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Journal of Clinical Endocrinology & Metabolism Vol. 72, No. 4 773-778
doi:10.1210/jcem-72-4-773
Copyright © 1991 by the Endocrine Society.
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Adrenocorticotropin Stimulation Test: Effects of Basal Cortisol Level, Time of Day, and Suggested New Sensitive Low Dose Test*

GABRIEL DICKSTEIN, CARMELA SHECHNER, WENDELL E. NICHOLSON, ITZHAK ROSNER, ZILA SHEN-ORR, FAYAD ADAWI and MICHAL LAHAV

Division of Endocrinology (G.D., C.S.) and Rheumatology Unit (I.R.), Haifa Medical Center (Bnai Zion) Haifa, Israel; Division of Endocrinology, Rambam Medical Center (Z.S.O., M.L.) Haifa, Israel; Endocine Unit, Rebecca Ziv Medical Center (F.A.) Zafed, Israel; and Division of Endocrinology, Vanderbilt University School of Medicine (W.E.N.) Nashville, Tennessee 37232

Address all correspondence and requests for reprints to: Gabriel Dickstein, M.D., Division of Endocrinology, Haifa Medical Center (Bnai Zion), P.O.B. 4940, Haifa 31048, Israel.

Adrenal response to iv administration of 1–24 ACTH (250 µg) was examined in normal volunteers under various conditions. The effect of basal cortisol levels was examined by performing the tests at 0800 h with and without pretreatment with dexamethasone. The effect of time of day was evaluated by performing the tests at 0800 h and at 1600 h, eliminating possible basal cortisol influence by pretreatment with dexamethasone. In the first set of tests, despite significantly different baseline levels, 30-min cortisol levels were not different (618 ± 50 vs. 590 ± 52 nmol/L). Afternoon cortisol levels in response to ACTH were found to be significantly higher than morning levels at 5 min (254 ± 50 vs. 144 ± 36 nmol/L, p < 0.01) and at 15 min (541 ± 61 vs. 433 ± 52 nmol/L, p < 0.02). This difference in response was no longer notable at 30 min (629 ± 52 and 591 ± 52 nmol/L).

We tried also to determine the lowest ACTH dose which will elicit a maximal cortisol response. No difference was found in cortisol levels at 30 and 60 min in response to 250 and 5 µg 1-24 ACTH. Using 1 µg ACTH, the 30-min response did not differ from that to 250 µg (704 ± 72 vs. 718 ± 55 nmol/L, respectively). However, the 60-min response to 1 µg was significantly lower (549 ± 61 vs. 842 ± 110 nmol/L, p < 0.01). Using this low dose ACTH test (1 µg, measuring 30-min cortisol level), we were able to develop a much more sensitive ACTH test, which enabled us to differentiate a subgroup of patients on long-term steroid treatment who responded normally to the regular 250 µg test, but had a reduced response to 1 µg.

The stability of 1–24 ACTH in saline solution, kept at 4 C, was checked. ACTH was found to be fully stable after 2 hs in a concentration of 5 µg/ml in glass tube and 0.5 µ/ml in plastic tube. It was also found to be fully stable, both immunologically and biologically, for 4 months, under these conditions.

We conclude that the 30-min cortisol response to ACTH is constant, unrelated to basal cortisol level or time of day. It is therefore the best criterion for measuring adrenal response in the short ACTH test. The higher afternoon responses at 5 and 15 min suggest greater adrenal sensitivity in the afternoon, but further studies are needed to clarify this issue. Cortisol response to 5 µg ACTH is maximal at both 30 and 60 min, and even 1 µg ACTH causes a maximal cortisol response at 30 min. This latter ACTH dose can be used for a sensitive ACTH test. 1–24 ACTH is stable when refrigerated in saline (4 C) for 4 months. (J Clin Endocrinol Metab 72: 773–778, 1991)

* This work was partially supported by a grant donated by the friends of the Rebecca Ziv Medical Center (Zafed, Israel).

Received September 4, 1990.




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