Waldenström's macroglobulinemia.
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Biomedical subjects
Publications and source records attributed to L V Avioli.
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Symptomatic osteopenia accompanied by subclinical hyperthyroidism developed in three women who were receiving excess thyroid hormone medication. Excessive thyroid replacement therapy resulted in mild hypercalcemia, hyperphosphatemia, and hyperphosphatasemia associated with diffuse skeletal demineralization and multiple fractures. Nondecalcified sections of double tetracycline-labeled iliac crest bone showed an accelerated rate of bone turnover with marked osteoclastosis and resorption of the cortical as well as the trabecular bone, typical of endogenous hyperthyroidism. Since thyroid hormones are among the most frequently prescribed medications, bone loss caused by exogenous hyperthyroidism may be more common than previously recognized.
Five young men had a similar syndrome of osteopenia and hypercalciuria, probably resorptive and absorptive, with histomorphometric data suggesting decreased bone mass with increased rate of bone formation. A search for causes of osteopenia, either primary or secondary, was unrewarding.
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Classic (type I) renal tubular acidosis in children in attended by growth retardation and rickets, abnormalities that can be corrected by alkali therapy alone. We have employed the NH4Cl-treated rachitic chick as a model to investigate vitamin D metabolism in the acidotic state. NH4Cl ingestion for 96 h was associated with a rise in serum calcium, a significant decrease in blood pH (7.42 +/- 0.08 vs 7.30 +/- 0.08, P less than 0.005), decreased [3H]1,25(OH)2D3 following [3H]25OHD D3 injections, and enhanced metabolic clearance of administered [3H]1,25(OH)2D3. The data collectively suggest that metabolic acidosis in the chick alters the production and degradation of 1,25(OH)2D3.
This study presents measurements of serum vitamin D metabolites, calcium and phosphorus as well as measurements of the equilibrium dissociation constant for duodenal 1,25(OH)2D3 receptor in 15-, 18-, 19-, and 20-day chick embryos in comparison to that in 1- and 118-day-old chicks and to vitamin D-deficient chicks. The present results showed that: (a) serum 1,25(OH)2D and 24,25(OH)2D levels rise from 15 and 18 to days 19 and 20 of embryonic development while serum phosphate levels are stable; (b) serum calcium levels rise at hatching to adult levels; (c) the duodenal 1,25(OH)2D3 receptor is detectable in 15-day-old embryo and has a Kd similar to that of 118-day-old vitamin D-replete chicks; and (d) the activity of 1,25(OH)2D3 receptor in chick duodenal cytosol is maximal at hatching.
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Twenty-six women with untreated postmenopausal osteoporosis underwent iliac crest biopsy following tetracycline-labeling and mineral metabolism studies. Histomorphometric assessment of their bone remodeling rates, including formation determined by the tetracycline-labeling technique, revealed considerable variation. Eight women had no evidence of active bone formation (inactive remodeling osteoporosis), whereas the others showed a spectrum of bone formation rates (active remodeling osteoporosis). Clinical and biochemical studies failed to predict the histomorphometric findings. Postmenopausal osteoporosis is a histologically heterogeneous disorder with morphologic expression in bone that cannot be predicted by single or combined routine clinical and laboratory parameters. Bone biopsy, necessary to identify the histologic lesion and assess skeletal dynamics, may prove to be important for optimal therapy of osteoporosis, as a variety of agents--with different effects on bone remodeling--are available.
Calcium homeostasis was studied in freely fed control, streptozotocin diabetic, long-term and short-term insulin-treated diabetic rats 7 wk after the induction of diabetes. In contrast to the short-term (5-12 day) diabetic rat model, intestinal absorption of calcium was markedly enhanced in chronically insulin-deficient animals. Moreover, conventional balance studies showed that these animals were in positive calcium balance despite severe hypercalciuria. Intestinal hyperabsorption of calcium in long-standing diabetic rats occurred despite low levels of circulating 1,25-dihydroxyvitamin D and hypercorticosteronism and was attended by hypercalcemia and suppression of both plasma parathyroid hormone (PTH) and urinary cyclic 3',5'-AMP (cAMP). Long-term insulin replacement completely normalized the intestinal hyperabsorption of calcium, corrected the plasma calcium, and significantly increased circulating PTH and urinary cAMP excretion. Insulin therapy also corrected the decreased plasma 1,25-dihydroxyvitamin D observed in untreated diabetic animals. Intestinal hyperabsorption of calcium appeared to be only partially corrected by short-term insulin therapy. The accumulated results reveal decided differences in calcium homeostasis and hormonal response between the rats with long-standing diabetes and those with diabetes of short duration.
Primary monolayer cultures of cells from normal mouse kidney were initiated and maintained in serum-free medium supplemented with insulin, transferrin and prostaglandin E1. Renal epithelial cells grow to confluence without detectable growth of fibroblasts. These cells contain an active 25(OH)D3 1-hydroxylase with half-maximal formation of 1,25(OH)2D3 achieved at a substrate concentration of 13.3 nM. Activity of this enzyme is increased by low calcium medium or parathyroid hormone and decreased by high calcium medium, high phosphate medium or 1,25(OH)2D3.
We have attempted to determine if the resistance of the X-linked hypophosphatemic mouse to the actions of 1,25(OH)2D3 is due to abnormal cytosolic receptors for this hormone. Cytoplasmic 1,25-dihydroxy-vitamin D3 [1,25(OH)3D3] receptors were demonstrated in hypophosphatemic (HYP) mouse tissues including intestine, kidney and testis. Cytosol preparations from 14 murine tissues were prepared using hypertonic buffer and incubated for three hours at 0 C with 1,25(OH)2 [23,24(n)-(-3)H]D3 ([3H]-1,25(OH)2D3). The results of studies using 5-20% sucrose density gradients revealed th at cytosol preparations from intestine, kidney and testis exhibited a 3.2 S peak which ws specific for 1,25(OH)2D3. Scatchard analysis of intestinal, renal and testicular cytosol preparations of Hyp mice revealed a single class of noninteracting binding sites with a range of equilibrium dissociation constants (KD) of 0.9-3.5 X 10(-10) M, and a range of specific binding sites of 15-317 fmol/mg protein. There were no significant differences in values of KD, and numbers of specific binding sites among Hyp and control mice. We conclude the reported resistance of Hyp mice to vitamin D is not due to abnormal 1,24(OH)2D3 receptor in Hyp mouse.
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