Full Access
Pathogenesis and medical treatment of secondary hyperparathyroidism
Masafumi Fukagawa MD,
Kiyoshi Kurokawa MD,
Masafumi Fukagawa MD
First Department of Internal Medicine, University of Tokyo School of Medicine, Tokyo, Japan
Search for more papers by this authorCorresponding Author
Kiyoshi Kurokawa MD
Tokai University Faculty of Medicine, Kanagawa, Japan
Dean's Office, Tokai University Faculty of Medicine, Boseidai, Isehara-shi, Kanagawa 259-11, JapanSearch for more papers by this authorMasafumi Fukagawa MD,
Kiyoshi Kurokawa MD,
Masafumi Fukagawa MD
First Department of Internal Medicine, University of Tokyo School of Medicine, Tokyo, Japan
Search for more papers by this authorCorresponding Author
Kiyoshi Kurokawa MD
Tokai University Faculty of Medicine, Kanagawa, Japan
Dean's Office, Tokai University Faculty of Medicine, Boseidai, Isehara-shi, Kanagawa 259-11, JapanSearch for more papers by this authorFirst published: 07 December 1998
Citations: 8
Abstract
Control of hyperparathyroidism is a major goal of the management of bone diseases in chronic dialysis patients. Severity of hyperparathyroidism has been evaluated mainly by the level of parathyroid hormone (PTH), however, parathyroid size can be another critical marker. Patients with larger parathyroid glands are usually more resistant to calcitriol pulse therapy than those with smaller glands. Large parathyroid glands with nodular hyperplasia are composed of cells more resistant to calcitriol due to lower density of calcitriol receptors. Responsiveness to calcitriol therapy was restored by selective destruction of large parathyroid glands (> 0.5 cm3) by ethanol injections under ultrasonographic guidance. Direct injections of calcitriol solution into enlarged glands were also effective in suppressing PTH and restoring responsiveness to calcitriol. These data suggest that size of parathyroid glands reflects the resistance to calcitriol and that prevention of parathyroid hyperplasia is mandatory for the successful medical management of hyperparathyroidism in chronic renal failure. Semin. Surg. Oncol. 13:73–77. © 1997 Wiley-Liss, Inc.
References
- 1 Malluche H, Faugere MC: Renal bone disease 1990: An unmet challenge for the nephrologist. [Review] Kidney Int 1990; 38: 192–211.
- 2 Akizawa T, Fukagawa M, Koshikawa S, Kurokawa K: Recent progress in management of secondary hyperparathyroidism of chronic renal failure. Curr Opin Nephrol Hypertens 1993; 2: 558–565.
- 3 Coburn JW, Llach F: Renal osteodystrophy. In RG Narins (ed): “ Maxwell and Kleeman's Clinical Disorders of Fluid and Electrolyte Metabolism.” 5th ed. New York: McGraw Hill, 1994, 1299–1377.
- 4 Felsenfeld AJ, Llach F: Parathyroid function in chronic renal failure [editorial]. Kidney Int 1993; 43: 771–789.
- 5 Kremer R, Boliver I, Goltzman D, Hendy GN: Influence of calcium and 1,25-dihydroxycholecalciferol on proliferation and proto-oncogene expression in primary cultures of bovine parathyroid cells. Endocrinology 1989; 125: 935–941.
- 6 Brown EM, Gamba G, Riccardi D, et al.: Cloning and characterization of an extracellular Ca2+ sensing receptor from bovine parathyroid. Nature 1993; 366: 575–580.
- 7 Szabo A, Merke J, Beier E, et al.: 1,25(OH)2 vitamin D3 inhibits parathyroid cell proliferation in experimental uremia. Kidney Int 1989; 35: 1049–1056.
- 8 Slatopolsky EA, Weerts C, Thielan J, et al.: Marked suppression of secondary hyperparathyroidism by intravenous administration of 1,25-dihydroxycholecalciferol in uremic patients. J Clin Invest 1984; 74: 2136–2143.
- 9 Delmez JA, Tindira C, Grooms P, et al.: Parathyroid hormone suppression by intravenous 1,25- dihydroxyvitamin D . A role for increased sensitivity to calcium. J Clin Invest 1989; 83: 1349–1355.
- 10 Fukagawa M, Okazaki R, Takano K, et al.: Regression of parathyroid hyperplasia by calcitriol-pulse therapy in patients on long-term dialysis. N Engl J Med 1990; 323: 421–422.
- 11 Fukagawa M, Kaname S, Igarashi T, et al.: Regulation of parathyroid hormone synthesis in chronic renal failure in rats. Kidney Int 1991; 39: 874–881.
- 12 Korkor AB: Reduced binding of [3H] 1,25-dihydroxyvitamin D3 in the parathyroid glands of patients with renal failure. N Engl J Med 1987; 316: 1573–1577.
- 13 Brown AJ, Dusso A, Lopez-Hilker S, et al.: 1,25-(OH)2D receptors are decreased in parathyroid glands from chronically uremic dogs. Kidney Int 1989; 35: 19–23.
- 14 Naveh-Many T., Marx R, Keshet E, et al.: Regulation of 1,25- dihydroxyvitamin D3 receptor gene expression by 1,25- dihydroxyvitamin D3 in the parathyroid in vivo. J Clin Invest 1990; 86: 1968–1975.
- 15 Hsu CH, Patel SR, Young EW, Vanholder R: The biological action of calcitriol in renal failure. [Editorial] [Review] Kidney Int 1994; 46: 605–612.
- 16 Lopez-Hilker S, Dusso AS, Rapp NS, et al.: Phosphorus restriction reverses secondary hyperparathyroidism in uremia independent of changes in calcium and calcitriol. Am J Physiol 1990; 259(3 Pt 2): F432–437.
- 17 Yi H, Fukagawa M, Yamato H, et al.: Prevention of enhanced parathyroid hormone secretion, synthesis and hyperplasia by mild dietary phosphorus restriction in early chronic renal failure in rats: Possible direct role of phosphorus. Nephron 1995; 70: 242–248.
- 18 Slatopolsky E, Finch J, Denda M, et al.: Phosphorus restriction prevents parathyroid gland growth. High phosphorus directly stimulates PTH secretion in vitro. J Clin Invest 1996; 96: 7534–2540.
- 19 Almaden Y, Canalejo A, Hernandez A, et al.: Direct effect of phosphorus on PTH secretion from whole rat parathyroid glands in vitro. J Bone Miner Res 1996; 7: 970–976.
- 20 Sriussadaporn S, Wong MS, Pike JW, Favus MJ: Tissue specificity and mechanism of vitamin D receptor up-regulation during dietary phosphorus restriction in the rat. J Bone Miner Res 1995; 10: 271–280.
- 21 Ureña P, Kubrusly M, Mannstadt M, et al.: The renal PTH/PTHrP receptor is down-regulated in rats with chronic renal failure. Kidney Int 1994; 45: 605–611.
- 22 Fukagawa M, Kitaoka M, Yi H, et al.: Serial evaluation of parathyroid size by ultrasonography is another useful marker for the longterm prognosis of calcitriol pulse therapy in chronic dialysis patients. Nephron 1994; 68: 221–228.
- 23 Tominaga Y, Takagi H: Molecular genetics of hyperparathyroid disease. Curr Opin Nephrol Hypertens 1996; 5: 336–341.
- 24 Fukuda N, Tanaka H, Tominaga Y, et al.: Decreased 1,25- dihydroxyvitamin D3 receptor density is associated with a more severe form of a parathyroid hyperplasia in chronic uremic patients. J Clin Invest 1993; 92: 1436–1443.
- 25 Drüeke TB: The pathogenesis of parathyroid gland hyperplasia in chronic renal failure. [Review] Kidney Int 1995; 48: 259–272.
- 26 Falchetti A, Bale AE, Amorosi A, et al.: Progression of uremic hyperparathyroidism involves allelic loss on chromosome 11. J Clin Endocrinol Metab 1993; 76: 139–144.
- 27 Quarles LD, Lobaugh B, Murphy G: Intact parathyroid hormone overestimates the presence and severity of parathyroid-mediated osseous abnormalities in uremia. J Clin Endocrinol Metab 1992; 75: 145–150.
- 28 Hercz G, Pei Y, Greenwood C, et al.: A plastic osteodystrophy without aluminum: The role of “suppressed” parathyroid function. Kidney Int 1993; 44: 860–866.
- 29 Goodman WG, Ramirez JA, Belin TR, et al.: Development of adynamic bone in patients with secondary hyperparathyroidism after intermittent calcitriol therapy. Kidney Int 1994; 46: 1160–1166.
- 30 Kurokawa K, Akizawa T, Suzuki M, et al.: Effect of 22-oxacalcitriol on hyperparathyroidism of dialysis patients: results of a preliminary study. Nephrol Dial Transplant 1996; 11: 121–129.
- 31 Fox J, Hadfield S, Petty BA, et al.: NPS R-568 inhibits parathyroid hormone secretion and stimulates calcitonin secretion in hyperparathyroid rats with chronic renal failure [abstract]. J Am Soc Nephrol 1993; 4: 719.
- 32 Giangrande A, Castiglioni A, Sorbiati L, Allaria P: Ultrasound guided percutaneous fine needle ethanol injection into parathyroid glands in secondary hyperparathyroidism. Nephrol Dial Transplant 1992; 7: 412–421.
- 33 Kitaoka M, Fukagawa M, Ogata E, Kurokawa K: Reduction of functioning parathyroid cell mass by ethanol injection in chronic dialysis patients. Kidney Int 1994; 46: 1110–1117.
- 34 Kitaoka M, Fukagawa M, Kurokawa K: Direct injection of calcitriol into parathyroid hyperplasia in chronic dialysis patients with severe parathyroid hyperfunction. Nephrology 1995; 1: 563–568.
- 35 Kazama J, Fukagawa M, Yi H, et al.: 24R,25-dihydroxyvitamin D3 ameliorates the high-turnover bone diseases without suppression parathyroid function in chronic renal failure in rats. Nephrology 1996; 2: 361–366.
- 36 Kazama JJ, Fukagawa M, Yi H, et al.: Fine structure of trabecular bone in uremic rats analyzed by microfocus X-ray imaging. [Abst] J Bone Miner Res 1996; 11: S490.
