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. ACTH124
(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. 1
).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.
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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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