An acute rise in serum phosphorus after single-dose oral metyrapone

Metyrapone, an 11 beta-hydroxylase inhibitor, is widely used as a pharmacologic test for ACTH reserve. During studies on the pharmacodynamics of metyrapone and the response of plasma 11-deoxycortisol and cortisol, we fortuitously noted a consistent change in serum phosphate but no other routine laboratory chemistry determination. For these studies 12 control subjects were given oral methyrapone (30 mg/kg) at midnight. Serum phosphate (P) concentration was measured in fasting subjects at 08:00 on the morning before and after the administration of metyrapone. In 11 of 12 subjects, serum P increased from a mean of 3.6 +/- 0.7 (SD) mg/100 ml to a mean of 4.2 +/- 0.07 (SD) mg/100 ml on the morning following the drug. No increase in P was noted following the same dose of metyrapone in four patients on acute or chronic steroid therapy or in patients with primary or secondary hypoadrenocorticism. In addition, two addisonian patients were given either a saline or a hydrocortisone infusion for four hours. While the hydrocortisone infusion resulted in a drop in serum P, there was no decrease during saline infusions. These findings suggest that an acute rise in serum P after a single dose of metyrapone might be a rapid indicator of adrenocortical blockade leading to increased ACTH secretion, and cortisol and/or ACTH might play a role in P homeostasis.