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Hypercalcemia (hypercalcaemia)

Introduction

Hypercalcaemia - presentation and management 1)

Hypercalcaemia is a common disorder normally caused by primary hyperparathyroidism (PHPT) or malignancy. A proportion of cases present as an emergency, which carries a significant mortality. Emergency management of hypercalcaemia is based on intravenous rehydration with normal saline but when this is inadequate, bisphosphonate therapy is used; more recently the novel anti-resorbtive agent denosumab has been shown to have a useful role in treatment.

Although parathyroidectomy is the only curative treatment for PHPT, this is indicated in a minority of cases.

Hyperuricaemia was associated with an unfavourable cardiovascular risk profile in HF patients. Treatment with low doses of allopurinol did not improve the prognosis of HF patients. 2)

A Quick Reference on Hypercalcemia. 3)

In dogs, neoplasia is the most common cause of hypercalcemia, followed by primary hyperparathyroidism, chronic kidney disease, and hypoadrenocorticism. In cats, idiopathic hypercalcemia is the most common cause, followed by chronic kidney disease and then neoplasia.

Cancer-Related Hypercalcemia. 4)

The most common causes include humoral hypercalcemia of malignancy mediated by parathyroid hormone-related peptide, osteolytic cytokine production, and excess 1,25-dihydroxy vitamin D production.

The active form of vitamin D3Form of vitamin D made in the skin when exposed to light. Also available in fish and meat. This secosteroid is sometimes converted into 25-D. Also known as cholecalciferol and activated 7-dehydrocholesterol. , calcitriol, is a potent antiproliferative compound. However, when effective antitumor doses of calcitriol are used, hypercalcemic effects are observed, thus blocking its therapeutic application. 5)

Infants

Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects. 6)

CYP2R1 has been identified as the most important 25-hydroxylase, and a critical role for CYP24A1 in humans was noted in studies showing that inactivating mutations in CYP24A1 are a probable cause of idiopathic infantile hypercalcemia.

Fungal infection

Successful treatment of an intra-pelvic fungal pseudomycetoma causing constipation and hypercalcaemia in a Persian cat. 7)

Why doesn't the use of olmesartan lead to hypercalcemia?

Since calcitriol (the active form of vitamin D) is a Vitamin D receptorA nuclear receptor located throughout the body that plays a key role in the innate immune response. (VDRThe Vitamin D Receptor. A nuclear receptor located throughout the body that plays a key role in the innate immune response.) agonist, and use of this substance can cause hypercalcemia, one may expect that olmesartanMedication taken regularly by patients on the Marshall Protocol for its ability to activate the Vitamin D Receptor. Also known by the trade name Benicar. , through effects on the VDR, may also cause hypercalcemia if the dosage is high. There is however no evidence that this is an effect of olmesartan, and the reason for the differing effects appears to reside in the non-VDR effects of calcitriol. 8)

Notes and comments

check for input https://www.marshallprotocol.com/search.php?s=1&q=hypercalcemia&forum_id=35

<DiseaseHierarchy>

This paper explains the out of range values for kidney and liver functions, which suggest that I may be a little premature in stopping the MP.

But it doesn't explain the elevated calcium results (which is at 3.00 mmol/L). This result has my GP really concerned as it could indicate malignancy.

Any comments?

Cheers Guss

Am J Med Sci. 1995 Aug;310(2):71-6.Case report: vitamin D-mediated hypercalcemia in fungal infections. Spindel SJ, Hamill RJ, Georghiou PR, Lacke CE, Green LK, Mallette LE. Source Section of Infectious Disease, Veterans Affairs Medical Center, Houston, TX 77030, USA. Abstract Hypercalcemia has been well described in a variety of neoplastic and granulomatous diseases. One mechanism for this hypercalcemia is via the excess production of 1,25-dihydroxyvitamin DPrimary biologically active vitamin D hormone. Activates the vitamin D nuclear receptor. Produced by hydroxylation of 25-D. Also known as 1,25-dihydroxycholecalciferol, 1,25-hydroxyvitamin D and calcitirol. from extra-renal sources. The authors describe an AIDS patient infected with Cryptococcus neoformans who had suggestive evidence of vitamin D-mediated hypercalcemia. He had an elevated serum 1,25-dihydroxyvitamin D value, a normal 25-hydroxyvitamin D value, and low values for parathyroid hormone and parathyroid hormone-related peptide. Most previously reported cases of hypercalcemia associated with fungal infections did not include sufficient evidence to implicate a role for excess 1,25-dihydroxyvitamin D production, except for two case reports involving patients with hypercalcemia with infections due to Pneumocystis carinii and Candida albicans. The authors' patient's hypercalcemia resolved during treatment of his underlying infection. Patients with hypercalcemia or in whom hypercalcemia develops during a disseminated fungal infection should have vitamin D metabolites measured as part of their work-up.

PMID: 7631647

References

1)
Hypercalcaemia - presentation and management .
Turner JJO
Clin Med (Lond)17p270-273(2017 Jun)
2)
Hyperuricaemia treatment in acute heart failure patients does not improve their long-term prognosis: a propensity score matched analysis from the AHEAD registry.
Pavlusova M, Jarkovsky J, Benesova K, Vitovec J, Linhart A, Widimsky P, Spinarova L, Zeman K, Belohlavek J, Malek F, Felsoci M, Kettner J, Ostadal P, Cihalik C, Spac J, Al-Hiti H, Fedorco M, Fojt R, Kruger A, Malek J, Mikusova T, Monhart Z, Bohacova S, Pohludkova L, Rohac F, Vaclavik J, Vondrakova D, Vyskocilova K, Bambuch M, Dostalova G, Havranek S, Svobodová I, Dusek L, Spinar J, Miklik R, Parenica J
Clin Cardiolp(2019 May 22)
3)
A Quick Reference on Hypercalcemia.
de Brito Galvão JF, Schenck PA, Chew DJ
Vet Clin North Am Small Anim Pract47p241-248(2017 Mar)
4)
Cancer-Related Hypercalcemia.
Goldner W
J Oncol Pract12p426-32(2016 May)
5)
Novel calcitriol analogue with an oxolane group: In vitro, in vivo, and in silico studies.
Obiol DJ, Martínez A, Ferronato MJ, Quevedo MA, Grioli SM, Alonso EN, Gómez G, Fall Y, Facchinetti MM, Curino AC
Arch Pharm (Weinheim)352pe1800315(2019 May)
6)
Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects.
Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet G
Physiol Rev96p365-408(2016 Jan)
7)
Successful treatment of an intra-pelvic fungal pseudomycetoma causing constipation and hypercalcaemia in a Persian cat.
Zafrany A, Ben-Oz J, Segev G, Milgram J, Zemer O, Jensen HE, Kelmer E
J Feline Med Surg16p369-72(2014 Apr)
8)
Improvement of impaired calcium and skeletal homeostasis in vitamin D receptor knockout mice by a high dose of calcitriol and maxacalcitol.
Shiizaki K, Hatamura I, Imazeki I, Moriguchi Y, Sakaguchi T, Saji F, Nakazawa E, Kato S, Akizawa T, Kusano E
Bone45p964-71(2009 Nov)
home/diseases/hypercalcemia.txt · Last modified: 07.27.2019 by sallieq
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