0021-972X/97/$03.00/0
`Journal of Clinical Endocrinology and Metabolism
`Copyright © 1997 by The Endocrine Society
`
`Vol. 82, No. 1
`Printed in U.S.A.
`
`LETTERS TO THE EDITOR
`
`Low Dose ACTH Test—A Word of Caution to the
`Word of Caution: When and How to Use Ita
`To the editor:
`
`In 1991 we introduced the low dose ACTH test (1). Since then, nu-
`merous papers (2– 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 ␮g 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 ␮g 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 ␮g 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 intra-
`venously. 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 insuffi-
`ciency 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 ␮g/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 ␮g/100mL cortisol level 30 min after injection)
`was achieved with the 1 ␮g 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.
`
`Gabriel Dickstein, MD and Carmela Shechner, MD
`Bnai Zion Medical Center
`Haifa 31048, Israel
`
`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.
`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 ␮g) adrenocorticotropin test in the evaluation of patients with pituitary
`diseases. J Clin Endocrinol Metab. 80:1301–1305.
`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.
`5. Daidoh H, Morita H, Mune T et al. 1995 Responses of plasma adrenocortical
`steroids to low dose ACTH in normal subjects. Clin Endocrinol. 43:311–315.
`6. Rasmuson S, Olsson T, Hagg E. 1996 A low dose ACTH test to assess the
`function of
`the hypothalamic-pituitary-adrenal axis. Clin Endocrinol.
`44:151–156.
`7. Streeten DHP. 1996 The potential for serious consequences from misinterpret-
`ing normal responses to the rapid adrenocorticotropin test—Author’s response
`(letter). J Clin Endocrinol Metab. 81:2406.
`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.
`
`Activity of the Renin-Angiotensin-Aldosterone Axis is
`Dependent on the Occurrence of Edema in Growth
`Hormone(GH)-Deficient Adults Treated with GHb
`
`To the editor:
`
`While the antinatriuretic properties of growth hormone (GH) have
`been known for more than 40 yr, the mechanism underlying this effect
`and, in particular, the role of the renin-angiotensin-aldosterone(RAA)
`axis as a mediator of GH-induced sodium retention remain contentious.
`While early studies using supraphysiologic doses of GH in normal
`subjects (1) and GH-deficient adults (2) demonstrated both acute and
`chronic activation of the RAA axis, a recent report by Hoffman et al. (3)
`showed no acute increase in aldosterone secretion in GH-deficient adults
`after 7 days treatment with physiologic doses (0.04U/kg/d) of GH. We
`report our examination of the RAA axis during chronic, physiologic GH
`administration.
`In a double-blind, placebo-controlled trial we examined the impact of
`6 months GH treatment on aldosterone and plasma renin activity (PRA)
`in 10 GH-deficient adults (aged 37.9 ⫾ 3.6 yr, mean ⫾ sem), diagnosed
`on the basis of a peak GH response of less than 10 mU/L after insulin-
`induced hypoglycemia (n ⫽ 9) or L-Dopa (n ⫽ 1). The study was
`approved by the local ethics committee, and all patients gave written,
`informed consent.
`Following treatment with GH at a dose of 0.125 U/kg/week for the
`first week and 0.25 U/kg/week thereafter, 5 patients developed symp-
`toms of fluid retention in the form of edema or arthralgia. This resolved
`spontaneously in 1 case and required a 25% reduction in GH dose in the
`remainder. Total body water, measured by bioelectrical impedance anal-
`ysis, increased by 3.3 ⫾ 1.6 l (P ⬍ 0.05). There was no significant change
`in body weight, blood pressure, or serum electrolytes. Similar to the data
`of Hoffman et al. (3) we demonstrated no significant change in upright
`aldosterone or PRA levels in the total group. However, when those
`patients with and without edema were compared, there was a trend for
`aldosterone and PRA levels to increase in those patients who developed
`edema and to fall in those who did not (Fig. 1). The failure of these
`changes to achieve statistical significance is likely the result of the small
`numbers within each subgroup.
`These data indicate that the lack of stimulation of the RAA axis seen
`in the acute setting following physiologic GH replacement (3) is also true
`of chronic GH administration. In addition, this study makes the original
`observation that the pattern of aldosterone and PRA response seen with
`GH treatment is probably dependent on the edema status of the patient.
`The demonstration that nonedematous GH-treated patients tended to
`have lower RAA activity is consistent with the hypothesis that sodium
`retention associated with GH is due to a direct renal tubular effect. The
`tendency for aldosterone and PRA levels to increase in those patients in
`
`a Received September 23, 1996. Accepted September 24, 1996. Address
`correspondence to: Gabriel Dickstein, Division of Endocrinology, Ore-
`gon Health Sciences University L607, 3181 SW Sam Jackson Park Road,
`Portland, Oregon 97201–3098.
`
`b Received August 16, 1996. Accepted September 27, 1996. Address
`for correspondence to Professor T.J. McKenna, Dept. of Investigative
`Endocrinology, University College Dublin & St. Vincent’s Hospital, Elm
`Park, Dublin 4, Ireland.
`
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