cholecalciferol and Hyperplasia

The results of recent studies suggest that uremic patients with large parathyroid hyperplasia are often resistant to active vitamin D3 therapy. Percutaneous ethanol injection has become an interesting option in such cases, although there are only a few publications on that subject. In this work we would like to present our experience with this method. 20 patients with serum iPTH > 400 pg/ml and 1-4 hyperplastic parathyroids (mean volume 1.07) underwent 56 percutaneous ethanol injection sessions under ultrasonographic guidance. In 9 patients a marked (> 75%), long-term (12-24 months) decrease in serum iPTH was achieved; lesser (> 50%) reduction in parathyroid activity persisted for 36-42 months in 5 out of 9 patients observed in this period. In almost every patient a significant reduction of alphacalcidol dose was possible. Our data confirm that percutaneous ethanol injection therapy is a useful and safe adjunct in severe uremic hyperparathyroidism treatment strategy which allows to restore the responsiveness to active vitamin D3 metabolites.

Topics: Adult; Aged; Cholecalciferol; Drug Resistance; Ethanol; Female; Humans; Hyperparathyroidism; Hyperplasia; Injections, Subcutaneous; Male; Middle Aged; Parathyroid Glands; Parathyroid Hormone; Ultrasonography; Uremia

Secondary hyperparathyroidism (2HPT), which is related to renal osteodystrophy (ROD), may occur in patients in the comparatively early stage of chronic renal failure (CRF). Secondary hyperparathyroidism patients with parathyroid hyperplasia showed resistance to vitamin D(3) treatment during long-term dialysis. At present, evaluation by ultrasonography is considered to be useful for confirming parathyroid hyperplasia. There are no clinical data associated with imaging evaluation of 2HPT in CRF patients. In the present study, the relationship among clinical and biochemical data, and parathyroid hyperplasia by ultrasonography, was evaluated in 12 patients (six males and six females) with end-stage renal failure (ESRF) before and at initiation of dialysis. Five patients showed an enlargement of parathyroid glands in ultrasonography. Levels of serum-intact parathyroid hormone (PTH) in patients with parathyroid hyperplasia (positive group) were significantly higher than in those without hyperplasia (negative group; 97.6 +/- 36.65 vs 17.4 +/- 4.45 pmol/L; P < 0.05). The levels of intact PTH were above 35.0 pmol/L in all five patients with hyperplasia. All patients in the positive group had never taken vitamin D(3) supplements. Calcium-containing phosphate binders were not prescribed before the present study, except in one patient. Parathyroid hyperplasia caused by 2HPT was recognized in patients before and at initiation of dialysis in this study. It appears that untreated 2HPT in CRF patients may progress to advanced 2HPT in ESRF before and/or after the early stage of dialysis. The levels of serum intact PTH are useful in predicting parathyroid hyperplasia.

Topics: Adult; Aged; Alkaline Phosphatase; Biomarkers; Calcium; Calcium Carbonate; Cholecalciferol; Dialysis; Female; Humans; Hyperparathyroidism, Secondary; Hyperplasia; Kidney Failure, Chronic; Male; Middle Aged; Parathyroid Glands; Parathyroid Hormone; Ultrasonography, Doppler, Color; Vitamins

Adrenal medullary hyperplasia and pheochromocytomas are induced in rats by a variety of non-genotoxic agents, and we have hypothesized that these agents induce lesions indirectly by stimulating chromaffin cell proliferation. Vitamin D3, which has not been previously associated with adrenal medullary proliferative lesions, is the most potent in vivo stimulus to chromaffin cell proliferation yet identified. The present investigation utilized the vitamin D3 model to prospectively test the relationship between mitogenicity and focal proliferative lesions in the adrenal medulla and to determine early events in the pathogenesis of these lesions. Charles River Crl:CD BR rats were treated with 0; 5000; 10,000; or 20,000 IU/kg/day of vitamin D3 in corn oil (5 ml/kg) by oral intubation. Rats were killed after 4, 8, 12, or 26 weeks of treatment, following a final week of labeling with bromodeoxyuridine (BrdU) using a mini-pump. Adrenal sections were double-stained for BrdU and phenylethanolamine-N-methyl transferase (PNMT) to discriminate epinephrine (E) from norepinephrine (NE) cells or for vesicular acetylcholine transporter (VAchT) to identify cholinergic nerve endings. Vitamin D3 caused a 4-5-fold increase in BrdU labeling at week 4, diminishing to a 2-fold increase by week 26. An initial preponderance of labeled E cells gave way to a preponderance of labeled NE cells. By week 26, 17/19 (89%) animals receiving the 2 highest doses of vitamin D3 had focal adrenal medullary proliferative lesions, in contrast to an absence of lesions in control rats. The lesions encompassed a spectrum including BrdU-labeled "hot spots" not readily visible on H and E sections, hyperplastic nodules, and pheochromocytomas. Lesions were usually multicentric, bilateral, and peripheral in location, and almost all were PNMT-negative. The lesions were not cholinergically innervated, suggesting autonomous proliferation. Hot spots, hyperplastic nodules, and pheochromocytomas appear to represent a continuum rather than separate entities. Their development might involve selective responses of chromaffin cell subsets to mitogenic signals, influenced by both innervation and corticomedullary interactions. A number of non-genotoxic compounds that induce pheochromocytomas in rats are known to affect calcium homeostasis. The results of this study provide further evidence to support the hypothesis that altered calcium homeostasis is indirectly involved in the pathogenesis of pheochromocytomas, via eff

Topics: Administration, Oral; Adrenal Gland Neoplasms; Adrenal Medulla; Animals; Body Weight; Bromodeoxyuridine; Carcinogenicity Tests; Carrier Proteins; Cholecalciferol; Cholinergic Fibers; Epinephrine; Hyperplasia; Kidney; Male; Membrane Transport Proteins; Nephrocalcinosis; Norepinephrine; Organ Size; Pheochromocytoma; Rats; Rats, Sprague-Dawley; Vesicular Acetylcholine Transport Proteins; Vesicular Transport Proteins

Although a high dose of vitamin D3 is known to cause arterial calcification and degeneration, its effect on intimal hyperplasia has never been studied. The aim of this study was to examine the influence of a moderate supplement of vitamin D3 on intimal hyperplasia in the balloon-injured rat carotid artery. Forty-four rats had balloon injury to the carotid artery; 22 were given oral vitamin D3 supplementation (0.25 microgram kg-1 day-1). Animals were killed at 4 weeks and the carotid arteries were perfusion fixed and assessed morphometrically by means of computerized image analysis of transverse sections. Mean (s.e.m.) intimal area was significantly greater in the vitamin D3-treated animals than in controls: 0.92(0.05) versus 0.71(0.07) mm2 (P = 0.02). The area of the media of both injured and uninjured arteries was not influenced by vitamin D3 administration. A small dose of vitamin D3 resulted in significant exacerbation of intimal hyperplasia in this rat carotid artery model and raises the question of the role of dietary vitamin D3 in restenosis following vascular intervention.

Topics: Animals; Carotid Artery Injuries; Carotid Artery, Common; Catheterization; Cholecalciferol; Hyperplasia; Male; Rats; Rats, Inbred WF; Tunica Intima

Ultrastructural observation was performed in C cells of sheep injected intramuscularly with a dose of 2 million IU of vitamin D3 daily for 10 days, 20 days and 30 days, respectively. After treatment with vitamin D3, hyperplasia and hypertrophy of C cells were noticed mainly at the periphery of the thyroid follicles. Most of hypertrophied C cells degranulated conspicuously and contained many prosecretory granules near the well developed Golgi apparatus which were in the actively secreting and packaging phase of their secretory cycle. The other C cells had prominent lamellar arrays of rough-endoplasmic reticulum and aggregations of free ribosomes in the cytoplasm which were interpreted to be in the actively synthesizing phase of their secretory cycle. Atrophic C cells which contained degenerative organelles in the cytoplasm were occasionally observed among the hypertrophied C cells. The present ultrastructural findings clarified that C cells synthesize and secrete calcitonin continuously due to prolonged hypercalcemia induced by long-term administration of excessive doses of vitamin D3 in sheep.

Topics: Animals; Cholecalciferol; Cytoplasmic Granules; Endoplasmic Reticulum; Golgi Apparatus; Hyperplasia; Hypertrophy; Injections, Intramuscular; Male; Microscopy, Electron; Mitochondria; Ribosomes; Sheep; Thyroid Gland

Hyperplasia and hypertrophy of C cells were demonstrated in sheep with hypercalcaemia induced by administration of vitamin D3 (2 million I.U. per day). After treatment with vitamin D3 for 10, 20 or 30 days, serum calcium values increased to 10.28, 11.86 and 10.44 mg per dl, respectively, compared to a normal concentration of around 9 mg per dl. Immunohistochemical reactions of calcitonin, chromogranin A and calcitonin gene-related peptide (CGRP) decreased, whereas intense neurone-specific enolase (NSE) immunoreactivity was noted in C cells. Immunohistochemical staining with anti-calcitonin, anti-chromogranin A, anti-CGRP and anti-NSE antisera was useful to demonstrate the functional state of stimulated C cells in sheep with hypercalcaemia.

Topics: Animals; Calcitonin; Calcitonin Gene-Related Peptide; Calcium; Cholecalciferol; Chromogranin A; Chromogranins; Hypercalcemia; Hyperplasia; Hypertrophy; Phosphopyruvate Hydratase; Sheep; Thyroid Gland

Topics: Animals; Calcitonin; Calcitonin Gene-Related Peptide; Cholecalciferol; Chromogranin A; Chromogranins; Hyperplasia; Hypertrophy; Immunohistochemistry; Male; Phosphopyruvate Hydratase; Rabbits; Somatostatin; Thyroid Gland

Topics: Animals; Cholecalciferol; Endocrine Glands; Fishes; Hypercalcemia; Hyperplasia; Male

Hypercalcemia was induced in Clarias batrachus by treating them with vitamin D3 (5,000 I.U./100 g body wt.) and/or 0.5% solution of CaCl2. The animals were killed on 1st, 3rd, 5th, 9th, 13th and 17th days after the initiation of the experiment. Histological preparations of the ultimobranchial gland (UBG) were made. The gland exhibits nuclear hypertrophy, hyperplasia and loss of staining response corresponding to the rise in serum calcium levels. At later intervals, the UBG shows exhaustion and degeneration which is evident from vacuolization and nuclear shrinkage of the ultimobranchial cells after day 13 in groups B and C and day 9 in group D.

Topics: Animals; Calcium Chloride; Cholecalciferol; Fishes; Hyperplasia; Hypertrophy; Male; Staining and Labeling; Time Factors; Ultimobranchial Body

Topics: Animals; Calcitonin; Calcium; Cholecalciferol; Chromatin; Cytoplasm; Dogs; Endoplasmic Reticulum; Epithelial Cells; Female; Glycogen; Histocytochemistry; Hypercalcemia; Hyperplasia; Hypertrophy; Male; Microscopy, Electron; Parathyroid Glands; Thyroid Gland