cholecalciferol and Sarcoidosis

Sarcoid epithelioid cells are believed to be a variant of tissue macrophages, which are derived from circulating monocytes in blood. Formation of monocytes and macrophages are controlled by hematopoietic growth factors, i.e.; colony-stimulating factors in the bone marrow. In the presence of colony-stimulating factors and/or vitamin D3, blood monocytes can proliferate and differentiate into epithelioid cells and multinucleated giant cells. Recent observations that sarcoid granulomas themselves produce colony-stimulating factors and vitamin D3 suggest vitamin D3 and colony-stimulating factors produced by sarcoid granulomas stimulate the proliferation and differentiation of circulating monocytes into macrophage-epithelioid cells, which form new sarcoid granulomas.

Topics: Cell Differentiation; Cell Division; Cholecalciferol; Colony-Stimulating Factors; Epithelioid Cells; Granuloma; Humans; Monocytes; Peptidyl-Dipeptidase A; Sarcoidosis

The sarcoid epithelioid cells are believed to be a variant of tissue macrophages, which derived from circulating monocytes in blood. Formation of monocytes and macrophages are controlled by hematopoietic growth factors, i.e; colony-stimulating factors in the bone marrow. In the presence of colony-stimulating factors and/or vitamin D3, blood monocytes can proliferate and differentiate into epithelioid cells and multinucleated giant cells. In view of the evidences that sarcoid granulomas produce colony-stimulating factors and active form of vitamin D3, these results suggest that active metabolites of vitamin D3 and colony-stimulating factors produced by sarcoid epithelioid cells, induces the differentiation and proliferation of circulating monocytes into macrophage-epithelioid cells, which in turn form sarcoid granulomas. Since sarcoidosis is a disorder of cell proliferation and differentiation, a question has been always kept in my mind whether the sarcoid granulomas are chronic inflammation per se or neoplastic in nature. Interestingly, cytogenetic studies revealed that most of the epithelioid cells were aneuploid; the chromosomal number ranged from the near-haploid to the near diploid number. In addition, The distribution of DNA content of the granuloma cells was fairly wide. Our observations raise a question whether the aneuploidy in sarcoid granulomas may be due to viral infection or exposure to carcinogens as in the case of neoplastic cells. It is also possible to speculate that the aneuploidy may be a mechanism of macrophage differentiation similar to immunoglobulin gene rearrangement in B lymphocytes. Further studies are required.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aneuploidy; Cell Differentiation; Cell Division; Cholecalciferol; Epithelioid Cells; Humans; Macrophage Colony-Stimulating Factor; Sarcoidosis

Topics: Alkalosis; Benzothiadiazines; Calcinosis; Cholecalciferol; Diuretics; Humans; Hypercalcemia; Hyperparathyroidism; Isotretinoin; Lithium; Osteitis Deformans; Sarcoidosis; Sodium Chloride Symporter Inhibitors; Tamoxifen; Tretinoin; Vitamin A

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Adult; Anti-Inflammatory Agents; Antineoplastic Agents; Azathioprine; Chloroquine; Cholecalciferol; Chronic Disease; Erythema Nodosum; Female; Humans; Levamisole; Lung Diseases; Lung Neoplasms; Lymphoma; Penicillamine; Sarcoidosis; Syndrome; Uveitis, Anterior

Topics: Calcium; Calcium Metabolism Disorders; Cholecalciferol; Cushing Syndrome; Diagnosis, Differential; Fanconi Syndrome; Fractures, Bone; Glomerular Filtration Rate; Humans; Hypercalcemia; Hyperparathyroidism; Hyperthyroidism; Kidney Calculi; Nephrocalcinosis; Osteitis Deformans; Osteoporosis; Parathyroid Hormone; Sarcoidosis

Extensive experimental evidence has established a significant role of calciferol in the maintenance of normal calcium homeostasis. Present knowledge indicates that vitamin D(3) must first be converted to 25-OH-D(3) and then to 1,25(OH)(2)D(3), the most active known form of the steroid. Many of the factors regulating the rate of production of this last steroid from its precurser have been evaluated, and the concept that vitamin D functions as a steroid hormone seems to be well established. Deranged action of calciferol, caused by impaired metabolism of the steroid or through altered sensitivity of target tissues, may be involved in the pathophysiology of several disease states with abnormal calcium metabolism. It is noted that liver disease, osteomalacia due to anticonvulsant therapy, chronic renal failure, hypophosphatemic rickets, hypoparathyroidism, hyperparathyroidism, sarcoidosis and idiopathic hypercalciuria have possible relation to alterations in metabolism or action of vitamin D. The future clinical availability of 1,25(OH)(2)D(3) and other analogs of this steroid may offer potential therapeutic benefit in the treatment of certain of the disease entities discussed.

Topics: Animals; Biological Transport, Active; Bone Resorption; Calcium; Calcium Metabolism Disorders; Cholecalciferol; Collagen; Homeostasis; Humans; Hydroxycholecalciferols; Hyperparathyroidism; Hypoparathyroidism; Hypophosphatemia, Familial; Intestinal Absorption; Kidney; Kidney Diseases; Liver; Liver Diseases; Sarcoidosis; Skin; Ultraviolet Rays; Vitamin D; Vitamin D Deficiency

Topics: Anticonvulsants; Bone and Bones; Bone Diseases; Calcium; Cell Membrane Permeability; Cholecalciferol; Cholesterol; Ergocalciferols; Gastrointestinal Diseases; Humans; Hypoparathyroidism; Hypophosphatemia, Familial; Intestinal Mucosa; Kidney; Kidney Failure, Chronic; Parathyroid Hormone; Sarcoidosis; Skin; Vitamin D

There are many causes of hypercalcemia, with hyperparathyroidism and malignancy accounting for 90% of cases. Sarcoidosis and the intake of vitamin D supplements may also cause hypercalcemia, although the occurrence rate is low if only one is involved. We herein report a sarcoidosis patient who developed hypercalcemia after taking cholecalciferol (vitamin D supplement) for a year.. A 62-year-old Japanese man presented with hypercalcemia and acute kidney injury along with symptoms of fatigue and appetite loss while being followed up for sarcoidosis.. We determined that a combination of cholecalciferol supplementation and sarcoidosis had led to hypercalcemia for several reasons. First, hypercalcemia had not been noted when this patient had first been admitted due to sarcoidosis-related respiratory failure several years earlier, which we presumed that was the highest sarcoidosis disease activity. Second, low serum 25-OH Vit.D3 and high 1,25-(OH)2 Vit.D3 levels were noted despite cholecalciferol supplementation for a year, suggesting that 1-α-hydroxylase overexpression caused by sarcoidosis accelerated the conversion from 25-OH Vit.D3 to 1,25-(OH)2 Vit.D3.. Although initially resistant to preservative management, the hypercalcemia promptly improved after starting corticosteroid treatment.. Hypercalcemia and acute kidney injury were normalized after corticosteroid treatment.. We should be aware of patients' medications, especially in patients with granulomatosis disease. The concomitant measurement of 25-OH Vit.D3 and 1,25-(OH)2 Vit.D3 levels is useful for determining the cause of hypercalcemia.

Topics: Acute Kidney Injury; Calcium; Cholecalciferol; Dietary Supplements; Humans; Hypercalcemia; Male; Middle Aged; Mixed Function Oxygenases; Sarcoidosis; Vitamin D

Vitamin D deficiency is common. It causes osteomalacia, may contribute to osteoporosis and is an independent risk factor for cancer, diabetes, multiple sclerosis, cardiovascular disease and all-cause mortality. We describe patients with a history of sarcoidosis who developed acute kidney injury due to hypercalcaemia following treatment with colecalciferol.

Topics: Acute Kidney Injury; Adult; Cholecalciferol; Humans; Hypercalcemia; Male; Sarcoidosis; Vitamin D Deficiency; Vitamins

Topics: Adult; Calcium; Cholecalciferol; Female; Humans; Hypercalcemia; Obesity; Parathyroid Hormone; Radiography; Sarcoidosis; Vitamin D; Vitamin D Deficiency

We report on a 61-year-old woman with coexisting early stage primary gastric plasmacytoma and sarcoidosis with hypercalcaemia. Laboratory data on admission showed hypercalcaemia, with 12.8 mg/dl, parathyroid hormone-related peptide (PTHrP) 1.2 pmol/l, C-PTHrP 69.5 pmol/l, and 1,25-dihydroxyvitamin D3 46.7 pg/ml. Neoplastic plasma cells proliferated in the propria mucosa of the stomach, showed a monoclonal immunoglobulin of cytoplasmic IgA (lambda light chain) and were positive for leucocyte common antigen and epithelial membrane antigen on paraffin section prepared from a stomach biopsy specimen. Russel bodies were present, as were crystals. Abundant sarcoid granulomas were observed in many of the regional lymph nodes around the stomach and in the dermis of a skin nodule. The patient underwent subtotal gastrectomy with administration of antimyeloma chemotherapy. We suggest that the hypercalcaemia in this patient was due to PTHrP production by neoplastic plasma cells.

Topics: Cholecalciferol; Female; Humans; Hypercalcemia; Immunohistochemistry; Middle Aged; Neoplasm Proteins; Parathyroid Hormone-Related Protein; Plasmacytoma; Proteins; Sarcoidosis; Stomach Neoplasms

A case of sarcoidosis is described which presented with hypercalcaemia and renal insufficiency. Initially, a calciol intoxication was diagnosed, because a high daily intake was suspected. However, vitamin D3 metabolites in the blood revealed normal concentrations of calcidiol, but extremely high concentrations of calcitriol. These features rejected the first diagnosis and pointed to high endogenous calcitriol production, which may take place in granulomatous diseases. This is caused by an increased 1-alpha-hydroxylation reaction in activated macrophages. Eventually, muscle biopsy revealed non-caseating granulomas, confirming the diagnosis of sarcoidosis.

Topics: Aged; Calcitriol; Cholecalciferol; Diagnosis, Differential; Female; Humans; Hypercalcemia; Muscles; Poisoning; Renal Insufficiency; Sarcoidosis

We studied effects of the hormonal form of vitamin D3 on the angiotensin-converting enzyme (ACE) activity of hepatic granulomas in mice infected with Schistosoma mansoni. During 7 to 11 weeks after infection, mice were given orally 0.1 or 1.0 microgram/kg of 1 alpha (OH)D3 or only medium solution every other day. Granulomatous livers were removed at 7, 9 and 11 weeks after infection, and ACE activity was measured in the granulomas isolated from each liver tissue using a fluorometric method. Oral administration of 0.1 or 1.0 microgram/kg/2 days of 1 alpha (OH)D3 for 4 weeks significantly enhanced ACE activity in the granuloma tissue. Since the DNA content relative to a unit weight of protein in the granulomas did not change with the 1 alpha (OH)D3 treatment, it is suggested that the elevated tissue ACE activity is due to an actual increase of the enzyme activity in each granuloma cell. The present observation may have relevance to sarcoid granulomas characterized by an increased tissue ACE activity, since macrophages from patients with sarcoidosis synthesize a biologically active hormonal form of vitamin D3. Namely hormonal form of vitamin D3 locally produced by macrophages is involved not only in systemic Ca++ metabolism but also in the stimulation of macrophages themselves to produce ACE in the granulomas.

Topics: Animals; Cholecalciferol; Female; Granuloma; Liver; Liver Diseases; Mice; Mice, Inbred BALB C; Peptidyl-Dipeptidase A; Sarcoidosis; Schistosomiasis mansoni

Hypercalcaemia in six patients with sarcoidosis was associated with elevated circulating 1,25-dihydroxy vitamin D3 (187-475 pmol/l): the concentration of this metabolite of vitamin D was a function of the concentration of its precursor, 25-hydroxy vitamin D which remained within the normal range. Corticosteroids, in reducing serum calcium, eliminated this abnormal substrate--product relationship by rapidly reducing circulating 1,25-dihydroxy vitamin D3 while having no effect on 25-hydroxy vitamin D. The fall in circulating 1,25-dihydroxy vitamin D3 preceded the fall of calcium. Studies on the clearance of exogenous 1,25-dihydroxy vitamin D3 indicated that during hypercalcaemic episodes, the plasma disappearance time of the sterol was delayed and that this reverted to normal with steroid therapy. Administration of vitamin D3 to these patients with sarcoidosis increased the circulating concentration of 1,25-dihydroxy vitamin D3 and this resulted in hypercalcaemia, thus accounting for their hypersensitivity to vitamin D and sunlight.

Topics: Adult; Aged; Calcifediol; Calcitriol; Cholecalciferol; Humans; Hydrocortisone; Hypercalcemia; Light; Male; Metabolic Clearance Rate; Middle Aged; Prednisolone; Sarcoidosis

Topics: Acute Kidney Injury; Aged; Bone Marrow Diseases; Cholecalciferol; Female; Humans; Hypercalcemia; Osteoporosis; Sarcoidosis

Topics: Adult; Aged; Bone Diseases; Calcitonin; Child; Cholecalciferol; Ergocalciferols; Humans; Hypercalcemia; Metabolic Diseases; New Zealand; Organophosphonates; Osteitis Deformans; Osteomalacia; Osteoporosis; Parathyroid Hormone; Sarcoidosis; Vitamin D; Vitamin D Deficiency

It is generally recognized that glucocorticoid administration may diminish calcium absorption in vivo as well as the active transport of calcium by the intestine in vitro. Recent studies by others have emphasized the possibility of an alteration in the metabolism of vitamin D to 25-hydroxycholecalciferol in accounting for the steroid effects on calcium absorption. The results obtained in the present studies fail to support this hypothesis. The present studies confirm that the administration of cortisone or other glucocorticoids to the rat interferes with the active transport of calcium by duodenal gut sacs in vitro. This abnormality is not due to an alteration in the permeability of the intestine to calcium, and it cannot be corrected by the administration of either massive doses of vitamin D(2) or modest doses of 25-hydroxycholecalciferol. Experiments concerned with the effects of cortisone on the level of the vitamin D-dependent duodenal calcium-binding protein, the amount of bioassayable vitamin D activity in the mucosa, and the distribution and metabolism of (3)H-vitamin D(3), did not provide evidence in favor of a harmone-related defect in either the localization of vitamin D or its metabolism to 25-hydroxycholecalciferol. Alterations in the transport of iron and D-galactose, not dependent on vitamin D, suggest that cortisone treatment may be responsible for more than a simple antagonism to the effects of vitamin D. The results of the present studies indicate that cortisone administration affects the cellular mechanisms mediating calcium transport in a manner that is opposite to the effects of vitamin D, but seems to be independent of any direct interaction with the parent vitamin or its metabolites. If a disorder in vitamin D metabolism is at all involved, it is at a step subsequent to 25-hydroxylation.

Topics: Animals; Biological Assay; Biological Transport, Active; Calcium; Calcium Chloride; Calcium Isotopes; Cholecalciferol; Cortisone; Drug Antagonism; Duodenum; Galactose; Ileum; Intestinal Mucosa; Intestine, Small; Leucine; Male; Rats; Sarcoidosis; Vitamin D

Topics: Carbon Isotopes; Cholecalciferol; Chromatography; Humans; Hypercalcemia; Nephrectomy; Osteomalacia; Sarcoidosis; Time Factors; Tritium; Vitamin D