Evaluation of 3 Hour Metyrapone Test in Children and Adolescents

Abstract

An evaluation of a new 3 h metyrapone test is presented. The test consists of one oral dose of metyrapone given at 08.00-09.00 hours, and determination of plasma deoxycortisol from a single capillary blood sample taken 3 h later. The test has been assessed in children and adolescents in conjunction with a 5 day metyrapone test, insulin test, vasopressin test, and ACTH test in forty-five reference subjects, in thirty-six hypopituitary subjects with normal or deficient ACTH secretion, in three subjects with primary adrenocortical disease and in ten subjects prior to and after pharmacological prednisone medication. During the first hour after metyrapone the plasma cortisol level decreased to almost the low level maintained for the rest of the 3 h period. The plasma deoxycortisol concentration was basally less than or equal to 35 nmol/l and increased continuously during the 3 h period to the mean level of 299 (95% confidence interval 133-669) nmol/l in the reference subjects. The new test proved to be as accurate as the insulin test in detecting ACTH deficiency. No significant rise was observed in the plasma somatotrophin (GH) level in those children who had a normal GH response to insulin hypoglycaemia.

Single-dose metyrapone test at 06.00 h: an accurate method for assessment of pituitary-adrenal reserve

“…Metyrapone tests have been developed in which levels of 11-deoxycortisol are used as criteria for normal pituitary-adrenal response (Spark 1971;Jubiz et al 1970b;Leisti 1977). These tests involve different time schedules for metyrapone admini¬ stration: 6 daily doses (Spark 1971), one large dose (2-3 g) at midnight (Jubiz et al 1970b), or one dose at 08.00 h (Leisti 1977).…”

“…Measuring plasma 11-deoxycortisol level at 08.00 h, rather than 24-h urine collection (Spark 1971), shortens the test to 24 h and simplifies it considerably. Different one-dose metyrapone test conducted at various times of the day (Jubiz et al 1970b; Leisti 1977) have been suggested, but have not been widely accepted since they do not necessarily show stimulation of adrenal corticosteroid production, but rather blockade of cortisol formation from 11-deoxycortisol, as total 17-OHCS levels are not shown to rise (Liddle 1981).…”

Plasma 11-deoxycortisol, androstenedione, testosterone and ACTH in comparison with the urinary excretion of tetrahydro-11-deoxycortisol as indices of the pituitary-adrenal response to oral metyrapone

“…The increase of S in plasma is accompanied by an augmented urinary excretion of tetrahydro-11-deoxycortisol (H4S). Short metyrapone tests (usually consisting of one dose of metyrapone) have been described (Jubiz et al 1970b;Zachmann et al 1974;Blichert-Toft 1975;Leisti 1977), but the conventional oral mety¬ rapone test is still widely used.Oral administration of metyrapone for three consecutive days results in a 95% inhibition of the 11-ß-hydroxylase, at a daily dose of 4.5 g (Cope et al 1966).The relative increase of urinary H4S after mety¬ rapone administration exceeds the relative rise in plasma S considerably (Zachmann et al 1974). …”

“…The increase of S in plasma is accompanied by an augmented urinary excretion of tetrahydro-11-deoxycortisol (H4S). Short metyrapone tests (usually consisting of one dose of metyrapone) have been described (Jubiz et al 1970b;Zachmann et al 1974;Blichert-Toft 1975;Leisti 1977), but the conventional oral mety¬ rapone test is still widely used.…”

Critical Evaluation of the 5-Day Metyrapone Test

“…Though shorter metyrapone tests have been suggested (24,31,41,46) the conventional oral metyrapone test probably continues to be the most widely used test of the hypothalamo-pituitary system. Yet, its interpretation has re mained problematic.…”