Investigation of hypercalcemia

Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Clinical biochemistry (Impact Factor: 2.28). 05/2012; 45(12):954-63. DOI: 10.1016/j.clinbiochem.2012.04.025
Source: PubMed


Hypercalcemia is a relatively common clinical finding. Primary hyperparathyroidism, hypercalcemia associated with malignancy and chronic renal failure (with calcium and vitamin D metabolite treatment or tertiary hyperparathyroidism) are the most common causes. Less common causes of hypercalcemia include vitamin D-related (granulomatous diseases, lymphoma, vitamin D intoxication), other endocrine (thyrotoxicosis), medications (milk-alkali, thiazides, lithium) and other causes (immobilization, familial hypocalciuric hypercalcemia). The clinical laboratory is central to the diagnosis and differential diagnosis of hypercalcemia. Its role has expanded from measuring routine chemistry tests such as total calcium, phosphate, creatinine and alkaline phosphate to include quantification of ionized calcium, parathyroid hormone (PTH) and vitamin D metabolites. In spite of this progress, the diagnosis and differential diagnosis of hypercalcemia can be significantly improved by: 1) increasing the availability and utilization of ionized calcium since total and corrected calcium are often inaccurate; 2) establishing more accurate reference intervals for parathyroid hormone by excluding individuals who are vitamin D insufficient or deficient; and 3) harmonizing intact PTH immunoassays.

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    • "Instead, severe hypercalcemia and high LDH levels were the only abnormal findings that might have been associated with his clinical manifestations. His hypercalcemia was not explained by hyperparathyroidism, hyperthyroidism, sarcoidosis, nephrogenic diabetes insipidus, or medications, such as lithium, calcitriol, vitamin D, or thiazides [5,11]. Although myeloma-related osteolysis or metastatic bone tumors, such as prostate cancer, were also considered in this case as a cause of hypercalcemia; however, laboratory tests, such as protein electrophoresis and prostatespecific antigen, as well as a chest and abdomen CT scan did not provide any evidence to confirm these diseases. "
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    ABSTRACT: Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of non-Hodgkin lymphoma. It usually presents with nonspecific symptoms, such as fever, rather than with overt lymphadenopathy. Reports of hypercalcemia, as the initial presentation of IVLBCL, are limited in the literature, despite it being a well-known complication of various solid cancers. We present a 68-year-old male with severe hypercalcemia and increased levels of serum parathyroid hormone-related protein. He was diagnosed with IVLBCL, involving the bone marrow and spleen, and was successfully treated with rituximab-containing chemotherapy. A few previous case reports have shown hypercalcemia in patients with IVLBCL. Much like our case, previous cases with hypercalcemia had advanced diseases, including bone marrow invasion. Although it was an extremely rare manifestation of IVLBCL, we suggest that IVLBCL should be a part of the differential diagnosis in patients with unexplained hypercalcemia. Therefore, an active work-up might be recommended, including positron emission tomography/ computed tomography scan and bone marrow examination, which may be useful for early diagnosis.
    Cancer Research and Treatment 07/2014; 46(3):307-311. DOI:10.4143/crt.2014.46.3.307 · 3.32 Impact Factor
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    • "In fact, despite many advantages, the limit in therapeutic applications of vitamin D and vitamin D analogues undeniably relies on the systemic toxicity often associated with long-term intake: hypercalcemia is the main risk associated to the supraphysiological doses of vitamin D necessary to reach the low local effective concentration [124, 125]. Thus, the introduction of new molecules with immunosuppressive features without causing significant hypercalcemia has been strongly encouraged [126]. "
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    ABSTRACT: The primary aim in the treatment of autoimmune inflammatory myopathies (IMs) is to recover muscle function. The presence of immune/inflammatory cell infiltrates within muscle tissues represents the common feature of different IM subtypes, albeit a correlation between muscular damage extent and inflammation degree is often lacking. Treatments for IMs are based on life-long immunosuppressive therapy, with the well known adverse effects; recovery is incomplete for many patients. More effective therapies, with reduced side-effects, are highly desirable. Vitamin D receptor (VDR) agonists emerge to retain pleiotropic anti-inflammatory properties, since they regulate innate and adaptive immunity by switching the immune response from proinflammatory T helper 1 (Th1) type to tolerogenic T helper 2 (Th2) type dominance. In skeletal muscle cells less hypercalcemic VDR ligands target powerful mediators of inflammation, such as TNF α and TNF α driven paths, without affecting immune or muscle cells viability, retaining the potentiality to counteract Th1 driven overreactivity established by the self-enhancing inflammatory loop between immune and skeletal muscle cells. This review summarizes those features of VDR agonists as candidates in future treatment of IM.
    BioMed Research International 05/2014; 2014(18):949730. DOI:10.1155/2014/949730 · 1.58 Impact Factor
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    • "The limit in therapeutic applications of vitamin D undoubtedly relies on the systemic toxicity associated with long-term intake of this hormone; in fact, the supraphysiological doses of vitamin D necessary to reach the low local effective concentration (about 10−10 M) are associated with the undesirable risk of hypercalcemia [3, 129]. Therefore, the introduction of new molecules with immunosuppressive features without causing significant hypercalcemia has been strongly encouraged since a while [130]. "
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    ABSTRACT: Understanding the many biological extraskeletal actions of vitamin D has increased in the past decades. Indeed, vitamin D and analogue molecules, besides the classical actions on bone metabolism, exert several beneficial effects on metabolic homeostasis, heart-cardiovascular, brain, and muscle physiological functions, throughout the interaction with the specific vitamin D receptor (VDR). In particular, VDR agonists powerfully control innate and adaptive immune system with favorable effects on human health. VDR ligands act as immunomodulators that are potent enough to retain anti-inflammatory effects, even though the mechanism underlying those effects is not yet fully elucidated. VDR agonists exert a significant suppression of inflammatory processes switching the immune response from T helper 1 (Th1) to T helper 2 (Th2) dominance and counteracting the self-enhancing inflammatory loop between immune and resident cells, especially by cytokine release impairment. Those molecules are able, indeed, to reduce the release of the interferon (IFN)γ-induced 10 kDa protein IP-10/CXCL10, a powerful chemokine driving Th1-mediated inflammation. Based on their features, VDR ligands show the potentiality to be included in immunosuppressive regimens, aimed to control auto- and alloimmune Th1-driven overreactivity, occurring, for example, in autoimmune disease or graft rejection.
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