Hypercalcaemia

Author(s):  
Ronen Levi ◽  
Justin Silver

Ionized calcium is essential for several physiological functions, including neuromuscular activation, endocrine and exocrine secretions, integrity of cellular bilayers, plasma coagulation, immune functions and bone metabolism. Extracellular fluid (ECF) calcium is uniquely controlled by its own calcium-sensing receptor, regulating the secretion of parathyroid hormone (PTH), synthesis of 1,25-dihydroxyvitamin D, and the renal reabsorption of filtered calcium (see Chapter 4.1). With the advent of the autoanalyser and routine determination of serum calcium levels, recognition of hypercalcaemia has become common. However, the clinical spectrum of hypercalcaemia varies from a laboratory-detected, asymptomatic mineral disorder to a life-threatening state.

2018 ◽  
Vol 178 (4) ◽  
pp. 425-430 ◽  
Author(s):  
Niranjan Tachamo ◽  
Anthony Donato ◽  
Bidhya Timilsina ◽  
Salik Nazir ◽  
Saroj Lohani ◽  
...  

Introduction Cosmetic injections with silicone and polymethylmethacrylate are not FDA approved for augmentation of body parts such as breast, buttock or legs, but they have been widely used for decades. Cosmetic injections can cause foreign body granulomas and occasionally severe and life-threatening hypercalcemia. We aimed to systematically analyze the published literature on cosmetic injection-associated hypercalcemia. Methods We searched relevant articles on hypercalcemia associated with various cosmetic injections and extracted relevant data on demographics, cosmetic injections used, severity of hypercalcemia, management and outcomes. Results We identified 23 eligible patients from 20 articles. Mean age was 49.83 ± 14.70 years with a female preponderance (78.26% including transgender females). Silicone was most commonly used, followed by polymethylmethacrylate and paraffin oil (43.48, 30.43, and 8.70% respectively). The buttock was the most common site followed by the breast (69.57% and 39.13% respectively). Hypercalcemia developed at mean duration of 7.96 ± 7.19 years from the initial procedure. Mean ionized calcium at presentation was 2.19 ± 0.61 mmol/L and mean corrected calcium at presentation was 3.43 ± 0.31 mmol/L. 1,25-Dihydroxyvitamin D (1,25(OH)2D or calcitriol) was elevated while 25-hydroxyvitamin D (25(OH)D) and PTH were low in majority of cases. Hypercalcemia was managed conservatively with hydration, corticosteroids and bisphosphonates in majority of cases. Surgery was attempted in 2 cases but was unsuccessful. Renal failure was the most common complication (82.35% cases) and 2 patients died. Conclusion Hypercalcemia from cosmetic injections can be severe and life threatening and can present years after the initial procedure. Cosmetic injection-associated granuloma should be considered a cause of hypercalcemia, especially in middle-aged females presenting with non-PTH-mediated, non-malignant hypercalcemia, which is often associated with elevated calcitriol; however, it should be noted that calcitriol level may be normal as well.


2013 ◽  
Vol 305 (8) ◽  
pp. F1109-F1117 ◽  
Author(s):  
Douglas K. Atchison ◽  
Pamela Harding ◽  
William H. Beierwaltes

1, 25-Dihydroxycholechalciferol (calcitriol) and 19-nor-1, 25-dihydroxyvitamin D2 (paricalcitol) are vitamin D receptor (VDR) agonists. Previous data suggest VDR agonists may actually increase renin-angiotensin activity, and this has always been assumed to be mediated by hypercalcemia. We hypothesized that calcitriol and paricalcitol would increase plasma renin activity (PRA) independently of plasma Ca2+ via hypercalciuria-mediated polyuria, hypovolemia, and subsequent increased β-adrenergic sympathetic activity. We found that both calcitriol and paricalcitol increased PRA threefold ( P < 0.01). Calcitriol caused hypercalcemia, but paricalcitol did not. Both calcitriol and paricalcitol caused hypercalciuria (9- and 7-fold vs. control, P < 0.01) and polyuria (increasing 2.6- and 2.2-fold vs. control, P < 0.01). Paricalcitol increased renal calcium-sensing receptor (CaSR) expression, suggesting a potential cause of paricalcitol-mediated hypercalciuria and polyuria. Volume replacement completely normalized calcitriol-stimulated PRA and lowered plasma epinephrine by 43% ( P < 0.05). β-Adrenergic blockade also normalized calcitriol-stimulated PRA. Cyclooxygenase-2 inhibition had no effect on calcitriol-stimulated PRA. Our data demonstrate that vitamin D increases PRA independently of plasma Ca2+ via hypercalciuria, polyuria, hypovolemia, and increased β-adrenergic activity.


1984 ◽  
Vol 30 (1) ◽  
pp. 56-61 ◽  
Author(s):  
P C Kao ◽  
D W Heser

Abstract With this dual-cartridge system we extract 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] from a single serum sample by using a nonpolar octadecylsilanol silica cartridge to adsorb the vitamin D metabolites and other nonpolar substances; the polar substances wash through the cartridge. The eluted material is then applied to a second alkylamine cartridge, which adsorbs the relatively polar hydroxylated metabolites; the less-polar substances are washed from the second cartridge. Elution from the second cartridge purifies and also separates 25(OH)D and 1,25(OH)2D with analytical recoveries near 90%. The monohydroxyl metabolites are determined by "high-performance" liquid chromatography (HPLC); the dihydroxyl metabolites are further purified by HPLC and determined by radioreceptor assay according to established procedures. Mean (+/- SD) winter normal values (34 subjects of both sexes; blood drawn in mid-April) were 18 +/- 5 micrograms/L for 25(OH)D and 25 +/- 7 ng/L for 1,25(OH)2D. In nine laboratory volunteers, the mean increase in the serum 25(OH)D3 value 5 h after ingestion of 50 micrograms of 25-hydroxycholecalciferol (Calderol) was 9 (SD 4) micrograms/L.


2019 ◽  
Vol 12 (2) ◽  
pp. e227141
Author(s):  
Daniel Chan ◽  
Wilsie Martillano Salas-Walinsundin ◽  
Fabian Kok Peng Yap ◽  
Mark Jean Aan Koh

We present a case that illustrates the fluctuations in calcium levels to be expected while managing an infant with maternal gestational diabetes mellitus who also develops subcutaneous fat necrosis (SCFN). There is initial hypocalcaemia due to functional hypoparathyroidism, requiring judicious calcium replacement. But with increased extrarenal production of 1,25-dihydroxyvitamin D due to granulomatous inflammation of subcutaneous adipose tissue, hypercalcaemia ensues. With a self-limiting course, SCFN of the newborn has an excellent prognosis and resolves spontaneously. However, aberrations in serum calcium levels can manifest in life-threatening complications and must hence be closely monitored.


2006 ◽  
Vol 290 (5) ◽  
pp. F1110-F1117 ◽  
Author(s):  
Huda Ismail Abdullah ◽  
Paulina L. Pedraza ◽  
Shoujin Hao ◽  
Karin D. Rodland ◽  
John C. McGiff ◽  
...  

Because nuclear factor of activated T cells (NFAT) has been implicated in TNF production as well as osmoregulation and salt and water homeostasis, we addressed whether calcium-sensing receptor (CaR)-mediated TNF production in medullary thick ascending limb (mTAL) cells was NFAT dependent. TNF production in response to addition of extracellular Ca2+ (1.2 mM) was abolished in mTAL cells transiently transfected with a dominant-negative CaR construct (R796W) or pretreated with the phosphatidylinositol phospholipase C (PI-PLC) inhibitor U-73122. Cyclosporine A (CsA), an inhibitor of the serine/threonine phosphatase calcineurin, and a peptide ligand, VIVIT, that selectively inhibits calcineurin-NFAT signaling, also prevented CaR-mediated TNF production. Increases in calcineurin activity in cells challenged with Ca2+ were inhibited after pretreatment with U-73122 and CsA, suggesting that CaR activation increases calcineurin activity in a PI-PLC-dependent manner. Moreover, U-73122, CsA, and VIVIT inhibited CaR-dependent activity of an NFAT construct that drives expression of firefly luciferase in transiently transfected mTAL cells. Collectively, these data verify the role of calcineurin and NFAT in CaR-mediated TNF production by mTAL cells. Activation of the CaR also increased the binding of NFAT to a consensus oligonucleotide, an effect that was blocked by U-73122 and CsA, suggesting that a calcineurin- and NFAT-dependent pathway increases TNF production in mTAL cells. This mechanism likely regulates TNF gene transcription as U-73122, CsA, and VIVIT blocked CaR-dependent activity of a TNF promoter construct. Elucidating CaR-mediated signaling pathways that regulate TNF production in the mTAL will be crucial to understanding mechanisms that regulate extracellular fluid volume and salt balance.


Author(s):  
Niek F. Dirks ◽  
Frans Martens ◽  
Dirk Vanderschueren ◽  
Jaak Billen ◽  
Steven Pauwels ◽  
...  

1999 ◽  
Vol 45 (8) ◽  
pp. 1347-1352 ◽  
Author(s):  
Gregory R Mundy ◽  
Theresa A Guise

Abstract Calcium homeostasis in the extracellular fluid is tightly controlled and defended physiologically. Hypercalcemia always represents considerable underlying pathology and occurs when the hormonal control of calcium homeostasis is overwhelmed. The major hormones that are responsible for normal calcium homeostasis are parathyroid hormone and 1,25-dihydroxyvitamin D; these hormones control extracellular fluid calcium on a chronic basis. Over- or underproduction of these hormones or the tumor peptide, parathyroid hormone-related peptide, are the major causes of aberrant extracellular fluid calcium concentrations. These hormonal defense mechanisms are reviewed here.


2019 ◽  
Vol 10 (3) ◽  
pp. 546-548 ◽  
Author(s):  
Connie M Weaver ◽  
Munro Peacock

ABSTRACT Calcium is the fifth most abundant element in the body with &gt;99% residing in the skeleton as hydroxyapatite, a complex calcium phosphate molecule. This mineral supplies the strength to bones that support locomotion, but it also serves as a reservoir to maintain serum calcium concentrations. Calcium plays a central role in a wide range of essential functions. Its metabolism is regulated by 3 major transport systems: intestinal absorption, renal reabsorption, and bone turnover. Calcium transport in these tissues is regulated by a sophisticated homeostatic hormonal system that involves parathyroid hormone, and 1,25-dihydroxyvitamin D in response to decreased serum ionized calcium, detected by the calcium-sensing receptor (1).


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