Low Dose ACTH Test—A Word of Caution to the Word of Caution: When and How to Use It1

Gabriel Dickstein, MD and Carmela Shechner, MD

Bnai Zion Medical Center Haifa 31048, Israel

In 1991 we introduced the low dose ACTH test (1). Since then, numerous papers (2, 3, 4, 5, 6) have confirmed our data. Lately, two contradictory letters in JCEM challenged the validity of the test. The first (7), based on feelings rather than facts, suggests that even 1 µg of ACTH might be too high a dose for a physiologic stimulation of the adrenal. The second (8) suggests (based on one case) that 1 µg may in some cases or situations be too low a dose for this purpose.

It is difficult to argue with the first letter (7), as no facts are given. However, while most investigators still use 250 µg ACTH as the adrenal stimulating dose, to speculate that 1:250 that amount is still too high seems speculative. The second letter (8) is based on a bizarre case in which subnormal response to the low dose ACTH test was noticed, but also no response was noticed to CRH, or to insulin challenge. A repeated low dose ACTH test was normal (though no data are given!).

The best explanation in our view to these results might be that, in the first low dose ACTH test, not all of the dose was administered intravenously. As this test was not done by the authors themselves, this possibility will probably never be confirmed or denied. However, it is very important to emphasize that, unlike the high dose ACTH test, where the dose is well above normal, in the low dose test all of the hormone must be introduced intravenously to get the normal response. In case of doubt the test should be repeated. We do agree with the authors that the low dose ACTH test should be used as a screening test, and another confirmatory test (we advocate the metyrapone test) should be done before lifetime steroid treatment is given. However, if the low dose ACTH test is normal, no further tests to exclude adrenal insufficiency are needed. The only cases in which the low dose ACTH test is of very little value are those of newly onset pituitary insufficiency (pituitary surgery or apoplexy) in which the adrenal response, even to low doses of ACTH is still preserved.

We would like also to reemphasize that 1–24 ACTH can be kept refrigerated in glass tubes at a concentration of 5 µg/mL for up to 4 months (1). This makes the test much easier, as only one dilution is needed immediately before injection.

We now have experience with more than 100 patients, in all of whom a normal response (>18 µg/100mL cortisol level 30 min after injection) was achieved with the 1 µg ACTH test. In summary, we have two words of caution about the low dose ACTH test: be sure that you inject the whole dose intravenously, and be sure that you do not test a patient with very recent pituitary insufficiency.

Footnotes

1 Address correspondence to: Gabriel Dickstein, Division of Endocrinology, Oregon Health Sciences University L607, 3181 SW Sam Jackson Park Road, Portland, Oregon 97201–3098. Back

Received September 23, 1996.

Accepted September 24, 1996.

References

  1. Dickstein G, Shechner C, Nicholson WF, et al. 1991 Adrenocorticotropin stimulation test: effects of basal cortisol level, time of the day, and suggested new sensitive low dose test. J Clin Endocrinol Metab. 72:773–778.[Abstract]
  2. Crowley S, Hindmarsh PC, Honour JW, Brook CGD. 1992 Reproducibility of the cortisol response to stimulation with a low dose of ACTH (1–24): the effect of basal cortisol levels and comparison of low-dose with high-dose secretory dynamics. J Endocrinol. 136:167–172.
  3. Tordjman K, Jaffe A, Grazas N, Apter C, Stern N. 1995 The role of the low dose (1 µg) adrenocorticotropin test in the evaluation of patients with pituitary diseases. J Clin Endocrinol Metab. 80:1301–1305.[Abstract]
  4. Brodie J, Soferman R, Kivity S et al. 1995 Low dose adrenocorticotropin test reveals impaired adrenal function in patients taking inhaled corticosteroids. J Clin Endocrinol Metab. 80:1243–1246.[Abstract]
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  7. Streeten DHP. 1996 The potential for serious consequences from misinterpreting normal responses to the rapid adrenocorticotropin test—Author’s response (letter). J Clin Endocrinol Metab. 81:2406.[Medline]
  8. Cohen O, Sidi Y, Barazin M, Karasik A. 1996 Low dose ACTH test—a word of caution (letter). J Clin Endocrinol Metab. 81:3129.[Medline]