Laboratoire de Neuroendocrinologie Expérimentale, INSERM U 501 (M.G., F.D., C.F., J.-G.V., S.B., A.D., C.O.) Laboratoire de Biochimie (M.G.) Service dEndocrinologie, Maladies Métaboliques et de la Nutrition (P.D., F.D., C.F., S.B., A.D., C.O.) Hôpital Nord, Marseille Cedex 20, France
In a recent paper Mayenknecht et al. (1) have shown that the
diagnostic sensitivities of the low (LDT) and high (HDT) dose
tetracosactin (ACTH 1-24) stimulation tests are almost identical. Their
conclusions are supported in part by the measurements of plasma
immunoreactive tetracosactin, which show that "In the HDT, plasma
tetracosactin rose to more than 60,000 pg/mL shortly after injection.
In the LDT, it rose to 1900 pg/mL." Based on these results and on the
observation that the response of the normal human adrenal to an
increment in plasma corticotropin to 7080 pg/mL is almost maximal
(2), the authors assumed that the LDT cannot be more sensitive than the
HDT. However, we feel that these tetracosactin measurements were
largely overestimated. Indeed, assuming a distribution space of 10 L,
injection of 1 µg (i.e. the dose used in the LDT) or 250
µg (i.e. the dose used in the HDT) tetracosactin would
give maximal plasma concentration of 100 and 25,000 pg/mL,
respectively. This discrepancy is most probably related to the
methodology used to measure plasma tetracosactin. Indeed, the authors
have used a radioimmunoassay (distributed by CIS) designed to measure
ACTH 1-39. They specify that the antiserum used in the assay recognizes
the N-terminal sequence of ACTH. However, this does not necessarily
imply that it recognizes equally ACTH 1-24 and ACTH 1-39. Our findings
indicate that the antiserum used in this radioimmunoassay crossreacts
about 5 times more (on a mass basis) with ACTH 1-24 than with ACTH
1-39. In addition, standard curves obtained with ACTH 1-24 or ACTH 1-39
are not strictly parallel [this can be explained by the fact that the
antiserum may contain several species of anti-ACTH immunoglobulins
having different affinity for ACTH 1-24 or ACTH 1-39]. As a
consequence, plasma tetracosactin levels measured using the CIS
antiserum and plotted against a standard curve generated with ACTH 1-39
will be overestimated by at least 5 times (see Fig. 1).
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These observations indicate that one should be very cautious when using a radioimmunoassay designed for a given peptide to measure another highly structurally related peptide; also, the plasma levels of tetracosactin reached after injection of 1 µg of this substance lie within a physiological range.
Footnotes
Received October 16, 1998. Address correspondence to: Michel Grino, M.D., Ph.D., Laboratoire de Neuroendocrinologie Expérimentale, INSERM U501, Faculté de Médecine Secteur Nord, Boulevard Pierre Dramard, 13916, Marseille Cedex 20, France.
References
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