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Letters to the Editor |
Klinikum Benjamin Franklin, Freie Universität Berlin 12200 Berlin, Germany
We appreciate the great interest in our paper on low- and high-dose corticotropin testing in normal controls and in patients with pituitary disease (1). A reply to all criticisms and questions raised would require the length of a full paper. Therefore, some topics will be addressed collectively.
Methods for plasma cortisol and ACTH 1-24 measurement. Our baseline cortisol levels in normals appear relatively high in comparison with other publications. However, all results (in normals, patients, and with the different tests) were obtained using the same cortisol RIA kit from Diagnostic Products Corp. This kit was recently evaluated with favorable results in comparison with a gas chromatographic-mass spectrometric method (2). Our assay is subject to a quality control every 4 months by the German Society of Clinical Chemistry.
Dr. Dickstein compares our ACTH 1-24 measurements after low-dose corticotropin 1-24 injection with other investigators’ results. The 1900 pg/mL value in venous blood of the opposite arm was obtained 1 min after injection. At 3 min, the value was 595 pg/mL, very similar to the 2-min value (546 pg/mL) obtained by Nye et al. We also showed that the ACTH 1-24 level fell below 100 pg/mL (an ACTH level below which the adrenal cortex is no longer maximally stimulated) about 12 min after low-dose ACTH injection (Fig. 1 of our paper). Therefore, 30 min after injection, cortisol secretion is no longer maximally stimulated, and plasma cortisol starts falling, while it is still rising in the high-dose test. A comparison of these ACTH/cortisol dynamics with those of the insulin hypoglycemia test is difficult, because in the latter, plasma ACTH reaches its maximum (in our normals around 194 pg/mL) between 30 and 60 min after injection and cortisol between 45 and 90 min. None of these ACTH levels is really "physiological."
"Cutoff levels" for the low- and high-dose
corticotropin tests and the insulin hypoglycemia test. An
advantage of our paper compared with others is the availability of a
fairly large group of endocrinologically normal controls for comparison
with the test results in patients. The same cortisol assay was used in
all instances. Therefore, we did not have to use reference levels
previously published by other groups using different analytical
methods. Furthermore, we have recently studied 25 healthy subjects (18
males, 7 females, age: 20–56 yr) with the insulin hypoglycemia test
(glucose nadir <40 µg/dL plus some clinical signs of hypoglycemia).
The results and the normal ranges of the low- and high-dose
corticotropin tests (as requested by Drs. Tordjman and Jaffe) are shown
in Fig. 1. The lowest maximal cortisol response in the insulin test was
21.7 µg/dL, and the mean response minus 2 SD was 20.6
µg/dL. Thus, our patients classified as having mild secondary adrenal
insufficiency (1) with cortisol responses to 18–20 µg/dL in the
insulin test ("group 3") certainly had an impaired cortisol
response for this center and according to the "cutoff" limit of 20
µg/dL as reported by Pavord et al. (3). It is also clear
from the data of Table 1
that the "cutoff" level of the low-dose test is lower than that of
the high-dose test at 30 min according to both the lower limit of
normal and the mean minus 2 SD level. We are wondering why
Tordjman et al. (4) used the same cutoff level of 18 µg/dL
(500 nmol/L) for both tests, although they state in their paper,
"Contrary to other investigators’ reports, in normal controls, we
did not observe a maximal stimulation after the administration of 1
µg ACTH," and they documented this in their figures 1 and 2.
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Footnotes
Address correspondence to Wolfgang Oelkers, Division of Endocrinology, Klinikum Benjamin Franklin, Freie Universitat Berlin, Hindenburghamm 30, 12200 Berlin, Germany.
Received September 9, 1998.
References
This article has been cited by other articles:
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  W. Oelkers Comment on Comparison of the Low Dose Short Synacthen Test (1 {micro}g), the Conventional Dose Short Synacthen Test (250 {micro}g), and the Insulin Tolerance Test for Assessment of the Hypothalamo-Pituitary-Adrenal Axis in Patients with Pituitary Disease J. Clin. Endocrinol. Metab., August 1, 1999; 84(8): 2973 - 2973. [Full Text]
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