Use of ketoconazole to probe the pathogenetic importance of 1,25-dihydroxyvitamin D in absorptive hypercalciuria

Neil A. Breslau, Glenn M. Preminger, Beverley V. Adams, Judy Otey, Charles Y C Pak

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Abstract

Ketoconazole was used to probe the pathogenetic importance of the serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] concentration in 19 patients with well characterized absorptive hypercalciuria (AH). Patients were studied while receiving a constant metabolic diet before and after 2 weeks of ketoconazole administration (600 mg daily). Twelve of the patients were classified as ketoconazole responders, because in conjunction with a reduction of serum 1,25-(OH)2D from 113 ± 36 to 70 ± 26 pmol/L, intestinal 47Ca absorption decreased from 76.3 ± 8.1% to 61.9 ± 7.7%, and 24-h urinary Ca excretion declined from 7.6 ±1.4 to 5.7 ± 1.1 mmol (P < 0.001 each). In these patients, intestinal 47Ca absorption was directly correlated with serum 1,25-(OH)2D levels and 24-h Ca excretion. In another group of 7 patients, termed ketoconazole nonrespondere, despite reduction of 1,25 (OH)2D from 122 ± 36 to 84 ± 17 pmol/L (P = 0.015), there was no significant change in intestinal Ca absorption (76.0 ± 8.2% to 72.1 ± 10.6%) or 24-h urinary Ca excretion (7.3 ± 1.3 to 7.2 ± 1.0 mmol). In these patients, neither intestinal Ca absorption nor urinary Ca excretion was correlated with serum 1,25-(OH)2D levels. It, thus, appears that AH is a heterogeneous disorder comprised of both vitamin D-dependent and vitamin D-independent subsets. Although useful to probe the pathogenesis of AH, chronic treatment with ketoconazole is not recom mended because of its generalized effects in inhibiting steroid synthesis.

Original languageEnglish (US)
Pages (from-to)1446-1452
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume75
Issue number6
StatePublished - Dec 1992

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Hypercalciuria
Ketoconazole
Intestinal Absorption
Vitamin D
Serum
Nutrition
Steroids
1,25-dihydroxyvitamin D
Diet

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

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Use of ketoconazole to probe the pathogenetic importance of 1,25-dihydroxyvitamin D in absorptive hypercalciuria. / Breslau, Neil A.; Preminger, Glenn M.; Adams, Beverley V.; Otey, Judy; Pak, Charles Y C.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 75, No. 6, 12.1992, p. 1446-1452.

Research output: Contribution to journalArticle

Breslau, Neil A. ; Preminger, Glenn M. ; Adams, Beverley V. ; Otey, Judy ; Pak, Charles Y C. / Use of ketoconazole to probe the pathogenetic importance of 1,25-dihydroxyvitamin D in absorptive hypercalciuria. In: Journal of Clinical Endocrinology and Metabolism. 1992 ; Vol. 75, No. 6. pp. 1446-1452.
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abstract = "Ketoconazole was used to probe the pathogenetic importance of the serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] concentration in 19 patients with well characterized absorptive hypercalciuria (AH). Patients were studied while receiving a constant metabolic diet before and after 2 weeks of ketoconazole administration (600 mg daily). Twelve of the patients were classified as ketoconazole responders, because in conjunction with a reduction of serum 1,25-(OH)2D from 113 ± 36 to 70 ± 26 pmol/L, intestinal 47Ca absorption decreased from 76.3 ± 8.1{\%} to 61.9 ± 7.7{\%}, and 24-h urinary Ca excretion declined from 7.6 ±1.4 to 5.7 ± 1.1 mmol (P < 0.001 each). In these patients, intestinal 47Ca absorption was directly correlated with serum 1,25-(OH)2D levels and 24-h Ca excretion. In another group of 7 patients, termed ketoconazole nonrespondere, despite reduction of 1,25 (OH)2D from 122 ± 36 to 84 ± 17 pmol/L (P = 0.015), there was no significant change in intestinal Ca absorption (76.0 ± 8.2{\%} to 72.1 ± 10.6{\%}) or 24-h urinary Ca excretion (7.3 ± 1.3 to 7.2 ± 1.0 mmol). In these patients, neither intestinal Ca absorption nor urinary Ca excretion was correlated with serum 1,25-(OH)2D levels. It, thus, appears that AH is a heterogeneous disorder comprised of both vitamin D-dependent and vitamin D-independent subsets. Although useful to probe the pathogenesis of AH, chronic treatment with ketoconazole is not recom mended because of its generalized effects in inhibiting steroid synthesis.",
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