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Ketoconazole Decreases the Serum Ionized Calcium and 1,25-Dihydroxyvitamin D Levels in Tuberculosis-Associated Hypercalcemia

Ketoconazole Decreases the Serum Ionized Calcium and 1,25-Dihydroxyvitamin D Levels in... Abstract • Objective. —To evaluate whether tuberculosis-associated hypercalcemia is related to abnormal synthesis of 1,25-dihydroxyvitamin D (1,25[OH]2D) and whether ketoconazole administration may be useful in treating tuberculosis-associated hypercalcemia. Design. —Case study. Setting. —Endocrine Unit, Pediatric Clinic, University of Pisa (Italy). Participants. —Two boys (aged 10.5 years and 14.7 years) with active tuberculosis and hypercalcemia. Measurements/Main Results. —At admission, serum 1,25-dihydroxyvitamin D levels were elevated. Oral ketoconazole administration (3.0 mg/kg every 8 hours) decreased 1,25-dihydroxyvitamin D levels within the first week of therapy (from 208.8 to 57.6 pmol/L [−72.4%] in one boy and from 321.6 to 115.2 pmol/L [−64.2%] in the other). We also found a coincident normalization of serum ionized calcium concentration (from 1.45 to 1.24 mmol/L [−13.0%] in one boy and from 1.55 to 1.26 mmol/L [−17.0%] in the other). Conclusions. —Abnormal elevated levels of 1,25-dihydroxyvitamin D caused hypercalcemia in our patients; ketoconazole administration may be effective in the treatment of hypercalcemia in patients with tuberculosis, which decreases 1,25-dihydroxyvitamin D synthesis.(AJDC. 1993;147:270-273) References 1. Shai F, Baker RK, Addrizzo JR, Wallach S. Hypercalcemia in mycobacterium infection . J Clin Endocrinol. 1972;34:251-256.Crossref 2. Abbasi AA, Chemplavil JK, Farah S, Muller BF, Arnstein AR. Hypercalcemia in active pulmonary tuberculosis . Ann Intern Med. 1979;90:324-328.Crossref 3. Kitrou MP, Phytou-Pallikari A, Tzannes SE, Virvidakis K, Mountolakis TD. Serum calcium during chemotherapy of active pulmonary tuberculosis . Eur J Respir Dis. 1983;64:347-354. 4. Davies PDO, Brown RC, Woodhead JS. Serum concentrations of vitamin D metabolites in untreated tuberculosis . Thorax . 1985;40:187-190.Crossref 5. Lind L, Ljunghall S. Hypercalcemia in pulmonary tuberculosis . Ups J Med Sci. 1990;95:157-160.Crossref 6. Shek CC, Natkunam A, Tsang V, Cockram CS, Swaminathan R. Incidence, causes and mechanism of hypercalcemia in a hospital population in Hong Kong . Q J Med. 1990;284:1277-1285.Crossref 7. Gerritsen J, Knol K. Hypercalcemia in a child with miliary tuberculosis . Eur J Pediatr. 1989;148:650-651.Crossref 8. Saggese G, Bertelloni S, Baroncelli GI, Fusaso C, Gualtieri M. Abnorme sintesi di 1,25-diidrossivitamina D ed ipercalcemia in bambini con tubercolosi . Pediatr Med Chir . 1989;11:529-532. 9. Davies PDO, Church HA, Brown RC, Charumilind A, Bejrachandra S, Bovornkitti S. Serum vitamin D and calcium metabolism in tuberculosis patients resident in two tropical environments . In: Norman AW, Schaefer K, Grigoleit HG, Van Herrath D, eds. Vitamin D: Molecular, Cellular and Clinical Endocrinology . Berlin, Germany; W de Gruyter & Co; 1988:979-980. 10. De Luca HF, Krisinger J, Darwish H. The vitamin D system: 1990 . Kidney Int. 1990;38 ( (suppl 29) ):S2-S8. 11. Epstein S, Stern PH, Bell NH, Dowdeswell I, Turner RT. Evidence for abnormal regulation of circulating 1,25-dihydroxyvitamin D in patients with pulmonary tuberculosis and normal calcium metabolism . Calcif Tissue Int. 1984;36:541-544.Crossref 12. Bell NH, Shary J, Shaw S, et al. Hypercalcemia associated with increased circulatory 1,25-dihydroxyvitamin D in a patient with pulmonary tuberculosis . Calcif Tissue Int. 1985;37:588-591.Crossref 13. Felsenfeld AJ, Drezner MK, Llach F. Hypercalcemia and elevated calcitriol in a maintenance dialysis patient with tuberculosis . Arch Intern Med. 1986;146:1941-1945.Crossref 14. Adams JS, Singer FR, Gacad MA, et al. Isolation and structural identification of 1,25-dihydroxyvitamin D produced by cultured alveolar macrophages in sarcoidosis . J Clin Endocrinol Metab. 1985;60:960-966.Crossref 15. Insogna KL, Dreyer BE, Mitnick M, Ellison AF, Broadus AE. Enhanced production rate of 1,25-dihydroxyvitamin D in sarcoidosis . J Clin Endocrinol Metab. 1988;66:72-75.Crossref 16. Henry HL. Effect of ketoconazole and miconazole on 25-hydroxyvitamin D in metabolism by cultured chick kidney cells . J Steroid Biochem . 1985;23:991-995.Crossref 17. Glass AR, Eil C. Ketoconazole-induced reduction in serum 1,25-dihydroxyvitamin D . J Clin Endocrinol Metab. 1986;63:766-769.Crossref 18. Saggese G, Ghirri P, Bertelloni S, Baroncelli GI, Cosenza G. Effects of ketoconazole on gonadal function and 1,25-dihydroxyvitamin D . Horm Res. 1987;28:287-288. 19. Glass AR, Eil C. Ketoconazole-induced reduction in serum 1,25-dihydroxyvitamin D and total serum calcium in hypercalcemic patients . J Clin Endocrinol Metab. 1988;66:934-938.Crossref 20. Adams JS, Sharma OP, Diz MM, Endres DB. Ketaconazole decreases the serum 1,25-dihydroxyvitamin D and calcium concentrations in sarcoidosis-associated hypercalcemia . J Clin Endocrinol Metab. 1990;70: 1090-1095.Crossref 21. Glass AR, Cerletty JM, Elliott W, Leman J, Gray RW, Eil C. Ketoconazole reduces elevated serum levels of 1,25-dihydroxyvitamin D in hypercalcemic sarcoidosis . J Endocrinol Invest . 1990;13:407-413.Crossref 22. Snider DE Jr, Rieder HL, Combs D, Bloch AB, Hayden CH, Smith MH. Tuberculosis in children . Pediatr Infect Dis J. 1988;7:271-278.Crossref 23. Saggese G, Bertelloni S, Baroncelli Gl, Perri G, Calderazzi A. Mineral metabolism and calcitriol therapy in idiopathic juvenile osteoporosis . AJDC . 1991;145:457-462. 24. Saggese G, Baroncelli Gl, Bertelloni S. Determination of parathyrin by immunoradiometric assay evaluated in normal children and in patients with various disorders of calcium metabolism . Clin Chem. 1991;37:1999-2001. 25. Need AG, Philips PJ, Chiu FTS, Prisk HM. Hypercalcemia associated with tuberculosis . BMJ . 1980;282:831.Crossref 26. Sena SF, Bowers GN Jr. Measurements of ionized calcium in biological fluids: ion-selective electrode method . Methods Enzymol . 1988;158: 320-334. 27. Cadranel J, Milleron B, Garabedian M, Aroun G. Serum concentrations of vitamin D metabolites in untreated tuberculosis . Thorax . 1985;40:639-640.Crossref 28. Cadranel J, Garabedian M, Milleron B, Guillozo H, Akoun G, Hance AJ. 1,25(OH),D3 production by lymphocytes and alveolar marcrophages recovered by lavage from normocalcemic patients with tuberculosis . J Clin Invest . 1990;85:1588-1593.Crossref 29. Reichel H, Koeffler HP, Barbers R, Norman AW. Regulation of 1,25-dihydroxyvitamin D production by cultured alveolar macrophages from normal human donors and from patients with puylmonary sarcoidosis . J Clin Endocrinol Metab. 1987;65:1201-1209.Crossref 30. Sonino N. The endocrine effects of ketoconazole . J Endocrinol Invest . 1986;9:341-347.Crossref 31. Bia MJ, Insogna K. Treatment of sarcoidosis-associated hypercalcemia with ketoconazole . Am J Kidney Dis. 1991;18:702-705.Crossref 32. Breckenridge A. Clinical significance of interactions with antifungal agents . Br J Dermatol. 1992;126 ( (suppl 39) ):19-22.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Diseases of Children American Medical Association

Ketoconazole Decreases the Serum Ionized Calcium and 1,25-Dihydroxyvitamin D Levels in Tuberculosis-Associated Hypercalcemia

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References (33)

Publisher
American Medical Association
Copyright
Copyright © 1993 American Medical Association. All Rights Reserved.
ISSN
0002-922X
DOI
10.1001/archpedi.1993.02160270032013
Publisher site
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Abstract

Abstract • Objective. —To evaluate whether tuberculosis-associated hypercalcemia is related to abnormal synthesis of 1,25-dihydroxyvitamin D (1,25[OH]2D) and whether ketoconazole administration may be useful in treating tuberculosis-associated hypercalcemia. Design. —Case study. Setting. —Endocrine Unit, Pediatric Clinic, University of Pisa (Italy). Participants. —Two boys (aged 10.5 years and 14.7 years) with active tuberculosis and hypercalcemia. Measurements/Main Results. —At admission, serum 1,25-dihydroxyvitamin D levels were elevated. Oral ketoconazole administration (3.0 mg/kg every 8 hours) decreased 1,25-dihydroxyvitamin D levels within the first week of therapy (from 208.8 to 57.6 pmol/L [−72.4%] in one boy and from 321.6 to 115.2 pmol/L [−64.2%] in the other). We also found a coincident normalization of serum ionized calcium concentration (from 1.45 to 1.24 mmol/L [−13.0%] in one boy and from 1.55 to 1.26 mmol/L [−17.0%] in the other). Conclusions. —Abnormal elevated levels of 1,25-dihydroxyvitamin D caused hypercalcemia in our patients; ketoconazole administration may be effective in the treatment of hypercalcemia in patients with tuberculosis, which decreases 1,25-dihydroxyvitamin D synthesis.(AJDC. 1993;147:270-273) References 1. Shai F, Baker RK, Addrizzo JR, Wallach S. Hypercalcemia in mycobacterium infection . J Clin Endocrinol. 1972;34:251-256.Crossref 2. Abbasi AA, Chemplavil JK, Farah S, Muller BF, Arnstein AR. Hypercalcemia in active pulmonary tuberculosis . Ann Intern Med. 1979;90:324-328.Crossref 3. Kitrou MP, Phytou-Pallikari A, Tzannes SE, Virvidakis K, Mountolakis TD. Serum calcium during chemotherapy of active pulmonary tuberculosis . Eur J Respir Dis. 1983;64:347-354. 4. Davies PDO, Brown RC, Woodhead JS. Serum concentrations of vitamin D metabolites in untreated tuberculosis . Thorax . 1985;40:187-190.Crossref 5. Lind L, Ljunghall S. Hypercalcemia in pulmonary tuberculosis . Ups J Med Sci. 1990;95:157-160.Crossref 6. Shek CC, Natkunam A, Tsang V, Cockram CS, Swaminathan R. Incidence, causes and mechanism of hypercalcemia in a hospital population in Hong Kong . Q J Med. 1990;284:1277-1285.Crossref 7. Gerritsen J, Knol K. Hypercalcemia in a child with miliary tuberculosis . Eur J Pediatr. 1989;148:650-651.Crossref 8. Saggese G, Bertelloni S, Baroncelli GI, Fusaso C, Gualtieri M. Abnorme sintesi di 1,25-diidrossivitamina D ed ipercalcemia in bambini con tubercolosi . Pediatr Med Chir . 1989;11:529-532. 9. Davies PDO, Church HA, Brown RC, Charumilind A, Bejrachandra S, Bovornkitti S. Serum vitamin D and calcium metabolism in tuberculosis patients resident in two tropical environments . In: Norman AW, Schaefer K, Grigoleit HG, Van Herrath D, eds. Vitamin D: Molecular, Cellular and Clinical Endocrinology . Berlin, Germany; W de Gruyter & Co; 1988:979-980. 10. De Luca HF, Krisinger J, Darwish H. The vitamin D system: 1990 . Kidney Int. 1990;38 ( (suppl 29) ):S2-S8. 11. Epstein S, Stern PH, Bell NH, Dowdeswell I, Turner RT. Evidence for abnormal regulation of circulating 1,25-dihydroxyvitamin D in patients with pulmonary tuberculosis and normal calcium metabolism . Calcif Tissue Int. 1984;36:541-544.Crossref 12. Bell NH, Shary J, Shaw S, et al. Hypercalcemia associated with increased circulatory 1,25-dihydroxyvitamin D in a patient with pulmonary tuberculosis . Calcif Tissue Int. 1985;37:588-591.Crossref 13. Felsenfeld AJ, Drezner MK, Llach F. Hypercalcemia and elevated calcitriol in a maintenance dialysis patient with tuberculosis . Arch Intern Med. 1986;146:1941-1945.Crossref 14. Adams JS, Singer FR, Gacad MA, et al. Isolation and structural identification of 1,25-dihydroxyvitamin D produced by cultured alveolar macrophages in sarcoidosis . J Clin Endocrinol Metab. 1985;60:960-966.Crossref 15. Insogna KL, Dreyer BE, Mitnick M, Ellison AF, Broadus AE. Enhanced production rate of 1,25-dihydroxyvitamin D in sarcoidosis . J Clin Endocrinol Metab. 1988;66:72-75.Crossref 16. Henry HL. Effect of ketoconazole and miconazole on 25-hydroxyvitamin D in metabolism by cultured chick kidney cells . J Steroid Biochem . 1985;23:991-995.Crossref 17. Glass AR, Eil C. Ketoconazole-induced reduction in serum 1,25-dihydroxyvitamin D . J Clin Endocrinol Metab. 1986;63:766-769.Crossref 18. Saggese G, Ghirri P, Bertelloni S, Baroncelli GI, Cosenza G. Effects of ketoconazole on gonadal function and 1,25-dihydroxyvitamin D . Horm Res. 1987;28:287-288. 19. Glass AR, Eil C. Ketoconazole-induced reduction in serum 1,25-dihydroxyvitamin D and total serum calcium in hypercalcemic patients . J Clin Endocrinol Metab. 1988;66:934-938.Crossref 20. Adams JS, Sharma OP, Diz MM, Endres DB. Ketaconazole decreases the serum 1,25-dihydroxyvitamin D and calcium concentrations in sarcoidosis-associated hypercalcemia . J Clin Endocrinol Metab. 1990;70: 1090-1095.Crossref 21. Glass AR, Cerletty JM, Elliott W, Leman J, Gray RW, Eil C. Ketoconazole reduces elevated serum levels of 1,25-dihydroxyvitamin D in hypercalcemic sarcoidosis . J Endocrinol Invest . 1990;13:407-413.Crossref 22. Snider DE Jr, Rieder HL, Combs D, Bloch AB, Hayden CH, Smith MH. Tuberculosis in children . Pediatr Infect Dis J. 1988;7:271-278.Crossref 23. Saggese G, Bertelloni S, Baroncelli Gl, Perri G, Calderazzi A. Mineral metabolism and calcitriol therapy in idiopathic juvenile osteoporosis . AJDC . 1991;145:457-462. 24. Saggese G, Baroncelli Gl, Bertelloni S. Determination of parathyrin by immunoradiometric assay evaluated in normal children and in patients with various disorders of calcium metabolism . Clin Chem. 1991;37:1999-2001. 25. Need AG, Philips PJ, Chiu FTS, Prisk HM. Hypercalcemia associated with tuberculosis . BMJ . 1980;282:831.Crossref 26. Sena SF, Bowers GN Jr. Measurements of ionized calcium in biological fluids: ion-selective electrode method . Methods Enzymol . 1988;158: 320-334. 27. Cadranel J, Milleron B, Garabedian M, Aroun G. Serum concentrations of vitamin D metabolites in untreated tuberculosis . Thorax . 1985;40:639-640.Crossref 28. Cadranel J, Garabedian M, Milleron B, Guillozo H, Akoun G, Hance AJ. 1,25(OH),D3 production by lymphocytes and alveolar marcrophages recovered by lavage from normocalcemic patients with tuberculosis . J Clin Invest . 1990;85:1588-1593.Crossref 29. Reichel H, Koeffler HP, Barbers R, Norman AW. Regulation of 1,25-dihydroxyvitamin D production by cultured alveolar macrophages from normal human donors and from patients with puylmonary sarcoidosis . J Clin Endocrinol Metab. 1987;65:1201-1209.Crossref 30. Sonino N. The endocrine effects of ketoconazole . J Endocrinol Invest . 1986;9:341-347.Crossref 31. Bia MJ, Insogna K. Treatment of sarcoidosis-associated hypercalcemia with ketoconazole . Am J Kidney Dis. 1991;18:702-705.Crossref 32. Breckenridge A. Clinical significance of interactions with antifungal agents . Br J Dermatol. 1992;126 ( (suppl 39) ):19-22.Crossref

Journal

American Journal of Diseases of Children – American Medical Association

Published: Mar 1, 1993

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