014. Hypercalcemia of malignancy usually presents with markedly elevated calcium levels and therefore, usually severely symptomatic. Several major mechanisms are responsible for the development of hypercalcemia of malignancy including parathyroid hormone-related peptide-mediated humoral hypercalcemia, osteolytic metastases-related hypercalcemia, 1,25 Vitamin D-mediated hypercalcemia, and parathyroid hormone-mediated hypercalcemia in patients with parathyroid carcinoma and extra parathyroid cancers. Diagnosis should include the history and physical examination as well as measurement of the above mediators of hypercalcemia. Management includes hydration, calcitonin, bisphosphonates, denosumab, and in certain patients, prednisone and cinacalcet. Patients with advanced underlying kidney disease and refractory severe hypercalcemia should be considered for hemodialysis. Hematology or oncology and palliative care specialists should be involved early to guide the options of cancer targeted therapies and help the patients and their closed ones with the discussion of comfort-oriented care. PMID:26713296

  4. Hypercalcemia of malignancy and new treatment options

    PubMed Central

    Sternlicht, Hillel; Glezerman, Ilya G

    2015-01-01

    Hypercalcemia of malignancy affects up to one in five cancer patients during the course of their disease. It is associated with both liquid malignancies, commonly multiple myeloma, leukemia, and non-Hodgkins lymphoma and solid cancers, particularly breast and renal carcinomas as well as squamous cell carcinomas of any organ. The clinical manifestations of hypercalcemia are generally constitutional in nature and not specific to the inciting malignancy. Such physical manifestations can range from malaise to lethargy and confusion. Constipation and anorexia are common. Acute kidney injury is likely the most frequently encountered manifestation of end organ damage. Symptomatology is closely linked to both the absolute elevation of serum calcium levels and the rapidity of calcium rise. The majority of cases are humoral in etiology and related to parathyroid hormone-related protein (PTHrP). Approximately 20% of cases are the result of direct bone metastasis with extra-renal 1,25-dihydroxyvitamin D (calcitriol) and ectopic parathyroid hormone production likely accounting for less than 1% of cases. The diagnosis of hypercalcemia of malignancy is confirmed either by an elevated PTHrP or by an evidence of bone metastasis in the appropriate clinical setting. Treatment is predicated on the patient’s symptoms and absolute serum calcium level. Interventions are aimed at lowering the serum calcium concentration by inhibiting bone resorption and increasing urinary calcium excretion, the former accomplished via bisphosphonate therapy and the latter with aggressive hydration. Novel therapies for refractory disease include denosumab, a monoclonal antibody against the receptor activator of nuclear factor κB ligand, and the calcimimetic cinacalcet. Finally, anti-PTHrP antibodies have been successfully deployed in animal models of disease. Despite the efficacy of the above therapies, hypercalcemia of malignancy portends an ominous prognosis, indicating advanced and often refractory

  5. Electrocardiographic manifestations of combined hypercalcemia and hypermagnesemia.

    PubMed

    Mosseri, M; Porath, A; Ovsyshcher, I; Stone, D

    1990-07-01

    Near drowning in the Dead Sea is a potentially lethal accident; the swallowing of the salty water causes acute combined hypercalcemia and hypermagnesemia, and this, rather than aspiration, is considered to be the main pathogenetic fator. The authors reviewed the electrocardiographic data of 37 patients who nearly drowned in the Dead Sea. Common findings in the acute phase included P wave changes, tendency for prolongation of P-R interval, prolongation of QRS complex, infra-His conduction disturbances, tendency for broadening and inversion of T wave, and the appearance of a prominent U wave. Three patients had potentially lethal ventricular tachyarrhythmias. The QaTc interval (beginning of QRS complex to apex of T wave, corrected for heart rate), the expected QaTc calculated from calcium blood level (QaTce), and their difference (DQaTc), were measured or calculated. The QaTc was found within normal limits and did not change during recovery from the Dead Sea water poisoning. The DQaTc correlated significantly with serum magnesium level (p less than 0.001). This correlation signifies that hypermagnesemia normalizes the QaTc interval, which is usually shortened by isolated hypercalcemia. Combined hypercalcemia and hypermagnesemia can be caused by swallowing excessively salty water. The potential cardiac complications require strict monitoring and electrocardiographic follow up study.

  6. Hypercalcemia in a patient with disseminated paracoccidioidomycosis: a case report.

    PubMed

    Almeida, Rafael Moura; Cezana, Loureno; Tsukumo, Daniela Miti Lemos; de Carvalho-Filho, Marco Antônio; Saad, Mário José Abdalla

    2008-08-08

    Hypercalcemia is well described in various granulomatous disorders, such as sarcoidosis, tuberculosis, berylliosis, leprosy and fungal infections. However, the association of Paracoccidioides brasiliensis and hypercalcemia is rare: to the best of our knowledge, only two cases have previously been reported, and neither had a clear documentation of the etiology of the hypercalcemia. We report the case of a 22-year-old man in whom disseminated infection with paracoccidioidomycosis was associated with hypercalcemia. The patient had a high normal serum level of 1,25-dihydroxyvitamin D and a suppressed parathyroid hormone value, an indication that the hypercalcemia was not mediated by parathyroid hormone and might be associated with 1,25-dihydroxyvitamin D. The episode resolved readily with administration of corticosteroids, an outcome suggesting that this is an effective treatment of hypercalcemia of this origin. On follow-up, while receiving antifungal therapy for P. brasiliensis the patient's calcium values remained normal.

  7. Renal medullary ''rings'': possible CT manifestation of hypercalcemia

    SciTech Connect

    Curry, N.S.; Gordon, L.; Gobien, R.P.; Lott, M.

    1984-01-01

    Bilateral dense rings in the renal medulla were found on noncontrasted computed tomography in a patient with marked hypercalcemia and suspected primary hyperparathyroidism. The rings were not present on plain radiographs and were obscured on contrasted scans, and may represent occult nephrocalcinosis. Associated findings--renal insufficiency induced by hypercalcemia and interstitial nephritis--may be reversible with early recognition of this CT finding.

  8. Hypercalcemia Caused by Metastatic Adamantinoma: Response to Radiotherapy

    PubMed Central

    Lyons, Janice A.; Budd, G. Thomas

    1999-01-01

    Purpose. To describe successful palliation of a patient with metastatic adamantinoma presenting with lung metastases and hypercalcemia resulting from a parathormone-like substance released from the tumor. Methods and materials. The records of a patient with a history of a tibial adamantinoma who presented with symptoms of hypercalcemia 20 years after the original surgery, as well as the literature concerning hypercalcemia and adamantinoma were reviewed and summarized. Results. After thorough review of the literature we found no prior reports of radiation being used for palliation of hypercalcemia associated with metastatic adamantinoma.We report rapid improvement in symptoms and normalization of serum calcium levels following a course of radiation therapy. The patient remains asymptomatic 15 months following radiotherapy despite a gradual return of elevated serum calcium levels. Discussion. Radiation therapy should be considered as a palliative option for patients who are not surgical candidates presenting with medically refractory hypercalcemia. PMID:18521262

  9. Subcutaneous fat necrosis, hypercalcemia, and prostaglandin E.

    PubMed

    Sharata, H; Postellon, D C; Hashimoto, K

    1995-03-01

    We present two patients with subcutaneous fat necroses (SCFN) in whom endocrinologic studies revealed an association with elevated prostaglandin E (PGE) levels. A boy born after prolonged labor complicated by meconium aspiration developed erythematous, indurated plaques over the back, arms, buttocks, and cheeks at 4 days of age. A biopsy specimen of involved skin showed panniculitis with foci of necrotic adipocytes containing radially arranged, needle-shaped clefts and a granulomatous infiltrate in the septae. Laboratory studies revealed hypercalcemia of 13.6 mg/dl (normal 8.8-10.1 mg/dl), elevated 1.25-1.25(OH)2D3, and increased urinary excretion of PGE2. The child was hospitalized and treated with systemic steroids and diuretics, with resolution of SCFN and hypercalcemia. The second patient was a girl born with cyanotic heart disease. A diagnosis of Ebstein anomaly was made, and intravenous PGE1 was started to keep patent the ductus arteriosus. Four days later erythematous, indurated plaques were noted on the knee, back, and anterior chest. A skin biopsy specimen revealed SCFN. There was no associated laboratory abnormality. On discontinuing PGE1, no new lesions formed and the existing panniculitis resolved. These two cases demonstrate the association between SCFN and elevated PGE levels (endogenous in patient 1, exogenous in patient 2). No previous reports of SCFN after the administration of PGE1 have appeared in the literature.

  10. Hypercalcemia in the emergency department: a missed opportunity.

    PubMed

    Royer, Anna Marie; Maclellan, Reid A; Stanley, J Daniel; Willingham, Trent B; Giles, W Heath

    2014-08-01

    Primary hyperparathyroidism is surgically correctable and frequently presents with mild hypercalcemia. The symptoms of hyperparathyroidism are nonspecific often leading to a delay in diagnosis until patients present with an acute condition. Literature suggests that up to 20 per cent of patients presenting to the emergency department (ED) found to have hypercalcemia are ultimately diagnosed with hyperparathyroidism. We performed a retrospective review from 2012 to 2013 of patients with hypercalcemia in our ED and analyzed their characteristics. One hundred sixty-eight patients were identified with hypercalcemia. Patient medical history, chief complaint, review of symptoms, discharge disposition, and primary care physician (PCP) status were evaluated. Eighty-four per cent were classified as mild (10.8 to 11.9 mg/dL), 11 per cent as moderate (12 to 14 mg/dL), and five per cent as severe (greater than 14 mg/dL). A definitive diagnosis of hyperparathyroidism was identified in 3.5 per cent (six of 168). Documentation of hypercalcemia as a diagnosis was present in all patients in the severe and 78 per cent in the moderate categories. However, only 21 per cent of patients with mild hypercalcemia had documentation addressing this diagnosis. Of concern, 24 per cent (41 of 168) of patients were identified with mild hypercalcemia and discharged from the ED with no definitive plan based on lack of a PCP. Additionally, 81 per cent of these patients had symptoms referable to hypercalcemia. Mild hypercalcemia found during ED workup rarely requires immediate medical treatment. However, a significant number of those patients will have hyperparathyroidism amendable to surgical correction. Therefore, an appropriate mechanism for outpatient hypercalcemia workup should be integrated into the patient's ED discharge plan.

  11. The effect of hypercalcemia on allograft calcification after kidney transplantation.

    PubMed

    Çeltik, Aygül; Şen, Sait; Yılmaz, Mümtaz; Demirci, Meltem Seziş; Aşçı, Gülay; Tamer, Abdülkerim Furkan; Sarsık, Banu; Hoşcoşkun, Cüneyt; Töz, Hüseyin; Ok, Ercan

    2016-11-01

    Persistent hypercalcemia after kidney transplantation (KTx) may cause nephrocalcinosis and graft dysfunction. The aim of this study was to evaluate patients with hypercalcemia and assess its effect on tubulointerstitial calcification. A total of 247 recipients were enrolled. Transient and persistent hypercalcemia was defined as hypercalcemia (corrected serum calcium >10.2 mg/dL) persisting for 6 and 12 months after KTx, respectively. The severity of calcification in the 0-h, 6- and 12-month protocol biopsies of patients with transient (n = 8) and persistent hypercalcemia (n = 20) was compared with a matched control group (n = 28). Twenty-eight patients were hypercalcemic at 6 months posttransplantation. Serum calcium levels were normalized in eight of them at the end of the first year. Dialysis duration was a positive predictor of persistent hypercalcemia. Tubulointerstitial calcification was detected in 70.6 and 90 % of patients with persistent hypercalcemia at 6 and 12 months posttransplantation, respectively. In 20 % of patients with transient hypercalcemia, severity of calcification regressed at 12 months posttransplantation along with normalization of serum calcium levels. Graft functions and histopathological findings (ci, ct, ci + ct, cv, ah, percentage of sclerotic glomeruli) were not different at 6 and 12 months posttransplantation. Hypercalcemia and persistent hyperparathyroidism are not rare after KTx. Tubulointerstitial calcification is more common and progressive among patients with persistent hypercalcemia. Normalization of calcium levels may contribute to regression of calcification in some patients.

  12. Hypercalcemia-leukocytosis syndrome associated with lung cancer.

    PubMed

    Hiraki, Akio; Ueoka, Hiroshi; Takata, Ichiro; Gemba, Kenichi; Bessho, Akihiro; Segawa, Yoshihiko; Kiura, Katsuyuki; Eguchi, Kenji; Yoneda, Toshiyuki; Tanimoto, Mitsune; Harada, Mine

    2004-03-01

    Hypercalcemia and leukocytosis are two of the most common paraneoplastic syndromes associated with various malignancies. Of note, concomitant manifestation of hypercalcemia and leukocytosis are occasionally observed in the same cancer patients. However, the relationship between these two paraneoplastic syndromes and clinical outcome is unclear. In the present study, we retrospectively investigated the occurrence of hypercalcemia (> or = 10.2 mg/dl after adjustment for serum albumin concentration), leukocytosis (> or = 14,000/mm3 with no evidence of infection) or both in lung cancer patients (1149 cases). There were 65 cases (5.7%) of hypercalcemia, 16 cases (1.4%) of leukocytosis and six cases (0.5%) of both hypercalcemia and leukocytosis at the time of first presentation. The occurrence of these two distinct paraneoplastic syndromes in the same patients was more frequent than could have been expected by chance alone (P < 0.001). There was a significant correlation between the hypercalcemia-leukocytosis syndrome and performance status (P = 0.002). Survivals of patients with hypercalcemia alone (median survival time: MST 3.8 months, n = 59), leukocytosis alone (MST 1.9 months, n = 10), and the hypercalcemia-leukocytosis syndrome (MST 1.5 months, n = 6) were significantly shorter than those without them (MST 9.5 months, n = 1074; P < 0.001). Moreover, survival of patients with the hypercalcemia-leukocytosis syndrome was significantly shorter than that of patients with hypercalcemia alone (P = 0.013). On the other hand, there was no significant difference in survival between the hypercalcemia-leukocytosis syndrome and leukocytosis alone (P = 0.47). Multivariate analysis of prognostic factors using the Cox proportional hazards model could not demonstrate that the hypercalcemia-leukocytosis syndrome had independent prognostic significance. In conclusion, our results suggest that the hypercalcemia-leukocytosis syndrome is an additional clinical entity of paraneoplastic

  13. Treatment of hypercalcemia of malignancy with intravenous etidronate. A controlled, multicenter study. The Hypercalcemia Study Group.

    PubMed

    Singer, F R; Ritch, P S; Lad, T E; Ringenberg, Q S; Schiller, J H; Recker, R R; Ryzen, E

    1991-03-01

    In a prospective, randomized, double-blind, multicenter study, 202 patients with cancer from 19 medical centers were treated for hypercalcemia of malignancy with daily intravenous infusions of etidronate disodium (136 patients) or saline alone (66 patients) for 3 consecutive days. Patients also received up to 3.25 L of saline daily during the treatment period. Of 157 patients for whom data could be evaluated for efficacy, 63% (72/114) of etidronate-treated and 33% (14/43) of saline-treated patients had a normalization of total serum calcium levels. When serum calcium levels were adjusted for albumin (147 assessable patients), 24% of the etidronate- and 7% of the saline-treated patients responded to treatment. No serious side effects or treatment-related deaths occurred. When accompanied by adequate hydration and diuresis, intravenous etidronate was safe and more effective than hydration and diuresis alone in controlling hypercalcemia of malignancy.

  14. Adrenal insufficiency presenting as hypercalcemia and acute kidney injury

    PubMed Central

    Ahn, Seung Won; Kim, Tong Yoon; Lee, Sangmin; Jeong, Jeong Yeon; Shim, Hojoon; Han, Yu min; Choi, Kyu Eun; Shin, Seok Joon; Yoon, Hye Eun

    2016-01-01

    Adrenal insufficiency is an uncommon cause of hypercalcemia and not easily considered as an etiology of adrenal insufficiency in clinical practice, as not all cases of adrenal insufficiency manifest as hypercalcemia. We report a case of secondary adrenal insufficiency presenting as hypercalcemia and acute kidney injury in a 66-year-old female. The patient was admitted to the emergency department with general weakness and poor oral intake. Hypercalcemia (11.5 mg/dL) and moderate renal dysfunction (serum creatinine 4.9 mg/dL) were shown in her initial laboratory findings. Studies for malignancy and hyperparathyroidism showed negative results. Basal cortisol and adrenocorticotropic hormone levels and adrenocorticotropic hormone stimulation test confirmed the diagnosis of adrenal insufficiency. With the administration of oral hydrocortisone, hypercalcemia was dramatically resolved within 3 days. This case shows that adrenal insufficiency may manifest as hypercalcemia and acute kidney injury, which implicates that adrenal insufficiency should be considered a cause of hypercalcemia in clinical practice. PMID:27536162

  15. Calcitonin produces hypercalcemia in leopard sharks.

    PubMed

    Glowacki, J; O'Sullivan, J; Miller, M; Wilkie, D W; Deftos, L J

    1985-02-01

    Calcitonin was detected by RIA in sera from four marine species, leopard sharks (Triakis semifasciata), horn sharks (Heterodontus francisci), thornback rays (Platyrhinoides triseriata), and kelp bass (Paralabrax clathratus). These animals have levels of calcitonin and calcium higher than freshwater and terrestrial species have. The administration of salmon calcitonin to bass (4 micrograms/kg BW) produced hypocalcemia and hypophosphatemia as has been reported for other bony vertebrates. In marked contrast, calcitonin produced a prompt hypercalcemia in sharks; the average was 9.8% increase in serum calcium in nine animals with no attendant change in phosphorus. These findings demonstrate that calcitonin can increase serum calcium in sharks. Because shark skeleton is composed of cartilage, this hypercalcemic effect of calcitonin does not require a bony skeleton.

  16. A Case of Carcinoid Tumor-Associated Hypercalcemia

    PubMed Central

    Siyam, Fadi; Abdullah, Obai; Gardner, Michael; Brietzke, Stephen; Sowers, James

    2012-01-01

    Hypercalcemia as a complication of carcinoid tumors is extremely rare. Accordingly, we report the case of a 55-year-old male with metastatic carcinoid tumor and hypercalcemia, which corrected when the patient was treated with octreotide for symptomatic relief of watery diarrhea. The etiology of the hypercalcemia is presumed to be a neoplastic expression of fibroblast growth factor-23, which was found to be inappropriately high-to-normal when other factors such as parathyroid hormone, calcitonin and vitamin D were appropriately low or low-to-normal. PMID:22493603

  17. Intravenous etidronate in the management of malignant hypercalcemia.

    PubMed

    Ryzen, E; Martodam, R R; Troxell, M; Benson, A; Paterson, A; Shepard, K; Hicks, R

    1985-03-01

    The treatment of hypercalcemia remains a common problem in the management of many patients with cancer. We have used intravenously administered etidronate disodium as a therapy for hypercalcemia in 26 patients with malignant disease. Patients with persistent hypercalcemia despite adequate hydration and a serum creatinine level less than or equal to 1.5 mg/dL were allowed on study. Treatment consisted of intravenously administered etidronate disodium at 7.5 mg/kg/day in 250 mL of saline infused over two hours on 1, 2, 3, or 4 consecutive days. The serum calcium level in 19 (73%) of 26 patients returned to the normal range with a mean response time of 3 +/- 2 days. Similar response rates were seen in patients with a variety of tumors, including breast cancer, non-small-cell lung cancer, and multiple myeloma. Intravenously administered etidronate appears to be safe and effective therapy for hypercalcemia in patients with malignant disease.

  18. Prevalence of hypercalcemia related to hypervitaminosis D in clinical practice.

    PubMed

    Pérez-Barrios, C; Hernández-Álvarez, E; Blanco-Navarro, I; Pérez-Sacristán, B; Granado-Lorencio, F

    2016-12-01

    Recent interest in vitamin D has led to a substantial increase in the use of vitamin D supplements. Vitamin D intoxication may be a concern as hypervitaminosis D can result in irreversible calcification of soft tissues so that it is important to detect early markers of vitamin D intoxication. Our aim was to assess the simultaneous presence of biochemical markers of vitamin D toxicity (i.e. hypervitaminosis D, hypercalcemia) and determine the concentrations of 25-OH-vitamin D at which the risk of hypercalcemia, and thus toxicity, might begin. We evaluated retrospectively a 6-year period during which 25.567 samples were assessed for 25-OH-vitamin D status by UHPLC. Hypervitaminosis D was defined at serum 25-OH-vitamin D >160 nmol/L. Serum and urine calcium, phosphorus and iPTH were also recorded, if available. Medical history revision was performed in subjects displaying simultaneously hypervitaminosis D and hypercalcemia. Overall, hypervitaminosis D was found in 475 samples (1.86%) of which 51 displayed hypercalcemia (11.1%). A total of 382 samples were identified as the first record of hypervitaminosis D and 39 presented hypercalcemia (10.2%), most of them at 25-OH-vitamin D levels between 161 and 375 nmol/L. Only in 15 subjects, hypercalcemia could be directly attributed to vitamin D and serum 25-OH-vitamin D ranged between 164 and 1139 nmol/l. In no case, serum calcium achieved concentrations considered as critical values (>13 mg/dl). Hypercalcemia due to vitamin D represented <4% of the total hypervitaminosis D detected and <0.1% of the tests performed. However, a highly variable response was observed and most subjects presented hypercalcemia at serum concentrations of 25-OH-vitamin D < 375 nmol/L. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  19. Severe hypercalcemia following denosumab treatment in a juvenile patient.

    PubMed

    Setsu, Nokitaka; Kobayashi, Eisuke; Asano, Naofumi; Yasui, Naoko; Kawamoto, Hiroshi; Kawai, Akira; Horiuchi, Keisuke

    2016-01-01

    A 10-year-old boy diagnosed with unresectable giant cell tumor of bone in the sacrum was treated with a bone modifying agent denosumab. Administration of denosumab showed excellent clinical response without any major complications, and the tumor was surgically removed afterwards. However, 4 months after discontinuing denosumab, the patient developed severe hypercalcemia (15.2 mg/dl). There was a sharp surge in the levels of bone resorption markers, indicating that disregulated overt bone resorption after the discontinuation of denosumab led to hypercalcemia. The patient was treated with bisphosphonate and barely recovered from the life-threatening conditions. This case shows that a robust rebound of bone resorption may occur following cessation of denosumab and suggests that hypercalcemia is an underappreciated side effect of denosumab therapy in children.

  20. A case of hypercalcemia associated with Castleman disease.

    PubMed

    Washington, Terri; Vora, Avni; Mihailescu, Dan

    2010-01-01

    To present a case of hypercalcemia associated with Castleman disease. The details of case presentation, evaluation, diagnosis, and treatment are reviewed in a 25-year-old woman with severe hypercalcemia, joint pain, conjunctival injection, and lymphadenopathy. Endocrinopathies such as primary hyperparathyroidism were ruled out. Infectious and rheumatologic laboratory evaluations revealed normal results. On a whole-body scan, the patient was noted to have diffusely increased osseous uptake in conjunction with increased periarticular uptake, consistent with a metabolic superscan. After extensive evaluation, the patient underwent a right axillary lymph node biopsy and was found to have multicentric Castleman disease. She was treated with high-dose corticosteroids and eventually immunomodulators to help control her disease. To the best of our knowledge, this is the first published case report demonstrating hypercalcemia in association with Castleman disease. The pathologic mechanism is likely bone turnover mediated by cytokines such as interleukin-6.

  1. Hodgkin's disease with hypercalcemia detected by thallium-201 scintigraphy

    SciTech Connect

    Linde, R.; Basso, L.

    1987-01-01

    A 53-yr-old man with hypercalcemia was referred after an unsuccessful operative attempt to find a parathyroid adenoma. Metabolic evaluation showed relatively suppressed levels of parathyroid hormone with an elevation of serum 1,25-dihydroxyvitamin D. Thallium-technetium dual isotope imaging revealed localized mediastinal thallium uptake. A vascular mediastinal lesion was then demonstrated by arteriography, with subsequent surgical removal of a mass that proved to be lymphocyte predominant Hodgkin's disease. This case is noteworthy for the finding of isolated lymphocyte predominant Hodgkin's disease in the chest, the association of elevated serum 1,25-dihydroxyvitamin D with hypercalcemia that resolved postoperatively, and the uptake of thallium by the tumor.

  2. Granulomatous Interstitial Nephritis Presenting as Hypercalcemia and Nephrolithiasis

    PubMed Central

    Sharmeen, Saika; Kalkan, Esra; Yi, Chunhui; Smith, Steven D.

    2016-01-01

    We report a case of acute kidney injury as the initial manifestation of sarcoidosis. A 55-year-old male was sent from his primary care physician's office with incidental lab findings significant for hypercalcemia and acute kidney injury with past medical history significant for nephrolithiasis. Initial treatment with intravenous hydration did not improve his condition. The renal biopsy subsequently revealed granulomatous interstitial nephritis (GIN). Treatment with the appropriate dose of glucocorticoids improved both the hypercalcemia and renal function. Our case demonstrates that renal limited GIN due to sarcoidosis, although a rare entity, can cause severe acute kidney injury and progressive renal failure unless promptly diagnosed and treated. PMID:26904327

  3. Paraneoplastic hypercalcemia in a dog with thyroid carcinoma

    PubMed Central

    Lane, Amy E.; Wyatt, Kenneth M.

    2012-01-01

    This case report describes a dog with thyroid carcinoma and paraneoplastic hypercalcemia. Following thyroidectomy the dog became hypocalcemic and required supplementation with calcitriol and calcium carbonate. During the following 2 years, attempts to reduce the supplementation resulted in hypocalcemia. The dog died from renal failure with no evidence of thyroid carcinoma. PMID:23543930

  4. Could primary hyperparathyroidism-related hypercalcemia induce hypercalcitoninemia?

    PubMed

    Conte-Devolx, B; Morlet-Barla, N; Roux, F; Sebag, F; Henry, J F; Niccoli, P

    2010-01-01

    To determine if primary hyperparathyroidism (pHPT) per se may be responsible of hypercalcitoninemia. pHPT induces chronic hypercalcemia that should be expected to be a potential stimulatory pathway of calcitonin (CT) secretion and to cause hypercalcitoninemia. We studied relationships between CT and pHPT-related chronic hypercalcemia in 122 patients aged 25-83 years who underwent parathyroid surgery. CT, calcium and PTH plasma levels were measured in all patients preoperatively. CT was measured by a current immunometric assay specific of mature CT monomer. Of our 122 patients with pHPT-related hypercalcemia, 120 (98.4%) had normal CT values of less than 10 pg/ml and two (1.6%) exhibited a mildly increased CT above 10 pg/ml (11 and 12 pg/ml, respectively). We evidenced no relationship between CT and calcium level or PTH level. Chronic pHPT-related hypercalcemia per se does not cause hypercalcitoninemia. The finding of pHPT concomitant with high CT levels should raise suspicion of multiple endocrine neoplasia type 2A. Copyright 2010 S. Karger AG, Basel.

  5. Paraneoplastic hypercalcemia in a dog with benign renal angiomyxoma.

    PubMed

    Gajanayake, Isuru; Priestnall, Simon L; Benigni, Livia; English, Kate; Summers, Brian A; Garden, Oliver A

    2010-09-01

    An 11-year-old, male, neutered crossbred Collie dog was presented for a history of polydipsia and polyuria. Diagnostic investigations revealed total and ionized hypercalcemia and an increased concentration of parathyroid hormone-related peptide. Abdominal ultrasonography and contrast-enhanced computed tomography of the abdomen revealed a right-sided, cystic-appearing renal mass. Cytological examination of ultrasound-guided aspirates of the mass revealed high numbers of spindle cells. The mass was removed en bloc via an ureteronephrectomy. Histopathological examination of the mass revealed neoplastic spindle cells in loosely packed and interlacing streams within a myxomatous stroma. Immunohistochemical examination with vimentin, von Willebrand Factor, and alpha-smooth muscle actin confirmed the mass to be a renal angiomyxoma. A minority of the neoplastic spindle cells showed positive cytoplasmic parathyroid hormone-related peptide immunostaining. The hypercalcemia resolved following surgery, and the parathyroid hormone-related peptide concentration returned to within the reference interval. The dog was no longer polydipsic or polyuric 1 year following surgery. The present report describes a previously unreported renal neoplasm causing paraneoplastic hypercalcemia and highlights the possibility of paraneoplastic hypercalcemia being caused by a benign neoplasm.

  6. Hypercalcemia, inappropriate calcitriol levels, and tuberculosis on hemodialysis.

    PubMed

    Peces, R; Pobes, A; Díaz-Corte, C; Gago, E

    2000-08-01

    We describe a female patient undergoing hemodialysis who developed tuberculosis, hypercalcemia, and inappropriately elevated calcitriol levels. These findings suggest ectopic production of calcitriol by tuberculous granulomas. Successful treatment of tuberculosis led to a substantial decrease in the levels of calcium and calcitriol.

  7. Bone scintigraphy of severe hypercalcemia following simvastatin induced rhabdomyolysis

    PubMed Central

    Mirza, Zubair B.; Hu, Sophia; Amorosa, Louis F.

    2016-01-01

    Summary Simvastatin induced rhabdomyolysis with renal failure is a well reported clinical entity with hyperkalemia recognized as a life threatening risk. The risk of delayed hypercalcemia during the recovery of renal function is not well appreciated as this varies in severity and can be caused by multiple mechanisms. We present a patient with high dose simvastatin induced rhabdomyolysis leading to late onset of severe hypercalcemia due to calcium phosphate deposition in muscles diagnosed by distinctive bone scintigraphy. A 60-year-old Asian male was admitted to the hospital for profound weakness one week following the initiation of simvastatin 80 mg daily post myocardial infarction. His clinical course was complicated by contrast nephropathy. One week later, he developed progressive weakness in all his extremities and inability to raise his head and eat. Simvastatin was discontinued at this point. CPK elevation to greater than 425,000 U was found, consistent with rhabdomyolysis. He became oliguric requiring hemodialysis. Muscle biopsy showed severe muscle necrosis and type 2 fiber atrophy. One month later, he developed hypercalcemia with suppressed intact PTH and 1, 25(OH) D levels. Whole body bone scintigraphy showed calcium phosphate deposition throughout his musculature. His calcium levels normalized in 1 week on hemodialysis. This patient’s experience illustrates the marked risk of delayed severe hypercalcemia from rhabdomyolysis due to dissolution of myocellular calcium phosphate deposits. It also provides an opportunity to review the different mechanisms of hypercalcemia especially in statin induced rhabdomyolysis. Recognition of this phenomenon is critical for appropriate follow up and treatment of such patients. PMID:28228795

  8. Serum osteocalcin (BGP) in tumor-associated hypercalcemia.

    PubMed

    Body, J J; Cleeren, A; Pot, M; Borkowski, A

    1986-12-01

    Serum osteocalcin (BGP) is a new marker of bone turnover that reportedly evaluates bone formation. Thus, its measurement could assess the bone formation rate in tumor-associated hypercalcemia. We measured concentrations of BGP and other parameters of bone metabolism in 54 untreated hypercalcemic cancer patients as compared to 109 healthy subjects. Primary tumor sites were breast (19), lung (11), head and neck (6), multiple myeloma (3), kidney (2), and various (11) or multiple (2). Mean BGP levels were higher in the hypercalcemic subjects, 4.6 +/- 0.4 (SEM) ng/ml, than in the normal subjects, 3.6 +/- 0.1 ng/ml (p less than .05), and were normalized in the 22 patients who could be reevaluated after successful treatment of hypercalcemia with intravenous aminohydroxypropylidene diphosphonate (APD). There was no correlation of BGP levels with age, sex, or renal function. Compared with the Gaussian distribution in the normal subjects, there was a considerable scatter of the data in hypercalcemic patients, suggesting the existence of defined subgroups with abnormally low or abnormally high values. However, we found no significant relationship of BGP concentrations with tumor site or histology or with bone metastatic involvement. We found also no significant correlation between concentrations of serum BGP and total or ionized calcium, alkaline phosphatase, parameters of bone resorption, and indices of parathyroid function. In summary, serum BGP levels were slightly elevated in tumor-associated hypercalcemia and were normalized after successful treatment of hypercalcemia. More importantly, BGP concentrations varied widely even in the subgroups of patients with hypercalcemia accompanying massive bone metastatic involvement or in the patients without detectable skeletal metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Severe hypercalcemia and hypernatremia in a patient treated with canagliflozin

    PubMed Central

    Winters, Stephen J

    2015-01-01

    Summary Drugs that inhibit the sodium-glucose co-transporter-2 (SGLT2) are an exciting novel, insulin-independent treatment for diabetes that block glucose reabsorption from the proximal tubules of the kidney, leading to increased glucose excretion and lower blood glucose levels. Inhibition of SGLT2 activity also reduces sodium reabsorption, which together with glycosuria produces a mild diuretic effect with the potential for dehydration and hyperkalemia. We report on a 60-year-old man with uncontrolled type 2 diabetes treated with insulin, glimepiride, metformin and canagliflozin, who was admitted with altered mental status after a syncopal episode. He had a 1-week history of ingestion of Tums for heartburn followed by poor appetite and lethargy. Laboratory work-up showed acute kidney injury, diabetic ketoacidosis (DKA), and parathyroid hormone-independent severe hypercalcemia of 17.4 mg/dl. DKA resolved with insulin treatment, and saline hydration led to improvement in hypercalcemia and renal function over 48 h, but was accompanied by a rapid increase in the serum sodium concentration from 129 to 162 mmol/l despite changing fluids to 0.45% saline. Urine studies were consistent with osmotic diuresis. Hypernatremia was slowly corrected with hypotonic fluids, with improvement in his mental status over the next 2 days. This is the first report of hypercalcemia associated with the use of a SLGT2 inhibitor. Although the exact mechanism is unknown, canagliflozin may predispose to hypercalcemia in patients ingesting excessive calcium because of dehydration from osmotic diuresis, with reduced calcium excretion and possible increased intestinal calcium absorption. Saline therapy and osmotic diuresis may lead to hypernatremia from electrolyte-free water loss. Learning points Canagliflozin, an SGLT2 inhibitor, may cause hypercalcemia in susceptible patients.Although the exact mechanisms are unknown, dehydration from osmotic diuresis and increased intestinal calcium

  10. Progressive disseminated histoplasmosis presenting with cachexia and hypercalcemia

    PubMed Central

    Khasawneh, Faisal A; Ahmed, Subhan; Halloush, Ruba A

    2013-01-01

    Histoplasmosis is a common endemic mycosis. The majority of infections involving this dimorphic fungus are asymptomatic. Manifestations in symptomatic patients are diverse, ranging from flu-like illness to a more serious disseminated disease. We present here a case of chronic disseminated histoplasmosis mimicking a metastatic cancer. We reviewed the literature for cases of disseminated histoplasmosis presenting with hypercalcemia, focusing particularly on clinical presentation, risk factors predisposing for fungal infection, and outcome. We report a case of a 65-year-old diabetic male who presented with unexplained weight loss and hypercalcemia. Multiple brain space-occupying lesions and bilateral adrenal enlargement were evident on imaging studies. Biopsies showed caseating granulomas with budding yeast, consistent with histoplasmosis. The patient’s symptoms resolved after liposomal amphotericin B and itraconazole therapy. Granulomatous diseases, including fungal infections, should be considered alongside malignancies, in patients with similar presentation. PMID:23467543

  11. Myocardial uptake of a bone tracer associated with hypercalcemia

    SciTech Connect

    Atkins, H.L.; Oster, Z.H.

    1984-11-01

    A patient with end-stage renal disease and hypercalcemia was referred for a radionuclide bone imaging study. Deposition of Tc-99m hydroxymethylenediphosphonate was apparent in the lungs and myocardium as well as in the skeleton. Renal uptake was also noted, despite anuria. Computed tomography demonstrated nephrocalcinosis but no myocardial calcification. The cause of myocardial uptake of tracer is unknown. Amyloidosis is suggested as a possibility but is not validated in this case.

  12. Impact of experimental hypercalcemia on routine haemostasis testing

    PubMed Central

    Lippi, Giuseppe; Salvagno, Gian Luca; Brocco, Giorgio; Gelati, Matteo; Favaloro, Emmanuel J.

    2017-01-01

    Background The blood to anticoagulant ratio is standardized according to the physiological calcium concentration in blood samples conventionally used for hemostasis testing. Specifically, one fixed volume of 0.109 mmol/L sodium citrate is added to 9 volumes of blood. Since little is known about the impact of hypercalcemia on the calcium-binding capacity of citrate, this study was planned to investigate the effect of experimental hypercalcemia on routine hemostasis testing. Methods Fifteen pooled citrated plasmas with matching lithium-heparin pooled plasma from patients with different values of prothrombin time (PT) were divided in three aliquots of 0.6mL each. The first paired aliquots of both citrate and lithium-heparin plasma were supplemented with 60μL of saline, the second paired aliquots with 30μL of saline and 30μL of calcium chloride and the third paired aliquots with 60μL of calcium chloride. Total and ionized calcium was measured in all aliquots of citrate and lithium-heparin plasma, whereas PT, activated partial thromboplastin time (APTT) and fibrinogen were measured in citrate plasma aliquots. Results Total calcium concentration gradually increased in both lithium-heparin and citrate plasma aliquots 2 and 3 compared to baseline aliquot 1. The concentration of ionized calcium also gradually increased in lithium-heparin plasma aliquots 2 and 3, whereas it remained immeasurable (i.e., <0.10 mmol/L) in all citrate plasma aliquots. No significant differences were observed for values of PT, APTT and fibrinogen in citrate plasma aliquots 2 and 3 compared to the baseline aliquot 1, with a mean bias was always comprised within the desirable quality specifications derived from biological variability data. Conclusion Hypercalcemia, up to severe hypercalcemia does not generate significant bias in results of first-line coagulations tests, so that hypothetical consideration of adjusting citrate-blood ratio is unjustified in hypercalcemic patients. PMID:28362859

  13. Impact of experimental hypercalcemia on routine haemostasis testing.

    PubMed

    Lippi, Giuseppe; Salvagno, Gian Luca; Brocco, Giorgio; Gelati, Matteo; Danese, Elisa; Favaloro, Emmanuel J

    2017-01-01

    The blood to anticoagulant ratio is standardized according to the physiological calcium concentration in blood samples conventionally used for hemostasis testing. Specifically, one fixed volume of 0.109 mmol/L sodium citrate is added to 9 volumes of blood. Since little is known about the impact of hypercalcemia on the calcium-binding capacity of citrate, this study was planned to investigate the effect of experimental hypercalcemia on routine hemostasis testing. Fifteen pooled citrated plasmas with matching lithium-heparin pooled plasma from patients with different values of prothrombin time (PT) were divided in three aliquots of 0.6mL each. The first paired aliquots of both citrate and lithium-heparin plasma were supplemented with 60μL of saline, the second paired aliquots with 30μL of saline and 30μL of calcium chloride and the third paired aliquots with 60μL of calcium chloride. Total and ionized calcium was measured in all aliquots of citrate and lithium-heparin plasma, whereas PT, activated partial thromboplastin time (APTT) and fibrinogen were measured in citrate plasma aliquots. Total calcium concentration gradually increased in both lithium-heparin and citrate plasma aliquots 2 and 3 compared to baseline aliquot 1. The concentration of ionized calcium also gradually increased in lithium-heparin plasma aliquots 2 and 3, whereas it remained immeasurable (i.e., <0.10 mmol/L) in all citrate plasma aliquots. No significant differences were observed for values of PT, APTT and fibrinogen in citrate plasma aliquots 2 and 3 compared to the baseline aliquot 1, with a mean bias was always comprised within the desirable quality specifications derived from biological variability data. Hypercalcemia, up to severe hypercalcemia does not generate significant bias in results of first-line coagulations tests, so that hypothetical consideration of adjusting citrate-blood ratio is unjustified in hypercalcemic patients.

  14. An unusual case of malignancy-related hypercalcemia.

    PubMed

    Doyle, Mary-Anne; Malcolm, Janine C

    2013-01-01

    To report the case of a 28-year-old woman who presented with hypercalcemia (total calcium =4.11 mmol/L), elevated parathyroid hormone (PTH) 24.6 pmol/L, normal parathyroid hormone-related peptide 7.8 pg/mL, and a 63 mm × 57 mm, poorly differentiated neuroendocrine carcinoma (small-cell type) pancreatic mass with liver metastases. Hypercalcemia was acutely managed with intravenous fluids, pamidronate and calcitonin. Investigations for multiple endocrine neoplasia type 1 and parathyroid adenoma were initiated. The identified neuroendocrine tumor was treated with cisplatinum/etoposide chemotherapy. The pancreatic mass (56 mm × 49 mm) and metastases decreased in size with chemotherapy and calcium levels normalized. Eight months later, calcium increased to 3.23 mmol/L, PTH increased to 48.2 pmol/L, and the pancreatic mass increased in size to 67 mm × 58 mm. The patient was given a trial of cinacalcet but was unable to tolerate it. Chemotherapy was restarted and resulted in a decrease in the pancreatic mass (49 mm × 42 mm), a reduction in PTH levels (16.6 pmol/L), and calcium levels (2.34 mmol/L). Ectopic PTH secreting tumors should be considered when there is no parathyroid related cause for an elevated PTH. Recognizing the association between PTH and hypercalcemia of malignancy may lead to an earlier detection of an undiagnosed malignancy.

  15. An unusual case of malignancy-related hypercalcemia

    PubMed Central

    Doyle, Mary-Anne; Malcolm, Janine C

    2014-01-01

    Objective To report the case of a 28-year-old woman who presented with hypercalcemia (total calcium =4.11 mmol/L), elevated parathyroid hormone (PTH) 24.6 pmol/L, normal parathyroid hormone-related peptide 7.8 pg/mL, and a 63 mm × 57 mm, poorly differentiated neuroendocrine carcinoma (small-cell type) pancreatic mass with liver metastases. Investigations and treatment Hypercalcemia was acutely managed with intravenous fluids, pamidronate and calcitonin. Investigations for multiple endocrine neoplasia type 1 and parathyroid adenoma were initiated. The identified neuroendocrine tumor was treated with cisplatinum/etoposide chemotherapy. Results The pancreatic mass (56 mm × 49 mm) and metastases decreased in size with chemotherapy and calcium levels normalized. Eight months later, calcium increased to 3.23 mmol/L, PTH increased to 48.2 pmol/L, and the pancreatic mass increased in size to 67 mm × 58 mm. The patient was given a trial of cinacalcet but was unable to tolerate it. Chemotherapy was restarted and resulted in a decrease in the pancreatic mass (49 mm × 42 mm), a reduction in PTH levels (16.6 pmol/L), and calcium levels (2.34 mmol/L). Conclusion Ectopic PTH secreting tumors should be considered when there is no parathyroid related cause for an elevated PTH. Recognizing the association between PTH and hypercalcemia of malignancy may lead to an earlier detection of an undiagnosed malignancy. PMID:24353437

  16. Hypercalcemia as a Cause of Kidney Failure: Case Report

    PubMed Central

    Stojceva-Taneva, Olivera; Taneva, Borjanka; Selim, Gjulsen

    2016-01-01

    BACKGROUND: Hypercalcemia is a common manifestation in clinical practice and occurs as a result of primary hyperparathyroidism, malignancy, milk-alkali syndrome, hyper or hypothyroidism, sarcoidosis and other known and unknown causes. Patients with milk-alkali syndrome typically are presented with renal failure, hypercalcemia, and metabolic alkalosis caused by the ingestion of calcium and absorbable alkali. This syndrome is caused by high intake of milk and sodium bicarbonate. CASE PRESENTATION: We present a 28-year old male admitted to hospital with a one-month history of nausea, vomiting, epigastric pain, increased blood pressure and worsening of renal function with hypercalcemia. His serum PTH level was almost undetectable; he had mild alkalosis, renal failure with eGFR of 42 ml/min, anemia, hypertension and abnormal ECG with shortened QT interval and ST elevation in V1-V4. He had a positive medical history for calcium-containing antacids intake and after ruling out primary hyperparathyroidism, malignancy, multiple myelomas, sarcoidosis, and thyroid dysfunction, it seemed plausible to diagnose him as having the milk-alkali syndrome. CONCLUSION: Although milk-alkali syndrome currently may be more probably a result of calcium and vitamin D intake in postmenopausal women, or in elderly men with reduced kidney function taking calcium-containing medications, one should not exclude the possibility of its appearance in younger patients taking calcium-containing medications and consider it a serious condition taking into account its possibility of inducing renal insufficiency. PMID:27335601

  17. A curious case of growth failure and hypercalcemia: Answers.

    PubMed

    Downie, Mallory L; Mulder, Jaap; Schneider, Rayfel; Lim, Lillian; Tehrani, Nasrin; Wasserman, Jonathan D; Fuchs, Shai; John, Rohan; Noone, Damien G; Hebert, Diane

    2017-08-07

    Sarcoidosis is a multisystem granulomatous disease of unknown etiology that rarely presents in childhood. Here, we report a case of pediatric sarcoidosis, presenting with renal failure and hypercalcemia. A previously well 14-year-old Caucasian boy was admitted to the Hospital for Sick Children, Canada, for hypertension and renal failure following work-up by his family physician for initial concerns of growth failure. On admission, his weight was 35 kg (<3rd percentile), his height was 148 cm (<3rd percentile), and his blood pressure was 154/116 mmHg (>99th percentile for height). Laboratory findings showed elevated creatinine (218 umol/L), hypercalcemia (3.21 mmol/L), and normocytic anemia (hemoglobin 105 g/L). His further assessment showed a urinary concentrating defect with hypercalciuria (calcium/creatinine 1.76 mmol/mmol) and nephrocalcinosis on ultrasound. His eye examination showed uveitis with conjunctival biopsy remarkable for granulomas, which led to pursuit of a diagnosis of possible sarcoidosis. Angiotensin Angiotensin-converting enzyme was found to be high at 96 U/L, and he had a renal biopsy that was consistent with interstitial nephritis with granulomas. Treatment was started with prednisone leading to resolution of his hypercalcemia but persistence of his mild chronic kidney disease. This case represents an atypical presentation of a rare pediatric disease and highlights the spectrum of renal manifestations and treatment options in sarcoidosis.

  18. A curious case of growth failure and hypercalcemia: Questions.

    PubMed

    Downie, Mallory L; Mulder, Jaap; Schneider, Rayfel; Lim, Lillian; Tehrani, Nasrin; Wasserman, Jonathan D; Fuchs, Shai; John, Rohan; Noone, Damien G; Hebert, Diane

    2017-08-07

    Sarcoidosis is a multisystem granulomatous disease of unknown etiology that rarely presents in childhood. Here, we report a case of pediatric sarcoidosis presenting with renal failure and hypercalcemia. A previously well 14-year-old Caucasian boy was admitted to the Hospital for Sick Children, Canada, for hypertension and renal failure following work-up by his family physician for initial concerns of growth failure. On admission, his weight was 35 kg (<3rd percentile), his height was 148 cm (≪3rd percentile), and his blood pressure was 154/116 mmHg (>99th percentile for height). Laboratory findings showed elevated creatinine (218 μmol/L), hypercalcemia (3.21 mmol/L), and normocytic anemia (hemoglobin 105 g/L). His further assessment showed a urinary concentrating defect with hypercalciuria (calcium/creatinine 1.76 mmol/mmol) and nephrocalcinosis on ultrasound. His eye examination showed uveitis with conjunctival biopsy remarkable for granulomas, which led to pursuit of a diagnosis of possible sarcoidosis. Angiotensin-converting enzyme was found to be high at 96 U/L, and he had a renal biopsy that was consistent with interstitial nephritis with granulomas. Treatment was started with prednisone leading to resolution of his hypercalcemia but persistence of his mild chronic kidney disease. This case represents an atypical presentation of a rare pediatric disease and highlights the spectrum of renal manifestations and treatment options in sarcoidosis.

  19. Dangerous nutrition? Calcium, vitamin D, and shark cartilage nutritional supplements and cancer-related hypercalcemia.

    PubMed

    Lagman, Ruth; Walsh, Declan

    2003-04-01

    The use of nutritional supplements in the general population and in cancer patients has become very popular. These supplements are not perceived as medications and are presumed to be safe by cancer patients, who may however be at risk for hypercalcemia. We note that many of our patients who have developed symptomatic hypercalcemia were taking vitamin D, calcium, or shark cartilage supplements. We report eight cases of hypercalcemia in cancer patients seen at the Cleveland Clinic Foundation in whom these nutritional supplements may have contributed to the prevalence or severity of hypercalcemia.

  20. Hypercalcemia in the Intensive Care Unit: A Review of Pathophysiology, Diagnosis, and Modern Therapy.

    PubMed

    Maier, Joshua D; Levine, Steven N

    2015-07-01

    Hypercalcemia may be seen in a variety of clinical settings and often requires intensive management when serum calcium levels are dramatically elevated. All of the many etiologies of mild hypercalcemia can lead to severe hypercalcemia. Knowledge of the physiologic mechanisms involved in maintaining normocalcemia and basic pathophysiology is essential for making a timely diagnosis and hence prompt institution of etiology-specific therapy. The development of new medications and critical reviews of traditional therapies have changed the treatment paradigm for severe hypercalcemia, calling for a more limited role for aggressive isotonic fluid administration and furosemide and an expanded role for calcitonin and the bisphosphonates. Experimental therapies such as denosumab show promise.

  1. Hypercalcemia and abnormal 1,25-dihydroxyvitamin D concentrations in leprosy.

    PubMed

    Ryzen, E; Rea, T H; Singer, F R

    1988-02-01

    Two patients with lepromatous leprosy and hypercalcemia are presented. Serum immunoreactive parathyroid hormone and urinary cyclic adenosine monophosphate concentrations were suppressed. Serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] concentrations were elevated in one patient and normal in the other. Urinary hydroxyproline excretion was slightly high in both patients. Hypercalcemia resolved excretion was slightly high in both patients. Hypercalcemia resolved with prednisone therapy. Abnormal 1,25-(OH)2D production and/or metabolism may play a role in the pathogenesis of hypercalcemia in some patients with leprosy.

  2. Cutaneous and systemic blastomycosis, hypercalcemia, and excess synthesis of calcitriol in a domestic shorthair cat.

    PubMed

    Stern, Joshua A; Chew, Dennis J; Schissler, Jennifer R; Green, Eric M

    2011-01-01

    A 9 yr old domestic shorthair cat was diagnosed with cutaneous and pulmonic blastomycosis. Severe persistent ionized hypercalcemia and excess circulating concentration of calcitriol were documented in association with blastomycosis. Ionized hypercalcemia resolved when the granulomatous lesions of blastomycosis resolved and the calcitriol levels decreased.

  3. Status epilepticus secondary to milk-alkali syndrome induced by hypercalcemia (oral antacids).

    PubMed

    Kashouty, Rabih; Yono, Noor; Al Samara, Mershed

    2011-10-01

    Milk-alkali syndrome is mainly caused by the ingestion of large amounts of calcium and absorbable alkali. This syndrome can lead to metastatic calcification, renal failure and metabolic alkalosis secondary to hypercalcemia. Hypercalcemia is rarely a cause of seizure activity. Very few case reports have been published linking seizure to hypercalcemia, but only one recent case report about mesial temporal sclerosis relates the seizure activity to Milk-alkali syndrome. This is another report regarding seizure associated with excess calcium carbonate intake, but without any evidence of mesial temporal sclerosis. The patient described in this article, suffered from status epilepticus most likely secondary to hypercalcemia. Evaluations for malignancy, thyroid, and parathyroid dysfunctions were non conclusive, therefore hypercalcemia in our patient was attributed to milk-alkali syndrome given the history of the prolonged calcium carbonate intake.

  4. Hypercalcemia in glycogen storage disease type I patients of Turkish origin.

    PubMed

    Kasapkara, Ciğdem Seher; Tümer, Leyla; Okur, Ilyas; Eminoğlu, Tuba; Ezgü, Fatih Süheyl; Hasanoğlu, Alev

    2012-01-01

    Glycogen storage disease type I (GSD I) is an autosomal recessive disorder caused by defects in the glucose-6-phosphatase complex. Deficient activity in the glucose-6-phosphatase-a (G6Pase) catalytic unit characterizes GSD IA and defects in the glucose-6-phosphate transporter protein (G6PC) characterize GSD IB. The main clinical characteristics involve fasting hypoglycemia, hyperuricemia, hyperlactatemia, and hyperlipidemia. Hypercalcemia arose as an unknown problem in GSD I patients, especially in those with insufficient metabolic control. The aim of the present study was to obtain the prevalence of hypercalcemia and to draw attention to the metabolic complications of GSD I patients, including hypercalcemia in poor metabolic control. Hypercalcemia frequency and the affecting factors were studied cross-sectionally in 23 GSD I pediatric subjects. Clinical diagnosis of GSD I was confirmed in all patients either through documentation of deficient G6Pase enzyme activity levels on liver biopsy samples or through G6PC gene sequencing of DNA. Hypercalcemia was detected in 78.3% of patients with GSD I. Different from the previous report about hypercalcemia in a GSD IA patient who had R83H and 341delG mutations, we could not identify any genotype-phenotype correlation in our GSD I patients. Hyperlactatemia and hypertriglyceridemia correlated significantly with hypercalcemia. Furthermore, no differences in serum calcium concentrations could be demonstrated between patients with optimal metabolic control. We observed hypercalcemia in our series of GSD I patients during acute metabolic decompensation. Therefore, we speculate that hypercalcemia should be considered as one of the problems of GSD I patients during acute attacks. It may be related with prolonged lactic acidosis or may be a pseudohypercalcemia due to hyperlipidemia that can be seen in GSD I patients with poor metabolic control.

  5. Thiazide-Associated Hypercalcemia: Incidence and Association With Primary Hyperparathyroidism Over Two Decades

    PubMed Central

    Griebeler, Marcio L.; Kearns, Ann E.; Ryu, Euijung; Thapa, Prabin; Hathcock, Matthew A.; Melton, L. Joseph

    2016-01-01

    Context: Thiazide diuretics, the antihypertensive agent prescribed most frequently worldwide, are commonly associated with hypercalcemia. However, the epidemiology and clinical features are poorly understood. Objective: To update the incidence of thiazide-associated hypercalcemia and clarify its clinical features. Patients and Methods: In a population-based descriptive study, Olmsted County, Minnesota, residents with thiazide-associated hypercalcemia were identified through the Rochester Epidemiology Project and the Mayo Clinic Laboratory Information System from 2002–2010 and were added to the historical cohort beginning in 1992. Main Outcome: Incidence rates were adjusted to the 2010 United States white population. Results: Overall, 221 Olmsted County residents were identified with thiazide-associated hypercalcemia an average of 5.2 years after initiation of treatment. Subjects were older (mean age, 67 years) and primarily women (86.4%). The incidence of thiazide-associated hypercalcemia increased after 1997 and peaked in 2006 with an annual incidence of 20 per 100 000, compared to an overall rate of 12 per 100 000 in 1992–2010. Severe hypercalcemia was not observed in the cohort despite continuation of thiazide treatment in 62.4%. Of patients discontinuing thiazides, 71% continued to have hypercalcemia. Primary hyperparathyroidism was diagnosed in 53 patients (24%), including five patients who underwent parathyroidectomy without thiazide discontinuation. Conclusions: Many patients with thiazide-associated hypercalcemia have underlying primary hyperparathyroidism. Additionally, a sharp rise in thiazide-associated hypercalcemia incidence began in 1998, paralleling the increase observed in primary hyperparathyroidism in this community. Case ascertainment bias from targeted osteoporosis screening is the most likely explanation. PMID:26751196

  6. Hypercalcemia-leukocytosis syndrome in a patient with cavitating squamous cell carcinoma of the lung

    PubMed Central

    2009-01-01

    Introduction Lung cancer is the leading cause of death among the cancers seen in the United States. Hypercalcemia and leukocytosis are two common paraneoplastic syndromes associated with lung cancer. Unfortunately patients presenting with Hypercalcemia- leukocytosis syndrome has a worse prognosis than patients presenting with lung cancer alone. Case presentation We present a 67 yr old Caucasian male with a history of active smoking presenting as pneumonia being diagnosed as cavitating squamous cell carcinoma of the lung with hypercalcemia-leukocytosis syndrome Conclusion There should be a high degree of suspicion to diagnose lung cancer in patients presenting with symptoms of paraneoplastic syndrome. PMID:19183491

  7. Case of Hypercalcemia Secondary to Hypervitaminosis A in a 6-Year-Old Boy with Autism

    PubMed Central

    Vyas, Arpita Kalla; White, Neil H.

    2011-01-01

    Vitamin A intoxication secondary to over-the-counter nutritional supplements and from its use in acne treatment has been described. However, there have been very few case reports of chronic hypervitaminosis A leading to hypercalcemia in the pediatric population. This paper describes a boy with hypercalcemia secondary to chronic vitamin A intoxication in the context of vitamin A usage for therapy of autism. In addition to discontinuation of vitamin A, hyperhydration, and furosemide, the hypercalcemia in this patient required the use of prednisone and pamidronate to normalize the calcium. PMID:22937283

  8. Rapid calcitonin response to experimental hypercalcemia in healthy horses.

    PubMed

    Rourke, K M; Kohn, C W; Levine, A L; Rosol, T J; Toribio, R E

    2009-05-01

    Calcium has important physiological functions, and disorders of calcium homeostasis are frequent in horses. We have made important progress understanding equine calcium homeostasis; however, limited information on equine calcitonin (CT) is available, in part because of the lack of validated CT assays. To determine the CT response to high ionized calcium (Ca(2+)) concentrations in healthy horses, we induced hypercalcemia in 10 healthy horses using a calcium gluconate 23% solution (5mg/kg; 120 mL/500 kg horse) infused over 4 min. Four horses were infused with 120 mL of 0.9% NaCl and used as controls. We validated a human-specific CT radioimmunoassay for use in horses. Serum Ca(2+) concentrations increased from 6.2+/-0.3mg/dL to 9.9+/-0.5mg/dL (4 min; P<0.01). Serum CT increased from 16.7+/-8.0 pg/mL to 87.1+/-55.8 pg/mL at 2 min, and 102.5+/-51.1 pg/mL at 4 min (P<0.01). Serum CT returned to baseline by 20 min, whereas serum Ca(2+) returned to baseline by 40 min. Of interest, CT concentrations returned to baseline despite hypercalcemia, suggesting thyroid gland C-cell CT depletion. Resting CT values higher than 40 pg/mL were considered abnormally elevated. No significant changes in serum Ca(2+) or CT concentrations were found in control horses. The coefficients of variation for the CT radioimmunoassay were lower than 11.9%. We conclude that the equine thyroid gland C-cell responds quickly to changes in extracellular Ca(2+) concentrations by secreting large quantities of CT into the systemic circulation, indicating that CT is important in equine calcium homeostasis. The human CT radioimmunoassay can be used to measure changes in equine CT.

  9. [Hypercalcemia related to PTH-rP revealing malignant hepatic epithelioid hemangioendothelioma].

    PubMed

    Boukhris, Imène; Azzabi, Samira; Kéchaou, Ines; Chérif, Eya; Kooli, Chékib; Romdhane, Khaled Ben; Omar, Souheil; Khalfallah, Narjes

    2016-01-01

    Hypercalcemia caused by tumor production of PTH-rp occurs most often in cases of squamous cell carcinoma of the lung, aerodigestive tract cancer, gynecological cancer and lymphoma. We report an exceptional case of PTH-rp related to a hepatic hemangioendothelioma. A 70 years-old male admitted for deterioration of the general state. The laboratory investigations revealed hypercalcemia, related to tumor production of PTH-rp. Imaging revealed tumoral hepatic lesions. Histopathological study and immunohistochemistry showed diffuse response for CD31 marker, CK20 (+) with CK7 (-) and hepatocyt antigen (-). The diagnosis of PTH-rp related to hepatic hemangioendothelioma was make. The patient died with recurrence of fatal hypercalcemia. Management of patients presenting with humoral hypercalcemia includes a vigorous search for tumor lesions. Elevated PTH-rp can be a bad prognostic factor. In front of tumoral liver lesions, a hepatic epithelioid hemangioendothelioma must be considered. Immunohistochemistry is necessary to make diagnosis.

  10. Study of Denosumab in the Treatment of Hypercalcemia of Malignancy in Subjects With Elevated Serum Calcium

    ClinicalTrials.gov

    2016-02-18

    Breast Cancer; Hypercalcemia of Malignancy; Colon Cancer; Endocrine Cancer; Head and Neck Cancer; Kidney Cancer; Lung Cancer; Lymphoma; Metastatic Cancer; Multiple Myeloma; Parathyroid Neoplasms; Renal Cancer; Thyroid Cancer; Hodgkin's Lymphoma; Non-Hodgkin's Lymphoma; Non-Small Cell Lung Cancer

  11. Richter's Syndrome with Hypercalcemia Induced by Tumor-Associated Production of Parathyroid Hormone-Related Peptide

    PubMed Central

    Watanabe, Naoki; Yasuda, Hajime; Morishita, Soji; Aota, Yasuo; Tomomatsu, Junichi; Tanaka, Masaru; Ohsaka, Akimichi; Komatsu, Norio

    2017-01-01

    Humoral hypercalcemia due to parathyroid hormone-related peptide (PTHrP) elevation is a well-known complication of various malignancies, but the situation is rare concerning hematological malignancies except for adult T-cell leukemia/lymphoma. We report a case of Richter's syndrome with humoral hypercalcemia, and demonstrate by reverse transcription polymerase chain reaction (RT-PCR) that peripheral blood PTHrP levels were 2,500-fold higher compared to healthy controls. PTHrP production by tumor cells in chronic lymphocytic leukemia (CLL) and Richter's syndrome has been previously demonstrated by nonquantitative methods such as immunohistochemistry and northern blot analysis, but this is the first report using the RT-PCR method. The presented case did not have hypercalcemia when initially diagnosed as small lymphocytic lymphoma (SLL), and as reported earlier, the development of hypercalcemia may be an indication of the transformation to Richter's syndrome in patients with CLL/SLL. PMID:28203174

  12. Chronic Myeloid Leukemia Associated Hypercalcemia: A Case Report and Literature Review

    PubMed Central

    Toro-Tobón, David; Agosto, Sarimar; Ahmadi, Sara; Koops, Maureen; Bruder, Jan M.

    2017-01-01

    Patient: Male, 58 Final Diagnosis: Hypercalcemia Symptoms: Confusion • dehydration Medication: — Clinical Procedure: — Specialty: Endocrinology and Metabolism Objective: Rare co-existance of disease or pathology Background: Hypercalcemia associated with chronic myeloid leukemia (CML) is an ominous sign. Although rare, several cases have been reported and multiple pathophysiologic mechanisms have been independently proposed. We present a patient case and a literature review of the clinical presentation and mechanisms of CML-associated hypercalcemia. Case Report: A 58-year-old male with a past medical history of CML diagnosed six years earlier, presented to the emergency department with one week of acute confusion, disorientation, polyuria, and polydipsia. On physical examination, we observed tachycardia, altered mental status, and dehydration. Blood analysis revealed leukocytosis, thrombocytosis, and marked hypercalcemia (18.6 mg/dL). His chest CT scan showed diffuse lytic lesions and bone destruction concerning for diffuse bone marrow involvement. The patient was diagnosed with hypercalcemia in the context of a CML blast phase. Treatment with hydration, calcitonin, and zoledronic acid lead to control of his symptoms and normalization of his serum calcium levels. After discharged, the patient was maintained on palliative treatment and zoledronic acid management without new episodes of hypercalcemia. However, eight months later, the patient died. Conclusions: Evidence from the literature demonstrates a highly variable clinical presentation of CML-associated hypercalcemia, commonly occurring during an accelerated or a blast phase, and associated with poor survival. Multiple mechanisms could be involved and are not exclusive of each other. Better understanding of the pathophysiologic mechanisms involved in CML-associated hypercalcemia could lead to improvement in clinical and laboratory evaluation of these patients and be the foundation for the development of

  13. Familial hypercalcemia and hypercalciuria: no mutations in the Ca2+-sensing receptor gene.

    PubMed

    Rodríguez-Soriano, J; Vallo, A; Quintela, M J; Pérez de Nanclares, G; Bilbao, J R; Castaño, L

    2001-09-01

    A 6-year-old boy presented with persistent hypercalcemia, hypercalciuria and nephrocalcinosis from early infancy. His 40-year-old father also had hypercalcemia and hypercalciuria. In both individuals serum values of intact parathyroid hormone (PTH) were repeatedly normal. Although these findings suggest a functional abnormality of the calcium-sensing receptor (CaR), no mutations in coding regions of the CaR gene could be demonstrated.

  14. Intravenous pamidronate in the treatment of severe idiopathic infantile hypercalcemia.

    PubMed

    Skalova, Sylva; Cerna, Lucie; Bayer, Milan; Kutilek, Stepan; Konrad, Martin; Schlingmann, Karl-Peter

    2013-03-01

    Idiopathic infantile hypercalcemia (IIH) is a rare disorder caused by CYP24A1 loss-of-function mutation, resulting in impaired degradation of 1,25-dihydroxyvitamin D3. Pamidronate, an intravenously administered bisphosphonate, which is a potent inhibitor of bone resorption, has been reported only once for treatment IIH. We present a case of a previously healthy 5-month-old boy with IIH, where calcemia peaked to 5 mmol/L. Treatment with methylprednisone and furosemide had only minor effects; therefore, 2 intravenous infusions of pamidronate (0.6 mg/kg per dose) corrected the serum calcium level to 2.95 mmol/L. Furthermore, CYP24A1 homozygous mutation p.R396W (c.1186c>t) was identified in this patient, confirming the clinical diagnosis of IIH. In conclusion, IIH has a favorable outcome once properly detected and appropriately treated. Pamidronate has a beneficial effect in those patients with IIH where glucocorticoids and furosemide fail to meet the expectations.  

  15. Hypercalcemia secondary to granulomatous disease caused by the injection of methacrylate: a case series

    PubMed Central

    Negri, Armando Luis; Rosa Diez, Guillermo; Del Valle, Elisa; Piulats, Elsa; Greloni, Gustavo; Quevedo, Alejandra; Varela, Federico; Diehl, Maria; Bevione, Pablo

    2014-01-01

    Summary Association of dysregulated calcium homeostasis and granulomatous disease is well established. There exist reports in the literature of granulomatous reactions produced by silicones associated with hypercalcemia. In this case series we report four young women that underwent methacrylate injections in gluteus, thighs and calves that developed granulomas with posterior appearance of hypercalcemia. This complication presented as subacute around 6 months after the procedure. The four patients have as common elements the presence of moderate to severe renal insufficiency, suppressed PTH and elevated calcitriol levels for the degree of renal function. In the image studies, two patients presented in the nuclear magnetic resonance of the gluteus hypodense nodular images compatible with granulomas. Two patients had a positron emission tomography performed showing increased metabolic activity in the muscles of the gluteal region compatible with granulomas. Two patients had a partial surgical resection of the gluteal lesions with the finding of methacrylate associated to foreign body granulomas. In these patients hypercalcemia was treated with oral or local injections of corticoids, intravenous bisphosphonates or ketoconazole with good response. Although the prevalence of this complication with methacrylate injection is not common, hypercalcemia secondary to granulomas should be considered in the differential diagnosis of patients with hypercalcemia when there is a history of this procedure, and especially if they have a reduction in their renal function. PMID:25002879

  16. Hypophosphatasia Presenting with Pyridoxine-Responsive Seizures, Hypercalcemia, and Pseudotumor Cerebri: Case Report

    PubMed Central

    Alanay, Yasemin; Alikaşifoğlu, Ayfer; Topçu, Meral; Mornet, Etienne; Özön, Alev; Kandemir, Nurgün

    2012-01-01

    Hypophosphatasia (HPP) is an inborn error of metabolism characterized by defective bone mineralization caused by a deficiency in alkaline phosphatase (ALP) activity due to mutations in the tissue-nonspecific ALP (TNALP) gene. The clinical expression of the disease is variable. Six forms of HPP are identified according to age at presentation and clinical features. Patients with the infantile form are normal at birth. First symptoms appear within the first 6 months of life. Along with skeletal findings, HPP patients may present with hypercalcemia, seizures, pseudotumor cerebri, and pulmonary insufficiency. Seizures in HPP are refractory to conventional antiepileptic drugs, but are responsive to pyridoxine. Herein, we report a case of HPP who presented with pyridoxine-responsive seizures in the early neonatal period and was found to have hypercalcemia, skeletal demineralization and increased intracranial pressure. Key words: Hypophosphatasia, pyridoxine-responsive seizures, bisphosphonates, alkaline phosphatase, bone resorption, hypercalcemia Conflict of interest:None declared. PMID:22394703

  17. Cinacalcet for Hypercalcemia Caused by Pulmonary Squamous Cell Carcinoma Producing Parathyroid Hormone-Related Peptide

    PubMed Central

    Bech, Anneke; Smolders, Koen; Telting, Darryl; de Boer, Hans

    2012-01-01

    Background Current treatments for hypercalcemia caused by lung cell carcinomas producing parathyroid hormone-related peptide (PTH-rp) have limited efficacy, probably because of their lack of effect on PTH-rp secretion. In this case study we explored the efficacy of the calcimimetic cinacalcet as suppressor of PTH-rp production. Patient A 57-year-old male with severe and recurrent hypercalcemia induced by a PTH-rp-producing squamous cell lung carcinoma, stage cT4N3M1b, poorly responding to standard treatments. Results Serum PTH-rp levels were not affected by saline, calcitonin or zoledronate. PTH-rp decreased during chemotherapy and cinacalcet monotherapy. The combination of chemotherapy plus cinacalcet was most effective in rapidly reducing serum calcium and PTH-rp. Conclusion This case study is the first to suggest that cinacalcet may be of value in some cases of PTH-rp-dependent hypercalcemia. Corroborative evidence is needed. PMID:22379470

  18. Hypercalcemia, Anemia, and Acute Kidney Injury: A Rare Presentation of Sarcoidosis

    PubMed Central

    Sharma, Neeraj; Tariq, Hassan; Uday, Kalpana; Skaradinskiy, Yevgeniy; Niazi, Masooma; Chilimuri, Sridhar

    2015-01-01

    We discuss a case of a 61-year-old woman who presented with substernal chest pain. She was found to have elevated calcium levels, anemia, and acute kidney injury. The hypercalcemia persisted despite therapy with fluids and bisphosphonates. She was found to have nonparathyroid hormone (PTH) mediated hypercalcemia. The chest X-ray did not reveal any pathology. Our Initial impression was likely underlying hematologic malignancy such as lymphoma or multiple myeloma. A bone marrow biopsy was performed that revealed nonnecrotizing granulomatous inflammation. Further workup revealed elevated vitamin 1,25 dihydroxy level, beta-two microglobulin level, and ACE levels. Noncontrast computed tomography (CT) scan of chest showed bilateral apical bronchiectasis, but did not show any lymphadenopathy or evidence of malignancy. Subsequently, a fiber optic bronchoscopy with transbronchial biopsy showed nonnecrotizing granulomatous inflammation consistent with sarcoidosis. After initiating glucocorticoid therapy, the patient's hypercalcemia improved and her kidney function returned to baseline. PMID:26199627

  19. Hypercalcemia and Lytic Bone Lesions Masquerading Inflammatory Arthritis Treated as Rheumatoid Arthritis.

    PubMed

    Salari, Masoumeh; Aboutorabi, Robab Bigom; Rezaieyazdi, Zahra

    2015-10-01

    Hyperparathyroidism is a complex clinical syndrome characterized by dysfunction in the metabolism of bone, calcium and phosphorus. Rheumatologic manifestations are common amongst patients with hyperparathyroidism. We report a 50-year-old woman with hypercalcemia, lytic bone lesions and inflammatory arthritis of both hands that were not resolved after parathyroidectomy. Laboratory evidence of elevated erythrocyte sedimentation rate, positive C-reactive protein (CRP) and high titers of anti-CCP and rheumatoid factor was diagnostic of rheumatoid arthritis (RA) according to European League Against Rheumatism criteria. Eventually, with the concomitant diagnoses of hyperparathyroidism and RA, she was treated with methotrexate and hydroxychloroquin. Hyperparathyroidism may present with rheumatologic manifestations, leading to an initial misdiagnosis. Furthermore, attention to this fact that hypercalcemia is not commonly associated with RA, and rather suggestive of a concomitant disorder, is crucial to the diagnosis of hyperparathyroidism in RA patients with hypercalcemia.

  20. Genetic linkage analysis in familial Benign (Hypocalciuric) Hypercalcemia: Evidence for locus heterogeneity

    SciTech Connect

    Heath, H. III; Otterud, B.; Leppert, M.F. ); Jackson, C.E. )

    1993-07-01

    Familial benign hypercalcemia (FBH, or hypocalciuric hypercalcemia) is characterized by inheritance, in an autosomal dominant pattern, of lifelong hypercalcemia without hypercalciuria, which is often mistaken for classical primary hyperparathyroidism. Recently, the FBH trait was linked, in four families, to chromosome 3q. The authors report genetic linkage analysis in 140 persons from five additional families having FBH (65 affected, 67 unaffected, and 8 unclassifiable). In four families, FBH mapped to chromosome 3q, between D3S1215 and D3S20, maximum multipoint lod score 12.9. By contrast, in the fifth kindred FBH mapped to chromosome 19p13.3, tightly linked to the marker loci D19S20 and D19S266 (two-point lod score at recombination fraction = .001 is 3.44 and 3.70, respectively). Thus, the FBH phenotype results from mutations at two separate loci on chromosomes 3q and 19p. 25 refs., 4 figs., 6 tabs.

  1. Carcinoma of Lung with Adrenal Hyperfunction and Hypercalcemia Treated by Parathyroidectomy

    PubMed Central

    Gault, M. Henry; Kinsella, T. Douglas

    1965-01-01

    A case of severe hypercalcemia secondary to carcinoma of the lung is described in which hypokalemic alkalosis, renal failure and pancreatitis were also present. The relative importance of the few bone metastases found at autopsy is considered, and a probable endocrine-like effect of the tumour in the development of the hypercalcemia is postulated. Treatment of the hypercalcemia included administration of corticosteroids and disodium EDTA, peritoneal dialysis and subtotal parathyroidectomy; the most effective of these was peritoneal dialysis. Subtotal parathyroidectomy failed to produce a further decrease in serum calcium values. The occurrence of hypokalemic alkalosis in the presence of increased adrenocortical function and its relationship to the carcinoma of the lung are discussed. The possibility that this neoplasm produced two factors which caused systemic effects ordinarily associated with the function of endocrine glands must be considered. PMID:14243867

  2. Genetic defect in CYP24A1, the vitamin D 24-hydroxylase gene, in a patient with severe infantile hypercalcemia

    USDA-ARS?s Scientific Manuscript database

    Idiopathic infantile hypercalcemia (IIH) is a disorder the genetic etiology and physiological basis of which are not well understood. The objective of the study was to describe the underlying physiology and genetic cause of hypercalcemia in an infant with severe IIH and to extend these genetic findi...

  3. [Hypercalcemia and multiple osteolytic lesions in a child with disseminated paracoccidioidomycosis and pulmonary tuberculosis].

    PubMed

    Tresoldi, Antonia T; Pereira, Ricardo M; Castro, Lelma C; Rigatto, Sumara Z P; Belangero, Vera M S

    2005-01-01

    To describe the case of a child with paracoccidioidomycosis who presented hypercalcemia with multiple osteolytic lesions. A 6-year-old boy was admitted with a one-month history of fever and hepatosplenomegaly. On admission, he looked sick, pale, and had disseminated lymphadenopathy and hepatosplenomegaly. The laboratory findings included anemia (hemoglobin = 6.8 g/dl), eosinophilia (1,222/mm3), thrombocytopenia (102,000/mm3), and hypoalbuminemia (serum albumin = 2.2 g/dl). Paracoccidioides brasiliensis was identified in bone marrow examination. In the second week after admission, the patient presented joint pain, poor activity and difficulty in walking. He presented hypercalcemia (maximum value = 14.9 mg%) and reduction in renal function, which lasted for two weeks. On the 42nd day after admission, his chest X-ray showed lytic lesions in clavicle, scapula, ribs, and humerus, with bilateral slipped capital humeral epiphysis. The patient presented nephrocalcinosis and nephrolithiasis, reduction in creatinine clearance and evidence of tubular lesions. At the end of the second month after admission, Mycobacterium tuberculosis was isolated in gastric washing. The child received treatment for paracoccidioidomycosis and tuberculosis and has not had any sequelae for 3 years. The development of symptomatic hypercalcemia leading to renal lesion, associated with multiple osteolytic lesions, had never been described in paracoccidioidomycosis. Although pulmonary tuberculosis was diagnosed and could be related to hypercalcemia, the sudden onset of hypercalcemia and its normalization without specific treatment for tuberculosis suggests that bone lysis was the most important factor in the genesis of hypercalcemia.

  4. Humoral Hypercalcemia in Uterine Cancers: A Case Report and Literature Review

    PubMed Central

    Nehru, Vijeyaluxmy Motilal; Garcia, Gwenalyn; Ding, Juan; Kong, Fanyi; Dai, Qun

    2017-01-01

    Patient: Female, 53 Final Diagnosis: Endometrial stromal sarcoma Symptoms: Abdominal distension Medication: — Clinical Procedure: — Specialty: Oncology Objective: Rare co-existance of disease or pathology Background: Paraneoplastic hypercalcemia is a well-described complication associated with a variety of malignancies. However, its incidence in gynecological malignancies is low. Case Report: A 53-year-old woman presented with progressive abdominal distention and irregular vaginal bleeding of several weeks’ duration. A contrast CT abdomen and pelvis was significant for a mass in the lower uterine/cervical region, multiple peritoneal and omental masses, enlarged pelvic and paraaortic lymph nodes, and large-volume ascites. A pelvic exam revealed a fungating vaginal mass, with biopsy showing a high-grade tumor with immunohistochemical staining positive for vimentin, CD10, and cyclin D1, consistent with endometrial stromal sarcoma. During her hospitalization, the patient became increasingly lethargic. Workup showed severe hypercalcemia and evidence of acute kidney injury. The patient did not have evidence of bony metastatic disease on imaging studies. Further laboratory evaluation revealed an elevated PTHrP of 301 pg/mL (nl 14–27), a depressed PTH level of 3 pg/mL (nl 15–65), and a depressed 25-OH vitamin D level of 16 ng/mL (nl 30–100), consistent with humoral hypercalcemia of malignancy. The patient was treated with pamidronate, calcitonin, and intravenous fluids. She eventually required temporary hemodialysis and denosumab for refractory hypercalcemia, which improved her electrolyte abnormalities and clinical status. Conclusions: Uterine malignancies of various histologies are increasingly recognized as a cause of humoral hypercalcemia. They are an important differential diagnosis in a woman with hypercalcemia and abnormal vaginal bleeding or abdominal symptoms. PMID:28057913

  5. 1,25-dihydroxyvitamin D and PTHrP mediated malignant hypercalcemia in a seminoma.

    PubMed

    Rodríguez-Gutiérrez, René; Zapata-Rivera, Maria Azucena; Quintanilla-Flores, Dania Lizeth; Camara-Lemarroy, Carlos Rodrigo; Lavalle-Gonzalez, Fernando Javier; González-González, José Gerardo; Villarreal-Pérez, Jesús Zacarías

    2014-04-10

    Seminomas have been rarely associated with malignant hypercalcemia. The responsible mechanism of hypercalcemia in this setting has been described to be secondary to 1,25-dihydroxyvitamin D secretion. The relationship with PTHrP has not been determined or studied.The aim of this study is to describe and discuss the case and the pathophysiological mechanisms involved in a malignant hypercalcemia mediated by 1,25-dihydroxyvitamin D and PTHrP cosecretion in a patient with seminoma. A 35-year-old man was consulted for assessment and management of severe hypercalcemia related to an abdominal mass. Nausea, polyuria, polydipsia, lethargy and confusion led him to the emergency department. An abdominal and pelvic enhanced CT confirmed a calcified pelvic mass, along with multiple retroperitoneal lymphadenopathy. Chest x-ray revealed "cannon ball" pulmonary metastases. The histopathology result was consistent with a seminoma. Serum calcium was 14.7 mg/dl, PTH was undetectable, 25-dihydroxyvitamin D was within normal values and PTHrP and 1,25-dihydroxyvitamin were elevated (35.0 pg/ml, and 212 pg/ml, respectively). After the first cycle of chemotherapy with bleomycin, etoposide and cisplatin, normocalcemia was restored. Both PTHrP and 1,25-dihydroxyvitamin D, dropped dramatically to 9.0 pg/ml and 8.0 pg/ml, respectively. The association of seminoma and malignant hypercalcemia is extremely rare. We describe a case of a patient with a seminoma and malignant hypercalcemia related to paraneoplastic cosecretion of 1,25-dihydroxyvitamin D and PTHrP. After successful chemotherapy, calcium, PTHrP and 1,25-Dihydroxyvitamin D returned to normal values.

  6. Ketotic hypercalcemia: a case series and description of a novel entity.

    PubMed

    Hawkes, Colin Patrick; Levine, Michael A

    2014-05-01

    The ketogenic diet is increasingly used in refractory epilepsy and is associated with clinically significant effects on bone and mineral metabolism. Although hypercalciuria and loss of bone mineral density are common in patients on the ketogenic diet, hypercalcemia has not previously been described. The aim of the study was to describe three children who developed hypercalcemia while on the ketogenic diet. A retrospective chart review of three children on the ketogenic with severe hypercalcemia was conducted. We describe three children on the ketogenic diet for refractory seizures who presented with hypercalcemia. Case 1 was a 5.5-year-old male with an undiagnosed, rapidly progressive seizure disorder associated with developmental regression. Case 2 was a 2.5-year-old male with a chromosomal deletion of 2q24.3, and case 3 was a 4.6-year-old male with cerebral cortex dysplasia. Patients had been on a ketogenic diet for 6 to 12 months before presentation. Daily intake of calcium and vitamin D was not excessive, and all three patients were not acidotic because they were taking supplemental bicarbonate. Each child had elevated serum levels of calcium and normal serum phosphate levels, moderately elevated urinary calcium excretion, and low levels of serum alkaline phosphatase, PTH, and 1,25-dihydroxyvitamin D. All patients responded to calcitonin. Hypercalcemia is an uncommon complication of the ketogenic diet, and these children may represent the severe end of a clinical spectrum of disordered mineral metabolism. The mechanism for hypercalcemia is unknown but is consistent with excess bone resorption and impaired calcium excretion.

  7. 1,25-dihydroxyvitamin D and PTHrP mediated malignant hypercalcemia in a seminoma

    PubMed Central

    2014-01-01

    Background Seminomas have been rarely associated with malignant hypercalcemia. The responsible mechanism of hypercalcemia in this setting has been described to be secondary to 1,25-dihydroxyvitamin D secretion. The relationship with PTHrP has not been determined or studied. The aim of this study is to describe and discuss the case and the pathophysiological mechanisms involved in a malignant hypercalcemia mediated by 1,25-dihydroxyvitamin D and PTHrP cosecretion in a patient with seminoma. Case presentation A 35-year-old man was consulted for assessment and management of severe hypercalcemia related to an abdominal mass. Nausea, polyuria, polydipsia, lethargy and confusion led him to the emergency department. An abdominal and pelvic enhanced CT confirmed a calcified pelvic mass, along with multiple retroperitoneal lymphadenopathy. Chest x-ray revealed “cannon ball” pulmonary metastases. The histopathology result was consistent with a seminoma. Serum calcium was 14.7 mg/dl, PTH was undetectable, 25-dihydroxyvitamin D was within normal values and PTHrP and 1,25-dihydroxyvitamin were elevated (35.0 pg/ml, and 212 pg/ml, respectively). After the first cycle of chemotherapy with bleomycin, etoposide and cisplatin, normocalcemia was restored. Both PTHrP and 1,25-dihydroxyvitamin D, dropped dramatically to 9.0 pg/ml and 8.0 pg/ml, respectively. Conclusion The association of seminoma and malignant hypercalcemia is extremely rare. We describe a case of a patient with a seminoma and malignant hypercalcemia related to paraneoplastic cosecretion of 1,25-dihydroxyvitamin D and PTHrP. After successful chemotherapy, calcium, PTHrP and 1,25-Dihydroxyvitamin D returned to normal values. PMID:24721620

  8. Lithium intoxication, hypercalcemia and "accidentally" induced food and water aversion: a case report.

    PubMed

    Bilanakis, Nikos; Gibiriti, Mariana

    2004-01-01

    Lithium is widely used in the management of patients with affective and other behavioral disorders. In addition to its therapeutic role, it is important to recognize that it occasionally causes severe side effects. Associated with its long-term use, parathyroid hypersecretion and hypercalcemia is a rare but reported side effect. A 54-year-old patient is reported who previously had a good response to lithium carbonate treatment of his bipolar disorder. Suddenly, and after 15 years of lithium carbonate use, he presented food and water aversion, hypercalcemia, lithium intoxication (SLi of 4.30 mmol/l) and acute renal insufficiency. Haemodialysis was carried out and the patient improved dramatically.

  9. Extensive Visceral Calcification Demonstrated on 99mTc-MDP Bone Scan in Patient with Carcinoma Penis and Hypercalcemia of Malignancy

    PubMed Central

    Gandhi, Sunny J.; Rabadiya, Bhavdeep

    2017-01-01

    Hypercalcemia is a common life-threatening complication associated with several malignancies. Parathyroid-related peptide has been shown to cause hypercalcemia in several solid tumors but rarely in penile cancer. We report a case of penile cancer with hypercalcemia causing metastatic visceral calcification in lungs, liver, and stomach detected on bone scan without significant abnormalities on CT scan. PMID:28533650

  10. Osteolytic bone lesions, severe hypercalcemia without circulating blasts: unusual presentation of childhood acute lymphoblastic leukemia.

    PubMed

    Bechir, Achour; Haifa, Regaieg; Atef, Ben Abdelkader; Emna, Bouslema; Asma, Achour; Nesrine, Ben Sayed; Yosra, Ben Youssef; Abdrrahim, Khelif

    2017-01-01

    Hypercalcemia and severe osteolytic lesions are rare complications of acute lymphoblastic leukemia (ALL) in childhood. We report a case of a 3 years old boy who presented with prolonged fever, nausea, vomiting and increasing lower limbs pain. Skeletal X-rays and CT scan showed severe osteolytic lesions of the skull and extremities. Her physical examination showed multiple cervical lymph nodes. In laboratory tests, he had severe hypercalcemia. Parathyroid hormone (PTH) was not elevated. Despite the absence of circulating blasts, bone marrow biopsy revealed B-precursor (ALL). Hypercalcemia was initially treated with intravenous isotonic sodium chloride solution and diuretics but the serum calcium level normalized only after the beginning of corticosteroids and chemotherapy. The child responded initially to chemotherapy and eventually relapsed and died of septic shock. Acute leukemia must be considered in differential diagnosis in patients with hypercalcemia. A detailed examination even when there no circulating blasts in their peripheral blood smear, and if in doubt bone marrow aspiration should must be taken into consideration.

  11. Osteolytic bone lesions, severe hypercalcemia without circulating blasts: unusual presentation of childhood acute lymphoblastic leukemia

    PubMed Central

    Bechir, Achour; Haifa, Regaieg; Atef, Ben Abdelkader; Emna, Bouslema; Asma, Achour; Nesrine, Ben Sayed; Yosra, Ben Youssef; Abdrrahim, Khelif

    2017-01-01

    Hypercalcemia and severe osteolytic lesions are rare complications of acute lymphoblastic leukemia (ALL) in childhood. We report a case of a 3 years old boy who presented with prolonged fever, nausea, vomiting and increasing lower limbs pain. Skeletal X-rays and CT scan showed severe osteolytic lesions of the skull and extremities. Her physical examination showed multiple cervical lymph nodes. In laboratory tests, he had severe hypercalcemia. Parathyroid hormone (PTH) was not elevated. Despite the absence of circulating blasts, bone marrow biopsy revealed B-precursor (ALL). Hypercalcemia was initially treated with intravenous isotonic sodium chloride solution and diuretics but the serum calcium level normalized only after the beginning of corticosteroids and chemotherapy. The child responded initially to chemotherapy and eventually relapsed and died of septic shock. Acute leukemia must be considered in differential diagnosis in patients with hypercalcemia. A detailed examination even when there no circulating blasts in their peripheral blood smear, and if in doubt bone marrow aspiration should must be taken into consideration. PMID:28690758

  12. Congenital sucrase-isomaltase deficiency presenting with failure to thrive, hypercalcemia, and nephrocalcinosis

    PubMed Central

    Belmont, John W; Reid, Barbara; Taylor, William; Baker, Susan S; Moore, Warren H; Morriss, Michael C; Podrebarac, Susan M; Glass, Nancy; Schwartz, I David

    2002-01-01

    Background Disaccharide Intolerance Type I (Mendelian Interance in Man database: *222900) is a rare inborn error of metabolism resulting from mutation in sucrase-isomaltase (Enzyme Catalyzed 3.2.1.48). Usually, infants with SI deficiency come to attention because of chronic diarrhea and nutritional evidence of malabsorption. Case Presentation We describe an atypical presentation of this disorder in a 10-month-old infant. In addition to chronic diarrhea, the child displayed severe and chronic hypercalcemia, the evaluation of which was negative. An apparently coincidental right orbital hemangioma was detected. Following identification of the SI deficiency, an appropriately sucrose-restricted, but normal calcium diet regimen was instituted which led to cessation of diarrhea, substantial weight gain, and resolution of hypercalcemia. Conclusions This case illustrates that, similar to congenital lactase deficiency (Mendelian Interance in Man database: *223000, Alactasia, Hereditary Disaccharide Intolerance Type II), hypercalcemia may complicate neonatal Sucrase-Isomaltase deficiency. Hypercalcemia in the presence of chronic diarrhea should suggest disaccharide intolerance in young infants. PMID:12014995

  13. [A case of sarcoidosis with hypercalcemia, urolithiasis, nephrocalcinosis and renal insufficiency].

    PubMed

    Nunohiro, T; Aoi, W; Kadota, J; Ueda, Y; Takahara, O; Yura, M

    1992-08-01

    A sixty nine-year-old woman was admitted to the hospital because of further examination of hypercalcemia. On July 1990, she complained of general fatigue and loss of appetite. She was pointed out to have hypercalcemia (15.1mg/dl), urolithiasis, and renal insufficiency. CT films of the chest showed swelling of the mediastinal lymphnodes and CT of the abdomen nephrocalcinosis. Ga-scintigraphy demonstrated an abnormal accumulation of gallium in the mediastinum. Levels of the parathyroid hormone was normal. Levels of the serum calcium (13.7mg/dl), angiotensin converting enzyme (30.4IU/L) and 1.25 (OH)2D (87PG/ml) were elevated. Giant cells were found in the biopsy specimen of the lung. A significant relationship between the serum calcium and creatinine were observed (r = 0.76, p < 0.02). Proximal fractional reabsorption of sodium showed to be suppressed (47.7%), and distal fractional reabsorption of sodium showed to be normal (88.4%). From these findings hypercalcemia and urolithiasis was suggested to result from sarcoidosis. The hypercalcemia and renal insufficiency improved with corticosteroid therapy.

  14. Primary clitoral adenocarcinoma with secondary hypercalcemia of malignancy in a dog.

    PubMed

    Neihaus, Steven A; Winter, Jennifer E; Goring, Robert L; Kennedy, F A; Kiupel, Matti

    2010-01-01

    This report describes a primary clitoral adenocarcinoma in a dog with secondary hypercalcemia of malignancy. A 10-year-old, spayed female basset hound was evaluated for a mass protruding from the vulva. The mass was excised, and a histological diagnosis of clitoral adenocarcinoma was made. No evidence of metastasis on thoracic radiographs or abdominal ultrasound was seen. Preoperative hypercalcemia resolved following excision of the mass. Cellular features were similar to an apocrine gland anal sac adenocarcinoma, and immunohistochemistry exhibited features noted with apocrine gland anal sac adenocarcinoma. No further treatment was elected by the owner. Internal iliac lymph-node metastasis was identified 4 weeks postoperatively, and hypercalcemia recurred 8 weeks postoperatively. The dog was euthanized 22 weeks postoperatively for signs related to hypercalcemia, including polyuria/polydipsia, lethargy, and weakness. A necropsy was performed and confirmed the presence of internal iliac lymph-node metastasis. The colon, rectum, and anal sacs were grossly and histologically normal. To our knowledge, this is the first reported case of clitoral neoplasia in the dog.

  15. Mutations Affecting G-Protein Subunit α11 in Hypercalcemia and Hypocalcemia

    PubMed Central

    Babinsky, Valerie N.; Head, Rosie A.; Cranston, Treena; Rust, Nigel; Hobbs, Maurine R.; Heath, Hunter; Thakker, Rajesh V.

    2013-01-01

    BACKGROUND Familial hypocalciuric hypercalcemia is a genetically heterogeneous disorder with three variants: types 1, 2, and 3. Type 1 is due to loss-of-function mutations of the calcium-sensing receptor, a guanine nucleotide–binding protein (G-protein)–coupled receptor that signals through the G-protein subunit α11 (Gα11). Type 3 is associated with adaptor-related protein complex 2, sigma 1 subunit (AP2S1) mutations, which result in altered calcium-sensing receptor endocytosis. We hypothesized that type 2 is due to mutations effecting Gα11 loss of function, since Gα11 is involved in calcium-sensing receptor signaling, and its gene (GNA11) and the type 2 locus are colocalized on chromosome 19p13.3. We also postulated that mutations effecting Gα11 gain of function, like the mutations effecting calcium-sensing receptor gain of function that cause autosomal dominant hypocalcemia type 1, may lead to hypocalcemia. METHODS We performed GNA11 mutational analysis in a kindred with familial hypocalciuric hypercalcemia type 2 and in nine unrelated patients with familial hypocalciuric hypercalcemia who did not have mutations in the gene encoding the calcium-sensing receptor (CASR) or AP2S1. We also performed this analysis in eight unrelated patients with hypocalcemia who did not have CASR mutations. In addition, we studied the effects of GNA11 mutations on Gα11 protein structure and calcium-sensing receptor signaling in human embryonic kidney 293 (HEK293) cells. RESULTS The kindred with familial hypocalciuric hypercalcemia type 2 had an in-frame deletion of a conserved Gα11 isoleucine (Ile200del), and one of the nine unrelated patients with familial hypocalciuric hypercalcemia had a missense GNA11 mutation (Leu135Gln). Missense GNA11 mutations (Arg181Gln and Phe341Leu) were detected in two unrelated patients with hypocalcemia; they were therefore identified as having autosomal dominant hypocalcemia type 2. All four GNA11 mutations predicted disrupted protein

  16. Mutations affecting G-protein subunit α11 in hypercalcemia and hypocalcemia.

    PubMed

    Nesbit, M Andrew; Hannan, Fadil M; Howles, Sarah A; Babinsky, Valerie N; Head, Rosie A; Cranston, Treena; Rust, Nigel; Hobbs, Maurine R; Heath, Hunter; Thakker, Rajesh V

    2013-06-27

    Familial hypocalciuric hypercalcemia is a genetically heterogeneous disorder with three variants: types 1, 2, and 3. Type 1 is due to loss-of-function mutations of the calcium-sensing receptor, a guanine nucleotide-binding protein (G-protein)-coupled receptor that signals through the G-protein subunit α11 (Gα11). Type 3 is associated with adaptor-related protein complex 2, sigma 1 subunit (AP2S1) mutations, which result in altered calcium-sensing receptor endocytosis. We hypothesized that type 2 is due to mutations effecting Gα11 loss of function, since Gα11 is involved in calcium-sensing receptor signaling, and its gene (GNA11) and the type 2 locus are colocalized on chromosome 19p13.3. We also postulated that mutations effecting Gα11 gain of function, like the mutations effecting calcium-sensing receptor gain of function that cause autosomal dominant hypocalcemia type 1, may lead to hypocalcemia. We performed GNA11 mutational analysis in a kindred with familial hypocalciuric hypercalcemia type 2 and in nine unrelated patients with familial hypocalciuric hypercalcemia who did not have mutations in the gene encoding the calcium-sensing receptor (CASR) or AP2S1. We also performed this analysis in eight unrelated patients with hypocalcemia who did not have CASR mutations. In addition, we studied the effects of GNA11 mutations on Gα11 protein structure and calcium-sensing receptor signaling in human embryonic kidney 293 (HEK293) cells. The kindred with familial hypocalciuric hypercalcemia type 2 had an in-frame deletion of a conserved Gα11 isoleucine (Ile200del), and one of the nine unrelated patients with familial hypocalciuric hypercalcemia had a missense GNA11 mutation (Leu135Gln). Missense GNA11 mutations (Arg181Gln and Phe341Leu) were detected in two unrelated patients with hypocalcemia; they were therefore identified as having autosomal dominant hypocalcemia type 2. All four GNA11 mutations predicted disrupted protein structures, and assessment on the

  17. Hypercalcemia induces targeted autophagic degradation of aquaporin-2 at the onset of nephrogenic diabetes insipidus.

    PubMed

    Khositseth, Sookkasem; Charngkaew, Komgrid; Boonkrai, Chatikorn; Somparn, Poorichaya; Uawithya, Panapat; Chomanee, Nusara; Payne, D Michael; Fenton, Robert A; Pisitkun, Trairak

    2017-05-01

    Hypercalcemia can cause renal dysfunction such as nephrogenic diabetes insipidus (NDI), but the mechanisms underlying hypercalcemia-induced NDI are not well understood. To elucidate the early molecular changes responsible for this disorder, we employed mass spectrometry-based proteomic analysis of inner medullary collecting ducts (IMCD) isolated from parathyroid hormone-treated rats at onset of hypercalcemia-induced NDI. Forty-one proteins, including the water channel aquaporin-2, exhibited significant changes in abundance, most of which were decreased. Bioinformatic analysis revealed that many of the downregulated proteins were associated with cytoskeletal protein binding, regulation of actin filament polymerization, and cell-cell junctions. Targeted LC-MS/MS and immunoblot studies confirmed the downregulation of 16 proteins identified in the initial proteomic analysis and in additional experiments using a vitamin D treatment model of hypercalcemia-induced NDI. Evaluation of transcript levels and estimated half-life of the downregulated proteins suggested enhanced protein degradation as the possible regulatory mechanism. Electron microscopy showed defective intercellular junctions and autophagy in the IMCD cells from both vitamin D- and parathyroid hormone-treated rats. A significant increase in the number of autophagosomes was confirmed by immunofluorescence labeling of LC3. Colocalization of LC3 and Lamp1 with aquaporin-2 and other downregulated proteins was found in both models. Immunogold electron microscopy revealed aquaporin-2 in autophagosomes in IMCD cells from both hypercalcemia models. Finally, parathyroid hormone withdrawal reversed the NDI phenotype, accompanied by termination of aquaporin-2 autophagic degradation and normalization of both nonphoshorylated and S256-phosphorylated aquaporin-2 levels. Thus, enhanced autophagic degradation of proteins plays an important role in the initial mechanism of hypercalcemic-induced NDI.

  18. Clinical and biochemical outcomes of cinacalcet treatment of familial hypocalciuric hypercalcemia: a case series

    PubMed Central

    2011-01-01

    Introduction Familial hypocalciuric hypercalcemia is a rare benign autosomal-dominant genetic disease with high penetrance. In most cases, patients with familial hypocalciuric hypercalcemia experience unspecific physical discomfort or asymptomatic disease. These patients are typically characterized by mild to moderately increased blood ionized calcium and a normal to slightly elevated serum parathyroid hormone. Case presentation Four female patients with familial hypocalciuric hypercalcemia with inactivating mutations in the CaSR gene were included in the treatment study. Three patients were related: two were siblings and one was the daughter of one of these. The ages of the related patients were 51 years, 57 years and 35 years. All three patients were carriers of the same mutation. The fourth patient, unrelated to the others, was 53 years old, and a carrier of a novel and previously unknown mutation leading to familial hypocalciuric hypercalcemia. All four patients were Caucasians of Danish nationality. Biochemically, all patients had elevated blood ionized calcium, serum parathyroid hormone, serum magnesium and total serum calcium, except one, whose serum parathyroid hormone was within the normal range prior to treatment. All patients were treated with cinacalcet in a dosage of 30 mg to 60 mg per day. Conclusion Three months after the initiation of cinacalcet treatment, all our patients experiencing clinical signs of hypercalcemia had improved in self -reported well-being and in biochemical parameters. None of our patients suffered adverse events to cinacalcet treatment. Biochemical markers of calcium homeostasis were improved and remained stable during the observation period of 12 months (two patients), 24 and 36 months, in both the symptomatic and the asymptomatic patients. PMID:22142470

  19. Hypercalcemia as Initial Presentation of Metastatic Adenocarcinoma of Gastric Origin: A Case Report and Review of the Literature

    PubMed Central

    Kumar, Abhishek; Kumar, Vinod; Kaur, Supreet; Maroules, Michael

    2016-01-01

    Hypercalcemia of malignancy due to metastatic gastric adenocarcinoma is extremely rare; in fact, to the best of our knowledge, only three case reports of hypercalcemia associated with metastatic gastric adenocarcinoma have been published in the literature to date. Herein, we report a rare case involving a 61-year-old African-American female who had hypercalcemia at initial presentation and who was later diagnosed with poorly differentiated gastric adenocarcinoma with extensive liver metastases, without bone involvement. She was found to have elevated parathyroid hormone-related peptide and normal parathyroid hormone levels. Despite aggressive treatment, she died within a few months of diagnosis. PMID:27752397

  20. Foscarnet-related Hypercalcemia During CMV Treatment in an Infant With SCID: A Case Report and Review of Literature.

    PubMed

    Rabinowicz, Shira; Somech, Raz; Yeshayahu, Yonatan

    2017-04-01

    Foscarnet is a main treatment for disseminated cytomegalovirus infection in immunocompromised patients. One of its documented side effects is hypocalcemia. Hypercalcemia, in contrast, was described anecdotally before, almost exclusively in adults with human immunodeficiency virus infection or posttransplantation. We describe a case of severe hypercalcemia during foscarnet treatment in an infant with IL-7 Rα deficient severe combined immunodeficiency, resolved after treatment cessation. We speculate that this unusual side effect is caused by foscarnet binding to the inorganic matrix of bone.

  1. Critical hypercalcemia following discontinuation of denosumab therapy for metastatic giant cell tumor of bone.

    PubMed

    Gossai, Nathan; Hilgers, Megan V; Polgreen, Lynda E; Greengard, Emily G

    2015-06-01

    We report a 14 year-old female with Giant Cell Tumor of Bone, successfully treated with denosumab, who developed critical hypercalcemia after completion of therapy. Five months after her last denosumab treatment, serum calcium rose to 16.5 mg/dL (normal 8.7-10.8 mg/dL), nearly double her prior level of 8.4 mg/dL while receiving denosumab. She required emergent intervention to treat her hypercalcemia, which was attributed to rebound osteoclast activity and osteopetrotic bone. Denosumab is widely used in adults and increasingly in pediatric oncology populations and our experience demonstrates the need for close monitoring for electrolyte derangements following discontinuation.

  2. Calcitriol-mediated Reversible Hypercalcemia in a Patient with Primary Adrenal Lymphoma

    PubMed Central

    Mir, Shahnaz Ahmad; Masoodi, Shariq Rashid; Wani, Arshad Iqbal; Ahmad, Syed Nisar; Hameed, Iqra

    2016-01-01

    Primary adrenal lymphomas (PAL) are rare occurrences with only less than 150 cases reported in the literature. Two-thirds of these cases were reported in the last decade due to the advancements in imaging techniques and immunohistochemistry. The non-specific signs and symptoms have resulted in a delayed onset of symptoms and diagnosis of these tumors. Reports of the results of chemotherapy are not gratifying, and most patients die within one year of the diagnosis. We report a 65-year-old male with adrenal non-Hodgkin’s lymphoma (NHL), who presented with hypercalcemia and renal failure. We reviewed all adrenal NHL cases presented with hypercalcemia and attempted to comprehend its etiology and overall survival effect. PMID:28090186

  3. Hypophosphatasia presenting with pyridoxine-responsive seizures, hypercalcemia, and pseudotumor cerebri: case report.

    PubMed

    Demirbilek, Hüseyin; Alanay, Yasemin; Alikaşifoğlu, Ayfer; Topçu, Meral; Mornet, Etienne; Gönç, Nazlı; Özön, Alev; Kandemir, Nurgün

    2012-03-01

    Hypophosphatasia (HPP) is an inborn error of metabolism characterized by defective bone mineralization caused by a deficiency in alkaline phosphatase (ALP) activity due to mutations in the tissue-nonspecific ALP (TNALP) gene. The clinical expression of the disease is variable. Six forms of HPP are identified according to age at presentation and clinical features. Patients with the infantile form are normal at birth. First symptoms appear within the first 6 months of life. Along with skeletal findings, HPP patients may present with hypercalcemia, seizures, pseudotumor cerebri, and pulmonary insufficiency. Seizures in HPP are refractory to conventional antiepileptic drugs, but are responsive to pyridoxine. Herein, we report a case of HPP who presented with pyridoxine-responsive seizures in the early neonatal period and was found to have hypercalcemia, skeletal demineralization and increased intracranial pressure.

  4. High-calcium exposure to frog heart: a simple model representing hypercalcemia-induced ECG abnormalities

    PubMed Central

    KAZAMA, Itsuro

    2016-01-01

    By simply adding a high concentration of calcium solution to the surface of the bullfrog heart, we reproduced electrocardiogram (ECG) abnormalities representing those observed in hypercalcemia, such as Osborn waves and shortening of the QT interval. The rise in extracellular calcium concentration may have activated the outward potassium currents during phase 3 of the action potential, and thus decreased its duration. In addition to the known decrease in the duration of phase 2, such changes in phase 3 were also likely to contribute to the shortening of the QT interval. The dual recordings of the action potential in cardiomyocytes and the ECG waves enabled us to demonstrate the mechanisms of ECG abnormalities induced by hypercalcemia. PMID:27773880

  5. High-calcium exposure to frog heart: a simple model representing hypercalcemia-induced ECG abnormalities.

    PubMed

    Kazama, Itsuro

    2017-01-20

    By simply adding a high concentration of calcium solution to the surface of the bullfrog heart, we reproduced electrocardiogram (ECG) abnormalities representing those observed in hypercalcemia, such as Osborn waves and shortening of the QT interval. The rise in extracellular calcium concentration may have activated the outward potassium currents during phase 3 of the action potential, and thus decreased its duration. In addition to the known decrease in the duration of phase 2, such changes in phase 3 were also likely to contribute to the shortening of the QT interval. The dual recordings of the action potential in cardiomyocytes and the ECG waves enabled us to demonstrate the mechanisms of ECG abnormalities induced by hypercalcemia.

  6. A Randomized Study Comparing Parathyroidectomy with Cinacalcet for Treating Hypercalcemia in Kidney Allograft Recipients with Hyperparathyroidism.

    PubMed

    Cruzado, Josep M; Moreno, Pablo; Torregrosa, José V; Taco, Omar; Mast, Richard; Gómez-Vaquero, Carmen; Polo, Carolina; Revuelta, Ignacio; Francos, José; Torras, Joan; García-Barrasa, Arantxa; Bestard, Oriol; Grinyó, Josep M

    2016-08-01

    Tertiary hyperparathyroidism is a common cause of hypercalcemia after kidney transplant. We designed this 12-month, prospective, multicenter, open-label, randomized study to evaluate whether subtotal parathyroidectomy is more effective than cinacalcet for controlling hypercalcemia caused by persistent hyperparathyroidism after kidney transplant. Kidney allograft recipients with hypercalcemia and elevated intact parathyroid hormone (iPTH) concentration were eligible if they had received a transplant ≥6 months before the study and had an eGFR>30 ml/min per 1.73 m(2) The primary end point was the proportion of patients with normocalcemia at 12 months. Secondary end points were serum iPTH concentration, serum phosphate concentration, bone mineral density, vascular calcification, renal function, patient and graft survival, and economic cost. In total, 30 patients were randomized to receive cinacalcet (n=15) or subtotal parathyroidectomy (n=15). At 12 months, ten of 15 patients in the cinacalcet group and 15 of 15 patients in the parathyroidectomy group (P=0.04) achieved normocalcemia. Normalization of serum phosphate concentration occurred in almost all patients. Subtotal parathyroidectomy induced greater reduction of iPTH and associated with a significant increase in femoral neck bone mineral density; vascular calcification remained unchanged in both groups. The most frequent adverse events were digestive intolerance in the cinacalcet group and hypocalcemia in the parathyroidectomy group. Surgery would be more cost effective than cinacalcet if cinacalcet duration reached 14 months. All patients were alive with a functioning graft at the end of follow-up. In conclusion, subtotal parathyroidectomy was superior to cinacalcet in controlling hypercalcemia in these patients with kidney transplants and persistent hyperparathyroidism.

  7. A Nonsecosteroidal Vitamin D Receptor Modulator Ameliorates Experimental Autoimmune Encephalomyelitis without Causing Hypercalcemia

    PubMed Central

    Na, Songqing; Ma, Yanfei; Zhao, Jingyong; Schmidt, Clint; Zeng, Qing Q.; Chandrasekhar, Srinivasan; Chin, William W.; Nagpal, Sunil

    2011-01-01

    Vitamin D receptor (VDR) agonists are currently the agents of choice for the treatment of psoriasis, a skin inflammatory indication that is believed to involve an autoimmune component. 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], the biologically active metabolite of vitamin D, has shown efficacy in animal autoimmune disease models of multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, and type I diabetes. However, the side effect of 1,25-(OH)2D3 and its synthetic secosteroidal analogs is hypercalcemia, which is a major impediment in their clinical development for autoimmune diseases. Hypercalcemia develops as a result of the action of VDR agonists on the intestine. Here, we describe the identification of a VDR modulator (VDRM) compound A that was transcriptionally less active in intestinal cells and as a result exhibited less calcemic activity in vivo than 1,25-(OH)2D3. Cytokine analysis indicated that the VDRM not only modulated the T-helper cell balance from Th1 to Th2 effector function but also inhibited Th17 differentiation. Finally, we demonstrate that the oral administration of compound A inhibited the induction and progress of experimental autoimmune encephalomyelitis in mice without causing hypercalcemia. PMID:21318047

  8. Severe hypercalcemia as a form of acute lymphoblastic leukemia presentation in children

    PubMed Central

    Martins, Andreia Luís; Moniz, Marta; Nunes, Pedro Sampaio; Abadesso, Clara; Loureiro, Helena Cristina; Duarte, Ximo; Almeida, Helena Isabel

    2015-01-01

    Hypercalcemia is a rare metabolic disorder in children and is potentially fatal. It has a wide differential diagnosis, including cancer. Here, we report the case of a previously healthy 3-year-old who was admitted to the emergency room with fatigue, hyporeactivity, fever and limping gait that had evolved over 5 days and that was progressively worsening. On examination the patient was unconscious (Glasgow coma score: 8). Laboratory tests indicated severe hypercalcemia (total calcium 21.39mg/dL, ionized calcium 2.93mmol/L) and microcytic anemia. Hyperhydration was initiated, and the child was transferred to the pediatric intensive care unit. Continuous venovenous hemodiafiltration with calcium-free solution was instituted, which brought progressive normalization of serum calcium and an improved state of consciousness. Zoledronate was administered, and metabolic and infectious causes and poisoning were excluded. The bone marrow smear revealed a diagnosis of acute lymphoblastic leukemia. Hypercalcemia associated with malignancy in children is rare and occurs as a form of cancer presentation or recurrence. Continuous venovenous hemodiafiltration should be considered in situations where there is imminent risk to life. PMID:26761480

  9. [Cardiovascular adaptability to acute hypercalcemia in the dog. The role of peroperative myocardial ischemia].

    PubMed

    Dumont, L; Stanley, P; Chartrand, C

    1985-01-01

    Since the hemodynamic consequences of acute hypercalcemia are altered by numerous interferences we have evaluated the role of peroperative myocardial ischemia on the adaptability to rapid calcium increment. Twenty-two dogs served as control and 16 were submitted to 1 hour of myocardial ischemia along with topical myocardial cooling. Each animal was equipped with blood flow transducer positioned around the ascending aorta and with central venous and aortic catheters. During each study 0.90 mEq of calcium was rapidly injected and hemodynamic data were recorded until base-line resetting. This experimental protocol was carried out 3 hours postoperatively and then daily during one month. Base-line hemodynamic data indicated the presence of myocardial failure in the experimental group in the immediate postoperative period only. Rapid calcium administration elicited transient positive inotropic response, widening of the arterial pulse pressure, reflex bradycardia and no evidence of peripheral vasoconstriction. In the early postoperative period (3 hours after surgery) the failing myocardium is more sensitive to the inotropic effect of hypercalcemia. Twenty-four hours after surgery both groups of animals have the same hemodynamic response to this stress; thereafter for both groups this response gradually decreased and finally stabilized by the 6th to 10th day after surgery. Acute hypercalcemia bears hemodynamic consequences that are amplified early after peroperative myocardial ischemia. However in long term this surgical component widely used clinically does not interfered with the cardiovascular adaptability to this pharmacological stress.

  10. Anti-arrhythmic effects of hypercalcemia in hyperkalemic, Langendorff-perfused mouse hearts

    PubMed Central

    Tse, Gary; Sun, Bing; Wong, Sheung Ting; Tse, Vivian; Yeo, Jie Ming

    2016-01-01

    The present study examined the ventricular arrhythmic and electrophysiological properties during hyperkalemia (6.3 mM [K+] vs. 4 mM in normokalemia) and anti-arrhythmic effects of hypercalcemia (2.2 mM [Ca2+]) in Langendorff-perfused mouse hearts. Monophasic action potential recordings were obtained from the left ventricle during right ventricular pacing. Hyperkalemia increased the proportion of hearts showing provoked ventricular tachycardia (VT) from 0 to 6 of 7 hearts during programmed electrical stimulation (Fisher's exact test, P<0.05). It shortened the epicardial action potential durations (APDx) at 90, 70, 50 and 30% repolarization and ventricular effective refractory periods (VERPs) (analysis of variance, P<0.05) without altering activation latencies. Endocardial APDx and VERPs were unaltered. Consequently, ∆APDx (endocardial APDx-epicardial APDx) was increased, VERP/latency ratio was decreased and critical intervals for reexcitation (APD90-VERP) were unchanged. Hypercalcemia treatment exerted anti-arrhythmic effects during hyperkalemia, reducing the proportion of hearts showing VT to 1 of 7 hearts. It increased epicardial VERPs without further altering the remaining parameters, returning VERP/latency ratio to normokalemic values and also decreased the critical intervals. In conclusion, hyperkalemia exerted pro-arrhythmic effects by shortening APDs and VERPs. Hypercalcemia exerted anti-arrhythmic effects by reversing VERP changes, which scaled the VERP/latency ratio and critical intervals. PMID:27588173

  11. [Association of hypercalcemia, elevated levels of calcitriol and tuberculosis in patients on hemodialysis].

    PubMed

    Peces, R; Díaz Corte, C

    2000-01-01

    Hypercalcemia is associated with numerous chronic granulomatous processes and chronic infections. Increased production of calcitriol by activated macrophages has been shown to be the cause in most cases. In this article, we describe three cases of hypercalcemia associated with inappropriately elevated calcitriol levels and suppressed PTH in hemodialysis. In addition to conventional techniques for tuberculosis diagnosis we used Ligase Chain Reaction (LCR) to detect mycobacterial DNA in pleural effusion with acid-fast stain and culture negativity. Antituberculous therapy was associated with a decrease in the levels of calcium, as well as in serum calcitriol concentrations, and a substantial increase in the levels of iPTH. The serum levels of 25(OH)D3 remained unchanged. These findings suggested ectopic production of calcitriol. The discussion reviews the previously reported cases of hypercalcemia and tuberculosis that occurred during hemodialysis, and concludes that ectopic production of calcitriol by tuberculous granulomas is extremely unusual and its demonstration requires a high index of suspicion. Molecular techniques are a potentially useful approach for early and rapid diagnosis of tuberculous infection in dialysis patients.

  12. The coexistence of hypercalcemia and hypoglycemia in a patient with a renal tumor and B cell lymphoma.

    PubMed

    Soutelo, Jimena; Moldes, Sofía; Frisone, Cielo; Salvá, Laura; Agostinis, Cecilia; Faraj, Gabriel

    2017-01-01

    Paraneoplastic syndromes are a heterogeneous group of malignant diseases caused by events which involve endocrine, immune and metabolic aspects and whose symptoms vary according to the substance produced and the primary tumor. Hypercalcemia is a frequent complication in cancer patients. Prognosis of cancer patients with hypercalcemia is usually poor. A factor called parathyroid hormone related peptide, whose actions are similar to those of the parathyroid hormone, is thought to be the most common cause of malignancy associated hypercalcemia. Non-islet hypoglycemic cell tumor consists of a rare syndrome characterized by the presence of a solid tumor and severe fasting hypoglycemia determined by an insulin-independent pathway. We report a case of a 59-year-old-man with a renal tumor and a T-cell rich large B cell lymphoma who was hospitalized due to severe hypercalcemia and hypoglycemia. The laboratory examination reported hypercalcemia with inhibited PTH and hypoglycemia with inhibited insulin secretion, arriving to the conclusion of tumoral peptide production. He received denosumab and corticoid therapy. The patient died one month later despite initial improvement after medical treatment. While a single paraneoplastic manifestation may be expected in most tumors, the coexistence of two or more of them is rare, except in hepatocellular carcinomas, and it has not yet been described in renal tumors.

  13. A randomized study evaluating cinacalcet to treat hypercalcemia in renal transplant recipients with persistent hyperparathyroidism.

    PubMed

    Evenepoel, P; Cooper, K; Holdaas, H; Messa, P; Mourad, G; Olgaard, K; Rutkowski, B; Schaefer, H; Deng, H; Torregrosa, J V; Wuthrich, R P; Yue, S

    2014-11-01

    Persistent hyperparathyroidism (HPT) after kidney transplantation (KTx) is associated with hypercalcemia, hypophosphatemia and abnormally high levels of parathyroid hormone (PTH). In this randomized trial, cinacalcet was compared to placebo for the treatment of hypercalcemia in adult patients with persistent HPT after KTx. Subjects were randomized 1:1 to cinacalcet or placebo with randomization stratified by baseline corrected total serum calcium levels (≤11.2 mg/dL [2.80 mmol/L] or >11.2 mg/dL [2.80 mmol/L]). The primary end point was achievement of a mean corrected total serum calcium value<10.2 mg/dL (2.55 mmol/L) during the efficacy period. The two key secondary end points were percent change in bone mineral density (BMD) at the femoral neck and absolute change in phosphorus; 78.9% cinacalcet- versus 3.5% placebo-treated subjects achieved the primary end point with a difference of 75.4% (95% confidence interval [CI]: 63.8, 87.1), p<0.001. There was no statistical difference in the percent change in BMD at the femoral neck between cinacalcet and placebo groups, p=0.266. The difference in the change in phosphorus between the two arms was 0.45 mg/dL (95% CI: 0.26, 0.64), p<0.001 (nominal). No new safety signals were detected. In conclusion, hypercalcemia and hypophosphatemia were effectively corrected after treatment with cinacalcet in patients with persistent HPT after KTx.

  14. Idiopathic Infantile Hypercalcemia, Presenting in Adulthood--No Longer Idiopathic Nor Infantile: Two Case Reports and Review.

    PubMed

    Tray, Kory A; Laut, Jeffrey; Saidi, Arya

    2015-01-01

    We present two unrelated cases of young adults with hypercalcemia, hypercalciuria, and nephrocalcinosis. Both had suppressed intact parathyroid hormone levels and high 1,25 vitamin D levels after only brief, low-dose, over-the-counter vitamin supplementation. Neither had evidence of a granulomatous disorder. Their presentation mimicked that of 1,25 hydroxy vitamin D intoxication. In both patients, the diagnosis of idiopathic infantile hypercalcemia was confirmed with immeasurably low 24,25 vitamin D levels. Both were found to have a loss-of-function mutation in the CYP24A1 gene, which encodes the vitamin D-metabolizing enzyme 25-hydroxyvitamin D 24-hydroxylase.

  15. A Young Woman With Recurrent Gestational Hypercalcemia and Acute Pancreatitis Caused by CYP24A1 Deficiency.

    PubMed

    Woods, Gina N; Saitman, Alec; Gao, Hanlin; Clarke, Nigel J; Fitzgerald, Robert L; Chi, Nai-Wen

    2016-10-01

    The CYP24A1 gene encodes a mitochondrial 24-hydroxylase that inactivates 1,25(OH)2 D. Loss-of-function mutations in CYP24A1 cause hypercalcemia, nephrolithiasis and nephrocalcinosis. We describe a woman with CYP24A1 deficiency and recurrent gestational hypercalcemia. Her first pregnancy, at age 20, resulted with the intrauterine demise of twin fetuses. Postpartum, she developed severe hypercalcemia (14 mg/dL), altered mental status, and acute pancreatitis. Her PTH was suppressed (6 pg/mL) and her 1,25(OH)2 D was elevated (165 and 195 pg/mL on postpartum day 1 and 5, respectively). Between one and three months postpartum, her serum calcium decreased from 11.4 to 10.2 mg/dL while her 1,25(OH)2 D level decreased from 83 to 24 pg/mL. Her 24-hour urine calcium was 277 mg. Six months postpartum, she became pregnant again. At 14 weeks, her albumin-corrected calcium level was 10.4 mg/dL and her 1,25(OH)2 D level exceeded 200 pg/mL. To establish the diagnosis of CYP24A1 deficiency, we showed her 24,25(OH)2 D level to be undetectable (<2 ng/mL). Exon sequencing of the CYP24A1 gene revealed a homozygous, 8-nucleotide deletion in exon 8, causing an S334V substitution and premature termination due to a frame shift (c.999_1006del, p.Ser334Valfs*9). To prevent hypercalcemia, she was advised to discontinue prenatal vitamins, avoid sun exposure and calcium-rich foods, and start omeprazole and a calcium binder (250 mg K-Phos-neutral with meals). Despite these measures, both hypercalcemia (11.5 mg/dL) and acute pancreatitis recurred. Labor was induced and a healthy, normocalcemic boy was delivered. In the absence of lactation, maternal hypercalcemia resolved within 2 months. This report shows that CYP24A1-deficient subjects may be normocalcemic at baseline. Hypercalcemia may be unmasked by pregnancy through the routine use of calciferol-containing prenatal vitamins, increased 1-alpha hydroxylation of VitD by the placenta and maternal kidney, and production of

  16. [Femoral osteolytic lesions with soft tissue tumors and hypercalcemia as presentation form of a B-cell lymphoma].

    PubMed

    Hernández Hernández, J L; Olmos Martínez, J M; Figols Ladrón de Guevara, J; Riancho Moral, J A; González Macías, J

    2000-05-01

    Hypercalcemia associated with haematological neoplasms account for 15 to 20% of hipercalcemia in malignancy, and occurs usually in patients with multiple myeloma. However, its incidence in patients with linfoma is low, and it is observed usually in T-cell linfomas. Bone affectation is also uncommon in patients with non-Hodgkin linfoma. It usually is seen as a late manifestation of the disease, and its occurrence as the form of presentation is exceptional. We hereby report a patient with a B-cell non-Hodgkin linfoma presenting with hypercalcemia and femoral osteolytic lesions.

  17. Philadelphia-positive T-cell acute lymphoblastic leukemia with polymyositis, migratory polyarthritis and hypercalcemia following a chronic myeloid leukemia.

    PubMed

    Lima, M; Coutinho, J; Bernardo, L; dos Anjos Teixeira, M; Casais, C; Canelhas, A; Queirós, L; Orfão, A; Justiça, B

    2002-03-01

    Transformation of chronic myeloid leukemia (CML) often results in acute myeloblastic or, less frequently, in precursor B-cell acute lymphoblastic leukemia (ALL). T-cell blast crisis is rare. Hypercalcemia has also been described as a rare complication of CML, but this usually occurs as a terminal event. Here we report a case of a 35-year-old woman who developed a CD4(+)/CD8(+) T-cell ALL 2 years after the diagnosis of a typical Ph(+) CML. Polymyositis and polyarthritis preceded by 4 months, and symptomatic hypercalcemia occurred just before blastic transformation, probably representing paraneoplastic manifestations of the disease.

  18. A Rare Case of Gestational Gigantomastia with Hypercalcemia: The Challenges of Management and Follow up

    PubMed Central

    Moazzami, Bahram; Chaichian, Shahla; Farahvash, Mohammad Reza; Taheri, Saeedeh; Ahmadi, Seyed Ali; Mokhtari, Majid; Sheibani, Kourosh

    2016-01-01

    Background: Gigantomastia is a breast disorder marked by exaggerated rapid growth of the breasts, generally bilaterally. Since this disorder is very rare and has been reported only in sparse case reports its etiology has yet to be fully established. Treatment is aimed at improving the clinical and psychological symptoms and reducing the treatment side effects; however, the best therapeutic option varies from case to case. Case Presentation: The present report described a case of gestational gigantomastia in a 30-year-old woman, gravida 2, parity 1, 17 week pregnant admitted to Pars Hospital, Tehran, Iran, on May 2014. The patient was admitted to hospital at week 17 of pregnancy, although her breasts initially had begun to enlarge from the first trimester. The patient developed hypercalcemia in her 32nd week of pregnancy. The present report followed this patient from diagnosis until the completion of treatment. Conclusion: Although gestational gigantomastia is a rare condition, its timely prognosis and careful examination of some conditions like hyperprolactinemia and hypercalcemia is essential in successful management of this condition. PMID:27921004

  19. Williams-Beuren syndrome hypercalcemia: is TRPC3 a novel mediator in calcium homeostasis?

    PubMed

    Letavernier, Emmanuel; Rodenas, Anita; Guerrot, Dominique; Haymann, Jean-Philippe

    2012-06-01

    Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder associated with hypercalcemia of unknown origin. This syndrome results from the deletion of contiguous genes on chromosome 7, including the general transcription factor IIi gene. The general transcription factor IIi gene encodes TFII-I, which suppresses cell-surface accumulation of transient receptor potential C3 (TRPC3) channels, involved in calcium transport in lymphocytes. We describe the case of a patient with WBS with hypercalcemia associated with abnormal TRPC3 expression. Analysis of peripheral lymphocytes revealed a sharp increase in TRPC3 expression, compared with control patients. To investigate the potential role of TRPC3 in calcium homeostasis, we performed specific immunostaining on the intestine and the kidney, major calcium-regulating tissues. We provide the first demonstration that TRPC3 is expressed in normal digestive epithelium and renal tubules in control patients, and overexpressed in the intestine in the patient with WBS. Taken together, these data suggest that calcium metabolism abnormalities observed in WBS may be attributable to TFII-I haploinsufficiency and subsequent TRPC3 overexpression, thereby increasing both digestive and renal calcium absorption. This original observation prompts further investigation of TRPC3 as a novel actor of calcium homeostasis.

  20. An Interesting Case of Life-Threatening Hypercalcemia Secondary to Atypical Parathyroid Adenoma versus Parathyroid Carcinoma

    PubMed Central

    Mishra, Ankur; Newman, David

    2014-01-01

    Context. Severe hypercalcemia is a life-threatening condition. Atypical parathyroid adenoma and parathyroid carcinomas are uncommon causes which can be difficult to differentiate. Objective. We report a case of a 36-year-old male with very high serum calcium due to a possible atypical parathyroid adenoma versus parathyroid carcinoma. Case Illustration. A serum calcium level of 23.2 mg/dl was noted on admission. He was initially treated with IV hydration, pamidronate, and salmon calcitonin to lower his calcium levels. He also underwent a surgical en bloc resection of parathyroid mass. Pathology showed a mixed picture consistent with possible atypical adenoma versus parathyroid carcinoma. However, due to the possible involvement of the recurrent laryngeal nerve, parathyroid carcinoma was more likely. Also after operation the patient developed hungry bones syndrome and his calcium was replaced vigorously. He continues to be on calcium, vitamin D, and calcitriol supplementation. Results. A review of the literature was conducted to identify previous studies pertaining to parathyroid adenomas and parathyroid cancer. Conclusion. We thereby conclude that hypercalcemia requires very careful monitoring especially after operation. Also it can be very difficult to distinguish between atypical parathyroid adenomas and parathyroid carcinomas as in our case and no clear cut guidelines yet exist to differentiate the two based on histology. PMID:24959180

  1. PTHrP-associated hypercalcemia of pregnancy resolved after delivery: a case report.

    PubMed

    Eller-Vainicher, Cristina; Ossola, Manuela Wally; Beck-Peccoz, Paolo; Chiodini, Iacopo

    2012-04-01

    A 35-year-old oriental woman, who was 32 weeks pregnant, was hospitalized with suspected preeclampsia. Subsequently, she developed stupor and lethargia. Biochemical assessment showed severe hypercalcemia (21 mg/dl) with undetectable parathyroid hormone (PTH) and markedly elevated PTH-related peptide (PTHrP) levels (26 pmol/l, normal values <1.1 pmol/l). The patient was treated with i.v. fluid administration, which resulted in an unsatisfactory reduction in serum calcium. Therefore, a cesarean section was performed to deliver the baby. Serum calcium levels promptly normalized after delivery with undetectable PTHrP levels. She delivered a healthy infant only presenting with transient mild jaundice and slightly prolonged QT interval with serum calcium level of 7.8-8.4 mg/dl (corrected for albumin levels). In the subsequent days, the patient developed a transient 'hungry bone' syndrome (calcium 6.7 mg/dl, phosphorous 2.1 mg/dl, and PTH 100.4 pg/ml). In conclusion, this pregnant patient presented with PTHrP-associated hypercalcemia, presumably of placental origin. Delivery resulted in prompt reduction of serum calcium levels and a transient 'hungry bone' syndrome.

  2. Hypercalcemia - discharge

    MedlinePlus

    ... calcium in them. Look for antacids that have magnesium. Ask your provider which ones are OK. Ask ... Leone KA. Calcium, magnesium, and phosphorus. In: Adams JG, ed. ... . 2nd ed. Philadelphia, PA: Elsevier Saunders; 2013:chap 166. ...

  3. Humoral hypercalcemia associated with gastric carcinoma secreting parathyroid hormone: a case report and review of the literature.

    PubMed

    Nakajima, Koji; Tamai, Masataka; Okaniwa, Shinji; Nakamura, Yoshiyuki; Kobayashi, Mutsuhiro; Niwa, Tomohiro; Horigome, Naoto; Ito, Nobuo; Suzuki, Satoru; Nishio, Shinichi; Komatsu, Mitsuhisa

    2013-01-01

    Hypercalcemia with concomitant elevation of serum parathyroid hormone (PTH) and PTH-related protein (PTHrP) levels was found in a patient with advanced gastric carcinoma and multiple liver metastases. The most common features are hypercalcemia associated with hypersecretion of PTHrP and physiological suppression of PTH secretion in the syndrome of humoral hypercalcemia of malignancy (HHM). Although we initially made a diagnosis of primary hyperparathyroidism concomitant with HHM due to gastric cancer, diagnostic imaging studies, such as echography, CT, sestamibi scintigraphy, and autopsy findings, did not reveal evidence of any parathyroid tumors or ectopic parathyroid glands in the mediastinum. Both primary and metastatic tumor cells showed positive staining with PTH-specific antibody as well as PTHrP-specific antibody on immunohistochemical examination. PTH concentration in the cytosolic fraction of the metastatic tumor was elevated compared to that from a control patient with no calcium metabolic disorders in vitro. These findings indicated that PTH secreted ectopically by gastric cancer cells, not by parathyroid glands, caused hypercalcemia in this patient. To our knowledge, this is the first case report of PTH-secreting gastric carcinoma cells. We report the case and a review of the previous reported PTH-secreting non-parathyroid tumors along with the mechanisms of secretion.

  4. Resolution of hypercalcemia and acute kidney injury after treatment for pulmonary tuberculosis without the use of corticosteroids.

    PubMed

    Araujo, Constance A A; Araujo, Nicole A A; Daher, Elizabeth F; Oliveira, José Daniel B; Kubrusly, Marcos; Duarte, Pastora M A; Silva, Sonia L; Araujo, Sonia M H A

    2013-03-01

    Abstract. Hypercalcemia caused by tuberculosis is rare and it is usually asymptomatic. Tuberculosis (TB) -related hypercalcemia associated with acute kidney injury (AKI) is rarely reported. We report a case of a 22-year-old immunocompetent man with 1-month history of daily fever, asthenia and weight loss. Laboratory findings on admission included serum calcium 14.9 mg/dL, urinary Ca(2+) 569.6 mg/24 hours, low level of parathyroid hormone, serum creatinine = 2.2 mg/dL and sodium fractional excretion (FeNa) 2.73%. The result of the tuberculin skin test was 17 mm. A chest X-ray revealed micronodular pulmonary infiltrate in the apex of the right lung, which was confirmed by computed tomography scan. The patient was diagnosed with hypercalcemia associated with pulmonary TB and AKI. A general improvement of the hypercalcemia and renal function was observed in the first 2 weeks after effective hydration and treatment of TB without corticosteroids. The patient was discharged with normal calcium levels and renal function.

  5. Hypercalcemia as the presenting feature of t-cell lymphoid blast crisis of ph-positive chronic myeloid leukemia.

    PubMed

    Nadal, E; Cervantes, F; Rosiñol, L; Talarn, C; Montserrat, E

    2001-03-01

    Hypercalcemia is a rare complication of chronic myeloid leukemia (CML), usually seen in the accelerated or blastic phases of the disease and associated with a poor prognosis. T-cell lymphoid phenotype is also an infrequent finding in the blast crisis (BC) of CML. A CML patient who had hypercalcemia as the presenting feature of a T-cell BC is reported. She was a 78 year-old woman who, at four months of CML diagnosis, developed weakness, bone pain, and mental confusion, with hypercalcemia being subsequently found. Although the peripheral blood and bone marrow were consistent with the chronic phase of CML, mediastinal enlargement, a soft tissue mass adjacent to the iliac bone, and multiple osteolytic lesions were seen. Serum levels of parathyroid hormone (PTH) and PTH-related peptide were normal, whereas the search for a second neoplasm was negative. The hypercalcemia initially responded to conventional treatment, but it reappeared two weeks later. Coincidentally, a high proportion of blast cells of T-cell origin at the cortical thymocyte stage were observed in the patient's peripheral blood and bone marrow, and she died shortly afterwards.

  6. Multiple endocrine neoplasia phenocopy revealed as a co-occurring neuroendocrine tumor and familial hypocalciuric hypercalcemia type 3.

    PubMed

    Hovden, Silje; Jespersen, Marie Louise; Nissen, Peter H; Poulsen, Per Løgstrup; Rolighed, Lars; Ladefoged, Søren A; Rejnmark, Lars

    2016-10-01

    Familial hypocalciuric hypercalcemia type 3 should be considered as differential diagnosis in patients with suspected primary hyperparathyroidism and/or suspected multiple neoplasia syndrome, as correct diagnosis will spare the patients for going through multiple futile parathyroidectomies and for the worry of being diagnosed with a cancer susceptibility syndrome.

  7. Jansen Metaphyseal Chondrodysplasia due to Heterozygous H223R-PTH1R Mutations With or Without Overt Hypercalcemia.

    PubMed

    Nampoothiri, Sheela; Fernández-Rebollo, Eduardo; Yesodharan, Dhanya; Gardella, Thomas J; Rush, Eric T; Langman, Craig B; Jüppner, Harald

    2016-11-01

    Jansen's metaphyseal chondrodysplasia (JMC) is a rare skeletal dysplasia characterized by abnormal endochondral bone formation and typically severe hypercalcemia despite normal/low levels of PTH. Five different heterozygous activating PTH/PTHrP receptor (PTH1R) mutations that change one of three different amino acid residues are known to cause JMC. Establishing the diagnosis of JMC during infancy or early childhood can be challenging, especially in the absence of family history and/or overt hypercalcemia. We therefore sought to provide radiographic findings supporting this diagnosis early in life. Three patients, a mother and her two sons, had radiographic evidence for JMC. However, obvious hypercalcemia and suppressed PTH levels were encountered only in both affected children. Sanger sequencing and endonuclease (SphI) digestion of PCR-amplified genomic DNA were performed to search for the H223R-PTH1R mutation. The heterozygous H223R mutation was identified in all three affected individuals. Surprisingly, however, the now 38-year-old mother was never overtly hypercalcemic and was therefore not diagnosed until her sons were found to be affected by JMC at the ages of 28 months and 40 days, respectively. The presented radiographic findings at different ages will help diagnose other infants/toddlers suspected of having JMC. The H223R mutation is typically associated with profound hypercalcemia despite low/normal PTH levels. However, the findings presented herein show that overt hypercalcemia is not always encountered in JMC, even if caused by this relatively frequent mutation, which is similar to observations with other PTH1R mutations that show less constitutive activity.

  8. Over-expression of CCL3 MIP-1alpha in a blastoid mantle cell lymphoma with hypercalcemia.

    PubMed

    Hattori, Norimichi; Nakamaki, Tsuyoshi; Ariizumi, Hirotsugu; Homma, Mayumi; Yamochi-Onizuka, Toshiko; Ota, Hidekazu; Tomoyasu, Shigeru

    2010-05-01

    We analyzed a case with the blastoid variant of mantle cell lymphoma (MCL-BV), a rare subtype of B-cell lymphoma, presenting with marked hypercalcemia at diagnosis. Enzyme-linked immunosorbent assay (ELISA) showed elevated serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-1alpha (MIP-1alpha), and type I collagen telopeptide, but not parathyroid hormone, calcitriol or parathyroid hormone-related peptide at diagnosis, suggesting local osteoclastic hypercalcemia in this case. By reverse transcription polymerase chain reaction (RT-PCR) analysis, we found predominant expression of mRNA for MIP-1alpha in addition to those for receptor-activator of nuclear-factor kappa B ligand (RANKL), TNF-alpha, and IL-6 in lymphoma cells obtained from the patient. Furthermore, recombinant MIP-1alpha significantly stimulated (3)H-thymidine uptake by isolated MCL cells in vitro. Treatment with intravenous fluids, bisphosphonate, and methylprednisolone followed by combination chemotherapy promptly corrects the hypercalcemia and successfully induced complete remission, which was accompanied by a decrease of these cytokines in the serum, including MIP-1alpha. In the present case, MIP-1alpha, an osteoclast-activating factor produced by mantle lymphoma cells, may contribute to the development of hypercalcemia. It likely acts through RANKL expression in tumor cells and/or stroma cells, as indicated in multiple myeloma (MM) and adult T-cell leukemia/lymphoma (ATLL). Furthermore, MIP-1alpha is also involved in the development of an aggressive phenotype on MCL by stimulating proliferation of these lymphoma cells. In summary, the present study demonstrated that MIP-1alpha is an important factor in the development of both hypercalcemia and an aggressive phenotype in some types of B-cell lymphoma.

  9. Hypercalcemia stimulates expression of intrarenal phospholipase A2 and prostaglandin H synthase-2 in rats. Role of angiotensin II AT1 receptors.

    PubMed Central

    Mangat, H; Peterson, L N; Burns, K D

    1997-01-01

    In chronic hypercalcemia, inhibition of thick ascending limb sodium chloride reabsorption is mediated by elevated intrarenal PGE2. The mechanisms and source of elevated PGE2 in hypercalcemia are not known. We determined the effect of hypercalcemia on intrarenal expression of cytosolic phospholipase A2 (cPLA2), prostaglandin H synthase-1 (PGHS-1), and prostaglandin H synthase-2 (PGHS-2), enzymes important in prostaglandin production. In rats fed dihydrotachysterol to induce hypercalcemia, Western blot analysis revealed significant upregulation of both cPLA2 and PGHS-2 in the kidney cortex and the inner and outer medulla. Immunofluorescence localized intrarenal cPLA2 and PGHS-2 to interstitial cells of the inner and outer medulla, and to macula densa and cortical thick ascending limbs in both control and hypercalcemic rats. Hypercalcemia had no effect on intrarenal expression of PGHS-1. To determine if AT1 angiotensin II receptor activation was involved in the stimulation of cPLA2 and PGHS-2 in hypercalcemia, we treated rats with the AT1 receptor antagonist, losartan. Losartan abolished the polydipsia associated with hypercalcemia, prevented the increase in cPLA2 protein in all regions of the kidney, and diminished PGHS-2 expression in the inner medulla. In addition, losartan completely prevented the increase in urinary PGE2 excretion in hypercalcemic rats. Intrarenal levels of angiotensin II were unchanged in hypercalcemia. These data indicate that hypercalcemia stimulates intrarenal cPLA2 and PGHS-2 protein expression. Our results further support a role for angiotensin II, acting on AT1 receptors, in mediating this stimulation. PMID:9329957

  10. AP2S1 and GNA11 mutations - not a common cause of familial hypocalciuric hypercalcemia.

    PubMed

    Hovden, Silje; Rejnmark, Lars; Ladefoged, Søren A; Nissen, Peter H

    2017-02-01

    Familial hypocalciuric hypercalcemia (FHH) type 1 is caused by mutations in the gene encoding the calcium-sensing receptor (CASR). Recently, mutations affecting codon 15 in the gene AP2S1 have been shown to cause FHH type 3 in up to 26% of CASR-negative FHH patients. Similarly, mutations in the gene GNA11 have been shown to cause FHH type 2. We hypothesized that mutations in AP2S1 and GNA11 are causative in Danish patients with suspected FHH and that these mutations are not found in patients with primary hyperparathyroidism (PHPT), which is the main differential diagnostic disorder. Cross-sectional study. We identified patients with unexplained hyperparathyroid hypercalcemia and a control group of verified PHPT patients through review of 421 patients tested for CASR mutations in the period 2006-2014. DNA sequencing of all amino acid coding exons including intron-exon boundaries in AP2S1 and GNA11 was performed. In 33 CASR-negative patients with suspected FHH, we found two (~6%) with a mutation in AP2S1 (p.Arg15Leu and p.Arg15His). Family screening confirmed the genotype-phenotype correlations. We did not identify any pathogenic mutations in GNA11. No pathogenic mutations were found in the PHPT control group. We suggest that the best diagnostic approach to hyperparathyroid hypercalcemic patients suspected to have FHH is to screen the CASR and AP2S1 codon 15 for mutations. If the results are negative and there is still suspicion of an inherited condition (i.e. family history), then GNA11 should be examined. © 2017 European Society of Endocrinology.

  11. Effect of calcium carbonate combined with calcitonin on hypercalcemia in hemodialysis patients.

    PubMed

    Wei, Yong; Kong, Xiang Lei; Li, Wen Bin; Wang, Zun Song

    2014-12-01

    This short-term study assessed the efficacy and safety of calcium carbonate combined with calcitonin in the treatment of hypercalcemia in hemodialysis patients. Patients (n=64) on hemodialysis for chronic kidney disease for more than 6 months were included based on total serum calcium more than 10.5 mg/dL. All patients were randomized (1:1) to receive calcium carbonate combined with calcitonin (Group I) or lanthanum carbonate (Group II) for 12 weeks. Blood levels of calcium, phosphorus and intact parathyroid hormone (iPTH) were measured every month, bone mass density (BMD) and coronary artery calcium scores (CACS) were measured at 3 months. During the study period, serum calcium decreased from 10.72 ± 0.39 to 10.09 ± 0.28 mg/dL (P < 0.05), serum phosphorus decreased from 6.79 ± 1.05 to 5.46 ± 1.18 mg/dL (P < 0.05), and serum iPTH levels in the Group I and Group II were not significantly different from the baseline. There were no significant differences in CACS in either group. There were no significant differences in the BMD values between Group I and baseline. In Group II, the BMD values at the lumbar spine and femoral neck were significantly lower than those before the trial and significantly lower than the corresponding values of Group I (P<0.05). Calcium carbonate combined with calcitonin and lanthanum carbonate were equally effective in the suppression of hypercalcemia in hemodialysis patients. There were no serious treatment-related adverse events in treatment with calcium carbonate combined with calcitonin. © 2014 The Authors. Therapeutic Apheresis and Dialysis © 2014 International Society for Apheresis.

  12. Cinacalcet hydrochloride relieves hypercalcemia in Japanese patients with parathyroid cancer and intractable primary hyperparathyroidism.

    PubMed

    Takeuchi, Yasuhiro; Takahashi, Shunsuke; Miura, Daishu; Katagiri, Makoto; Nakashima, Noriaki; Ohishi, Hiroko; Shimazaki, Ryutaro; Tominaga, Yoshihiro

    2016-11-21

    Pharmacological treatment of hypercalcemia is essential for patients with parathyroid carcinoma and intractable primary hyperparathyroidism (PHPT). Use of the calcimimetic cinacalcet hydrochloride (cinacalcet) is an option to treat such patients. We investigated the efficacy and safety of cinacalcet in Japanese patients with parathyroid carcinoma and intractable PHPT. Five Japanese patients with parathyroid carcinoma and two with intractable PHPT were enrolled in an open-label, single-arm study consisting of titration and maintenance phases. Cinacalcet doses were titrated until the albumin-corrected serum calcium concentration decreased to 10.0 mg/dL or less or until dose escalation was considered not necessary or feasible. Serum calcium concentration at the baseline was 12.1 ± 1.3 mg/dL (mean ± standard deviation; range 10.4-14.6 mg/dL) and decreased to 10.1 ± 1.6 mg/dL (range 8.6-13.3 mg/dL) at the end of the titration phase with cinacalcet at a dosage of up to 75 mg three times a day. At the end of the titration phase, at least a 1 mg/dL reduction in serum calcium concentration from the baseline was observed in five patients (three with carcinoma and two with PHPT), and it decreased to the normocalcemic range in five patients (three with carcinoma and two with PHPT). Common adverse events were nausea and vomiting. One patient discontinued participation in the study because of an adverse event, liver disorder. Cinacalcet effectively relieved hypercalcemia in 60% of the Japanese patients with parathyroid carcinoma and might be effective in those with intractable PHPT. The drug might be tolerable and safe at a dosage of at most 75 mg three times a day.

  13. Hypercalcemia and renal function impairment associated with vitamin D toxicity: case report.

    PubMed

    Guerra, Vanessa; Vieira Neto, Osvaldo Merege; Laurindo, Alan Fernandes; Paula, Francisco Jose Albuquerque de; Moysés Neto, Miguel

    2016-12-01

    Nowadays vitamin D (25-OHD) deficiency is supposed to be a global epidemic condition. Expectedly, vitamin D measurement and intake exponentially increased in Brazil in this decade. Although the benefit of vitamin D to general health is still in debate, its indiscriminate use potentially may lead to enhance the incidence of vitamin D intoxication, which is considered a rare disorder. We report a case of a 70 year old diabetic male with chronic renal disease (blood creatinine of 1.6 mg/dL) who progressed suddenly to acute kidney injury (blood creatinine of 5.7 mg/dL) associated with hypercalcemia and high blood levels of vitamin D. Vitamin D and calcitriol were discontinued and hypercalcemia was managed by hydration followed by furosemide. Thereafter, disodium pamidronate was administered and the patient did not undergo on dialysis. It took approximately 14 months to normalize 25-OHD levels and blood creatinine returned to basal levels only after 24 months. The indicated labeling dosage was 2000 IU, but most likely the vitamin D manipulated preparation was higher as the vitamin D blood levels were very high. Although rare, vitamin D intoxication is becoming more frequent as the patients use frequently manipulated preparations that could be subject to errors in the manufacturing and labeling of the tablets or capsules. The present report alerts to the potential increase in the incidence of severe vitamin D intoxication due to the frequent use of this secosteroid as a nutritional supplement. At the same time, it is necessary to improve regulation on the nutrient supplement market.

  14. The calcium-sensing receptor (CaSR) defends against hypercalcemia independently of its regulation of parathyroid hormone secretion

    PubMed Central

    Quinn, Steven J.; Egbuna, Ogo I.; Baxi, Khanjan; Butters, Robert; Pang, Jian L.; Pollak, Martin R.; Goltzman, David; Brown, Edward M.

    2009-01-01

    The calcium-sensing receptor (CaSR) controls parathyroid hormone (PTH) secretion, which, in turn, via direct and indirect actions on kidney, bone, and intestine, maintains a normal extracellular ionized calcium concentration (Ca2+o). There is less understanding of the CaSR's homeostatic importance outside of the parathyroid gland. We have employed single and double knockout mouse models, namely mice lacking PTH alone (CaSR+/+ PTH−/−, referred to as C+P−), lacking both CaSR and PTH (CaSR−/− PTH−/−, C−P−) or wild-type (CaSR+/+ PTH+/+, C+P+) mice to study CaSR-specific functions without confounding CaSR-mediated changes in PTH. The mice received three hypercalcemic challenges: an oral Ca2+ load, injection or constant infusion of PTH via osmotic pump, or a phosphate-deficient diet. C−P− mice show increased susceptibility to developing hypercalcemia with all three challenges compared with the other two genotypes, whereas C+P− mice defend against hypercalcemia similarly to C+P+ mice. Reduced renal Ca2+ clearance contributes to the intolerance of the C−P− mice to Ca2+ loads, as they excrete less Ca2+ at any given Ca2+o than the other two genotypes, confirming the CaSR's direct role in regulating renal Ca2+ handling. In addition, C+P+ and C+P−, but not C−P−, mice showed increases in serum calcitonin (CT) levels during hypercalcemia. The level of 1,25(OH)2D3 in C−P− mice, in contrast, was similar to those in C+P− and C+P+ mice during an oral Ca2+ load, indicating that increased 1,25(OH)2D3 production cannot account for the oral Ca2+-induced hypercalcemia in the C−P− mice. Thus, CaSR-stimulated PTH release serves as a “floor” to defend against hypocalcemia. In contrast, high-Ca2+o-induced inhibition of PTH is not required for a robust defense against hypercalcemia, at least in mice, whereas high-Ca2+o-stimulated, CaSR-mediated CT secretion and renal Ca2+ excretion, and perhaps other factors, serve as a “ceiling” to limit

  15. The Biochemical Profile of Familial Hypocalciuric Hypercalcemia and Primary Hyperparathyroidism during Pregnancy and Lactation: Two Case Reports and Review of the Literature

    PubMed Central

    Saad, N. M. A.

    2016-01-01

    Background. Primary hyperparathyroidism (PHPT) and Familial Hypocalciuric Hypercalcemia (FHH) result in different maternal and fetal complications in pregnancy. Calcium to creatinine clearance ratio (CCCR) is commonly used to help distinguish these two conditions. Physiological changes in calcium handling during pregnancy and lactation can alter CCCR, making it a less useful tool to distinguish PHPT from FHH. Cases. A 25-year-old female presented with hypercalcemia and an inappropriately normal PTH. Her CCCR was 0.79% before pregnancy and rose to 1.99% in her second trimester. The proband's mother and neonate had asymptomatic hypercalcemia. Genetic analysis revealed a CaSR mutation consistent with FHH. A 19-year-old female presented with a history of nephrolithiasis who underwent emergent caesarean section at 29 weeks of gestation for severe preeclampsia. At delivery, she was diagnosed with hypercalcemia with an inappropriately normal PTH and a CCCR of 2.67%, which fell to 0.88% during lactation. Parathyroidectomy cured her hypercalcemia. Pathology confirmed a parathyroid adenoma. Conclusion. These cases illustrate the influence of pregnancy and lactation on renal calcium indices, such as the CCCR. To avoid diagnostic error of women with hypercalcemia during pregnancy and lactation, calcium biochemistry of first-degree relatives and genetic testing of select patients are recommended. PMID:27957351

  16. Basal and pentagastrin-stimulated levels of calcitonin in thyroid and peripheral veins during normocalcemia and chronic hypercalcemia in humans.

    PubMed Central

    Ericsson, M; Berg, M; Ingemansson, S; Jernby, B; Järhult, J

    1981-01-01

    The calcitonin secretion from the thyroid C-cells was studied with a peroperative method. The calcitonin concentrations in thyroid venous effluent and peripheral veins were determined in patients who underwent operations because of thyroid and parathyroid disease. In normocalcemia the thyroid vein level of calcitonin was significantly higher than that in peripheral vein. In chronic hypercalcemia no gradient over the thyroid was demonstrable. After injection of pentagastrin into a thyroid artery a very pronounced, but transient, increase in calcitonin concentration was registered. No difference in peak value between normo- and hypercalcemia was demonstrable. The peripheral vein level was unchanged. The peroperative method is very sensitive. A marked peak in thyroid vein corresponds to unchanged values in peripheral vein. The method invites further studies with other secretagogues and receptor-blocking substances. PMID:7259337

  17. Hypercalcemia in a male-to-female transgender patient after body contouring injections: a case report

    PubMed Central

    2014-01-01

    Introduction Body contouring injections by non-licensed providers are frequently sought out by a subset of the male-to-female transgender community. Although short-term side effects such as pulmonary embolism and injection site infection are well known, long-term consequences of such practices are less well studied. Case presentation Here we describe the case of a 40-year-old African American male-to-female transgender patient who presented to our institution with hypercalcemia and acute renal failure secondary to body contouring injections with industrial strength silicone by non-licensed providers, a decade prior to her visit. Work-up revealed an extensive granulomatous inflammatory process in the injection area resulting in electrolyte abnormalities and kidney injury. The patient’s lab results and symptoms responded well to long-term corticosteroid treatment and correlated with treatment adherence. Conclusion Affected patients can sometimes present with unusual clinical symptoms many years after silicone injections. In a constantly growing transgender community that often utilizes non-licensed providers for silicone injections, the medical community will likely face an increasing number of patients with long-term side effects of such practices. Therefore, it is imperative for physicians to recognize such cases promptly and initiate potentially life-saving treatment. PMID:24572248

  18. Mutations in AP2S1 cause familial hypocalciuric hypercalcemia type 3

    PubMed Central

    Nesbit, M. Andrew; Hannan, Fadil M.; Howles, Sarah A.; Reed, Anita A.C.; Cranston, Treena; Thakker, Clare E.; Gregory, Lorna; Rimmer, Andrew J.; Rust, Nigel; Graham, Una; Morrison, Patrick J.; Hunter, Steven J.; Whyte, Michael P.; McVean, Gil; Buck, David; Thakker, Rajesh V.

    2012-01-01

    Adaptor protein-2 (AP2), a central component of clathrin-coated vesicles (CCVs), is pivotal in clathrin-mediated endocytosis which internalises plasma membrane constituents such as G protein-coupled receptors (GPCRs)1-3 . AP2, a heterotetramer of alpha, beta, mu and sigma subunits, links clathrin to vesicle membranes and binds to tyrosine-based and dileucine-based motifs of membrane-associated cargo proteins1,4. Here, we show that AP2 sigma subunit (AP2S1) missense mutations, which all involved the Arg15 residue (Arg15Cys, Arg15His and Arg15Leu) that forms key contacts with dileucine-based motifs of CCV cargo proteins4, result in familial hypocalciuric hypercalcemia type 3 (FHH3), an extracellular-calcium homeostasis disorder affecting parathyroids, kidneys and bone5-7 These AP2S1 mutations occurred in >20% of FHH patients without calcium-sensing GPCR (CaSR) mutations which cause FHH18-12. AP2S1 mutations decreased the sensitivity of CaSR-expressing cells to extracellular-calcium and reduced CaSR endocytosis, likely through a loss of interaction with a C-terminus CaSR dileucine-based motif whose disruption also decreased intracellular signalling. Thus, our results reveal a new role for AP2 in extracellular-calcium homeostasis. PMID:23222959

  19. Acute hypercalcemia and cardiac autotransplantation in dogs: long-term hemodynamic adaptability.

    PubMed

    Dumont, L; Stanley, P; Chartrand, C

    1986-11-01

    Cardiac autotransplantation (excision and reimplantation) is a unique model that isolates totally the cardiac afferent and efferent neural pathways and results in hemodynamic misadaptability to many provocative tests. Since the cardiovascular response to acute hypercalcemia is modulated by numerous factors among which the autonomic innervation plays a major role, the hemodynamic response to bolus administration of calcium gluconate was compared in normal and cardiac autotransplanted dogs. Twenty-two animals underwent an autotransplantation while a sham procedure was performed in 18 animals. Each dog was equipped with an electromagnetic flow probe positioned around the ascending aorta and with central venous and aortic catheters. Hemodynamic data were collected daily during 1 month, before and during rapid intravenous administration of calcium gluconate (0.90 mEq). Baseline hemodynamic studies indicate that for both groups myocardial failure is evident in the immediate postoperative period; despite progressive recovery, the autotransplants always show lower cardiovascular performance. Calcium administration elicits transient positive inotropism, which is more important in presence of myocardial failure; this is true for both control and autotransplanted dogs. In the early postoperative period, hemodynamic adaptability to this stress is impaired in the autotransplants. However, long-term results indicate that minimal differences subsist over time in response to calcium administration, and when they are observed, they result from interferences in baroreceptor regulation and reflexes.

  20. Mutational Spectrum of CYP24A1 Gene in a Cohort of Italian Patients with Idiopathic Infantile Hypercalcemia.

    PubMed

    Gigante, Maddalena; Santangelo, Luisa; Diella, Sterpeta; Caridi, Gianluca; Argentiero, Lucia; D''Alessandro, Maria Michela; Martino, Marida; Stea, Emma Diletta; Ardissino, Gianluigi; Carbone, Vincenza; Pepe, Silvana; Scrutinio, Domenico; Maringhini, Silvio; Ghiggeri, Gian Marco; Grandaliano, Giuseppe; Giordano, Mario; Gesualdo, Loreto

    2016-01-01

    Loss-of-function mutations in the CYP24A1 gene, which encodes the vitamin D-24 hydroxylase, have been recognized as a cause of elevated 1,25-dihydroxyvitamin D concentrations, hypercalcemia, hypercalciuria, nephrocalcinosis and nephrolithiasis in infants and adults. As only a case report describing 2 adult patients has been reported in Italian population, we report here the mutation analysis of CYP24A1 gene in an Italian cohort of 12 pediatric and adult patients with idiopathic infantile hypercalcemia (IIH). We performed mutational screening of CYP24A1 gene in a cohort of 12 Italian patients: 8 children with nephrocalcinosis, hypercalcemia and PTH levels <10 pg/ml and 4 adult patients with nephrolithiasis, mild hypercalcemia and PTH levels <10 pg/ml from 11 unrelated Italian families. Clinical and biochemical data were collected. Genomic DNA was extracted from peripheral blood leucocytes using standard methods, and whole coding sequence of CYP24A1 gene was analysed in all patients and family members by polymerase chain reaction and direct sequencing. The potential pathogenicity of the newly identified missense mutations was evaluated by 3 different in silico approaches (Sorting Intolerant from Tolerant, Polyphen and Mutation Taster) and by comparative analysis in 14 different species using ClustalW software. CYP24A1 bi-allelic mutations were found in 8 individuals from 7 Italian families (7/11; 64%). Overall, 6 different CYP24A1 mutations, including one small deletion (p.Glu143del), 4 missense mutations (p.Leu148Pro; p.Arg396Trp; p.Pro503Leu; p.Glu383Gln) and one nonsense mutation (p.Tyr220*) were identified. Two out of 6 mutations (p.Tyr220* and p.Pro503Leu) were not previously described. Moreover, a new CYP24A1 variant was identified by genetic screening of asymptomatic controls. To the best of our knowledge, this is the first report of a CYP24A1 molecular analysis performed in an Italian cohort of adult and pediatric Italian patients. This study (1) confirms

  1. Incidence of hypercalcemia, hypercalciuria and related factors in patients treated with recombinant human parathyroid hormone (1-84).

    PubMed

    Luna-Cabrera, F; Justicia-Rull, E A; Caricol-Pérez, M P; Soler-Vizán, E; Mesa-López, C M; Ruiz-Ruiz, M A; De La Torre-López, L E

    2012-04-01

    The aim of this paper was to determine the incidence of hypercalcemia and hypercalciuria (and related factors) in 22 postmenopausal women with osteoporosis treated with PTH (1-84) in daily practice. Osteoporosis was defined as history of osteoporotic fracture or a T score less than -3 SD on bone densitometry. Patients were treated with PTH (1-84), 100 mcg/daily, for 12 months. Clinical and laboratory data at baseline and after 6 months of treatment were assessed. The mean age was 71.9 years. The incidence of hypercalcemia and the hypercalciuria were 6 events. Increase in serum calcium levels showed a statistically significant correlation with 24-hour urinary calcium (rho [ρ]=0.83, P<0.001), serum alkaline phosphatase (ρ=0.76, P=0.001), total proteins (ρ=0.77, P=0.005), and β-CTx (ρ=0.82, P=0.002). On the other hand, 24-hour urinary calcium excretion correlated significantly with β-CTx (ρ=0.83, P=0.002), alkaline phosphatase (ρ=0.73, P=0.005), total proteins (ρ=0.73, P=0.02), and serum phosphate (ρ=0.58, P=0.04). When the group of patients with and without hypercalcemia were compared, there were statistically significant differences in increases of β-CTx and baseline β-CTx values, whereas the group of patients with and without hypercalciuria showed significant differences in serum calcium increases and baseline values of T score at the femoral neck. The incidence of hypercalcemia and hypercalciuria after treatment with PTH (1-84) is similar to that expected according to the product's technical specifications. There was a significant correlation between increases of serum calcium, urinary calcium excretion, serum alkaline phosphatase, and β-CTx after treatment with PTH (1-84). Baseline β-CTx values were significantly lower in patients who developed hypercalcemia than in those with normal serum calcium levels.

  2. Maternal Hypercalcemia Due to Failure of 1,25-Dihydroxyvitamin-D3 Catabolism in a Patient With CYP24A1 Mutations

    PubMed Central

    Hsiao, Edward C.; O'Donnell, Betsy; Salmeen, Kirsten; Nussbaum, Robert; Krebs, Michael; Baumgartner-Parzer, Sabina; Kaufmann, Martin; Jones, Glenville; Bikle, Daniel D.; Wang, YongMei; Mathew, Allen S.; Shoback, Dolores; Block-Kurbisch, Ingrid

    2015-01-01

    Context: Calcium metabolism changes in pregnancy and lactation to meet fetal needs, with increases in 1,25-dihydroxyvitamin D [1,25-(OH)2D] during pregnancy playing an important role. However, these changes rarely cause maternal hypercalcemia. When maternal hypercalcemia occurs, further investigation is essential, and disorders of 1,25-(OH)2D catabolism should be carefully considered in the differential diagnosis. Case: A patient with a childhood history of recurrent renal stone disease and hypercalciuria presented with recurrent hypercalcemia and elevated 1,25-(OH)2D levels during pregnancy. Laboratory tests in the fourth pregnancy showed suppressed PTH, elevated 1,25-(OH)2D, and high-normal 25-hydroxyvitamin D levels, suggesting disordered vitamin D metabolism. Analysis revealed low 24,25-dihydroxyvitamin D3 and high 25-hydroxyvitamin D3 levels, suggesting loss of function of CYP24A1 (25-hydroxyvitamin-D3-24-hydroxylase). Gene sequencing confirmed that she was a compound heterozygote with the E143del and R396W mutations in CYP24A1. Conclusions: This case broadens presentations of CYP24A1 mutations and hypercalcemia in pregnancy. Furthermore, it illustrates that patients with CYP24A1 mutations can maintain normal calcium levels during the steady state but can develop hypercalcemia when challenged, such as in pregnancy when 1,25-(OH)2D levels are physiologically elevated. PMID:26097993

  3. Familial Hypocalciuric Hypercalcemia Types 1 and 3 and Primary Hyperparathyroidism: Similarities and Differences.

    PubMed

    Vargas-Poussou, Rosa; Mansour-Hendili, Lamisse; Baron, Stéphanie; Bertocchio, Jean-Philippe; Travers, Caroline; Simian, Christophe; Treard, Cyrielle; Baudouin, Véronique; Beltran, Sonia; Broux, Françoise; Camard, Odile; Cloarec, Sylvie; Cormier, Catherine; Debussche, Xavier; Dubosclard, Emmanuelle; Eid, Celine; Haymann, Jean-Philippe; Kiando, Soto Romuald; Kuhn, Jean-Marc; Lefort, Guy; Linglart, Agnes; Lucas-Pouliquen, Bernadette; Macher, Marie-Alice; Maruani, Gérard; Ouzounian, Sophie; Polak, Michel; Requeda, Elisabeth; Robier, Dominique; Silve, Caroline; Souberbielle, Jean-Claude; Tack, Ivan; Vezzosi, Delphine; Jeunemaitre, Xavier; Houillier, Pascal

    2016-05-01

    Familial hypocalciuric hypercalcemia (FHH) is a genetically heterogeneous condition resembling primary hyperparathyroidism (PHPT) but not curable by surgery; FHH types 1, 2, and 3 are due to loss-of-function mutations of the CASR, GNA11, or AP2S1 genes, respectively. This study aimed to compare the phenotypes of patients with genetically proven FHH types 1 or 3 or PHPT. This was a mutation analysis in a large cohort, a cross-sectional comparison of 52 patients with FHH type 1, 22 patients with FHH type 3, 60 with PHPT, and 24 normal adults. There were no interventions. Abnormalities of the CASR, GNA11, and AP2S1 genes, blood calcium, phosphate, and PTH concentrations, urinary calcium excretion were measured. In 133 families, we detected 101 mutations in the CASR gene, 68 of which were previously unknown, and in 19 families, the three recurrent AP2S1 mutations. No mutation was detected in the GNA11 gene. Patients with FHH type 3 had higher plasma calcium concentrations than patients with FHH type 1, despite having similar PTH concentrations and urinary calcium excretion. Renal tubular calcium reabsorption levels were higher in patients with FHH type 3 than in those with FHH type 1. Plasma calcium concentration was higher whereas PTH concentration and urinary calcium excretion were lower in FHH patients than in PHPT patients. In patients with FHH or PHPT, all data groups partially overlapped. In our population, AP2S1 mutations affect calcium homeostasis more severely than CASR mutations. Due to overlap, the risk of confusion between FHH and PHPT is high.

  4. Calcium Signaling Regulates Trafficking of Familial Hypocalciuric Hypercalcemia (FHH) Mutants of the Calcium Sensing Receptor

    PubMed Central

    Grant, Michael P.; Stepanchick, Ann

    2012-01-01

    Calcium-sensing receptors (CaSRs) regulate systemic Ca2+ homeostasis. Loss-of-function mutations cause familial benign hypocalciuric hypercalcemia (FHH) or neonatal severe hyperparathyroidism (NSHPT). FHH/NSHPT mutations can reduce trafficking of CaSRs to the plasma membrane. CaSR signaling is potentiated by agonist-driven anterograde CaSR trafficking, leading to a new steady state level of plasma membrane CaSR, which is maintained, with minimal functional desensitization, as long as extracellular Ca2+ is elevated. This requirement for CaSR signaling to drive CaSR trafficking to the plasma membrane led us to reconsider the mechanism(s) contributing to dysregulated trafficking of FHH/NSHPT mutants. We simultaneously monitored dynamic changes in plasma membrane levels of CaSR and intracellular Ca2+, using a chimeric CaSR construct, which allowed explicit tracking of plasma membrane levels of mutant or wild-type CaSRs in the presence of nonchimeric partners. Expression of mutants alone revealed severe defects in plasma membrane targeting and Ca2+ signaling, which were substantially rescued by coexpression with wild-type CaSR. Biasing toward heterodimerization of wild-type and FHH/NSHPT mutants revealed that intracellular Ca2+ oscillations were insufficient to rescue plasma membrane targeting. Coexpression of the nonfunctional mutant E297K with the truncation CaSRΔ868 robustly rescued trafficking and Ca2+ signaling, whereas coexpression of distinct FHH/NSHPT mutants rescued neither trafficking nor signaling. Our study suggests that rescue of FHH/NSHPT mutants requires a steady state intracellular Ca2+ response when extracellular Ca2+ is elevated and argues that Ca2+ signaling by wild-type CaSRs rescues FHH mutant trafficking to the plasma membrane. PMID:23077345

  5. Prevalence of incidental thyroid nodules in ultrasound studies of dogs with hypercalcemia (2008-2013).

    PubMed

    Pollard, Rachel E; Bohannon, Laurie K; Feldman, Edward C

    2015-01-01

    Ultrasound is commonly used to evaluate the cervical region in dogs with hypercalcemia due to suspected hyperparathyroidism. Incidental thyroid nodules may be detected during these studies, however little information has been published to guide clinical decision-making when this occurs. The purpose of this cross-sectional study was to determine the prevalence of incidental thyroid nodules in hypercalcemic dogs undergoing cervical ultrasound at our hospital during the period of 2008-2013. Dogs with a palpable neck mass were excluded. Cervical ultrasound images for each dog were retrieved and reviewed by a board certified veterinary radiologist who was unaware of patient outcome. Presence, number, and dimensions of thyroid nodules were recorded. Results of thyroid nodule aspirate, biopsy or necropsy were recorded from medical records when available. Ninety-one dogs met inclusion criteria. Of these, 14/91 (15%) dogs had at least one thyroid nodule. Mean (± standard deviation) thyroid gland nodule length, width, and height were 1.51 ± 0.74, 0.96 ± 0.73, and 0.75 ± 0.36 cm, respectively. A histologic diagnosis was available for the incidental thyroid lesions in eight dogs, including one dog with two nodules. Confirmed diagnoses for these nodules were thyroid cyst (3/9, 33%), thyroid adenoma (3/9, 33%), thyroid adenocarcinoma (2/9, 22%) and nodular hyperplasia (1/9, 11%). Findings indicated that incidental thyroid nodules may be present in hypercalcemic dogs with no palpable neck mass and no clinical signs of thyroid disease. Some of these nodules may be malignant and therefore a recommendation for cytology or biopsy may be justified.

  6. Slight hypercalcemia is not associated with positive responses in the Comet Assay in male rat liver.

    PubMed

    Thiel, Anette; Hamel, Annie; Schaefer, Katrien; Cardoso, Renato; Beilstein, Paul

    2017-08-01

    Maintenance of physiological levels of intracellular and extracellular calcium is essential for life. Increased intracellular calcium levels are involved in cell death (apoptosis and necrosis) and are associated with positive responses in the Comet assay in vitro. In addition, high calcium and vitamin D intakes were reported to induce apoptosis in adipose tissue in obese mice and to increase DNA-migration in the Comet assay. To investigate increased serum concentration of calcium as a potential confounding factor in the regulatory Comet assay in vivo, we induced mild hypercalcemia in male Wistar rats by 3-day continuous intravenous infusion of calcium gluconate and performed the Comet assay in the liver in line with regulatory guidelines. The results of the study showed that mild increases in serum calcium concentration (up to 1.4 times above the concurrent control) and increased urinary calcium concentration (up to 27.8 times above the concurrent control) results in clinical signs like mild tremor, faster respiration rate and decreased activity in a few animals. However, under the conditions of the study, no increase in the %Tail DNA in the Comet assay and no indication of liver damage as determined by histopathological means were observed. Thus, mild increases in plasma calcium did not lead to positive results in a genotoxicity assessment by the Comet assay in the rat liver. This result is important as it confirms the reliability of this assay for regulatory evaluation of safety. Copyright © 2017 DSM Nutritional Products AG. Published by Elsevier B.V. All rights reserved.

  7. Identification of AP2S1 mutation and effects of low calcium formula in an infant with hypercalcemia and hypercalciuria.

    PubMed

    Fujisawa, Yasuko; Yamaguchi, Rie; Satake, Eiichirou; Ohtaka, Konosuke; Nakanishi, Toshiki; Ozono, Keiichi; Ogata, Tsutomu

    2013-12-01

    Although AP2S1 has recently been shown to be a causative gene for familial hypocalciuric hypercalcemia type 3 (FHH3), knowledge about FHH3 remains poor. Our objective was to report AP2S1 mutation and effects of low calcium formula in a patient with hypercalcemia and hypercalciuria. This Japanese female infant was found to have hypercalcemia by a routine laboratory test for poor weight gain on breast feeding. At 49 days of age, serum calcium (adjusted by Payne's formula) was 13.1 mg/dL, intact PTH 27 pg/mL, and urinary calcium-to-creatinine ratio 1.29 mg/mg. There was no evidence for hyperparathyroidism, PTHrP-producing neoplasm, and vitamin D excess. These data, except for hypercalciuria, appeared to be consistent with defective calcium-sensing receptor-mediated signaling. With use of low calcium formula containing 2.6 mg/dL of calcium, she showed catch-up growth, and serum calcium was decreased, as was urinary calcium-to-creatinine ratio. Furthermore, feeding with a mixture of low calcium formula and standard formula with a 2:1 ratio maintained serum calcium ∼12 mg/dL without markedly increasing serum PTH. Although no pathologic mutation was detected in CASR or GNA11, a presumably de novo heterozygous mutation (p.Arg15Leu), a previously reported causative mutation for FHH3, was identified in AP2S1 of this patient. The results imply that lack of hypocalciuria does not necessarily argue against the presence of AP2S1 mutations. The early infantile age of this patient would have played a certain role in the occurrence of hypercalciuria, and low calcium formula is worth attempting in infants with FHH.

  8. Familial pheochromocytoma, hypercalcemia, and von Hippel-Lindau disease. A ten year study of a large family.

    PubMed

    Atuk, N O; McDonald, T; Wood, T; Carpenter, J T; Walzak, M P; Donaldson, M; Gillenwater, J Y

    1979-05-01

    Long-term epidemiological and laboratory studies were carried out in a kindred with familial pheochromocytoma associated with von Hippel-Lindau disease. Thirteen members were affected by the syndrome and the trait appears to be transmitted in an autosomal dominant fashion. Of 13 patients, 7 had pheochromocytoma alone. Of the remaining six patients, one had pheochromocytoma combined with von Hippel-Lindau disease, four had pheochromocytoma with retinal disease only, and a single patient had a retinal lesion without pheochromocytoma. In four patients, pheochromocytoma antedated the development of retinal lesions. Ten members also had mild hypercalcemia without accompanying elevations of PTH in the 4 patients in whom this was determined. In all, hypercalcemia was corrected with removal of tumors, and no patient had a return of hypercalcemia in the absence of recurrent increases in urinary catecholamines. The clinical presentations in 12 patients varied markedly, as did their urinary excretion rates of norepinephrine, epinephrine and their metabolites. However, an analysis of the data revealed significant correlations not previously described between the urinary excretion of free catecholamines (norepinephrine plus epinephrine), blood pressure, the free catecholamine content of the tumor and the age of the patient. Urinary excretion of free norepinephrine plus epinephrine appear to be decreased with advancing age (p less than 0.001). Both systolic and diastolic blood pressures and the age of the patient were inversely correlated (p less than 0.01). A significant inverse relationship between the tumor content of free catecholamines and the age of the patients was, although to a lesser degree, also present (p less than 0.05). As a whole, the size of the tumors and their norepinephrine content were not correlated. We present a concept that, in familial pheochromocytoma, the metabolism of catecholamines is altered by the process of aging, and that this change modifies the

  9. Hypercalcemia during the osteogenic phase after rat marrow ablation coincides with increased bone resorption assessed by the NTx marker.

    PubMed

    Gorski, J P; Apone, S; Shaffer, K A; Batchelder, A; Jean, W; Williams, J A; Shacter, E; Eyre, D R

    2000-07-01

    Marrow ablation is a model of bone turnover in which the excavated tibial intramedullary cavity is rapidly and reproducibly filled by osteoblasts with new woven bone (days 6-8), which is then rapidly resorbed by osteoclasts (days 10-15). We showed previously (Magnuson et al., 1997) that marrow ablation induces a dramatic hypercalcemia and hypercalciuria in rats that unexpectedly peaked at the time of maximal osteogenesis and continued throughout the subsequent resorption phase. Based upon the amount of calcium mobilized and a peak of urinary hydroxyproline, we suggested that the hypercalcemia and hypercalciuria were due to increased systemic osteoclastic bone resorption induced by marrow ablation. We now apply a new enzyme-linked immunosorbent assay for rodent alpha(2)(I) N-telopeptide (NTx), a marker of bone resorption, to the marrow ablation model to demonstrate that excretion of NTx parallels that of calcium release in the operated control group. Specifically, maximal NTx/creatinine excretion coincides with the onset of hypercalcemia on days 7-8. A peak of NTx was also observed in methylprednisolone- and deflazacort-treated ablated animals. Analyses for urinary free deoxypyridinoline crosslink failed to detect a significant ablation-induced change in excretion. Interleukin 6 activity was increased in all operated control and glucocorticoid-treated groups after marrow ablation, whereas serum parathyroid hormone remained at presurgical levels in operated controls throughout the 15-day study period. The NTx results confirm that bilateral tibial marrow ablation induces a burst of extratibial bone resorption and hypercalcemia 7-8 days later. We have estimated that the osteogenic phase of the ablation model deposits 40 mg of calcium as hydroxyapatite crystals within the intramedullary cavity on days 6-8; this represents 33%-50% of the total blood calcium content of a young rat. We hypothesize that the size and rapidity of this demand for ionized calcium is met through

  10. Hypercalcemia and diffuse osteolytic lesions in a 45-year-old patient with myeloid sarcoma with megakaryocytic differentiation

    PubMed Central

    Goud, Aditya; Abdelqader, Abdelhai; Dahagam, Chanukya; Jabaji, Ramez; Kumar, Pallavi; Aboulafia, Albert; Selinger, Stephen

    2016-01-01

    Acute megakaryocytic leukemia is a rare form of acute myeloid leukemia that carries a poor prognosis. As most cases of osteolytic lesions are due to plasma cell and myeloid malignancies, maintaining a broad differential directly influences clinical course. We document a 45-year-old patient with progressive constitutional symptoms, osteolytic bone lesions in the setting of hypercalcemia, who developed acutely worsening pancytopenia. The diagnosis of myeloid sarcoma with megakaryocytic differentiation was made after obtaining tissue from osteolytic bone that stained strong for CD34. Immunohistochemical testing underscores the importance of how serologic and urine testing remains limited and can delay early diagnosis in this disease. PMID:27124159

  11. Denosumab is Effective for Controlling Serum Calcium Levels in Patients with Humoral Hypercalcemia of Malignancy Syndrome: A Case Report on Parathyroid Hormone-related Protein-producing Cholangiocarcinoma

    PubMed Central

    Ashihara, Norihiro; Nakajima, Koji; Nakamura, Yoshiyuki; Kobayashi, Mutsuhiro; Shirahata, Kumiko; Maeda, Chika; Uehara, Takeshi; Gomi, Daisuke; Ito, Nobuo

    2016-01-01

    Hypercalcemia resulting in the elevation of serum parathyroid hormone-related protein (PTHrP) and suppression of serum PTH was observed in a patient with advanced cholangiocarcinoma (CCC) and multiple lymph node metastases. We confirmed humoral hypercalcemia of malignancy based on PTHrP-producing CCC. Chemotherapy with gemcitabine and cisplatin could not control the patient's serum PTHrP levels and the patient was affected with bisphosphonate-refractory hypercalcemia. We administered a single dose of denosumab, an anti-receptor activator of nuclear factor-kappaB ligand monoclonal antibody, and the patient's serum calcium levels remained close to the normal range for approximately 3 weeks without additional treatment. PMID:27904108

  12. A novel mutation of the calcium-sensing receptor gene in a German subject with familial hypocalciuric hypercalcemia and primary hyperparathyroidism.

    PubMed

    Papadakis, Marios; Meurer, Natalie; Margariti, Theodora; Meyer, Anke; Weyerbrock, Norbert; Dotzenrath, Cornelia

    2016-10-01

    The coexistence of familial hypocalciuric hypercalcemia (FHH) and primary hyperparathyroidism (PHPT) is extremely rare. Genetic evidence has demonstrated a causal relationship between FHH and the presence of inactivating mutations in the calcium-sensing receptor gene. We herein report a 60-year-old German patient who was referred for hypercalcemia and increased PTH levels found incidentally during normal routine blood tests. The patient underwent surgical exploration and the diagnosis of PHPT was histologically confirmed. One week later, the follow-up blood tests revealed recurrent hypercalcemia, and the possibility of FHH was reconsidered. Genetic analysis was performed and revealed a novel heterozygous CaSR single missense mutation (Arg551Gly) within the extracellular CaSR domain. We report a novel heterozygous missense inactivating mutation within the extracellular CaSR domain in a German subject with FHH and histologically proven PHPT.

  13. MANAGEMENT OF ACUTE RENAL FAILURE WITH DELAYED HYPERCALCEMIA SECONDARY TO SARCOCYSTIS NEURONA-INDUCED MYOSITIS AND RHABDOMYOLYSIS IN A CALIFORNIA SEA LION (ZALOPHUS CALIFORNIANUS).

    PubMed

    Alexander, Amy B; Hanley, Christopher S; Duncan, Mary C; Ulmer, Kyle; Padilla, Luis R

    2015-09-01

    A 3-yr-old captive-born California sea lion (Zalophus californianus) developed Sarcocystis neurona-induced myositis and rhabdomyolysis that led to acute renal failure. The sea lion was successfully managed with fluid therapy, antiprotozoals, antibiotics, anti-inflammatories, antiemetics, gastroprotectants, and diuretics, but developed severe delayed hypercalcemia, a syndrome identified in humans after traumatic or exertion-induced rhabdomyolysis. Treatment with calcitonin was added to the management, and the individual recovered fully. The case emphasizes that animals with rhabdomyolysis-induced renal failure risk developing delayed hypercalcemia, which may be life threatening, and calcium levels should be closely monitored past the resolution of renal failure.

  14. Persistent arthralgia, vomiting and hypercalcemia as the initial manifestations of hyperthyroidism: A case report

    PubMed Central

    Liu, Jingfang; Tang, Xulei; Cheng, Jianguo; Yang, Xiaomei; Wang, Yan

    2017-01-01

    A 53-year-old woman presented with persistent edema and pain of the metacarpophalangeal and proximal interphalangeal joints and the wrist, knee and ankle joints, with more recent intermittent nausea and vomiting. Treatment for rheumatoid arthritis and osteoarthritis was ineffective. No clinical manifestations typical of hyperthyroidism were observed. The results of the thyroid function tests were as follows: Thyroid-stimulating hormone, 0.003 µIU/ml; triiodothyronine (T3), 4.44 ng/ml;, thyroxine (T4) >30 µg/dl; free T3, 14.03 pg/ml; and free T4, 8.84 ng/dl. The laboratory tests revealed an elevated serum calcium level (2.96 mmol/l); moderate hypophosphatemia (0.84 mmol/l); significantly reduced serum intact parathyroid hormone (4.8 pg/ml); normal 25-hydroxy vitamin D (52.13 nmol/l) and bone-specific alkaline phosphatase (22.1 ng/ml); and elevated osteocalcin (128.8 ng/ml). X-ray and quantitative ultrasound examinations revealed extensive osteoporosis of the hands, skull, knees and pelvis, with a bone mineral density of 0.254 g/cm2 (T-score, −3.2). Anti-thyroid therapy (methimazole, 30 mg/day; salmon calcitonin, 50 IU/day; and alendronate, 70 mg/week) was initiated. After 2 weeks, the serum calcium and phosphate levels were normalized (2.44 and 1.19 mmol/l, respectively) and calcitonin was discontinued. After 3 months, the patient had no nausea, vomiting or joint pain, and her appetite was normal, with a weight gain of ~10 kg. Euthyroidism was achieved and the serum calcium and phosphate levels were normalized (2.31 and 1.12 mmol/l, respectively) and maintained for 6 months, by which time the osteocalcin level had diminished (80.40 ng/ml). This rare case of arthralgia, hypercalcemia and extensive osteoporosis as the first manifestations of hyperthyroidism suggests that, even without typical symptoms, hyperthyroidism should be considered in the differential diagnosis of patients with persistent arthralgia. PMID:28357106

  15. The Calcium-Sensing Receptor Is Necessary for the Rapid Development of Hypercalcemia in Human Lung Squamous Cell Carcinoma12

    PubMed Central

    Lorch, Gwendolen; Viatchenko-Karpinski, Serge; Ho, Hsiang-Ting; Dirksen, Wessel P; Toribio, Ramiro E; Foley, John; Györke, Sandor; Rosol, Thomas J

    2011-01-01

    The calcium-sensing receptor (CaR) is responsible for the regulation of extracellular calcium (Ca2+o) homeostasis. CaR activation has been shown to increase proliferation in several cancer cell lines; however, its presence or function has never been documented in lung cancer. We report that Ca2+o-activated CaR results in MAPK-mediated stimulation of parathyroid hormone-related protein (PTHrP) production in human lung squamous cell carcinoma (SCC) lines and humoral hypercalcemia of malignancy (HHM) in vivo. Furthermore, a single nucleotide polymorphism in CaR identified from a hypercalcemia-inducing lung SCC reduced the receptor's activation threshold leading to increased PTHrP expression and secretion. Increasing the expression of either wild-type CaR or a CaR variant with a single nucleotide polymorphism in the cytoplasmic domain was both necessary and sufficient for lung SCC to induce HHM. Because lung cancer patients who frequently develop HHM and PTHrP expression in lung cancer has been only partially explained, the significance of our findings indicates that CaR variants may provide a positive feedback between PTHrP and calcium and result in the syndrome of HHM. PMID:21532883

  16. Identification and Functional Characterization of a Calcium-Sensing Receptor Mutation in an Infant with Familial Hypocalciuric Hypercalcemia

    PubMed Central

    Papadopoulou, Anna; Gole, Evangelia; Melachroinou, Katerina; Meristoudis, Christos; Siahanidou, Tania; Papadimitriou, Anastasios

    2016-01-01

    Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant disorder, associated with inactivating mutations of the calcium-sensing receptor (CaSR). To evaluate the functional significance of a CaSR mutation, identified in a young infant who presented with hypercalcemia and hypocalciuria. The CaSR gene coding sequences were analyzed by polymerase chain reaction amplification and direct sequencing analysis. The mutation identified was introduced by site-directed mutagenesis into a wild-type (WT) CaSR plasmid, and human embryonic kidney 293 T cells were transfected with either the WT or mutant CaSR. The function of the mutated CaSR protein was analyzed by evaluating the free intracellular calcium [(Ca2+)i] response after challenge with extracellular calcium (Ca2+). We identified a heterozygous mutation c.772_773delGTinsA in exon 4 resulting in the substitution of amino acid valine (Val) with amino acid arginine (Arg) and the premature pause of the translation 46 amino acids later (Val258ArgfsTer47). Functional assay showed that cells transfected with the mutant CaSR had a significantly poorer response to extracellular Ca2+ stimulation compared with the WT. We have shown that the c.772_773delGTinsA mutation causes a significant alteration of CaSR function leading to features of FHH in an affected young infant since the first months of life. PMID:27087013

  17. A novel SLC12A1 gene mutation associated with hyperparathyroidism, hypercalcemia, nephrogenic diabetes insipidus, and nephrocalcinosis in four patients.

    PubMed

    Wongsaengsak, Sariya; Vidmar, Alaina P; Addala, Ananta; Kamil, Elaine S; Sequeira, Paola; Fass, Benjamin; Pitukcheewanont, Pisit

    2017-04-01

    Solute Carrier Family 12 member 1 (SLC12A1) gene encodes the sodium-potassium-chloride co-transporter (NKCC2) at the apical membrane of the thick ascending loop of Henle (TAL). Bartter's syndrome (BS) type I is a rare, autosomal recessive, renal tubular disorder associated with mutation of the SLC12A1 gene. Presenting features include: hypokalemic metabolic alkalosis, hypercalciuria and nephrocalcinosis. The many allelic variants reported present with a spectrum of phenotypes, biochemical abnormalities and clinical severities. However, to date, only two reports have described hyperparathyroidism and hypercalcemia in patients with SLC12A1 gene mutations. We describe 4 patients with 4 novel mutation variants in the SLC12A1 gene (c.735C>G, c.1137del, c.2498-2499del, and c.1833delT) presenting with variable degrees of hyperparathyroidism, hypercalcemia, hypokalemic metabolic alkalosis, nephrocalcinosis, and nephrogenic diabetes insipidus. The link between calcium and parathyroid hormone abnormalities in patients with SLC12A1 mutations is unclear; the cases described suggest an association between primary hyperparathyroidism and loss of function mutation of SLC12A1, which may result in an aberrant threshold of the calcium sensing receptor at the level of the kidney.

  18. Primary hyperoxaluria in an adult presenting with end-stage renal failure together with hypercalcemia and hypothyroidism.

    PubMed

    Karadag, Serhat; Gursu, Meltem; Aydin, Zeki; Uzun, Sami; Dogan, Oner; Ozturk, Savas; Kazancioglu, Rumeyza

    2011-10-01

    Primary hyperoxaluria (PH) is a rare genetic disorder characterized by overproduction of oxalate due to specific enzyme deficiencies in glyoxylate metabolism. The primary clinical presentation is in the form of recurrent urolithiasis, progressive nephrocalcinosis, end-stage renal disease, and systemic oxalosis. Herein, we present a case of PH who was diagnosed at 47 years of age after 6 years on hemodialysis. He presented with fatigue, anorexia, weight loss, and was found to have cachexia, diffuse edema, hepatomegaly, ascites, hypercalcemia, hyperphosphatemia, hypoalbuminemia, low parathyroid hormone levels, lytic and resorptive areas in the vertebrae, diffusely increased echogenity of the liver, multiple renal stones, and bilateral nephrocalcinosis. Bone marrow biopsy showed calcium oxalate crystals and crystal granulomas. The liver biopsy could not be performed. The absence of an identifiable reason for secondary forms, the severity of the clinical presentation, and pathological findings led to the diagnosis of PH2. He died while waiting for a potential liver and kidney donor. The presented case is consistent with the literature as he had renal stone disease in the third decade and end-stage renal disease in the fifth decade. Hypercalcemia was thought to be due to osteoclast-stimulating activity of macrophages constituting the granuloma. Erythropoietin-resistant anemia and hypothyroidism were thought to be due to accumulation of oxalate in the bone marrow and thyroid gland, respectively. It is very important to keep in mind the possibility of PH when faced with a patient with nephrocalcinosis and oxalate stone disease.

  19. Abnormal lung and liver uptake of gallium-67 and technetium-99m MDP in hypercalcemia of lymphoma with metastatic pulmonary calcification

    SciTech Connect

    Sullivan, W.T.; Orzel, J.A.; Reed, K.D.; Bower, J.H.

    1986-08-01

    Abnormal pulmonary uptake of Ga-67 citrate and Tc-99m MDP and reversible liver uptake of Tc-99m MDP was seen in a patient with hypercalcemia of lymphoma and biopsy-proven metastatic pulmonary calcification. Abnormal lung uptake of Tc-99m MDP may confirm the diagnosis of pulmonary calcification, lessening the need for invasive procedures to evaluate pathologic lung uptake of Ga-67 citrate.

  20. Hypercalcemia, hypervitaminosis A and 3-epi-25-OH-D3 levels after consumption of an "over the counter" vitamin D remedy. a case report.

    PubMed

    Granado-Lorencio, F; Rubio, E; Blanco-Navarro, I; Pérez-Sacristán, B; Rodríguez-Pena, R; García López, F J

    2012-06-01

    Intoxication from vitamin D supplements has been rarely reported but, nowadays, it occurs more frequently. 3-epi-25-OH-D(3) is highly prevalent in adults and it is considered of biological relevance. We report a case of vitamin D toxicity with hypercalcemia, acute renal failure and hypervitaminosis A after consuming an over-the-counter vitamin D supplement. Our data suggest that the contribution of 3-epi-25-OH-D(3) is not altered during vitamin D toxicity, although the serum levels of 25-OH-D(3) and 3-epi-25-OH-D(3) may display a different rate of clearance. The patient also displayed hypervitaminosis A unrelated to diet, possibly caused by renal failure related to the hypercalcemia induced by vitamin D toxicity. Because of the increasing use of over-the-counter vitamin D supplements and the potential iatrogenic hypercalcemia related to hypervitaminosis A, the present case highlights the importance of evaluating both the use of (non-) prescribed medication and vitamin A status during vitamin D toxicity. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Prevalence of hypercalcemia of malignancy among pediatric cancer patients in the UK Clinical Practice Research Datalink database

    PubMed Central

    Jick, Susan; Li, Lin; Gastanaga, Victor M; Liede, Alexander; Hernandez, Rohini K

    2017-01-01

    Background The reported proportion of cancer patients who experience hypercalcemia of malignancy (HCM) is low, particularly in the pediatric population, ranging between <1% and 5%. HCM can be observed with any type of tumor in children and occurs most commonly with leukemia. While HCM is a potentially fatal condition, the prevalence of HCM is not well understood in pediatric cancer patients. Methods Using the UK Clinical Practice Research Datalink, we identified pediatric cancer patients with recorded corrected serum calcium (CSC) from 2003 through 2014. Hypercalcemic patients (CSC ≥10.8 mg/dL) were classified into 4 CSC levels. We estimated the annual prevalence of HCM using Byar’s method. Results Among 517 pediatric cancer patients, leukemia, lymphoma, and brain tumors were the most frequent cancer types. The prevalence of HCM overall (grade 1 or higher) ranged from 0.24% to 0.81% between 2003 and 2014. There were too few cases to compare prevalence by type of cancer. Conclusion We provide the first systematic analysis using a UK population-based data source to estimate the number of pediatric cancer patients affected with HCM by grade. Our findings showed that the prevalence of pediatric HCM was very low (0.24%–0.81%) over the 12-year study period, which is consistent with previous study of adult cancer patients in the UK (0.20%–0.67%). PMID:28670142

  2. Hypocalcemia increases and hypercalcemia decreases the steady-state level of parathyroid hormone messenger RNA in the rat.

    PubMed Central

    Yamamoto, M; Igarashi, T; Muramatsu, M; Fukagawa, M; Motokura, T; Ogata, E

    1989-01-01

    To examine the effects of serum calcium concentrations on PTH biosynthesis, rats were made hyper- (serum total calcium, approximately 3.5 mM) or hypocalcemic (approximately 1.25 mM) and steady-state levels of PTH mRNA in parathyroid cells were measured by the primer extension method using a 32P-labeled synthetic oligomer. PTH mRNA levels increased about twofold in the rats made slightly hypocalcemic by infusion of calcium-free solution and decreased slightly in those made hypercalcemic by CaCl2 infusion (120-150 mumol/h) compared with the levels present in nonfasting control rats. Infusion of calcitonin (0.5 U/h) or EGTA (90 mumol/h) with calcium-free solution increased PTH mRNA levels further (two- to sevenfold) above the levels present in animals infused with calcium-free solution alone. These changes in PTH mRNA levels were observed after 48- but not 24-h infusion, and there was an inverse correlation between PTH mRNA levels and serum calcium concentrations. The results suggest that changes in serum calcium concentrations in the near physiological range regulate the biosynthesis of PTH by affecting steady-state levels of PTH mRNA when hypercalcemia or hypocalcemia continues for a relatively long period. Images PMID:2493484

  3. Hypercalcemia, hypercalciuria, and kidney stones in long-term studies of vitamin D supplementation: a systematic review and meta-analysis.

    PubMed

    Malihi, Zarintaj; Wu, Zhenqiang; Stewart, Alistair W; Lawes, Carlene Mm; Scragg, Robert

    2016-10-01

    Vitamin D supplementation is increasingly being used in higher doses in randomized controlled trials (RCTs). However, adverse events from very large annual doses of vitamin D have been shown in 2 RCTs, whereas in a third RCT, low-dose vitamin D, with calcium supplements, was shown to increase kidney stone risk. We analyzed the side effects related to calcium metabolism in RCTs, specifically hypercalcemia, hypercalciuria, and kidney stones, in participants who were given vitamin D supplements for ≥24 wk compared with in subjects in the placebo arm. The following 3 main online databases were searched: Ovid Medline (PubMed), EMBASE, and the Cochrane Library. Software was used for the meta-analysis. A total of 48 studies with 19,833 participants were identified, which reported ≥1 of the following side effects: hypercalcemia, hypercalciuria, or kidney stones. Of these studies, kidney stones were reported in only 9 trials with a tendency for fewer subjects reporting stones in the vitamin D arm than in the placebo arm (RR: 0.66, 95% CI: 0.41, 1.09; P = 0.10). In 37 studies, hypercalcemia was shown with increased risk shown for the vitamin D group (RR: 1.54; 95% CI: 1.09, 2.18; P = 0.01). Similar increased risk of hypercalciuria was shown in 14 studies for the vitamin D group (RR: 1.64; 95% CI: 1.06, 2.53; P = 0.03). In subgroup analyses, it was shown that the effect of vitamin D supplementation on risk of hypercalcemia, hypercalciuria, or kidney stones was not modified by baseline 25-hydroxyvitamin D, vitamin D dose and duration, or calcium co-supplementation. Long-term vitamin D supplementation resulted in increased risks of hypercalcemia and hypercalciuria, which were not dose related. However, vitamin D supplementation did not increase risk of kidney stones. Additional large RCTs of long-term vitamin D supplementation are required to confirm these findings. © 2016 American Society for Nutrition.

  4. A Case of Hypercalcemia and Overexpression of CYP27B1 in Skeletal Muscle Lesions in a Patient with HIV Infection After Cosmetic Injections with Polymethylmethacrylate (PMMA) for Wasting.

    PubMed

    Hindi, Sahar M; Wang, Yongmei; Jones, Kirk D; Nussbaum, Jesse C; Chang, Yongen; Masharani, Umesh; Bikle, Daniel; Shoback, Dolores M; Hsiao, Edward C

    2015-12-01

    Foreign body-induced granuloma is an uncommon yet clinically significant cause of hypercalcemia. The molecular mechanisms are uncertain, although extrarenal calcitriol production has been proposed. We describe severe hypercalcemia associated with increased levels of plasma calcitriol in a patient with HIV and local granulomatous reaction 5 years after injection of polymethylmethacrylate (PMMA) as dermal filler for cosmetic body sculpting. Extensive evaluation revealed no identifiable cause of increased calcitriol levels. Nuclear imaging was remarkable for diffuse uptake in the subcutaneous tissues of the buttocks. Subsequent muscle biopsy and immunohistochemical staining showed strong local expression of CYP27B1 within histiocytes surrounding globules of PMMA. This case highlights an unfortunate complication of dermal fillers and shows that inflammatory cells can express high levels of CYP27B1 even without frank granulomas. The growing trend of body contour enhancement using injectable fillers should raise suspicion for this cause of hypercalcemia in clinical practice. Patients with HIV who receive this treatment for lipodystrophy or other cosmetic purposes may have increased susceptibility to hypercalcemia in the setting of underlying chronic inflammation. This may be a concern when changing anti-retroviral therapy, since alterations in levels of HIV viremia may initiate or contribute to worsening hypercalcemia.

  5. A Case of Hypercalcemia and Overexpression of CYP27B1 in Skeletal Muscle Lesions in a Patient with HIV Infection after Cosmetic Injections with Polymethylmethacrylate (PMMA) for Wasting

    PubMed Central

    Hindi, Sahar M.; Wang, Yongmei; Jones, Kirk D.; Nussbaum, Jesse C.; Chang, Yongen; Masharani, Umesh; Bikle, Daniel; Shoback, Dolores M.; Hsiao, Edward C.

    2016-01-01

    Foreign body-induced granuloma is an uncommon yet clinically significant cause of hypercalcemia. The molecular mechanisms are uncertain, although extrarenal calcitriol production has been proposed. We describe severe hypercalcemia associated with increased levels of plasma calcitriol in a patient with HIV and local granulomatous reaction five years after injection of polymethylmethacrylate (PMMA) as dermal filler for cosmetic body sculpting. Extensive evaluation revealed no identifiable cause of increased calcitriol levels. Nuclear imaging was remarkable for diffuse uptake in the subcutaneous tissues of the buttocks. Subsequent muscle biopsy and immunohistochemical staining showed strong local expression of CYP27B1 within histiocytes surrounding globules of PMMA. This case highlights an unfortunate complication of dermal fillers and shows that inflammatory cells can express high levels of CYP27B1 even without frank granulomas. The growing trend of body contour enhancement using injectable fillers should raise suspicion for this cause of hypercalcemia in clinical practice. Patients with HIV who receive this treatment for lipodystrophy or other cosmetic purposes may have increased susceptibility to hypercalcemia in the setting of underlying chronic inflammation. This may be a concern when changing anti-retroviral therapy, since alterations in levels of HIV viremia may initiate or contribute to worsening hypercalcemia. PMID:26253396

  6. Stepwise CaSR, AP2S1, and GNA11 sequencing in patients with suspected familial hypocalciuric hypercalcemia.

    PubMed

    Szalat, Auryan; Shpitzen, Shoshana; Tsur, Anat; Zalmon Koren, Ilana; Shilo, Shmuel; Tripto-Shkolnik, Liana; Durst, Ronen; Leitersdorf, Eran; Meiner, Vardiella

    2017-03-01

    Patients with familial hyperparathyroidism and low urinary calcium excretion may have familial hypocalciuric hypercalcemia (FHH) with mutations in one of three genes: the calcium-sensing receptor (CaSR) defining FHH-type 1, the adaptor-related protein complex 2 (AP2S1) related to FHH-type 3 or the G-protein subunit alpha11 (GNA11) associated with FHH-type 2. We aimed to evaluate the presence of mutations in these genes and to identify phenotypic specificities and differences in these patients. Selected patients were recruited for genetic evaluation. After informed consent was signed, blood for DNA extraction was obtained and genetic sequencing of CaSR was done. In negative cases, we further performed sequencing of AP2S1 and GNA11. A total of 10 index cases were recruited. CaSR sequencing yielded three missense heterozygous mutations (30%): c.554G > A (p.I32V) previously characterized by our team, c.1394 G > A (p.R465Q) and a novel expected disease-causing mutation c.2479 A > C (p.S827R). We identified 2 additional patients (20%) carrying the deleterious recurrent mutation c.44G > T (p.R15L) in the AP2S1 gene. No GNA11 mutation was found. Clinically, patients with AP2S1 mutations had significant cognitive and behavioral disorders, and higher blood calcium and magnesium levels than patients with FHH1. CaSR and AP2S1 sequencing is worthwhile in patients with familial hyperparathyroidism and phenotype suggesting FHH as it can diagnose up to 50% of cases. GNA11 mutations seem much rarer. Learning disabilities in these patients, associated with higher serum calcium and magnesium levels may suggest the presence of AP2S1 rather than CaSR mutation and may guide the first step in the genetic evaluation.

  7. Targeted 25-hydroxyvitamin D3 1α-hydroxylase adoptive gene therapy ameliorates dss-induced colitis without causing hypercalcemia in mice.

    PubMed

    Li, Bo; Baylink, David J; Walter, Michael H; Lau, Kin-Hing William; Meng, Xianmei; Wang, Jun; Cherkas, Andriy; Tang, Xiaolei; Qin, Xuezhong

    2015-02-01

    Systemic 1,25(OH)2D3 treatment ameliorating murine inflammatory bowel diseases (IBD) could not be applied to patients because of hypercalcemia. We tested the hypothesis that increasing 1,25(OH)2D3 synthesis locally by targeting delivery of the 1α-hydroxylase gene (CYP27B1) to the inflamed bowel would ameliorate IBD without causing hypercalcemia. Our targeting strategy is the use of CD11b(+)/Gr1(+) monocytes as the cell vehicle and a macrophage-specific promoter (Mac1) to control CYP27B1 expression. The CD11b(+)/Gr1(+) monocytes migrated initially to inflamed colon and some healthy tissues in dextran sulfate sodium (DSS) colitis mice; however, only the migration of monocytes to the inflamed colon was sustained. Adoptive transfer of Gr1(+) monocytes did not cause hepatic injury. Infusion of Mac1-CYP27B1-modified monocytes increased body weight gain, survival, and colon length, and expedited mucosal regeneration. Expression of pathogenic Th17 and Th1 cytokines (interleukin (IL)-17a and interferon (IFN)-α) was decreased, while expression of protective Th2 cytokines (IL-5 and IL-13) was increased, by the treatment. This therapy also enhanced tight junction gene expression in the colon. No hypercalcemia occurred following this therapy. In conclusion, we have for the first time obtained proof-of-principle evidence for a novel monocyte-based adoptive CYP27B1 gene therapy using a mouse IBD model. This strategy could be developed into a novel therapy for IBD and other autoimmune diseases.

  8. Clinical evaluation of incadronate in korean patients with malignancy-associated hypercalcemia: An open-label, multicenter study

    PubMed Central

    Kim, Sung-Bae; Lee, Jung Shin; Kim, Heung Tae; Im, Yong Hyuck; Kim, Tae Won; Ryoo, Baek Yeol; Park, Yeon Hee; Park, Joon Oh; Park, Keunchil; Katoh, Hitoshi; Yamamoto, Minoru

    2007-01-01

    Abstract Background: Incadronate has been found to lessen the increase in corrected serum calcium levels in malignancy-associated hypercalcemia (MAH) in a Phase III study in Japan. The drug is currently used to treat MAH in Japan. Objective: The purpose of this study was to assess the clinical usefulness of incadronate in patients with MAH. Methods: This open-label study was conducted at 3 medical institutions in Korea. Korean patients with MAH (corrected serum calcium levels ≥11.0 mg/dL) were given a single 10-mg IV infusion of incadronate over 2 to 4 hours in 500 to 1000 mL of normal saline. Corrected calcium levels were determined and subjective symptoms and objective findings (ie, bone pain, spontaneous pain, pain from contusion, tenderness, other pain, loss of appetite, nausea and/or vomiting, thirst, constipation, fatigue, and disturbance of consciousness) were used to monitor the effectiveness of the drug for 6 days after the infusion. Symptoms were evaluated using a 4-point scale (0 = none to 3 = severe). Adverse events (AEs) were identified by patients' reports, and adverse drug events (ADEs) were assessed by the investigators throughout the study. Results: Twenty-four Korean patients (18 [75%]male, 6 [25%]female; mean age, 56.5 years) were included in the study; data from 22 and 24 patients were used to assess effectiveness and tolerability, respectively. Corrected serum calcium level was significantly decreased on day 6 after treatment compared with pretreatment on day 0 (baseline) (9.51 [0.89] mg/dL vs 11.83 [0.89] mg/dL; P < 0.001). The antihypercalcemic effect of incadronate became apparent as an inhibition of bone absorption a few days after infusion. Corrected serum calcium level was significantly decreased on days 2 to 6 (P < 0.001) after treatment compared with pretreatment at baseline. Evaluation of symptoms showed significant improvement in the incadronate-treated group (mean total score [range] at baseline, 8 [1–23] and day 6, 5.5 [1–17

  9. Multi-organ dysfunction in bodybuilding possibly caused by prolonged hypercalcemia due to multi-substance abuse: case report and review of literature.

    PubMed

    Schäfer, C N; Guldager, H; Jørgensen, H L

    2011-01-01

    A 26-year-old male bodybuilder was admitted to the surgical department of a Danish community hospital for hematemesis. During the clinical interview, he revealed that he had recently finished a course of anabolic steroids and erythropoietin. The patient also had a previous history of infections and chronic ulcers due to paraffin-oil injections in both upper arms one year before. Over the course of the next few hours, the patient developed signs of multi-organ dysfunction, including pancreatitis, hemorrhagic gastritis, nephropathy with temporary anuria, and respiratory insufficiency, and was transferred to the ICU. After manometric monitoring on the patient's upper arms proved difficult, invasive blood pressure monitoring was used and revealed that the patient was in a state of hypertensive crisis. This case of multi-organ dysfunction was possibly caused by multi-substance-induced hypercalcemia. © Georg Thieme Verlag KG Stuttgart · New York.

  10. Vitamin D intoxication with severe hypercalcemia due to manufacturing and labeling errors of two dietary supplements made in the United States.

    PubMed

    Araki, Takako; Holick, Michael F; Alfonso, Bianca D; Charlap, Esti; Romero, Carla M; Rizk, Dahlia; Newman, Lisa G

    2011-12-01

    More than 50% of Americans use dietary supplements, and 60-70% fail to report this use to their physicians. Intoxication from vitamin D supplements has been rarely reported but may now occur more frequently. This may be attributable to an increase in vitamin D supplement intake due to the findings that deficiency is common and has been associated with a number of disease states. We report two cases of vitamin D intoxication with dietary supplements made in the United States caused by manufacturing and labeling errors. Case histories were obtained, and serial laboratory data (calcium and vitamin D metabolites) were measured. Each dietary supplement was analyzed by UV spectrophotometry followed by HPLC. In both cases, repetitive inquiries were required to elicit the use of dietary supplements. Because of significant manufacturer errors and a labeling error, patients had been consuming more than 1000 times the recommended daily dose of vitamin D(3). Hypercalcemia is directly proportional to serum 25-hydroxyvitamin D [25(OH)D] but not 1,25-dihydroxyvitamin D levels. It took approximately 1 yr to normalize 25(OH)D levels. However, once 25(OH)D levels decreased below 400 ng/ml, both patients became normocalcemic and asymptomatic without long-term sequelae. Although rare, vitamin D intoxication should be considered in the differential diagnosis of hypercalcemia. Patients should be asked whether they are using dietary supplements, and serial questioning may be required because patients may not consider these supplements to be potential health risks. Errors in the manufacturing and labeling of dietary supplements made in the United States may place individuals at increased risks for side effects.

  11. Serum calcitonin may falsely estimate tumor burden in chronic hypercalcemia: a case of prostatic and multiple bone metastases from medullary thyroid cancer.

    PubMed

    Kim, Hee Kyung; Bae, Woo Kyun; Choi, Yoo Duk; Shim, Hyun Jeong; Yoon, Jee Hee; Kang, Ho-Cheol

    2014-03-01

    Medullary thyroid cancer (MTC) is a calcitonin (Ct)-secreting tumor of the parafollicular or C cells of the thyroid gland. Higher serum Ct levels are associated with larger tumor size, distant metastases, and prognosis. We report herein a case of prostate and multiple bone metastases of nonfamilial MTC with mildly elevated Ct levels. A 73-year-old man who was found to have a 2.5 cm MTC in the left thyroid lobe with cervical lymph node metastases presented with confused mental status because of severe hypercalcemia (albumin-modified serum calcium concentration 15.2 mg/dL) associated with multiple bone metastases. Prostate biopsy was performed because the patient had frequent urination with mildly elevated serum prostate-specific antigen (5.297 ng/mL). Histologically, the prostate was diagnosed as MTC metastasis, forming a tissue architecture closely resembling the previously diagnosed MTC, and the cells were positive for Ct, carcinoembryonic antigen, and thyroid transcription factor 1. Although the patient had multiple MTC metastases, basal and calcium-stimulated serum Ct levels were not significantly elevated, measuring 22.7 pg/mL (normal <10 pg/mL) and 22.1 pg/mL, respectively. A chronic hypercalcemic state may exhaust Ct reserves and diminish the Ct response to an acute intravenous calcium injection. Therefore, the Ct level of a patient in a hypercalcemic state should be carefully interpreted. To our knowledge, this is the first reported case in the literature in which serum Ct levels were not significantly increased when associated with hypercalcemia, and an MTC metastasis to the prostate.

  12. In vivo and in vitro characterization of neonatal hyperparathyroidism resulting from a de novo, heterozygous mutation in the Ca2+-sensing receptor gene: normal maternal calcium homeostasis as a cause of secondary hyperparathyroidism in familial benign hypocalciuric hypercalcemia.

    PubMed Central

    Bai, M; Pearce, S H; Kifor, O; Trivedi, S; Stauffer, U G; Thakker, R V; Brown, E M; Steinmann, B

    1997-01-01

    We characterized the in vivo, cellular and molecular pathophysiology of a case of neonatal hyperparathyroidism (NHPT) resulting from a de novo, heterozygous missense mutation in the gene for the extracellular Ca2+ (Ca2+(o))-sensing receptor (CaR). The female neonate presented with moderately severe hypercalcemia, markedly undermineralized bones, and multiple metaphyseal fractures. Subtotal parathyroidectomy was performed at 6 wk; hypercalcemia recurred rapidly but the bone disease improved gradually with reversion to an asymptomatic state resembling familial benign hypocalciuric hypercalcemia (FBHH). Dispersed parathyroid cells from the resected tissue showed a set-point (the level of Ca2+(o) half maximally inhibiting PTH secretion) substantially higher than for normal human parathyroid cells (approximately 1.8 vs. approximately 1.0 mM, respectively); a similar increase in set-point was observed in vivo. The proband's CaR gene showed a missense mutation (R185Q) at codon 185, while her normocalcemic parents were homozygous for wild type (WT) CaR sequence. Transient expression of the mutant R185Q CaR in human embryonic kidney (HEK293) cells revealed a substantially attenuated Ca2+(o)-evoked accumulation of total inositol phosphates (IP), while cotransfection of normal and mutant receptors showed an EC50 (the level of Ca2+(o) eliciting a half-maximal increase in IPs) 37% higher than for WT CaR alone (6.3+/-0.4 vs. 4.6+/-0.3 mM Ca2+(o), respectively). Thus this de novo, heterozygous CaR mutation may exert a dominant negative action on the normal CaR, producing NHPT and more severe hypercalcemia than typically seen with FBHH. Moreover, normal maternal calcium homeostasis promoted additional secondary hyperparathyroidism in the fetus, contributing to the severity of the NHPT in this case with FBHH. PMID:9011580

  13. Recurrence of Hyperparathyroid Hypercalcemia in a Patient With the HRPT-2 Mutation and a Previous Parathyroid Carcinoma in Hyperparathyroidism-Jaw Tumor Syndrome

    PubMed Central

    Mele, Marco; Rolighed, Lars; Jespersen, MarieLouise; Rejnmark, Lars; Christiansen, Peer

    2016-01-01

    Introduction Cancer in the parathyroid gland is rare, but parathyroid cancer is occasionally seen in relation to genetic abnormalities. Due to a limited amount of evidence, the optimal handling of these cases is not clear. Furthermore, the presence of a malignant parathyroid tumor is rarely known at the time of the initial operation; therefore, re-operations are often necessary. The aim of this study was to present the case of a patient with a previously diagnosed jaw tumor and parathyroid carcinoma that presents as a recurrence of hyperparathyroid hypercalcemia. Case Presentation A 41-year-old patient who was already diagnosed with a parathyroid carcinoma and a jaw tumor caused by a CDC73 mutation, presented with biochemical evidence of increasing parathyroid hormone (PTH) and calcium levels after a previous total parathyroidectomy. The patient’s ionized calcium increased to 1.55 mmol/L and PTH increased to 16.0 pmol/L. A previous genetic analysis revealed a mutation in the CDC73 gene. There was no family history of hyperparathyroidism. We performed a sestamibi scintigraphy and an 11-C methionine (MET) positron emission tomography (PET) scan that showed a recurrence on the left side of the trachea. The patient underwent a third neck operation for the removal of a tumor on the left side of the trachea. The pathology report revealed that the tumor was a lymph node metastasis from the previous parathyroid carcinoma. The patient is currently enrolled in our follow-up regime. Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is a rare autosomal dominant disorder characterized by a parathyroid adenoma or carcinoma, fibro-osseous lesions (ossifying fibroma) of the mandible and maxilla, and renal cysts and tumors. This autosomal dominant familial cancer syndrome has been reported with a variable and incomplete penetrance, and up to 10% of gene carriers do not show any clinical manifestations. Here we present a patient’s case and discuss the literature related to this

  14. Markedly reduced activity of mutant calcium-sensing receptor with an inserted Alu element from a kindred with familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism.

    PubMed Central

    Bai, M; Janicic, N; Trivedi, S; Quinn, S J; Cole, D E; Brown, E M; Hendy, G N

    1997-01-01

    Missense mutations have been identified in the coding region of the extracellular calcium-sensing receptor (CASR) gene and cause human autosomal dominant hypo- and hypercalcemic disorders. The functional effects of several of these mutations have been characterized in either Xenopus laevis oocytes or in human embryonic kidney (HEK293) cells. All of the mutations that have been examined to date, however, cause single putative amino acid substitutions. In this report, we studied a mutant CASR with an Alu-repetitive element inserted at codon 876, which was identified in affected members of families with the hypercalcemic disorders, familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT), to understand how this insertion affects CASR function. After cloning of the Alu-repetitive element into the wild-type CASR cDNA, we transiently expressed the mutant receptor in HEK293 cells. Expression of mutant and wild-type receptors was assessed by Western analysis, and the effects of the mutation on extracellular calcium (Ca2+(o)) and gadolinium (Gd3+(o)) elicited increases in the cytosolic calcium concentration (Ca2+(i)) were examined in fura-2-loaded cells using dual wavelength fluorimetry. The insertion resulted in truncated receptor species that had molecular masses some 30 kD less than that of the wild-type CASR and exhibited no Ca2+(i) responses to either Ca2+(o) or Gd3+(o). A similar result was observed with a mutated CASR truncated at residue 876. However, the Alu mutant receptor had no impact on the function of the coexpressed wild-type receptor. Interestingly, the Alu mutant receptor demonstrated decreased cell surface expression relative to the wild-type receptor, whereas the CASR (A877stop) mutant exhibited increased cell surface expression. Thus, like the missense mutations that have been characterized to date in families with FHH, the Alu insertion in this family is a loss-of-function mutation that produces hypercalcemia by

  15. Identification of a cDNA encoding a parathyroid hormone-like peptide from a human tumor associated with humoral hypercalcemia of malignancy

    SciTech Connect

    Mangin, M.; Webb, A.C.; Dreyer, B.E.; Posillico, J.T.; Ikeda, K.; Weir, E.C.; Stewart, A.F.; Bander, N.H.; Milstone, L.; Barton, D.E.

    1988-01-01

    Humoral hypercalcemia of malignancy is a common paraneoplastic syndrome that appears to be mediated in many instances by a parathyroid hormone-like peptide. Poly(A)/sup +/ RNA from a human renal carcinoma associated with this syndrome was enriched by preparative electrophoresis and used to construct an enriched cDNA library in phage lambdagt10. The library was screened with a codon-preference oligonucleotide synthesized on the basis of a partial N-terminal amino acid sequence from a human tumor-derived peptide, and a 2.0 kilo-base cDNA was identified. The cDNA encodes a 177 amino acid protein consisting of a 36 amino acid leader sequence and a 141 amino acid mature peptide. The first 13 amino acids of the deduced sequence of the mature peptide display strong homology to human PTH, with complete divergence thereafter. RNA blot-hybridization analysis revealed multiple transcripts in mRNA from tumors associated with the humor syndrome and also in mRNA from normal human keratinocytes. Southern blot analysis of genomic DNA from humans and rodents revealed a simple pattern compatible with a single-copy gene. The gene has been mapped to chromosome 12.

  16. Extensive extraosseous localization of bone imaging agent in a patient with renal failure and rhabdomyolysis accompanied by combined hypercalcemia and hyperphosphatemia

    SciTech Connect

    Shih, W.J.; Flueck, J.; O'Connor, W.; Domstad, P.A.

    1989-03-01

    Four sequential Tc-99m pyrophosphate (PYP) imaging studies were performed in a 28-year-old man with high fever and exudate pharyngitis associated with renal failure. Radiotracer localization in the left ventricle (LV), lungs, kidneys, and skeletal muscles were seen in two, initial imaging studies. In the second and third imaging studies, area of increase in activity was seen in the left-sided bowel. In studies done two months later (in the third study), the radioactivity in the skeletal muscles was no longer seen. Studies obtained nine months (in the fourth study) after the first imaging showed less radiotracer localization in the LV, lungs, and kidneys as compared to that seen in the initial study. Myocardial necrosis and microcalcification were proved by LV biopsy. The exact mechanism of extraosseous bone-imaging agent localization is unknown. However, this phenomenon may be related to renal failure, rhabdomyolysis, hypercalcemia, hyperphosphatemia, or elevated parathyroid hormone. The Tc-99m PYP imaging study is useful and sensitive in the detection of extraosseous tissue calcification and monitoring of the disease process.

  17. A G‐protein Subunit‐α11 Loss‐of‐Function Mutation, Thr54Met, Causes Familial Hypocalciuric Hypercalcemia Type 2 (FHH2)

    PubMed Central

    Gorvin, Caroline M; Cranston, Treena; Hannan, Fadil M; Rust, Nigel; Qureshi, Asjid; Nesbit, M Andrew

    2016-01-01

    ABSTRACT Familial hypocalciuric hypercalcemia (FHH) is a genetically heterogeneous disorder with three variants, FHH1 to FHH3. FHH1 is caused by loss‐of‐function mutations of the calcium‐sensing receptor (CaSR), a G‐protein coupled receptor that predominantly signals via G‐protein subunit alpha‐11 (Gα11) to regulate calcium homeostasis. FHH2 is the result of loss‐of‐function mutations in Gα11, encoded by GNA11, and to date only two FHH2‐associated Gα11 missense mutations (Leu135Gln and Ile200del) have been reported. FHH3 is the result of loss‐of‐function mutations of the adaptor protein‐2 σ‐subunit (AP2σ), which plays a pivotal role in clathrin‐mediated endocytosis. We describe a 65‐year‐old woman who had hypercalcemia with normal circulating parathyroid hormone concentrations and hypocalciuria, features consistent with FHH, but she did not have CaSR and AP2σ mutations. Mutational analysis of the GNA11 gene was therefore undertaken, using leucocyte DNA, and this identified a novel heterozygous GNA11 mutation (c.161C>T; p.Thr54Met). The effect of the Gα11 variant was assessed by homology modeling of the related Gαq protein and by measuring the CaSR‐mediated intracellular calcium (Ca2+ i) responses of HEK293 cells, stably expressing CaSR, to alterations in extracellular calcium (Ca2+ o) using flow cytometry. Three‐dimensional modeling revealed the Thr54Met mutation to be located at the interface between the Gα11 helical and GTPase domains, and to likely impair GDP binding and interdomain interactions. Expression of wild‐type and the mutant Gα11 in HEK293 cells stably expressing CaSR demonstrate that the Ca2+ i responses after stimulation with Ca2+ o of the mutant Met54 Gα11 led to a rightward shift of the concentration‐response curve with a significantly (p < 0.01) increased mean half‐maximal concentration (EC50) value of 3.88 mM (95% confidence interval [CI] 3.76–4.01 mM), when compared with the wild

  18. A G-protein Subunit-α11 Loss-of-Function Mutation, Thr54Met, Causes Familial Hypocalciuric Hypercalcemia Type 2 (FHH2).

    PubMed

    Gorvin, Caroline M; Cranston, Treena; Hannan, Fadil M; Rust, Nigel; Qureshi, Asjid; Nesbit, M Andrew; Thakker, Rajesh V

    2016-06-01

    Familial hypocalciuric hypercalcemia (FHH) is a genetically heterogeneous disorder with three variants, FHH1 to FHH3. FHH1 is caused by loss-of-function mutations of the calcium-sensing receptor (CaSR), a G-protein coupled receptor that predominantly signals via G-protein subunit alpha-11 (Gα11 ) to regulate calcium homeostasis. FHH2 is the result of loss-of-function mutations in Gα11 , encoded by GNA11, and to date only two FHH2-associated Gα11 missense mutations (Leu135Gln and Ile200del) have been reported. FHH3 is the result of loss-of-function mutations of the adaptor protein-2 σ-subunit (AP2σ), which plays a pivotal role in clathrin-mediated endocytosis. We describe a 65-year-old woman who had hypercalcemia with normal circulating parathyroid hormone concentrations and hypocalciuria, features consistent with FHH, but she did not have CaSR and AP2σ mutations. Mutational analysis of the GNA11 gene was therefore undertaken, using leucocyte DNA, and this identified a novel heterozygous GNA11 mutation (c.161C>T; p.Thr54Met). The effect of the Gα11 variant was assessed by homology modeling of the related Gαq protein and by measuring the CaSR-mediated intracellular calcium (Ca(2+) i ) responses of HEK293 cells, stably expressing CaSR, to alterations in extracellular calcium (Ca(2+) o ) using flow cytometry. Three-dimensional modeling revealed the Thr54Met mutation to be located at the interface between the Gα11 helical and GTPase domains, and to likely impair GDP binding and interdomain interactions. Expression of wild-type and the mutant Gα11 in HEK293 cells stably expressing CaSR demonstrate that the Ca(2+) i responses after stimulation with Ca(2+) o of the mutant Met54 Gα11 led to a rightward shift of the concentration-response curve with a significantly (p < 0.01) increased mean half-maximal concentration (EC50 ) value of 3.88 mM (95% confidence interval [CI] 3.76-4.01 mM), when compared with the wild-type EC50 of 2.94 mM (95% CI 2.81-3.07

  19. Humoral hypercalcemia of malignancy: severe combined immunodeficient/beige mouse model of adult T-cell lymphoma independent of human T-cell lymphotropic virus type-1 tax expression.

    PubMed

    Richard, V; Lairmore, M D; Green, P L; Feuer, G; Erbe, R S; Albrecht, B; D'Souza, C; Keller, E T; Dai, J; Rosol, T J

    2001-06-01

    The majority of patients with adult T-cell leukemia/lymphoma (ATL) resulting from human T-cell lymphotropic virus type-1 (HTLV-1) infection develop humoral hypercalcemia of malignancy (HHM). We used an animal model using severe combined immunodeficient (SCID)/beige mice to study the pathogenesis of HHM. SCID/beige mice were inoculated intraperitoneally with a human ATL line (RV-ATL) and were euthanized 20 to 32 days after inoculation. SCID/beige mice with engrafted RV-ATL cells developed lymphoma in the mesentery, liver, thymus, lungs, and spleen. The lymphomas stained positively for human CD45RO surface receptor and normal mouse lymphocytes stained negatively confirming the human origin of the tumors. The ATL cells were immunohistochemically positive for parathyroid hormone-related protein (PTHrP). In addition, PTHrP mRNA was highly expressed in lymphomas when compared to MT-2 cells (HTLV-1-positive cell line). Mice with lymphoma developed severe hypercalcemia. Plasma PTHrP concentrations were markedly increased in mice with hypercalcemia, and correlated with the increase in plasma calcium concentrations. Bone densitometry and histomorphometry in lymphoma-bearing mice revealed significant bone loss because of a marked increase in osteoclastic bone resorption. RV-ATL cells contained 1.5 HTLV-1 proviral copies of the tax gene as determined by quantitative real-time polymerase chain reaction (PCR). However, tax expression was not detected by Western blot or reverse transcriptase (RT)-PCR in RV-ATL cells, which suggests that factors other than Tax are modulators of PTHrP gene expression. The SCID/beige mouse model mimics HHM as it occurs in ATL patients, and will be useful to investigate the regulation of PTHrP expression by ATL cells in vivo.

  20. Improved Screening Test for Idiopathic Infantile Hypercalcemia Confirms Residual Levels of Serum 24,25-(OH)2 D3 in Affected Patients.

    PubMed

    Kaufmann, Martin; Morse, Nicole; Molloy, Billy Joe; Cooper, Donald P; Schlingmann, Karl Peter; Molin, Arnaud; Kottler, Marie Laure; Gallagher, J Christopher; Armas, Laura; Jones, Glenville

    2017-07-01

    CYP24A1 mutations are now accepted as a cause of idiopathic infantile hypercalcemia (IIH). A rapid liquid-chromatography tandem mass spectrometry (LC-MS/MS)-based blood test enabling measurement of the 25-OH-D3 :24,25-(OH)2 D3 ratio (R) can identify IIH patients on the basis of reduced C24-hydroxylation of 25-OH-D3 by CYP24A1 in vivo. Although values of this ratio are significantly elevated in IIH, somewhat surprisingly, serum 24,25-(OH)2 D3 remains detectable. The current study explores possible explanations for this including: residual CYP24A1 enzyme activity in individuals with certain CYP24A1 genotypes, expression of alternative C24-hydroxylases, and the possibility of isobaric contamination of the 24,25-(OH)2 D3 peak on LC-MS/MS. We employed an extended 20-min run time on LC-MS/MS to study serum vitamin D metabolites in patients with IIH due to mutations of CYP24A1 or SLC34A1; in unaffected heterozygotes and dialysis patients; in patients with vitamin D deficiency; as well as in normal subjects exhibiting a broad range of 25-OH-D levels. We identified 25,26-(OH)2 D3 as a contaminant of the 24,25-(OH)2 D3 peak. In normals, the concentration of 24,25-(OH)2 D3 greatly exceeds 25,26-(OH)2 D3 ; however, 25,26-(OH)2 D3 becomes more significant in IIH with CYP24A1 mutations and in dialysis patients, where 24,25-(OH)2 D3 levels are low when CYP24A1 function is compromised. Mean R in 30 IIH-CYP24A1 patients was 700 (range, 166 to 2168; cutoff = 140) as compared with 31 in 163 controls. Furthermore, patients possessing CYP24A1 L409S alleles exhibited higher 24,25-(OH)2 D3 levels and lower R (mean R = 268; n = 8) than patients with other mutations. We conclude that a chromatographic approach which resolves 24,25-(OH)2 D3 from 25,26-(OH)2 D3 produces a more accurate R that can be used to differentiate pathological states where CYP24A1 activity is altered. The origin of the residual serum 24,25-(OH)2 D3 in IIH patients appears to be multifactorial. © 2017

  1. [Hypercalcemia caused by generalized sarcoidosis].

    PubMed

    Hierl, T; Libicher, M; Nawroth, P; Ziegler, R; Kasperk, C

    2000-12-08

    A 70-year-old man with a 23-year history of recurrent nephrolithiasis was admitted for evaluation of hypercalcaemia (maximal calcium concentration 3.24 mmol/l). Physical examination on admission was unremarkable except for sensory neuropathy in the right foot. Chest radiogram, subsequent transbronchial lung biopsy, gallium scintigraphy and magnetic resonance imaging (MRI) of the vertebrae indicated generalized sarcoidosis, predominantly affecting the mediastinum, lumbar vertebrae and nerves of the distal limbs. Parathormone level was reduced, while the levels of vitamin D metabolites were normal. Serum calcium level became normal within 2 weeks of starting glucocorticoid treatment. Hypercalcaemia can occur in the course of sarcoidosis even in the absence of a elderly increased level of 1,25-dihydroxyvitamin D3. In this case the cause of the hypercalcaemia of a year's duration may have been due to lymphomacrophagocytic infiltration of the bone of several vertebrae as demonstrated by MRI of the vertebral columns but not by conventional radiography. In this case an increase in cytokine secretion by macrophages may have played an important role in addition to the level of 1,25-dihydroxyvitamin D3 at the upper limit of normal that, in view of the renal failure, could only have been caused by extrarenal production. Cytokines (e.g. interleukin-1 beta and tumour necrosis factor alpha) secreted by activated macrophages are among the most powerful stimulators of bone reabsorption.

  2. A novel vitamin D3 analog, 22-oxa-1,25-dihydroxyvitamin D3, inhibits the growth of human breast cancer in vitro and in vivo without causing hypercalcemia.

    PubMed

    Abe, J; Nakano, T; Nishii, Y; Matsumoto, T; Ogata, E; Ikeda, K

    1991-08-01

    Although 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] has been shown to inhibit the growth of certain malignant cells, its hypercalcemic effect has prevented clinical application. We have recently developed a novel vitamin D3 analog, 22-oxa-1,25-(OH)2D3 (OCT), that is capable of promoting differentiation and inhibiting proliferation without inducing hypercalcemia. The present study was undertaken to determine whether OCT could be applied for the treatment of breast cancer with or without estrogen receptor (ER). OCT inhibited the proliferation of both ER-positive (MCF-7, T-47D, and ZR-75-1) and ER-negative breast cancer cells (MDA-MB-231 and BT-20) in vitro in a time- and dose-dependent manner, as determined by cell number and [3H]thymidine uptake. The antiproliferative effect was observed with a concentration as low as 10(-11) M OCT, and treatment of MCF-7 cells with 10(-8) M OCT for 8 days caused more than a 50% reduction in cell number compared with that of vehicle-treated cells. OCT was approximately 1 order of magnitude more potent than 1,25-(OH)2D3 in inhibiting the proliferation of MCF-7 cells. The in vivo effect of OCT was examined in athymic mice implanted with ER-negative MX-1 tumor, which was established as the xenograft derived from human breast carcinoma. Intratumor administration of OCT three times a week remarkably delayed the growth of MX-1 tumor in a time- and dose-dependent manner. The antitumor effect of 1 microgram/kg BW OCT was greater than that of 500 microgram/kg BW adriamycin, and the relative tumor weights in each group on day 26 were 29.7% and 50.5% of that in the vehicle-treated group, respectively. The effects of OCT and adriamycin were additive, and the relative tumor weight after 26 days of combined treatment was 21.7% of that in the vehicle-treated group. Oral administration of OCT was also effective, and the relative tumor weight in the OCT-treated group (1 microgram/kg BW) was 54.6 +/- 0.1% (mean +/- SEM) of that in the vehicle

  3. Metabolic Bone Disease in the Context of Metastatic Neuroendocrine Tumor: Differentiation from Skeletal Metastasis, the Molecular PET–CT Imaging Features, and Exploring the Possible Etiopathologies Including Parathyroid Adenoma (MEN1) and Paraneoplastic Humoral Hypercalcemia of Malignancy Due to PTHrP Hypersecretion

    PubMed Central

    Ranade, Rohit; Basu, Sandip

    2017-01-01

    Three cases of metabolic bone disease in the setting of metastatic neuroendocrine tumor (NET) are illustrated with associated etiopathologies.  One of these cases harbored mixed lesions in the form of vertebral metastasis (biopsy proven) while the other skeletal lesions were caused due to metabolic bone disease related to multiple parathyroid adenomas. While the metastatic lesion was positive on 68Ga-DOTATATE positron emission tomography-computed tomography (PET-CT), the lesions of metabolic bone disease were negative and the 18F-fluoride PET-CT demonstrated the features of metabolic bone scan. Similar picture of metabolic bone disease [18-sodium fluoride (18NaF)/68Ga-DOTATATE mismatch] was documented in the other two patients, while fluorodeoxyglucose (FDG)-PET-CT was variably positive, primarily showing tracer uptake in the metabolic skeletal lesions of the patient with hypersecretion of parathyroid hormone-related protein (PTHrP) by the underlying tumor. Discordance between 18NaF PET-CT and 68Ga-DOTATATE PET-CT serves as a good marker for identification of metabolic bone disease and diagnosing such a clinical entity. In a patient of NET with metabolic bone disease and hypercalcemia, thus, two causes need to be considered: (i) Coexisting parathyroid adenoma in multiple endocrine neoplasia type I (MEN-I) syndrome and (ii) humoral hypercalcemia of malignancy (HHM) related to hypersecretion of PTHrP by the tumor. The correct diagnosis of metabolic bone disease in metastatic NET can alter the management substantially. Interestingly, peptide receptor radionuclide therapy (PRRT) can emerge as a very promising treatment modality in patients of metabolic bone disease caused by HHM in the setting of NET. PMID:28217023

  4. TRPV4 mutations and cytotoxic hypercalcemia in axonal Charcot-Marie-Tooth neuropathies

    PubMed Central

    Shi, Y.; Fecto, F.; Donaghy, M.; Nicholson, G.; McEntagart, M.E.; Crosby, A.H.; Wu, Y.; Lou, H.; McEvoy, K.M.; Siddique, T.; Dyck, P.J.

    2011-01-01

    Objective: To improve understanding of TRPV4-associated axonal Charcot-Marie-Tooth (CMT) neuropathy phenotypes and their debated pathologic mechanism. Methods: A total of 17 CMT2C phenotypic families with vocal cord and diaphragmatic involvement and 36 clinically undifferentiated CMT2 subjects underwent sequencing analysis of the coding region of TRPV4. Functional studies of mutant proteins were performed using transiently transfected cells for TRPV4 subcellular localization, basal and stimulated Ca2+ channel analysis, and cell viability assay with or without channel blockade. Results: Two TRPV4 mutations R232C and R316H from 17 CMT2C families were identified in the ankyrin repeat domains. The R316H is a novel de novo mutation found in a patient with CMT2C phenotype. The family with R232C mutation had individuals with and without vocal cord and diaphragm involvement. Both mutant TRPV4 proteins had normal subcellular localization in HEK293 and HeLa cells. Cells transfected with R232C and R316H displayed increased intracellular Ca2+ levels and reversible cell death by the TRPV channel antagonist, ruthenium red. Conclusion: TRPV4 ankyrin domain alterations including a novel de novo mutation cause axonal CMT2. Individuals with the same mutation may have nondistinct CMT2 or have phenotypic CMT2C with vocal cord paresis. Reversible hypercalcemic gain-of-function of mutant TRPV4 instead of loss-of-function appears to be pathologically important. The reversibility of cell death by channel blockade provides an attractive area of investigation in consideration of treatable axonal degeneration. PMID:21288981

  5. [Treatment of multiple myeloma with intravenous pamidronate. Pain prevention and suppression of hypercalcemia risk].

    PubMed

    Díaz, Carlos; Soutelo, María J; Quiroga, Luis; Palmer, Luis; Lutfi, Rubén

    2004-01-01

    In a prospective clinical study, with the patient as its own control, we selected patients with stage III multiple myeloma. We treated them monthly with intravenous (i.v.) Disodic Pamidronate: 90 mg in 2 to 21 cycles. Four patients died during the study. The remaining 13 patients presented reduced bone resorption urinary markers (D-Pyr mainly) as well as urinary calcium (bone turnover reduction). Both effects (metabolic interchange reduction and calcium variation) did not show a direct relationship, being the 1st magnitude proportional to the baseline level and the 2nd independent from it. We noted pain reduction (VAS: visual analogs scale), low analgesic consumption, and the absence of future skeletal problems. The treatment tolerance was good. All these factors contribute to justify the welfare of the patient demonstrated by ECOG (Eastern Cooperative Oncology Group), not only improving the average results but also extending this improvement to future results. Our observation suggests that under strict procedures, this treatment could be very adequate in patients with advanced multiple myeloma independent of the state of the disease at the beginning of the study.

  6. Quantitative and three-dimensional aspects of the rat parathyroid gland in normo-, hypo-, and hypercalcemia.

    PubMed

    Wernerson, A; Svensson, O; Reinholt, F P

    1995-10-01

    The ultrastructure of the rat parathyroid has been under study for more than 35 years, but controversies still exist, especially regarding structure-function relationships. The present review focuses on recent morphological parathyroid research on rats under normal conditions and in various states of disturbed calcium metabolism. To facilitate discussions on functional aspects, current biochemical data, particularly those dealing with the regulation of parathyroid hormone synthesis and release, are also considered. Our results from quantitative studies and from investigations employing serial sectioning form the basis for the discussions. A central issue is whether the parathyroid secretory cells undergo secretory cycles. Prompted by results obtained from improved fixation procedures and serial sectioning, we question the basis for the theory of secretory cycles. Since the rat parathyroid secretory cell is polar, a single section is not an appropriate sample for estimating functional activity and for comparing the structure and distribution of intracellular components of adjacent cells. The heterogeneity in ultrastructural appearance of intracellular vesicles calls for the use of specific markers in relating the structure of the vesicular compartment to intracellular processing of hormone. The importance of unbiased quantitative techniques is illustrated in discussions on cell number and size for estimating the response of the parathyroid gland to different functional states or disorders demanding changes in secretion of parathyroid hormone, e.g., hyper- and hypocalcemia.

  7. Regulation of parathyroid hormone gene expression by hypocalcemia, hypercalcemia, and vitamin D in the rat.

    PubMed Central

    Naveh-Many, T; Silver, J

    1990-01-01

    In vivo in the rat 1,25(OH)2D3 decreases and a low calcium increases PTH mRNA levels. We now report the effect of 3 and 8 wk of changes in dietary vitamin D and calcium on PTH mRNA levels. PTH mRNA levels were increased by 3 wk of calcium deficiency (five times), a vitamin D-deficient diet (two times), and combined deficiency (10 times), but not changed by high calcium. Vitamin D-deficient-diet rats' PTH mRNA did not decrease after a single large dose of 1,25(OH)2D3, but did decrease partially after repeated daily doses of 1,25(OH)2D3. Rats after a vitamin D-, calcium-deficient (-D-Ca) diet did not respond to changes in serum calcium at 1 h. Flow cytometry of isolated cells from parathyroid-thyroid tissue separated the smaller parathyroid from the larger thyroid cells and allowed an analysis of parathyroid cell number. In normal vitamin D/normal calcium (NDNCa) rats the parathyroid cells were 24.7 +/- 3.4% (n = 6) of the total cell number, whereas in -D-Ca rats they were 41.8 +/- 6.6% (n = 6) (P less than 0.05). That is, -D-Ca rats had 1.7 times the number of cells, whereas they had 10 times the amount of PTH mRNA, indicating the major contribution (6 times) of increased PTH gene expression per cell. Moreover, a calcium-deficient, more so than a vitamin D-deficient diet, amplifies the expression of the PTH gene, and vitamin D is necessary for an intact response of PTH mRNA to 1,25(OH)2D3 or calcium. Images PMID:2212016

  8. Cinacalcet HCl Reduces Hypercalcemia in Primary Hyperparathyroidism across a Wide Spectrum of Disease Severity

    PubMed Central

    Peacock, Munro; Bilezikian, J. P.; Bolognese, M. A.; Borofsky, Michael; Scumpia, Simona; Sterling, L. R.; Cheng, Sunfa; Shoback, Dolores

    2011-01-01

    Context: Primary hyperparathyroidism (PHPT) is characterized by elevated serum calcium (Ca) and increased PTH concentrations. Objective: The objective of the investigation was to establish the efficacy of cinacalcet in reducing serum Ca in patients with PHPT across a wide spectrum of disease severity. Design and Setting: The study was a pooled analysis of data from three multicenter clinical trials of cinacalcet in PHPT. Patients : Patients were grouped into three disease categories for analysis based on the following: 1) history of failed parathyroidectomy (n = 29); 2) meeting one or more criteria for parathyroidectomy but without prior surgery (n = 37); and 3) mild asymptomatic PHPT without meeting criteria for either above category (n = 15). Intervention: The intervention in this study was treatment with cinacalcet for up to 4.5 yr. Outcomes: Measurements in the study included serum Ca, PTH, phosphate, and bone-specific alkaline phosphatase, and areal bone mineral density (aBMD). Vital signs, safety biochemical and hematological indices, and adverse events were monitored throughout the study period. Results: The extent of cinacalcet-induced serum Ca reduction, proportion of patients achieving normal serum Ca (≤10.3 mg/dl), reduction in serum PTH, and increase in serum phosphate were similar across all three categories. Except for decreased aBMD at the total femur indicated for parathyroidectomy group at 1 yr, no significant changes in aBMD occurred. The efficacy of cinacalcet was maintained for up to 4.5 yr of follow-up. AEs were mild and similar across the three categories. Conclusions: Cinacalcet is equally effective in the medical management of PHPT patients across a broad spectrum of disease severity, and overall cinacalcet is well tolerated. PMID:20943783

  9. Factors predicting the acute effect of pamidronate on serum calcium in hypercalcemia of malignancy.

    PubMed

    Gallacher, S J; Fraser, W D; Logue, F C; Dryburgh, F J; Cowan, R A; Boyle, I T; Ralston, S H

    1992-12-01

    In this study we retrospectively reviewed results of the first 9 days of treatment with pamidronate at doses of 30 mg (n = 13), 45 mg (n = 9), and 90 mg (n = 13) in an attempt to see what factors influenced the response of serum calcium to pamidronate. The nadir of serum calcium obtained post treatment was correlated with pretreatment levels of nephrogenous cyclic adenosine monophosphate (NcAMP), the renal tubular threshold for phosphate reabsorption (TmPO4), and the renal tubular threshold for calcium reabsorption (TmCa). Using the post treatment serum calcium levels, patients were divided into "good" and "poor" responders depending on whether a normal serum calcium was obtained. Pretreatment NcAMP was significantly correlated with the magnitude of the response of serum calcium (r = 0.45, P = 0.0001). Pretreatment NcAMP was significantly higher in the poor responders (mean +/- SEM): 65.0 +/- 9.4 nmol/liter GF (poor responders) versus 29.6 +/- 6.3 (good responders), P = 0.004. NcAMP as a predictor of the acute response of serum calcium showed a sensitivity of 93% and a specificity of 72%. Pretreatment TmPO4 was negatively correlated with the serum calcium response post treatment (r = -0.41, P = 0.003). However, though TmPO4 tended to be lower in the poor responders, this was not statistically significant [0.65 mmol/liter GF +/- 0.09 (poor responders) versus 0.76 mmol/liter GF +/- 0.06 (good responders)]. As a predictor of the acute response of serum calcium, TmPO4 was less good with a sensitivity of 70% and specificity of 58%. No significant correlation was present between TmCa and the serum calcium response.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Prostaglandin receptor EP2 mediates PGE2 stimulated hypercalcemia in mice in vivo.

    PubMed

    Li, Xiaodong; Tomita, Masato; Pilbeam, Carol C; Breyer, Richard M; Raisz, Lawrence G

    2002-04-01

    Prostaglandin E2 (PGE2) can stimulate bone resorption by a cyclic AMP-dependent pathway. Two PGE2 receptors, EP2 and EP4 have been shown to play a role in PGE2 stimulation of osteoclast formation. In primary osteoblastic cell cultures from EP2 wild type (EP2 +/+) mice, PGE2 (0.1 microM) increased cyclic AMP production 3.5-fold, but PGE2 had no effect on cells from mice in which the EP2 receptor had been deleted (EP2 -/-). To examine the role of the EP2 receptor in the resorption response in vivo we injected PGE2 in EP2 -/- mice, and compared them with EP2 +/+ mice. Injection of PGE2 (3 mg/kg, four times daily for three days) in 9- to 12-month-old male mice on a 129 SvEv background increased serum calcium from 9.8 +/- 0.5 to 10.7 +/- 0.3 mg/dl (P < 0.01) in EP2 +/+ mice but not in EP2 -/- mice (10.1 +/- 0.3 vs. 10.2 +/- 0.3 mg/dl). PGE2 injection (6 mg/kg twice a day for three days) in 3-4 month old male mice on a C57 BL/6 X 129 SvEv background increased calcium from 8.2 +/- 0.1 to 9.0 +/- 0.3 mg/dl (P < 0.05) in EP2 +/+ mice but had no effect in EP2-/- mice (8.4 +/- 0.1 vs. 8.3 +/- 0.2 mg/dl). Injection of PGE2 over the calvariae of EP2 +/+ and EP2-/- mice increased the expression of receptor activator of nuclear factor kappaB ligand (RANKL) both locally and in the tibia, but RANKL responses were lower in EP2 -/- mice. We conclude that EP2 receptor plays a role in the hypercalcemic response to PGE2. This impaired response in EP2 -/- mice may be due to decreased ability to stimulate cyclic AMP and in part, to a smaller increase in the expression of RANKL mRNA.

  11. Mineralization defect but no effect on hypercalcemia during clodronate treatment in secondary hyperparathyroidism.

    PubMed

    Ring, T; Sodemann, B; Nielsen, C; Melsen, F; Kornerup, H J

    1995-09-01

    In four patients with severe secondary hyperparathyroidism, treatment with clodronate caused no decrease in serum calcium. In one of the patients treatment for seven months was associated with a severe mineralization defect which was not caused by aluminium. This lesion was reversible upon termination of clodronate treatment. In a single patient without hyperparathyroidism, a precipitous decrease in serum calcium was observed due to clodronate. However, long-term treatment with clodronate did not ameliorate ectopic calcification in this patient. It is concluded that in severe secondary hyperparathyroidism, clodronate does not always decrease serum calcium. Our experience suggest that clodronate like other bisphosphonates may inhibit bone mineralization.

  12. Hypercalcemia and calcinosis in Florida horses: implication of the shrub, Cestrum diurnum, as the causative agent.

    PubMed

    Krook, L; Wasserman, R H; Shively, J N; Tashjian, A H; Brokken, T D; Morton, J F

    1975-01-01

    A chronic debilitating disease is described in Florida horses. There is progress weight loss and lameness of increasing severity. Plasma calcium is elevated to moderate or severe degree. Anatomical changes include dystrophic calcinosis of elastic tissues, viz. major arteries, tendons and ligaments. A generalized osteopetrosis is present and may be related to hypoparathyroidsim and hypercalcitoninism. The presence of Cestrum diurnum (day-blooming jessamine, day cestrum, wild jasmin) in areas accessible to affected animals, the observation that leaves of the plant were stripped in these areas, and the finding of a potent, active vitamin D-like substance in this plant constitute strong evidence that Cestrum diurnum is the agent causing the abnormalities of mineral metabolism.

  13. Cinacalcet hydrochloride in combination with alendronate normalizes hypercalcemia and improves bone mineral density in patients with primary hyperparathyroidism.

    PubMed

    Faggiano, A; Di Somma, C; Ramundo, V; Severino, R; Vuolo, L; Coppola, A; Panico, F; Savastano, S; Lombardi, G; Colao, A; Gasperi, M

    2011-06-01

    Cinacalcet is effective in controlling the biochemical abnormalities in patients with primary hyperparathyroidism (PHPT) but it seems to be less effective on bone mineral density (BMD). In the same patients, bisphosphonates are reported to be effective on bone resorption but less effective on calcium and PTH excess. In this study, the efficacy of cinacalcet in combination with alendronate has been retrospectively evaluated in patients with PHPT. Twenty-three patients with PHPT who had not been operated were retrospectively investigated. Cinacalcet was evaluated in combination with alendronate in 10 of the 23 patients, and in monotherapy in 13 other patients. Serum calcium, phosphorus and PTH, 24 h urine calcium and phosphorus as well as BMD, evaluated by DXA and expressed as T-score, were measured before and after treatment. In all patients serum calcium and phosphorus and urinary calcium excretion were effectively and stably controlled and PTH was significantly decreased after treatment. There was no difference in the rate of serum calcium and PTH decrease between subjects treated with cinacalcet plus alendronate and those treated with cinacalcet alone. T-score increased by 9.6% at lumbar spine and 3.9% at femur level in the cinacalcet plus alendronate subgroup and was unchanged in the cinacalcet subgroup (P < 0.01). In patients with PHPT, the biochemical abnormalities are rapidly improved by cinacalcet regardless from the administration in monotherapy or in combination with alendronate. BMD is significantly improved in patients receiving cinacalcet plus alendronate and stable in those receiving cinacalcet in monotherapy.

  14. Two squamous cell carcinomas not associated with humoral hypercalcemia produce a potent bone resorption-stimulating factor which is interleukin-1 alpha.

    PubMed

    Fried, R M; Voelkel, E F; Rice, R H; Levine, L; Gaffney, E V; Tashjian, A H

    1989-08-01

    Conditioned medium (CM) from two squamous cell carcinoma cell lines, SCC-9 and SCC-13, stimulated bone resorption in neonatal mouse calvariae in organ culture. Enhanced bone resorption induced by CM was associated with an increased production of prostaglandin-E2 (PGE2) by the calvariae. Complete inhibition of stimulated PGE2 synthesis by indomethacin only partially inhibited bone resorption-stimulating activity (BRSA) in the CM. Neither SCC-9 nor SCC-13 CM stimulated cAMP production in rat osteosarcoma cells (ROS 17/2.8). The BRSA in CM was completely inhibited by an antibody to interleukin-1 alpha (IL-1 alpha). Fractionation of SCC-9 CM by gel filtration and HPLC ion exchange chromatography revealed a single peak of BRSA and PGE2 synthesis-stimulating activity at 17-20K (termed SCMII). In mouse calvariae, SCMII increased medium Ca2+ and PGE2 in a dose-dependent manner at concentrations from 20 ng protein/ml to a maximum of 500 ng protein/ml. Preincubation of SCMII with antibody to IL-1 alpha completely inhibited SCMII-induced bone resorption. SCMII also enhanced thymocyte proliferation with activity that was equivalent to 353 U/ml IL-1. Antibodies to IL-1 beta and tumor necrosis factor had no effect on SCMII-induced bone resorption. Using specific enzyme-linked immunosorbent assays for IL-1 alpha and IL-1 beta, IL-1 alpha was measured in high concentrations in both crude and partially purified fractions of SCC-9 and SCC-13 CM. In contrast, IL-1 beta was either undetectable or present in amounts below those that stimulate bone resorption. In addition, SCMII did not enhance cAMP production in bone cells. We conclude that the BRSA produced by the two squamous cell carcinoma cell lines SCC-9 and SCC-13 is IL-1 alpha.

  15. End Stage Renal Disease-induced Hypercalcemia May Promote Aortic Valve Calcification via Annexin VI Enrichment of Valve Interstitial Cell Derived-Matrix Vesicles.

    PubMed

    Cui, Lin; Rashdan, Nabil A; Zhu, Dongxing; Milne, Elspeth; Ajuh, Paul; Milne, Gillian; Helfrich, Miep; Lim, Kelvin; Prasad, Sai; Lerman, Daniel; Vesey, Alex; Dweck, Marc; Jenkins, W S; Newby, David; Farquharson, Colin; Macrae, Vicky E

    2017-03-30

    Patients with end-stage renal disease (ESRD) have elevated circulating calcium (Ca) and phosphate (Pi), and exhibit accelerated progression of calcific aortic valve disease (CAVD). We hypothesised that matrix vesicles (MVs) initiate the calcification process in CAVD. Ca induced rat valve interstitial cells (VICs) calcification at 4.5 mM (16.4 fold; P < 0.05) whereas Pi treatment alone had no effect. Ca (2.7 mM) and Pi (2.5 mM) synergistically induced calcium deposition (10.8 fold; P < 0.001) in VICs. Ca treatment increased the mRNA of the osteogenic markers Msx2, Runx2 and Alpl (P < 0.01). MVs were harvested by ultracentrifugation from VICs cultured with control or calcification media (containing 2.7 mM Ca and 2.5 mM Pi) for 16 h. Proteomics analysis revealed the marked enrichment of exosomal proteins, including CD9, CD63, LAMP-1 and LAMP-2 and a concomitant up-regulation of the Annexin family of calcium-binding proteins. Of particular note Annexin VI was shown to be enriched in calcifying VIC-derived MVs (51.9 fold; P < 0.05). Through bioinformatic analysis using Ingenuity Pathway Analysis (IPA), the up-regulation of canonical signalling pathways relevant to cardiovascular function were identified in calcifying VIC-derived MVs, including aldosterone, Rho kinase and metal binding. Further studies using human calcified valve tissue revealed the co-localisation of Annexin VI with areas of MVs in the extracellular matrix by transmission electron microscopy (TEM). Together these findings highlight a critical role for VIC-derived MVs in CAVD. Furthermore, we identify calcium as a key driver of aortic valve calcification, which may directly underpin the increased susceptibility of ESRD patients to accelerated development of CAVD. This article is protected by copyright. All rights reserved.

  16. [Severe hypercalcemia as a complication of intensive treatment for osteoporosis due to steroid therpay in 17-year-old girl with the nephrotic syndrome].

    PubMed

    Ksiazek, Ewelina; Majewski, Marek; Borzecka, Halina; Sikora, Przemysław; Bieniaś, Beata; Zajaczkowska, Małgorzata

    2008-01-01

    In the article, 17-year-old girl with iatrogenic severe hipercalcemia was presented. The girl was treated since the age of 12 years for steroid-sensitive minimal change disease. Due to steroid therapy osteoporosis developed and intensive treatment with active form of vitamin D and high doses of calcium was started. She was admitted to our clinic in severe general state with abdominal pain, vomiting, dehydration, muscle weakness, hypertension and mental confusion. Severe hipercalcemia with nephrocalcinosis was diagnosed. The history revealed that the girl had increased the doses of drugs intentionally. The authors emphasized the need for careful monitoring of prophylaxis and treatment for osteoporosis due to steroid therapy.

  17. Explanation in Expert Systemss: A Survey

    DTIC Science & Technology

    1988-12-01

    HYPERPARATHYROIDISM CAUSE RENAL STONES? Renal stones are caused by hypercalcemia Hypercalcemia is caused by hyperparathyroidism ** EXPERTISE 6 ** HOW...DOES HYPERPARATHYROIDISM CAUSE RENAL STONES? Renal stones are caused by increased urinary calcium Increased urinaxy calcium is caused by hypercalcemia... hyperparathyroidism Figure 20: Explanations Tailored to Level of Expertise 5.2.3 Tailoring to User’s Level of Expertise Another consideration to be

  18. Nonconvulsive Status Epilepticus in Elderly Patients Receiving SSRIs; Euglycemic Diabetic Ketoacidosis Associated with Canagliflozin Use in a Type 1 Diabetic Patient; Duloxetine-Induced Galactorrhea; Canagliflozin-Associated Severe Hypercalcemia and Hypernatremia; Vemurafenib-Induced Fanconi Syndrome

    PubMed Central

    Mancano, Michael A.

    2015-01-01

    The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration’s (FDA’s) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA’s MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner. PMID:26912914

  19. Hypercalcemic Disorders in Children.

    PubMed

    Stokes, Victoria J; Nielsen, Morten F; Hannan, Fadil M; Thakker, Rajesh V

    2017-09-15

    Hypercalcemia is defined as a serum calcium concentration that is greater than 2 standard deviations above the normal mean, which in children may vary with age and sex, reflecting changes in the normal physiology at each developmental stage. Hypercalcemic disorders in children may present with hypotonia, poor feeding, vomiting, constipation, abdominal pain, lethargy, polyuria, dehydration, failure to thrive and seizures. In severe cases renal failure, pancreatitis and reduced consciousness may also occur and older children and adolescents may present with psychiatric symptoms. The causes of hypercalcemia in children can be classified as parathyroid hormone (PTH)-dependent or PTH-independent, and may be congenital or acquired. PTH-independent hypercalcemia, i.e. hypercalcemia associated with a suppressed PTH, is commoner in children than PTH-dependent hypercalcemia. Acquired causes of PTH-independent hypercalcemia in children include hypervitaminosis; granulomatous disorders and endocrinopathies. Congenital syndromes associated with PTH-independent hypercalcemia include idiopathic infantile hypercalcemia (IIH); William's syndrome; and inborn errors of metabolism. PTH-dependent hypercalcemia is usually caused by parathyroid tumors, which may give rise to primary hyperparathyroidism (PHPT) or tertiary hyperparathyroidism, which usually arises in association with chronic renal failure and in the treatment of hypophosphatemic rickets. Acquired causes of PTH-dependent hypercalcemia in neonates include maternal hypocalcemia and extra-corporeal membrane oxygenation. PHPT usually occurs as an isolated non-syndromic and non-hereditary endocrinopathy, but may also occur as a hereditary hypercalcemic disorder such as familial hypocalciuric hypercalcemia, neonatal severe primary hyperparathyroidism, and familial isolated primary hyperparathyroidism, and less commonly, as part of inherited complex syndromic disorders such as multiple endocrine neoplasia (MEN). Advances in

  20. A Case of Solitary Kidney Atrophy Due to Primary Hyperparathyroidism

    PubMed Central

    Lin, Yu-Ting; Jiang, Jiunn-Song; Fang, Yu-Wei; Tsai, Ming-Hsien

    2016-01-01

    Abstract Although primary hyperparathyroidism (PHPT) is asymptomatic in most patients, its main clinical manifestation is nephrolithiasis. In general, hypercalcemia would lead to unilateral renal stones, which may become bilateral over time. We present a rare case of a large unilateral asymptomatic ureteral stone in a patient with hypercalcemia secondary to PHPT, which eventually led to renal atrophy. The diagnosis of PHPT should be considered in patients with hypercalcemia and renal stones, as asymptomatic PHPT may result in a devastating renal outcome. PMID:26765435

  1. A Case of Solitary Kidney Atrophy Due to Primary Hyperparathyroidism: A Case Report.

    PubMed

    Lin, Yu-Ting; Jiang, Jiunn-Song; Fang, Yu-Wei; Tsai, Ming-Hsien

    2016-01-01

    Although primary hyperparathyroidism (PHPT) is asymptomatic in most patients, its main clinical manifestation is nephrolithiasis. In general, hypercalcemia would lead to unilateral renal stones, which may become bilateral over time. We present a rare case of a large unilateral asymptomatic ureteral stone in a patient with hypercalcemia secondary to PHPT, which eventually led to renal atrophy.The diagnosis of PHPT should be considered in patients with hypercalcemia and renal stones, as asymptomatic PHPT may result in a devastating renal outcome.

  2. [SCREENING OF PRIMARY HYPERPARATHYROIDISM IN PATIENTS WITH UROLITHIASIS].

    PubMed

    Rogozin, D S; Sergiyko, S V; Rogozina, A A

    2015-01-01

    The aim of research was to study the rate of hypercalcemia and primary hyperparathyroidism among patients with uroli- thiasis. The investigation included 645 patients with urolithiasis. Patients were divided into 2 groups: with normocalcemia and hypercalcemia. The rate of hypercalcemia consisted of 18,9% among patients with urolithiasis. This frequency was 10-20 times higher than in a similar rate of general population. There were no significant differences in age, sex, history of urolithiasis and stone localization between two groups. The data obtained showed an importance of screening of hypercalcemia in patients with urolithiasis regardless the severity of clinical course.

  3. PubMed Central

    Bergeron, R.; Martin, N.; Moreau, A.

    1995-01-01

    The most frequent, potentially fatal, metabolic complication in cancer patients is hypercalcemia. After a discussion of cancer-associated hypercalcemia, we propose an individualized intervention model based on an analysis of the clinical situation, the prognosis, and available treatment options. PMID:7773028

  4. Functional metastatic parathyroid adenocarcinoma in a dog

    PubMed Central

    Kishi, Erin N.; Holmes, Shannon P.; Abbott, Jeffrey R.; Bacon, Nicholas J.

    2014-01-01

    A 12-year-old dachshund dog was presented for persistent hypercalcemia and hyperparathyroidism despite bilateral parathyroidectomy. Magnetic resonance imaging of the head, neck, and cranial mediastinum identified an increased number of cranial mediastinal lymph nodes with heterogeneous signal intensity. Hypercalcemia and hyperparathyroidism resolved after surgery to remove multiple cranial mediastinal lymph nodes, one of which contained presumed metastatic parathyroid tissue. PMID:24688141

  5. Vitamin D Toxicity in Adults: A Case Series from an Area with Endemic Hypovitaminosis D

    PubMed Central

    Koul, Parvaiz A.; Ahmad, Sheikh Hilal; Ahmad, Feroze; Jan, Rafi A.; Shah, S.U.; Khan, Umar H.

    2011-01-01

    Vitamin D deficiency state is endemic to the Kashmir valley of the Indian subcontinent. Physicians often treat patients with high doses of vitamin D for various ailments and on occasion the prescribed doses far exceed the requirements of the patients. Ten cases of hypercalcemia due to vitamin D intoxication are presented with features of vomiting, polyuria, polydipsia, encephalopathy and renal dysfunction. All the patients had demonstrable hypercalcemia and vitamin D levels were high in nine of the 10 cases. The patients had received high doses of vitamin D and no other cause of hypercalcemia was identified. Treatment of hypercalcemia resulted in clinical recovery in nine cases. We conclude that hypervitaminosis D must be considered in the differential diagnosis of patients with hypercalcemia in endemically vitamin D deficient areas. A careful history and appropriate biochemical investigation will unravel the diagnosis in most of the cases. PMID:22043417

  6. [Hipercalcemia and non-Hodgkin's lymphomas. Report of three patients (author's transl)].

    PubMed

    Saro, E; Redón, J; Herranz, C; Munarriz, B; Montalar, J; Caballero, M

    1980-05-10

    Three out of 140 patients with non-hodgkin's lymphoma treated in a Department of Internal Medicine showed hypercalcemia during their clinical course. Hypercalcemia was symptomatic in two patients causing renal failure in one of them and a metabolic encephalopathy in the other. In the third case hypercalcemia was a casual finding. Serum calcium levels varied between 14.8 and 16.6 mg/100 ml; serum phosphate and tubular reabsorption of phosphate were normal. Alkaline phosphatase were high in the three cases. Bone disease was present in two cases. Transient responses were obtained with the administration of prednisone and calcitonin associated to forced diuresis. Indomethacin was ineffective. Pathogenesis of hypercalcemia could be related to the release of an osteoclastic activator factor. The role of prostaglandins and the presence of PTH-like mechanisms were discarded in our cases by indirect methods. The poor prognosis of patients with non-hogkin's lymphoma and hypercalcemia in stressed.

  7. Abnormal Calcium Levels During Trauma Resuscitation Are Associated With Increased Mortality, Increased Blood Product Use, and Greater Hospital Resource Consumption: A Pilot Investigation.

    PubMed

    MacKay, Emily J; Stubna, Michael D; Holena, Daniel N; Reilly, Patrick M; Seamon, Mark J; Smith, Brian P; Kaplan, Lewis J; Cannon, Jeremy W

    2017-09-01

    Admission hypocalcemia predicts both massive transfusion and mortality in severely injured patients. However, the effect of calcium derangements during resuscitation remains unexplored. We hypothesize that any hypocalcemia or hypercalcemia (either primary or from overcorrection) in the first 24 hours after severe injury is associated with increased mortality. All patients at our institution with massive transfusion protocol activation from January 2013 through December 2014 were identified. Patients transferred from another hospital, those not transfused, those with no ionized calcium (Ca) measured, and those who expired in the trauma bay were excluded. Hypocalcemia and hypercalcemia were defined as any level outside the normal range of Ca at our institution (1-1.25 mmol/L). Receiver operator curve analysis was also used to further examine significant thresholds for both hypocalcemia and hypercalcemia. Hospital mortality was compared between groups. Secondary outcomes included advanced cardiovascular life support, damage control surgery, ventilator days, and intensive care unit days. The massive transfusion protocol was activated for 77 patients of whom 36 were excluded leaving 41 for analysis. Hypocalcemia occurred in 35 (85%) patients and hypercalcemia occurred in 9 (22%). Mortality was no different in hypocalcemia versus no hypocalcemia (29% vs 0%; P = .13) but was greater in hypercalcemia versus no hypercalcemia (78% vs 9%; P < .01). Receiver operator curve analysis identified inflection points in mortality outside a Ca range of 0.84 to 1.30 mmol/L. Using these extreme values, 15 (37%) had hypocalcemia with a 60% mortality (vs 4%; P < .01) and 9 (22%) had hypercalcemia with a 78% mortality (vs 9%; P < .01). Patients with extreme hypocalcemia and hypercalcemia also received more red blood cells, plasma, platelets, and calcium repletion. Hypocalcemia and hypercalcemia occur commonly during the initial resuscitation of severely injured patients. Mild hypocalcemia

  8. Similarity of synthetic peptide from human tumor to parathyroid hormone in vivo and in vitro.

    PubMed

    Horiuchi, N; Caulfield, M P; Fisher, J E; Goldman, M E; McKee, R L; Reagan, J E; Levy, J J; Nutt, R F; Rodan, S B; Schofield, T L

    1987-12-11

    One mechanism considered responsible for the hypercalcemia that frequently accompanies malignancy is secretion by the tumor of a circulating factor that alters calcium metabolism. The structure of a tumor-secreted peptide was recently determined and found to be partially homologous to parathyroid hormone (PTH). The amino-terminal 1-34 region of the factor was synthesized and evaluated biologically. In vivo it produced hypercalcemia, acted on bone and kidney, and stimulated 1,25-dihydroxy-vitamin D3 formation. In vitro it interacted with PTH receptors and, in some systems, was more potent than PTH. These studies support a long-standing hypothesis regarding pathogenesis of malignancy-associated hypercalcemia.

  9. Effects of calcium infusion on secretion and motor activity of totally isolated canine stomach perfused with homologous blood.

    PubMed

    Kowalewski, K; Kolodej, A

    1976-01-01

    Isolated, ex vivo perfused, canine stomachs were used for this study. Gastric secretion, myoelectrical activity and mechanical activity were recorded during stimulation of gastric function with pentagastrin or histamine alone or combined with calcium gluconate. Secretagogues and calcium were infused into the gastric arterial circulation. Hypercalcemia induced significant inhibition of pentagastrin, stimulated gastric secretion, but did not affect the secretion stimulated by histamine. Hypercalcemia also induced an increase of frequency of cycles of electrical control activity and a decrease of mechanical activity of the gastric antrum. The effect of hypercalcemia on gastric motor function was similar in the nonstimulated stomach and during the infusion of secretagogues used in this experiment.

  10. Metastatic Calcinosis Cutis: A Case in a Child with Acute Pre-B Cell Lymphoblastic Leukemia

    PubMed Central

    Castanedo-Cázares, Juan Pablo; Reyes-Herrera, Amalia; Hernández-Blanco, Diana; Oros-Ovalle, Cuauhtémoc; Torres-Álvarez, Bertha

    2015-01-01

    Hypercalcemia in children with malignancy is an uncommon condition. It has been described in leukemia patients with impaired renal excretion of calcium or osteolytic lesions. Metastatic calcinosis cutis (MCC) may develop if hypercalcemia persists. We report the case of a 5-year-old girl with an atypical dermatosis and unspecific gastrointestinal symptoms. Considered clinical diagnoses were xanthomas, histiocytosis, molluscum contagiosum, and nongenital warts. Cutaneous histological analysis showed amorphous basophilic deposits in the dermis suggestive of calcium deposits. Laboratory tests confirmed serum hypercalcemia. Extensive investigations such as bone marrow biopsy established the diagnosis of an acute pre-B cell lymphoblastic leukemia. Hypercalcemia in hematopoietic malignancies is unusual, especially as initial manifestation of the disease. Careful review of the literature fails to reveal previous reports of these peculiar cutaneous lesions of MCC in children with leukemia. PMID:26346120

  11. Parathyroid cancer

    MedlinePlus

    ... due to parathyroid cancer: A drug called gallium nitrate, which lowers the calcium level in the blood ... Hypercalcemia Multiple endocrine neoplasia (MEN) I Parathyroid gland removal Review Date 2/11/2016 Updated by: Todd ...

  12. [Nephrocalcinosis and subcutaneous fat necrosis].

    PubMed

    Gomes, Cláudia; Lobo, Luísa; Azevedo, António Siborro; Simão, Carla

    2015-01-01

    Subcutaneous fat necrosis of the newborn is an uncommon, transient and self-healing panniculits. This entity generally follows an uncomplicated course, however there are rare and important complications. The authors present a case of a newborn with subcutaneous fat necrosis complicated by hypercalcemia and nephrocalcinosis. The pathogenesis of hypercalcemia is not fully understood and the nephrocalcinosis can evolve to chronic kidney disease. Clinicians should be aware of subcutaneous fat necrosis as a possible risk factor for hypercalcemia and patients should have serial serum and urinary calcium determinations for up to 6 months after the appearance of the skin lesions. The early diagnosis and prompt treatment of hypercalcemia are essential to prevent severe complications.

  13. Extensive visceral calcification demonstrated on Tc-99m MDP bone scan in patient with sphenoidal sinus carcinoma and hypercalcaemia of malignancy: a bad prognostic sign.

    PubMed

    Usmani, S; Khan, H A; Abu Huda, F; Al Nafisi, N; Al Mohannadi, S

    2011-01-01

    Sphenoidal sinus carcinoma is a rare cause of hypercalcemia of malignancy. We report on a 37-year-old male with sphenoidal sinus carcinoma with intracranial extension who developed hypercalcemia of malignancy with progressing disease and demonstrated diffuse metastatic visceral calcifications of lungs, myocardium, stomach, kidneys and thyroid on follow-up 99mTc-methylene diphosphonate bone scan. In the absence of extensive skeletal metastases, bone scan help confirm humoral nature of hypercalcaeimia.

  14. Vitamin D Supplementation: Not So Simple in Sarcoidosis.

    PubMed

    Sodhi, Amik; Aldrich, Thomas

    2016-09-01

    Americans are increasingly receiving vitamin D supplementation, often based on low-measured 25-hydroxy-vitamin D (25-OH-vit D). In sarcoidosis, there is often increased metabolism of 25-OH-vit D to 1,25-dihydroxy-vitamin D (1,25-OH-vit D), so 25-OH-vit D may remain low, despite high levels of 1,25-OH-vit D. In such cases, vitamin D supplementation may lead to hypercalcemia. We randomly selected 196 patients with sarcoidosis who received at least 1 prescription of vitamin D between 2005 and 2011 and 196 control patients. Primary outcome was the incidence of hypercalcemia during the 2 years following the vitamin D prescription. A secondary outcome was the proportion of patients who had received vitamin D prescriptions and who had adequate blood work performed before the prescription. The 25-OH-vit D and 1,25-OH-vit D levels were measured in only 70% and 23%, respectively, of those receiving supplementation. Hypercalcemia was noted more frequently in the group that received vitamin D (42.3%) as compared with the nonsupplemented group (18.3%), P < 0.0001. Patients who received a vitamin D prescription developed moderate and severe hypercalcemia more frequently (12.8%) as compared to the group that did not receive vitamin D (3.6%), P = 0.001. In multivariate analysis, having a prescription for vitamin D increased the risk of developing hypercalcemia to approximately 2-fold. The risk of developing hypercalcemia (odds ratio = 4.1) was increased with renal failure. Our study demonstrates that a substantial proportion of patients with sarcoidosis who receive vitamin D are not getting appropriate pretesting. This increases their risk for developing hypercalcemia. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  15. [Palliative therapy in cancer. 4. Palliation of the symptoms from a malignant tumor. (2)].

    PubMed

    Urushizaki, I

    1990-08-01

    Patients suffering from malignant disease will probably develop some metabolic abnormality of electrolytes. Hypernatremia is defined as an elevation of serum natrium over 150 mEq/l and caused by decrease of water intake, low level of ADH secretion and impaired response of kidney to ADH. Hyponatremia below 135 mEq/l of serum natrium is caused by SI-DAH, sick cell syndrome and increased loss of natrium from the kidney. On the other hand, hyperkalemia is defined as an elevation of serum kalium over 5.0 mEq/l and caused by acute tumor cell lysis syndrome, adrenal and renal insufficiency. Hypokalemia is caused by kalium loss from kidney and hypersecretion of mineral corticoid. Hypercalcemia is found in the high frequency among patients with malignant disease. Hypercalcemia is defined as an elevation of serum calcium over 11.0 mg/dl, although the most important aspect is the level of ionized calcium. The excess calcium causes defective urinary concentration with polydipsia, nausea and vomiting leading to volume depletion. At serum calcium levels about 13.8 mg/dl, there may be rapid deterioration or renal function, dehydration, coma and cardiac arrhythmias. Hypercalcemia is rarely the first manifestation of cancer. There are three principle pathogenic causes of malignant hypercalcemia, 1) hypercalcemia is a feature of several hematological cancers, including Burkitt's lymphoma, T cell leukemia, but most commonly with myeloma. The hypercalcemia in these myeloma patients is due to the secretion of an osteoclast activator, a lymphokine by the myeloma cells. 2) all patients with bony metastases have biochemical evidence of increased bone resorption. However, not all patients with bony metastases develop hypercalcemia. Probably the hypercalcemia is due partially to increased renal tubular reabsorption of calcium, mediated by a humoral factor, with activity similar to that of parathormone. 3) hypercalcemia in the patients without bony metastases is due to increased bone

  16. ANALYSIS OF FACTORS AFFECTING OUTCOME OF ULTRASOUND-GUIDED RADIOFREQUENCY HEAT ABLATION FOR TREATMENT OF PRIMARY HYPERPARATHYROIDISM IN DOGS.

    PubMed

    Bucy, Daniel; Pollard, Rachel; Nelson, Richard

    2017-01-01

    Radiofrequency (RF) parathyroid ablation is a noninvasive treatment for hyperparathyroidism in dogs. There are no published data assessing factors associated with RF parathyroid ablation success or failure in order to guide patient selection and improve outcome. The purpose of this retrospective analytical study was to determine whether imaging findings, biochemical data, or concurrent diseases were associated with RF heat ablation treatment failure. For inclusion in the study, dogs must have had a clinical diagnosis of primary hyperparathyroidism, undergone cervical ultrasound and RF ablation of abnormal parathyroid tissue, and must have had at least 3 months of follow-up information available following the date of ultrasound-guided parathyroid ablation. Dogs were grouped based on those with recurrent or persistent hypercalcemia and those without recurrent or persistent hypercalcemia following therapy. Parathyroid nodule size, thyroid lobe size, nodule location, and presence of concurrent disease were recorded. Recurrence of hypercalcemia occurred in 9/32 dogs that had ablation of abnormal parathyroid tissue (28%) and one patient had persistent hypercalcemia (3%) following parathyroid ablation. Nodule width (P = 0.036), height (P = 0.028), and largest cross-sectional area (P = 0.023) were larger in dogs that had recurrent or persistent hypercalcemia following ablation. Hypothyroidism was more common in dogs with recurrent disease (P = 0.044). Radiofrequency ablation was successful in 22/32 (69%) dogs. Larger parathyroid nodule size and/or concurrent hypothyroidism were associated with treatment failure in dogs that underwent ultrasound-guided RF parathyroid nodule ablation.

  17. Kidney function and influence of sunlight exposure in patients with impaired 24-hydroxylation of vitamin D due to CYP24A1 mutations.

    PubMed

    Figueres, Marie-Lucile; Linglart, Agnès; Bienaime, Frank; Allain-Launay, Emma; Roussey-Kessler, Gwenaelle; Ryckewaert, Amélie; Kottler, Marie-Laure; Hourmant, Maryvonne

    2015-01-01

    Loss-of-function mutations of CYP24A1, the enzyme that converts the major circulating and active forms of vitamin D to inactive metabolites, recently have been implicated in idiopathic infantile hypercalcemia. Patients with biallelic mutations in CYP24A1 present with severe hypercalcemia and nephrocalcinosis in infancy or hypercalciuria, kidney stones, and nephrocalcinosis in adulthood. We describe a cohort of 7 patients (2 adults, 5 children) presenting with severe hypercalcemia who had homozygous or compound heterozygous mutations in CYP24A1. Acute episodes of hypercalcemia in infancy were the first symptom in 6 of 7 patients; in all patients, symptoms included nephrocalcinosis, hypercalciuria, low parathyroid hormone (PTH) levels, and higher than expected 1,25-dihydroxyvitamin D levels. Longitudinal data suggested that in most patients, periods of increased sunlight exposure tended to correlate with decreases in PTH levels and increases in calcemia and calciuria. Follow-up of the 2 adult patients showed reduced glomerular filtration rate and extrarenal manifestations, including calcic corneal deposits and osteoporosis. Cases of severe PTH-independent hypercalcemia associated with hypercalciuria in infants should prompt genetic analysis of CYP24A1. These patients should be monitored carefully throughout life because they may be at increased risk for developing chronic kidney disease. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  18. Hysteresis and calcium set-point for the calcium parathyroid hormone relationship in healthy horses.

    PubMed

    Toribio, Ramiro E; Kohn, Catherine W; Sams, Richard A; Capen, Charles C; Rosol, Thomas J

    2003-02-15

    Abnormalities in calcium (Ca(2+)) homeostasis are reported in horses with several pathological conditions; however, there is little information on Ca(2+) regulation in horses. The objectives of the present study were to determine the Ca(2+) set-point in healthy horses, to determine whether the Ca(2+)/parathyroid hormone (PTH) response curves were characterized by hysteresis, and to determine if the order of experimentally induced hypocalcemia or hypercalcemia had an effect on PTH secretion. The Ca(2+) set-point and hysteresis were determined in 12 healthy horses by infusing Na(2)EDTA and calcium gluconate. The Ca(2+) set-point was 1.37 +/- 0.05 mmol/L, which is higher than values reported for humans and dogs (1.0-1.2 mmol/L). Hysteresis was present during hypocalcemia and hypercalcemia. Horses in which hypocalcemia was followed by hypercalcemia secreted more PTH (7440 +/- 740 pmol min/L) than horses in which hypercalcemia was followed by hypocalcemia (5990 +/- 570 pmol min/L). This study has demonstrated that the Ca(2+) set-point in the horse is higher than in other domestic animals and man. We have shown that the Ca(2+)/PTH relationship in horses is sigmoidal and displays hysteresis during both hypocalcemia and hypercalcemia, and that extracellular Ca(2+) concentrations may affect the response of the parathyroid gland to hypocalcemia.

  19. PubMed Central

    Brunette, M.; Gerbeaux, S.

    1963-01-01

    Several reports of idiopathic hypercalcemia of childhood have been published since Lightwood in 1932 described dwarfism associated with mental retardation, strabismus, hypercalcemia, nephrocalcinosis and osteosclerosis. The present paper adds two new cases. The first patient was 15 months old when first seen with stunted physical and mental growth, a systolic murmur, and a serum calcium value of 13 mg. %. This child suffered several severe infections and in spite of a low calcium intake and the administration of chelating agents her blood calcium rose until death six months later. The other patient, three years old, also had delayed physical and mental development, typical facies, a systolic murmur, skeletal lesions, and nephrocalcinosis. Varied therapeutic attempts failed. Idiopathic hypercalcemia of childhood is reviewed in the light of the 94 reports already published. ImagesFig. 1Fig. 2Figs. 4a-bFig. 4cFig. 4dFig. 4e PMID:14079128

  20. Urolithiasis and primary parathyroid adenoma: report of one case.

    PubMed

    Lee, Jing-Sheng; Lau, Beng-Huat; Yeh, Ming-Lun; Lee, Chin-Cheng

    2003-01-01

    A 12-year-old girl was admitted to ward because of persistent left flank pain, vomiting, and hematuria. A stone was located at the ureteropelvic junction of the left kidney, as determined by means of abdominal sonography. Metabolic investigation for a renal stone revealed that she had hypercalcemia, hypophosphatemia, and hypercalciuria. Hyperparathyroidism was diagnosed based on the hypercalcemia and inappropriately elevated serum parathyroid hormone level. A parathyroid adenoma was successfully diagnosed by using thallium/technetium subtraction parathyroid scanning. Extracorporeal shock wave lithotripsy was performed to treat the renal stone, and the parathyroid adenoma was successfully removed. The patient's postoperative course was uneventful. This case is presented because urolithiasis and hyperparathyroidism are rare in children. Metabolic evaluation is mandatory in children with a renal stone. Further investigation for the hyperparathyroidism should be performed if hypercalcemia associated with hypercalciuria is documented.

  1. Tracheal epithelial-myoepithelial carcinoma associated with sarcoid-like reaction: A case report

    PubMed Central

    Dong, Huawei; Tatsuno, Brent K.; Betancourt, Jaime; Oh, Scott S.

    2014-01-01

    Epithelial-myoepithelial carcinomas are rare tumors that primarily originate in the salivary glands but have also been found in the tracheobronchial tree. We report the first case of epithelial-myoepithelial carcinoma associated with sarcoidosis. A 61 year old Hispanic man presented with altered mental status and hypercalcemia. Imaging revealed diffuse intra-thoracic and intra-abdominal lymphadenopathy. A diagnostic bronchoscopy was performed where an incidental tracheal nodule was discovered and biopsied. Pathology was consistent with epithelial-myoepithelial carcinoma. Lymph node biopsy demonstrated non-caseating granulomas consistent with sarcoidosis. Patient underwent tracheal resection of the primary tumor with primary tracheal reconstruction. Hypercalcemia subsequently normalized with clinical improvement. Repeat CT imaging demonstrated complete resolution of lymphadenopathy. Our findings are suggestive of a possible paraneoplastic sarcoid-like reaction to the epithelial-myoepithelial carcinoma with associated lymphadenopathy and symptomatic hypercalcemia. PMID:26029574

  2. Usefulness of nuclear whole-body bone scanning for diagnosis of leprosy.

    PubMed

    Marquez, Hector; McDevitt, Joseph; Öz, Orhan K; Wachsmann, Jason

    2017-10-01

    Leprosy, or Hansen's disease, is rare in the United States. Given its rarity, as well as the pathognomonic dermatologic findings, there are few cases in which nuclear medicine imaging plays a role in the diagnostic workup. We present a 39-year-old man who presented with chronic abdominal pain, skin ulcers, and hypercalcemia who underwent computed tomography of the chest and a whole-body bone scan to evaluate for possible underlying neoplasm due to his profound hypercalcemia. Although the diagnosis of leprosy had been established by lower-extremity skin biopsy upon admission, workup for other potential concurrent etiologies of hypercalcemia was performed before initiating therapy. We present the computed tomography scans, nuclear medicine images, and corresponding skin findings of this case.

  3. Creutzfeldt-Jakob-Like Syndrome due to Hypercalcemic Encephalopathy.

    PubMed

    Rösche, Johannes; Sieveking, Catharina; Kampf, Christina; Benecke, Reiner

    2015-10-01

    Hypercalcemia can cause a subacute syndrome of progressive dementia and marked changes in the electroencephalogram (EEG). We report a case of iatrogenic hypercalcemia with a close correlation between the clinical course and the EEG changes. A 73-year-old woman presented with a subacute syndrome of progressive dementia and bursts of 1.5 to 2 Hz intermittent rhythmic delta activity superimposed on a low-voltage background activity in the EEG. Clinical and EEG abnormalities rapidly resolved after normalization of serum calcium levels. As part of the diagnostic workup of a subacute progressive dementia, a serum calcium level and an EEG should be obtained to detect a Creutzfeldt-Jakob like syndrome in hypercalcemia. Unlike in Creutzfeldt-Jakob disease, and Creutzfeldt-Jakob-like syndrome induced by lithium intoxication, there are rarely myoclonic jerks and periodic discharges in hypercalcemic encephalopathy.

  4. A Rare Case of Petrified Ear

    PubMed Central

    Buikema, Kathryn E.; Adams, Erin G.

    2012-01-01

    Calcification or ossification of the auricle, also referred to as petrified ear, is a rare diagnosis in dermatology. In medical literature, it has most often been attributed to trauma, hypothermia and frostbite, or hypercalcemia secondary to a metabolic or endocrine disorder, such as Addison's disease. Here, we report the clinical and radiologic findings of a 79-year-old African American male whose unilateral petrified auricle was an incidental finding. He had a preceding history of hyperparathyroidism and subsequent hypercalcemia treated with a subtotal parathyroidectomy three years prior to presentation. In addition to laboratory analysis, a history and physical examination was performed which revealed no other signs of hypercalcemia. Radiologic studies demonstrated partial ossification of the external auricular cartilage on the left side. The patient was diagnosed with the rare occurrence of a petrified ear. In light of this case, we provide a discussion concerning the possible etiologies of this diagnosis including appropriate patient evaluation and possible treatment recommendations. PMID:23259082

  5. Use of cinacalcet and sunitinib to treat hypercalcaemia due to a pancreatic neuroendocrine tumor.

    PubMed

    Valdes-Socin, Hernan; Almanza, Matilde Rubio; Fernández-Ladreda, Mariana Tomé; Daele, Daniel Van; Polus, Marc; Chavez, Marcela; Beckers, Albert

    2017-09-18

    Neuroendocrine tumors (NETs) can secrete hormones, including ectopic secretions, but they have been rarely associated with malignant hypercalcemia. A 52-year-old man with a history of diabetes mellitus was diagnosed with a pancreatic tumor. A pancreatic biopsy confirmed a well-differentiated pancreatic NET (pNET). The patient subsequently developed liver metastasis and hypercalcemia with high 1,25 OH vitamin D and suppressed parathyroid hormone (PTH) levels. Hypercalcemia was refractory to chemotherapy, intravenous saline fluids, diuretics, calcitonin and zoledronate. Cinacalcet administration (120 mg/day) resulted in a significant calcium reduction. Hypocalcemia was observed when sunitinib was added three months later and cinacalcet was stopped. Subsequently, the calcium and PTH levels normalized. After six months, we observed 20% shrinkage of the pancreatic tumor and necrosis of a liver metastasis. Cinacalcet is an allosteric activator of the calcium receptor agonist, and it is used for severe hypercalcemia in patients with primary (benign and malignant) hyperparathyroidism. In this patient, cinacalcet demonstrated a calcium lowering effect, normalized hypophosphatemia, and improved the clinical condition of the patient. The mechanism through which cinacalcet improved PTH-rp mediated hypercalcemia is still unclear, but studies have suggested that a potential mechanism is the activation of calcitonin secretion. Sunitinib is an oral multi-targeted tyrosine kinase inhibitor used to treat advanced pNETs. The hypocalcemic effects of sunitinib have not been previously described in a patient with pNET. Here, we report for the first time the successful combination of cinacalcet and sunitinib in the treatment of a pNET patient presenting with malignant hypercalcemia.

  6. Primary Hyperparathyroidism: Effects on Bone Health.

    PubMed

    Zanocco, Kyle A; Yeh, Michael W

    2017-03-01

    Primary hyperparathyroidism (PHPT) is the most common cause of chronic hypercalcemia. With the advent of routine calcium screening, the classic presentation of renal and osseous symptoms has been largely replaced with mild, asymptomatic disease. In hypercalcemia caused by PHPT, serum parathyroid hormone levels are either high, or inappropriately normal. A single-gland adenoma is responsible for 80% of PHPT cases. Less frequent causes include 4-gland hyperplasia and parathyroid carcinoma. Diminished bone mineral density and nephrolithiasis are the major current clinical sequelae. Parathyroidectomy is the only definitive treatment for PHPT, and in experienced hands, cure rates approach 98%.

  7. Self-diagnosis of hyperparathyroidism during pregnancy resulting in parathyroidectomy and uncomplicated delivery.

    PubMed

    Medza, Aleksandra; Obolonczyk, Lukasz; Lewalska, Anna; Buss, Tomasz; Peksa, Rafal; Siekierska-Hellmann, Malgorzata; Berendt-Obolonczyk, Monika; Wisniewski, Piotr; Sworczak, Krzysztof

    2017-03-06

    Primary hyperparathyroidism is a condition with hypercalcemia and elevated parathyroid hormone (PTH). Typically, treating patients with such disease does not pose a problem for doctors, unless the patient is pregnant. Firstly, pregnancy may mask signs of hypercalcemia. Secondly, treatment should be applied with special care for immature fetus. If undiagnosed and untreated, it is life-threatening for the mother and the baby. The main cause of primary hyperparathyroidism is parathyroid adenoma, which should be removed surgically in second trimester. If the patient is monitored by a multidisciplinary team, the risk of mortality and pregnancy loss is reduced.

  8. Squamous Cell Carcinoma of the Renal Pelvis as a Result of Long-Standing Staghorn Calculi

    PubMed Central

    Jongyotha, Kamonchanok; Sriphrapradang, Chutintorn

    2015-01-01

    We report on a 79-year-old woman with staghorn calculi who presented with severe hypercalcemia. She was later found to have humoral hypercalcemia of malignancy caused by a rare tumor, squamous cell carcinoma of the renal pelvis. Chronic irritation, infection and inflammation from staghorn stones cause squamous metaplasia, leading to squamous cell carcinoma of the renal collecting system. The prognosis is very poor, with a 5-year survival rate of <10%. This case highlights the importance of awareness of a very rare and aggressive carcinoma in a patient with long-standing nephrolithiasis. PMID:26557077

  9. The Pathophysiology and Clinical Aspects of Hypercalcemic Disorders

    PubMed Central

    Lee, David B. N.; Zawada, Edward T.; Kleeman, Charles R.

    1978-01-01

    For the purposes of this review, the vast and increasingly complex subject of hypercalcemic disorders can be broken down into the following categories: (1) Physiochemical state of calcium in circulation. (2) Pathophysiological basis of hypercalcemia. (3) Causes of hypercalcemia encountered in clinical practice: causes indicated by experience at the University of California, Los Angeles; neoplasia; hyperparathyroidism; nonparathyroid endocrinopathies; pharmacological agents; possible increased sensitivity to vitamin D; miscellaneous causes. (4) Clinical manifestations and diagnostic considerations of hypercalcemic disorders. (5) The management of hypercalcemic disorders: general measures; measures for lowering serum calcium concentration; measures for correcting primary causes—the management of asymptomatic hyperparathyroidism. PMID:362722

  10. Nivolumab in Treating Patients With HTLV-Associated T-Cell Leukemia/Lymphoma

    ClinicalTrials.gov

    2017-07-26

    Acute Adult T-Cell Leukemia/Lymphoma; Adult T-Cell Leukemia/Lymphoma; CD3 Positive; CD4-Positive Neoplastic Cells Present; Chronic Adult T-Cell Leukemia/Lymphoma; HTLV-1 Infection; Hypercalcemia; Lymphomatous Adult T-Cell Leukemia/Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma; Smoldering Adult T-Cell Leukemia/Lymphoma

  11. Prolonged fever associated with primary hyperparathyroidism.

    PubMed Central

    Ricci, J; Vlasschaert, J; Salit, I E

    1984-01-01

    A 36-year-old woman presented with hypercalcemia, hypercalciuria, elevated serum parathyroid hormone levels and prolonged fever. Surgical removal of the hyperplastic and adenomatous parathyroid glands led to reversal of the biochemical abnormalities as well as return of her temperature to normal. PMID:6467119

  12. Four Case Histories and a Literature Review of Williams Syndrome and Autistic Behavior.

    ERIC Educational Resources Information Center

    Gillberg, Christopher; Rasmussen, Peder

    1994-01-01

    This paper summarizes the case histories of four young children with concurrent autistic disorder and Williams syndrome. Williams syndrome comprises a peculiar facial appearance, learning disorder, and often hypercalcemia, mild microcephaly, large blood vessel stenosis, and a specific behavioral phenotype. Literature on Williams syndrome is…

  13. Sarcoidosis presenting as granulomatous myositis in a 16-year-old adolescent.

    PubMed

    Orandi, Amir B; Eutsler, Eric; Ferguson, Cole; White, Andrew J; Kitcharoensakkul, Maleewan

    2016-11-10

    Sarcoidosis is a multi-system disease characterized by the presence of non-caseating epithelioid granulomas in affected tissues, including skeletal muscle. These organized collections of immune cells have important pathophysiologic action including cytokine production leading to inflammation as well as enzymatic conversion of cholecalciferol to calcitriol via 1-α hydroxylase. There are limited reports of isolated granulomatous myositis causing hypercalcemia in pediatric patients. Our patient uniquely presented with symptoms from hypercalcemia and renal insufficiency caused by an overwhelming burden of granulomatous myositis in her lower extremities, but was otherwise asymptomatic. A 16 year old Caucasian female presented with protracted symptoms of fatigue, nausea and prominent weight loss with laboratory evidence of hypercalcemia and renal insufficiency. She lacked clinical and physical findings of arthritis, weakness, rash, uveitis, fever, lymphadenopathy or respiratory symptoms. After extensive negative investigations, re-examination yielded subtle soft tissue changes in her lower extremities, with striking MRI findings of extensive myositis without correlative weakness or serum enzyme elevation. Biopsy showed the presence of non-caseating epithelioid granulomas and calcium oxalate crystals. The patient responded well to prednisone and methotrexate but relapsed with weaning of steroids. She reachieved remission with addition of adalimumab. Sarcoidosis should be considered in patients presenting with symptomatic hypercalcemia with no apparent causes and negative routine workup. The absences of decreased muscle strength or elevated muscle enzymes do not preclude the diagnosis of granulomatous myositis.

  14. [Pneumococcal septic arthritis revealing a multiple myeloma].

    PubMed

    Renou, F; Gerber, A; Moiton, M-P; Ferrandiz, D; Yvin, J-L

    2007-03-01

    The most common presenting features of multiple myeloma are bone pain, anemia, renal failure or hypercalcemia. Bacterial infection as the initial presentation of this desease is rare. We report the case of a 62-year-old man with pneumococcal septic arthritis of the knee revealing a multiple myeloma. Pneumococcal infection should lead to a suspicion of underlying illness and especially the multiple myeloma.

  15. Four Case Histories and a Literature Review of Williams Syndrome and Autistic Behavior.

    ERIC Educational Resources Information Center

    Gillberg, Christopher; Rasmussen, Peder

    1994-01-01

    This paper summarizes the case histories of four young children with concurrent autistic disorder and Williams syndrome. Williams syndrome comprises a peculiar facial appearance, learning disorder, and often hypercalcemia, mild microcephaly, large blood vessel stenosis, and a specific behavioral phenotype. Literature on Williams syndrome is…

  16. Emergency medicine: A comprehensive review

    SciTech Connect

    Kravis, T.C.; Warner, C.G.

    1987-01-01

    This book contains 91 chapters divided among 14 sections. Some of the chapter titles are: Transfusions; Minor Lacerations and Abrasions; Diabetic Emergencies; Adrenal Insufficiency; Hypercalcemia; Medical Genetics; Burns; Hazardous Materials; Gastrointestinal Emergencies; Infectious Disease Emergencies; Reye's Syndrome; Bites and Stings; and Hypothermia.

  17. Lithium-associated primary hyperparathyroidism complicated by nephrogenic diabetes insipidus.

    PubMed

    Aksakal, Nihat; Erçetin, Candaş; Özçınar, Beyza; Aral, Ferihan; Erbil, Yeşim

    2015-01-01

    Lithium-associated hyperparathyroidism is the leading cause of hypercalcemia in lithium-treated patients. Lithium may lead to exacerbation of pre-existing primary hyperparathyroidism or cause an increased set-point of calcium for parathyroid hormone suppression, leading to parathyroid hyperplasia. Lithium may cause renal tubular concentration defects directly by the development of nephrogenic diabetes insipidus or indirectly by the effects of hypercalcemia. In this study, we present a female patient on long-term lithium treatment who was evaluated for hypercalcemia. Preoperative imaging studies indicated parathyroid adenoma and multinodular goiter. Parathyroidectomy and thyroidectomy were planned. During the postoperative course, prolonged intubation was necessary because of agitation and delirium. During this period, polyuria, severe dehydration, and hypernatremia developed, which responded to controlled hypotonic fluid infusions and was unresponsive to parenteral desmopressin. A diagnosis of nephrogenic diabetes insipidus was apparent. A parathyroid adenoma and multifocal papillary thyroid cancer were detected on histopathological examination. It was thought that nephrogenic diabetes insipidus was masked by hypercalcemia preoperatively. A patient on lithium treatment should be carefully followed up during or after surgery to prevent life-threatening complications of previously unrecognized nephrogenic diabetes insipidus, and the possibility of renal concentrating defects on long-term lithium use should be sought, particularly in patients with impaired consciousness.

  18. Sleeping Parathyroid Tumor: Rapid Hyperfunction after Removal of the Dominant Tumor

    PubMed Central

    Simonds, William F.; Weinstein, Lee S.; Collins, Michael T.; Kebebew, Electron; Nilubol, Naris; Phan, Giao Q.; Libutti, Steven K.; Remaley, Alan T.; Van Deventer, Manuel; Marx, Stephen J.

    2012-01-01

    Context: Due to frequent multiplicity of tumors in multiple endocrine neoplasia type 1, it may be difficult to decide when to stop a parathyroid exploration. A fall of intraoperative serum PTH by a certain percentage during parathyroid surgery is often used as one criterion for ending the operation. Results: We report two patients with primary hyperparathyroidism due to multiple endocrine neoplasia type 1 who had their first parathyroidectomy at the National Institutes of Health. In both cases, two and a half glands were removed, an extensive search was done for an occult parathyroid tumor, and intraoperative PTH decreased markedly to the lower limits of normal, suggesting a successful operation. Despite this, both patients became hypercalcemic within 3 d after the operation and showed persistent primary hyperparathyroidism. Detailed findings suggest the following course: chronic hypercalcemia had caused near total suppression of PTH secretion by an undiscovered parathyroid tumor (sleeping parathyroid tumor). When the hypercalcemia decreased after surgery due to the removal of the dominant parathyroid tumor(s), the abnormal yet previously suppressed tumor rapidly began to oversecrete PTH and thus caused postoperative hypercalcemia. Conclusions: Even a fall of the intraoperative PTH to the lower limits of the normal range cannot guarantee that removal of all parathyroid tumors has been complete in cases with multiple tumors. These findings likely reflect strikingly differing PTH secretory functions among distinct tumors in the same patient, with hypercalcemia at least from a dominant tumor suppressing PTH secretion by one or more other parathyroid tumors. PMID:22508712

  19. Williams syndrome: a case series.

    PubMed

    Kandasamy, Subapriya; Saxena, Deepti; Kishore, Yougal; Phadke, Shubha R

    2014-05-01

    Pediatricians awareness about malformation syndromes can help in their timely diagnosis. Williams syndrome is a microdeletion syndrome associated with characteristic facial features and behavioral phenotype. Diagnosis can be confirmed by fluorescence-in-situ hybridization or multiplex ligation probe amplification. Correct diagnosis can help in diagnosing hypercalcemia and cardiac defects, and providing genetic counseling to the family.

  20. Brown tumor and staghorn calculi in primary hyperparathyroidism.

    PubMed

    Philip George, Arun Jacob; Banerji, John S

    2013-08-01

    A case of primary hyperparathyroidism with bilateral renal staghorn calculi and brown tumor right thumb is reported in these images, along with the appropriate sequential management. Percutaneous nephrolithotomy (PCNL)was done after management of hypercalcemia and after parathyroidectomy. This case highlights the need for urologists and general practitioners to have a holistic approach in patient management.

  1. Computer-Aided Medical Diagnosis. Literature Review

    DTIC Science & Technology

    1978-12-15

    BOUCKAERT, A., Computer-aided diagnosis of goitres in a cancer department, Int. J. Bio-’Med. Comput., 3 (1972) p. 3. BOYLE, J. A., GREIG, W. R., FRANKLIN, D...toxic goitre , Q. J. Med., 35 (1966) p. 565. Bricetti, A. B. and Bleich, H. L., A computer program that evaluates patients with hypercalcemia, J

  2. Bioinspired colorimetric detection of calcium(II) ions in serum using calsequestrin-functionalized gold nanoparticles.

    PubMed

    Kim, Sunghyun; Park, Jeong Won; Kim, Dongkyu; Kim, Daejin; Lee, In-Hyun; Jon, Sangyong

    2009-01-01

    Seeing is sensing: Calsequestrin (CSQ) functionalized gold nanoparticles undergo calcium-dependent CSQ polymerization, which results in a clear color change (see picture) together with precipitation. The sensing system is specific for Ca(2+) ions and the differences between normal and disease-associated abnormal (hypercalcemia) Ca(2+) ion levels in serum can be distinguished with the naked eye.

  3. Lithium-associated primary hyperparathyroidism complicated by nephrogenic diabetes insipidus

    PubMed Central

    Aksakal, Nihat; Erçetin, Candaş; Özçınar, Beyza; Aral, Ferihan; Erbil, Yeşim

    2015-01-01

    Lithium-associated hyperparathyroidism is the leading cause of hypercalcemia in lithium-treated patients. Lithium may lead to exacerbation of pre-existing primary hyperparathyroidism or cause an increased set-point of calcium for parathyroid hormone suppression, leading to parathyroid hyperplasia. Lithium may cause renal tubular concentration defects directly by the development of nephrogenic diabetes insipidus or indirectly by the effects of hypercalcemia. In this study, we present a female patient on long-term lithium treatment who was evaluated for hypercalcemia. Preoperative imaging studies indicated parathyroid adenoma and multinodular goiter. Parathyroidectomy and thyroidectomy were planned. During the postoperative course, prolonged intubation was necessary because of agitation and delirium. During this period, polyuria, severe dehydration, and hypernatremia developed, which responded to controlled hypotonic fluid infusions and was unresponsive to parenteral desmopressin. A diagnosis of nephrogenic diabetes insipidus was apparent. A parathyroid adenoma and multifocal papillary thyroid cancer were detected on histopathological examination. It was thought that nephrogenic diabetes insipidus was masked by hypercalcemia preoperatively. A patient on lithium treatment should be carefully followed up during or after surgery to prevent life-threatening complications of previously unrecognized nephrogenic diabetes insipidus, and the possibility of renal concentrating defects on long-term lithium use should be sought, particularly in patients with impaired consciousness. PMID:26504422

  4. A Longitudinal Study of Bone Turnover, Menopause, Aging and Ethnicity as Risk Factors for Osteoporosis

    DTIC Science & Technology

    2001-04-01

    the attached report. Work is underway on the corresponding manuscripts. 14. SUBJECT TERMS 15. NUMBER OF PAGES Osteoporosis 35 16. PRICE CODE 17...hyperthyroidism, hypercalcemia, chronic liver disease, anorexia nervosa, or bulimia . In addition, data for women who initiated HRT at Follow-ups 01 or 02 were

  5. Serum calcium level of freshwater snake, Natrix piscator, in response to vitamin D3 administration.

    PubMed

    Srivastav, A K; Srivastav, S P; Srivastav, S K; Swarup, K

    1986-01-01

    The effect of i.m. injection of vitamin D3 (25 IU/100 g b.wt) on serum calcium level was investigated in Natrix piscator. This treatment evokes hypercalcemia at day 3 which progresses up to day 5. Thereafter, a decline was observed in the serum calcium level at day 10 and day 15.

  6. Parathyroid adenoma associated with neurofibromatosis: Correlative scintigraphic and magnetic resonance imaging

    SciTech Connect

    Vogelzang, P.J.; Oates, E.; Bankoff, M.S.

    1989-03-01

    Correlative imaging by dual-isotope thallium/technetium subtraction scintigraphy, computed tomography, and magnetic resonance imaging demonstrated a pathologically proven parathyroid adenoma in a 62-year-old man with known neurofibromatosis, who presented with hypercalcemia and an elevated parathormone level. The association between neurofibromatosis and primary hyperparathyroidism is discussed.

  7. Renal function in hypercalcemic dogs during hydropenia and during saline infusion.

    PubMed

    Lins, L E

    1979-06-01

    The effects of calcium-gluconate infusions on renal function were studied in unanesthetised dogs. Each dog was studied during hydropenia and saline infusion. Hypercalcemia, mean serum calcium 3.85 mmol/l (hydropenia) and 3.62 mmol/l (saline infusion), increased fractional excretion of sodium (CNa/CIn), calcium (CCa/CIn), and magnesium (CMg/CIn). The increase was significantly higher in saline-expanded dogs than in hydropenic dogs. Fractional excretion of potassium (CK/CIn) was increased in hydropenia but remained unchanged in saline-expanded animals. Fractional excretion of phosphate (Cp/CIn) was not consistently changed by hypercalcemia. Fractional excretion of chloride (CCl/CIn) was markedly increased in saline-expanded dogs but was not changed in hydropenia. Urine osmolality was reduced in hydropenic dogs but unchanged in saline-expanded dogs. In hydropenic as well as in saline-expanded dogs tubular reabsorption of solute-free water (TcH2O/CIn) increased during the first hour of hypercalcemia. In hydropenic dogs hypercalcemia caused a slight but significant decrease in blood pH, standard bicarbonate, and base excess. In hydropenic as well as in saline-expanded dogs glomerular filtration rate (CIn), renal plasma flow (CPAH), and filtration fraction were unaffected.

  8. CO2-Induced Kidney Calcification

    DTIC Science & Technology

    1977-02-01

    Crumb, Martinez-Muldonado, Eknoyan, and Suki 1974). The same authors reported that hypercalcemia causes an increased bicarbonate reabsorption, but...1253-1255. Crumb, Ch. K., M. Martinez-Muldonado, G. Eknoyan, and N. Suki . 1974. Effect of volume expansion, purified parathyroid extract and

  9. Follow-Up During Early Infancy of Newborns Diagnosed with Subcutaneous Fat Necrosis

    PubMed Central

    Akın, Leyla; Sarıcı, Dilek; Yılmaz, İbrahim; Balkanlı, Süleyman; Kurtoğlu, Selim

    2011-01-01

    Subcutaneous fat necrosis of the newborn (ScFN) is an uncommon condition caused by generalized and/or local tissue hypoperfusion. The skin lesions of ScFN tend to improve spontaneously. However, ScFN may also lead to complications which cause serious problems. The severity of the etiologic factors contributing to the development of the disease determines the severity of complications. Therefore, these patients should be closely monitored for complications, especially for hypercalcemia which may be life-threatening. The severity and duration of hypercalcemia are associated with the extensity of skin lesions. We present a newborn who developed ScFN as a result of systemic hypotension. The ScFN resolved after the first few weeks of life, but the patient developed mild hypercalcemia during the 4-month follow-up period. The infant was breast-fed during follow-up, and vitamin D prophylaxis was not initiated. The hypercalcemia resolved within four months without any complications. We would like to draw attention to the need to monitor serum calcium levels in these infants and to refrain from initiating vitamin D prophylaxis in the first months of life. Conflict of interest:None declared. PMID:22155466

  10. Bone lymphoma with multiple negative bone biopsies.

    PubMed

    Riaz, Irbaz Bin; Khan, Muhammad Shahzeb; Mazursky, Konstantin; Husnain, Muhammad; Anwer, Faiz

    2017-09-01

    This article describes a 71-year-old man with right knee pain, prerenal azotemia, hypercalcemia, and a mass in the distal femur. Although testing, including bone marrow biopsy, initially ruled out myeloma, an open surgical biopsy eventually confirmed the diagnosis as lymphoma involving the bone with classic histologic findings of mature B-cell neoplasm of germinal cell origin.

  11. Hypoparathyroidism: Less Severe Hypocalcemia With Treatment With Vitamin D2 Compared With Calcitriol.

    PubMed

    Streeten, Elizabeth A; Mohtasebi, Yasaman; Konig, Manige; Davidoff, Lisa; Ryan, Kathleen

    2017-05-01

    Options for chronic treatment of hypoparathyroidism include calcitriol, recombinant human parathyroid hormone, and high-dose vitamin D (D2). D2 is used in a minority of patients because of fear of prolonged hypercalcemia and renal toxicity. There is a paucity of recent data about D2 use in hypoparathyroidism. Compare renal function, hypercalcemia, and hypocalcemia in patients with hypoparathyroidism treated chronically with either D2 (D2 group) or calcitriol. A retrospective study of patients with hypoparathyroidism treated at the University of Maryland Hospital. Participants were identified by a billing record search with diagnosis confirmed by chart review. Thirty patients were identified; 16 were treated chronically with D2, 14 with calcitriol. Data were extracted from medical records. Serum creatinine and calcium, hospitalizations, and emergency department (ED) visits for hypercalcemia and hypocalcemia. D2 and calcitriol groups were similar in age (58.9 ± 16.7 vs 50.9 ± 22.6 years, P = 0.28), sex, and treatment duration (17.8 ± 14.2 vs 8.5 ± 4.4 years, P = 0.076). Hospitalization or ED visits for hypocalcemia occurred in none of the D2 group vs four of 14 in the calcitriol group (P = 0.03); three in the calcitriol group had multiple ED visits. There were no differences between D2 and calcitriol groups in hospitalizations or ED visits for hypercalcemia, serum creatinine or calcium, or kidney stones. We found less morbidity from hypocalcemia in hypoparathyroid patients treated chronically with D2 compared with calcitriol and found no difference in renal function or morbidity from hypercalcemia. Treatment with D2 should be considered in patients with hypoparathyroidism, particularly in those who experience recurrent hypocalcemia.

  12. Clinical and economic aspects of sevelamer therapy in end-stage renal disease patients.

    PubMed

    Ossareh, Shahrzad

    2014-01-01

    Phosphate control is still a great challenge in chronic kidney disease (CKD), and in spite of the great improvements in dialysis techniques, achievement of the goals for mineral metabolism control is still far from ideal. Aluminum hydroxide has been largely abandoned due to the high risk of aluminum toxicity, while the use of calcium-based phosphate binders may cause hypercalcemia, overzealous parathyroid suppression, and extraskeletal calcification. Sevelamer hydrochloride has been introduced as an efficient medication for phosphate control, with a lower risk of hypercalcemia and parathyroid suppression. Various clinical trials have compared the risk of vascular calcification between sevelamer and calcium salts with inconsistent results. In spite of these inconsistencies, the Kidney Disease Outcomes Quality Initiative (KDOQI) suggests non-calcium phosphate binders as the preferred phosphate binder in dialysis patients with severe vascular and/or other soft-tissue calcifications and in those with hypercalcemia or parathyroid hormone (PTH) <150 mg/dL. The Kidney Disease Improving Global Outcome (KDIGO) limits the use of non-calcium phosphate binders to patients with hypercalcemia. Regarding the effect on mortality, the results of clinical trials are again inconsistent. The other important aspect of using sevelamer is the issue of price, which is substantially higher than calcium-based phosphate binders. Reviewing the studies on economic aspects shows that sevelamer increases quality-adjusted life-years (QALY) and possibly life years, with a higher cost compared to calcium-based phosphate binders. In conclusion, sevelamer is a very useful drug for phosphate control, reduction of hypercalcemia, and lessening the risk of adynamic bone disease, with probable reduction in vascular calcification and possible reduction in mortality rate. It has a higher economic burden on health care systems compared to calcium-based phosphate binders. This may affect its extensive use

  13. Successful treatment of neonatal severe hyperparathyroidism with cinacalcet in two patients

    PubMed Central

    Cabrera, Susanne M; Imel, Erik A

    2015-01-01

    Summary Neonatal severe hyperparathyroidism (NSHPT) is a rare disorder caused by inactivating calcium-sensing receptor (CASR) mutations that result in life-threatening hypercalcemia and metabolic bone disease. Until recently, therapy has been surgical parathyroidectomy. Three previous case reports have shown successful medical management of NSHPT with cinacalcet. Here we present the detailed description of two unrelated patients with NSHPT due to heterozygous R185Q CASR mutations. Patient 1 was diagnosed at 11 months of age and had developmental delays, dysphagia, bell-shaped chest, and periosteal bone reactions. Patient 2 was diagnosed at 1 month of age and had failure to thrive, osteopenia, and multiple rib fractures. Cinacalcet was initiated at 13 months of age in patient 1, and at 4 months of age in patient 2. We have successfully normalized their parathyroid hormone and alkaline phosphatase levels. Despite the continuance of mild hypercalcemia (11–12 mg/dl), both patients showed no hypercalcemic symptoms. Importantly, patient 1 had improved neurodevelopment and patient 2 never experienced any developmental delays after starting cinacalcet. Neither experienced fractures after starting cinacalcet. Both have been successfully managed long-term without any significant adverse events. These cases expand the current literature of cinacalcet use in NSHPT to five successful reported cases. We propose that cinacalcet may be considered as an option for treating the severe hypercalcemia and metabolic bone disease found in infants and children with inactivating CASR disorders. Learning points NSHPT due to mutations in the CASR gene occurs with hypercalcemia and metabolic bone disease, but not always with severe critical illness in infancy.NSHPT should be considered in the differential diagnosis for a newborn with a bell-shaped chest, osteopenia, and periosteal reactions.Neurodevelopmental consequences may occur in children with hypercalcemia and may improve during

  14. Hypercalcemic effect of catecholamines and its prevention by thyrocalcitonin.

    PubMed

    Hsu, W H; Cooper, C W

    1975-12-18

    Earlier work by others has shown that the catecholamines, epinephrine and isoproterenol, can raise blood calcium levels in parathyroidectomized but not intact rats, and can restrict the hypocalcemic effect of injected thyrocalcitonin (TCT). The present findings support this earlier work, further showing that such catecholamines can produce hypercalcemia in rats after removal of the thyroid gland by acute thyroparathyroidectomy (TPTX) and indicating that these drugs may raise blood calcium by mobilizing calcium from bone. Rats were fasted overnight, subjected to TPTX and concurrently injected with adrenergic agonist or antagonist drugs alone or in combination. Epinephrine, isoproterenol, and the beta-2 adrenergic agonist, salbutamol, in doses greater than or equal to 1 mg/kg raised blood calcium from low normal levels (approximately 9-10 mg/100 ml) by 1.5 to 2 mg/100 ml (p less than 0.01). Hypercalcemia was apparent by 1 hour after injection and lasted for 1-4 hours. The extent of Ca elevation was dose-related. Pretreatment of rats with the alpha-adrenergic antagonist, phenoxybenzamine, enhanced the effect of epinephrine while pretreatment with the beta-antagonist, propranolol, reduced the effect of isoproterenol. The more selective beta-2 antagonist, butoxamine, but not the beta-1 antagonist, practolol, also reduced the hypercalcemic effect of isoproterenol in TPTX rats. These results suggest that catecholamine-induced hypercalcemia in TPTX rats is mediated by beta-2 adrenergic receptors. Related studies using rats prelabeled with 45Ca further suggest that the catecholamines, like parathyroid hormone, may act to raise blood calcium by mobilizing calcium from bone. The fact that these catecholamines could induce marked hypercalcemia in acutely TPTX rats but not in intact rats indicated that endogenous TCT protects the thyroid intact rat against hypercalcemia. The present findings support this idea in showing that isoproterenol and salbutamol raised levels of

  15. Primary hyperparathyroidism mimicking hyperemesis gravidarum.

    PubMed

    Benson, Brian C; Guinto, Roy E; Parks, Jonathan R

    2013-01-01

    Nausea and vomiting are common complaints during pregnancy. Their severity and persistence can lead to the diagnosis of hyperemesis gravidarum, which is associated with weight loss, ketonuria, and decreased fetal birth weight. Hypercalcemia in pregnancy can confound these common gastrointestinal symptoms as well as have its own intrinsic maternal-fetal risks. A 23-year-old woman was diagnosed with primary hyperparathyroidism after multiple visits to the emergency department and the obstetrical clinic with symptoms of nausea and vomiting. Her symptoms were initially attributed to hyperemesis gravidarum and only after multiple hospital visits was her hypercalcemia discovered. Her workup led to the diagnosis of primary hyperparathyroidism caused by a solitary parathyroid adenoma. The patient was treated conservatively with intravenous fluids and eventually surgical resection of the parathyroid adenoma which led to complete resolution of her symptoms. This case demonstrates the diagnostic and therapeutic challenges associated with hyperparathyroidism in pregnancy.

  16. Radioiodine-induced thyroid storm. Case report and literature review

    SciTech Connect

    McDermott, M.T.; Kidd, G.S.; Dodson, L.E. Jr.; Hofeldt, F.D.

    1983-08-01

    Thyroid storm developed following radioiodine therapy in a 43-year-old man with Graves' disease, weight loss, myopathy, severe thyrotoxic hypercalcemia, and a pituitary adenoma. The hypercalcemia may have been a significant, and previously unreported, predisposing factor for the radioiodine-associated thyroid storm. This case and 15 other well-documented cases of radioiodine-associated storm found in the literature are reviewed, as are several other cases of less severe exacerbations of thyrotoxicosis associated with radioiodine therapy. Although not often seen, these complications are often fatal. High-risk patients, such as the elderly, those with severe thyrotoxicosis, and those with significant underlying diseases, may benefit from preventive measures such as the judicious use of thyrostatic medications during the periods before and after isotope administration.

  17. Parathyroid carcinoma masquerading as morning sickness in pregnancy.

    PubMed

    Panchani, Roopal; Varma, Tarun; Goyal, Ashutosh; Tripathi, Sudhir

    2013-10-01

    Incidence of primary hyperparathyroidism (PHP) in pregnancy is 8/100,000 population/year with less than 200 cases reported. Physiological changes associated with pregnancy make a diagnosis of PHP difficult and 80% are asymptomatic. High index of suspicion is required as physiological hypocalcemia related to hemodilution, increased glomerular filtration rate resulting in maternal hypercalciuria and gestational hypoalbuminemia can mask hypercalcemia of PHP. Maternal and fetal complication rates are high. Early recognition followed by appropriate management and treatment significantly reduces complications. Here, we present a rare case of parathyroid carcinoma in pregnancy and highlight the difficulties in diagnosis given the non-specific symptoms related to hypercalcemia. We have also discussed the management of PHP during the pregnancy. PHP is a preventable cause of fetal and maternal morbidity and mortality.

  18. Normocalcemic primary hyperparathyroidism

    PubMed Central

    Bilezikian, John P.; Silverberg, Shonni J.

    2011-01-01

    SUMMARY Primary hyperparathyroidism is a common disorder of mineral metabolism characterized by incompletely regulated, excessive secretion of parathyroid hormone from one or more of the parathyroid glands. The historical view of this disease describes two distinct entities marked by two eras. When primary hyperparathyroidism was first discovered about 80 years ago, it was always symptomatic with kidney stones, bone disease and marked hypercalcemia. With the advent of the multichannel autoanalyzer about 40 years ago, the clinical phenotype changed to a disorder characterized by mild hypercalcemia and the absence of classical other features of the disease. We may now be entering a 3rd era in the history of this disease in which patients are being discovered with normal total and ionized serum calcium concentrations but with parathyroid hormone levels that are consistently elevated. In this article, we describe this new entity, normocalcemic primary hyperparathyroidism, a forme fruste of the disease. PMID:20485897

  19. Unusual ¹⁸F-FDG PET/CT finding of an oxyphil parathyroid adenoma in a patient with Hodgkin's Lymphoma.

    PubMed

    Niccoli-Asabella, Artor; Ferrari, Cristina; Antonica, Filippo; Scardapane, Arnaldo; Rubini, Domenico; Rubini, Giuseppe

    2014-01-01

    Malignancy-associated hypercalcemia is a complication of advanced tumours that is associated to a poor prognosis. Thorough evaluation to establish its cause is essential because some patients may actually have undiagnosed primary hyperparathyroidism. We report a case of a patient affected by Hodgkin's Lymphoma and persistent hypercalcemia with an incidental (18)F-FDG PET/CT finding in the anterior neck region, not ascribable to malignancy, confirmed with (99m)Tc-sestamibi scintigraphy. It was removed by minimally invasive surgery. It was shown to be an oxyphil parathyroid adenoma localized in an unusual site. Copyright © 2013 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  20. Cinacalcet hydrochloride (Sensipar)

    PubMed Central

    2005-01-01

    Currently, >300,000 patients with end-stage renal disease require dialysis. Secondary hyperparathyroidism is a serious complication of end-stage renal disease and can lead to renal osteodystrophy and other organ failure. Vitamin D sterols and phosphate binders are used to treat hyperparathyroidism, but they can cause hypercalcemia, which contributes to vascular and soft-tissue calcification. Cinacalcet (Sensipar) is the first agent in its class that treats secondary hyperparathyroidism by increasing the sensitivity of calcium sensing receptors. It is also indicated for the treatment of hypercalcemia in patients with parathyroid carcinoma. All clinical trials concluded that cinacalcet is effective for the reduction of parathyroid hormone, serum calcium, phosphorus, and calcium-phosphate product levels. Cinacalcet is available as a once-daily oral therapy. Adverse effects are generally mild. PMID:16200170

  1. Multiple myeloma presenting as acute pancreatitis.

    PubMed

    Mishra, Shakti Bedanta; Azim, Afzal; Mukherjee, Arindam

    2017-09-01

    A 36 year old male presented to the emergency department with severe epigastric pain, nausea, vomiting without hematemesis, diarrhea and anorexia. He presented with respiratory distress, shock and fever at the emergency. He was intubated and shifted to the intensive care unit with the diagnosis of acute pancreatitis with hypercalcemia and an elevated amylase and lipase's well as thrombocytopenia and elevated creatinine. CT scan of abdomen was done which showed lytic bone lesions in the spine and necrosis of the pancrease. He was evaluated for multiple myeloma and it was confirmed in a bone marrow biopsy. Multiple myeloma usually is seen in patients aged more than 60 yrs. The typical presentation of multiple myeloma is anemia, back pain, and an elevated sedimentation rate. Patients with multiple myeloma have hypercalcemia but it's rarely manifested as acute pancreatitis. This case shows a rare presentation of multiple myeloma as acute pancreatitis in a younger adult. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Muscular Sarcoidosis Detected by F-18 FDG PET/CT in a Hypercalcemic Patient

    PubMed Central

    Han, Eun Ji; Jang, Yi Sun; Lee, In Suk; Lee, Jong Min; Kang, Siwon

    2013-01-01

    Sarcoidosis is a systemic granulomatous disease of unknown etiology that involves many organs, occasionally mimicking malignancy. We herein report a 50-yr-old woman of muscular sarcoidosis of chronic myopathic type, manifested by hypercalcemia and muscle wasting. Besides insignificant hilar lymphadenopathy, her sarcoidosis was confined to generalized atrophic muscles and therefore, F-18 FDG PET/CT alone among conventional imaging studies provided diagnostic clues for the non-parathyroid-related hypercalcemia. On follow-up PET/CT during low-dose steroid treatment, FDG uptake in the muscles disappeared whereas that in the hilar lymph nodes remained. PET/CT may be useful in the evaluation of unexpected disease extent and monitoring treatment response in suspected or known sarcoidosis patients. PMID:24015050

  3. A case of acute psychosis in an adolescent male.

    PubMed

    Babar, Ghufran; Alemzadeh, Ramin

    2014-01-01

    Primary hyperparathyroidism (PHPT) is a disorder of calcium homeostasis. We report the case of a 17-year-old adolescent male, who presented with an acute psychosis coinciding with severe hypercalcemia and markedly elevated intact parathyroid hormone (iPTH) level and low vitamin D level. A Sestamibi scan showed a positive signal inferior to the left lobe of the thyroid gland. He had only a partial response to the initial medical and psychiatric management. The enlarged parathyroid gland was resected surgically and postoperatively serum calcium and iPTH levels normalized. The histopathology was compatible with a benign adenoma. Patient's acute psychotic symptoms resolved gradually after surgery; however he remained under psychiatric care for the behavioral issues for about 6 months after surgery. While psychosis is a rare clinical manifestation of hypercalcemia secondary to PHPT in pediatric population, it should be considered as a clinical clue in an otherwise asymptomatic pediatric patient.

  4. Needle in a haystack-parathyroid gland in a 10-day old infant: a case report and literature review.

    PubMed

    Ismail, Adel; Abbas, Tariq O; Al-Khalaf, Fawziya

    2011-01-01

    Neonatal severe primary hyperparathyroidism (NSPHT) is a rare autosomal recessive disorder of calcium homeostasis. It presents shortly after birth and is characterized by striking hyperparathyroidism, marked hypercalcemia, and hyperparathyroid bone disease. It is caused by mutations of the calcium-sensing receptor (CASR), the ionized calcium sensor for the parathyroid cells, the parafollicular thyroid C cells, and the kidney epithelium, as well as cells in bone and intestine. Without early intervention, which frequently requires surgical removal of the hyperplastic parathyroids, the patients often succumb to complications of hypercalcemia and respiratory failure. Finding the parathyroid gland in small neonates is not an easy task. Here we report on a patient with neonatal hyperparathyroidism who was treated by total parathyroidectomy and discuss the various ways of helping to find the parathyroid glands during surgery at this young age.

  5. [Metabolic encephalopathy secondary to vitamin D intoxication].

    PubMed

    Herrera Martínez, Aura; Viñals Torràs, Montserrat; Muñoz Jiménez, Ma Concepción; Arenas de Larriva, Antonio Pablo; Molina Puerta, Ma José; Manzano García, Gregorio; Gálvez Moreno, Ma Ángeles; Calañas-Continente, Alfonso

    2014-10-25

    The association between vitamin D deficiency and increased risk of, among others, cardiovascular and autoimmune diseases has lead in the last years to an enhanced interest in the usage of supplements to achieve the normalization of plasmatic values at 25(OH) D. Apparently this search for normalization is resulting in an higher incidence on vitamin D intoxication. We present the case of an 81 years old woman with metabolic encephalopathy and renal failure secondary to iatrogenic vitamin D intoxication. Calcium and vitamin D oral supplements were prescribed after an osteoporotic vertebral fracture. The patient improved clinically as well as analytically after receiving treatment with diuretics and hydration. We emphasize the importance of discarding hypercalcemia as a cause of metabolic encephalopathy; moreover we highly recommend keeping vitamin D intoxication in mind as an uncommon although always possible etiology of reversible hypercalcemia and renal failure.

  6. Diagnosis and treatment of primary hyperparathyroidism in a bobcat (Lynx rufus).

    PubMed

    Goodnight, Andrea L; Gottfried, Sharon D; Emanuelson, Karen

    2011-09-01

    An 18-yr-old male bobcat (Lynx rufus) presented with chronic moderate weight loss and acute onset of anorexia and lethargy. Hypercalcemia and azotemia were present on the serum chemistry panel. Abdominal ultrasound revealed hyperechoic renal cortices, but no evidence of neoplasia. Ionized calcium and 25-hydroxyvitamin D were mildly elevated, intact parathyroid hormone was severely elevated, and parathormone-related protein was undetected, suggesting primary hyperparathyroidism with possible renal dysfunction. Azotemia lessened in severity following diuresis, but hypercalcemia persisted; thus primary hyperparathyroidism was considered the most probable differential diagnosis. A second ultrasound including the cervical region revealed a solitary intraparenchymal left thyroid nodule. The nodule was surgically excised; histopathology confirmed a parathyroid adenoma. Although primary hyperparathyroidism was suspected, diagnosis was not achieved from serum chemistry values alone. This case emphasizes the importance of diagnostic imaging and histopathology in the investigation of persistently abnormal laboratory values.

  7. Impact of CRAB Symptoms in Survival of Patients with Symptomatic Myeloma in Novel Agent Era

    PubMed Central

    Nakaya, Aya; Fujita, Shinya; Satake, Atsushi; Nakanishi, Takahisa; Azuma, Yoshiko; Tsubokura, Yukie; Hotta, Masaaki; Yoshimura, Hideaki; Ishii, Kazuyoshi; Ito, Tomoki; Nomura, Shosaku

    2017-01-01

    The acronym CRAB summarizes the most typical clinical manifestations of multiple myeloma, these being hypercalcemia, renal failure, anemia, and bone disease. CRAB can be used to distinguish between active, symptomatic multiple myeloma and monoclonal gammopathy of undermined significance or smoldering myeloma. The distinction is relevant not only for classification and diagnosis but also for therapy. CRAB factors influence the prognosis of multiple myeloma. However, it is unclear whether the presence of CRAB factors has an influence on the prognosis of myeloma treated with novel agents. In the current study, patients with hypercalcemia and bone disease showed a significantly worse prognosis, whereas anemia and renal failure showed no difference in survival. Novel agents used for treatment of patients with renal failure suggested a favorable outcome compared with conventional therapy. Bone disease was the most common factor and may have the strongest prognostic value in symptomatic myeloma patients using novel agents. PMID:28286629

  8. New aspects of treatment of renal bone disease in dialysis patients.

    PubMed

    Spasovski, G

    2007-07-01

    The abnormalities in bone and mineral metabolism in chronic kidney disease patients are associated with an increased risk of fractures, vascular calcifications and cardiovascular diseases. A few decades ago hyperphosphatemia and the common development of secondary hyperparathyroidism were thought to be the main problem to deal with. Since dietary phosphate restriction and haemodialysis were not proven to be sufficient measures to reduce phosphorus, phosphate-binding therapy has been widely instituted as a treatment option. Various types of phosphate binders employed over the years have contributed to the changing spectrum of renal osteodystrophy from high to low bone turnover along with the shift from hypocalcemia and negative calcium balance towards hypercalcemia and the positive calcium balance. Thus, hypercalcemia instead of hyperphosphatemia is nowadays associated with the increased risk of vascular calcification, morbidity and mortality in the dialysis population. Besides the very expensive non-calcium based phosphate binders, at least two common tools may be helpful in the treatment of hypercalcemia and adynamic bone. A reduced daily use of calcium carbonate/acetate up to 1g per main meal is an easily manageable and inexpensive tool. The second option for stimulation of parathyroid gland activity and bone turnover is the lowering of the dialysate calcium concentration. In conclusion, an aggressive treatment of hyperphosphatemia and calcium overload might lead towards an opposite effect of hypoparathyroidism and hypercalcemia. Reasonable treatment strategies based on a careful monitoring should be employed in order to prevent related consequences and to contribute to a better long-term quality of life and survival of dialysis patients.

  9. Antacids, altered mental status, and milk-alkali syndrome.

    PubMed

    Watson, Simon C; Dellinger, Bonnie B; Jennings, Katie; Scott, Lancer A

    2012-01-01

    The frequency of milk-alkali syndrome decreased rapidly after the development of histamine-2 antagonists and proton pump inhibitors for the treatment of peptic ulcer disease; however, the availability and overconsumption of antacids and calcium supplements can still place patients at risk (D. P. Beall et al., 2006). Here we describe a patient who presented with altered mental status, hypercalcemia, metabolic alkalosis, and acute renal failure in the context of ingesting large amounts of antacids to control dyspepsia.

  10. Metal Compounds in Therapy and Diagnosis

    NASA Astrophysics Data System (ADS)

    Abrams, Michael J.; Murrer, Barry A.

    1993-08-01

    There is increasing interest in the use of metal-containing compounds in medicine. This review describes several therapeutic applications, such as the use of platinum complexes in cancer chemotherapy, gold compounds in the treatment of arthritis, gallium in hypercalcemia, bismuth in anti-ulcer medication, and sodium nitroprusside in hypertension. The use of metal radionuclides in diagnosis and radiotherapy and the role of paramagnetic metal complexes as contrast agents in magnetic resonance imaging are also discussed.

  11. Prevention of Post-Radiotherapy Failure in Prostate Cancer by Vitamin D

    DTIC Science & Technology

    2006-03-01

    7 Laboratory studies: Summary Vitamin D3 (Calcitriol) has been used both alone and in combination with chemotherapeutic agents such as...Docetaxel to suppress the growth of prostate tumors. However vitamin D3 has also been shown to upregulate the levels of androgen receptor in prostate...tumor cells in culture and in addition has been linked to dose-limiting hypercalcemia. Here we confirm those data indicating that 0.1μM vitamin D3

  12. [Differential diagnosis of reduced uptake images revealed by bone scan: about a case of acute lymphoblastic leukemia].

    PubMed

    Bahadi, Nisrine; Biyi, Abdelhamid; Oueriagli, Salah Nabih; Doudouh, Abderrahim

    2016-01-01

    If increased uptake during bone scan usually bring to light many bone pathologies, reduced uptakes are a rare occurrence and they require careful analysis to avoid erroneous interpretations. We report the case of a 17-year old admitted with diffuse bone pain, hypercalcemia and thrombopenia. Bone scan showed areas of low uptakes. Bone marrow tests allowed the diagnosis of acute lymphoblastic leukemia. This case report aims to discuss the main differential diagnoses based on such bone scan abnormalities.

  13. A Case Report of 20 Lung Radiofrequency Ablation Sessions for 50 Lung Metastases from Parathyroid Carcinoma Causing Hyperparathyroidism

    SciTech Connect

    Tochio, Maki Takaki, Haruyuki; Yamakado, Koichiro; Uraki, Junji; Kashima, Masataka; Nakatsuka, Atsuhiro; Takao, Motoshi; Shimamoto, Akira; Tarukawa, Tomohito; Shimpo, Hideto; Takeda, Kan

    2010-06-15

    A 47-year-old man presented with multiple lung metastases from parathyroid carcinoma that caused hyperparathyroidism and refractory hypercalcemia. Lung radiofrequency (RF) ablation was repeated to decrease the serum calcium and parathyroid hormone levels and improve general fatigue. Pulmonary resection was combined for lung hilum metastases. The patient is still alive 4 years after the initial RF session. He has received 20 RF sessions for 50 lung metastases during this period.

  14. Phase I study of weekly DN-101, a new formulation of calcitriol, in patients with cancer.

    PubMed

    Beer, Tomasz M; Javle, Milind M; Ryan, Christopher W; Garzotto, Mark; Lam, Gilbert N; Wong, Alvin; Henner, W David; Johnson, Candace S; Trump, Donald L

    2007-04-01

    DN-101 is a new, high-dose, oral formulation of calcitriol under investigation for the treatment of cancer. We sought to evaluate the tolerability and pharmacokinetics (PK) of weekly doses of DN-101 in patients with advanced cancer. Patients who completed a previously reported single dose escalation study of DN-101 [Beer et al. (2005) Clin Cancer Res 11:7794-7799] were eligible for this continuation weekly dosing study. Cohorts of 3-10 patients were treated at doses of 15, 30, 45, 60, and 75 microg calcitriol. Once 45 microg was established as the maximum tolerated dose (MTD), this cohort was expanded to include 18 patients. Dose limiting toxicity (DLT) was defined as > or =grade 2 hypercalcemia or > or =grade 3 persistent treatment-related toxicities. Thirty-seven patients were recruited. DLT of transient reversible grade 2 hypercalcemia (serum calcium of 11.6-12.5 mg/dL) occurred in two of six patients treated with 60 microg of DN-101. No DLT was observed in the 18 patients who received DN-101 weekly at 45 microg. Overall, DN-101 was well tolerated. The most frequent adverse events were fatigue (27%), hypercalcemia (19%, including five grade 1, two grade 2, and no grade 3 or 4 events), and grade 1 nausea (16%). PK parameters following repeat dosing were comparable to those for the initial dose (n = 4). The MTD for weekly DN-101 was established as 45 mug. The DLTs observed were two episodes of rapidly reversible grade 2 hypercalcemia in two of the six patients treated at 60 microg weekly. Repeat doses of DN-101 at 45 microg weekly are well tolerated and this dose is suitable for studies of weekly DN-101 in cancer patients.

  15. [Vademecum of skeletal complications of malignancy].

    PubMed

    Py, Céline; Dietrich, Pierre-Yves; Ben Aïssa, Assma

    2013-05-22

    Bone metastasis is a frequent complication for cancer patients leading pain, fracture, spinal cord compression and hypercalcemia. A multidisciplinary approach is strongly recommended to optimize the different treatment options (i.e. radiotherapy, surgery and vertebroplasty) in the context of the underlying cancer. The effectiveness of bisphosphonates and denosumab to reduce skeletal events has widely been demonstrated. Prevention and treatment of bone complications are crucial for maintaining the independence and quality of life of patients.

  16. Cinacalcet administration by gastrostomy tube in a child receiving peritoneal dialysis.

    PubMed

    Nichols, Kristen R; Knoderer, Chad A; Johnston, Bethanne; Wilson, Amy C

    2014-07-01

    A 2-year-old male with chronic kidney disease with secondary hyperparathyroidism developed hypercalcemia while receiving calcitriol, without achieving a serum parathyroid hormone concentration within the goal range. Cinacalcet 15 mg (1.2 mg/kg), crushed and administered via gastrostomy tube, was added to the patient's therapy. This therapy was effective in achieving targeted laboratory parameters in our patient despite instructions in the prescribing information that cinacalcet should always be taken whole.

  17. Cinacalcet Administration by Gastrostomy Tube in a Child Receiving Peritoneal Dialysis

    PubMed Central

    Knoderer, Chad A.; Johnston, Bethanne; Wilson, Amy C.

    2014-01-01

    A 2-year-old male with chronic kidney disease with secondary hyperparathyroidism developed hypercalcemia while receiving calcitriol, without achieving a serum parathyroid hormone concentration within the goal range. Cinacalcet 15 mg (1.2 mg/kg), crushed and administered via gastrostomy tube, was added to the patient’s therapy. This therapy was effective in achieving targeted laboratory parameters in our patient despite instructions in the prescribing information that cinacalcet should always be taken whole. PMID:25309151

  18. Cinacalcet Monotherapy in Neonatal Severe Hyperparathyroidism: A Case Study and Review

    PubMed Central

    Gannon, Anthony W.; Monk, Heather M.

    2014-01-01

    Context: Neonatal severe hyperparathyroidism (NSHPT) is a severe form of familial hypocalciuric hypercalcemia characterized by severe hypercalcemia and skeletal demineralization. In most cases, NSHPT is due to biallelic loss-of-function mutations in the CASR gene encoding the calcium-sensing receptor (CaSR), but some patients have heterozygous mutations. Conventional treatment consists of iv saline, bisphosphonates, and parathyroidectomy. Objective: The aim of this project was to characterize the molecular basis for NSHPT in an affected newborn and to describe the response to monotherapy with cinacalcet. Methods: Clinical and biochemical features were monitored as cinacalcet therapy was initiated and maintained. Genomic DNA was obtained from the proband and parents. The CASR gene was amplified by PCR and sequenced directly. Results: The patient was a full-term male who developed hypotonia and respiratory failure soon after birth. He was found to have multiple fractures and diffuse bone demineralization, with a marked elevation in serum ionized calcium (1.99 mmol/L) and elevated serum levels of intact PTH (1154 pg/mL); serum 25-hydroxyvitamin D was low, and fractional excretion of calcium was reduced. The serum calcium level was not reduced by iv saline infusion. Based on an extensive family history of autosomal dominant hypercalcemia, a diagnosis of NSHPT was made, and cinacalcet therapy was initiated with a robust and durable effect. Molecular studies revealed a heterozygous R185Q missense mutation in the CASR in the patient and his father, whereas normal sequences for the CASR gene were present in the patient's mother. Conclusions: We describe the first use of cinacalcet as monotherapy for severe hypercalcemia in a newborn with NSHPT. The rapid and durable response to cinacalcet suggests that a trial of calcimimetic therapy should be considered early in the course of NSHPT. PMID:24203066

  19. Tumor-Host Interactions in Breast Cancer Bone Metastasis

    DTIC Science & Technology

    2004-06-01

    can have serious complications, including hypercalcemia, pain, pathologic fractures and central nervous compromise (spinal cord or nerve root...compression)’. Bone metastases are the most common cause of pain for cancer patients, resulting from either mechanical or chemical stimulation of pain...involved in osteoblast stimulation of osteoclastogenesis. Many of these, for example PTHrP, IL-6, IL- 11 and M-CSF, are expressed by tumor cells 1

  20. [Slipped capital femoral epiphysis associated with hyperparathyroidism. A case report].

    PubMed

    Khiari, Karima; Cherif, Lotfi; Ben Abdallah, Nejib; Maazoun, Imen; Hadj Ali, Insaf; Bentaarit, Chokri; Turki, Sami; Ben Maïz, Hedi

    2003-12-01

    Slippage of the upper femoral epiphysis can occur in association with multiple endocrine imbalances. A case of slipped femoral epiphysis with primary hyperparathyroidism is reported. The patient was an adolescent, 16 Years of age, who presented bilateral slipped epiphysis. Investigation showed that he had hypercalcemia (3.1 mmol/l) related to primary hyperparathyroidism. A parathyroid adenoma was removed. Outcome was favorable and the slipped femoral epiphyses did not require a specific treatment.

  1. Primary hyperparathyroidism associated to thrombocytopenia: an issue to consider?

    PubMed Central

    De Keukeleire, Steven; Muylle, Kristoff; Tsoumalis, Georgios; Vermeulen, Stefan; Vogelaers, Dirk

    2017-01-01

    Summary Primary hyperparathyroidism (PHPT) is probably the most common endocrine disorder of the parathyroid glands, causing hypercalcemia. It is diagnosed often in persons with elevated serum calcium levels. However, hematological manifestations, such as thrombocytopenia are less known. In this case we describe the possible association of PHPT with reversible thrombocytopenia after parathyroidectomy. This hematological abnormality can be included in the spectrum of possible causes, including seemingly non-specific symptoms, in the decision tree towards surgical assessment. PMID:28740534

  2. Diverse clinical manifestations of pheochromocytomas.

    PubMed

    Badui, E; Mancilla, R; Szymanski, J J; Garcia-Rubi, D; Estañol, B

    1982-03-01

    Many difficulties are encountered by clinicians in attempting to diagnose pheochromocytomas. We describe several patients with unusual clinical features. These include sudden death, cerebral hemorrhage, refractory congestive heart failure, acute abdominal pain, and hypercalcemia. In 2 patients, the rare association of this tumor and pregnancy was observed. Two subjects had sudden death, 1 during a pneumoencephalogram and another during an epidural block. The clinicians should be aware of these manifestations of pheochromocytomas.

  3. Late neonatal hypocalcemic tetany as a manifestation of unrecognized maternal primary hyperparathyroidism.

    PubMed

    Çakır, Ufuk; Alan, Serdar; Erdeve, Ömer; Atasay, Begüm; Şıklar, Zeynep; Berberoğlu, Merih; Arslan, Saadet

    2013-01-01

    Maternal primary hyperparathyroidism causing hypercalcemia during pregnancy can suppress fetal and neonatal parathyroid hormone secretion. We report a newborn with transient hypoparathyroidism presented by hypocalcemic seizure and tetany on the 21st postnatal day in whom the final diagnosis was asymptomatic maternal primary hyperparathyroidism. Neonatal hypocalcemia usually occurs early in life in infants of maternal primary hyperparathyroidism, and although it is very rare, further investigation for unexplained late-onset hypocalcemia may reveal this diagnosis.

  4. Dual antiplasmodial activity of vitamin D3 and its analog, 22-oxacalcitriol, by direct and indirect mechanisms.

    PubMed

    Yamamoto, Kiichi; Iwagami, Moritoshi; Seki, Takenori; Kano, Shigeyuki; Ota, Nobuo; Ato, Manabu

    2017-04-01

    Recent evidence suggests that 1α,25-dihydroxyvitamin D3 (calcitriol, VD3), the active form of vitamin D (VD), can inhibit the proliferation of microorganisms. In the present study, we conducted in vitro experiments and utilized in vivo murine models to investigate the antimalarial activity of VD3 and its analog, 22-oxacalcitriol (22-OCT), which was designed to cause less hypercalcemia than VD3. VD3 and 22-OCT treatments effectively resolved a Plasmodium chabaudi (Pc) infection in wild-type mice. Reduced parasitemia was observed during the acute phase of infection in the presence of VD3 and 22-OCT, followed by a delayed peak during the chronic stage of infection. Some anti-Pc activity was observed in VD receptor knockout (KO) mice. VD3 and 22-OCT also completely inhibited the proliferation of P. falciparum (Pf) in human red blood cells in vitro. Plasma levels of interferon (IFN)-γ in VD3-treated B10 and B6 mice were lower than those in vehicle-treated animals, and VD3 resolved a Pc infection in IFN-γ-KO mice, which greatly improved survival. These data suggest that the protective effects of VD3 are elicited through an IFN-γ-independent mechanism. Effective antiplasmodial doses of VD3 and 22-OCT resulted in a loss of body weight in mice. This loss in body weight occurred concomitantly with the development of hypercalcemia. Zoledronic acid partially attenuated VD3-induced hypercalcemia and abrogated the antiparasitic effects of VD3. This study highlights a potential therapeutic role for VD3 in the treatment of malarial infections and shows that hypercalcemia is excellent indicator of the antiplasmodial activity of VD3.

  5. Idiopathic massive myocardial calcification: a case report and review of the literature.

    PubMed

    Shackley, Brit S; Nguyen, Thao P; Shivkumar, Kalyanam; Finn, Paul J; Fishbein, Michael C

    2011-01-01

    We report a rare case of massive myocardial calcification in a 42-year-old male who presented with symptoms of congestive heart failure and arrhythmia. Myocardial calcification is most commonly associated with myocardial infarction or, less commonly, hypercalcemia. This case is particularly unusual due to the lack of any known predisposing risk factors, including normal coronary arteries, normal renal function, and normal serum calcium levels. Alternative etiologies are discussed accompanied by a review of the literature.

  6. Senile Cardiac Calcification Syndrome: A Rare Case of Extensive Calcification of Left Ventricular Papillary Muscle

    PubMed Central

    Kim, Eun Jin; Song, Bong Gun; Sohn, Hyung Rae; Hong, Su-Min; Park, Dong Won; Heo, Seung Hye; Kim, Kye Yeon; Cho, Wook-Hyun; Choi, Suk-Koo

    2011-01-01

    Extensive papillary muscle calcification is uncommon and only scarce literature about causes and the clinical significance is available, whereas small calcific deposits are common findings in elderly people and are located most commonly at the apex. Papillary muscle calcification has been associated with coronary artery disease, dilated cardiomyopathy, mitral valve disease, hypercalcemia, and increased calcium phosphate product in end stage renal disease. We reported a rare case of extensive calcification of anterolateral papillary muscle diagnosed by echocardiography and multidetector computed tomography.

  7. High serum parathyroid hormone and calcium are risk factors for hypertension in Japanese patients.

    PubMed

    Yagi, Shusuke; Aihara, Ken-ichi; Kondo, Takeshi; Endo, Itsuro; Hotchi, Junko; Ise, Takayuki; Iwase, Takashi; Akaike, Masashi; Matsumoto, Toshio; Sata, Masataka

    2014-01-01

    Excess parathyroid hormone (PTH), known as primary hyperparathyroidism (pHPT), results in hypercalcemia and bone loss. Recent studies have shown that PTH is associated with the occurrence of hypertension in Western countries; however, controversy remains regarding high serum levels of PTH and calcium as risk factors for hypertension in Japanese patients. We retrospectively enrolled 114 consecutive Japanese patients who visited our hospital for examination and treatment of hypercalcemia and/or hypertension with serum calcium levels ≥ 9.8 mg/dL. To estimate the prevalence of hypertension, the patients were categorized according to calcium levels into hypercalcemic (10.2-13.4 mg/dL) and normocalcemic (9.8-10.1 mg/dL) groups, which were further categorized into high PTH (50-440 pg/mL) and low PTH (8-49 pg/mL) groups. The prevalence of hypertension was higher in patients with hypercalcemia than in patients with normocalcemia in both the high and low PTH groups. The prevalence of hypertension was higher in patients with high serum PTH levels than in patients with low serum PTH levels in both the hypercalcemic and normocalcemic groups. Logistic multiple regression analysis determined that serum calcium (P < 0.05) and PTH (P < 0.01) levels were positive contributors to hypertension. In conclusion, high serum levels of PTH and calcium are risk factors for hypertension in Japanese patients.

  8. Parathyroid-hormone-related protein in sarcoidosis.

    PubMed Central

    Zeimer, H. J.; Greenaway, T. M.; Slavin, J.; Hards, D. K.; Zhou, H.; Doery, J. C.; Hunter, A. N.; Duffield, A.; Martin, T. J.; Grill, V.

    1998-01-01

    Parathyroid-hormone-related protein (PTHrP) is the main mediator of the humoral hypercalcemia of malignancy. It is also detected in many normal adult and fetal tissues. Altered calcium metabolism occurs in sarcoidosis, and two cases of sarcoidosis with hypercalcemia and elevated plasma PTHrP are described. An archival study of 20 lymph node biopsies with the pathological diagnosis of sarcoidosis was performed. Immunohistochemistry using a polyclonal antiserum to human PTHrP and in situ hybridization using a riboprobe to human PTHrP were performed on the lymph node biopsies. Immunohistochemistry for PTHrP was also performed on the biopsies from the two cases with elevated plasma levels. Immunohistochemical analysis detected PTHrP in macrophages within granulomata in 17 of the 20 (85%) biopsies. In situ hybridization detected a positive signal for messenger RNA in the granulomata of 11 of 19 (58%) biopsies. PTHrP immunoreactivity and PTHrP gene expression are present in sarcoid granulomata. PTHrP may contribute to the hypercalcemia of sarcoidosis. Images Figure 1 PMID:9422518

  9. Cholecalciferol.

    PubMed

    Peterson, Michael E; Fluegeman, Kerstin

    2013-02-01

    The primary source of exposure to cholecalciferol in dogs and cats is ingestion of rodenticide baits with vitamin D3 as the active ingredient. Other sources of this toxin are human medications and rarely, contaminated pet food. Although the reported lethal dose 50% for cholecalciferol is 88 mg/kg, deaths have been seen with an individual exposure of 2 mc g/kg in dogs. Clinical signs are induced by profound hypercalcemia affecting multiple body systems. Clinical presentations may include anorexia, depression, muscle weakness, vomiting, polyuria, polydipsia, dehydration, abdominal pain, hematemesis, melena, and bradycardia. Tissue mineralization may develop if calcium × phosphorous product is greater than 60. Serum testing for hypercalcemia, hyperphosphatemia, and decreased serum parathyroid hormone are confirmatory. Initial treatment relies upon decontamination with emesis induction followed by administration of pulse-dose activated charcoal designed to interfere with the extensive enterohepatic recirculation of toxin. Medical management is designed to decrease serum calcium levels by use of intravenous fluid diuresis with administration of furosemide and prednisolone. Biphosphate pamidronate is used to inhibit calcium release from the bone. Phosphate binders aid in decreasing phosphate availability to interact with calcium. The prognosis is better if treatment is instituted early before development of hypercalcemia and hyperphosphatemia enables tissue mineralization to progress.

  10. Prediction of serum ionized calcium concentration by serum total calcium measurement in cats.

    PubMed

    Schenck, Patricia A; Chew, Dennis J

    2010-07-01

    Feline serum samples (n = 434) were classified as hypercalcemic, normocalcemic, or hypocalcemic based on both total calcium (tCa) and ionized calcium (iCa) concentrations. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive diagnostic likelihood ratio (PDLR), and negative diagnostic likelihood ratio (NDLR) were calculated for prediction of hypercalcemia and hypocalcemia in all samples, in hypoalbuminemic cats, and in those with chronic renal failure (CRF) as compared with cats that had other conditions. Diagnostic discordance in prediction of iCa using tCa was 40%. Sensitivity of tCa in prediction of ionized hypercalcemia was low and specificity was high. The PDLR for prediction of ionized hypercalcemia or hypocalcemia was low in all cats, especially in those with CRF. Due to the high level of diagnostic discordance, tCa should not be used to predict iCa concentration. Concentration of iCa should be measured directly when accurate assessment of calcium status is needed.

  11. Persistent Primary Hyperparathyroidism, Severe Vitamin D Deficiency, and Multiple Pathological Fractures

    PubMed Central

    Carvallo-Venegas, Mauricio; Vargas-Castilla, Jorge Alberto; Balcázar-Hernández, Lourdes Josefina; Gregor-Gooch, Julián Malcolm Mac

    2016-01-01

    Persistent primary hyperparathyroidism (PHPT) refers to the sustained hypercalcemia state detected within the first six months following parathyroidectomy. When it coexists with severe vitamin D deficiency, the effects on bone can be devastating. We report the case of a 56-year-old woman who was sent to this center because of persistent hyperparathyroidism. Her disease had over 3 years of evolution with nephrolithiasis and hip fracture. Parathyroidectomy was performed in her local unit; however, she continued with hypercalcemia, bone pain, and pathological fractures. On admission, the patient was bedridden with multiple deformations by fractures in thoracic and pelvic members. Blood pressure was 100/80, heart rate was 86 per minute, and body mass index was 19 kg/m2. Calcium was 14 mg/dL, parathormone 1648 pg/mL, phosphorus 2.3 mg/dL, creatinine 2.4 mg/dL, urea 59 mg/dL, alkaline phosphatase 1580 U/L, and vitamin D 4 ng/mL. She received parenteral treatment of hypercalcemia and replenishment of vitamin D. The second surgical exploration was radioguided by gamma probe. A retroesophageal adenoma of 4 cm was resected. Conclusion. Persistent hyperparathyroidism with severe vitamin D deficiency can cause catastrophic skeletal bone softening and fractures. PMID:27525132

  12. [Cancer and electrolytes imbalance].

    PubMed

    Shibata, Hiroyuki

    2010-06-01

    The electrolyte imbalance in advanced cancer patients, including hyperkalemia, hypercalcemia and hyponatremia, can be induced by various factors. Hyperkalemia is occasionally induced by chemotherapy for very large malignant tumors, due to tumor lysis syndrome. Hypercalcemia and hyponatremia are often observed in patients with breast cancer, renal cancer, prostate cancer, and the like, as a paraneoplastic syndrome. Some part of hypercalcemia results from osteolysis, but the majority is induced by hormonal factors, such as parathyroid hormone-related protein. One of the paraneoplastic causes of hyponatremia is antidiuretic hormone-producing tumor. These disorders could be morbid or even motile, resulting from encephalopathy or arrhythmia in some cases. However, it should be kept in mind that they could be improved or cured by prompt treatment. Recently, after approval of the molecular targeted drugs for epidermal growth factor receptors, such as cetuximab and panitumumab, the incidence of hypomagnesia with use of these monoclonal antibodies, is relatively frequent. In addition, small molecular targeted drugs, such as m-TORinhibitors and ABL kinase inhibitors, also exert adverse reactions including hypomagnesia and hypophosphatemia. Careful monitoring of the serum concentration of magnesium and phosphate ions, to which little attention was paid previously, is a key issue in these cases.

  13. Concurrence of primary hyperparathyroidism and metastatic breast carcinoma affected a parathyroid gland.

    PubMed

    Lee, Sang Hee; Kim, Bo Hyun; Bae, Min Jung; Yi, Yang Seon; Kim, Won Jin; Jeon, Yun Kyung; Kim, Sang Soo; Kim, Yong Ki; Kim, In Joo

    2013-08-01

    Involvement of the parathyroid glands by metastatic tumor is rare. Breast is 1 of the primary sites in metastatic cancers. We introduce a rare case of metastatic breast carcinoma affecting a parathyroid gland, which was clinically combined with parathyroid gland hyperplasia. A 65-year-old woman was referred due to hypercalcemia and constipation. The patient had a history of left breast carcinoma. She was admitted to the hospital because of the recent discovery of hypercalcemia and elevation of PTH. A Tc99m-sestamibi scan showed retained uptake in the right thyroid and in the lower pole of the left thyroid gland. Aspiration biopsy results revealed that the nodule in the posterior portion of the right thyroid was metastatic breast cancer and the nodule in the left thyroid gland was the hyperplastic parathyroid gland. This case illustrates that hyperparathyroidism caused by parathyroid hyperplasia was concurrent with metastatic breast cancer to a parathyroid gland without disseminated systemic metastasis. Although this case is very uncommon and it is not clear whether there is a relationship between breast cancer and primary hyperparathyroidism, that possibility should always be considered as the cause of hypercalcemia in patients with breast cancer.

  14. New options for the management of hyperparathyroidism after renal transplantation

    PubMed Central

    Douthat, Walter Guillermo; Chiurchiu, Carlos Raul; Massari, Pablo Ulises

    2012-01-01

    The persistence and severity of hyperparathyroidism (HPT) post-renal transplantation is relatively frequent and primarily associated with the timing and its magnitude in the pre-transplant period and with the presence of parathyroid adenomas. HPT after renal transplantation is clinically manifested with hypercalcemia, hypophosphatemia, bone pain, fractures, and in more serious cases with cardiovascular calcifications that affect the survival. The primary clinical objective for patients with secondary HPT after renal transplantation is to obtain a level of parathyroid hormone (PTH) adequate to the renal transplanted function and to normalize levels of calcium, phosphorus and vitamin D. In many cases during this period, the development of hypercalcemia and/or hypophosphatemia makes it necessary to take different therapeutic measures. The use of vitamin D or its analogues has been extrapolated from the management of pre-transplant HPT obtaining variable outcomes, although its use is limited by its capacity to produce hypercalcemia. Calcimimetics are drugs that have proven be effective in reducing PTH levels in patients with HPT on dialysis and has been effective in reducing up to 50% PTH levels in moderate to severe HPT in post-renal transplantation.When HPT persists after renal transplantation and does not respond to medical treatment, invasive management by percutaneous ethanol injection therapy of parathyroid glands or parathyroidectomy should be considered. The emergence of new methods for the management of HPT expands the availability of therapeutic tools for transplant patients. PMID:24175195

  15. Iatrogenic vitamin D toxicity in an infant--a case report and review of literature.

    PubMed

    Ketha, Hemamalini; Wadams, Heather; Lteif, Aida; Singh, Ravinder J

    2015-04-01

    Public concern over vitamin D deficiency has led to widespread use of over the counter (OTC) vitamin D (-D3 or -D2) supplements, containing up to 10,000 IU/unit dose (400 IU=10μg). Overzealous use of such supplements can cause hypercalcemia due to vitamin D toxicity. Infants are particularly vulnerable to toxicity associated with vitamin D overdose. OTC supplements are not subject to stringent quality control regulations from FDA and high degree of variability in vitamin D content in OTC pills has been demonstrated. Other etiologies of vitamin D induced hypercalcemia include hyperparathyroidism, granulomatous malignancies like sarcoidosis and mutations in the CYP24A1 gene. The differential diagnosis of hypercalcemia should include iatrogenic and genetic etiologies. C24-hydroxylation and C3-epimerization are two important biochemical pathways via which 25-hydroxyvitamin D3 (25(OH)D3) is converted to its metabolites, 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) or its C3 epimer, 3-epi-25-OH-D3 respectively. Mutations in the CYP24A1 gene cause reduced serum 24,25(OH)2D3 to 25(OH)D3 ratio (<0.02), elevated serum 1,25-dihydroxyvitamin D (1,25(OH)2D3), hypercalcemia, hypercalciuria and nephrolithiasis. Studies in infants have shown that 3-epi-25(OH)D3 can contribute 9-61.1% of the total 25(OH)D3. Therefore, measurements of parathyroid hormone (PTH) and vitamin D metabolites 25(OH)D3, 1,25(OH)2D3, 3-epi-25(OH)D3 and 24,25(OH)2D3 are useful to investigate whether the underlying cause of vitamin D toxicity is iatrogenic versus genetic. Here we report a case of vitamin D3 associated toxicity in a 4-month-old female who was exclusively breast-fed and received an oral liquid vitamin D3 supplement at a dose significantly higher than recommended on the label. The vitamin D3 content of the supplement was threefold higher (6000 IU of D/drop) than listed on the label (2000 IU). Due to overdosing and higher vitamin D3 content, the infant received ∼50,000 IU/day for two months

  16. Elevations in serum and urinary calcium with parathyroid hormone (1-84) with and without alendronate for osteoporosis.

    PubMed

    Antoniucci, Diana M; Sellmeyer, Deborah E; Bilezikian, John P; Palermo, Lisa; Ensrud, Kristine E; Greenspan, Susan L; Black, Dennis M

    2007-03-01

    The effect of PTH therapy on serum and urinary calcium levels and the risk of hypercalcemia or hypercalciuria has not been formally evaluated. The objective was to examine changes in serum and urinary calcium associated with PTH(1-84) therapy in the PaTH trial and the extent to which a defined algorithm resolved the elevated values. A total of 178 postmenopausal women were randomized to PTH(1-84) either alone or in combination with alendronate during the first year of the PaTH study. The main outcome measures were fasting serum calcium at baseline and 1, 3, and 12 months and 24-h urinary calcium at baseline and 3 months. In 14% of participants, serum calcium more than 10.5 mg/dl (>2.6 mmol/liter) developed. Following the defined algorithm, 58% of elevated measurements were normal on repeat testing; 38% required discontinuation of calcium and vitamin D supplementation, and one necessitated a decrease in PTH injection frequency to normalize serum calcium. One participant developed transient hypercalcemia between study visits and required hospitalization; the episode resolved with iv hydration and PTH discontinuation. Baseline characteristics associated with the development of hypercalcemia were serum calcium [relative hazards = 1.9 per 0.5 mg/dl (0.12 mmol/liter); 95% confidence interval = 1.1-3.2] and serum 1,25-dihydroxyvitamin D [relative hazard = 1.9 per 10 pg/ml (26 pmol/liter); 95% confidence interval = 1.2-3.1]. Fifteen women (8%) developed hypercalciuria [urinary calcium > 400 mg (100 mmol)/24 h or calcium/creatinine ratio > 0.4]; 80% of cases resolved after discontinuing calcium and vitamin D, 13% without intervention, and one after PTH injection frequency was decreased. Higher baseline urinary calcium excretion was associated with development of hypercalciuria [relative hazard = 1.5 per 50 mg/d (12.5 mmol/d); 95% confidence interval = 1.2-4.0]. Proportions of patients with elevated serum and urinary calcium were similar on single and combination therapy

  17. Effects of disodium EDTA and calcium infusion on prolactin and thyrotropin responses to thyrotropin-releasing hormone in healthy man.

    PubMed

    Dudczak, R; Waldhäusl, W K; Bratusch-Marrain, P

    1983-03-01

    To determine the impact of induced hypo- and hypercalcemia on TRH (400 micrograms)-stimulated TSH and PRL release, healthy subjects (n = 11) were infused with 5% glucose in water (n = 11), disodium EDTA (n = 11), or calcium gluconate (n = 7). TRH was given as an iv bolus 60 min (5% glucose and EDTA) and 120 min (calcium) after initiation of the respective infusion. Basal plasma concentrations of TSH remained unchanged during induced hypo- and hypercalcemia, whereas those of PRL fell during the latter (P less than 0.05). The mean sum of increments (0-90 min) in PRL and TSH was considerably greater during hypocalcemia than during hypercalcemia (PRL, P less than 0.002; TSH, P less than 0.005). The increments in the plasma hormone concentration above basal after iv TRH were increased compared to those in normocalcemia (PRL, 98.4 +/- 37.9 ng/ml; TSH, 38.9 +/- 11.8 microU/ml) during hypocalcemia [PRL, 128 +/- 47.8 ng/ml (P less than 0.002); TSH, 46.7 +/- 12.8 microU/ml; (P less than 0.005)], but were impaired during hypercalcemia [PRL, 70.1 +/- 27 ng/ml (P less than 0.002); TSH, 28.9 +/- 8.5 microU/ml (P less than 0.025)]. The mean sum of increments in PRL was related to concentrations of both serum calcium (r = -0.59; P less than 0.01) and PTH (r = 0.51; P less than 0.05). A relation was also seen between the incremental responses of TSH and serum calcium (r = -0.52; P less than 0.05), PTH (r = 0.55; P less than 0.01), and phosphorus (r = -0.55; P less than 0.01). We conclude that in healthy man, TRH-mediated release of both PRL and TSH are inversely related to serum calcium concentrations in such a manner that hormone secretion is enhanced by acute hypocalcemia, but blunted by hypercalcemia.

  18. Ethacrynic acid and 1 alpha,25-dihydroxyvitamin D3 cooperatively inhibit proliferation and induce differentiation of human myeloid leukemia cells.

    PubMed

    Makishima, M; Honma, Y

    1996-09-01

    The active form of vitamin D, 1 alpha,25-dihydroxyvitamin D3 (VD3), inhibits proliferation and induces differentiation of leukemia cells, but its clinical use is limited by the adverse effect of hypercalcemia. In this study we found that the loop diuretic ethacrynic acid, which is used to treat hypercalcemia, enhanced the differentiation of human leukemia cells induced by VD3. Ethacrynic acid alone inhibited the proliferation of human promyelocytic HL-60 cells while only slightly increasing differentiation markers such as nitroblue tetrazolium (NBT)-reducing and lysozyme activities. Ethacrynic acid effectively enhanced the growth-inhibiting action of VD3. In the presence of ethacrynic acid, VD3 increased the NBT-reducing and lysozyme activities and the CD11b expression of HL-60 cells more effectively than VD3 alone. Other loop diuretics, furosemide and bumetanide, also enhanced the differentiation of HL-60 cells induced by VD3, but to a lesser extent than ethacrynic acid. The differentiation of HL-60 cells induced by all-trans retinoic acid, dimethyl sulfoxide or phorbol-12-myristate 13-acetate was also enhanced by ethacrynic acid with increasing NBT-reducing and lysozyme activities and the expression of CD11b or CD14 surface antigen. Morphologically, ethacrynic acid enhanced the monocytic differentiation of HL-60 cells induced by VD3 and phorbol ester and the granulocytic differentiation by retinoic acid and dimethyl sulfoxide. Other human myelomonocytic leukemia ML-1, U937, P39/TSU and P31/FUJ cells were induced to differentiate by VD3 and this was also enhanced by ethacrynic acid. The long-term culture of HL-60 cells showed that ethacrynic acid plus VD3 induced the complete growth arrest of HL-60 cells. Therefore ethacrynic acid, which is used to treat hypercalcemia, enhanced the proliferation-inhibiting and differentiation-inducing activities of VD3 and the combination of ethacrynic acid and VD3 may be useful in therapy for myeloid leukemia.

  19. Management of hyperphosphatemia in patients with renal failure.

    PubMed

    Ghazali, A; Ben Hamida, F; Bouzernidj, M; el Esper, N; Westeel, P F; Fournier, A

    1993-07-01

    Phosphate retention plays a major role in the pathogenesis of hyperparathyroidism at all stages of renal insufficiency. Dietary phosphate restriction is mandatory only for adults and is not advised for children because of the recommended diet allowance. Dietary restriction is usually not sufficient, and phosphate binders are almost always necessary when the glomerular filtration rate falls below 40 mL/min. Because long-term administration of aluminum phosphate binders is associated with risk of aluminum intoxication despite the use of so-called "safe doses", alternative phosphate binders should be used. Magnesium hydroxide and carbonate can be used only for dialysis patients because a low dialysate magnesium concentration is necessary to prevent the hazards of hypermagnesemia. Therefore, the major alternative is the use of alkaline salts of calcium. The most recently proposed salt, acetate, has a higher phosphate-binding capacity than carbonate but exposes patients to the same incidence of hypercalcemia despite the use of half the dose of elemental calcium. These salts should be taken with meals in order to complex more dietary phosphate and decrease calcium absorption and therefore the risk of hypercalcemia. Oral calcium alone, without 1 alpha OH-vitamin D3 derivatives, can prevent hyperphosphatemia and hyperparathyroidism in most uremic patients before dialysis and in about half of the patients dialyzed with a dialysate calcium of 1.5 to 1.65 mmol/L. 1 alpha OH-vitamin D3 derivatives, which increase intestinal absorption of phosphate, should be used only when hyperphosphatemia has been prevented by oral calcium and diet and when plasma parathyroid hormone levels increase above three times the upper limit of normal. To decrease hypercalcemic risk, patients should be given 1 alpha OH-vitamin D3 derivatives, preferably at night, as an intermittent bolus (intravenous or oral). In dialysis patients, the dialysate concentration of calcium may have to be further

  20. Dose-response effect of ergocalciferol therapy on serum 25-hydroxyvitamin D concentration during critical illness.

    PubMed

    Dickerson, Roland N; Berry, Scott C; Ziebarth, Jamie D; Swanson, Joseph M; Maish, George O; Minard, Gayle; Brown, Rex O

    2015-10-01

    The aim of this study was to evaluate the dose-response relationship between ergocalciferol therapy and serum 25-hydroxyvitamin D concentrations in enterally fed, critically ill patients with traumatic injuries. A retrospective cohort of critically ill patients with traumatic injuries and vitamin D deficiency (25-OH vitamin D <50 nmol/L) were given either 50 000 IU of liquid ergocalciferol weekly, twice weekly, or three times weekly while in the intensive care unit (ICU). Serum 25-OH vitamin D and ionized calcium concentrations were monitored weekly. Ergocalciferol therapy was stopped when the serum 25-OH vitamin D was >75 nmol/L, if the patient experienced hypercalcemia (ionized calcium >1.34 mmol/L), when the patient was discharged from the ICU, or if enteral nutrition was discontinued. Sixty-five patients (16, 18, and 31 per dosage group) were examined. One (6%), two (11%), and eight (26%) patients achieved normal 25-OH vitamin D concentrations after 2 to 4 wk of ergocalciferol therapy for each dosage group, respectively (P < 0.001). Serum 25-OH vitamin D concentrations improved from 36 ± 6, 40 ± 7, and 37 ± 6 nmol/L to 50 ± 15, 54 ± 21, and 62 ± 17 nmol/L, respectively, after 2 wk of ergocalciferol therapy (P < 0.001) Two (13%), one (6%), and seven (23%) patients developed hypercalcemia for each dosage group, respectively (P = NS). Ergocalciferol therapy improved baseline serum 25-OH vitamin D concentrations but was inadequate for consistently achieving normal serum concentrations of 25-OH vitamin D during critical illness. The trend in increasing appearance of mild hypercalcemia for the highest dosage group is concerning. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Effect of lanthanum carbonate vs. calcium carbonate on serum calcium in hemodialysis patients: a crossover study.

    PubMed

    Toida, Tatsunori; Fukudome, Keiichi; Fujimoto, Shouichi; Yamada, Kazuhiro; Sato, Yuji; Chiyotanda, Susumu; Kitamura, Kazuo

    2012-09-01

    Lanthanum carbonate (LC) is a non-calcium-containing phosphate binder and shows a comparable effect with other phosphate binders on hyperphosphatemia in dialysis patients. LC also contributes to a reduced oral calcium load compared with calcium carbonate (CaC) treatment. However, no crossover studies which compare the influence on serum calcium level between treatments with LC and CaC in hemodialysis (HD) patients have been carried out. After washout for 2 weeks, 50 patients on HD were randomized (1 : 1) to receive LC or CaC for 3 months. Thereafter, patients underwent a second 2-week washout period and were switched to the alternative binder for the next 3 months. Mineral and bone metabolism markers were measured with the changes of vitamin D doses. The serum phosphate level showed a similar decrease from baseline to 3 months in both groups. During the study periods, hypercalcemia was observed only in patients taking CaC. The dose of vitamin D analogue was increased more frequently in the patients of the LC group compared with LC group. The iPTH level showed a significant decrease in the CaC group, but not in the LC group. Serum levels of BAP, TRAP5b, and ALP were significantly elevated in the LC group, whereas the FGF-23 level showed a significant decrease. LC effectively reduced the serum phosphate level (like CaC) and allowed the vitamin D analogue dosage to be increased without hypercalcemia in HD patients. LC is one of the useful phosphate binders without hypercalcemia. (UMIN-CTR registration number: UMIN000002331).

  2. A phase I study to determine the maximum tolerated dose and safety of oral LR-103 (1α,24(S)Dihydroxyvitamin D2) in patients with advanced cancer.

    PubMed

    Wisinski, Kari B; Ledesma, Wendy M; Kolesar, Jill; Wilding, George; Liu, Glenn; Douglas, Jeffrey; Traynor, Anne M; Albertini, Mark; Mulkerin, Daniel; Bailey, Howard H

    2015-12-01

    The objective of this study was to determine the maximum tolerated dose and safety of LR-103, a Vitamin D analogue, in patients with advanced cancer. In Step A, patients received oral LR-103 once daily in 14-day cycles with intra-patient dose escalation per accelerated dose escalation design. Dose limiting toxicity for Step A was defined as ≥grade 2 hypercalcemia and/or >grade 2 other toxicities. Starting dose was 5 µg/day. Step B used a 3+3 design starting at Step A maximum tolerated dose with 28-day cycles. Dose limiting toxicity was defined as ≥grade 3 hypercalcemia or any grade 3 or 4 non-hematologic toxicity, except hypercalciuria. Twenty-one patients were enrolled; eight were treated in Step A. At dose level 3 (15 µg/day), two patients had dose limiting toxicity. One had grade 4 hyperuricemia. The other had grade 4 GGT plus grade 3 alkaline phosphatase, fatigue and urinary tract infection (UTI). Dose level 2 (10 µg/day) was the maximum tolerated dose for Step A and was starting dose for Step B. The dose was escalated to dose level 5 (30 µg/day) with a patient experiencing grade 3 dose limiting toxicity of hypercalcemia. The study was discontinued before reaching the maximum tolerated dose due to sponsor decision. Modest increases in serum osteocalcin and calcium and decrease in parathyroid hormone were noted. Best response was stable disease; four patients were on therapy for six months or longer. Step A dose limiting toxicities limited accelerated dose escalation. The maximum tolerated dose of LR-103 was not reached prior to study termination and this agent is no longer being developed. © The Author(s) 2014.

  3. Calcium-prostaglandin interaction on the action of antidiuretic hormone in the dog.

    PubMed

    Berl, T; Erickson, A E

    1982-04-01

    The effect of interaction between calcium and prostaglandin (PG) on the action of antidiuretic hormone (ADH) was studied in the water-diuresing anesthetized dog. Maximal urinary osmolality after 100 mU or ADH was 331 +/- 24 in the normocalcemic state versus only 228 +/- 31 mosmol/kg (P less than 0.01) in dogs made acutely hypercalcemic when their serum Ca concentration was increased from 8.9 +/- 0.2 to 11.6 +/- 0.4 mg/100 ml (P less than 0.001). To define the role of PG in this effect, studies were performed in the presence of PG inhibition with indomethacin (10 mg/kg). The antidiuretic response to 100 mU of ADH was decreased by hypercalcemia, as maximal osmolality was 1,096 +/- 65 in the normocalcemic PG-inhibited dog but only 555 +/- 50 mosmol/kg in the acutely hypercalcemic PG-inhibited dog (P less than 0.001). Conversely, the effect of PG inhibition to enhance the hydroosmotic effect of ADH was also demonstrable in acutely hypercalcemic dogs, as maximal urinary osmolality following 100 mU of ADH was 257 +/- 9 before and 557 +/- 60 mosmol/kg after PG inhibition (P less than 0.001). These studies demonstrate, therefore, that the effect of acute hypercalcemia on the hydroosmotic response to vasopressin is not dependent on the synthesis of an endoperoxide metabolite. Likewise, hypercalcemia blunts but does not abolish the effect of PG inhibitors to potentiate the hydroosmotic effect of ADH.

  4. [Chloroquine--miscellaneous properties of the antimalarial drug].

    PubMed

    Jarzyna, Robert

    2002-01-01

    Chloroquine is a drug with over 60 years of safe clinical use in the treatment of malaria. The multiple mechanisms of chloroquine action have appeared to be useful in the therapy of many miscellaneous disorders well beyond its original antimalarial purposes. This paper is focused on the application of chloroquine for the treatment of malaria, porphyria cutanea tarda, rheumatoid arthritis, palindromic rheumatism and lupus. The possibility of the use of chloroquine in the therapy of other disorders such as diabetes mellitus, AIDS, hyperlipidemia, sarcoidosis, hypercalcemia, and melanoma is reviewed. Mechanisms of action of the drug as well as side effects on metabolism are discussed in view of recent discoveries.

  5. Small Cell Carcinoma of the Ovary (Hypercalcemic Type): Malignant Rhabdoid Tumor

    PubMed Central

    Kascak, Peter; Zamecnik, Michal; Bystricky, Branislav

    2016-01-01

    We present a rare case of malignant rhabdoid tumor (ovarian small cell carcinoma of hypercalcemic type) in a 24-year-old female with fulminant course. Clinically, hypercalcemia was not found at the time of primary diagnosis. However, it appeared later during the course of tumor progression. Histologically, the tumor showed classical features of small cell carcinoma of hypercalcemic type. Therapy included radical surgery with adjuvant chemotherapy. Despite this intensive therapy, the disease recurred and the patient died 10 months after the diagnosis. We discuss the diagnosis and therapy of this tumor, as well as its recent classification as malignant rhabdoid tumor. PMID:27462229

  6. Rare Skeletal Complications in the Setting of Primary Hyperparathyroidism

    PubMed Central

    Sabanis, Nikos; Gavriilaki, Eleni; Paschou, Eleni; Kalaitzoglou, Asterios; Papanikolaou, Dimitrios; Ioannidou, Pinelopi; Vasileiou, Sotirios

    2015-01-01

    Parathyroid carcinoma represents an extremely rare neoplasm with diverse clinical manifestations which vary from asymptomatic patients to severe complications of hypercalcemia or parathyrotoxicosis while skeletal involvement is rather common. Herein we aimed at presenting a unique case of a young patient with rare aggressive skeletal complications of parathyroid cancer that initially were misdiagnosed. Ossification of the cervical ligamentum flavum and skull tumor illustrates erosive bonny lesions of hyperparathyroidism that in association with previous medical history of recurrent nephrolithiasis and biochemical findings guide the diagnosis. We suggest that increased awareness and holistic approach are needed in order to recognize and further investigate signs and symptoms of hyperparathyroidism. PMID:26664767

  7. Potential pathophysiological mechanisms in osteonecrosis of the jaw

    PubMed Central

    Landesberg, Regina; Woo, Victoria; Cremers, Serge; Cozin, Matthew; Marolt, Darja; Vunjak-Novakovic, Gordana; Kousteni, Stavroula; Raghavan, Srikala

    2015-01-01

    Bisphosphonates are used in the treatment of hypercalcemia of malignancy, skeletal complications associated with metastastic bone disease, Paget’s disease, and osteoporosis. Osteonecrosis of the jaw (ONJ) is a recently described clinical condition that has been associated with the use of nitrogen-containing bisphosphonates. Reports describing this entity first appeared in the literature in 2003. While there have been significant numbers of case reports and a limited number of retrospective and prospective studies examining risk factors associated with ONJ, the pathophysiology of this condition remains elusive. In this review, we explore proposed mechanisms underlying ONJ development and identify potential areas for future investigation. PMID:21291478

  8. A Comparison of Parathyroid Hormone-related Protein (1–36) and Parathyroid Hormone (1–34) on Markers of Bone Turnover and Bone Density in Postmenopausal Women: The PrOP Study

    PubMed Central

    Horwitz, Mara J; Augustine, Marilyn; Kahn, Leila; Martin, Emily; Oakley, Christine C; Carneiro, Raquel M; Tedesco, Mary Beth; Laslavic, Angela; Sereika, Susan M; Bisello, Alessandro; Garcia-Ocaña, Adolfo; Gundberg, Caren M; Cauley, Jane A; Stewart, Andrew F

    2013-01-01

    Parathyroid hormone-related protein (PTHrP)(1–36) increases lumbar spine (LS) bone mineral density (BMD), acting as an anabolic agent when injected intermittently, but has not been directly compared to parathyroid hormone (PTH)(1–34). We performed a three month, randomized, prospective study in 105 postmenopausal women with low bone density or osteoporosis comparing daily subcutaneous injections of PTHrP(1–36) to PTH(1–34). Thirty-five women were randomized to each of three groups: PTHrP(1–36) 400 μg/d; PTHrP(1–36) 600 μg/d; and PTH(1–34) 20 μg/d. The primary outcomes measures were changes in amino-terminal telopeptides of procollagen 1 (PINP) and carboxy-terminal telopeptides of collagen 1 (CTX). Secondary measures included safety parameters, 1,25(OH)2vitamin D and BMD. The increase in bone resorption (CTX) by PTH(1–34) (92%) (p<0.005) was greater than for PTHrP(1–36) (30%) (p<0.05). PTH(1–34) also increased bone formation (PINP) (171%) (p<0.0005) more than either dose of PTHrP(1–36) (46 & 87%). The increase in PINP was earlier (day 15) and greater than the increase in CTX for all three groups. LS BMD increased equivalently in each group (p<0.05 for all). Total hip (TH) and femoral neck (FN) BMD increased equivalently in each group but were only significant for the two doses of PTHrP(1–36) (p<0.05) at the TH, and for PTHrP(1–36) 400 (p<0.05) at the FN. PTHrP(1–36) 400 induced mild, transient (day 15) hypercalcemia. PTHrP(1–36) 600 required a dose reduction for hypercalcemia in three subjects. PTH(1–34) was not associated with hypercalcemia. Each peptide induced a marked biphasic increase in 1,25(OH)2D. Adverse events (AE) were similar among the three groups. This study demonstrates that PTHrP(1–36) and PTH(1–34) cause similar increases in LS BMD. PTHrP(1–36) also increased hip BMD. PTH(1–34) induced greater changes in bone turnover than PTHrP(1–36). PTHrP(1–36) was associated with mild transient hypercalcemia. Longer

  9. Incremental Value of 18F-Fluorocholine PET/CT in the Localization of Double Parathyroid Adenomas.

    PubMed

    Lalire, Paul; Ly, Sang; Deguelte, Sophie; Patey, Martine; Morland, David

    2017-03-01

    A 73-year-old man displaying primary hyperparathyroidism with severe hypercalcemia (Ca: 4.1 mmol/l, PTH > 600 pmol/l) was referred for preoperative localization of a parathyroid adenoma. Tc-pertechnetate and Tc-sestaMIBI dual tracer scintigraphy displayed a mild focal uptake in the projection of the right thyroid lobe with negative ultrasonography. F-Fluorocholine PET/CT was quickly performed considering this discrepancy and not only confirmed the scintigraphic findings but also revealed a second contralateral focus of increased uptake, both later confirmed by operative consideration (the two other parathyroid glands are considered normal by the surgeon), pathology, and intraoperative parathyroid hormone assessment.

  10. Risk factors for skeletal-related events (SREs) and factors affecting SRE-free survival for nonsmall cell lung cancer patients with bone metastases.

    PubMed

    Ulas, Arife; Bilici, Ahmet; Durnali, Ayse; Tokluoglu, Saadet; Akinci, Sema; Silay, Kamile; Oksuzoglu, Berna; Alkis, Necati

    2016-01-01

    Skeletal-related events (SREs) for nonsmall cell lung cancer (NSCLC) patients with bone metastasis lead to serious morbidity. The aim of this study was to determine risk factors for SREs in NSCLC patients with bone metastasis and the factors influencing SRE-free survival and overall survival (OS). From 2000 to 2012, we evaluated retrospectively 835 NSCLC patients. Three hundred and thirty-five of them with bone metastasis were included in the study. SREs and the other prognostic factors were evaluated by univariate and multivariate analysis for SRE-free survival and OS. SREs were detected in 244 patients (72.8 %). The most common SREs were the need for radiotherapy (43.2 %) and malignant hypercalcemia (17.6 %). The median time to first SRE was 3.5 months at the median follow-up of 17 months. A multivariate analysis showed that the presence of bone metastasis at diagnosis (p < 0.001), the number of bone metastasis (p = 0.001), baseline hypercalcemia (p = 0.004), and the presence of palliative radiotherapy (p = 0.04) were independent prognostic factors for SRE-free survival. A logistic regression analysis identified that the presence of bone metastasis at diagnosis [odds ratio (OR), 12.6], number of bone metastasis (OR, 3.05), and baseline hypercalcemia (OR, 0.33) were found to be predictive factors in the developing of SRE. The median OS time for patients with SRE was worse than that for patients without SRE (7 vs 12 months, respectively). For OS, male gender, ECOG performance status (PS), high lactate dehydrogenase (LDH) level, hypoalbuminemia, the presence of bone metastasis at diagnosis, the number of bone metastasis, the presence of SREs, the presence of bisphosphonate therapy, and palliative radiotherapy were independent prognostic indicators for OS by the multivariate analysis. Our results indicated that the frequency of SREs was high and the presence of bone metastasis at the time of diagnosis, baseline hypercalcemia, and multiple bone

  11. Williams-Beuren syndrome associated with single kidney and nephrocalcinosis: a case report.

    PubMed

    Abidi, Kamel; Jellouli, Manel; Ben Rabeh, Rania; Hammi, Yousra; Gargah, Tahar

    2015-01-01

    Williams-Beuren syndrome is a rare neurodevelopmental disorder, characterized by congenital heart defects, abnormal facial features, mental retardation with specific cognitive and behavioral profile, growth hormone deficiency, renal and skeletal anomalies, inguinal hernia, infantile hypercalcaemia. We report a case with Williams-Beuren syndrome associated with a single kidney and nephrocalcinosis complicated by hypercalcaemia. A male infant, aged 20 months presented growth retardation associated with a psychomotor impairment, dysmorphic features and nephrocalcinosis. He had also hypercalciuria and hypercalcemia. Echocardiography was normal. DMSA renal scintigraphy showed a single functioning kidney. The FISH generated one ELN signal in 20 metaphases read and found the presence of ELN deletion, with compatible Williams-Beuren syndrome.

  12. [Metabolic emergencies in critically ill cancer patients].

    PubMed

    Namendys-Silva, Silvio A; Hernández-Garay, Marisol; García-Guillén, Francisco J; Correa-García, Paulina; Herrera Gómez, Angel; Meneses-García, Abelardo

    2013-11-01

    Severe metabolic alterations frequently occur in critically ill cancer patients; hypercalcemia, hypocalcemia, hyponatremia, tumor lysis syndrome, metabolic complications of renal failure and lactic acidosis. Cancer patients with metabolic emergencies should be treated in a medical oncology department or an intensive care unit. Most metabolic emergencies can be treated properly when they are identified early. The clinician should consider that the prognosis of critically ill cancer patients depends on their primary disease, comorbidities and organ failure. Copyright AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

  13. Unusual presentations of enlarged parathyroid cysts: two case reports.

    PubMed

    Pire, Aurore; Buemi, Antoine; Camboni, Alessandra; Darius, Tom; De Pauw, Luc; Mourad, Michel

    2017-01-05

    Parathyroid cysts are infrequently encountered and have a variable presentation pattern depending on their size, location and secreting character. We report two cases of parathyroid cysts characterized by their uncommon clinical presentation. In the first case the patient presented with a large cervical cystic mass without hypercalcemia, while in the second case, the patient experienced a hypercalcemic crisis associated with acute renal failure. The variable pattern of clinical manifestations is discussed. Parathyroid cysts are a rare entity. Surgical resection is the key to therapy when hyperparathyroidism or local compression are identified.

  14. Syndromes that Link the Endocrine System and Genitourinary Tract.

    PubMed

    Özlük, Yasemin; Kılıçaslan, Işın

    2015-01-01

    The endocrine system and genitourinary tract unite in various syndromes. Genitourinary malignancies may cause paraneoplastic endocrine syndromes by secreting hormonal substances. These entities include Cushing`s syndrome, hypercalcemia, hyperglycemia, polycythemia, hypertension, and inappropriate ADH or HCG production. The most important syndromic scenarios that links these two systems are hereditary renal cancer syndromes with specific genotype/phenotype correlation. There are also some very rare entities in which endocrine and genitourinary systems are involved such as Carney complex, congenital adrenal hyperplasia and Beckwith-Wiedemann syndrome. We will review all the syndromes regarding manifestations present in endocrine and genitourinary organs.

  15. 7q11.23 deletions in Williams syndrome arise as a consequence of unequal meiotic crossover

    SciTech Connect

    Urban, Z.; Csiszar, K.; Boyd, C.D.

    1996-10-01

    Williams syndrome (WS) is a multisystem disorder characterized by mental retardation, a specific neurobehavioral profile, characteristic facies, infantile hypercalcemia, cardiovascular abnormalities, progressive joint limitation, hermas, and soft skin. Recent studies have shown that hemizygosity at the elastin (ELN) gene locus on chromosome 7q is associated with WS. Furthermore, two FISH studies using cosmid recombinants containing the 5{prime} or the 3{prime} end of the ELN gene revealed deletion of the entire ELN gene in 90%-96% of classical WS cases. However, the size of the 7q11.23 deletions and the mechanism by which these deletions arise are not known. 15 refs., 2 figs., 1 tab.

  16. Small Cell Carcinoma of the Ovary, Hypercalcemic Type: Report of a Bilateral Case in a Teenager Associated with SMARCA4 Germline Mutation.

    PubMed

    Lavrut, Pierre-Marie; Le Loarer, François; Normand, Charline; Grosos, Céline; Dubois, Rémi; Buenerd, Annie; Conter, Cécile; Dijoud, Frédérique; Blay, Jean-Yves; Collardeau-Frachon, Sophie

    2016-01-01

    Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), is a highly aggressive neoplasm that typically occurs in young females. Paraneoplastic hypercalcemia is associated in two thirds of the cases. Recent studies demonstrated that this rare tumor harbors the same molecular features of malignant rhabdoid tumor secondary to SMARCA4/BRG1 mutations. We illustrate herein a typical bilateral case of SCCOHT with comprehensive molecular characterization in a 14-year-old girl. We also discuss the value of SMARCA4 immunostaining in the diagnostic approach of undifferentiated ovarian and pelvic malignancies.

  17. Use of alkaline calcium salts as phosphate binder in uremic patients.

    PubMed

    Fournier, A; Morinière, P; Ben Hamida, F; el Esjer, N; Shenovda, M; Ghazali, A; Bouzernidj, M; Achard, J M; Westeel, P F

    1992-10-01

    In order to prevent aluminum toxicity induced by the association of aluminum phosphate binder with 1 alpha(OH) vitamin D3 derivatives and the use of deferoxamine with its own hazards to diagnose and treat this toxicity, we have shown in 1982 that it was possible to replace the iatrogenic association of aluminum phosphate binder with 1 alpha OH vitamin D derivatives by oral calcium carbonate taken with the meals in order to bind phosphate and correct the negative calcium balance. This led to the disappearance of the crippling aluminic osteomalacia and adynamic bone diseases in our center. The effectiveness of CaCO3 without 1 alpha(OH)D3 derivatives in the control of hyperparathyroidism in dialysis patients has been proven by the appearance in four patients of our dialysis population of an histological idiopathic adynamic bone disease associated with relative hypoparathyroidism, and by the finding that more than 50% of our dialysis population treated by this sole treatment have plasma concentration of intact PTH below twice the upper limit of normal (that is, the threshold above which only significant histological osteitis fibrosa is observed). Besides the compliance problem, the limit of CaCO3 is the occurrence of hypercalcemia which occurs in about 8% of the measurements. Since calcium acetate binds twice as much phosphate for the same dose of elemental calcium as CaCO3, its use has been recommended. However, clinical experience has shown that in spite of the fact that half the dose of calcium element given as acetate does actually control predialysis plasma phosphate as well as CaCO3, the incidence of hypercalcemia is not decreased, probably because calcium availability at the alkaline pH of the intestine is much greater with Ca acetate. When hypercalcemia is frequent (and not explained by autonomized hyperparathyroidism, adynamic bone disease, overtreatment with vitamin D, granulomatosis or neoplasia) it is necessary either to decrease the dose of calcium and

  18. Predictive Value of Ionized Calcium in Critically Ill Patients: An Analysis of a Large Clinical Database MIMIC II

    PubMed Central

    Zhang, Zhongheng; Xu, Xiao; Ni, Hongying; Deng, Hongsheng

    2014-01-01

    Background and Objective ionized calcium (iCa) has been investigated for its association with mortality in intensive care unit (ICU) patients in many studies. However, these studies are small in sample size and the results are conflicting. The present study aimed to establish the association of iCa with mortality by using a large clinical database. Methods Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC II) database was used for analysis. Patients older than 15 years were eligible, and patients without iCa measured during their ICU stay were excluded. Demographic data and clinical characteristics were extracted and compared between survivors and non-survivors. iCa measure on ICU admission was defined as Ca0; Camax was the maximum iCa during ICU stay; Camin was the minimum value of iCa during the ICU stay; Camean was the arithmetic mean iCa during ICU stay. Main results A total of 15409 ICU admissions satisfied our inclusion criteria and were included in our analysis. The prevalence of hypocalcemia on ICU entry was 62.06%. Ca0 was significantly lower in non-survivors than in survivors (1.11±0.14 vs 1.13±0.10 mmol/l, p<0.001). In multivariate analysis, moderate hypocalcemia in Ca0 was significantly associated with increased risk of death (OR: 1.943; 95% CI: 1.340–2.817), and mild hypercalcemia was associated with lower mortality (OR: 0.553, 95% CI: 0.400–0.767). While moderate and mild hypocalcemia in Camean is associated with increased risk of death (OR: 1.153, 95% CI: 1.006–1.322 and OR: 2.520, 95% CI: 1.485–4.278), hypercalcemia in Camean is not significantly associated with ICU mortality. Conclusion The relationship between Ca0 and clinical outcome follows an “U” shaped curve with the nadir at the normal range, extending slightly to hypercalcemia. Mild hypercalcemia in Ca0 is protective, whereas moderate and mild hypocalcemia in Camean is associated with increased risk of death. PMID:24736693

  19. Unusual presentation in a case of primary hyperparathyroidism

    PubMed Central

    Airaghi, Lorena; Pisano, Giuseppina; Pulixi, Edoardo; Benti, Riccardo; Baldini, Marina

    2011-01-01

    This report describes a case of classic severe primary hyperparathyroidism (PH) with clinical presentation that is very infrequent nowadays, which was osteitis fibrosa cystica. As bone scintigraphy demonstrated multiple areas of increasing uptake associated with hypercalcemia, a thorough investigation was conducted to exclude the neoplasms which most frequently are responsible for bone secondarisms. A fludeoxyglucose (FDG) positron emission tomography/CT demonstrated diffuse and multiple foci of increased FDG uptake and a focal uptake at the left thyroid region. Parathyroid function was studied, revealing unexpectedly high parathyroid hormone (PTH) levels. Further tests confirmed the diagnosis of PH and localized a parathyroid adenoma in the lower left side. PMID:22279485

  20. Review of cinacalcet hydrochloride in the management of secondary hyperparathyroidism.

    PubMed

    Yousaf, Farhanah; Charytan, Chaim

    2014-02-01

    Cinacalcet is the first Food and Drug Administration-approved calcimimetic for the treatment of secondary hyperparathyroidism in dialysis patients. It is effective in improving control of parathyroid hormone, serum calcium, phosphorus, and calcium-phosphorus product. The calcium-lowering effect of cinacalcet overcomes the limitations of standard therapy associated hypercalcemia. There is evidence to suggest that cinacalcet has important clinical implications, which extend beyond its relevance in the treatment of secondary hyperparathyroidism. This review summarizes the evidence regarding the role of cinacalcet in the treatment of secondary hyperparathyroidism, disrupted bone mineral metabolism, cardiovascular disease, and mortality. In addition, the cost implications of cinacalcet are briefly explored.

  1. Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma.

    PubMed

    Kyle, Robert A; San-Miguel, Jesus F; Mateos, Maria-Victoria; Rajkumar, S Vincent

    2014-10-01

    Monoclonal gammopathy of undetermined significance (MGUS) is characterized by an M spike less than 3 g/dL and a bone marrow containing fewer than 10% plasma cells without evidence of CRAB (hypercalcemia, renal insufficiency, anemia, or bone lesions). Light chain MGUS has an abnormal free light chain (FLC) ratio, increased level of the involved FLC, no monoclonal heavy chain, and fewer than 10% monoclonal plasma cells in the bone marrow. Smoldering multiple myeloma has an M protein of at least 3 g/dL and/or at least 10% monoclonal plasma cells in the bone marrow without CRAB features.

  2. Development of a Multivariate Predictive Model to Estimate Ionized Calcium Concentration from Serum Biochemical Profile Results in Dogs.

    PubMed

    Danner, J; Ridgway, M D; Rubin, S I; Le Boedec, K

    2017-08-20

    Ionized calcium concentration is the gold standard to assess calcium status in dogs, but measurement is not always available. (1) To predict ionized calcium concentration from biochemical results and compare the diagnostic performance of predicted ionized calcium concentration (piCa) to those of total calcium concentration (tCa) and 2 corrected tCa formulas; and (2) to study the relationship between biochemical results and variation of measured ionized calcium concentration (miCa). A total of 1,719 dogs with both miCa and biochemical profile results available. Cross-sectional study. Using 1,200 dogs, piCa was determined using a multivariate adaptive regression splines model. Its accuracy and performance were tested on the remaining 519 dogs. The final model included creatinine, albumin, tCa, phosphorus, sodium, potassium, chloride, alkaline phosphatase, triglycerides, and age, with tCa, albumin, and chloride having the highest impact on miCa variation. Measured ionized calcium concentration was better correlated with piCa than with tCa and corrected tCa and had higher overall diagnostic accuracy to diagnose hypocalcemia and hypercalcemia, but not significantly for hypercalcemia. For hypercalcemia, piCa was as sensitive (64%) but more specific (99.6%) than tCa and corrected tCa. For hypocalcemia, piCa was more sensitive (21.8%) and as specific (98.4%) as tCa. Positive and negative predictive values of piCa were high for both hypercalcemia (90% and 98%, respectively) and hypocalcemia (70.8% and 87.7%, respectively). Predicted ionized calcium concentration can be obtained from readily available biochemical and patient results and seems more useful than tCa and corrected tCa to assess calcium disorders in dogs when miCa is unavailable. Validation on external data, however, is warranted. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  3. Diuretics and disorders of calcium homeostasis.

    PubMed

    Grieff, Marvin; Bushinsky, David A

    2011-11-01

    Diuretics commonly are administered in disorders of sodium balance. Loop diuretics inhibit the Na-K-2Cl transporter and also increase calcium excretion. They are often used in the treatment of hypercalcemia. Thiazide diuretics block the thiazide-sensitive NaCl transporter in the distal convoluted tubule, and can decrease calcium excretion. They are often used in the treatment of nephrolithiasis. Carbonic anhydrase inhibitors decrease bicarbonate absorption and the resultant metabolic acidosis can increase calcium excretion. Their use can promote nephrocalcinosis and nephrolithiasis. This review will address the use of diuretics on disorders of calcium homeostasis. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Atypical Williams syndrome in an infant with complete atrioventricular canal defect.

    PubMed

    Ahrens-Nicklas, Rebecca C; Reichert, Sara L; Zackai, Elaine H; Kaplan, Paige B

    2015-12-01

    Williams-Beuren Syndrome (WBS) is a well-described microdeletion syndrome characterized by specific dysmorphic facial features, peripheral pulmonic stenosis, supravalvular aortic stenosis, hypercalcemia, feeding difficulties, gastroesophageal reflux, short stature, and specific intellectual disabilities (such as visual spatial problems). WBS is caused by 7q11.23 deletions that contain multiple genes known to contribute to the above phenotype. We report a neonate with a complete atrioventricular canal (CAVC) defect, an atypical cardiac lesion for WBS, and few typical phenotypic features of WBS, diagnosed at 20 days of life. © 2015 Wiley Periodicals, Inc.

  5. Multiple Myeloma, Version 3.2017, NCCN Clinical Practice Guidelines in Oncology.

    PubMed

    Kumar, Shaji K; Callander, Natalie S; Alsina, Melissa; Atanackovic, Djordje; Biermann, J Sybil; Chandler, Jason C; Costello, Caitlin; Faiman, Matthew; Fung, Henry C; Gasparetto, Cristina; Godby, Kelly; Hofmeister, Craig; Holmberg, Leona; Holstein, Sarah; Huff, Carol Ann; Kassim, Adetola; Liedtke, Michaela; Martin, Thomas; Omel, James; Raje, Noopur; Reu, Frederic J; Singhal, Seema; Somlo, George; Stockerl-Goldstein, Keith; Treon, Steven P; Weber, Donna; Yahalom, Joachim; Shead, Dorothy A; Kumar, Rashmi

    2017-02-01

    Multiple myeloma (MM) is caused by the neoplastic proliferation of plasma cells. These neoplastic plasma cells proliferate and produce monoclonal immunoglobulin in the bone marrow causing skeletal damage, a hallmark of multiple myeloma. Other MM-related complications include hypercalcemia, renal insufficiency, anemia, and infections. The NCCN Multiple Myeloma Panel members have developed guidelines for the management of patients with various plasma cell dyscrasias, including solitary plasmacytoma, smoldering myeloma, multiple myeloma, systemic light chain amyloidosis, and Waldenström's macroglobulinemia. The recommendations specific to the diagnosis and treatment of patients with newly diagnosed MM are discussed in this article.

  6. Evaluation of intense renal parenchymal activity (hot kidneys) on bone scintigraphy

    SciTech Connect

    Bernard, M.S.; Hayward, M.; Hayward, C.; Mundy, L. )

    1990-04-01

    The bone scintigrams of 600 patients performed over a 12-month period were reviewed. Thirty-six demonstrated abnormalities of the urinary tract of which six cases of intense renal parenchymal activity (hot kidneys) were found. Two cases were related to treatment with the new antineoplastic agent mitoxantrone. In one patient it was related to treatment with calcitonin. Neither of these associations has been previously reported. Recognized causes of hypercalcemia and recent radiotherapy were present in two patients. No cause could be found in the final patient.

  7. Absence of gallium-67 avidity in diffuse pulmonary calcification

    SciTech Connect

    Lecklitner, M.L.; Foster, R.W.

    1985-09-01

    Diffuse pulmonary uptake by bone-seeking radiopharmaceuticals has been reported previously but, in the same patient, would pulmonary uptake of Ga-67 citrate yield clinically meaningful results. A patient with hypercalcemia and renal failure in whom bone scintigraphy demonstrated striking diffuse bilateral pulmonary uptake, but subsequent gallium imaging demonstrated no evidence of pulmonary uptake greater than body background, is discussed. We conclude that pulmonary uptake of gallium cannot be attributed to calcium deposition and should carry the same clinical significance in regard to inflammatory and malignant lesions as would be assigned to patients without pulmonary calcific deposits.

  8. [Role of NO-dependent mechanisms at normal prenansy and on background of disturbance of utero placental blood circulation of white rats].

    PubMed

    Ivanova, A S; Sitnikova, O G; Nazarov, S B

    2012-01-01

    Condition of NO-dependent mechanisms, free-radical processes and calcium level in normal and on background of disturbance of uteroplacental circulation of white rats is studied. At normal pregnancy at animals activity of NO-dependent mechanisms increases, free radical processes are activated, hypocalcemia is appeared. Being injected of antagonist NO (10 mg/kg) and disturbance of uteroplacental circulation similar changes in the form of reducing of a level of nitrites, activation of free radical processes and hypercalcemia are observed. At the combined pathology synthesis of NO and nitrothyrosine increases, that in such conditions plays the protective role, providing adaptation of disturbance of uteroplacental circulation for needs of a fetus.

  9. Aortopulmonary ectopic parathyroid gland and concurrent thymolipoma.

    PubMed

    Abu Abeeleh, Mahmoud; Bani Hani, Amjad; Ghaith, Ata; Alodwan, Tareq; Bani Ismail, Zuhair; Alshehabat, Musa

    2016-10-01

    Ectopic parathyroid adenomas are considered the main cause of primary hyperparathyroidism. However, concurrent parathyroid and thymic pathologies are rarely diagnosed in the same patient. A 47-year-old man with history of diabetes mellitus, hypertension, and myasthenia gravis presented with persistent hypercalcemia. Laboratory investigations, computed tomography, and technetium-99 m sestamibi scintigraphy revealed ectopic parathyroid glands, a mediastinal mass, and an enlarged thymus. The patient underwent thymectomy and mass excision via a median sternotomy. Histopathology was consistent with ectopic parathyroid adenoma and thymolipoma. The serum calcium and parathormone concentrations normalized within 48 hours after surgery. © The Author(s) 2016.

  10. Calcium-Alkali Syndrome in the Modern Era

    PubMed Central

    Patel, Ami M.; Adeseun, Gbemisola A.; Goldfarb, Stanley

    2013-01-01

    The ingestion of calcium, along with alkali, results in a well-described triad of hypercalcemia, metabolic alkalosis, and renal insufficiency. Over time, the epidemiology and root cause of the syndrome have shifted, such that the disorder, originally called the milk-alkali syndrome, is now better described as the calcium-alkali syndrome. The calcium-alkali syndrome is an important cause of morbidity that may be on the rise, an unintended consequence of shifts in calcium and vitamin D intake in segments of the population. We review the pathophysiology of the calcium-alkali syndrome. PMID:24288027

  11. At the crossroads: EGFR and PTHrP signaling in cancer-mediated diseases of bone

    PubMed Central

    Nickerson, Nicole; Riese, David J.; Hollenhorst, Peter C.; Lorch, Gwendolen; Foley, Anne M.

    2014-01-01

    The epidermal growth factor receptor is a well-established cancer therapeutic target due to its stimulation of proliferation, motility, and resistance to apoptosis. Recently, additional roles for the receptor have been identified in growth of metastases. Similar to development, metastatic spread requires signaling interactions between epithelial-derived tumor cells and mesenchymal derivatives of the microenvironment. This necessitates reactivation of developmental signaling molecules, including the hypercalcemia factor parathyroid hormone-related protein. This review covers the variations of epidermal growth factor receptor signaling in cancers that produce bone metastases, regulation of parathyroid hormone-related protein, and evidence that the two molecules drive cancer-mediated diseases of bone. PMID:22684584

  12. Effect of various vitamin D metabolites on serum calcium and inorganic phosphate in the freshwater snake Natrix piscator.

    PubMed

    Srivastav, A K; Srivastav, S K; Singh, S; Norman, A W

    1995-10-01

    Vitamin D3 (650 pmol and 6.50 nmol/100 g body wt), 25-hydroxyvitamin D (650 pmol and 6.50 nmol/100 g body wt), and 1,25-dihydroxyvitamin D (65 pmol and 650 pmol/100 g body wt) were administered daily to the freshwater snake Natrix piscator for 15 days. Both serum calcium and inorganic phosphate levels were increased significantly in all of the treated groups. This is the first report of hypercalcemia and hyperphosphatemia in reptiles induced by 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D.

  13. Hyper Vitaminosis D: Are we Overprescribing Vitamin D?

    PubMed

    Hemachandar, R; Shanmugam, Lokesh; Malepati, Balakrishna; Venugopal, Suresh

    2014-01-01

    Vitamin D, the sunshine vitamin is now considered to be a hormone due to its important role in many physiological functions. Vitamin D deficiency has been associated with many disorders ranging from bone diseases, cardiovascular diseases to cancer. Hence, there is a recent surge in the empirical prescription of vitamin D for various disorders without documentation of vitamin D deficiency and monitoring the treatment. We report a case of iatrogenic hypercalcemia and acute kidney injury due to vitamin D toxicity after empirical and overzealous use of vitamin D and calcium supplements. We present this case to remind clinicians the importance of monitoring the patients treated with mega doses of vitamin D.

  14. Hyper Vitaminosis D: Are we Overprescribing Vitamin D?

    PubMed Central

    Hemachandar, R; Shanmugam, Lokesh; Malepati, Balakrishna; Venugopal, Suresh

    2014-01-01

    Vitamin D, the sunshine vitamin is now considered to be a hormone due to its important role in many physiological functions. Vitamin D deficiency has been associated with many disorders ranging from bone diseases, cardiovascular diseases to cancer. Hence, there is a recent surge in the empirical prescription of vitamin D for various disorders without documentation of vitamin D deficiency and monitoring the treatment. We report a case of iatrogenic hypercalcemia and acute kidney injury due to vitamin D toxicity after empirical and overzealous use of vitamin D and calcium supplements. We present this case to remind clinicians the importance of monitoring the patients treated with mega doses of vitamin D. PMID:25657969

  15. [Vascular Calcification - Pathological Mechanism and Clinical Application - . Vascular calcification in klotho deficient environment].

    PubMed

    Hasegawa, Tomoka; Yamamoto, Tomomaya; Hongo, Hiromi; Tsuboi, Kanako; Amizuka, Norio

    2015-05-01

    Klotho deficient (kl/kl) mice exhibit Möncheberg's vascular calcification in the tunica media due to hyperphosphatemia and hypercalcemia by mediating the disrupted signaling of FGF23/klotho axis. Recent studies have hypothesized the mechanism of medial vascular calcification : Vascular smooth muscle cells acquired excessive intake of phosphate ions undergo a phenotypic differentiation into osteoblasts and induce biological calcification in the tunica media. It is useful to clarify the underlying cellular mechanism of vascular calcification for the development of the treatment and preventive medicine. This review will introduce the histological and ultrastructual findings on medial vascular calcification in kl/kl mice.

  16. The ultrastructure of nephrocalcinosis induced in chicks by Cestrum diurnum leaves.

    PubMed

    Sarkar, K; Narbaitz, R; Pokrupa, R; Uhthoff, H K

    1981-01-01

    Powdered Cestrum diurnum leaves, mixed with two diets differing in calcium and phosphorus contents, produced nephrocalcinosis in young chicks regardless of serum calcium elevation. The calcific deposits, found in both proximal and distal portions of cortical tubules, began either in the cytoplasm or in lysosomal bodies as a unilaminar spheroid structure containing apatite crystals. The ultrastructural characteristics of intraluminal concretions suggested that they were formed intracellularly but later were extruded into the lumen. The extent of calcific deposits increased with duration and with hypercalcemia. Although Cestrum contains an analog of 1,25-dihydroxycholecalciferol, neither mitochondria nor basal lamina contained calcific deposits described in nephrocalcinosis secondary to hypervitaminosis D.

  17. HYPOALDOSTERONISM IN A MATSCHIE'S TREE KANGAROO (DENDROLAGUS MATSCHIEI).

    PubMed

    Whoriskey, Sophie T; Bartlett, Susan L; Baitchman, Eric

    2016-06-01

    A 20-yr-old female Matschie's tree kangaroo (Dendrolagus matschiei) was diagnosed with hypoaldosteronism, a rare condition in which the body fails to produce normal amounts of the mineralocorticoid aldosterone. Aldosterone plays a key role in body salt homeostasis, increasing sodium reabsorption and promoting excretion of potassium. Hypoaldosteronism resulted in decreased appetite, lethargy, and weight loss in conjunction with hyponatremia, hyperkalemia, and hypercalcemia in this tree kangaroo. The animal was successfully managed with mineralocorticoid replacement using desoxycorticosterone pivalate. To the authors' knowledge this is the first report of hypoaldosteronism in a tree kangaroo and one of the few reports in the veterinary literature in any species.

  18. Retrospective Study Looking at Cinacalcet in the Management of Hyperparathyroidism after Kidney Transplantation

    PubMed Central

    Mawad, Habib; Bouchard, Hugues; Tran, Duy; Ouimet, Denis; Bell, Robert Zoël; Bezzaoucha, Sarah; Boucher, Anne; Collette, Suzon; Pichette, Vincent; Senécal, Lynne

    2017-01-01

    Objectives. The primary objective of this study is to evaluate the use of cinacalcet in the management of hyperparathyroidism in kidney transplant recipients. The secondary objective is to identify baseline factors that predict cinacalcet use after transplantation. Methods. In this single-center retrospective study, we conducted a chart review of all patients having been transplanted from 2003 to 2012 and having received cinacalcet up to kidney transplantation and/or thereafter. Results. Twenty-seven patients were included with a mean follow-up of 2.9 ± 2.4 years. Twenty-one were already taking cinacalcet at the time of transplantation. Cinacalcet was stopped within the first month in 12 of these patients of which 7 had to restart therapy. The main reason for restarting cinacalcet was hypercalcemia. Length of treatment was 23 ± 26 months. There were only 3 cases of mild hypocalcemia. There was no statistically significant association between baseline factors and cinacalcet status a year later. Conclusions. Discontinuing cinacalcet within the first month of kidney transplantation often leads to hypercalcemia. Cinacalcet appears to be an effective treatment of hypercalcemic hyperparathyroidism in kidney transplant recipients. Further studies are needed to evaluate safety and long-term benefits. PMID:28386475

  19. Primary hyperparathyroidism with low intact PTH levels in a 14-year-old girl.

    PubMed

    Benaderet, Amanda D; Burton, Amy M; Clifton-Bligh, Roderick; Ashraf, Ambika P

    2011-08-01

    Primary hyperparathyroidism (PHPT) is usually associated with hypercalcemia and inappropriately elevated serum PTH. Our objective was to identify the reason(s) for a low serum intact PTH in a child with PHPT. A 14-yr-old Caucasian girl presented with pancreatitis, nephrolithiasis, hypercalcemia ranging from 13.2 to 17.5 mg/dl, and a low serum intact PTH. She had an ultrasound and technetium-99m-sestamibi scintigraphy confirming the presence of a parathyroid adenoma. The preoperative serum intact PTH assays performed at Quest Diagnostics, Nichols Institute, were low even after serial dilutions, whereas the intraoperative turbo PTH assay was elevated at 3618 pg/ml. C-terminal and cyclase-activating PTH assays for PTH were also elevated. PTH gene sequence analysis performed from DNA extracted both from the parathyroid adenoma and the patient's peripheral blood leukocytes was negative for a mutation in the PTH gene sequence. The contrasting values on the intact PTH assay and the turbo PTH assay suggest that the adenoma was producing an aberrant PTH molecule that was not detected by the routine intact PTH assay. Because there was no change in PTH gene sequence, this could be indicative of a posttranslational change in the PTH molecule that would not be recognized solely by DNA sequencing. Therefore, a low or normal PTH measurement against the backdrop of clinical and biochemical hyperparathyroidism needs measurement with a variety of assays.

  20. Repetition of continuous PTH treatments followed by periodic withdrawals exerts anabolic effects on rat bone.

    PubMed

    Etoh, Masaya; Yamaguchi, Akira

    2010-11-01

    Various animal experiments and human studies have shown that intermittent injections of parathyroid hormone (PTH) exert anabolic effects on bone, whereas continuous PTH treatment decreases the bone mass and causes hypercalcemia in animals. However, limited data are available with regard to the effects of a repetitive regimen of continuous treatments of PTH followed by periodic withdrawals on the bone metabolism. We investigated the effects of this regimen by comparing the findings of intermittent and continuous PTH treatments in rats. Infusions of PTH for 24 h followed by 6-day withdrawal periods from PTH transiently increased the serum calcium levels on day 1, but these levels were within the normocalcemic range. The repetition of 4 cycles of continuous PTH infusions followed by PTH withdrawals as well as intermittent PTH treatment increased the trabecular bone thickness, osteoblast surface, and bone formation rate. Continuous PTH infusions followed by PTH withdrawals also increased the cortical thickness of the femoral diaphysis and the osteoid volume in trabecular bones, whereas the continuous treatment failed to induce these changes. These findings suggest that continuous PTH treatment followed by PTH withdrawal is a potential regimen that can induce the anabolic effects of PTH in bone metabolism without inducing hypercalcemia.

  1. Brown Tumor of the Thoracic Spine: First Manifestation of Primary Hyperparathyroidism

    PubMed Central

    Tezcaner, Tugan; Coven, Ilker; Terzi, Aysen

    2015-01-01

    Brown tumors also called as osteoclastomas, are rare nonneoplastic lesions that arise in the setting of primary or secondary hyperparathyroidism. Parathyroid adenomas or hyperplasia constitute the major Brown tumor source in primary hyperparathyroidism while chronic renal failure is the leading cause in secondary hyperparathyroidism. Most of the patients with the diagnosis of primary hyperparathyroidism present with kidney stones or isolated hypercalcemia. However, nearly one third of patients are asymptomatic and hypercalcemia is found incidentally. Skeletal involvement such as generalized osteopenia, bone resorption, bone cysts and Brown tumors are seen on the late phase of hyperparathyroidism. The symptoms include axial pain, radiculopathy, myelopathy and myeloradiculopathy according to their locations. Plasmocytoma, lymphoma, giant cell tumors and metastates should be ruled out in the differential diagnosis of Brown tumors. Treatment of Brown tumors involve both the management of hyperparathyroidism and neural decompression. The authors report a very rare spinal Brown tumor case, arisen as the initial manifestation of primary hyperparathyroidism that leads to acute paraparesis. PMID:26587196

  2. Comparison of low and high dose of vitamin D treatment in nutritional vitamin D deficiency rickets.

    PubMed

    Cesur, Yaşar; Caksen, Hüseyin; Gündem, Alpaslan; Kirimi, Ercan; Odabaş, Dursun

    2003-01-01

    In this study, we compared three different therapy modes (150,000 IU, 300,000 IU, and 600,000 IU vitamin D p.o.) in infants with nutritional vitamin D deficiency rickets (VDR). Our purpose was to determine the most effective dosage of vitamin D with least side effects for treating VDR. The study included 56 patients, 3-36 months of age, with nutritional VDR and 20 age-matched control infants. In all infants, serum calcium, phosphorus, alkaline phosphatase, magnesium, serum 25-hydroxycholecalciferol, plasma intact parathormone levels and urinary Ca/creatine ratio were determined. Of 56 patients, 52 were able to be followed long-term. These patients were reexamined on the 3rd day, 7-10th day, and 25-30th day after treatment. On the 30th day post-treatment, we did not find any difference between the doses in the improvement of rickets. However, hypercalcemia was present in eight infants who had been administered 300,000 IU (two infants) and 600,000 IU (six infants) of vitamin D. In conclusion, our findings showed that 150,000 IU or 300,000 IU of vitamin D was adequate in the treatment of VDR, but 600,000 IU of vitamin D may carry the risk of hypercalcemia.

  3. Role of Vitamin D in Chronic Kidney Disease

    PubMed Central

    Patel, Tejas; Singh, Ajay K.

    2009-01-01

    Decline in renal function is directly related to cardiovascular mortality. However, traditional risk factors do not fully account for the high mortality in these patients. Activated vitamin D, a hormone produced by the proximal convoluted tubule of the kidney, appears to have beneficial effects beyond suppressing parathyroid hormone. However, activated vitamin D can also cause hypercalcemia and hyperphosphatemia in chronic kidney disease (CKD). Newer agents such as vitamin D receptor activators (VDRAs, e.g., paricalcitol) suppress PTH with reduced risk of hypercalcemia and hyperphosphatemia. Recent evidence from animal and preliminary human studies supports an association between VDRAs and reduced risk of CVD deaths, irrespective of PTH levels. New pathways of vitamin D regulation have also been discovered, namely the roles of fibroblast growth factor-23 and klotho. Although tremendous work has been done to advance our understanding of the effects of vitamin D in health and CKD, more investigations and randomized trials need to be performed to elucidate the mechanistic underpinnings of this effect. PMID:19371802

  4. Primary hyperparathyroidism-jaw tumor syndrome: a confusing and forgotten diagnosis

    PubMed Central

    PICIU, DOINA; PICIU, ANDRA; BARBUS, ELENA; PESTEAN, CLAUDIU; LARG, MARIA IULIA; FETICA, BOGDAN

    2016-01-01

    Background Primary hyperparathyroidism is caused by the excessive growth of parathormone secretion, its consequence being hypercalcemia. The parathyroid adenoma is responsible for over half of primary hyperparathyroidism cases. The mandibular tumor can be the initial sign in the case of primary hyperparathyroidism. Case presentation We present the case of a 33 year old patient with history of a mandibular operated tumor, repetitive pathological fractures and hypercalcemia manifestations. The level of the parathormone at the first measurement indicated a very high value. The parathyroid scintigraphy with 99mTc-MIBI (methoxy-isobutyl-isonitrile) evidenced a high uptake of the tracerin the superior mediastinum, suggestive for an ectopic parathyroid adenoma. The histopathological examination after surgery leads to the diagnosis of parathyroid adenoma. The association between the primary hyperparathyroidism, the mandibular tumour, the clinical history and the nuclear imaging lead to the diagnosis of primary hyperparathyroidism – Jaw tumor syndrome. Conclusion The hyperparathyroidism - Jaw tumor syndrome has a special clinical importance because of the severe and progressive symptomatology, and because of the risk of developing neoplasia of parathyroid glands, which have a reserved prognosis. PMID:27857527

  5. Primary Hyperparathyroidism and Pancreatitis: A Rare Association with Multiple Facets

    PubMed Central

    Fall, C. A.; Ndiaye, B.; Mbaye, M.; Diedhiou, I.; Ndiaye, A. R.; Diawara, P. S.; Fall, F.; Mbaye, P. S.; Gning, S. B.

    2016-01-01

    Primary hyperparathyroidism (PHPT) is rarely associated with the occurrence of acute or chronic pancreatitis. Hypercalcemia plays a major role in the pathogenesis. We report five cases of pancreatitis revealing PHPT. Patients and Methods. This is a retrospective study of 4 years, including all patients admitted to intensive care unit or gastroenterology department, for an acute or chronic pancreatitis revealing primary hyperparathyroidism. Results. We included 5 patients, all female, with mean age 54 years [40–76 years]. The PHPT was in all cases revealed by acute pancreatitis (AP). This one was oedematous in four cases and severe in one case. It occurred twice in calcified chronic pancreatitis (CCP). There was hypercalcemia in all cases. The PHPT was associated with a high rate of parathyroid hormone in 4 cases. The secreting lesion was an adenoma in 5 cases. Two patients had in addition bilateral renal calcifications. The outcome was favorable in 4 patients among whom 3 have had parathyroid surgery. A death was noted by superinfection of necrosis in the case of severe AP. Conclusion. The occurrence of pancreatitis during hyperparathyroidism is rare. Normal or elevated calcemia during acute or chronic pancreatitis should always get attention. PMID:27774509

  6. Reversible vascular calcifications associated with hypervitaminosis D.

    PubMed

    Cirillo, Massimo; Bilancio, Giancarlo; Cirillo, Chiara

    2016-02-01

    A 64-year-old man was hospitalized in 2002 with symptoms of stupor, weakness, and renal colic. The clinical examination indicated borderline hypertension, small masses in the glutei, and polyuria. Laboratory tests evidenced high serum concentrations of creatinine, calcium, and phosphate. Imaging assessments disclosed widespread vascular calcifications, gluteal calcifications, and pelvic ectasia. Subsequent lab tests indicated suppressed serum parathyroid hormone, extremely high serum 25-hydroxy vitamin D, and normal serum 1,25-dihydroxy vitamin D. Treatment was started with intravenous infusion of saline and furosemide due to the evidence of hypercalcemia. Prednisone and omeprazole were added given the evidence of hypervitaminosis D. The treatment improved serum calcium, kidney function, and consciousness. The medical history disclosed recent treatment with exceptionally high doses of slow-release intra-muscular cholecalciferol and the recent excretion of urinary stones. The patient was discharged when it was possible to stop the intravenous treatment. The post-discharge treatment included oral hydration, furosemide, prednisone and omeprazole for approximately 6 months up to complete resolution of the hypercalcemia. The patient came back 12 years later because of microhematuria. Lab tests were normal for calcium/phosphorus homeostasis and kidney function. Imaging tests indicated only minor vascular calcifications. This is the first evidence of reversible vascular calcifications secondary to hypervitaminosis D.

  7. An unexpected cause of acute kidney injury in a patient with ANCA associated vasculitis.

    PubMed

    Choudhry, Wajid M; Nori, Uday S; Nadasdy, Tibor; Satoskar, Anjali A

    2016-05-01

    Diagnostic kidney biopsies sometimes yield clinically unsuspected diagnoses. We present a case of a 69-year-old woman with established ANCA-associated vasculitis (AAV) of 4 years duration who was in clinical remission following cytotoxic therapy and was on maintenance immunosuppression. She presented to the hospital with acute kidney injury (AKI), symptoms suggestive of a systemic vasculitis, and in addition had hypercalcemia, metabolic alkalosis. A relapse in the AAV was suspected but a diagnostic kidney biopsy showed acute tubular necrosis, patchy interstitial inflammation, and calcium phosphate deposits. It was found that the patient recently started consuming large doses of over-the-counter calcium-containing antacids and vitamin Dcontaining multivitamin supplements. Cessation of these drugs led to improvement of renal function to baseline. This case highlights several teaching points: (1) the kidney biopsy can prove to be critically important even in cases where there appears to be a more obvious clinical diagnosis, (2) AK due to calcium-alkali syndrome has characteristic histopathological changes, and (3) that the triad of hypercalcemia, metabolic alkalosis, and AKI is exclusively associated with the ingestion of excessive quantities of calcium-containing antacids. The physician should keep this in mind, and pro-actively seek pertinent medication history from the patient. A brief review of calcium-alkali syndrome is given.

  8. Efficacy and safety of human parathyroid hormone-(1-84) in increasing bone mineral density in postmenopausal osteoporosis.

    PubMed

    Hodsman, Anthony B; Hanley, David A; Ettinger, Mark P; Bolognese, Michael A; Fox, John; Metcalfe, Anna J; Lindsay, Robert

    2003-11-01

    Daily sc injections of N-terminal analogs of PTH increase bone mass and decrease fractures in osteoporotic women. We investigated the efficacy and safety of human PTH-(1-84) (full-length PTH) in the treatment of postmenopausal osteoporosis in a double-blind, placebo-controlled study. The women (n = 50-53/group) self-administered PTH (50, 75, or 100 microg) or placebo by daily sc injection for 12 months. PTH treatment induced time- and dose-related increases in lumbar spine bone mineral density (BMD). The 100-microg dose increased BMD significantly at 3 months (+2.0%) and 12 months (+7.8%). BMD underestimated the anabolic effect of PTH in lumbar spine (bone mineral content, +10.0%) because bone area increased significantly (+2.0%). A nonsignificant decrease (-0.9%) in total hip BMD occurred during the first 6 months with the 100-microg dose, but this trend reversed (+1.6%) during the second 6 months. Bone turnover markers increased during the first half of the study and were maintained at elevated levels during the second 6 months. Protocol compliance was excellent (95-98%), and treatment was generally safe and well tolerated. Dose-related incidences of transient hypercalcemia occurred, but only one patient (100-microg group) was withdrawn because of repeated hypercalcemia. Thus, full-length PTH was efficacious and safe over 12 months.

  9. Decrease in the Prevalence of Pancreatitis Associated with Primary Hyperparathyroidism: Experience at a Tertiary Referral Center.

    PubMed

    Janka-Zires, Marcela; Hernández-Calleros, Jorge; Gómez-Pérez, Francisco Javier; Uscanga-Domínguez, Luis Federico; Pelaez-Luna, Mario César; Almeda-Valdés, Paloma

    2015-01-01

    Hypercalcemia is a rare but well recognized cause of acute and chronic pancreatitis. Hypercalcemia-related pancreatitis is mainly caused by primary hyperparathyroidism. The prevalence of pancreatitis in hyperparathyroidism varies worldwide and additional disease-modifying factors may play a role in its development. In 1988 the prevalence of pancreatitis secondary to primary hyperparathyroidism at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), a referral center in Mexico City, was 12.1% (95% CI: 6.7-21). To describe the current prevalence of pancreatitis secondary to primary hyperparathyroidism at the INCMNSZ. We reviewed 385 cases of primary hyperparathyroidism seen at the hospital between 1987 and 2012. 26 cases with acute or chronic pancreatitis associated with primary hyperparathyroidism were documented, with a prevalence of 6.7% (95% CI: 4.6-9.7), which was lower than the 12.1% previously reported. In the present study, 20% had a history of alcohol consumption, 10% of gallstones, and 20% of ureteral calculi, compared with the previously reported 32.0, 34.6, and 40.0%, respectively. The average calcium levels were 13.1 and 13.8 mg/dl in the previous and current series, respectively. We found a decrease in the prevalence of pancreatitis associated with primary hyperparathyroidism from 12.1% (95% CI: 6.7-21) to 6.7% (95% CI: 4.6-9.7).

  10. [Vitamin D-related progressive renal insufficiency in an elderly patient with postsurgical hypoparathyroidism associated with extensive brain calcification].

    PubMed

    Fujiwara, Takuya

    2012-01-01

    We present a 76-year-old female patient with dementia who has postsurgical hypoparathyroidism associated with extensive brain calcification and progressive renal insufficiency. She had been treated with vitamin D combined with calcium or vitamin D alone due to hypoparathyroidism for 8 years. However, intermittent hypercalcemia including hypercalcemic crisis (serum Ca 15.2 mg/dL) and progressive renal dysfunction had developed. This patient was transferred to our long-term care hospital because of worsening dementia. Since laboratory data at admission revealed hypercalcemia and azotemia, alfacalcidol (1 microg/day) was discontinued. However, severe hypocalcemia (3.9 mg/dL) occurred later, while her azotemia was improved. With a low dose of alfacalcidol(0.25 microg/day), the serum calcium level is now below normal (approximately 7.0 mg/dL). There is neither hypocalcemic symptom nor exacerbation of renal insufficiency. From the clinical history of recurrent hypercalcemic episodes and renal calculi observed on computed tomography, the progression of renal insufficiency was considered to be related to persistent hypercalciuria caused by vitamin D and calcium, especially vitamin D therapy.

  11. Heterotopic ossification as an unusual complication after Guillain-Barré syndrome: a case report.

    PubMed

    Ryu, Su-Ra; Kim, Jae-Hyung; Choi, In-Sung; Han, Jae-Young; Lee, Sam-Gyu

    2008-03-01

    Heterotopic ossification (HO) is the abnormal development of bone within soft tissue. It is frequently encountered after traumatic brain injury or spinal cord injury, rather than lower motoneuron disease. It has been reported as a rare complication in Guillain-Barré syndrome (GBS). We present the case of a 31-year-old woman who suffered from pain and swelling with limitation of the passive range of motion on right hip joint, and who had been diagnosed with GBS about 1 year previously. She was wheelchair-bound and had incomplete tetraplegia with flaccidity. She was diagnosed as HO based on the radiologic imaging study. She did not reveal any encephalopathy-related symptoms or signs, and hypercalcemia, and/or related metabolic derangement during 1.5-year follow-up period. Owing to the paucity of other causative factors, we presumed that the long-time hypomobility, even though not accompanied by hypercalcemia, played a major role for the development of HO. Early active rehabilitative management was initiated. The outcome is not promising because of her long-standing paralyzed state; however, it was possible to prevent the aggravation of HO.

  12. [Clinical and biochemical picture of primary hyperparathyroidism based on 155 observed cases].

    PubMed

    Marcinkowski, W; Nieszporek, T; Kokot, F; Podwiński, A; Niemiec, A; Wieczorek, M

    2000-01-01

    In this study, the biochemical and clinical profile of primary hyperparathyroidism, diagnosed in 155 patients (106 females and 49 males) in the Department of Nephrology of the Silesian University School of Medicine in the years 1972-1998 was analyzed. The mean age of patients was 48.5 +/- 12.8 years. In all cases the diagnosis was confirmed by the pathomorphological examination. In the majority of cases PNP was diagnosed in a phase of advanced organic injuries. The leading clinical finding in these patients was nephrolithiasis. Asymptomatic hypercalcemia was diagnosed only in 9% of cases. In the years 1972-1992 elevated serum total calcium concentration was found in 92.6% while after introduction of routine estimation of ionized calcium concentration in 1993, hypercalcemia was found in all patients. The incidence of hypercalciuria increased significantly in patients diagnosed in the period 1993-1998 while in this same period the incidence of impaired renal function declined significantly. The elevated serum PTH was found in 86% of patients regardless whether C-terminal fragments of PTH or intact PTH-1-84 were assessed. Elevated levels of ionized serum calcium with normal or increased plasma iPTH-1-84 level are the most constant symptoms of primary hyperparathyroidism.

  13. Cinacalcet Treatment of Primary Hyperparathyroidism

    PubMed Central

    Rothe, H. M.; Liangos, O.; Biggar, P.; Petermann, A.; Ketteler, M.

    2011-01-01

    Although parathyroidectomy remains the only curative approach to most primary hyperparathyroidism cases, medical treatment with cinacalcet HCl has been proven to be a reasonable alternative for several patient subgroups. Cinacalcet almost always controls hypercalcemia and hypophosphatemia sufficiently. PTH levels are lowered, and cognitive parameters improve. While an increase in bone mineral density DEXA scan scores was not demonstrated in cinacalcet trials, the same applies to more than half of patients after parathyroidectomy. Medical therapy should be first choice in patients with hyperplasia in all glands rather than an isolated adenoma (10–15%), patients with persisting HPT following unsuccessful surgery or inoperable cases due to comorbidities, and patients detected in lab screens for hypercalcemia before developing symptoms who should be treated early but are usually reluctant to undergo surgery. Nephrolithiasis was not found to occur more frequently in cinacalcet trial groups, but urine calcium excretion as one major risk factor of this complication of primary HPT may increase on cinacalcet. Patients carrying the rs1042636 polymorphism of the calcium-sensing receptor gene respond more sensitively to cinacalcet and have a higher risk of calcium stone formation. Cinacalcet is usually administered twice daily but three or four doses per day should be discussed to mimic the beneficial pulsatile PTH-pattern. PMID:21461394

  14. Cardiac and pulmonary calcification in a hemodialysis patient: partial regression 4 years after parathyroidectomy.

    PubMed

    Di Leo, C; Gallieni, M; Bestetti, A; Tagliabue, L; Cozzolino, M; Carpani, P; Pozzato, C; Tarolo, G L; Brancaccio, D

    2003-01-01

    The reversibility of extraskeletal calcifications in dialysis patients is an important and unresolved issue. Although periarticular calcifications have been shown to be reversible, little data are available on vascular or parenchymal calcifications. A patient on maintenance hemodialysis with severe hyperparathyroidism, hypercalcemia and hyperphosphatemia was admitted to undergo parathyroidectomy. A preoperative total body bone scintigraphy was performed to better evaluate a lytic lesion in the pelvis, the histology of which proved to be a "brown tumor". The scan showed the typical findings of renal osteodystrophy, but also a diffuse extra-skeletal uptake of bone tracer in the lungs, kidneys, femoral arteries and myocardium. After surgery, good control of serum calcium, phosphate (Ca x P product < 50 mg2/dl2) and PTH levels was maintained during 4 years of follow-up. Bone scans were repeated after 2 and 4 years, showing marked improvement of periarticular uptake at the ends of long bones. Extraosseous calcium deposition was still markedly evident, but progressively decreased (at 4 years: heart -36%, lungs -18%). In this dialysis patient, extraskeletal calcification of visceral organs (particularly in the heart and the lungs) due to prolonged hypercalcemia and hyperphosphatemia was partially reversible by parathyroidectomy followed by good long-term control of serum phosphate and calcium.

  15. Efficacy and safety of lanthanum carbonate versus calcium-based phosphate binders in patients with chronic kidney disease: a systematic review and meta-analysis.

    PubMed

    Zhai, Chun-Juan; Yang, Xiao-Wei; Sun, Jing; Wang, Rong

    2015-03-01

    We conducted this review to assess the relative efficacy and safety of lanthanum carbonate versus calcium-based phosphate binders in chronic kidney disease. We systematically searched PubMed, EMBASE, the Cochrane Controlled Trial Register of Controlled Trials and Chinese Biological Medical Database for randomized controlled trials comparing lanthanum carbonate with calcium-based phosphate binders in adult patients with chronic kidney disease. Study quality was assessed using the criteria outlined in the Cochrane Handbook for Systematic Reviews of intervention. Meta-analysis was conducted by reviewer manager software, version 5.3. Eleven trials with 1,501 participants were included. Lanthanum carbonate appeared to be associated with a significant reduction in progression of vascular calcification and a beneficial effect on bone outcomes without aluminum-like toxicity. Lanthanum carbonate achieved similar proportions of phosphate-controlled patients (RR 0.63, 95% CI 0.27-1.44) with lower incidence of hypercalcemia (RR 0.13, 95% CI 0.05-0.35) in comparison with calcium-based phosphate binders. Lanthanum carbonate was associated with significantly lower serum calcium, similar serum Ca × P product and higher serum iPTH compared with calcium salts in patients with chronic kidney disease. Lanthanum carbonate could delay the progression of vascular calcification and benefit chronic kidney disease patients on bone outcomes. Lanthanum carbonate could achieve similar proportion of phosphate-controlled patients as calcium-based phosphate binders with lower incidence of hypercalcemia.

  16. Patient education for phosphorus management in chronic kidney disease

    PubMed Central

    Kalantar-Zadeh, Kamyar

    2013-01-01

    Objectives: This review explores the challenges and solutions in educating patients with chronic kidney disease (CKD) to lower serum phosphorus while avoiding protein insufficiency and hypercalcemia. Methods: A literature search including terms “hyperphosphatemia,” “patient education,” “food fatigue,” “hypercalcemia,” and “phosphorus–protein ratio” was undertaken using PubMed. Results: Hyperphosphatemia is a strong predictor of mortality in advanced CKD and is remediated via diet, phosphorus binders, and dialysis. Dietary counseling should encourage the consumption of foods with the least amount of inorganic or absorbable phosphorus, low phosphorus-to-protein ratios, and adequate protein content, and discourage excessive calcium intake in high-risk patients. Emerging educational initiatives include food labeling using a “traffic light” scheme, motivational interviewing techniques, and the Phosphate Education Program – whereby patients no longer have to memorize the phosphorus content of each individual food component, but only a “phosphorus unit” value for a limited number of food groups. Phosphorus binders are associated with a clear survival advantage in CKD patients, overcome the limitations associated with dietary phosphorus restriction, and permit a more flexible approach to achieving normalization of phosphorus levels. Conclusion: Patient education on phosphorus and calcium management can improve concordance and adherence and empower patients to collaborate actively for optimal control of mineral metabolism. PMID:23667310

  17. Chronic Vitamin D Intoxication in Captive Iberian Lynx (Lynx pardinus).

    PubMed

    Lopez, Ignacio; Pineda, Carmen; Muñoz, Luis; Raya, Ana; Lopez, Guillermo; Aguilera-Tejero, Escolástico

    2016-01-01

    To document the biochemical and pathologic features of vitamin D intoxication in lynx and to characterize mineral metabolism in healthy lynx, blood samples were obtained from 40 captive lynx that had been receiving excessive (approximately 30 times the recommended dose) vitamin D3 in the diet, and from 29 healthy free ranging lynx. Tissue samples (kidney, stomach, lung, heart and aorta) were collected from 13 captive lynx that died as a result of renal disease and from 3 controls. Vitamin D intoxication resulted in renal failure in most lynx (n = 28), and widespread extraskeletal calcification was most severe in the kidneys and less prominent in cardiovascular tissues. Blood minerals and calciotropic hormones in healthy lynx were similar to values reported in domestic cats except for calcitriol which was higher in healthy lynx. Changes in mineral metabolism after vitamin D intoxication included hypercalcemia (12.0 ± 0.3 mg/dL), hyperphosphatemia (6.3 ± 0.4 mg/dL), increased plasma calcidiol (381.5 ± 28.2 ng/mL) and decreased plasma parathyroid hormone (1.2 ± 0.7 pg/mL). Hypercalcemia and, particularly, hyperphosphatemia were of lower magnitude that what has been previously reported in the course of vitamin D intoxication in other species. However, extraskeletal calcifications were severe. The data suggest that lynx are sensitive to excessive vitamin D and extreme care should be taken when supplementing this vitamin in captive lynx diets.

  18. Chronic Vitamin D Intoxication in Captive Iberian Lynx (Lynx pardinus)

    PubMed Central

    Muñoz, Luis; Raya, Ana; Lopez, Guillermo; Aguilera-Tejero, Escolástico

    2016-01-01

    To document the biochemical and pathologic features of vitamin D intoxication in lynx and to characterize mineral metabolism in healthy lynx, blood samples were obtained from 40 captive lynx that had been receiving excessive (approximately 30 times the recommended dose) vitamin D3 in the diet, and from 29 healthy free ranging lynx. Tissue samples (kidney, stomach, lung, heart and aorta) were collected from 13 captive lynx that died as a result of renal disease and from 3 controls. Vitamin D intoxication resulted in renal failure in most lynx (n = 28), and widespread extraskeletal calcification was most severe in the kidneys and less prominent in cardiovascular tissues. Blood minerals and calciotropic hormones in healthy lynx were similar to values reported in domestic cats except for calcitriol which was higher in healthy lynx. Changes in mineral metabolism after vitamin D intoxication included hypercalcemia (12.0 ± 0.3 mg/dL), hyperphosphatemia (6.3 ± 0.4 mg/dL), increased plasma calcidiol (381.5 ± 28.2 ng/mL) and decreased plasma parathyroid hormone (1.2 ± 0.7 pg/mL). Hypercalcemia and, particularly, hyperphosphatemia were of lower magnitude that what has been previously reported in the course of vitamin D intoxication in other species. However, extraskeletal calcifications were severe. The data suggest that lynx are sensitive to excessive vitamin D and extreme care should be taken when supplementing this vitamin in captive lynx diets. PMID:27243456

  19. Glucocorticoid regulation of the vitamin D receptor.

    PubMed

    Hidalgo, Alejandro A; Trump, Donald L; Johnson, Candace S

    2010-07-01

    Many studies indicate calcitriol has potent anti-tumor activity in different types of cancers. However, high levels of vitamin D can produce hypercalcemia in some patients. Glucocorticoids are used to ameliorate hypercalcemia and to enhance calcitriol anti-tumor activity. Calcitriol in combination with the glucocorticoid dexamethasone (Dex) increased vitamin D receptor (VDR) protein levels and ligand binding in squamous cell carcinoma VII (SCC). In this study we found that both calcitriol and Dex induce VDR- and glucocorticoid receptor (GR)-mediated transcription respectively, indicating both hormone receptors are active in SCC. Pre-treatment with Dex increases VDR-mediated transcription at the human CYP24A1 promoter. Whereas, pre-treatment with other steroid hormones, including dihydrotestosterone and R1881, has no effect on VDR-mediated transcription. Real-time PCR indicates treatment with Dex increases Vdr transcripts in a time-dependent manner, suggesting Dex may directly regulate expression of Vdr. Numerous putative glucocorticoid response elements (GREs) were found in the Vdr gene. Chromatin immuno-precipitation (ChIP) assay demonstrated GR binding at several putative GREs located within the mouse Vdr gene. However, none of the putative GREs studied increase GR-mediated transcription in luciferase reporter assays. In an attempt to identify the response element responsible for Vdr transcript regulation, future studies will continue to analyze newly identified GREs more distal from the Vdr gene promoter.

  20. The calcium-sensing receptor: physiology, pathophysiology and CaR-based therapeutics.

    PubMed

    Brown, E M

    2007-01-01

    The extracellular calcium (Ca(o)2+)-sensing receptor (CaR) enables the parathyroid glands and other CaR-expressing cells to sense alterations in the level of Ca(o)2+ and to respond with changes in function that are directed at normalizing the blood calcium concentration. In addition to the parathyroid gland, the kidney is a key site for Ca(o)2(+)-sensing that enables it to make physiologically relevant alterations in divalent cation and water metabolism. Several disorders of Ca(o)2(+)-sensing arise from inherited or acquired abnormalities that "reset" the serum calcium concentration upward or downward. Inactivating mutations produce a benign form of hypercalcemia when present in the heterozygous state, termed Familial Hypocalciuric Hypercalcemia (FHH), while homozygous mutations produce a much more severe hypercalcemic disorder resulting from marked hyperparathyroidism, called Neonatal Severe Hyperparathyroidism (NSHPT). Activating mutations cause a hypocalcemic syndrome of varying severity, termed autosomal dominant hypocalcemia or hypoparathyroidism. Inactivating or activating antibodies directed at the CaR produce the expected hyper- or hypocalcemic syndromes, respectively. "Calcimimetic" CaR activators and "calcilytic" CaR antagonists have been developed. The calcimimetics are currently in use for controlling severe hyperparathyroidism in patients receiving dialysis treatment for end stage renal disease or with parathyroid cancer. Calcilytics are being evaluated as a means of inducing a "pulse" in the circulating parathyroid hormone (PTH) concentration, which would mimic that resulting from injection of PTH, an established anabolic form of treatment for osteoporosis.

  1. Glucocorticoid Regulation of the Vitamin D Receptor

    PubMed Central

    Hidalgo, Alejandro A.; Trump, Donald L.; Johnson, Candace S.

    2010-01-01

    Many studies indicate calcitriol has potent anti-tumor activity in different types of cancers. However, high levels of vitamin D can produce hypercalcemia in some patients. Glucocorticoids are used to ameliorate hypercalcemia and to enhance calcitriol anti-tumor activity. Calcitriol in combination with the glucocorticoid dexamethasone (Dex) increased vitamin D receptor (VDR) protein levels and ligand binding in squamous cell carcinoma VII (SCC). In this study we found that both calcitriol and Dex induce VDR- and glucocorticoid receptor (GR)-mediated transcription respectively, indicating both hormone receptors are active in SCC. Pre-treatment with Dex increases VDR-mediated transcription at the human CYP24A1 promoter. Whereas, pre-treatment with other steroid hormones, including dihydrotestosterone and R1881, has no effect on VDR-mediated transcription. Real-time PCR indicates treatment with Dex increases Vdr transcripts in a time-dependent manner, suggesting Dex may directly regulate expression of Vdr. Numerous putative glucocorticoid response elements (GREs) were found in the Vdr gene. Chromatin immunoprecipitation (ChIP) assay demonstrated GR binding at several putative GREs located within the mouse Vdr gene. However, none of the putative GREs studied increase GR-mediated transcription in luciferase reporter assays. In an attempt to identify the response element responsible for Vdr transcript regulation, future studies will continue to analyze newly identified GREs more distal from the Vdr gene promoter. PMID:20398752

  2. Hypercalcemic crisis: a clinical review.

    PubMed

    Ahmad, Shazia; Kuraganti, Gayatri; Steenkamp, Devin

    2015-03-01

    Hypercalcemia is a common metabolic perturbation. However, hypercalcemic crisis is an unusual endocrine emergency, with little clinical scientific data to support therapeutic strategy. We review the relevant scientific English literature on the topic and review current management strategies after conducting a PubMed, MEDLINE, and Google Scholar search for articles published between 1930 and June 2014 using specific keywords: "hypercalcemic crisis," "hyperparathyroid crisis," "parathyroid storm," "severe primary hyperparathyroidism," "acute hyperparathyroidism," and "severe hypercalcemia" for articles pertaining to the diagnosis, epidemiology, clinical presentation, and treatment strategies. Despite extensive clinical experience, large and well-designed clinical studies to direct appropriate clinical care are lacking. Nonetheless, morbidity and mortality rates have substantially decreased since early series reported almost universal fatality. Improved outcomes can be attributed to modern diagnostic capabilities, leading to earlier diagnosis, along with the recognition that primary hyperparathyroidism is the most common etiology for hypercalcemic crisis. Hypercalcemic crisis is an unusual endocrine emergency that portends excellent outcomes if rapid diagnosis, medical treatment, and definitive surgical treatment are expedited. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. [Surgery of the parathyroid gland].

    PubMed

    Fukunari, Nobuhiro

    2012-11-01

    The introduction of various techniques for minimally invasive parathyroidectomy (MIP) has changed both the conceptual and surgical approach to parathyroid disease. The perceived advantages of minimally invasive surgery among both clinicians and patients have been a major factor in the development of new surgical techniques, as well as refinement of preoperative localization techniques such as high-sensitive ultrasound and technetium sestamibi scanning. MIP for primary hyperparathyroidism has become an accepted part of endocrine surgical practice worldwide. In recent years, medical management of hyperparathyroidism has been made possible with the use of therapeutics specifically aimed at the calcium-sensing receptor, a cell-surface protein widely viewed as the primary regulator of parathyroid hormone secretion. The calcimimetic agent cinacalcet is approved for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis and for the treatment of hypercalcemia in patients with parathyroid carcinoma. Cinacalcet is also expected to be useful in the treatment of intractable hypercalcemia in patients with primary hyperparathyroidism for whom parathyroidectomy is indicated but surgery is clinically inappropriate or contraindicated.

  4. Ultrastructural evaluation of parathyroid glands and thyroid C cells of cattle fed Solanum malacoxylon.

    PubMed Central

    Collins, W. T.; Capen, C. C.; Döbereiner, J.; Tokarnia, C. H.

    1977-01-01

    Fine structural alterations of thyroid C cells and parathyroid chief cells were evaluated after feeding dried leaves of the calcinogenic plant, Solanum malacoxylon, to cattle for 1, 6 and 32 days. Thyroid C cells initially were degranulated in response to the hypercalcemia, and parathyroid chief cells accumulated secretory granules. There was hypertrophy of thyroid C cells with well-developed secretory organelles but few secretory granules in the cytoplasm after 6 days of feeding S. malacoxylon. Inactive chief cells with dispersed profiles of endoplasmic reticulum and increased lysosomal bodies predominated in the parathyroid glands. Multiple foci of soft tissue mineralization were present in the heart, lung, and kidney. Thyroid C cells underwent hypertrophy and hyperplasia after 32 days of S. malacoxylon, and parathyroid chief cells were inactive or atrophic in response to the long-term hypercalcemia. Severe soft tissue mineralization was present throughout the cardiovascular system, lung, kidney, and spleen. These ultrastructural changes in thyroid C cells and parathyroid chief cells plus the widespread soft tissue mineralization observed after feeding cattle small amounts of S. malacoxylon are consistent with the recent evidence that leaves of this plant are a potent source of the active metabolite, 1,25-dihydroxycholecalciferol, of vitamin D. Images Figure 7 Figure 8 Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:869016

  5. Effects of Treatment of Renal Osteodystrophy on Bone Histology

    PubMed Central

    Malluche, Hartmut H.; Mawad, Hanna; Monier-Faugere, Marie-Claude

    2008-01-01

    Renal osteodystrophy is characterized by abnormalities in bone turnover, mineralization, and bone volume. The effects of treatment modalities for renal osteodystrophy on bone should be analyzed with respect to these abnormalities. The major treatment modalities for renal osteodystrophy include phosphate binders, vitamin D compounds, and calcimimetics. Aluminum-containing phosphate binders have been shown to be toxic to bone secondary to their effects on bone turnover, mineralization, and bone volume. The use of calcium-based phosphate binders has been associated with the development of adynamic bone disease (low bone turnover), bone loss, and worsening of vascular calcifications. New nonaluminum, noncalcium phosphate binders have been developed (sevelamer hydrochloride and lanthanum carbonate). These agents show a potential for improvement in bone turnover and bone volume. Patients with renal osteodystrophy are deficient in calcitriol and often in calcidiol. Calcidiol deficiency has been underappreciated and deserves to be addressed in the treatment of patients with renal osteodystrophy. Calcitriol replacement therapy by daily oral administration is associated with frequent episodes of hypercalcemia and suppression of bone turnover in patients with stages 3 to 5 chronic kidney disease. Pulse oral or intravenous calcitriol administration induces frequent episodes of hypercalcemia or hyperphosphatemia, respectively, and achieves the same degree of correction of bone abnormalities. There are no data on the effects of paricalcitol or doxercalciferol on human bone. Experimental data, however, show that these two analogues and maxacalcitol may control serum parathyroid hormone levels without suppressing bone turnover. Calcimimetics lower parathyroid hormone levels and bone turnover. PMID:18988701

  6. Effects of treatment of renal osteodystrophy on bone histology.

    PubMed

    Malluche, Hartmut H; Mawad, Hanna; Monier-Faugere, Marie-Claude

    2008-11-01

    Renal osteodystrophy is characterized by abnormalities in bone turnover, mineralization, and bone volume. The effects of treatment modalities for renal osteodystrophy on bone should be analyzed with respect to these abnormalities. The major treatment modalities for renal osteodystrophy include phosphate binders, vitamin D compounds, and calcimimetics. Aluminum-containing phosphate binders have been shown to be toxic to bone secondary to their effects on bone turnover, mineralization, and bone volume. The use of calcium-based phosphate binders has been associated with the development of adynamic bone disease (low bone turnover), bone loss, and worsening of vascular calcifications. New nonaluminum, noncalcium phosphate binders have been developed (sevelamer hydrochloride and lanthanum carbonate). These agents show a potential for improvement in bone turnover and bone volume. Patients with renal osteodystrophy are deficient in calcitriol and often in calcidiol. Calcidiol deficiency has been underappreciated and deserves to be addressed in the treatment of patients with renal osteodystrophy. Calcitriol replacement therapy by daily oral administration is associated with frequent episodes of hypercalcemia and suppression of bone turnover in patients with stages 3 to 5 chronic kidney disease. Pulse oral or intravenous calcitriol administration induces frequent episodes of hypercalcemia or hyperphosphatemia, respectively, and achieves the same degree of correction of bone abnormalities. There are no data on the effects of paricalcitol or doxercalciferol on human bone. Experimental data, however, show that these two analogues and maxacalcitol may control serum parathyroid hormone levels without suppressing bone turnover. Calcimimetics lower parathyroid hormone levels and bone turnover.

  7. Current concepts regarding calcium metabolism and bone health in sarcoidosis.

    PubMed

    Baughman, Robert P; Papanikolaou, Ilias

    2017-09-01

    Vitamin D supplementation is widespread used in the general population. In sarcoidosis, up to 50% of patients, especially postmenopausal women and those taking corticosteroids, show evidence of increased bone fragility. The purpose of this review is to provide an evidence-based rationale on how to treat sarcoidosis patients with bone health issues. Evidence from observational studies show that decreased 25-hydroxy vitamin D is common in sarcoidosis. However, the great majority of sarcoidosis patents have normal or often elevated levels of 1,25-dihydroxy vitamin D (calcitriol), a marker associated with disease activity. High calcitriol levels may often be associated with hypercalcemia and hypercalcuria. The few interventional randomized controlled studies in the field, suggest that vitamin D supplementation may not be well tolerated because of hypercalcemia, moreover without substantial benefit on bone health and risk for fractures in these patients. Vitamin D supplementation may be withheld in sarcoidosis patients with bone fragility, unless calcitriol levels are below normal limits. A treating scheme is proposed.

  8. Can SPECT change the surgical strategy in patients with primary hyperparathyroidism?

    PubMed

    Iervolino, Letícia; Scalisse, Nilza Maria; Maeda, Sergio Setsuo

    2012-06-01

    Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia in outpatients. It is more common in females, after menopause, and the prevalence is 1 to 4:1000 in the general population. Patients with PHPT have abnormal regulation of PTH secretion, resulting in elevated serum calcium and inappropriately high or normal PTH in relation to the calcium value. Sporadic PTH-secreting adenoma alone accounts for 90% of cases of PHPT, while multiglandular hyperplasia is more common in familial hyperparathyroidism syndromes (5%) and parathyroid carcinomas represent less than 1% of cases. Only after making sure there is functional autonomy of one or more parathyroid glands, localization imaging tests should be performed to guide a possible surgical procedure. It is important to highlight that these tests have limitations and can yield false-positive and false-negative results. There are cases in which the parathyroid gland is difficult to be located, requiring a combination of imaging methods for pre-operative localization, such as (99m)Tc-pertechnetate, SPECT, SPECT/CT, and US. We describe the case of a 50-year-old female patient diagnosed with PHPT, who underwent a surgical procedure without success, with maintenance of hypercalcemia and hyperparathyroidism. In this case, the hyperfunctioning parathyroid was located in the retrotracheal region only after scintigraphy combined with SPECT/CT were used.

  9. Structural Basis for Antibody Discrimination between Two Hormones That Recognize the Parathyroid Hormone Receptor

    SciTech Connect

    McKinstry, William J.; Polekhina, Galina; Diefenbach-Jagger, Hannelore; Ho, Patricia W.M.; Sato, Koh; Onuma, Etsuro; Gillespie, Matthew T.; Martin, T. John; Parker, Michael W.

    2009-08-18

    Parathyroid hormone-related protein (PTHrP) plays a vital role in the embryonic development of the skeleton and other tissues. When it is produced in excess by cancers it can cause hypercalcemia, and its local production by breast cancer cells has been implicated in the pathogenesis of bone metastasis formation in that disease. Antibodies have been developed that neutralize the action of PTHrP through its receptor, parathyroid hormone receptor 1, without influencing parathyroid hormone action through the same receptor. Such neutralizing antibodies against PTHrP are therapeutically effective in animal models of the humoral hypercalcemia of malignancy and of bone metastasis formation. We have determined the crystal structure of the complex between PTHrP (residues 1-108) and a neutralizing monoclonal anti-PTHrP antibody that reveals the only point of contact is an {alpha}-helical structure extending from residues 14-29. Another striking feature is that the same residues that interact with the antibody also interact with parathyroid hormone receptor 1, showing that the antibody and the receptor binding site on the hormone closely overlap. The structure explains how the antibody discriminates between the two hormones and provides information that could be used in the development of novel agonists and antagonists of their common receptor.

  10. Hypercalcemic crisis resulting from near drowning in an indoor public bath.

    PubMed

    Matsumoto, Ryusaku; Yamada, Go; Amano, Aya; Yamada, Tomoko; Hamamatsu, Keita; Murabe, Hiroyuki; Yokota, Toshihiko

    2013-01-01

    Male, 66. Hypercalcemic crisis. Near drowning state. - - Critical care medicine. Challenging differential diagnosis. Hypercalcemic crisis, generally caused by malignancy or primary hyperparathyroidism, is a life-threatening emergency that can result in multi-organ failure. Lowering the patient's calcium level immediately and determining the correct etiology are essential. We report a case of hypercalcemic crisis with a novel etiology. A 66-year-old male presented to the emergency room in cardiac arrest with a ventricular arrhythmia after being discovered submerged in an indoor public bath. He underwent cardioversion and was emergently intubated. Computed tomography showed bilateral pulmonary edema, suspected from water aspiration. Laboratory data revealed severe hypercalcemia and mild hypernatremia. Following three days of continuous hemodiafiltration, serum Ca decreased to and remained within normal limits. We concluded the etiology of hypercalcemia was absorption of Ca resulting from aspirated water. Near drowning can be a cause of hypercalcemic crisis. For cases of near drowning, it is important to investigate the source of the aspirated water and consider electrolyte abnormalities in the diagnosis.

  11. Combination of Oral Vitamin D3 with Photodynamic Therapy Enhances Tumor Cell Death in a Murine Model of Cutaneous Squamous Cell Carcinoma

    PubMed Central

    Anand, Sanjay; Rollakanti, Kishore R.; Horst, Ronald L.; Hasan, Tayyaba; Maytin, Edward V.

    2014-01-01

    Photodynamic therapy (PDT), in which 5-ALA (a precursor for protoporphyrin IX, PpIX) is administered prior to exposure to light, is a nonscarring treatment for skin cancers. However, for deep tumors, ALA-PDT is not always effective due to inadequate production of PpIX. We previously developed and reported a combination approach in which the active form of vitamin D3 (calcitriol) is given systemically prior to PDT to improve PpIX accumulation and to enhance PDT-induced tumor cell death; calcitriol, however, poses a risk of hypercalcemia. Here, we tested a possible strategy to circumvent the problem of hypercalcemia by substituting natural dietary vitamin D3 (cholecalciferol; D3) for calcitriol. Oral D3 supplementation (10 days of a 10-fold elevated D3 diet) enhanced PpIX levels 3- to 4-fold, and PDT-mediated cell death 20-fold, in subcutaneous A431 tumors. PpIX levels and cell viability in normal tissues were not affected. Hydroxylated metabolic forms of D3 were only modestly elevated in serum, indicating minimal hypercalcemic risk. These results show that brief oral administration of cholecalciferol can serve as a safe neoadjuvant to ALA-PDT. We suggest a clinical study, using oral vitamin D3 prior to PDT, should be considered to evaluate this promising new approach to treating human skin cancer. PMID:24807677

  12. The Abnormal Phenotypes of Cartilage and Bone in Calcium-Sensing Receptor Deficient Mice Are Dependent on the Actions of Calcium, Phosphorus, and PTH

    PubMed Central

    Tao, Chunxiang; Ding, Guoxian; Karaplis, Andrew; Brown, Edward; Goltzman, David; Miao, Dengshun

    2011-01-01

    Patients with neonatal severe hyperparathyroidism (NSHPT) are homozygous for the calcium-sensing receptor (CaR) mutation and have very high circulating PTH, abundant parathyroid hyperplasia, and severe life-threatening hypercalcemia. Mice with homozygous deletion of CaR mimic the syndrome of NSHPT. To determine effects of CaR deficiency on skeletal development and interactions between CaR and 1,25(OH)2D3 or PTH on calcium and skeletal homeostasis, we compared the skeletal phenotypes of homozygous CaR–deficient (CaR−/−) mice to those of double homozygous CaR– and 1α(OH)ase–deficient [CaR−/−1α(OH)ase−/−] mice or those of double homozygous CaR– and PTH–deficient [CaR−/−PTH−/−] mice at 2 weeks of age. Compared to wild-type littermates, CaR−/− mice had hypercalcemia, hypophosphatemia, hyperparathyroidism, and severe skeletal growth retardation. Chondrocyte proliferation and PTHrP expression in growth plates were reduced significantly, whereas trabecular volume, osteoblast number, osteocalcin-positive areas, expression of the ALP, type I collagen, osteocalcin genes, and serum ALP levels were increased significantly. Deletion of 1α(OH)ase in CaR−/− mice resulted in a longer lifespan, normocalcemia, lower serum phosphorus, greater elevation in PTH, slight improvement in skeletal growth with increased chondrocyte proliferation and PTHrP expression, and further increases in indices of osteoblastic bone formation. Deletion of PTH in CaR−/− mice resulted in rescue of early lethality, normocalcemia, increased serum phosphorus, undetectable serum PTH, normalization in skeletal growth with normal chondrocyte proliferation and enhanced PTHrP expression, and dramatic decreases in indices of osteoblastic bone formation. Our results indicate that reductions in hypercalcemia play a critical role in preventing the early lethality of CaR−/− mice and that defects in endochondral bone formation in CaR−/− mice result from effects of the

  13. Gemini Vitamin D Analogs Inhibit Estrogen Receptor Positive and Estrogen Receptor Negative Mammary Tumorigenesis without Hypercalcemic Toxicity

    PubMed Central

    Lee, Hong Jin; Paul, Shiby; Atalla, Nadi; Thomas, Paul E.; Lin, Jennie; Yang, Ill; Buckley, Brian; Lu, Gang; Zheng, Xi; Lou, You-Rong; Conney, Allan H.; Maehr, Hubert; Uskokovic, Milan; Suh, Nanjoo

    2009-01-01

    Numerous preclinical, epidemiological and clinical studies have suggested the benefits of vitamin D and its analogs for the prevention and treatment of cancer. However, the hypercalcemic effects have limited the use of 1α,25(OH)2D3, the hormonally active form of vitamin D. To identify vitamin D analogs with better efficacy and low toxicity, we have tested more than 60 novel Gemini vitamin D analogs with a unique structure of two side chains for growth inhibition of breast cancer cells. Our initial studies found that some Gemini analogs are many-fold more active than 1α,25(OH)2D3 in growth inhibition assay. In vivo experiments were designed to study the inhibitory effect of selected Gemini vitamin D analogs against mammary carcinogenesis by using (a) an N-methyl-N-nitrosourea-induced estrogen receptor (ER)-positive mammary tumor model and (b) an MCF10DCIS.com xenograft model of ER-negative mammary tumors. Among vitamin D analogs we tested, Gemini 0072 [1α,25-dihydroxy-20S-21(3-trideuteromethyl-3-hydroxy-4,4,4-trideuterobutyl)-23-yne-26,27-hexafluoro-19-nor-cholecalciferol] and Gemini 0097 [1α,25-dihydroxy-20R-21(3-trideuteromethyl-3-hydroxy-4,4,4-trideuterobutyl)-23-yne-26,27-hexafluoro-19-nor-cholecalciferol] administration inhibited by 60% the NMU-induced mammary tumor burden compared to the NMU-treated control group, but these compounds were devoid of hypercalcemia toxicity. In an ER-negative xenograft model, Gemini 0097 significantly suppressed tumor growth without hypercalcemia toxicity. We found that the inhibitory effect of Gemini 0097 was associated with an increased level of cyclin dependent kinase inhibitor p21 and the insulin-like growth factor binding protein 3 in both ER-positive and ER-negative mammary tumors. Our results suggest that Gemini vitamin D analogs may be potent agents for the prevention and treatment of both ER-positive and ER-negative breast cancer without hypercalcemia toxicity. PMID:19138995

  14. PT19c, Another Nonhypercalcemic Vitamin D2 Derivative, Demonstrates Antitumor Efficacy in Epithelial Ovarian and Endometrial Cancer Models

    PubMed Central

    Kawar, Nada; Maclaughlan, Shannon; Horan, Timothy C.; Uzun, Alper; Lange, Thilo S.; Kim, Kyu K.; Hopson, Russell; Singh, Ajay P.; Sidhu, Preetpal S.; Glass, Kyle A.; Shaw, Sunil; Padbury, James F.; Vorsa, Nicholi; Arnold, Leggy A.; Moore, Richard G.; Brard, Laurent

    2013-01-01

    Hypercalcemia remains a major impediment to the clinical use of vitamin D in cancer treatment. Approaches to remove hypercalcemia and development of nonhypercalcemic agents can lead to the development of vitamin D–based therapies for treatment of various cancers. In this report, in vitro and in vivo anticancer efficacy, safety, and details of vitamin D receptor (VDR) interactions of PT19c, a novel nonhypercalcemic vitamin D derived anticancer agent, are described. PT19c was synthesized by bromoacetylation of PTAD-ergocalciferol adduct. Broader growth inhibitory potential of PT19c was evaluated in a panel of chemoresistant breast, renal, ovarian, lung, colon, leukemia, prostate, melanoma, and central nervous system cancers cell line types of NCI60 cell line panel. Interactions of PT19c with VDR were determined by a VDR transactivation assay in a VDR overexpressing VDR-UAS-bla-HEK293 cells, in vitro VDR-coregulator binding, and molecular docking with VDR-ligand binding domain (VDR-LBD) in comparison with calcitriol. Acute toxicity of PT19c was determined in nontumored mice. In vivo antitumor efficacy of PT19c was determined via ovarian and endometrial cancer xenograft experiments. Effect of PT19c on actin filament organization and focal adhesion formation was examined by microscopy. PT19c treatment inhibited growth of chemoresistant NCI60 cell lines (log10GI50 ~ −4.05 to −6.73). PT19c (10 mg/kg, 35 days) reduced growth of ovarian and endometrial xenograft tumor without hypercalcemia. PT19c exerted no acute toxicity up to 400 mg/kg (QDx1) in animals. PT19c showed weak VDR antagonism, lack of VDR binding, and inverted spatial accommodation in VDR-LBD. PT19c caused actin filament dysfunction and inhibited focal adhesion in SKOV-3 cells. PT19c is a VDR independent nonhypercalcemic vitamin D–derived agent that showed noteworthy safety and efficacy in ovarian and endometrial cancer animal models and inhibited actin organization and focal adhesion in ovarian cancer

  15. PT19c, Another Nonhypercalcemic Vitamin D2 Derivative, Demonstrates Antitumor Efficacy in Epithelial Ovarian and Endometrial Cancer Models.

    PubMed

    Kawar, Nada; Maclaughlan, Shannon; Horan, Timothy C; Uzun, Alper; Lange, Thilo S; Kim, Kyu K; Hopson, Russell; Singh, Ajay P; Sidhu, Preetpal S; Glass, Kyle A; Shaw, Sunil; Padbury, James F; Vorsa, Nicholi; Arnold, Leggy A; Moore, Richard G; Brard, Laurent; Singh, Rakesh K

    2013-11-01

    Hypercalcemia remains a major impediment to the clinical use of vitamin D in cancer treatment. Approaches to remove hypercalcemia and development of nonhypercalcemic agents can lead to the development of vitamin D-based therapies for treatment of various cancers. In this report, in vitro and in vivo anticancer efficacy, safety, and details of vitamin D receptor (VDR) interactions of PT19c, a novel nonhypercalcemic vitamin D derived anticancer agent, are described. PT19c was synthesized by bromoacetylation of PTAD-ergocalciferol adduct. Broader growth inhibitory potential of PT19c was evaluated in a panel of chemoresistant breast, renal, ovarian, lung, colon, leukemia, prostate, melanoma, and central nervous system cancers cell line types of NCI60 cell line panel. Interactions of PT19c with VDR were determined by a VDR transactivation assay in a VDR overexpressing VDR-UAS-bla-HEK293 cells, in vitro VDR-coregulator binding, and molecular docking with VDR-ligand binding domain (VDR-LBD) in comparison with calcitriol. Acute toxicity of PT19c was determined in nontumored mice. In vivo antitumor efficacy of PT19c was determined via ovarian and endometrial cancer xenograft experiments. Effect of PT19c on actin filament organization and focal adhesion formation was examined by microscopy. PT19c treatment inhibited growth of chemoresistant NCI60 cell lines (log10GI50 ~ -4.05 to -6.73). PT19c (10 mg/kg, 35 days) reduced growth of ovarian and endometrial xenograft tumor without hypercalcemia. PT19c exerted no acute toxicity up to 400 mg/kg (QDx1) in animals. PT19c showed weak VDR antagonism, lack of VDR binding, and inverted spatial accommodation in VDR-LBD. PT19c caused actin filament dysfunction and inhibited focal adhesion in SKOV-3 cells. PT19c is a VDR independent nonhypercalcemic vitamin D-derived agent that showed noteworthy safety and efficacy in ovarian and endometrial cancer animal models and inhibited actin organization and focal adhesion in ovarian cancer cells.

  16. [Vitamin D treatment and renal osteodystrophy: indications and modalities].

    PubMed

    Fournier, A; Morinière, P; Yverneau-Hardy, P; Westeel, P F; Mazouz, H; el Esper, N; Ghazali, A; Boudailliez, B

    1995-01-01

    1. 1 alpha (OH) vitamin D3 derivatives have an inconstant long term inhibitory effect on PTH secretion. As a matter of fact they act by three mechanisms, one of these being antagonistic: 1) a direct inhibitory action on the prepro-PTH gene; 2) an indirect inhibitory action by increasing plasma calcium; 3) an indirect stimulatory action by increasing plasma phosphate. These two latter phenomena are due to the stimulation of the intestinal absorption of these ions as well as to an intrinsic osteolytic action which may override the inhibition of the bone release of these ions in relation with the decrease of the PTH plasma levels. 2. The use of 1 alpha (OH)D3 derivatives in patients on chronic dialysis is justified in about 30% of the patients on dialysis when in spite of native vitamin D repletion and adequate predialysis control of plasma calcium (2.5 +/- 2 mmol/l) and of plasma phosphate (1.4 - 1.7 mmol/l), the PTH plasma levels are 3 or 5 fold the upper limit of normal whether the patient is on hemodialysis or on CAPD. When hyperphosphatemia is > 1.7 mmol/l it is first necessary to correct it by the use of higher doses of alkaline calcium salts given with the meals as phosphate binder together with a negative perdialytic calcium balance induced by a lower dialysate calcium in order to avoid hypercalcemia. Control of hyperphosphatemia is indeed a necessary prerequisite for the long term PTH suppressive efficacy of 1 alpha OH vitamin D derivatives. 3. The use of 1 alpha(OH)D3 derivatives in the treatment of the predialysis uremic patients is even more limited because there is no additional mean to decrease the risk of hypercalcemia when oral calcium is used as phosphate binder because of the danger of aluminum and magnesium phosphate binders. Fortunately in the adult, oral calcium used as phosphate binder in association with phosphate restriction and correction of possible vitamin D depletion and acidosis is usually efficace to control hyperparathyroïdism without 1

  17. Gemini vitamin D analogues inhibit estrogen receptor-positive and estrogen receptor-negative mammary tumorigenesis without hypercalcemic toxicity.

    PubMed

    Lee, Hong Jin; Paul, Shiby; Atalla, Nadi; Thomas, Paul E; Lin, Xinjie; Yang, Ill; Buckley, Brian; Lu, Gang; Zheng, Xi; Lou, You-Rong; Conney, Allan H; Maehr, Hubert; Adorini, Luciano; Uskokovic, Milan; Suh, Nanjoo

    2008-11-01

    Numerous preclinical, epidemiologic, and clinical studies have suggested the benefits of vitamin D and its analogues for the prevention and treatment of cancer. However, the hypercalcemic effects have limited the use of 1alpha,25(OH)(2)D(3), the hormonally active form of vitamin D. To identify vitamin D analogues with better efficacy and low toxicity, we have tested >60 novel Gemini vitamin D analogues with a unique structure of two side chains for growth inhibition of breast cancer cells. Our initial studies found that some Gemini analogues are 5-15 times more active than 1alpha,25(OH)(2)D(3) in growth inhibition assay. In vivo experiments were designed to study the inhibitory effect of selected Gemini vitamin D analogues against mammary carcinogenesis by using (a) an N-methyl-N-nitrosourea-induced estrogen receptor (ER)-positive mammary tumor model and (b) an MCF10DCIS.com xenograft model of ER-negative mammary tumors. Among vitamin D analogues we tested, Gemini 0072 [1alpha,25-dihydroxy-20S-21(3-trideuteromethyl-3-hydroxy-4,4,4-trideuterobutyl)-23-yne-26,27-hexafluoro-19-nor-cholecalciferol] and Gemini 0097 [1alpha,25-dihydroxy-20R-21(3-trideuteromethyl-3-hydroxy-4,4,4-trideuterobutyl)-23-yne-26,27-hexafluoro-19-nor-cholecalciferol] administration inhibited by 60% the NMU-induced mammary tumor burden compared with the NMU-treated control group, but these compounds were devoid of hypercalcemia toxicity. In an ER-negative xenograft model, Gemini 0097 significantly suppressed tumor growth without hypercalcemia toxicity. We found that the inhibitory effect of Gemini 0097 was associated with an increased level of cyclin-dependent kinase inhibitor p21 and the insulin-like growth factor binding protein 3 in both ER-positive and ER-negative mammary tumors. Our results suggest that Gemini vitamin D analogues may be potent agents for the prevention and treatment of both ER-positive and ER-negative breast cancer without hypercalcemia toxicity.

  18. Inecalcitol, an analog of 1,25D₃, displays enhanced antitumor activity through the induction of apoptosis in a squamous cell carcinoma model system

    PubMed Central

    Ma, Yingyu; Yu, Wei-Dong; Hidalgo, Alejandro A.; Luo, Wei; Delansorne, Remi; Johnson, Candace S.; Trump, Donald L.

    2013-01-01

    Epidemiological data suggest an important role of vitamin D signaling in cancer development and progression, and experimental studies demonstrate that the active vitamin D metabolite 1α, 25-dihydroxyvitamin D₃ (1,25D₃) has broad spectrum antitumor activity. Hypercalcemia has often been suggested to limit the clinical application of these data. The 14-epi-analog of 1,25D₃, inecalcitol [19-nor-14-epi-23-yne-1,25-(OH)₂D₃; TX522], was developed to have superagonistic antitumor activities but low hypercalcemia potential. We examined the antitumor activity of inecalcitol and the underlying mechanisms in a murine squamous cell carcinoma (SCC) model system. In vitro, compared with 1,25D₃, inecalcitol showed enhanced vitamin D receptor (VDR)-mediated transcriptional activity. Inecalcitol suppressed SCC cell proliferation in a dose-dependent manner with an IC₅₀ value 30 times lower than that of 1,25D₃. Both inecalcitol and 1,25D₃ induced a comparable level of G₀/G₁ cell cycle arrest in SCC cells. The level of apoptosis induced by inecalcitol was markedly higher than that of 1,25D₃. Apoptosis was mediated through the activation of the caspase 8/10- caspase 3 pathway. Further, inecalcitol markedly inhibited the mRNA and protein expression of c-IAP1 and XIAP compared with 1,25D₃. In vivo, inecalcitol inhibits SCC tumor growth in a dose-dependent fashion. Notably, inecalcitol induced a significantly higher level of apoptosis in the SCC xenograft model. While in vitro inecalcitol demonstrates apparent enhanced VDR binding and antiproliferative effects compared to 1,25D₃, in vivo these advantages disappear; at doses of inecalcitol that have equivalent antitumor effects, similar hypercalcemia is seen. This may be explained by the pharmacokinetics of 1,25D₃ vs. inecalcitol and attributed to the much shorter serum half-life of inecalcitol.We show that inecalcitol has potent antitumor activity in the SCC model system, and this is associated with a

  19. A Phase I trial of calcitriol (1,25-dihydroxycholecalciferol) in patients with advanced malignancy.

    PubMed

    Smith, D C; Johnson, C S; Freeman, C C; Muindi, J; Wilson, J W; Trump, D L

    1999-06-01

    Vitamin D is a steroid hormone best known for its activity in regulating calcium and bone metabolism. Epidemiological evidence suggests that vitamin D may play a role in inhibiting the development of colon and prostate cancer. Vitamin D receptors are expressed in many types of malignant cells; in vitro and in vivo vitamin D and vitamin D analogues are active in suppressing the development and inhibiting the growth of numerous human and animal tumors. The major toxicity of the active form of vitamin D, 1,25-dihydroxycholecalciferol (calcitriol), is the induction of hypercalcemia. There are no data indicating the maximum tolerated dose of calcitriol administered every other day (QOD) s.c. We hypothesized that this route and schedule would permit administration of higher doses of calcitriol, which might have anticancer activity. We conducted a Phase I trial of calcitriol given s.c. QOD in patients with advanced solid tumors. Thirty-six patients were entered at doses ranging from 2 to 10 microg QOD; dose-limiting toxicity (hypercalcemia) occurred in three of three patients entered at the 10-microg QOD dose. Hypercalciuria occurred at all dose levels examined. No other toxicity was seen. Assessment of serum calcitriol concentrations by a RIA revealed a decrease in concentration-time curves on day 7 compared to day 1 of therapy. A dose-dependent increase in peak serum level and estimated area under the concentration-time curve was seen. The maximum serum levels occurred at the 10-microg QOD dose: 288 +/- 74 and 321 +/- 36 pg/ml at days 1 and 7, respectively. The normal range of calcitriol serum concentration, determined using this assay, is 16-56 pg/ml. Serum calcitriol levels were maintained at near peak concentrations for at least 8 h following s.c. injection. This study indicates that substantial doses of calcitriol can be administered via this route with tolerable toxicity. Studies to explore approaches to ameliorate the hypercalcemia induced by calcitriol and to

  20. CYP24A1 loss of function: Clinical phenotype of monoallelic and biallelic mutations.

    PubMed

    Carpenter, Thomas O

    2017-01-16

    CYP24A1, encoding the vitamin D-24-hydroxylase, is of major clinical and physiologic importance, serving to regulate the catabolism of 1,25-(OH)2D, the physiologically active vitamin D metabolite. In addition to facilitating catabolism of 1,25-(OH)2D, CYP24A1 also enhances the turnover and elimination of 25-OHD, the abundant precursor metabolite and storage form of the vitamin. CYP24A1 can be stimulated hormonally by 1,25-(OH)2D and by FGF23, whereas CYP27B1, encoding the vitamin D-1α-hydroxylase, is stimulated hormonally by parathyroid hormone (PTH) and downregulated by FGF23. Thus CYP24A1 and CYP27B1, together, provide for alternate and regulated fates of 25-OHD, and control the availability of the active metabolite, 1,25-(OH)2D, depending upon physiologic needs. These two enzymes, are therefore central to the homeostatic control of vitamin D metabolism, and as a result affect calcium metabolism in critical ways. Disruption of CYP24A1 in mice results in elevated circulating 1,25-(OH)2D, substantiating the importance of the enzyme in the maintenance of vitamin D metabolism. The consequential skeletal phenotype in these mice further demonstrates the biologic sequelae of the disruption of the vitamin D pathway, and illustrates a specific developmental pathology mediated largely by oversupply of 1,25-(OH)2D. More recent evidence has identified loss of function mutations in CYP24A1 in association with hypercalcemia, hypercalciuria and nephrolithiasis in humans. Initial reports described certain variant mutations in CYP24A1 as an unrecognized cause of "Idiopathic Infantile Hypercalcemia," and more recently older children and adults have been identified with a similar phenotype. Over 25 likely disease-causing variants are described. Homozygous and compound heterozygote mutations account for the overwhelming majority of cases, however the heterozygous loss-of-function mutations of CYP24A1 do not appear to consistently result in symptomatic hypercalcemia. Considerations

  1. Systemic and renal vascular responses to dietary calcium and vitamin D.

    PubMed

    Zawada, E T; TerWee, J A; McClung, D E

    1986-11-01

    To assess the consequences of hypercalcemia on systemic and renal hemodynamics, vasoactive hormones, and water and electrolyte excretion in intact, conscious mongrel dogs, measurements in 10 dogs receiving 100 mg/kg calcium gluconate and 10,000 U/kg vitamin D daily for 2 weeks were compared with measurements made in 10 time-control dogs not receiving calcium or vitamin D. Hypercalcemia induced by dietary supplementation with calcium and vitamin D resulted in profoundly reduced glomerular filtration rate (40 vs 78 ml/min in controls; p less than 0.005), estimated renal plasma flow (145 vs 267 ml/min in controls; p less than 0.005), and renal blood flow (254 vs 441 ml/min in controls; p less than 0.005). Renal resistance was significantly increased in the hypercalcemic dogs (0.57 +/- 0.07 vs 0.28 +/- 0.01 mm Hg/ml/min; p less than 0.005). Hypercalcemia also resulted in increased fractional excretion of water (4.8 vs 1.4% in controls; p less than 0.005), sodium (1.4 vs 0.6% in controls; p less than 0.005), calcium (1.7 vs 0.7% in controls; p less than 0.01), and magnesium (10.2 vs 4.1% in controls; p less than 0.005). Systolic blood pressure (160 vs 172 mm Hg in controls; p less than 0.05) and stroke volume were lower (0.024 vs 0.036 L/beat in controls; p less than 0.005) in hypercalcemic dogs, presumably because of the diuresis, while total peripheral resistance was higher (36 vs 31 mm Hg/L/min; p less than 0.05) in controls. Magnesium levels were significantly lower in the experimental group (1.3 vs 1.7 mg/dl in controls; p less than 0.0005). Aldosterone levels, plasma renin activity, and urinary prostaglandin excretion were not significantly affected.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Hypophosphatasia.

    PubMed

    Linglart, Agnès; Biosse-Duplan, Martin

    2016-06-01

    Hypophosphatasia is a rare disorder due to a mutation in the ALPL gene encoding the alkaline phosphatase (ALP) leading to a diminished activity of the enzyme in bone, liver, and kidney. Hypophosphatasia is a heterogeneous disease, ranging from extreme life-threatening forms revealed at birth in young infants presenting with severely impaired bone mineralization, seizures, and hypercalcemia, to young adults with premature exfoliation of their teeth without any other symptom. We will review the challenges of the clinical, biochemical, radiological, and genetic diagnosis. Schematically, the diagnosis relies on low ALP levels and, in most cases, on the genetic defect in the ALPL gene. An enzyme replacement therapy is now developed for hypophosphatasia; early results in the severe form of the disease are extremely encouraging. However, multidisciplinary care remains the core of treatment of hypophosphatasia encompassing nutritional support, adjustment of calcium and phosphate intake, monitoring of vitamin D levels, careful and personalized physical therapy, and regular dental monitoring and care.

  3. Biphosphonates-related osteonecrosis of the jaw: Clinical and physiopathological considerations

    PubMed Central

    Borgioli, Alberto; Viviani, Christian; Duvina, Marco; Brancato, Leila; Spinelli, Giuseppe; Brandi, Maria Luisa; Tonelli, Paolo

    2009-01-01

    Since osteonecrosis of the jaw was related to biphosphonate administration by Marx, studies showing clinical symptoms, drug and surgical therapies overwhelmed the literature. Furthermore, the literature demonstrated the correlation between chronic biphosphonate adsumption and osteonecrosis of the jaw onset. Nitrogen-containing biphosphonates are widely used for the management of metastatic cancer, for prevention and treatment of osteoporosis, for the treatment of Paget's disease, and for the management of acute hypercalcemia. According to our experience, the treatment of BRON-J's lesions is difficult and prolonged. For this reason, in order to avoid these complications it is mandatory to perform a risk staging in patients who must undergo biphosphonate administration. When pharmacologic treatments with antibiotics and local antiseptics are not able to control the development of BRON-J's complications, the clinicians should perform radical surgical treatments such as the resection of the bone involved. PMID:19436626

  4. Bisphosphonate therapy for women with breast cancer and at high risk for osteoporosis.

    PubMed Central

    Morris, Gloria J.; Mitchell, Edith P.

    2007-01-01

    Bisphosphonates are effective inhibitors of osteoclast activity and bone resorption, and are standard treatments for osteoporosis, hypercalcemia of malignancy, and metabolic bone disease. Bisphosphonates have also been established to effectively reduce skeletal-related events due to malignancy metastatic to bone. Bisphosphonates are now being incorporated into breast cancer treatment regimens in order to combat osteoporosis caused by ovarian suppression, chemotherapy treatment, aromatase inhibitors and the postmenopausal state itself. A large body of evidence suggests that African-American women are at higher risk for osteoporosis-related morbidity than their Caucasian counterparts. In this review, we highlight recommendations toward screening for osteoporosis in high-risk populations. We summarize the mechanisms of action of bisphosphonates in the treatment of osteoporosis and then summarize national recommendations toward incorporating the use of bisphosphonates as support for the bone health of breast cancer patients, as well as patients at high risk for osteoporosis. Images Figure 1 Figure 3 PMID:17304967

  5. Milk-alkali syndrome in a middle-aged woman after ingesting large doses of calcium carbonate: a case report

    PubMed Central

    2009-01-01

    Introduction Most cases of hypercalcaemia are secondary to malignancy or primary hyperparathyroidism. Here we report a case of hypercalcaemia that we have attributed to milk-alkali syndrome. Case presentation A 51-year-old Caucasian woman with a past history of thyroidectomy and parathyroidectomy secondary to thyroid cancer developed an altered mental state and had an extremely high calcium concentration of 22.8 mg/dl (5.7 mmol/l). Investigations included work up for malignancy and hyperparathyroidism. However, the hypercalcaemia was attributed to ingestion of large doses of calcium carbonate, leading to milk-alkali syndrome. She was managed with intravenous fluids and withdrawal of calcium carbonate. The patient responded well to treatment, with normalization of the calcium concentration and clinical improvement. Conclusion We present this case to remind clinicians of the importance of detailed history taking and of milk-alkali syndrome as a cause of hypercalcemia. PMID:20181207

  6. Radiographic features of plasma cell leukemia in the maxilla: A case report

    PubMed Central

    Wong, Phillip; Kashtwari, Deeba

    2016-01-01

    Plasma cell leukemia (PCL) is an aggressive form of multiple myeloma where there is hematogenous spread of abnormal plasma cells into the periphery. This is opposed to multiple myeloma, where the abnormal plasma cells stay in the bone marrow. PCL is more common in males than females, and is also more common in African-Americans than Caucasians. Signs and symptoms of PCL include, but are not limited to, renal insufficiency, hypercalcemia, anemia, lytic bone lesions, thrombocytopenia, hepatomegaly, and splenomegaly. Here, we discussed a case of a 71-year-old Caucasian female recently diagnosed with primary PCL with radiographic features of this disease throughout the body, with an emphasis on the maxillofacial skeleton and relevance from a dental standpoint. PMID:28035306

  7. Incidental detection of gastrointestinal stromal tumor by Tc-99m MDP bone scan.

    PubMed

    Shepherd, Timothy M; Idakoji, Ibrahim A; Pampaloni, Miguel H

    2012-02-01

    This case demonstrates extraosseous 99m-technetium methylene diphosphonate (Tc-99m MDP) accumulation from a gastrointestinal stromal tumor. A 75-year-old woman underwent a temporal bone CT for conductive hearing loss that showed sclerosis in the right occipital condyle. Follow-up Tc-99m MDP bone scan for osseous metastases instead showed a mass-like extraosseous accumulation of Tc-99m MDP in the anterior left upper quadrant. Differential diagnoses included gastric cancer, lymphoma, metastatic melanoma, systemic hypercalcemia, or heterotopic mesenteric ossification. Contrast CT showed a well-circumscribed mass arising from the stomach, and subsequent pathology confirmed gastrointestinal stromal tumor. These tumors rarely can contain osteoclast-like giant cells and should be considered for extraosseous Tc-99m MDP accumulation.

  8. Primary hyperparathyroidism

    PubMed Central

    Madkhali, Tarıq; Alhefdhi, Amal; Chen, Herbert; Elfenbein, Dawn

    2016-01-01

    Primary hyperparathyroidism is a common endocrine disorder caused by overactivation of parathyroid glands resulting in excessive release of parathyroid hormone. The resultant hypercalcemia leads to a myriad of symptoms. Primary hyperparathyroidism may increase a patient’s morbidity and even mortality if left untreated. During the last few decades, disease presentation has shifted from the classic presentation of severe bone and kidney manifestations to most patients now being diagnosed on routine labs. Although surgery is the only curative therapy, many advances have been made over the past decades in the diagnosis and the surgical management of primary hyperparathyroidism. The aim of this review is to summarize the characteristics of the disease, the work up, and the treatment options. PMID:26985167

  9. MAJOR MOLECULAR GENETIC DRIVERS IN SPORADIC PRIMARY HYPERPARATHYROIDISM

    PubMed Central

    ARNOLD, ANDREW

    2016-01-01

    Primary hyperparathyroidism is primarily due to a solitary parathyroid adenoma but multi-gland disease, parathyroid carcinoma, and ectopic parathyroid hormone production can occur. Although primary hyperparathyroidism mostly presents sporadically, strong familial predispositions also exist. Much is known about heritable genetic mutations responsible for these syndromes, including multiple endocrine neoplasia types 1 and 2A, hyperparathyroidism-jaw tumor syndrome, and familial hypocalciuric hypercalcemia. Acquired mutations in common sporadic hyperparathyroidism have also been discovered. Here we focus on the most common and well-established genetic drivers: 1) involvement of the oncogene cyclin D1 in human neoplasia was first established in parathyroid adenomas, followed by recognition of its importance in other tumor types including breast cancer and B-lymphoid malignancy; and 2) somatic mutation of the MEN1 gene, first identified as the source of pathogenic germline mutations in patients with familial endocrinopathies, is found in a substantial fraction of non-familial parathyroid adenomas. PMID:28066056

  10. Bilateral genu valgum: an unusual presentation of juvenile primary hyperparathyroidism

    PubMed Central

    Sharma, Shruti; Kumar, Sunil

    2016-01-01

    Primary hyperparathyroidism is a generalized disorder of bone and mineral metabolism caused by autonomous secretion of parathyroid hormone. It is primarily seen in adults with typical age of presentation between third and fifth decades of life. Juvenile hyperparathyroidism is a rare disorder. The common presentations in order of incidence are fatigue and lethargy, headache, nephrolithiasis, nausea, abdominal pain, vomiting and polydipsia. Though skeletal symptoms include bone pains and fractures, but the presence of limb deformity is atypical. We report a case of young girl who presented with isolated progressive genu valgum of both lower limbs and pigeon-shaped chest deformity. She was found to have hypercalcemia and hypophosphatemia with raised parathyroid hormone levels. The neck imaging showed a single adenoma in the left inferior parathyroid gland. The surgical removal of parathyroid adenoma was performed. PMID:27471596

  11. [A case of bisphosphonate-related osteonecrosis of the jaw in a patient who had received intravenous bisphosphonates].

    PubMed

    Ishikawa, Tohru

    2014-02-01

    Bisphosphonates(BPs)have been widely used for the treatment of hypercalcemia associated with cancer, multiple myeloma bone diseases, and bone metastasis of solid cancers. Many cases of bisphosphonate-related osteonecrosis of the jaw (BRONJ)have been reported in Japan. We report a case of a patient who developed BRONJ after tooth extraction even though the administration of BPs had been discontinued for 23 months. The patient was a 74-year-old woman who had received intravenous BPs from 2003 through 2008. She underwent tooth extraction in 2010. The bone in the extraction socket was exposed for more than 8 weeks. A clinical diagnosis of BRONJ was made. Discontinuation of BPs before surgical dental treatment did not appear to prevent BRONJ in this patient who had received intravenous BPs.

  12. Space medicine considerations: Skeletal and calcium homeostasis

    NASA Technical Reports Server (NTRS)

    Schneider, Victor B.

    1989-01-01

    Based on the information obtained from space missions, particularly Skylab and the longer Salyut missions, it is clear that bone and mineral metabolism is substantially altered during space flight. Calcium balance becomes increasingly more negative throughout the flight, and the bone mineral content of the os calcis declines. The major health hazards associated with skeletal changes include the signs and symptoms of hypercalcemia with rapid bone turnover, the risk of kidney stones because of hypercalciuria, the lengthy recovery of lost bone mass after flight, the possibility of irreversible bone loss (particularly the trabecular bone), the possible effects of metastated calcification in the soft tissues, and the possible increase in fracture potential. For these reasons, major efforts need to be directed toward elucidating the fundamental mechanisms by which bone is lost in space and developing more effective countermeasures to prevent both short-term and long-term complications.

  13. Metabolic pancreatitis: Etiopathogenesis and management.

    PubMed

    Kota, Sunil Kumar; Krishna, S V S; Lakhtakia, Sandeep; Modi, Kirtikumar D

    2013-09-01

    Acute pancreatitis is a medical emergency. Alcohol and gallstones are the most common etiologies accounting for 60%-75% cases. Other important causes include postendoscopic retrograde cholangiopancreatography procedure, abdominal trauma, drug toxicity, various infections, autoimmune, ischemia, and hereditary causes. In about 15% of cases the cause remains unknown (idiopathic pancreatitis). Metabolic conditions giving rise to pancreatitis are less common, accounting for 5%-10% cases. The causes include hypertriglyceridemia, hypercalcemia, diabetes mellitus, porphyria, and Wilson's disease. The episodes of pancreatitis tend to be more severe. In cases of metabolic pancreatitis, over and above the standard routine management of pancreatitis, careful management of the underlying metabolic abnormalities is of paramount importance. If not treated properly, it leads to recurrent life-threatening bouts of acute pancreatitis. We hereby review the pathogenesis and management of various causes of metabolic pancreatitis.

  14. Effect of doxercalciferol (1alpha-hydroxyvitamin D2) on PTH, bone turnover and bone mineral density in a hemodialysis patient with persistent secondary hyperparathyroidism post parathyroidectomy.

    PubMed

    Parisi, M S; Oliveri, B; Somoza, J; Mautalen, C

    2003-06-01

    The efficacy and safety of the vitamin D analog, doxercalciferol (1alpha-hydroxyvitamin D2, 1alphaD2) in the treatment of secondary hyperparathyroidism in hemodialysis patients has been previously reported. We report these effect of 16-week 1alphaD2 treatment on mineral metabolism and bone mineral density (BMD) in a hemodialysis patient with persistent secondary hyperparathyroidism post parathyroidectomy, resistant to previous calcitriol treatment. Levels of iPTH, bone-specific alkaline phosphatase and serum type I collagen C telopeptide were above normal at baseline and were substantially decreased with 1alphaD2 treatment (-92%, -63% and -53%, respectively). BMD increased in all areas: total skeleton (+6.5%), lumbar spine (+6.9%) and total femur (+4.3%). The patient showed no hypercalcemia, and phosphorus levels remained between 3.3 and 6.2 mg/dl.

  15. The role of RANK-ligand inhibition in cancer: the story of denosumab.

    PubMed

    Castellano, Daniel; Sepulveda, Juan Manuel; García-Escobar, Ignacio; Rodriguez-Antolín, Alfredo; Sundlöv, Anna; Cortes-Funes, Hernán

    2011-01-01

    The diagnosis of bone metastases is an event with certain consequences for the patient. They often mean pain and can also mean pathological fractures, hypercalcemia, and spinal cord compression, all synonymous with a diminished quality of life and often also hospitalization. Since the advent of the intravenous bisphosphonates, things began to look a bit brighter for patients with bone metastases-bone destruction was kept at bay a little longer. The next generation of bone metastasis treatments is well on its way in clinical development, and among them, the most advanced drug is denosumab. Denosumab is a fully human monoclonal antibody that inhibits osteoclast maturation, activation, and function by binding to receptor activator of nuclear factor kappa B ligand, with the final result being a reduced rate of bone resorption. In this review, we give an overview of relevant preclinical and clinical data regarding the use of denosumab in patients with solid tumors in general and prostate cancer in particular.

  16. Recent advances in antimultiple myeloma drug development

    PubMed Central

    Wang, Nuozhou; Bartlow, Patrick; Ouyang, Qin; Xie, Xiang-Qun

    2015-01-01

    Multiple myeloma (MM) is the second most common hematological malignancy and is characterized by the aberrant proliferation of terminally differentiated plasma B cells with impairment in apoptosis capacity. Particularly, osteolytic bone diseases and renal failure resulting from hyperparaproteinemia and hypercalcemia have been the major serious sequelae that are inextricably linked with MM tumor progression. Despite the introduction of new treatment regimens, problematic neuropathy, thrombocytopenia, drug resistance and high MM relapse rates continue to plague the current therapies. New chemical agents are in development on the basis of understanding several signaling pathways and molecular mechanisms like tumor necrosis factor-α, proteasome, PI3K and MARKs. This review focuses on the most recent patents and clinical trials in the development of new medicine for the treatment of multiple myeloma. Furthermore, the important signaling pathways involved in the proliferation, survival and apoptosis of myeloma cells will be discussed. PMID:24998287

  17. Clinical expression of familial Williams-Beuren syndrome in a Turkish family.

    PubMed

    Parlak, Mesut; Nur, Banu Güzel; Mıhçı, Ercan; Durmaz, Erdem; Karaüzüm, Sibel Berker; Akcurin, Sema; Bircan, İffet

    2014-01-01

    Williams-Beuren syndrome (WBS) is a rare genetic disorder characterized by distinctive facial features, intellectual disability with a typical neurobehavioral profile, cardiovascular anomalies, and occasional infantile hypercalcemia. Majority of cases occur sporadically, and only a few cases of familial WBS have been reported. Although pre- and post-natal growth retardation is a common clinical feature of the syndrome, growth hormone deficiency is detected only in a few patients. To our knowledge, there has only been one report about familial Williams-Beuren syndrome in the Turkish population. Here, we report on the three molecular cytogenetically confirmed familial Williams-Beuren syndromes detected in a family with familial short stature. The father, daughter, and son analyzed with clinical and laboratory findings, and reasons of the short stature in Williams-Beuren syndrome are discussed through the literature.

  18. Osteonecrosis of the Torus Palatinus in the Setting of Long-Term Oral Bisphosphonate Use--A Case Report.

    PubMed

    Ryan, Joshua L; Larson, Eric

    2016-01-01

    Bisphosphonates are medications used orally and intravenously for a variety of conditions including cancer metastatic to bone, hypercalcemia of malignancy, Paget's disease and osteoporosis. Osteonecrosis of the jaw has been related to bisphosphonate use. Osteonecrosis of the jaw most commonly occurs in the setting of intravenous bisphosphonate use and concomitant dental work or trauma. Oral bisphosphonates have much less risk of osteonecrosis of the jaw. We present an interesting case of a patient on an oral bisphosphonate for an extended period of time (nine years), with a torus palatinus, who burned her palate while eating a slice of pizza. Over six months later, she presented with an area of denuded bone and diagnosis consistent with osteonecrosis of the torus palatinus.

  19. Bisphosphonates and osteonecrosis of the jaws: science and rationale.

    PubMed

    Gutta, Rajesh; Louis, Patrick J

    2007-08-01

    Bisphosphonates as a group of drugs were introduced for the management of various conditions such as osteoporosis, Paget's disease, multiple myeloma, hypercalcemia of malignancy, breast cancer, prostate cancer, and other tumors. This group of drugs has improved the quality of life in many patients with proven efficacy in limiting pain and skeletal-related events. The controversy of osteonecrosis of the jaws and bisphosphonates is a recent and growing problem. Osteonecrosis of the jaws is recognized as a serious complication of bisphosphonate therapy, more commonly with the intravenous form of the drugs. However, there is limited scientific understanding about the association between osteonecrosis of the jaws and bisphosphonates. In the present article we discuss various mechanisms of action of bisphosphonates, the rationale for occurrence of osteonecrosis in the jaws, and treatment guidelines for the condition.

  20. Intrathyroidal parathyroid hyperplasia in tertiary hyperparathyroidism

    PubMed Central

    Kim, Byung Seup; Ryu, Han Suk; Kang, Kyung Ho; Park, Sung Jun

    2013-01-01

    We report herein a case of intrathyroidal parathyroid hyperplasia in a patient with tertiary hyperparathyroidism. The patient was recommended for parathyroidectomy due to sustained hypercalcemia after kidney transplantation. Preoperative radiologic evaluations showed a benign-looking thyroid mass and three enlarged parathyroid glands. Intraoperative intact parathyroid hormone (iPTH) level and frozen biopsy results indicated a missed parathyroid gland after immediate subtotal parathyroidectomy. Then, a secondary partial resection of thyroid including the thyroid nodule was performed. An excised intrathyroid nodule was diagnosed to be parathyroid hyperplasia by frozen biopsy, and intraoperative iPTH level abruptly decreased. A benign-looking thyroidal mass in patients with secondary or tertiary hyperparathyroidism should be carefully evaluated considering the possibility of an intrathyroidal parathyroid hyperplasia. PMID:24964443

  1. Primary Hyperparathyroidism in Pregnancy: A Two-Case Report and Literature Review

    PubMed Central

    Herrera-Martínez, A. D.; Bahamondes-Opazo, R.; Palomares-Ortega, R.; Muñoz-Jiménez, C.; Gálvez-Moreno, M. A.; Quesada Gómez, J. M.

    2015-01-01

    Primary hyperparathyroidism (PHPT) in pregnant women is an uncommon disease. It could be easily misdiagnosed because of physiologic changes during pregnancy; in some cases, patients could remain asymptomatic maintaining elevated calcium serum levels, and this situation represents a threat to the health of both mother and fetus. We present two cases of PHPT during pregnancy and their evolution after surgical treatment in the second trimester; there were no observed complications during pregnancy or delivery in our patients. Early diagnosis and medical/surgical treatment in PHPT are necessary for avoiding maternal and fetal complications which could not be predicted based on duration or severity of hypercalcemia. An appropriate management of PHPT during pregnancy is necessary for preserving the health of both the woman and the fetus. PMID:25893124

  2. Bisphosphonate induced osteochemonecrosis of the jaws: an ounce of prevention may be worth a pound of cure.

    PubMed

    Hellstein, John W; Marek, Cindy L

    2006-01-01

    Patient exposure to bisphosphonate drugs for the management of hypercalcemia of malignancy, osteolytic lesions of metastatic cancer and osteoporosis has led to increasing reports of osteochemonecrosis of the jaws (bis-phossy jaw). This serious and debilitating condition requires dental practitioners to be alert for signs and symptoms of this syndrome. Thus far, nitrogen containing bisphosphonates have been implicated as a causative agent. While only a small fraction of patients who have taken these agents will develop osteochemonecrosis, it seems that patients who have received intravenous bisphosphonates are at greater risk than those who have taken oral agents. Tooth extractions are the most frequently reported predisposing dental procedure. While appropriate management strategies for patients with osteochemonecrosis of the jaws are evolving, we are suggesting rational preventive protocols and therapies based upon current experience and knowledge. These recommendations may change over time as the profession gains more experience in managing these patients.

  3. Experimental acute toxicity of xylitol in dogs.

    PubMed

    Xia, Z; He, Y; Yu, J

    2009-10-01

    The Cases of xylitol poisoning in dogs are increasing as a result of ingestion of xylitol-containing products. Eighteen adult, clinically normal Pekingese dogs were orally dosed with 1 or 4 g/kg xylitol in aqueous solution. Blood samples were collected before and after dosing. Plasma insulin concentrations of both treated groups rose sharply from 20 min after xylitol dosing, peaking at 40 min. Hypoglycemia followed the increase in insulin concentration, with blood glucose values started to decrease 30 min after dosing. Other plasma biochemistry changes associated with xylitol administration were increased alanine aminotransferase and aspartate aminotransferase activities, hypophosphatemia, hypokalemia, and hypercalcemia. Plasma sodium and chloride concentrations remained normal. This study established a biochemical basis for diagnosis and treatment of xylitol poisoning in dogs.

  4. [Normocalcemic primary hyperparathyroidism: a growing problem].

    PubMed

    Martínez Díaz-Guerra, Guillermo; Guadalix Iglesias, Sonsoles; Hawkins Carranza, Federico

    2013-08-04

    Normocalcemic primary hyperparathyroidism is at present one of the most common reasons for consultation in bone metabolism units. It is characterized by increased levels of intact parathyroid hormone in the presence of normal serum calcium (total and ionized) in generally asymptomatic individuals. The differential diagnosis should be considered in all situations that occur with secondary hyperparathyroidism. Its natural history is not well known, and it does not always progress to hypercalcemia. As a recently recognized entity, there are still no specific recommendations for its management. In this review we discuss some aspects of this entity, emphasizing the importance of a proper laboratory diagnosis, assessing possible signs or symptoms associated such as kidney stones or osteoporosis, which can help the clinician to take a conservative or interventionist attitude.

  5. Negative regulation of parathyroid hormone-related protein expression by steroid hormones.

    PubMed

    Kajitani, Takashi; Tamamori-Adachi, Mimi; Okinaga, Hiroko; Chikamori, Minoru; Iizuka, Masayoshi; Okazaki, Tomoki

    2011-04-15

    Elevated parathyroid hormone-related protein (PTHrP) is responsible for humoral hypercalcemia of malignancy (HHM), which is of clinical significance in treatment of terminal patients with malignancies. Steroid hormones were known to cause suppression of PTHrP expression. However, detailed studies linking multiple steroid hormones to PTHrP expression are lacking. Here we studied PTHrP expression in response to steroid hormones in four cell lines with excessive PTHrP production. Our study established that steroid hormones negatively regulate PTHrP expression. Vitamin D receptor, estrogen receptor α, glucocorticoid receptor, and progesterone receptor, were required for repression of PTHrP expression by the cognate ligands. A notable exception was the androgen receptor, which was dispensable for suppression of PTHrP expression in androgen-treated cells. We propose a pathway(s) involving nuclear receptors to suppress PTHrP expression.

  6. Notch2 transduction by feline leukemia virus in a naturally infected cat.

    PubMed

    Watanabe, Shinya; Ito, Jumpei; Baba, Takuya; Hiratsuka, Takahiro; Kuse, Kyohei; Ochi, Haruyo; Anai, Yukari; Hisasue, Masaharu; Tsujimoto, Hajime; Nishigaki, Kazuo

    2014-04-01

    Feline leukemia virus (FeLV) induces neoplastic and nonneoplastic diseases in cats. The transduction of cellular genes by FeLV is sometimes observed and associated with neoplastic diseases including lymphoma and sarcoma. Here, we report the first natural case of feline Notch2 transduction by FeLV in an infected cat with multicentric lymphoma and hypercalcemia. We cloned recombinant FeLVs harboring Notch2 in the env gene. Notch2 was able to activate expression of a reporter gene, similar to what was previously reported in cats with experimental FeLV-induced thymic lymphoma. Our findings suggest that the transduction of Notch2 strongly correlates with FeLV-induced lymphoma.

  7. Role of SPECT and SPECT/CT in the Surgical Treatment of Primary Hyperparathyroidism

    PubMed Central

    Taubman, Michele L.; Goldfarb, Melanie; Lew, John I.

    2011-01-01

    Primary hyperparathyroidism is the most common cause of hypercalcemia in the outpatient population. This condition is usually the result of a single hyperfunctioning parathyroid gland. Targeted parathyroidectomy guided by intraoperative parathyroid hormone monitoring (IPM) through a small cervical incision has replaced traditional bilateral neck exploration (BNE) as the initial approach in the surgical treatment of primary hyperparathyroidism at many medical centers worldwide. Preoperative sestamibi-technetium 99m scintigraphy serves as an important prerequisite for successful targeted parathyroidectomy. Single-photon emission computed tomography (SPECT) and CT fusion, however, is a recent imaging technique that provides a three-dimensional functional image with advanced contrast resolution to greatly improve preoperative localization of parathyroid tumors. PMID:21776381

  8. Controversies in the management of parathyroid carcinoma: A case series and review of the literature.

    PubMed

    Medas, Fabio; Erdas, Enrico; Loi, Giulia; Podda, Francesco; Pisano, Giuseppe; Nicolosi, Angelo; Calò, Pietro Giorgio

    2016-04-01

    Parathyroid carcinoma is a rare malignancy representing less than 1% of primary hyperparathyroidism cases. Its management is controversial due to lack of large-scale, multicentric studies. We report 8 new cases of parathyroid carcinoma and review the literature. Preoperative diagnosis of carcinoma was possible in 2 (25%) cases. Unclear surgical margins were present in 5 (62.5%) patients; 4 of them underwent subsequent re-exploration and ipsilateral hemithyroidectomy, in one case associated to central lymph node dissection. Recurrent disease is reported in 2 (25%) patients. Considering the high incidence of local recurrence in case of unclear surgical margins, a re-exploration with ipsilateral hemithyroidectomy is indicated in these patients. A neck dissection should be performed only in case of clinically involved lymph nodes, avoiding prophylactic lymphectomy. An aggressive approach is indicated in case of local or distant recurrence to reduce hypercalcemia.

  9. Vitamin D supplementation in the elderly: review of safety and effectiveness of different regimes.

    PubMed

    Byrne, P M; Freaney, R; McKenna, M J

    1995-06-01

    Vitamin D deficiency is common in the elderly, especially in countries where effective sunlight or exposure to sunlight is limited. Two regimes for vitamin D supplementation--low-dose daily oral administration and intermittent high-dose administration--were examined with regard to safety and effectiveness. Eleven papers reporting studies in 449 elderly subjects were reviewed. On low-dose continuous supplementation mean concentration of 25 hydroxyvitamin D (25(OH)D) ranged from 57 to 105 nmol/L compared to 55 to 87 nmol/L following high-dose supplementation. These mean values fall within the physiological range for young adults. Hypercalcemia occurred in only 3 subjects and was associated with a predisposing cause in 2 of 3 subjects. We suggest that low dose continuous supplementation (10 to 20 micrograms daily) is the regime of choice but high-dose intermittent supplementation (2.5 mg six monthly) may be suitable where compliance is poor.

  10. Relapse of Multiple Myeloma Presenting as Extramedullary Plasmacytomas in Multiple Organs

    PubMed Central

    Köse, Murat; Buraniqi, Ersida; Akpinar, Timur Selçuk; Kayacan, Seyit Mehmet; Tükek, Tufan

    2015-01-01

    Multiple myeloma is a neoplastic plasma cell disorder. It is characterized by collections of abnormal plasma cells accumulating in the bone marrow, where they interfere with the production of normal blood cells. It usually presents as a multisystemic involvement, whose symptoms and signs vary greatly. Some patients have slowly progressive disease while others have aggressive clinical behavior by extramedullary involvement. In addition to renal failure, anemia, hypercalcemia, lytic bone lesions, and immunodeficiency, it also affects multiple organ system, such as pancreas, adrenal glands, kidney, skin, lung, liver, spleen, lymph nodes, and bone. To raise awareness of the variable presentations of this disease, we report a 53-year-old male patient, with multiple myeloma in his first remission who relapsed with extramedullary plasmacytomas (EMPs) involving multiple organs, such as pancreas, adrenal glands, kidney, skin, lung, liver, spleen, and lymph nodes. PMID:25694834

  11. Mineral and bone disorder and vascular calcification in patients with chronic kidney disease.

    PubMed

    Peres, Luis Alberto Batista; Pércio, Pedro Paulo Verona

    2014-01-01

    Vascular calcifications has been associated with bone and mineral disorders. The alterations in the serum level of calcium concentrations and phosphate are importants factors implicated in the arterial calcification in chronic kidney disease. The pathogenesis of vascular calcification is a complex mechanism and not completely clear, being able to correspond to an active process of cellular transformation and heterotopic ossification. Beyond the hypercalcemia and hyperphosphatemia, they are involved in this process changes in the metabolism of inhibitors and promoters of calcification such as fetuin A, osteopontin, osteoprotegerin, and matrix gla protein. For the diagnosis of the calcified arterial injury are available several complementary methods, a method of estimate of the cardiovascular risk based on plain radiographs of the lumbar column and another method based on simple x-rays of the pelvis and hands. Below, we will present a review approching the link between vascular calcifications and mineral disorders.

  12. Bisphosphonates and atherosclerosis: why?

    PubMed

    Bevilacqua, M; Dominguez, L J; Rosini, S; Barbagallo, M

    2005-01-01

    The increasing knowledge on bone calcification processes has revealed some similarities with vascular tissue, where calcifications of arteries and cardiac valves contribute to several cardiovascular problems, such as heart failure, systolic hypertension, and myocardial and peripheral ischemic disease. Bisphosphonates have been used extensively for over two decades for the treatment of diseases associated with excessive bone resorption, i.e., osteoporosis, osteolytic bone metastasis, hypercalcemia and Paget's disease, by blocking osteoclastic function. Etidronate, pamidronate and clodronate has been shown to inhibit the development of experimental atherosclerosis, and proposed mechanisms for this action include inhibition of arterial calcification and lipid accumulation, degradation of atherogenic LDL-cholesterol and reduced foam cell formation. Bisphosphonates inhibit various enzymes involved in cholesterol biosynthesis and suppress macrophages in atheromatous lesions. The possibility of pharmacological agents that effectively treat both osteoporosis and atherosclerosis is attractive, however, current evidence is not conclusive and further research is necessary to confirm these actions in the clinical setting.

  13. The Science and Practice of Bone Health in Oncology: Managing Bone Loss and Metastasis in Patients With Solid Tumors

    PubMed Central

    Lipton, Allan; Uzzo, Robert; Amato, Robert J.; Ellis, Georgiana K.; Hakimian, Behrooz; Roodman, G. David; Smith, Matthew R.

    2011-01-01

    Cancer and its treatment can compromise bone health, leading to fracture, pain, loss of mobility, and hypercalcemia of malignancy. Bone metastasis occurs frequently in advanced prostate and breast cancers, and bony manifestations are commonplace in multiple myeloma. Osteoporosis and osteopenia may be consequences of androgen-deprivation therapy for prostate cancer, aromatase inhibition for breast cancer, or chemotherapy-induced ovarian failure. Osteoporotic bone loss and bone metastasis ultimately share a pathophysiologic pathway that stimulates bone resorption by increasing the formation and activity of osteoclasts. Important mediators of pathologic bone metabolism include substances produced by osteoblasts, such as RANKL, the receptor activator of nuclear factor kappa B ligand, which spurs osteoclast differentiation from myeloid cells. Available therapies are targeted to various steps in cascade of bone metastasis. PMID:19878635

  14. Williams syndrome starts making sense

    SciTech Connect

    Ashkenas, J.

    1996-10-01

    1996 may be marked as a transitional year in the study of Williams syndrome (WS), when the causes of this complex condition and a practical way to investigate began to come into focus. WS presents a remarkable collection of symptoms that affect blood vessels, growth, intelligence, and behavior. WS commonly leads to infantile hypercalcemia, retardation of growth, prematurely wrinkled skin, supraventricular aortic stenosis (SVAS), and sensitivity to loud noise. Children with this condition are often mentally retarded, with distinctive {open_quotes}elfin{close_quotes} facial features, a hoarse voice, and an {open_quotes}engaging{close_quotes} personality. Their cognitive deficits may be minimal or profound but typically involve a specific pattern of strengths and weaknesses, with better-than-average face recognition but little ability to recognize how parts of patterns that they see fit into a whole. 36 refs.

  15. Bisphosphonates: Mechanism of Action and Role in Clinical Practice

    PubMed Central

    Drake, Matthew T.; Clarke, Bart L.; Khosla, Sundeep

    2009-01-01

    Bisphosphonates are primary agents in the current pharmacological arsenal against osteoclast-mediated bone loss due to osteoporosis, Paget disease of bone, malignancies metastatic to bone, multiple myeloma, and hypercalcemia of malignancy. In addition to currently approved uses, bisphosphonates are commonly prescribed for prevention and treatment of a variety of other skeletal conditions, such as low bone density and osteogenesis imperfecta. However, the recent recognition that bisphosphonate use is associated with pathologic conditions including osteonecrosis of the jaw has sharpened the level of scrutiny of the current widespread use of bisphosphonate therapy. Using the key words bisphosphonate and clinical practice in a PubMed literature search from January 1, 1998, to May 1, 2008, we review current understanding of the mechanisms by which bisphosphonates exert their effects on osteoclasts, discuss the role of bisphosphonates in clinical practice, and highlight some areas of concern associated with bisphosphonate use. PMID:18775204

  16. Vitamin D and Risk for Vitamin A Intoxication in an 18-Month-Old Boy

    PubMed Central

    Barreca, Massimo; Galiano, Rossella; Galati, Maria Concetta; Raiola, Giuseppe

    2016-01-01

    An 18-month-old boy presented with abdominal pain, vomiting, diarrhea, and poor appetite for 6 days. He had been given a multivitamin preparation once daily, containing 50.000 IU of vitamin D and 10.000 IU of vitamin A for a wide anterior fontanelle for about three months. He presented with hypercalcemia, low levels of parathyroid hormone (PTH), and very high serum 25-hydroxyvitamin D (25-OHD) levels. Renal ultrasound showed nephrocalcinosis. He did not have sign or symptom of vitamin A intoxication. Patient was successfully treated with intravenous hydration, furosemide, and prednisolone. With treatment, serum calcium returned rapidly to the normal range and serum 25-OHD levels were reduced progressively. In conclusion the diagnosis of vitamin D deficiency rickets without checking 25-OHD levels may cause redundant treatment that leads to vitamin D intoxication (VDI). PMID:27478669

  17. The Role of RANK-Ligand Inhibition in Cancer: The Story of Denosumab

    PubMed Central

    Sepulveda, Juan Manuel; García-Escobar, Ignacio; Rodriguez-Antolín, Alfredo; Sundlöv, Anna; Cortes-Funes, Hernán

    2011-01-01

    The diagnosis of bone metastases is an event with certain consequences for the patient. They often mean pain and can also mean pathological fractures, hypercalcemia, and spinal cord compression, all synonymous with a diminished quality of life and often also hospitalization. Since the advent of the intravenous bisphosphonates, things began to look a bit brighter for patients with bone metastases—bone destruction was kept at bay a little longer. The next generation of bone metastasis treatments is well on its way in clinical development, and among them, the most advanced drug is denosumab. Denosumab is a fully human monoclonal antibody that inhibits osteoclast maturation, activation, and function by binding to receptor activator of nuclear factor kappa B ligand, with the final result being a reduced rate of bone resorption. In this review, we give an overview of relevant preclinical and clinical data regarding the use of denosumab in patients with solid tumors in general and prostate cancer in particular. PMID:21285392

  18. Solitary Extramedullary Plasmacytoma of the Liver without Systemic Monoclonal Gammopathy

    PubMed Central

    Lee, Jun-Young; Kim, Hyun-Jung; Bae, Sang-Byung; Kim, Chan-Kyu; Kim, Jung Hoon; Lee, Nam-Su; Lee, Kyu-Taeg; Park, Sung-Kyu; Jin, So-Young; Hong, Dae-Sik; Park, Hee-Sook

    2007-01-01

    Extramedullary plasmacytoma of the liver is a very rare tumor. Although a few cases of extramedullary plasmacytoma of the liver have been reported, we could not find any report on truly localized extramedullary plasmacytoma of the liver in the literature. The patient was a 63-yr-old man who exhibited a solitary liver mass on dynamic computed tomography and magnetic resonance imaging. Histologically, the tumor was composed of mature plasma cells with mild atypia. Immunohistochemistry demonstrated monoclonal IgG and Kappa light chain expression. Bone marrow examination revealed no abnormalities. There was no evidence of a monoclonal protein in the serum and urine, lytic bone lesions, anemia, renal insufficiency, and hypercalcemia. The patient was treated with 5,000 cGy of radiotherapy, and the tumor disappeared 6 months after treatment. PMID:17728524

  19. Williams-Beuren syndrome associated with single kidney and nephrocalcinosis: a case report

    PubMed Central

    Abidi, Kamel; Jellouli, Manel; Rabeh, Rania Ben; Hammi, Yousra; Gargah, Tahar

    2015-01-01

    Williams-Beuren syndrome is a rare neurodevelopmental disorder, characterized by congenital heart defects, abnormal facial features, mental retardation with specific cognitive and behavioral profile, growth hormone deficiency, renal and skeletal anomalies, inguinal hernia, infantile hypercalcaemia. We report a case with Williams-Beuren syndrome associated with a single kidney and nephrocalcinosis complicated by hypercalcaemia. A male infant, aged 20 months presented growth retardation associated with a psychomotor impairment, dysmorphic features and nephrocalcinosis. He had also hypercalciuria and hypercalcemia. Echocardiography was normal. DMSA renal scintigraphy showed a single functioning kidney. The FISH generated one ELN signal in 20 metaphases read and found the presence of ELN deletion, with compatible Williams-Beuren syndrome. PMID:26958139

  20. Nuclear Imaging and Minimally Invasive Surgery in the Management of Hyperparathyroidism*

    PubMed Central

    Judson, Benjamin L.; Shaha, Ashok R.

    2013-01-01

    Primary hyperparathyroidism is the most common cause of hypercalcemia, and the treatment is primarily surgical. Because of biochemical screening, more patients now present with asymptomatic primary hyperparathyroidism, and consensus guidelines have been developed for the treatment of these patients. There is now considerable interest in minimally invasive approaches to the treatment of hyperparathyroidism. Sestamibi scanning as a localizing study, used in combination with anatomic imaging and intraoperative rapid parathyroid hormone assays, has enabled focused surgical approaches. Patients with localizing studies that indicate a single parathyroid adenoma are candidates for such approaches, including unilateral neck exploration, minimally invasive single-gland exploration, or endoscopic exploration instead of the traditional approach of bilateral neck exploration. Nuclear imaging is also critical to the successful management of patients with persistent or recurrent hyperparathyroidism. PMID:18927330

  1. Primary hyperparathyroidism and Klinefelter's syndrome in a young man

    PubMed Central

    Pellegrino, M; Attanasio, R; Guarnieri, V; Maffè, A; Borretta, G

    2015-01-01

    Summary We report the association of primary hyperparathyroidism (PHPT) and Klinefelter's syndrome (KS) in a 22-year-old male complaining of worsening fatigue. PHPT was asymptomatic at the diagnosis, but the patient had worsening hypercalcemia and osteoporosis, and developed acute renal colic. He then underwent parathyroidectomy with resection of a single adenoma and normalization of calcium and parathyroid hormone levels. Clinical and therapeutic implications of this rare association are discussed. Learning points The coexistence of KS and PHPT is very uncommon.Patients with mild PHPT often have nonspecific symptoms that may be confused and superimposed with those of hypogonadism.KS patients, especially when young and already osteoporotic at diagnosis, should be screened for other causes of secondary osteoporosis, in particular PHPT. PMID:25859391

  2. Subcutaneous fat necrosis of the newborn.

    PubMed

    Repiso-Jiménez, J B; Márquez, J; Sotillo, I; García-Bravo, B; Camacho, F

    1999-05-01

    Subcutaneous fat necrosis of the newborn (SFN) is an uncommon disease that affects newborns who have suffered from tissue hypoxia during or following delivery. This disease appears during the first weeks of life. It consists of indurate, erythematous or purple-erythematous nodules and plaques in the skin. Histology of a biopsy specimen shows granulomatous necrosis in the subcutis with radial crystals in lipocytes and giant cells. Spontaneous resolution in a few weeks is usual, but the mobilization of calcium from the necrosed subcutis together with the action of some hormones may cause hypercalcemia and certain serious complications. A newborn female child developed SFN after dystocic delivery causing cerebral frontal lobe hemorrhage. The skin nodules resolved spontaneously in a few weeks and no complications were observed 1 year later.

  3. Investigation of deletions at 7q11.23 in 44 patients referred for Williams-Beuren syndrome, using FISH and four DNA polymorphisms.

    PubMed

    Brøndum-Nielsen, K; Beck, B; Gyftodimou, J; Hørlyk, H; Liljenberg, U; Petersen, M B; Pedersen, W; Petersen, M B; Sand, A; Skovby, F; Stafanger, G; Zetterqvist, P; Tommerup, N

    1997-01-01

    Williams syndrome (WS) is associated with a submicroscopic deletion of the elastin gene (ELN) at 7q11.23. The deletion encompasses closely linked DNA markers. We have investigated 44 patients referred for possible WS using fluorescence in situ hybridization (FISH) analysis with a P1 clone containing an insert from the ELN, as well as performing genotype analysis of patients and parents with four DNA polymorphisms. Twenty-four patients were found to have deletions, 19 of whom were found clinically to have typical WS. The facial features were especially characteristic. None of the patients without detectable deletions was reported to have typical WS features, although one had supravalvular aortic stenosis, hypercalcemia, and mental retardation. No evidence was found in this material for variability of the size of the deletion. Our study supports the usefulness of analysis of ELN deletion in WS patients, both for confirmation of diagnosis and for genetic counselling.

  4. TREATMENT OF RENAL CARCINOMA IN A BINTURONG (ARCTICTIS BINTURONG) WITH NEPHRECTOMY AND A TYROSINE KINASE INHIBITOR.

    PubMed

    Thompson, Kimberly A; Patterson, Jon; Fitzgerald, Scott D; Needle, David; Harrison, Tara

    2016-12-01

    A 13-yr-old female binturong ( Arctictis binturong ) presented with a 1 wk history of decreased appetite. The animal was thin, with hypercalcemia (calcium 12.2 mg/dl). A right renal mass was identified on ultrasound and removed via nephrectomy. Histopathology indicated a renal adenocarcinoma. Treatment with toceranib phosphate, a tyrosine-kinase inhibitor, was initiated and well tolerated by the animal. Four months after initial diagnosis radiographs indicated metastases to the lungs and the animal was euthanized. Necropsy revealed disseminated adenocarcinoma. Although treatment did not prevent metastasis, it was minimally invasive and well tolerated by the animal with minimal side effects. Review of records at the institution revealed that the cause of death for the primary case's dam and sire was disseminated renal carcinoma. These cases suggest that there may be a hereditary component to development of renal neoplasia in binturongs. Renal carcinoma should be considered an aggressive neoplasia in binturongs with a poor prognosis.

  5. Estimation of influence of high doses of cholecalciferol on thyroid parafollicular and respiratory tract neuroendocrine cells; preliminary investigations.

    PubMed

    Sawicki, B; Zbucki, R L; Winnicka, M M; Kasacka, I; Nowosielski, C; Hukałowicz, K

    2004-01-01

    The aim of this study was to compare what changes are caused by high doses of cholecalciferol (100,000 UI vD3) and CaCl2 on thyroid parafollicular (C) cells and airways neuroendocrine (NE) cells in rat. Overdosage of vD3 and CaCl2 causes hypocalcaemia and strong hypercalcitoninemia in blood; C cells showed mainly signs of hypertrophy; simultaneously, the number of strong calcitoninpositive cells decreased significantly (statistically significant changes). Immunohistochemical reactions, detecting CGRP, somatostatin, synaptophysin and neuronspecific enolase did not fall under statistic analysis. Airways NE cells re-acted to hypercalcemia differently than C cells--they probably respond to different regulatory mechanisms.

  6. Venous thromboembolism in patients with monoclonal gammopathy of undetermined significance.

    PubMed

    Muslimani, Alaa A; Spiro, Timothy P; Chaudhry, Asif A; Taylor, Harris C; Jaiyesimi, Ishmael; Daw, Hamed A

    2009-12-01

    Monoclonal gammopathy of undetermined significance (MGUS) is defined by the presence of a serum M-protein at a concentration of 3 g/dL or less, with less than 10% plasma cells in the bone marrow, and the absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the plasma cell proliferative process. The annual risk of MGUS progressing to a symptomatic plasma cell proliferation or other related malignancy is approximately 1%. The association between malignancy and venous thromboembolism (VTE) is well recognized. In this retrospective study of MGUS patients, VTE was seen in 8% (9/112) of patients, a rate that is 22.8-fold higher than that in the general population (P is less than .001). Although many studies have identified VTE as a marker for subsequent malignancy, we did not find a significant difference in the incidence of VTE as a function of the risk factor group.

  7. Metabolic pancreatitis: Etiopathogenesis and management

    PubMed Central

    Kota, Sunil Kumar; Krishna, S.V.S.; Lakhtakia, Sandeep; Modi, Kirtikumar D.

    2013-01-01

    Acute pancreatitis is a medical emergency. Alcohol and gallstones are the most common etiologies accounting for 60%-75% cases. Other important causes include postendoscopic retrograde cholangiopancreatography procedure, abdominal trauma, drug toxicity, various infections, autoimmune, ischemia, and hereditary causes. In about 15% of cases the cause remains unknown (idiopathic pancreatitis). Metabolic conditions giving rise to pancreatitis are less common, accounting for 5%-10% cases. The causes include hypertriglyceridemia, hypercalcemia, diabetes mellitus, porphyria, and Wilson's disease. The episodes of pancreatitis tend to be more severe. In cases of metabolic pancreatitis, over and above the standard routine management of pancreatitis, careful management of the underlying metabolic abnormalities is of paramount importance. If not treated properly, it leads to recurrent life-threatening bouts of acute pancreatitis. We hereby review the pathogenesis and management of various causes of metabolic pancreatitis. PMID:24083160

  8. Lithium nephrotoxicity.

    PubMed

    Oliveira, Jobson Lopes de; Silva Júnior, Geraldo Bezerra da; Abreu, Krasnalhia Lívia Soares de; Rocha, Natália de Albuquerque; Franco, Luiz Fernando Leonavicius G; Araújo, Sônia Maria Holanda Almeida; Daher, Elizabeth de Francesco

    2010-01-01

    Lithium has been widely used in the treatment of bipolar disorder. Its renal toxicity includes impaired urinary concentrating ability and natriuresis, renal tubular acidosis, tubulointerstitial nephritis progressing to chronic kidney disease and hypercalcemia. The most common adverse effect is nephrogenic diabetes insipidus, which affects 20-40% of patients within weeks of lithium initiation. Chronic nephropathy correlates with duration of lithium therapy. Early detection of renal dysfunction should be achieved by rigorous monitoring of patients and close collaboration between psychiatrists and nephrologists. Recent experimental and clinical studies begin to clarify the mechanisms by which lithium induces changes in renal function. The aim of this study was to review the pathogenesis, clinical presentation, histopathological aspects and treatment of lithium-induced nephrotoxicity.

  9. [Renal side effects of long-term lithium therapy].

    PubMed

    Ibbeken, C; Becker, J U; Baumgärtel, M W

    2012-01-01

    Lithium is widely used in the treatment of bipolar disorders. Long-term administration of lithium often leads to side effects concerning the subjects: nephrology, endocrinology and surgery. This review emphasizes nephrotoxicity.Lithium treatment may disturb responsiveness to antidiuretic hormone (ADH), causing a nephrogenic diabetes insipidus. Furthermore long-term lithium therapy may trigger hyperparathyreoidism with hypercalcemia and chronic interstitial nephritis with development of microcysts. Long-term patients have an increased risk to develop impaired renal function. Lithium-induced endstage renal disease is rare. Termination of lithium treatment may decrease the risk of progression.To ensure security of lithium treatment regular controls of urine osmolarity, lithium-, creatinine- , thyroid stimulating hormone- and calcium-levels are essential. Patients with decreased renal function should be referred to a specialist early.

  10. [Lithium and chronic kidney disease: a pathology which remains relevant].

    PubMed

    Félix, Paula; Stoermann-Chopard, Catherine; Martin, Pierre-Yves

    2010-03-03

    Lithium continues to be the standard for acute and maintenance treatment of bipolar mood disorders despite the availability of alternative agents. Lithium has a narrow therapeutic index and can result in considerable toxicity. Acute renal intoxication is well-known but chronic kidney disease should be in each doctor's mind. The main manifestations are nephrogenic diabetes insipidus (NDI) and tubulointerstitial nephritis. For NDI, the potassium sparing diuretic amiloride or a thiazide diuretic can improve polyuria. Lithium-induced ESRD in chronic tubulointerstitial nephritis is not uncommon and more prevalent (> 1% among long-term lithium patients) than previously thought. The risk of renal failure may persist even after lithium discontinuation. Additional kidney manifestations of lithium exposure include renal tubular acidosis and hypercalcemia.

  11. Robotic excision of a huge parathyroid adenoma via a retroauricular approach.

    PubMed

    Lee, Jeon Mi; Byeon, Hyung Kwon; Choi, Eun Chang; Koh, Yoon Woo

    2015-01-01

    Primary hyperparathyroidism results from the overproduction of parathyroid hormone by 1 or more autonomously hyperfunctioning parathyroid glands and often causes hypercalcemia. Once this condition has been diagnosed, the treatment of choice is surgical removal. There have been many attempts to remove the hyperfunctioning gland with minimally invasive surgical techniques, with cure rates comparable with those of conventional techniques. On the basis of our initial surgical experiences of robotic thyroidectomy and other head and neck surgeries via a retroauricular (RA) approach, we have recently successfully performed robotic excision of a huge parathyroid tumor via an RA approach on a 44-year-old woman who had been diagnosed with a parathyroid adenoma. It is the first to describe in detail the successful completion of a robotic parathyroidectomy via an RA approach.

  12. Paraneoplastic syndromes in olfactory neuroblastoma

    PubMed Central

    Gabrych, Anna; Czapiewski, Piotr; Sworczak, Krzysztof

    2015-01-01

    Olfactory neuroblastoma (ONB) is a rare malignant neoplasm of sinonasal tract, derived from olfactory epithelium. Unilateral nasal obstruction, epistaxis, sinusitis, and headaches are common symptoms. Olfactory neuroblastoma shows neuroendocrine differentiation and similarly to other neuroendocrine tumors can produce several types of peptic substances and hormones. Excess production of these substances can be responsible for different types of endocrinological paraneoplastic syndromes (PNS). Moreover, besides endocrinological, in ONB may also occur neurological PNS, caused by immune cross-reactivity between tumor and normal host tissues in the nervous system. Paraneoplastic syndromes in ONB include: syndrome of inappropriate ADH secretion (SIADH), ectopic ACTH syndrome (EAS), humoral hypercalcemia of malignancy (HHM), hypertension due to catecholamine secretion by tumor, opsoclonus-myoclonus-ataxia (OMA) and paraneoplastic cerebellar degeneration. Paraneoplastic syndromes in ONB tend to have atypical features, therefore diagnosis may be difficult. In this review, we described initial symptoms, patterns of presentation, treatment and outcome of paraneoplastic syndromes in ONB, reported in the literature. PMID:26199564

  13. Nuclear microprobe imaging of gallium nitrate in cancer cells

    NASA Astrophysics Data System (ADS)

    Ortega, Richard; Suda, Asami; Devès, Guillaume

    2003-09-01

    Gallium nitrate is used in clinical oncology as treatment for hypercalcemia and for cancer that has spread to the bone. Its mechanism of antitumor action has not been fully elucidated yet. The knowledge of the intracellular distribution of anticancer drugs is of particular interest in oncology to better understand their cellular pharmacology. In addition, most metal-based anticancer compounds interact with endogenous trace elements in cells, altering their metabolism. The purpose of this experiment was to examine, by use of nuclear microprobe analysis, the cellular distribution of gallium and endogenous trace elements within cancer cells exposed to gallium nitrate. In a majority of cellular analyses, gallium was found homogeneously distributed in cells following the distribution of carbon. In a smaller number of cells, however, gallium appeared concentrated together with P, Ca and Fe within round structures of about 2-5 μm diameter located in the perinuclear region. These intracellular structures are typical of lysosomial material.

  14. Aortopulmonary window parathyroid gland causing primary hyperparathyroidism in men type 1 syndrome.

    PubMed

    Tonelli, Francesco; Biagini, Carlo; Giudici, Francesco; Cioppi, Federica; Brandi, Maria Luisa

    2016-01-01

    Primary hyperparathyroidism (HPT) is the most common endocrinopathy in Multiple Endocrine Neoplasia type 1 (MEN1) syndrome. Supernumerary and/or ectopic parathyroid glands, potentially causes of persistent or recurrent HPT after surgery, have been previously described. However, this is the first ever described case of ectopic parathyroid gland localized in the aortopulmunary window causing HPT in MEN1. After a consistent concordant pre-operative imaging assessment the patient, a 16 years old male affected by a severe hypercalcemia, underwent surgery. The parathyroid was found very deeply near the tracheal bifurcation, hidden by the aortic arch itself and for this reason not visible at the beginning of the dissection but only after being identified by palpation for its typical consistence. The intraoperative PTH decreased at normal level 10 min after removal of the ectopic gland. The patient remained with normal value of calcemia and PTH during the 10 months of follow-up.

  15. Asperger's disorder and Williams syndrome: a case report.

    PubMed

    Kilinçaslan, Ayse; Tanidir, Canan; Tutkunkardaş, Mustafa Deniz; Mukaddes, Nahit Motavalli

    2011-01-01

    Williams syndrome (WS) is a genetic disorder caused by the hemizygous microdeletion in chromosome 7q11.23. It is characterized by dysmorphic face, cardiovascular disease, idiopathic hypercalcemia, mental retardation, and an uneven profile of cognitive-linguistic abilities and deficits. The presence of autistic features in individuals with WS is a controversial issue. While there are reports that describe them as overly friendly with excessive sociability and good empathic skills, some recent studies focus more on the qualitative impairment of their social abilities. Here, we report the clinical presentation and follow-up of an eight-year-old boy with WS and clear problems in his social interaction, non-verbal communication and circumscribed interests. To our knowledge, this is the first case report on the coexistence of WS and Asperger's disorder. It also differs from previous papers on the comorbidity of WS and autism spectrum disorders, by depicting a highly verbal, nonretarded child followed for seven years through adolescence.

  16. International Myeloma Working Group Consensus Statement for the Management, Treatment, and Supportive Care of Patients With Myeloma Not Eligible for Standard Autologous Stem-Cell Transplantation

    PubMed Central

    Palumbo, Antonio; Rajkumar, S. Vincent; San Miguel, Jesus F.; Larocca, Alessandra; Niesvizky, Ruben; Morgan, Gareth; Landgren, Ola; Hajek, Roman; Einsele, Hermann; Anderson, Kenneth C.; Dimopoulos, Meletios A.; Richardson, Paul G.; Cavo, Michele; Spencer, Andrew; Stewart, A. Keith; Shimizu, Kazuyuki; Lonial, Sagar; Sonneveld, Pieter; Durie, Brian G.M.; Moreau, Philippe; Orlowski, Robert Z.

    2014-01-01

    Purpose To provide an update on recent advances in the management of patients with multiple myeloma who are not eligible for autologous stem-cell transplantation. Methods A comprehensive review of the literature on diagnostic criteria is provided, and treatment options and management of adverse events are summarized. Results Patients with symptomatic disease and organ damage (ie, hypercalcemia, renal failure, anemia, or bone lesions) require immediate treatment. The International Staging System and chromosomal abnormalities identify high- and standard-risk patients. Proteasome inhibitors, immunomodulatory drugs, corticosteroids, and alkylating agents are the most active agents. The presence of concomitant diseases, frailty, or disability should be assessed and, if present, treated with reduced-dose approaches. Bone disease, renal damage, hematologic toxicities, infections, thromboembolism, and peripheral neuropathy are the most frequent disabling events requiring prompt and active supportive care. Conclusion These recommendations will help clinicians ensure the most appropriate care for patients with myeloma in everyday clinical practice. PMID:24419113

  17. Primary hyperparathyroidism in pregnancy.

    PubMed

    Kamenický, Peter; Lecoq, Anne-Lise; Chanson, Philippe

    2016-06-01

    Primary hyperparathyroidism (PHPT) is one of the most common endocrine disorders in the general population but is rarely diagnosed during pregnancy. Symptoms of gestational PHPT may be unrecognized, or masked by physiological changes in calcium homeostasis associated with pregnancy. Gestational PHPT may have severe consequences for both mother and fetus. However, nowadays, gestational PHPT is usually diagnosed in earlier stages and milder forms, with low complication rates. Treatment should be individually tailored according to gestational age, the severity of hypercalcemia, and the risk-benefit balance. The conservative approach is preferred in mild forms, whereas surgery, usually performed during the second trimester, is reserved for symptomatic hypercalcemic PHPT. Given the young age of the patients, genetic causes should be considered.

  18. Bone and body mass changes during space flight

    NASA Astrophysics Data System (ADS)

    Schneider, V.; Oganov, V.; LeBlanc, A.; Rakmonov, A.; Taggart, L.; Bakulin, A.; Huntoon, C.; Grigoriev, A.; Varonin, L.

    Long duration space flight has shown us that humans have significant bone loss and mineral changes because they are living in microgravity. Skylab and the longer Salyut and Mir missions, are providing us useful data and allowing us to explore the mechanism involved in skeletal turnover. Bone redistribution occurs throughout space flight with bone loss predominately in the weight bearing bones of posture and locomotion. The primary health hazards which may occur during space flight induced by skeletal changes include signs and symptoms of hypercalcemia, and the risk of kidney stones and metastatic calcification. After flight lengthy recovery of bone mass and the possible increase in the risk of bone fracture should be considered. Continued research studies are being directed toward determining the mechanisms by which bone is lost in space and developing more effective countermeasures by both the US (Schneider and McDonald, 1984 and Schneider, LeBlanc & Huntoon, 1993) and Russian (Grigoriev et. al., 1989) space programs.

  19. Calcium bioavailability of nanonized pearl powder for adults.

    PubMed

    Chen, H S; Chang, J H; Wu, J S B

    2008-11-01

    The present study was aimed to evaluate the calcium bioavailability of pearl powder for humans. Both the nanonized pearl powder (NPP) and the micronized pearl powder (MPP) prepared by a dry grinder were tested. A group of healthy adults free from hyperthyroidism, hypercalcemia, and hypocalcemia were recruited as the subjects for oral administration with the pearl powder. The bioavailability was evaluated by the serum total calcium increment, the serum intact parathyroid hormone (iPTH) reduction, and the urine calcium/creatinine ratio increment in 6 h after administration. The results show better absorption and retention of calcium from NPP, as reflected with the shorter time elapsed before the maximum concentration of calcium appeared in the serum, higher iPTH reduction, more calcium absorption, and higher maximum calcium concentration (C(max)) in serum after ingestion, than that from MPP. We conclude that pearl powder is a beneficial source of calcium for adults and that nanonization improves its calcium bioavailability.

  20. Historical perspectives on the clinical development of bisphosphonates in the treatment of bone diseases.

    PubMed

    Francis, M D; Valent, D J

    2007-01-01

    Bisphosphonates (formerly termed diphosphonates) were first synthesized in the late 1800s; however, their clinical use has been relatively recent. The bisphosphonates' affinity for hydroxyapatite crystal surface led Procter and Gamble to test these compounds in dental, then medical applications. With key input from university researchers, this led to the medical use of the first bisphosphonate, etidronate disodium in 1968 to treat a young patient with myositis ossificans progressiva. Further clinical research led to widespread medical application for the bisphosphonate class including use as a diagnostic in radionuclide bone imaging agents, treatment of osteoporosis, Paget's disease of bone, hypercalcemia of malignancy and metastatic bone disease. The historical development of bisphosphonates provides an excellent example of how observations and knowledge obtained at the basic science level were applied and successfully tested in the clinic. The end result of these efforts has provided health care professionals with diagnostic and therapeutic tools to improve the lives of patients.

  1. [Efficacy and safety of lanthanum carbonate in chronic kidney disease patients with hyperphosphataemia].

    PubMed

    Laville, Maurice

    2011-06-01

    Hyperphosphataemia is a frequent complication in patients with chronic kidney disease and is associated with increased cardiovascular morbidity. Lanthanum carbonate is a calcium-free phosphate binder indicated in patients with chronic kidney disease. Its digestive absorption is minimal (<0,002%). This minimal quantity is rapidly excreted by the hepatobiliary system, but there is an initial accumulation in liver and bone, which reaches a plateau within a few weeks. Long-term follow-up until six years did not show any bone or liver toxicity. Efficacy and safety of lanthanum carbonate have been assessed in randomized trials. The most common side effects reported were gastrointestinal and occurred with a similar incidence than with placebo and other phosphate binders. Hypercalcemia was less frequent than with calcium carbonate. This review highlights pharmacokinetic, pharmacodynamic and clinical (efficacy and safety) properties of lanthanum carbonate and discusses its place in the management of hyperphosphataemia in patients with chronic kidney disease.

  2. [Genetic basis for skeletal disease. Clinical characteristics of hypophosphatasia and its treatment].

    PubMed

    Ozono, Keiichi

    2010-08-01

    Hypophosphatsia is caused by the defect of tissue-nonspecific alkaline phosphatase (ALP), and exhibits hypomineralization of skeleton and rachitic change of bone. The most severe form of hypophosphatasia is a perinatal form, which is also called a lethal form. However, some patients of this form can survive due to advances in neonatology. Other forms consist of infantile, childhood, adult and odonto types. Conventional therapies for hypophosphatasia are administration of vitamin B6 for convulsion and low calcium-containing milk for hypercalcemia. Bone marrow transplantation has been reported to treat several patients with hypophosphatasia. However, the method must be developed which improves the survival of donor mesenchymal cells in patients. Recombinant bone-targeted ALP therapy is now on clinical trial in Canada and U.S.A and expected to be available in near future.

  3. [Role of bone-density-conserving agents in the treatment for pain in patients with bone metastases].

    PubMed

    Zhabina, A S; Semiglazova, T Yu

    2015-01-01

    Bones are the fourth area of metastases of malignant tumors that significantly burden the disease reducing the quality of life of a patient as cause pain, threat pathological fracture, deteriorate limb function, and develop hypercalcemia. Treatment of patients should be comprehensive and base on the rational use of systemic therapy and local impacts. The use of bisphosphonates inhibits bone resorption and progression of bone metastases, reduces the risk of complications due to metastatic bone disease including pain. Bisphosphonates significantly reduce the incidence of SRE in patients with bone metastases, diminish the need for analgesic radiotherapy, postpone terms of SRE occurrence, reduce pain syndrome as well as the need for analgetics. They also easily tolerated by patients.

  4. Mechanisms of radio-protection by catecholamines in the hamster /Mesocricetus auratus/

    NASA Technical Reports Server (NTRS)

    Prewitt, R. L.; Musacchia, X. J.

    1975-01-01

    Experiments were conducted on normal and splenectomized male and female hamsters between 2 and 3 months old subjected to a whole-body exposure of 1000 or 2000 rads in a Co-60 source with a view toward evaluating their radio-protection by norepinephrine, isoproterenol, and phenylephrine. Vasoconstriction hypoxia mechanism of radio-protection is examined along with the hypothesis that isoproterenol protects by hypercalcemia-induced cell proliferation. Radiation experiment results are found to be consistent with the hypothesis that stimulation of alpha receptors results in radio-protection through a tissue hypoxia mechanism. Beta agonists seem to protect by a hypotensive-hypoxia mechanism. The catecholamines protect against the hematopoietic syndrome, but show no evidence of protection against the gastrointestinal syndrome.

  5. Correlation of Serum and Ionized Calcium in Patients with Calcium Nephrolithiasis

    PubMed Central

    Milicevic, Snjezana; Bijelic, Radojka; Jakovljevic, Branislava; Krivokuca, Marija; Krivokuca, Vladimir

    2014-01-01

    Introduction: Pathogenesis of kidney stones includes many factors, whereas uroliths, as a generic term for kidney stones, are of a different composition. In pathogenesis of calcium urolithiasis hypercalcemia/hypercalciuria takes a significant place. Hypercalcemia exists when the serum calcium is of increased values, along with measurement and calculation of physiologically active calcium, when there are differences in the Ph of the blood or albumin. Goal: the goal of this research is to determine the correlation of values of the serum (CaS) and ionized calcium (Ca++) in patients with the calcium nephrolithiasis, whom have been established not to have hyperparathyroidism and malign diseases. Material and methods: the research was prospective and implemented at the Clinical Center in Banja Luka, at the Urology Clinic, in the period between 1st April 2012 – 1st January 2013 and it included 120 patients with the calcium lithiasis of the upper part of the urinary tract, divided into three age categories. Diagnosis of the calcium lithiasis of the upper part of the urinary tract was established on the basis of the ultrasonography of the urinary tract as well as native urinary tract/intravenous urography and chemical analysis of the stone in patients with spontaneous stone emission or after some of the methods for active removal of the stone. Chemical laboratory analysis of the serum and ionized calcium was done for all the patients, with 3ml of blood being taken for establishing the aforementioned parameters (1-2 ml of the serum) in vacuumed test tubes or glass tubes of capillary blood. Increased parathormone values (PHT) and history of malignity were excluding factors. Results: out of the 120 patients observed, Cs(S) had the value in the reference interval with most of them, that is, in 110 patients (91.7%). Those, whose value was out of the interval, are of an older age (all above 40). Average value of this parameter amounted to 2.3017, with an average difference (the

  6. Epitheliotropic cutaneous lymphoma (mycosis fungoides) in a dog.

    PubMed

    Bhang, Dong Ha; Choi, Ul Soo; Kim, Min Kyu; Choi, Eun-Hwa; Kang, Min-Soo; Hwang, Cheol-Yong; Kim, Dae-Yong; Youn, Hwa Young; Lee, Chang Woo

    2006-03-01

    A seven-year-old castrated male Yorkshire terrier dog was presented for a recurrent skin disease. Erythematous skin during the first visit progressed from multiple plaques to patch lesions and exudative erosion in the oral mucosa membrane. Biopsy samples were taken from erythematous skin and were diagnosed with epitheliotropic T cell cutaneous lymphoma by histopathology and immunochemical stain. In serum chemistry, the dog had a hypercalcemia (15.7 mg/dl) and mild increased alkaline phosphatase (417 U/l). Immunohistochemistry was performed to detect parathyroid hormone-related peptide (PTH-rP) in epitheliotropic cutaneous lymphoma tissues but the neoplastic cells were not labeled with anti-PTH-rP antibodies. The patient was treated with prednisolone and isotretinoin. However, the dog died unexpectedly.

  7. [Regulatory mechanism of calcium metabolism.

    PubMed

    Ozono, Keiichi

    It is often difficult for terrestrial animals to take enough calcium. To maintain serum or extracellular calcium levels is very important for muscle and nerve function. Two major regulators to increase the serum calcium levels are parathyroid hormone(PTH)and vitamin D. PTH binds to the G protein coupling receptor, PTH1R, and increases intracellular cAMP levels. Impirement in the PTH signalling causes many diseases such as pseudohypoparathyroidism and acrodysostosis with hormone resistance. Vitamin D is activated to 1,25-dihydroxyvitamin D[1,25(OH)2D]by two steps of hydroxylation which occurs in the Liver and Kidney. Then, 1,25(OH)2D binds to vitamin D receptor(VDR), which works as a ligand-dependent transcription factor. Hypocalcemia and hypercalcemia are caused by various disorders including abnormal regulation of PTH and vitamin D production and their signal transduction.

  8. [Difficulties in renal osteodystrophy treatment in patient undergoing long-term renal replacement therapy--a case study].

    PubMed

    Jander, Anna; Kałuzyńska, Anna; Tkaczyk, Marcin

    2010-01-01

    Abnormal mineral metabolism and altered bone structure and composition occur early in the course of chronic kidney disease. We present difficulties in renal osteodystrophy treatment in patient undergoing renal replacement therapy for twenty two years (dialysis, transplant, dialysis), which is not in the waiting list for kidney transplant (patient disagreement). Due to failure of conventional therapy of hyperparathyroidism (calcium, phosphate binders, vitamin D) he was needed parathyroidectomy twice. Now he presents a very low PTH level but hyperphosphatemia, hypercalcemia and calcium/phosphate product over upper limit. This disturbances led to extra skeletal calcification (skin, vessels, eyes - "red eyes syndrome", central nervous system). Even now having new phosphate binders we cannot keep plasma phosphate, calcium in normal range, probably due to inadequate diet and non-compliance. Effective therapy is still difficult in this patient.

  9. Assessment of the free binding energy of 1,25-dihydroxyvitamin D3 and its analogs with the human VDR receptor model.

    PubMed

    Kamel, Karol; Kolinski, Andrzej

    2012-01-01

    1,25-dihydroxyvitamin D(3) has quite significant anticancer properties, but its strong calcemic effect in principle excludes it as a potential anticancer drug. Currently, a lot of effort is being devoted to develop potent anticancer analogs of 1,25-dihydroxyvitamin D(3) that would not induce hypercalcemia during therapy. In this work, the free binding energy of the VDR receptor with 1,25-dihydroxyvitamin D(3) and its three potent analogs (EB 1089, KH 1060 and RO 25-9022) is calculated and compared with each other. With this approach, we could estimate the relative binding affinity of the most potent analog, RO 25-9022, and also revealed a quite distinct mechanism of its interaction with VDR.

  10. [Amyloidosis of the tongue as a possible diagnostic manifestation of plasmacytoma].

    PubMed

    Hoefert, S; Schilling, E; Philippou, S; Eufinger, H

    1999-01-01

    Plasmocytic non-Hodgkin's lymphoma is the most common tumor of bone and bone marrow, typically diagnosed by symptoms such as monoclonal paraproteinemia, proteinuria, anemia and hypercalcemia. In its progress, deposits of amyloids in almost all organs can be observed. However, plasmacytomas which are diagnosed by macroglossia of primarily unknown etiology are rare. This case report presents a 61-year-old woman who suffered from a persistent swelling of the tongue with painful ulcerations. A biopsy led to the diagnosis of primary systemic amyloidosis of the light-chain type, which subsequently proved to be a plasmacytoma with lambda light-chains stage II after Durie and Salmon. In the course of the disease the patient developed further deposits of amyloids in the whole gastro-enteric system. Macroglossia as a primary manifestation of plasmacytoma is rarely described in medical literature. However, reports on deposits of amyloid in the tongue in advanced stages of disease are well known.

  11. Multi-organ involvement of Heterobilharzia americana infection in a dog presented for systemic mineralization.

    PubMed

    Corapi, Wayne V; Ajithdoss, Dharani K; Snowden, Karen F; Spaulding, Kathy A

    2011-07-01

    Canine schistosomiasis due to Heterobilharzia americana is a clinically underdiagnosed disease in dogs, which is found primarily in the Gulf Coast and south Atlantic region of the United States. A 3-year-old dog from Texas with a clinical diagnosis of systemic mineralization of unknown origin in the absence of evidence of hypercalcemia was found at necropsy to have severe disseminated H. americana infection involving the liver, pancreas, small and large intestine, lungs, and kidneys. Calcification of many of the large number of H. americana eggs gave the false impression of soft-tissue mineralization on radiographic and ultrasonographic images. Polymerase chain reaction amplification and sequencing of DNA derived from formalin-fixed sections of small intestine and liver, using primers specific for a 487-base pair segment of the H. americana small subunit ribosomal RNA gene, confirmed the presence of H. americana.

  12. Psammomatous Squamous Cell Carcinoma of the Skin.

    PubMed

    Schuler, Andrew; Smith, Emily; Chen, Stephanie; Chan, May P; Harms, Paul W

    2017-09-20

    Psammoma bodies (PBs) are concentric, lamellated calcifications commonly observed in malignancies such as papillary thyroid carcinoma and serous carcinoma of the ovary in which they may serve prognostic value. PBs are rare in cutaneous squamous cell carcinoma (cSCC), with only 1 previously reported case. Here, we present 3 cases of cSCC displaying PBs. One case occurred in the setting of end-stage renal disease, whereas the other 2 cases were in patients who did not have comorbid conditions that might predispose to hypercalcemia and dystrophic calcification. All 3 tumors demonstrated classic immunophenotypic findings of cSCC. Our findings indicate that PBs are a rare but recurrent phenomenon in cSCC, with unknown prognostic significance. The potential for PB formation in cSCC should be kept in mind, as this may represent a diagnostic pitfall in tumors with limited sampling or unusual morphologies.

  13. Cardiovascular manifestations of Williams syndrome: imaging findings.

    PubMed

    Gray, J Cranston; Krazinski, Aleksander W; Schoepf, U Joseph; Meinel, Felix G; Pietris, Nicholas P; Suranyi, Pal; Hlavacek, Anthony M

    2013-01-01

    Williams syndrome is a relatively common (1 in 10,000 live births) genetic disorder caused by a deletion involving chromosome 7 that results in a variety of clinically significant abnormalities, including developmental delay, behavioral changes, hypercalcemia, and a distinct "elfin" facial appearance. Congenital cardiovascular disease that presents in childhood is responsible for most of the morbidity and mortality associated with this disorder. The purpose of this pictorial essay is to review imaging findings of some of the more common cardiovascular manifestations of Williams syndrome and to highlight some of the unique anatomic variations that can be seen in these patients. Copyright © 2013 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

  14. Is it time for preemptive drug treatment of asymptomatic (smoldering) multiple myeloma?

    PubMed

    Fawole, Adewale; Abonour, Rafat; Stender, Michael; Shatavi, Seerin; Gaikazian, Susanna; Anderson, Joseph; Jaiyesimi, Ishmael

    2015-01-01

    Asymptomatic (smoldering) multiple myeloma is a heterogeneous plasma cell proliferative disorder with a variable rate of progression to active multiple myeloma or related disorders. Hypercalcemia, renal insufficiency, anemia, bone lesions or recurrent bacterial infections characterize active multiple myeloma. Some patients with asymptomatic myeloma develop active disease rapidly, and others can stay asymptomatic for many years. Those who are likely to progress within the first 2 years of diagnosis have been categorized as having high-risk disease. The availability of novel agents in the treatment of active multiple myeloma and our better understanding of the heterogeneity of asymptomatic multiple myeloma have spurred interest in the early treatment of these patients. We have reviewed the current proposed definitions of high-risk asymptomatic multiple myeloma, the concerns about future therapy in view of the transient nature, remissions and toxicities of the therapies, and the eventual relapses that characterize this incurable disease.

  15. Remarkable shrinkage of sarcomatoid renal cell carcinoma with single-agent gemcitabine.

    PubMed

    Fujiwara, Yoshiro; Kiura, Katsuyuki; Tabata, Masahiro; Takigawa, Nagio; Hotta, Katsuyuki; Umemura, Shigeki; Omori, Masako; Gemba, Kenichi; Ueoka, Hiroshi; Tanimoto, Mitsune

    2008-04-01

    A 60-year-old Japanese man presented to our hospital with a painful left hip. Computed tomography showed a tumor in the left kidney and metastases in the left gluteus maximus muscle and lung. The pathological diagnosis of a biopsy specimen obtained from a metastatic lesion in the left gluteus maximus muscle was sarcomatoid renal cell carcinoma. On admission, his general condition was extremely poor. He was confined to bed because of severe left hip pain and confusion, possibly caused by hypercalcemia. This seriously ill patient suffering from advanced sarcomatoid renal cell carcinoma was treated with single-agent gemcitabine, resulting in symptom relief and a dramatic improvement in his status; all of the tumors had regressed significantly by the 11th dose of gemcitabine. These findings indicate that single-agent gemcitabine is one of the few chemotherapeutic agents effective for palliation in patients with sarcomatoid renal cell carcinoma, even those with poor performance status.

  16. [Brown bone tumor as the first manifestation of primary hyperparathyroidism].

    PubMed

    Marcos García, M; Pino Rivero, V; Keituqwa Yáñez, T; Alcaraz Fuentes, M; Trinidad Ruiz, G; Blasco Huelva, A

    2003-01-01

    We report a clinical case of a 26 years old female who had a 2 years evolution chin tumour with hypercalcemia (11.8 mg/dl) and PTH (paratohormone) of 761 pg/ml. She underwent a CT scan and MRI of the mandible, as well as a biopsy followed by excision of the tumour by the maxilofacial surgeons. Our ENT Department asked for a Scintigraphy (Tc99s-mibi) and thoracic-cervical CT, which showed a lesion that turned out to be an adenoma of the lower right parathyroid gland after surgery and pathological examination. The patient suffered a Primary hyperparathyroidism that was the main stimulus for the Brown Tumour made up by macrophagos and multinuclear giant cells, being this the first manifestation of the metabolic disorder. This form of hyperparathyroidism is very rare in the clinic. We do a literature review to establish the differential diagnosis for such pathology.

  17. Ectopic calcification in lambs from feeding the plant Cestrum diurnum.

    PubMed

    Simpson, C F; Bruss, M L

    1979-01-01

    Hypercalcemia and ectopic calcification were induced in 5 lambs by supplementing the diet with the dried leaves of the plant Cestrum diurnum, for 8 to 9 weeks. Lambs developed mineralization of blood vessels, heart, kidneys, and lungs. These tissues were examined by light and electron microscopy. In the vascular tissue there was calcification of elastic fibers in the hyperplastic intima and the media, along with mineralization of mitochondria of aortic smooth muscle cells. Myocardial cells and their mitochondria were mineralized. In the kidney, there was calcification of the epithelium of the distal convoluted tubules and collecting tubules, Bowman's capsule, and the mesangial cells of the glomeruli. In the lung, there was mineralization of the alveolar septal walls and the bronchi and bronchioles. Feeding of the calcinogenic plant to lambs caused extensive soft tissue calcification. Results of the study indicated that degeneration was the early soft tissue lesion in this plant toxicity.

  18. Influence of gas stunning and halal slaughter (no stunning) on rabbits welfare indicators and meat quality.

    PubMed

    Nakyinsige, K; Sazili, A Q; Zulkifli, I; Goh, Y M; Abu Bakar, F; Sabow, A B

    2014-12-01

    This study assessed the effect of gas stunning which has not been conducted until now in comparison with slaughter without stunning on the welfare and meat quality of rabbits. Eighty male New Zealand White rabbits were divided into two groups of 40 animals and subjected to either halal slaughter without stunning (HS) or gas stunning using 61.4% CO2, 20.3% oxygen and 18.3 % nitrogen (GS). Analysis of the sticking blood revealed that both slaughter procedures caused a substantial increase in the levels of catecholamines, hypercalcemia, hyperglycemia, lactic acidemia and an increase in enzyme activities. The ultimate pH of the Longissimus lumborum muscle did not differ between treatments. GS exhibited higher lightness and cooking loss, and lower glycogen and MFI than HS. This indicates that both GS and HS can be significant stressors although the amount of stress may be below the threshold to negatively affect rabbit meat quality.

  19. Calcium metabolism in space flight.

    PubMed

    Neuman, W F

    1970-01-01

    Immobilization has been shown repeatedly to induce a loss of skeletal substance accompanied by hypercalcemia and hypercalcuria. Older data from paraplegics, polio patients, fracture patients and immobilized normal volunteers are reviewed. More recent studies of bone densitometry on normal volunteers and astronauts of Gemini flights IV, V, and VII are reported briefly. Finally, metabolic balance studies from Gemini VII are summarized. The balance data suggest that adequate calcium intake and programmed exercise may control the problem of calcium mobilization. However, there are disquieting discrepancies between the densitometric results (which show bone losses) and the balance data (which show no bone loss). Either the densitometric results are in error or there occur alarming intraskeletal transfers of bone mineral not detected by the balance approach.

  20. Mechanisms of radio-protection by catecholamines in the hamster /Mesocricetus auratus/

    NASA Technical Reports Server (NTRS)

    Prewitt, R. L.; Musacchia, X. J.

    1975-01-01

    Experiments were conducted on normal and splenectomized male and female hamsters between 2 and 3 months old subjected to a whole-body exposure of 1000 or 2000 rads in a Co-60 source with a view toward evaluating their radio-protection by norepinephrine, isoproterenol, and phenylephrine. Vasoconstriction hypoxia mechanism of radio-protection is examined along with the hypothesis that isoproterenol protects by hypercalcemia-induced cell proliferation. Radiation experiment results are found to be consistent with the hypothesis that stimulation of alpha receptors results in radio-protection through a tissue hypoxia mechanism. Beta agonists seem to protect by a hypotensive-hypoxia mechanism. The catecholamines protect against the hematopoietic syndrome, but show no evidence of protection against the gastrointestinal syndrome.

  1. Undiagnosed renal sarcoidosis in a patient with chronic interstitial nephritis.

    PubMed

    Dong, Wenfang; Qiu, Bin; Liu, Hongfeng; He, Leren

    2017-09-05

    A 53-year-old female was admitted to hospital, with acute elevation of SCr and hypercalcemia, on a 5-year history of chronic interstitial nephritis and stage III chronic kidney disease (CKD). Extensive workup failed to yield a definitive diagnosis concerning the cause of the disorder. Intense uptake of (18)F-FDG in the spleen and liver was detected by PET/CT imaging with negative angiotensin-converting enzyme (ACE) in serum. The spleen and the hypermetabolism nodules of the liver were resected for histopathologic examination and turned out to be noncaseating granulomas, likely sarcoidosis. Combined with clinical features, the final diagnosis for this patient was sarcoidosis, involving the kidneys, spleen, liver, and lungs.

  2. Primary hyperparathyroidism due to parathyroid carcinoma.

    PubMed

    Mendoza, V; Hernández, A F; Márquez, M L; Delgadillo, M A; Peña, J; Mercado, M

    1997-01-01

    Most cases of primary hyperparathyroidism are due to either a parathyroid adenoma or to parathyroid hyperplasia. Parathyroid carcinoma is a very rare cause of hyperparathyroidism. Although the diagnosis of parathyroid carcinoma is usually established based on pathological criteria of vascular and capsular invasion, some clinical and biochemical features differentiate it from benign forms of hyperparathyroidism. We report the case of a middle-aged woman with a long standing history of nephrolithiasis, who presented with a palpable neck mass, weight loss, severe hypercalcemia and hypophosphatemia, as well as very high serum levels of intact parathyroid hormone. Surgical neck exploration revealed a large tumor that invaded trachea, esophagus, reccurrent laryngeal nerve, right apical pleura and right carotid artery. Pathological examination confirmed the invasive nature of the tumor. Along with the case report, we review the literature and discuss the diagnostic and therapeutic options of this rare condition.

  3. Systemic Sarcoidosis with Thyroid Involvement.

    PubMed

    Okuma, Hideyuki; Hashimoto, Koshi; Wang, Xin; Ohkiba, Noriaki; Murooka, Nozomi; Akizuki, Norikazu; Inazawa, Takeshi; Ogawa, Yoshihiro

    2017-08-15

    A 66-year-old woman, who was diagnosed with iritis, visited our hospital due to general malaise. A blood analysis revealed hypercalcemia. Computed tomography revealed mediastinal and hilar lymph node hyperplasia. Moreover, (67)Gallium scintigraphy demonstrated strong accumulation in the lesions, suggesting sarcoidosis. A core needle biopsy (CNB) of the hypoechoic areas of the thyroid was performed because the patient refused to undergo a bronchoscopic examination. The scattering of slightly acidophilic epithelioid cell granulomas was observed in the pathological examination of the biopsy specimen. Based on this finding, the patient was diagnosed with sarcoidosis. Although sarcoidosis rarely involves the thyroid gland, in the present case, thyroid CNB was an alternative diagnostic method that allowed a pathological diagnosis to be obtained.

  4. Human stanniocalcin: a possible hormonal regulator of mineral metabolism.

    PubMed Central

    Olsen, H S; Cepeda, M A; Zhang, Q Q; Rosen, C A; Vozzolo, B L

    1996-01-01

    We have isolated a human cDNA clone encoding the mammalian homolog of stanniocalcin (STC), a calcium- and phosphate-regulating hormone that was first described in fishes where it functions in preventing hypercalcemia. STC has a unique amino acid sequence and, until now, has remained one of the few polypeptide hormones never described in higher vertebrates. Human STC (hSTC) was found to be 247 amino acids long and to share 73% amino acid sequence similarity with fish STC. Polyclonal antibodies to recombinant hSTC localized to a distinct cell type in the nephron tubule, suggesting kidney as a possible site of synthesis. Recombinant hSTC inhibited the gill transport of calcium when administered to fish and stimulated renal phosphate reabsorption in the rat. The evidence suggests that mammalian STC, like its piscine counterpart, is a regulator of mineral homeostasis. Images Fig. 5 Fig. 6 PMID:8700837

  5. Ionized calcium in exchange transfusion with THAM-buffered ACD blood

    PubMed Central

    Friedman, Z.; Hanley, W. B.; Radde, I. C.

    1972-01-01

    In 20 exchange transfusions with THAM-buffered ACD blood 5 ml. of 2% calcium gluconate (8 mg. elemental calcium) was injected after each 100 ml. of blood exchanged. Plasma ionized calcium decreased significantly during the procedure, although after each injection of calcium gluconate, levels returned briefly to normal. Ten minutes after the end of exchange ionized calcium had returned to pre-exchange levels and remained there until at least 30 mins. postexchange. Total calcium also increased significantly. Short periods of extreme hypercalcemia (between 7 and 8 mEq./l.) were noted after each injection of calcium gluconate. The amount of calcium gluconate was insufficient to counteract the calcium-chelating effect of citrate. If no heparinized blood is available we suggest adding heparin and calcium chloride to THAM-buffered ACD blood to avoid the repeated sudden fluctuations between low and high calcium ion activity. PMID:4629427

  6. Meta-analysis: vitamin D compounds in chronic kidney disease.

    PubMed

    Palmer, Suetonia C; McGregor, David O; Macaskill, Petra; Craig, Jonathan C; Elder, Grahame J; Strippoli, Giovanni F M

    2007-12-18

    Vitamin D compounds are widely used to prevent and treat secondary hyperparathyroidism. To determine whether vitamin D therapy improves biochemical markers of mineral metabolism and cardiovascular and mortality outcomes in chronic kidney disease. MEDLINE (January 1966 to July 2007), EMBASE (January 1980 to July 2007), and Cochrane databases were searched without language restriction. Randomized, controlled trials of vitamin D compounds in chronic kidney disease were identified. Two authors independently extracted data. Seventy-six trials were identified for inclusion; 3667 participants were enrolled. Vitamin D compounds did not reduce the risk for death, bone pain, vascular calcification, or parathyroidectomy. Compared with placebo, established vitamin D sterols were associated with an increased risk for hypercalcemia (relative risk, 2.37 [95% CI, 1.16 to 4.85]) and hyperphosphatemia (relative risk, 1.77 [CI, 1.15 to 2.74]) but did not show a consistent reduction in parathyroid hormone (PTH) levels. Compared with placebo, more recently developed vitamin D analogues were associated with hypercalcemia (relative risk, 5.15 [CI, 1.06 to 24.97]) but not hyperphosphatemia, and levels of PTH were reduced (weighted mean difference, -10.77 pmol/L [CI, -20.51 to -1.03 pmol/L]). For suppression of PTH, intravenous administration was superior to oral vitamin D, but higher intravenous doses were used. Few studies reported patient-level outcomes, including mortality (8 of 76 trials), and only 5 trials directly compared the effects of treatment with newer vitamin D compounds versus established ones. Heterogeneity in some comparisons remained unexplained by metaregression analyses. Vitamin D compounds do not consistently reduce PTH levels, and beneficial effects on patient-level outcomes are unproven. The value of vitamin D treatment for people with chronic kidney disease remains uncertain.

  7. [Current therapy of endocrine organ tumors (adrenal and parathyroid glands)].

    PubMed

    Nakano, M; Tajima, A; Aso, Y

    1988-02-01

    Since the adrenal or parathyroid cancer is a clinically rare entity. We often have difficulty in its diagnosis and treatment. The adrenocortical cancer is usually classified into two categories--endocrinologically functioning or non-functioning. The incidence is not different between them. It is often found in an advanced stage as it does not show clinical manifestation before it has grown up to a large tumor. Only an effective agent for the adrenal cancer is op'-DDD so far. Recently, cisplatin, VP-16 (etoposide) and others are administered as trial use. Most of malignant pheochromocytomas are endocrinologically active and they often cause hypertension leading to death. Therefore it is important to control hypertension in malignant pheochromocytoma. Chemotherapy and irradiation are not effective for it. Recently, 131I-MIBG (metaiodobenzylguanidine) is found to be useful not only for diagnosis but also treatment of malignant pheochromocytoma. 131I-MIBG is accumulated specifically in the chromaffin cells and with helpful to find out metastatic foci. It is also used in a large amount as a specific irradiation therapy for this malignancy. Parathyroid cancer is found in approximately 3 percent of primary hyperparathyroidism. Clinically it usually reveal serum calcium level higher than 14 mg/dl, bone lesions and renal dysfunction in addition to palpable cervical tumors adhering with skin. Sometimes it is difficult to differentiate malignancy from adenoma in histology. Most cases develop local recurrences and distant metastases in due course and dies of hypercalcemia. It is very important to control hypercalcemia in inoperable cases. As both chemotherapy and radiation therapy render no effect on this malignancy. Surgery is a sole strategy for it.

  8. Calcitriol resistance in hemodialysis patients with secondary hyperparathyroidism.

    PubMed

    Negri, Armando L; Brandenburg, Vincent M; Brandemburg, Vincent M

    2014-06-01

    Nonselective vitamin D receptor activators (VDRA), such as calcitriol and alfacalcidol, have been successfully used in the treatment of secondary hyperparathyroidism (SHPT) in hemodialysis. Despite their beneficial effects on the control of serum PTH levels, their use has been limited by intolerance (development of hypercalcemia and hyperphosphatemia with consecutive cardiovascular toxicity). Apart from becoming intolerant, in 20-30 % of patients who use nonselective VDRA, serum PTH levels do not decrease appropriately despite increasing doses of these agents. These patients are considered calcitriol-resistant patients. Thus, calcitriol resistance and intolerance are two sides of the same coin: active vitamin D failure. Despite the clinical relevance of active vitamin D failure, definitions of resistance and intolerance are imprecise and have varied over time. More selective VDRA claim to produce less hypercalcemia and hyperphosphatemia and could help clinicians to overcome intolerance. Also, some studies have also shown that paricalcitol can be even useful in resistant patients. Significant limitations of iPTH as a reliable and useful clinical biomarker have been increasingly appreciated. There is evidence that intact PTH concentration must differ by 72 % between any two measurements before it can be considered a significant change. VDR polymorphisms could be involved in the development of SHPT in CKD patients. Interestingly, a higher incidence of the b allele of the VDR BsmI gene variant has been shown to be present in SHPT. The BsmI genotype can also affect the response of hemodialysis to IV calcitriol. A challenge for the future will be to establish biomarkers such as laboratory determinations or ultrasound findings that can help us to early identify those patients who will not respond appropriately to calcitriol or exhibit intolerable side effects .

  9. Daily nasal spray of hPTH(1-34) for 3 months increases bone mass in osteoporotic subjects: a pilot study.

    PubMed

    Matsumoto, T; Shiraki, M; Hagino, H; Iinuma, H; Nakamura, T

    2006-10-01

    Although intermittent parathyroid hormone (PTH) injection can lead to strong anabolic effects on bone, daily subcutaneous injection is a disadvantage for patient acceptance. We have developed a nasal spray formula of parathyroid peptide [hPTH(1-34)] with peak serum hPTH(1-34) concentrations by nasal spray of 1,000 microg similar to those by subcutaneous injections of 20 microg hPTH(1-34). To determine the clinical efficacy and safety of nasal hPTH(1-34) spray, a randomized, open-labeled clinical trial was conducted in subjects with osteoporosis. Ninety osteoporotic subjects age 52-84 years (mean 66.5 years) were randomly assigned to receive either 250 microg (PTH250, n=31), 500 microg (PTH500, n=30), or 1,000 microg (PTH1000, n=29) of daily nasal hPTH(1-34) spray for 3 months. All received daily supplements of 300 mg calcium and 200 IU vitamin D(3). Daily nasal hPTH(1-34) spray for 3 months increased lumbar bone mineral density (L-BMD) in a dose-dependent manner, and the PTH1000 group showed a 2.4% increase in L-BMD from baseline. Only the 1,000-microg dose produced consistent and statistically significant changes in markers of bone turnover; after 3 months, median serum type I procollagen N-propeptide (PINP) and osteocalcin increased 14.8% and 19.4% from baseline, while urinary type I collagen N-telopeptide (NTX) decreased 16.4%. Seven subjects developed transient hypercalcemia at 3 h after nasal hPTH(1-34) spray, but none of the subjects developed sustained hypercalcemia. These observations demonstrate that nasal hPTH(1-34) spray is safe and well tolerated and can rapidly increase L-BMD. The results warrant further studies to examine its long-term efficacy on bone mass and fractures.

  10. A phase 2, randomized, placebo-controlled, dose-ranging study of the calcium-sensing receptor antagonist MK-5442 in the treatment of postmenopausal women with osteoporosis.

    PubMed

    Halse, Johan; Greenspan, Susan; Cosman, Felicia; Ellis, Graham; Santora, Arthur; Leung, Albert; Heyden, Norman; Samanta, Suvajit; Doleckyj, Steven; Rosenberg, Elizabeth; Denker, Andrew E

    2014-11-01

    MK-5442 is an orally bioavailable calcium-sensing receptor antagonist that is hypothesized to stimulate bone formation by stimulating endogenous secretion of a pulse of PTH. Earlier clinical and preclinical studies demonstrated increased bone mineral density (BMD) after treatment. Our objective was to identify a dose of MK-5442 that produces osteoanabolic effects without excessive hypercalcemia. This was a randomized, double-blind, placebo-controlled, parallel-group trial of private or institutional practice. In total, 383 postmenopausal women with osteoporosis were administered daily oral MK-5442 (2.5, 5, 7.5, 10, or 15 mg) or placebo. Serum PTH and calcium, bone turnover markers, areal BMD, and safety were evaluated. A dose-dependent transient increase in PTH occurred after an MK-5442 dose and lasted more than 3.5 hours. Compared with placebo, significant increases in bone formation markers (serum procollagen 1 N-terminal peptide and bone-specific alkaline phosphatase) were observed by 6 months, whereas bone resorption markers (serum C-telopeptide of type 1 collagen, urine N-telopeptides of type 1 collagen) initially decreased but were also significantly increased by 6 months. Despite the biochemical marker changes suggestive of an anabolic response, there were no statistically significant differences between any dose of MK-5442 and placebo in percent change from baseline at month 6 in any of the BMD endpoints. The frequency of hypercalcemia (trough serum calcium ≥ 10.8 mg/dL) was greater with higher MK-5442 doses. In postmenopausal women with low bone mass, treatment with MK-5442 resulted in transient pulses of PTH. Bone formation markers increased quickly and bone resorption markers decreased temporarily, suggestive of an anabolic window. However, there were no increases in BMD versus placebo.

  11. A Phase 2, Randomized, Placebo-Controlled, Dose-Ranging Study of the Calcium-Sensing Receptor Antagonist MK-5442 in the Treatment of Postmenopausal Women With Osteoporosis

    PubMed Central

    Greenspan, Susan; Cosman, Felicia; Ellis, Graham; Santora, Arthur; Leung, Albert; Heyden, Norman; Samanta, Suvajit; Doleckyj, Steven; Rosenberg, Elizabeth; Denker, Andrew E.

    2014-01-01

    Context: MK-5442 is an orally bioavailable calcium-sensing receptor antagonist that is hypothesized to stimulate bone formation by stimulating endogenous secretion of a pulse of PTH. Earlier clinical and preclinical studies demonstrated increased bone mineral density (BMD) after treatment. Objective: Our objective was to identify a dose of MK-5442 that produces osteoanabolic effects without excessive hypercalcemia. Design and Setting: This was a randomized, double-blind, placebo-controlled, parallel-group trial of private or institutional practice. Participants and Intervention: In total, 383 postmenopausal women with osteoporosis were administered daily oral MK-5442 (2.5, 5, 7.5, 10, or 15 mg) or placebo. Main Outcome Measures: Serum PTH and calcium, bone turnover markers, areal BMD, and safety were evaluated. Results: A dose-dependent transient increase in PTH occurred after an MK-5442 dose and lasted more than 3.5 hours. Compared with placebo, significant increases in bone formation markers (serum procollagen 1 N-terminal peptide and bone-specific alkaline phosphatase) were observed by 6 months, whereas bone resorption markers (serum C-telopeptide of type 1 collagen, urine N-telopeptides of type 1 collagen) initially decreased but were also significantly increased by 6 months. Despite the biochemical marker changes suggestive of an anabolic response, there were no statistically significant differences between any dose of MK-5442 and placebo in percent change from baseline at month 6 in any of the BMD endpoints. The frequency of hypercalcemia (trough serum calcium ≥10.8 mg/dL) was greater with higher MK-5442 doses. Conclusion: In postmenopausal women with low bone mass, treatment with MK-5442 resulted in transient pulses of PTH. Bone formation markers increased quickly and bone resorption markers decreased temporarily, suggestive of an anabolic window. However, there were no increases in BMD versus placebo. PMID:25166719

  12. Multiple myeloma: diagnosis and treatment.

    PubMed

    Nau, Konrad C; Lewis, William D

    2008-10-01

    Multiple myeloma, the most common bone malignancy, is occurring with increasing frequency in older persons. Typical symptoms are bone pain, malaise, anemia, renal insufficiency, and hypercalcemia. Incidental discovery on comprehensive laboratory panels is common. The disease is diagnosed with serum or urine protein electrophoresis or immunofixation and bone marrow aspirate analysis. Skeletal radiographs are important in staging multiple myeloma and revealing lytic lesions, vertebral compression fractures, and osteoporosis. Magnetic resonance imaging and positron emission tomography or computed tomography are emerging as useful tools in the evaluation of patients with myeloma; magnetic resonance imaging is preferred for evaluating acute spinal compression. Nuclear bone scans and dual energy x-ray absorptiometry have no role in the diagnosis and staging of myeloma. The differential diagnosis of monoclonal gammopathies includes monoclonal gammopathy of uncertain significance, smoldering (asymptomatic) and symptomatic multiple myeloma, amyloidosis, B-cell non-Hodgkin lymphoma, Waldenström macroglobulinemia, and rare plasma cell leukemia and heavy chain diseases. Patients with monoclonal gammopathy of uncertain significance or smoldering multiple myeloma should be followed closely, but not treated. Symptomatic multiple myeloma is treated with chemotherapy followed by autologous stem cell transplantation, if possible. Melphalan, prednisolone, dexamethasone, vincristine, doxorubicin, bortezomib, and thalidomide and its analogue lenalidomide have been used successfully. It is important that family physicians recognize and appropriately treat multiple myeloma complications. Bone pain is treated with opiates, bisphosphonates, radiotherapy, vertebroplasty, or kyphoplasty; nephrotoxic nonsteroidal anti-inflammatory drugs should be avoided. Hypercalcemia is treated with isotonic saline infusions, steroids, furosemide, or bisphosphonates. Because of susceptibility to infections

  13. Primary hyperparathyroidism masquerading as rickets: diagnostic challenge and treatment outcomes.

    PubMed

    Dutta, Deep; Kumar, Manoj; Das, Ram Narayan; Datta, Saumik; Biswas, Dibakar; Ghosh, Sujoy; Mukhopadhyay, Satinath; Chowdhury, Subhankar

    2013-01-01

    Primary hyperparathyroidism (PHPT) is extremely uncommon among children and is more likely to be associated with genetic syndromes, multiglandular involvement, and more severe symptoms. Rickets can very rarely be the presenting feature of PHPT in children. Rickets was diagnosed in a 12-year-old girl presenting with short stature, genu valgum, eversion deformity at the ankle joints, and flat feet. Radiograms showed generalized osteopenia, widening of the distal ends of the long bones along with splaying, cupping and fraying. Biochemical evaluation revealed low serum calcium (7.8 mg/dL), low phosphorus (1.4 mg/dL), vitamin-D deficiency [25-hydroxy-vitamin-D (25(OH)D): 8.7 ng/mL], and elevated intact parathyroid hormone (PTH, 811 pg/mL). Re-evaluation due to lack of clinical improvement following vitamin-D and calcium supplementation revealed hypercalcemia 11.9 mg/dL, normal 25(OH)D 41 ng/mL, persistence of elevated PTH 632 pg/mL. A 99mTc-sestamibi scan showed increased uptake at the lower pole of the right lobe of the thyroid. A right inferior parathyroidectomy was performed. Histopathology revealed chief cell type parathyroid adenoma. Last evaluated 4 months after surgery, the bone pains and proximal weakness had resolved, with significant improvement in the patient's quality of life. Rickets in the setting of PHPT often masks the classical phenotype of PHPT. In a child with rickets, lack of improvement following vitamin-D supplementation, hypercalcemia at presentation or following vitamin-D supplementation are warning signs which necessitate further evaluation to rule out PHPT.

  14. High-dose vitamin d intervention in infants--effects on vitamin d status, calcium homeostasis, and bone strength.

    PubMed

    Holmlund-Suila, Elisa; Viljakainen, Heli; Hytinantti, Timo; Lamberg-Allardt, Christel; Andersson, Sture; Mäkitie, Outi

    2012-11-01

    Guidelines in Finland recommend 10 μg of vitamin D3 daily for all infants. Recent observations suggest that this may be insufficient to maintain optimal serum 25-hydroxyvitamin D (S-25-OHD). The aim of the study was to evaluate effects of various vitamin D doses and determine a dose ensuring S-25-OHD of at least 80 nmol/liter in infants without signs of vitamin D excess. We conducted a randomized double-blind intervention study. Cord blood was obtained at birth for S-25-OHD; 113 infants were randomized to receive vitamin D3 10, 30, or 40 μg/d from age 2 wk to 3 months. An investigator-initiated study was performed in a single maternity hospital in Helsinki, Finland. S-25-OHD, calcium homeostasis, and skeletal characteristics were evaluated with peripheral quantitative computed tomography at age 3 months. Baseline S-25-OHD was similar in all three groups (median, 53 nmol/liter). At 3 months, the mean S-25-OHD values were 88, 124, and 153 nmol/liter, and the minimum values were 46, 57, and 86 nmol/liter in the groups receiving 10, 30, and 40 μg (ANOVA; P < 0.001). No hypercalcemia occurred; plasma calcium, serum PTH, and urine calcium excretion was similar between the groups. Peripheral quantitative computed tomography showed a trend toward larger tibial total bone and cortical bone area with higher vitamin D doses. Vitamin D3 supplementation with up to 40 μg/d from age 2 wk to 3 months was safe and caused no hypercalcemia or hypercalciuria. The 40-μg dose maintained S-25-OHD above 80 nmol/liter in all infants. More extensive and longer intervention studies are necessary to assess long-term effects.

  15. Hepatocellular carcinoma cells express 25(OH)D-1α-hydroxylase and are able to convert 25(OH)D to 1α,25(OH)₂D, leading to the 25(OH)D-induced growth inhibition.

    PubMed

    Chiang, Kun-Chun; Yen, Cho-Li; Yeh, Chun-Nan; Hsu, Jun-Te; Chen, Li-Wei; Kuo, Sheng-Fong; Wang, Shang-Yu; Sun, Chi-Chin; Kittaka, Atsushi; Chen, Tai C; Yeh, Ta-Sen; Hsu, Shu-Yuan; Juang, Horng-Heng

    2015-11-01

    Hepatocellular carcinoma (HCC) is the most diagnosed liver cancer without effective treatments available for advanced HCC. Vitamin D is getting popular due to its anti-cancer characteristics. However, the clinical application of 1α,25(OH)2D, the active form of vitamin, is hampered by its hypercalcemia side effect. 1α,25(OH)2D is converted from 25(OH)D, the index of serum vitamin D status, by CYP27B1, which is originally found in kidneys but recently detected in non-renal tissues. 25(OH)D has been shown to repress some cancers expressing CYP27B1 due to the local conversion of 25(OH)D to 1α,25(OH)2D, which works in a intra-, auto-, or paracrine manner and thus minimizes the risk of hypercalcemia. In this study, we found CYP27B1 expression in human hepatocyte, HCC, and HepG2 cells. As we treated HepG2 cells with 25(OH)D, the 1α,25(OH)2D target gene CYP24A1 expression was increased and was further upregulated as CYP27B1 transfection or downregulated as CYP27B1 knockdown. Other 1α,25(OH)2D target genes in HepG2 cells, p21 and p27 were also stimulated by 25(OH)D after CYP27B1 transfection. Further, 25(OH)D could inhibit HepG2 cells growth, which was potentiated by CYP27B1 transfection. Collectively, we showed for the first time that HCC expressed CYP27B1 and was able to covert 25(OH)D to 1α,25(OH)2D in vitro, thus responsive to 25(OH)D treatment. Our data justifies the application of 25(OH)D and CYP27B1 gene transfection therapy in further HCC treatment studies.

  16. Clodronate news of efficacy in osteoporosis

    PubMed Central

    Nardi, Alfredo; Ventura, Lorenzo; Cozzi, Luisella; Tonini, Greta

    2016-01-01

    Summary Clodronate belongs to Bisphosphonates family and it has been studied especially for osteoporosis treatment, Paget’s disease, osteolytic metastases, hypercalcemia malignancy and some childhood skeletal diseases. Besides the osteoporosis treatment, it has been successfully used for treating tumoral osteolysis and for bone localization of multiple myeloma, hypercalcemia malignancy, primary hyperparathyroidism, Paget’s disease and algodystrophy. Filipponi study showed a statistically significant reduction of the incidence of vertebral fractures after 4 years of treatment with clodronate, intravenously administered at a dose of 200 mg every three weeks. Frediani study, published in 2003 on BONE, proved the clodronate efficacy in the prevention of fractures caused by glucocorticoid-induced osteoporosis (GIO). Clodronate doses of 800 mg/day per os and 100 mg i.m./week are substantially equivalent, because the oral absorption is about 1,9%. A higher efficacy on BMD was documented in various works, especially in cohorts of patients with a greater fracture risk, using higher doses (1600 mg per os). This has led to the hypothesis of using clodronate 200 mg i.m. formulation. Clodronate is an osteoporosis drug that can be assumed in different doses (100 mg i.m./week, clodronate 200 mg i.m. every 2 weeks) considering the risk band, identified by algorithms (FRAX o DeFRA), by BMD and by the presence of at least one risk factor. That means that it is possible to envisage a differentiated use of clodronate adapting the doses to the fracture risk and to the severity of pain symptoms, thus promoting a greater adherence to the therapy. To conclude clodronate is helpful in reducing fracture risk, is safe, well tolerated, and has a good rate cost/effectiveness in patients with fracture risk over 7% established with FRAX. PMID:27252741

  17. Initial amino acid intake influences phosphorus and calcium homeostasis in preterm infants--it is time to change the composition of the early parenteral nutrition.

    PubMed

    Bonsante, Francesco; Iacobelli, Silvia; Latorre, Giuseppe; Rigo, Jacques; De Felice, Claudio; Robillard, Pierre Yves; Gouyon, Jean Bernard

    2013-01-01

    Early aggressive parenteral nutrition (PN), consisting of caloric and nitrogen intake soon after birth, is currently proposed for the premature baby. Some electrolyte disturbances, such as hypophosphatemia and hypercalcemia, considered unusual in early life, were recently described while using this PN approach. We hypothesize that, due to its impact on cell metabolism, the initial amino acid (AA) amount may specifically influence the metabolism of phosphorus, and consequently of calcium. We aim to evaluate the influence of AA intake on calcium-phosphorus metabolism, and to create a calculation tool to estimate phosphorus needs. Prospective observational study. Phosphate and calcium plasma concentrations and calcium balance were evaluated daily during the first week of life in very preterm infants, and their relationship with nutrition was studied. For this purpose, infants were divided into three groups: high, medium and low AA intake (HAA, MAA, LAA). A calculation formula to assess phosphorus needs was elaborated, with a theoretical model based on AA and calcium intake, and the cumulative deficit of phosphate intake was estimated. 154 infants were included. Hypophosphatemia (12.5%) and hypercalcemia (9.8%) were more frequent in the HAA than in the MAA (4.6% and 4.8%) and in the LAA group (0% and 1.9%); both p<0.001. Calcium-phosphorus homeostasis was influenced by the early AA intake. We propose to consider phosphorus and calcium imbalances as being part of a syndrome, related to incomplete provision of nutrients after the abrupt discontinuation of the placental nutrition at birth (PI-ReFeeding syndrome). We provide a simple tool to calculate the optimal phosphate intake. The early introduction of AA in the PN soon after birth might be completed by an early intake of phosphorus, since AA and phosphorus are (along with potassium) the main determinants of cellular growth.

  18. Initial Amino Acid Intake Influences Phosphorus and Calcium Homeostasis in Preterm Infants – It Is Time to Change the Composition of the Early Parenteral Nutrition

    PubMed Central

    Bonsante, Francesco; Iacobelli, Silvia; Latorre, Giuseppe; Rigo, Jacques; De Felice, Claudio; Robillard, Pierre Yves; Gouyon, Jean Bernard

    2013-01-01

    Background Early aggressive parenteral nutrition (PN), consisting of caloric and nitrogen intake soon after birth, is currently proposed for the premature baby. Some electrolyte disturbances, such as hypophosphatemia and hypercalcemia, considered unusual in early life, were recently described while using this PN approach. We hypothesize that, due to its impact on cell metabolism, the initial amino acid (AA) amount may specifically influence the metabolism of phosphorus, and consequently of calcium. We aim to evaluate the influence of AA intake on calcium-phosphorus metabolism, and to create a calculation tool to estimate phosphorus needs. Methods Prospective observational study. Phosphate and calcium plasma concentrations and calcium balance were evaluated daily during the first week of life in very preterm infants, and their relationship with nutrition was studied. For this purpose, infants were divided into three groups: high, medium and low AA intake (HAA, MAA, LAA). A calculation formula to assess phosphorus needs was elaborated, with a theoretical model based on AA and calcium intake, and the cumulative deficit of phosphate intake was estimated. Results 154 infants were included. Hypophosphatemia (12.5%) and hypercalcemia (9.8%) were more frequent in the HAA than in the MAA (4.6% and 4.8%) and in the LAA group (0% and 1.9%); both p<0.001. Discussion Calcium-phosphorus homeostasis was influenced by the early AA intake. We propose to consider phosphorus and calcium imbalances as being part of a syndrome, related to incomplete provision of nutrients after the abrupt discontinuation of the placental nutrition at birth (PI-ReFeeding syndrome). We provide a simple tool to calculate the optimal phosphate intake. The early introduction of AA in the PN soon after birth might be completed by an early intake of phosphorus, since AA and phosphorus are (along with potassium) the main determinants of cellular growth. PMID:23977367

  19. Efficacy and safety of calcium acetate-magnesium carbonate in the treatment of hyperphosphatemia in dialysis patients.

    PubMed

    Helal, Imed; Elkateb, Hanene; Hedri, Hafedh; Hajri, Malika; Hamida, Fethi Ben

    2016-01-01

    A phosphate binder combining calcium and magnesium offers an interesting therapeutic option to control hyperphosphatemia in dialysis patients. We investigated the effectiveness and tolerance of calcium acetate-magnesium carbonate (Ca-Mg). This is a 16-week prospective study including 16 dialysis patients. After an initial two-week washout period, serum phosphorus (sPho) ≥1.8 mmol/L, serum calcium (sCa) ≤2.6 mmol/L, and serum magnesium ≤1.5 mmol/L were the main inclusion criteria. The initial dose of Ca-Mg depended on sPho level and was titrated for every two weeks to have a sPho ≤ 1.8 mmol/L. A second two-week washout period followed the 12 weeks of treatment. Ca-Mg significantly reduced the mean sPho levels from 2.14 to 1.75 mmol/L by the end of the 12-week treatment period (P <0.006). Two weeks after the completion of the Ca-Mg study, the mean sPho levels increased to 2.2 mmol/L. The mean sCa levels did not significantly change during the Ca-Mg trial. The mean serum intact parathyroid hormone declined significantly from 446 pg/mL at the beginning of the study to 367 pg/mL at the end of the 12-week treatment period (P = 0.0002). Digestive tolerance was good in all patients which allowed good compliance. There were no episodes of hypercalcemia. However, six patients had a moderate hypermagnesemia (21 episodes) requiring adjustment of treatment dose. The Ca-Mg proved to be effective in the control of hyperphosphatemia in dialysis patients with good clinical and biological tolerance. Thus, in patients with hypercalcemia or poor tolerance to calcium carbonate, Ca-Mg might be a good alternative.

  20. Beneficial effects of better control of secondary hyperparathyroidism with paricalcitol in chronic dialysis patients.

    PubMed

    Capuano, Alfredo; Serio, Vittorio; Pota, Andrea; Memoli, Bruno; Andreucci, Vittorio E

    2009-01-01

    Treatment of secondary hyperparathyroidism (SHPT) with calcitriol is often limited by the occurrence of hypercalcemia, hyperphosphatemia and risk of vascular calcifications. Paricalcitol, a vitamin D analogue with lower calcemic and phosphatemic effects, is successfully utilized in dialysis patients, although some uncertainty remains about the optimal dosage. Amelioration of survival in hemodialysis patients has been correlated to the use of calcitriol and, even better, paricalcitol. We evaluated 1-year treatment with paricalcitol in 12 chronic hemodialysis patients with moderate-severe SHPT previously treated with intravenous calcitriol. Starting dose of paricalcitol was calculated according to the severity of the disease by the formula: intact parathyroid hormone (iPTH)/80, and successive titration performed according to the NKF-DOQI guidelines. Paricalcitol caused a rapid decrease in serum levels of iPTH with a consistent percentage of values falling below 150 pg/mL in the first months of treatment. Although the occurrence of hypercalcemia was not significantly different between treatment with calcitriol and paricalcitol, a slight but significant increase in mean calcium levels was observed during paricalcitol treatment. A significant amelioration of erythropoiesis and acid-base balance was observed during paricalcitol treatment. Paricalcitol efficiently suppresses PTH secretion in dialysis patients with SHPT, with a moderate calcemic, but not a phosphatemic, effect. The dose of paricalcitol calculated as iPTH/80 may cause acute lowering of bone turnover. The improvement of anemia control and the amelioration of acid-base balance are 2 important additive effects of the better control of SHPT that may improve survival of hemodialysis patients.

  1. Deletions of the elastin gene in Williams Syndrome

    SciTech Connect

    Greenberg, F.; Nickerson, E.; McCaskill, C.

    1994-09-01

    To investigate deletions in the elastin gene in patients with Williams Syndrome (WS), we screened 37 patients and their parents for deletions in the elastin gene by both fluorescence in situ hybridization (FISH) using cosmid cELN272 containing the 5{prime} end of the elastin gene and by polymerase chain reaction (PCR) using a primer pair which amplifies intron 17 in the elastin gene, producing a polymorphic amplification product. Thirty-two patients have been investigated by both the FISH and PCR techniques, one patient was studied only by PCR, and 4 patients were studied only by FISH. Overall, 34 of 37 patients (92%) were deleted for the elastin gene. Using the PCR marker, 14 patients were informative and 12 were shown to be deleted [maternal (n=5) and paternal (n=7)]. Using cosmid cELN272, 33 of 36 patients demonstrated a deletion of chromosome 7q11.23. In one family, both the mother and daughter were deleted due to an apparently de novo deletion arising in the mother. Three patients were not deleted using the elastin cosmid; 2 of these patients have classic WS. Another non-deleted patient has the typical facial features and hypercalcemia but normal intelligence. These three patients will be important in delineating the critical region(s) responsible for the facial features, hypercalcemia, mental retardation and supravalvular aortic stenosis (SVAS). There was not an absolute correlation between deletions in elastin and SVAS, although these individuals may be at risk for other cardiovascular complications such as hypertention. Since the majority of WS patients are deleted for a portion of the elastin gene, most likely this marker will be an important diagnostic tool, although more patients will need to be studied. Those patients who are not deleted but clinically have WS will be missed using only this one marker. Expansion of the critical region to other loci and identification of additional markers will be essential for identifying all patients with WS.

  2. Calcitonin, the forgotten hormone: does it deserve to be forgotten?

    PubMed Central

    Felsenfeld, Arnold J.; Levine, Barton S.

    2015-01-01

    Calcitonin is a 32 amino acid hormone secreted by the C-cells of the thyroid gland. Calcitonin has been preserved during the transition from ocean-based life to land dwellers and is phylogenetically older than parathyroid hormone. Calcitonin secretion is stimulated by increases in the serum calcium concentration and calcitonin protects against the development of hypercalcemia. Calcitonin is also stimulated by gastrointestinal hormones such as gastrin. This has led to the unproven hypothesis that postprandial calcitonin stimulation could play a role in the deposition of calcium and phosphate in bone after feeding. However, no bone or other abnormalities have been described in states of calcitonin deficiency or excess except for diarrhea in a few patients with medullary thyroid carcinoma. Calcitonin is known to stimulate renal 1,25 (OH)2 vitamin D (1,25D) production at a site in the proximal tubule different from parathyroid hormone and hypophosphatemia. During pregnancy and lactation, both calcitonin and 1,25D are increased. The increases in calcitonin and 1,25D may be important in the transfer of maternal calcium to the fetus/infant and in the prevention and recovery of maternal bone loss. Calcitonin has an immediate effect on decreasing osteoclast activity and has been used for treatment of hypercalcemia. Recent studies in the calcitonin gene knockout mouse have shown increases in bone mass and bone formation. This last result together with the presence of calcitonin receptors on the osteocyte suggests that calcitonin could possibly affect osteocyte products which affect bone formation. In summary, a precise role for calcitonin remains elusive more than 50 years after its discovery. PMID:25815174

  3. Parathyroid scintigraphy, histopathology correlation in patients with tropical pancreatitis and coexisting primary hyperparathyroidism

    PubMed Central

    Padma, Subramanyam; Sundaram, Palaniswamy Shanmuga

    2013-01-01

    Purpose: Tropical pancreatitis (TP) is a juvenile, non-alcoholic type of chronic pancreatitis and is highly prevalent in Kerala, India. Increasing prevalence of TP and its varied manifestations prompted us to undertake this retrospective analysis. We attempted to study the incidence of TP in patients with primary hyperparathyroidism (PHPT) and correlate with calcium levels, scintigraphy and histopathology findings. Materials and Methods: Records of 44 hypercalcemic patients with raised parathormone (PTH) were analyzed. Clinical, biochemical and imaging findings were noted to look for diabetes mellitus and pancreatitis. All patients underwent dual phase 99m Technetium methoxy isobutyl isonitrile parathyroid scintigraphy in our department between January 2007 and 2010. Gamma probe assisted minimally invasive parathyroidectomy was performed. Histopathological correlation was obtained in all patients. Results: Our study shows 18% (8/44 patients) incidence of TP in patients with PHPT (compared to 7% reported in 1970's) in Kerala. Results show involvement of middle aged, non-alcoholic males. No direct association between severity of diabetes, pancreatitis and PHPT was noted in our series. Parathyroid adenoma was the most common underlying pathology. All TP patients’ clinical outcome improved post parathyroidectomy. TP patients with PHPT demonstrated adenomas, mainly composed of oxyphilic cells. Non pancreatitis group interestingly showed a varied picture of adenoma, hyperplasia with predominance of chief cells histologically. Conclusion: There is a 2.6 fold increase in the incidence of TP (18%) in patients with PHPT. Hypercalcemia may be the causative factor leading to TP in PHPT patients in our limited series. The data suggests a causal association between pancreatitis and PHPT. Patients presenting with either one or a combination of hypercalcemia, pancreatic dysfunction or raised PTH need to be thoroughly evaluated as their management is interlinked. PMID:24019667

  4. Selective Calcium-Dependent Inhibition of ATP-gated P2X3 Receptors by Bisphosphonates-induced Endogenous ATP analogue ApppI.

    PubMed

    Ishchenko, Yevheniia; Shakirzyanova, Anastasia; Giniatullina, Raisa; Skorinkin, Andrei; Bart, Geneviev; Turhanen, Petri; Maatta, Jorma; Monkkonen, Jukka; Giniatullin, Rashid

    2017-04-12

    Pain is the most unbearable symptom accompanying primary bone cancers and bone metastases. Bone resorptive disorders are often associated with hypercalcemia contributing to the pathological process. Nitrogen-containing bisphosphonates (NBP) are efficiently used to treat bone-cancers and metastases. NBP, apart from their toxic effect on cancer cells, also provide analgesia via poorly understood mechanisms. We have previously shown, that NBP, by inhibiting the mevalonate pathway, induced the formation of the novel ATP-analogues such as ApppI which can potentially be involved in NBP analgesia. In this study, we used patch-clamp technique to explore the action of ApppI on native ATP-gated P2X receptors in rat sensory neurons and rat and human P2X3, P2X2 and P2X7 receptors expressed in HEK cells. We found, that while ApppI has weak agonist activity, it is a potent inhibitor of P2X3 receptors operating in the nanomolar range. The inhibitory action of ApppI was completely blocked in hypercalcemia-like conditions and was stronger on human than on rat P2X3 receptors. In contrast, P2X2 and P2X7 receptors were insensitive to ApppI, suggesting a high selectivity of ApppI for the P2X3 receptor subtype. NBP, metabolite IPP and endogenous AMP, did not exert any inhibitory action indicating that only intact ApppI has inhibitory activity. The Ca(2+)-dependent inhibition was stronger in trigeminal neurons preferentially expressing desensitizing P2X3 subunits than in nodose ganglia neurons, which also express non-desensitizing P2X2 subunits. Altogether, we characterized previously unknown purinergic mechanisms of NBP-induced metabolites and suggest ApppI as the endogenous pain inhibitor contributing to the cancer treatment with NBP.

  5. Evaluation of the potential therapeutic role of a new generation of vitamin D analog, MART-10, in human pancreatic cancer cells in vitro and in vivo.

    PubMed

    Chiang, Kun-Chun; Yeh, Chun-Nan; Hsu, Jun-Te; Yeh, Ta-sen; Jan, Yi-yin; Wu, Chun-Te; Chen, Huang-Yang; Jwo, Shyh-Chuan; Takano, Masashi; Kittaka, Atsushi; Juang, Horng-Heng; Chen, Tai C

    2013-04-15

    Pancreatic cancer is a lethal disease with no known effective chemotherapy and radiotherapy, and most patients are diagnosed in the late stage, making them unsuitable for surgery. Therefore, new therapeutic strategies are urgently needed. 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] is known to possess antitumor actions in many cancer cells in vitro and in vivo models. However, its clinical use is hampered by hypercalcemia. In this study, we investigated the effectiveness and safety of a new generation, less calcemic analog of 1α,25(OH)2D3, 19-nor-2α-(3-hydroxypropyl)-1α,25-dihydroxyvitamin D3 (MART-10), in BxPC-3 human pancreatic carcinoma cells in vitro and in vivo. We demonstrate that MART-10 is at least 100-fold more potent than 1α,25(OH)2D3 in inhibiting BxPC-3 cell proliferation in a time- and dose-dependent manner, accompanied by a greater upregulation of cyclin-dependent kinase inhibitors p21 and p27 and a greater downregulation of cyclin D3 and cyclin-dependent kinases 4 and 5, leading to a greater increase in the fraction of cells in G0/G1 phase. No induction of apoptosis and no effect on Cdc25 phosphatases A and C were observed in the presence of either MART-10 or 1α,25(OH)2D3. In a xenograft mouse model, treatment with 0.3 µg/kg body weight of MART-10 twice/week for 3 weeks caused a greater suppression of BxPC-3 tumor growth than the same dose of 1α,25(OH)2D3 without inducing hypercalcemia and weight loss. In conclusion, MART-10 is a promising agent against pancreatic cancer growth. Further clinical trial is warranted.

  6. Vitamin D Signaling Modulators in Cancer Therapy.

    PubMed

    Luo, Wei; Johnson, Candace S; Trump, Donald L

    2016-01-01

    The antiproliferative and pro-apoptotic effects of 1α,25-dihydroxycholecalciferol (1,25(OH)2D3, 1,25D3, calcitriol) have been demonstrated in various tumor model systems in vitro and in vivo. However, limited antitumor effects of 1,25D3 have been observed in clinical trials. This may be attributed to a variety of factors including overexpression of the primary 1,25D3 degrading enzyme, CYP24A1, in tumors, which would lead to rapid local inactivation of 1,25D3. An alternative strategy for improving the antitumor activity of 1,25D3 involves the combination with a selective CYP24A1 inhibitor. The validity of this approach is supported by numerous preclinical investigations, which demonstrate that CYP24A1 inhibitors suppress 1,25D3 catabolism in tumor cells and increase the effects of 1,25D3 on gene expression and cell growth. Studies are now required to determine whether selective CYP24A1 inhibitors+1,25D3 can be used safely and effectively in patients. CYP24A1 inhibitors plus 1,25D3 can cause dose-limiting toxicity of vitamin D (hypercalcemia) in some patients. Dexamethasone significantly reduces 1,25D3-mediated hypercalcemia and enhances the antitumor activity of 1,25D3, increases VDR-ligand binding, and increases VDR protein expression. Efforts to dissect the mechanisms responsible for CYP24A1 overexpression and combinational effect of 1,25D3/dexamethasone in tumors are underway. Understanding the cross talk between vitamin D receptor (VDR) and glucocorticoid receptor (GR) signaling axes is of crucial importance to the design of new therapies that include 1,25D3 and dexamethasone. Insights gained from these studies are expected to yield novel strategies to improve the efficacy of 1,25D3 treatment. © 2016 Elsevier Inc. All rights reserved.

  7. Primary hyperparathyroidism in pediatric patients.

    PubMed

    Kollars, Josh; Zarroug, Abdalla E; van Heerden, Jon; Lteif, Aida; Stavlo, Penny; Suarez, Luis; Moir, Christopher; Ishitani, Michael; Rodeberg, David

    2005-04-01

    Primary hyperparathyroidism (HPT) is unusual in children. We reviewed our experience with HPT to better characterize these children. The retrospective review of patients <19 years old who underwent parathyroid resection for primary HPT from 1970 to 2000 was performed at a single institution.. Fifty-two patients were identified. Median age was 16.8 years (range: 4-18.9) with a female-to-male ratio of 3:2. Eighty-five percent had an elevated parathyroid hormone (PTH) level, and 15% had an inappropriately normal PTH level during hypercalcemia. Serum calcium was elevated in all patients except for 2 with multiple endocrine neoplasma (MEN)-IIA and 1 with familial non-MEN HPT, but both had elevated PTH levels. Alkaline phosphatase levels were significantly higher in children with documented bone involvement. At presentation 41 patients (79%) were symptomatic and end-organ damage (nephrocalcinosis, nephrolithiasis, acute pancreatitis, or bone involvement) occurred in 23 patients (44%). Thirty-four patients (65%) had a single adenoma; hyperplasia was identified in 16 patients (27%), and of these cases, 57% occurred in patients diagnosed with MEN-I. Short-term complications included transient hypocalcemia in 29 patients (56%) and transient vocal cord paralysis in 2 patients (4%). Long-term complications were significant for permanent hypocalcemia in 2 patients (4%) and no recurrent laryngeal nerve injuries. No parathyroid abnormalities were identified during exploration in 4 (8%) children. Long-term follow-up was achieved in 98% of patients for a mean and median of 13 years. Resolution of hypercalcemia was achieved in 94% of cases. The diagnosis of primary HPT in pediatric patients is frequently delayed, is commonly symptomatic, and has significant morbidity. For children in whom HPT is suspected, evaluation of serum calcium and PTH levels is diagnostic in 100% of children. Parathyroid resection is effective at restoring normal serum calcium, has few complications, and is

  8. Neuroendocrine thymic carcinoma metastatic to the parathyroid gland that was reimplanted into the forearm in patient with multiple endocrine neoplasia type 1 syndrome: a challenging management dilemma.

    PubMed

    Shifrin, Alexander L; LiVolsi, Virginia A; Zheng, Min; Lann, Danielle E; Fomin, Svetlana; Naylor, Evan C; Mencel, Peter J; Fay, Angela M; Erler, Brian S; Matulewicz, Theodore J

    2013-01-01

    To describe a unique case of a metastatic thymic carcinoma to the hyperplastic parathyroid gland and to present a challenging management dilemma. Our patient is 60-year-old, intellectually disabled man with history of the multiple endocrine neoplasia type 1 (MEN1) syndrome, a surgery in 1985 for hypercalcemia with removal of one parathyroid gland, surgery in 2007 with findings of extensively necrotic well differentiated neuroendocrine carcinoma (carcinoid tumor) of the thymus. In 2012, he presented with persistent hypercalcemia (calcium level 11.7 mg/dL [range, 8.6-10.2]), and a parathyroid hormone (PTH) level of 225 pg/mL (range, 15-65 pg/mL). He underwent a repeat neck exploration with removal of 2 small inferior and a large left superior 4.5 × 2.5 × 1.5 cm parathyroid glands, all of which showed hyperplasia on intraoperative frozen section. A small portion of the superior gland was reimplanted into the patient's forearm. Final pathology showed the presence of a focus of neuroendocrine tumor within the left superior parathyroid gland with immunostain identical to the thymic carcinoma. His postoperative PTH level was 14 pg/mL and calcium 8.5 mg/dL. A positron emission tomography-computed tomography (PET-CT) and octreotide scans revealed an extensive metastatic disease within the lung, mediastinum, and bones. We decided to leave a portion of the reimplanted parathyroid gland with possible metastatic thymic carcinoid in his forearm because of the presence a widespread metastatic disease and his intellectual disability that would result in noncompliance with calcium replacement in case of permanent hypocalcemia. Metastatic thymic carcinoma to the parathyroid gland has never been reported in the literature. We have described the first case and presented a challenging management dilemma.

  9. Evaluation of parathyroid autograft growth and function in hemodialysis patients

    SciTech Connect

    Karsenty, G.; Petraglia, A.; Bourdeau, A.; Gambini, D.J.; Moreau, J.F.; Lecharpentier, Y.; Zingraff, J.; Bournerias, F.; Buisson, C.; Dubost, C.

    1986-07-01

    The aim of our study was to evaluate the function and growth of parathyroid tissue autografted into the forearm of hemodialysis patients using several presently available methods. In a dynamic study, the secretory function of autografted tissue was evaluated in seven patients using either zero calcium dialysate or calcium infusion. In an additional prospective study, seven patients had repeated determinations of plasma immunoreactive parathyroid hormone (iPTH) concentration on samples from both forearms, a radionuclide evaluation of autograft function using thallium-201 chloride, and real time ultrasonography. Light microscopy analysis was performed in two patients. The dynamic study demonstrated that induction of hypocalcemia was followed by an increase, and induction of hypercalcemia by a decrease in circulating iPTH in both forearms using three different radioimmunoassays similar to what has been reported for normal parathyroid tissue. A significant gradient (ie, greater than 2.0) of plasma iPTH concentration in samples from both forearms was observed in only three out of the seven patients of the prospective study. Two of these patients disclosed an increased uptake of /sup 201/TI chloride at the site of autografted tissue and had an echographically detectable mass. In both, hyperplastic parathyroid tissue was removed. At present, the remaining third patient does not have other features of recurrent hyperparathyroidism. In conclusion, autotransplanted parathyroid tissue of hemodialysis patients shows an adequate response to physiologic stimuli such as hypo- and hypercalcemia. Dynamic tests, therefore, appear to be a useful tool in the assessment of its function. In addition, radionuclide and echographic studies may be reliable adjuncts in the detection of marked parathyroid autograft hyperplasia.

  10. New Conclusions Regarding Comparison of Sevelamer and Calcium-Based Phosphate Binders in Coronary-Artery Calcification for Dialysis Patients: A Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Li, Shaomin; Chen, Yanbing; Wang, Yanni; Lou, Tanqi

    2015-01-01

    Background Sevelamer hydrochloride is used widely, but its impact upon cardiovascular calcification, cardiovascular mortality, all-cause mortality and hospitalization is not known. Outcomes Primary outcome was cardiovascular calcification (coronary artery calcification scores (CACS) and aortic calcification scores (ACS)). Secondary outcomes were serum characteristics, hospitalization, cardiovascular mortality and all-cause mortality. Risk ratio (RR), mean differences and standard mean difference with 95% confidence intervals (CIs) were pooled using random- or fixed-effects models. Results We identified 31 studies (on 23 randomized controlled trials with 4395 participants). An analysis pooling showed a significant decrease in serum levels of phosphate with calcium-based phosphate binders (CBPBs) by 0.17 mg/dL [mean difference (MD), 95% CI, 0.03, 0.31] than sevelamer. A significant difference in the change of CACS by –102.66 [MD: 95% CI, –159.51, –45.80] and ACS by –1008.73 [MD, 95% CI, –1664.75, –352.72] between sevelamer and CBPBs was observed. Prevalence of hypercalcemia (serum levels of calcium >10.2–10.5 mg/dL and >11.0 mg/dL) was significantly smaller for sevelamer (RR = 0.44, 95% CI, 0.33, 0.58; RR = 0.24, 95% CI, 0.14, 0.40). No significant difference was found in hospitalization, all-cause mortality or cardiovascular mortality. Conclusions This meta-analysis suggests that sevelamer benefits dialysis patients in terms of CACS, ACS and hypercalcemia. PMID:26230677

  11. Calcium effects and systemic exposure of vitamin D3 analogues after topical treatment of active vitamin D3-containing ointments in rats.

    PubMed

    Hosomi, Atsushi; Hirabe, Maho; Tokuda, Takuya; Nakamura, Hiroaki; Amano, Toru; Okamoto, Tadao

    2016-10-05

    Topical agents containing vitamin D3 (VD3) analogues such as calcipotriol, maxacalcitol and tacalcitol and the combination of calcipotriol/betamethasone dipropionate (betamethasone) are prescribed for patients with psoriasis. However, they are known to occasionally cause hypercalcemia, and the frequency of hypercalcemia is suggested to vary according to the VD3 analogue used. In this study, to address the reason for these differences, the calcemic effects of maxacalcitol-, calcipotriol- and calcipotriol/betamethasone-containing ointments in rats were evaluated. The serum calcium levels in rats treated with ointments containing maxacalcitol, but not calcipotriol or calcipotriol/betamethasone, were significantly elevated, which is consistent with clinical observations. The serum concentration of VD3 analogue in rats treated with ointments containing calcipotriol and calcipotriol/betamethasone was lower than that in rats treated with maxacalcitol-containing ointment. Thus, the calcemic effects appear to be associated with the systemic exposure of VD3 analogues in rats. To understand the mechanism underlying the different systemic exposures of VD3 analogues, skin permeation and metabolic stability of VD3 analogues were evaluated. The cumulative amount of calcipotriol permeated through rat skin was significantly lower than that of maxacalcitol. On the other hand, the metabolic clearance of calcipotriol in rat hepatocytes was higher than that of maxacalcitol. Similar results were obtained using human skin and human hepatocytes. The current study demonstrates that the lower calcemic effects of calcipotriol- and calcipotriol/betamethasone-containing ointments are caused by the low systemic exposure of calcipotriol according to low skin permeability and rapid hepatic elimination after topical application. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  12. [Clinical and biological forms of secondary hyperparathyroidism in dialysis patients].

    PubMed

    Jean, Guillaume; Souberbielle, Jean-Claude; Lorriaux, Christie; Mayor, Brice; Hurot, Jean-Marc; Deleaval, Patrick; Chazot, Charles

    2012-02-01

    The diagnosis and treatment of hyperparathyroidism (HPT) are not yet well standardized in chronic renal failure patients. The aim of this study was to identify the main types of HPT on the basis of clinical and biological findings in a haemodialysis population. Between 2004 and 2010, all patients undergoing haemodialysis were observed and treated using the same strategy: conventional therapy with vitamin D supplements, phosphate binders, dialysate calcium adjusted to serum parathyroid hormone (PTH) level and calcitriol analogues (CA), along with regular bone marker analysis. Wherever required, cinacalcet (CC) was administered and parathyroidectomy (PTX) was performed. Of the 520 patients, 158 were classified as having HPT (30%) with a serum PTH level greater than 300 pg/mL. From this population, we identified five main types of HPT: (1) HPT with 'no bone impact' had normal or low bone marker levels (n=28, 17.7%); (2) 'secondary' HPT had elevated bone marker levels, but showed favorable response to CT (n=59, 37.7%); (3) 'tertiary' HPT was accompanied with hypercalcemia and required CC or PTX in case of CT failure (n=11, 6.9%); (4) 'mixed' HPT could not be completely treated with CT and required CC or PTX (n=57, 36%); (5) 'resistant' HPT did not show hypercalcemia, but required PTX after CT and CC failure (n=3, 1.8%). CC was prescribed in 51% cases, CA in 76%, and PTX in 7% of cases. We typified HPT on the basis of physiopathology and stages of HPT progression. Further studies on HPT that focus on bone marker levels are required to establish well-defined treatment strategies. In our study, HPT cases did not show uniform findings in Hémodialyse (HD) patients because of the variation in the stages of the disease at the time of diagnosis.

  13. 1-alpha-Hydroxyvitamin D3 derivatives in the treatment of renal bone diseases: justification and optimal modalities of administration.

    PubMed

    Fournier, A; Morinière, P H; Oprisiu, R; Yverneau-Hardy, P; Westeel, P F; Mazouz, H; el Esper, N; Ghazali, A; Boudailliez, B

    1995-01-01

    The use of 1 alpha-hydroxyvitamin D3 [1 alpha(OH)D3] derivatives in a uremic patient is justified only in the treatment of hyperparathyroidism (i.e. when plasma intact parathyroid hormone - PTH - levels are above five or three times the upper limit of normal according to whether the patient is on continuous ambulatory peritoneal dialysis or on hemodialysis and between 0.5-1.5, 1-2 and 2-3 times the upper limit of normal for a creatinine clearance of, respectively, 30, between 30 and 10, or below 10 ml/min/1.73 m2). The following prerequisites have however to be satisfied: (1) a good vitamin D3 repletion should be secured by plasma 25(OH(D) levels of 20-30 ng/ml (if necessary by administration of native vitamin D or 25(OH)D3), and (2) phosphate retention (which is aggravated by the increased phosphate intestinal absorption induced by the 1 alpha (OH)D derivatives) and the consequent possible hyperphosphatemia should be prevented or corrected by the oral administration of alkaline salts of calcium given before the meals as phosphate binders without inducing hypercalcemia. These prerequisites explain the narrow therapeutical margin of 1 alpha (OH)D3 derivatives in uremic patients before dialysis (more so in the adult than in the child) and the possible broadening of this margin in the patients on dialysis by the use of low dialysate calcium concentrations (1.25-1.00 mmol/l) in order to prevent hypercalcemia by inducing a negative perdialytic calcium balance. Once hyperphosphatemia is prevented by oral calcium, 1 alpha (OH)D3 derivatives have the advantage to suppress the transcription of the prepro PTH gene by a mechanism independent of an increase in plasma calcium. Controlled randomized trials have not confirmed the claimed advantage in efficacy and safety of the parenteral versus the oral route nor of the intermittent versus the daily mode of their administration. The advantages of using the so called 'nonhypercalcemic hyperphosphatemic' vitamin D3 derivatives in

  14. A 7-day continuous infusion of PTH or PTHrP suppresses bone formation and uncouples bone turnover.

    PubMed

    Horwitz, Mara J; Tedesco, Mary Beth; Sereika, Susan M; Prebehala, Linda; Gundberg, Caren M; Hollis, Bruce W; Bisello, Alessandro; Garcia-Ocaña, Adolfo; Carneiro, Raquel M; Stewart, Andrew F

    2011-09-01

    Human in vivo models of primary hyperparathyroidism (HPT), humoral hypercalcemia of malignancy (HHM), or lactational bone mobilization for more than 48 hours have not been described previously. We therefore developed 7-day continuous-infusion models using human parathyroid hormone(1-34) [hPTH(1-34)] and human parathyroid hormone-related protein(1-36) [hPTHrP(1-36)] in healthy human adult volunteers. Study subjects developed sustained mild increases in serum calcium (10.0 mg/dL), with marked suppression of endogenous PTH(1-84). The maximal tolerated infused doses over a 7-day period (2 and 4 pmol/kg/h for PTH and PTHrP, respectively) were far lower than in prior, briefer human studies (8 to 28 pmol/kg/h). In contrast to prior reports using higher PTH and PTHrP doses, both 1,25-dihydroxyvitamin D(3) [1,25(OH)(2) D(3) ] and tubular maximum for phosphorus (TmP/GFR) remained unaltered with these low doses despite achievement of hypercalcemia and hypercalciuria. As expected, bone resorption increased rapidly and reversed promptly with cessation of the infusion. However, in contrast to events in primary HPT, bone formation was suppressed by 30% to 40% for the 7 days of the infusions. With cessation of PTH and PTHrP infusion, bone-formation markers abruptly rebounded upward, confirming that bone formation is suppressed by continuous PTH or PTHrP infusion. These studies demonstrate that continuous exposure of the human skeleton to PTH or PTHrP in vivo recruits and activates the bone-resorption program but causes sustained arrest in the osteoblast maturation program. These events would most closely mimic and model events in HHM. Although not a perfect model for lactation, the increase in resorption and the rebound increase in formation with cessation of the infusions are reminiscent of the maternal skeletal calcium mobilization and reversal that occur following lactation. The findings also highlight similarities and differences between the model and HPT. Copyright

  15. Parathyroid carcinoma: biochemical and pathologic response to DTIC.

    PubMed

    Calandra, D B; Chejfec, G; Foy, B K; Lawrence, A M; Paloyan, E

    1984-12-01

    Parathyroid carcinoma is a rare cause of hyperparathyroidism. Cure results from successful en bloc resection. However, because of its rarity, the malignant nature may not be appreciated at the initial operative procedure and as a result, definitive resection may not be accomplished. However, even with extensive en bloc resections, local recurrences do occur and patients die of metabolic derangements associated with hypercalcemia. Thus in addition to operative intervention, palliative chemotherapy may be required to control the hypercalcemia. Radiotherapy has been unsuccessful. A single case of nonfunctioning parathyroid carcinoma responding to treatment with methotrexate, Adriamycin, cyclophosphamide, and CCNU has been reported. We report a case of recurrent functioning parathyroid carcinoma treated with dacarbazine (DTIC) in which biochemical and pathologic evidence of at least a partial response was seen. The patient, a 33-year-old woman, had undergone five previous neck explorations during a 26-month period for aggressive locally recurrent disease. Before DTIC therapy the intact parathyroid hormone (PTH) level was 1032 pg Eq/ml (normal 163 to 347 pg Eq/ml) and the serum calcium level was 16.8 mg/dl (normal 8.8 to 10.0 mg/dl). After a course of DTIC there was a marked improvement in her clinical status and biochemical parameters (intact PTH 545 pg Eq/ml; serum calcium 11.8 mg/dl). For 2 months her condition stabilized, with PTH levels between 700 and 760 pg Eq/ml and serum calcium levels between 10.2 and 16.0 mg/dl. With a slowly progressive rise in biochemical parameters a second course of DTIC was initiated and a marked drop in serum calcium levels (5.7 mg/dl) occurred, but PTH levels remained unchanged. A progressive course of septicemia, malnutrition, and disseminated intravascular clotting ultimately lead to her death 4 weeks later. At autopsy examination the tumor was confined to the neck. Grossly and microscopically there was extensive central as well as

  16. Comparison of the effects of daily and intermittent-dose calcitriol on serum parathyroid hormone and ionized calcium concentrations in normal cats and cats with chronic renal failure.

    PubMed

    Hostutler, Roger A; DiBartola, Stephen P; Chew, Dennis J; Nagode, Larry A; Schenck, Patricia A; Rajala-Schultz, Päivi J; Drost, W Tod

    2006-01-01

    Chronic renal failure is complicated by secondary hyperparathyroidism, which traditionally has been controlled by dietary restriction of phosphorus and administration of phosphorus binders. Early treatment of patients with chronic renal failure with calcitriol may be indicated because once established, parathyroid gland hyperplasia does not readily resolve with therapy. Daily and intermittent dosing of calcitriol will decrease plasma parathyroid hormone concentration in normal cats and cats with chronic renal failure without causing ionized hypercalcemia. Ten normal cats; 10 cats with chronic renal failure. Phase 1 was daily calcitriol administration (2.5 ng/kg PO q24h) for 14 days. Phase 2 was intermittent calcitriol administration (8.75 ng/kg PO q84h) for 14 days. A 7-day washout period separated phases 1 and 2. Before each phase, calcitriol, parathyroid hormone, and ionized calcium concentrations were measured. On days 1, 2, and 3 of both phases, serum ionized calcium concentrations were measured. On the last day of both phases, calcitriol, parathyroid hormone, and ionized calcium concentrations were measured 0, 2, 4, and 6 hours after calcitriol administration. Overall, serum parathyroid hormone concentrations were significantly higher in cats with chronic renal failure than in normal cats (P = .022), but serum parathyroid hormone concentrations for both normal cats and cats with chronic renal failure were not significantly different before and after 14 days of treatment with calcitriol, regardless of whether calcitriol was administered daily or intermittently. Adverse effects of calcitriol administration (specifically ionized hypercalcemia) were not seen in either feline group during either phase of the study over the 3-day evaluation after calcitriol administration was initiated. At the dosages used, calcitriol treatment did not result in significant differences in serum parathyroid hormone concentrations before and after treatment in both normal cats and

  17. Calcium and bone homeostasis in heterozygous carriers of CYP24A1 mutations: A cross-sectional study.

    PubMed

    Cools, M; Goemaere, S; Baetens, D; Raes, A; Desloovere, A; Kaufman, J M; De Schepper, J; Jans, I; Vanderschueren, D; Billen, J; De Baere, E; Fiers, T; Bouillon, R

    2015-12-01

    Bi-allelic CYP24A1 mutations can cause idiopathic infantile hypercalcemia (IIH), adult-onset nephrocalcinosis, and possibly bone metabolism disturbances. It is currently unclear if heterozygous carriers experience clinical problems or biochemical abnormalities. Our objective is to gain insight in the biochemical profile and health problems in CYP24A1 heterozygotes. Cross-sectional evaluation of participants. Data of previously reported carriers are reviewed. Outpatient clinic of a tertiary care hospital. Participants were eight family members of an infant with a well-characterized homozygous CYP24A1 mutation c.1186C>T p.(Arg396Trp). Serum vitamin D metabolites. Symptoms or biochemical signs of hypercalcemia, hypercalciuria or nephrocalcinosis. Bone health in heterozygous as compared to wild type (WT) subjects. Genotyping by Sanger sequencing; vitamin D metabolites by liquid chromatography tandem mass spectrometry; renal, calcium and bone markers by biochemical analyses; presence of nephrocalcinosis by renal ultrasound; bone health by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Six participants were heterozygous carriers of the mutation. None of the heterozygous subjects had experienced IIH. One had a documented history of nephrolithiasis, two others had complaints compatible with this diagnosis. No major differences between WT and heterozygous subjects were found regarding bone health, serum or urinary calcium or 25OHD/24,25(OH)2D ratio. Literature reports on three out of 33 heterozygous cases suffering from IIH. In all three, the 25OHD/24,25(OH)2D ratio was highly elevated. Nephrocalcinosis was frequently reported in family members of IIH cases. Small sample size, lack of a large control group. Our and literature data suggest that most heterozygous CYP24A1 mutation carriers have a normal 25OHD/24,25(OH)2D ratio, are usually asymptomatic and have a normal skeletal status but may possibly be at increased risk of nephrocalcinosis

  18. Short-term effects of high-dose oral vitamin D3 in critically ill vitamin D deficient patients: a randomized, double-blind, placebo-controlled pilot study.

    PubMed

    Amrein, Karin; Sourij, Harald; Wagner, Gerit; Holl, Alexander; Pieber, Thomas R; Smolle, Karl Heinz; Stojakovic, Tatjana; Schnedl, Christian; Dobnig, Harald

    2011-01-01

    Vitamin D deficiency is encountered frequently in critically ill patients and might be harmful. Current nutrition guidelines recommend very low vitamin D doses. The objective of this trial was to evaluate the safety and efficacy of a single oral high-dose vitamin D3 supplementation in an intensive care setting over a one-week observation period. This was a randomized, double-blind, placebo-controlled pilot study in a medical ICU at a tertiary care university center in Graz, Austria. Twenty-five patients (mean age 62 ± 16 yrs) with vitamin D deficiency [25-hydroxyvitamin D (25(OH)D) ≤ 20 ng/ml] and an expected stay in the ICU >48 hours were included and randomly received either 540,000 IU (corresponding to 13.5 mg) of cholecalciferol (VITD) dissolved in 45 ml herbal oil or matched placebo (PBO) orally or via feeding tube. The mean serum 25(OH)D increase in the intervention group was 25 ng/ml (range 1-47 ng/ml). The highest 25(OH)D level reached was 64 ng/ml, while two patients showed a small (7 ng/ml) or no response (1 ng/ml). Hypercalcemia or hypercalciuria did not occur in any patient. From day 0 to day 7, total serum calcium levels increased by 0.10 (PBO) and 0.15 mmol/L (VITD; P < 0.05 for both), while ionized calcium levels increased by 0.11 (PBO) and 0.05 mmol/L (VITD; P < 0.05 for both). Parathyroid hormone levels decreased by 19 and 28 pg/ml (PBO and VITD, ns) over the seven days, while 1,25(OH)D showed a transient significant increase in the VITD group only. This pilot study shows that a single oral ultra-high dose of cholecalciferol corrects vitamin D deficiency within 2 days in most patients without causing adverse effects like hypercalcemia or hypercalciuria. Further research is needed to confirm our results and establish whether vitamin D supplementation can affect the clinical outcome of vitamin D deficient critically ill patients. EUDRACT NUMBER: 2009-012080-34 GERMAN CLINICAL TRIALS REGISTER (DRKS): DRKS00000750.

  19. The other side of vitamin D therapy: 
a case series of acute kidney injury due to malpractice-related vitamin D intoxication
.

    PubMed

    Wani, Muzafar; Wani, Imtiaz; Banday, Khurshid; Ashraf, Mohd

    2016-11-01

    Vitamin D deficiency is highly prevalent in Indian Kashmir. Many people get injectable vitamin D (600,000 IU/injection). At times, the dose prescribed is far above the permissible limit. We report 62 patients with malpractice-related vitamin D intoxication, presenting with hypercalcemia and acute kidney injury (AKI). The diagnosis was made on basis of (1) history of multiple intramuscular vitamin D injections (2) toxic serum levels of 25-OH vitamin D and (3) exclusion of common causes of hypercalcemia (malignancy and hyperparathyroidism). Their presentation was either de novo AKI in 51 (group 1) or acute on top of chronic kidney disease in 11 (group 2). The mean age was 60 ± 14 vs. 62 ± 13 years, approximate number of vitamin D injections received ranged from 4 to 28 (2.4 - 16.8 million units) vs. 3 to 24 (1.8 - 14.4 million units), mean creatinine at presentation was 3.2 ± 0.9 vs. 4.5 ± 1.1 mg/dL, which decreased to 1.2 ± 0.2 vs. 3.3 ± 1.0 mg/dL, mean serum calcium on admission was 13.7 ± 1.4 vs. 13.6 ± 2.0 mg/dL which decreased to 10.7 ± 1.2 vs. 11.0 ± 1.0 mg/dL on follow-up of 7.2 ± 0.6 months, mean vitamin D level was 313.3 ± 54.8 (range 235 - 375) vs. 303.7 ± 48.4 (range 210 - 375) nmol/L and mean PTH was 18.1 ± 9.6 (range 6.2 - 32) vs. 52.3 ± 12.6 (range 28 - 88) pg/mL in group 1 vs. group 2, respectively. The clinical presentation was weakness, constipation, abdominal pain, nausea, vomiting, anorexia, altered sensorium, and oliguria. The treatment received was intravenous fluids (normal saline) in all in group 1 and in 8/11 in group 2, short course of steroids (prednisolone) in 44, and bisphosphonate in 6. This is the largest case series of AKI secondary to vitamin D toxicity ever reported.
.

  20. Experience with cinacalcet in primary hyperparathyroidism: results after 1 year of treatment

    PubMed Central

    García-Martín, Antonia; Luque-Pazos, Alessandra

    2013-01-01

    Objectives: To assess the characteristics of patients with primary hyperparathyroidism (PHPT) treated with cinacalcet and to evaluate its efficacy in reducing serum calcium and parathyroid hormone (PTH) concentrations after 1 year of treatment. Methods: The study included 20 patients with PHPT who had completed at least 12 months of treatment with cinacalcet (eight patients for refusal of parathyroidectomy, three for surgery not possible due to comorbidities and nine for progressive hypercalcemia prior to surgery). We recorded clinical and biochemical data at baseline, and after 3, 6 and 12 months of treatment. We also monitored adverse events. Cinacalcet was administered in increasing doses until normal serum calcium was reached or side effects preventing a further increase occurred. Results: After 3 months of treatment, serum calcium significantly decreased (11.73 ± 0.85 versus 10.71 ± 1.63 mg/dl, p < 0.001) and serum phosphorus significantly increased (2.41 ± 0.48 versus 2.63 ± 0.70 mg/dl, p = 0.004) while no significant change occurred in PTH (181.91 ± 102.37 versus 195.47 ± 111.71 pg/ml, p = 0.695). No further variation was observed after 6 months compared with 3 months of follow up. However, after 12 months of treatment, there was a significant decrease in PTH concentrations compared with baseline (181.91 ± 102.37 versus 152.47± 70.16 pg/ml, p = 0.028) as well as serum calcium (11.73 ± 0.85 versus 10.20± 0.95 mg/dl, p < 0.001); serum phosphorus significantly increased (2.41 ± 0.48 versus 2.71 ± 0.43 mg/dl, p = 0.01). Normocalcemia (S-Ca < 10.2 mg/dl) was achieved in 55% of patients. The medication was usually well tolerated (83.4%). Most common adverse events were nausea and vomiting, especially at the beginning of therapy. Conclusion: Cinacalcet rapidly reduced serum calcium in patients with PHPT and this reduction remained stable after 1 year of treatment. We also observed a decrease in PTH. Cinacalcet is an effective alternative in nonsurgical