Increased Plasma 17-Hydroxyprogesterone Response to ACTH in Patients with Nonhyperfunctioning Adrenal Adenomas Is Not Due to a Deficiency in 21-Hydroxylase Activityd

Miklós Tóth, Károly Rácz and Edit Gláz

Gastroenterological and Endocrinological Research Group Semmelweis University Medical School Budapest, Hungary

According to earlier studies, patients with nonhyperfunctioning adrenal adenomas often show an increased plasma 17-hydroxyprogesterone response to ACTH stimulation (1, 2, 3, 4, 5, 6, 7, 8, 9). In most studies the frequency of this hormonal abnormality ranged between 30% and 70%, probably reflecting the method used for the definition of normal 17-hydroxyprogesterone response. Although the meaning of increased plasma 17-hydroxyprogesterone response after ACTH stimulation in patients with nonhyperfunctioning adrenal adenomas has not been clearly elucidated, several reports considered this finding as an indication for the presence of a decreased activity of the steroid 21-hydroxylase enzyme (1, 2, 3, 4, 5, 6, 7). However, only very few patients were reinvestigated for this abnormality after surgical removal of these adenomas (3, 4, 5).

To address this question, we measured basal and ACTH-stimulated plasma 17-hydroxyprogesterone and cortisol concentrations in 78 patients with nonhyperfunctioning adrenal adenomas both before and after adrenal surgery, as well as in 60 healthy subjects. ACTH1–24 (Cortrosyn Depot, Organon) was given im at 1400 h, and blood was drawn the next morning for measurements of plasma cortisol and 17-hydroxyprogesterone.

ACTH-stimulated plasma 17-hydroxyprogesterone and cortisol levels before adrenal surgery were significantly higher in patients with nonhyperfunctioning adenomas compared with those found in healthy subjects (17-hydroxyprogesterone, 1928 ± 215 vs. 601 ± 36 ng/dL, mean ± SE, P < 0.001; cortisol, 82.8 ± 5.7 vs. 46.3 ± 2.1 µg/dL, P < 0.001). None of the healthy subjects but 53% of patients with nonhyperfunctioning adrenal adenomas had ACTH-stimulated plasma 17-hydroxyprogesterone concentrations higher than 1500 ng/dL (Fig. 1Go).In these patients, adrenal surgery resulted in a substantial decrease of ACTH-stimulated plasma 17-hydroxyprogesterone (499 ± 54 ng/dL) and cortisol concentrations (34.7 ± 2.3 µg/dL). In addition, ACTH-stimulated plasma 17-hydroxyprogesterone and cortisol levels showed significant positive correlations with the size of adenomas (r = 0.27 between plasma 17-hydroxyprogesterone and tumor size, P = 0.025; r = 0.40 between plasma cortisol and tumor size, P < 0.001). Even stronger positive correlation was found between the plasma 17-hydroxyprogesterone and cortisol responses to ACTH (r = 0.50, P < 0.001).



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Figure 1. Cumulative frequency curves of ACTH-stimulated plasma 17-hydroxyprogesterone levels in 60 healthy subjects and in 78 patients with nonhyperfunctioning adrenal adenomas before and after unilateral adrenalectomy.

 
From these results it seems likely that the increased plasma 17-hydroxyprogesterone and cortisol responses after ACTH stimulation, which is present in a large proportion of patients with nonhyperfunctioning adrenal adenomas, are mainly attributable to the tumoral mass rather than the nontumorous adrenal tissues. The strong positive correlation between the tumor diameter and ACTH-stimulated plasma 17-hydroxyprogesterone as well as cortisol levels argues against the hypothesis that 21-hydroxylase deficiency may be the cause of the increased 17-hydroxyprogesterone response to ACTH in these patients.

Footnotes

Address correspondence to: Miklós Tóth, M.D., 2nd Department of Medicine, Semmelweis University Medical School, Szentkirályi u. 46., H-1088 Budapest, Hungary.

Received June 23, 1998.

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