SpringerLink
Log in

Repetitive graded ACTH stimulation test for adrenal insufficiency

  • Original Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

ACTH stimulation is useful in assessing the hypothalamo-pituitary-adrenal axis. However, there is still some debate about the proper dose and interpretation. We designed a new protocol using repetitive graded ACTH stimulation. Thirty-two patients with the diagnosis of adrenal insufficiency (AI) were studied. After taking samples for baseline ACTH and cortisol, 1 μg fresh-prepared ACTH (Synacthen (1–24)) was injected intravenously, then 5, 50 and 100 μg at hourly interval. Cortisol responses were measured at 30, 60, 120, 180 and 240 min. The secondary AI group (26 subjects) had cortisol responses in between those of the control group (8 subjects) and the primary AI group (6 subjects). The minimal overlap between the secondary AI group and the control group occurred at a 30-min cortisol response after 1 μg ACTH stimulation, using 20 μg/dl as the cut-off level. There was only one exception which showed an episodic release at 30 min. There were 5, 10 and 9 patients with secondary AI who responsed normally to 5, 50 and 100 μg ACTH stimulation, respectively. Maximal cortisol increments of the primary AI group were all below 4 μg/dl. Although there were 11 cases of secondary AI whose cortisol responses overlapped with those of primary AI, only two of them had a cortisol increment less than 4 μg/dl. Our new protocol combines the advantage of the low dose ACTH stimulation test, a sensitive method for detecting mild AI, and the ACTH infusion test, a longer test to mimic surgical stress.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Grinspoon S.K., Biller B.M.K. Laboratory assessment of adrenal insufficiency. J. Clin. Endocrinol. Metab. 1994, 79: 923–931.

    CAS  PubMed  Google Scholar 

  2. Oelkers W. Dose-response aspects in the clinical assessment of the hypothalamo-pituitary-adrenal axis and low dose adrenocorticotropin test. Eur. J. Endocrinol. 1996, 135: 27–33.

    Article  CAS  PubMed  Google Scholar 

  3. Jones S.L., Trainer P.J., Wass J.A.H., Besser G.M., Grossman A. An audit of the insulin tolerance test in adult subjects in an acute investigation unit over one year. Clin. Endocrinol. 1994, 41: 123–128.

    Article  CAS  Google Scholar 

  4. Shah A., Stanhope R., Matthew D. Hazards of pharmacological tests of growth hormone secretion in childhood. B.M.J. 1992, 304: 173–174.

    Article  CAS  Google Scholar 

  5. Hurel S.J., Thompson C.J., Watson M.J., Harris M.M., Baylis P.H., Kendall-Taylor P. The short Synacthen test and insulin stress test in the assessment of the hypothalamic-pituitary-adrenal axis. Clin. Endocrinol. 1996, 44: 141–146.

    Article  CAS  Google Scholar 

  6. Wang T.W.M., Wong M.S., Smith J.F., Howlett T.A. The use of the short tetracosatrin test for the investigation of suspected pituitary hypofunction. Ann. Clin. Biochem. 1996, 33: 112–118.

    Article  PubMed  Google Scholar 

  7. Price A., Ross R. Interpretation of cortisol response to synacthen. Ann. Clin. Biochem. 1996, 33: 175–176.

    Article  PubMed  Google Scholar 

  8. Rasmuson S., Olsson T., Hagg E. A low dose ACTH test to assess the function of the hypothalamic-pituitary-adrenal axis. Clin. Endocrinol. 1996, 44: 151–156.

    Article  CAS  Google Scholar 

  9. Kelestimur F., Akgun A., Gunay O. A comparison between short synacthen test and depot synacthen test in the evaluation of cortisol reserve of adrenal gland in normal subjects. J. Endocrinol. Invest. 1995, 18: 823–826.

    CAS  PubMed  Google Scholar 

  10. Soule S.G., Fahie-Wilson M., Tomlinson S. Failure of the short ACTH test to unequivocally diagnose long-standing symptomatic secondary hypoadrenalism. Clin. Endocrinol. (Oxf.) 1996, 44: 137–140.

    Article  CAS  Google Scholar 

  11. Cohen O., Sidi Y., Barazin M., Karasik A. Low dose ACTH test — A word of caution. J. Clin. Endocrinol. Metab. 1996, 81: 3129–3130.

    Article  CAS  PubMed  Google Scholar 

  12. Streeten D.H.P., Anderson G.H., Bonaventura M. The potential for serious consequences from misinterpreting normal responses to the rapid adrenocorticotropin test. J. Clin. Endocrinol. Metab. 1996, 81: 285–290.

    CAS  PubMed  Google Scholar 

  13. Crowley S., Hindmarsh P.C., Holownia P., Honour J.W., Brook C.G.D. The use of low doses of ACTH in the investigation of adrenal function in man. J. Endocrinol. 1991, 130: 475–479.

    Article  CAS  PubMed  Google Scholar 

  14. Broide J., Soferman R., Kivity S., Golander A., Dickstein G., Spirer Z., Weisman Y. Low dose adrenocorticotropin test reveals impaired adrenal function in patients taking inhaled corticosteroids. J. Clin. Endocrinol. Metab. 1995, 80: 1243–1246.

    CAS  PubMed  Google Scholar 

  15. Tordjman K., Jaffe A., Grazas N., Apter C., Stern N. The role of the low dose (1 μg) adrenocorticotropin test in the evaluation of patients with pituitary disease. J. Clin. Endocrinol. Metab. 1995, 80: 1301–1305.

    CAS  PubMed  Google Scholar 

  16. Dickstein G., Shechner C., Nicholson W.E., Rosner I., Shen-Orr Z., Adawi F., Lahav M. Adrenocorticotropin stimulation test: effects of basal cortisol level, time of day, and suggested new sensitive low dose test. J. Clin. Endocrinol. Metab. 1991, 72: 773–778.

    Article  CAS  PubMed  Google Scholar 

  17. Daidoh H., Morita H., Mune T., Murayama M., Hanafusa, N. H., Shibata H., Yasuda K. Response of plasma adrenocortical steroids to low dose ACTH in normal subjects. Clin. Endocrinol. (Oxf.) 1995, 43: 311–315.

    Article  CAS  Google Scholar 

  18. Crowley S., Hindmarsh P.C., Honour J.W., Brook C.G.D. 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. 1993, 136: 167–172.

    Article  CAS  PubMed  Google Scholar 

  19. Thaler L.M., Blevins L.S. The low dose (1 μg) adrenocorticotropin stimulation test in the evaluation of patients with suspected central adrenal insufficiency. J. Clin. Endocrinol. Metab. 1998, 83: 2726–2729.

    CAS  PubMed  Google Scholar 

  20. Abdu T.A.M., Elhadd T.A., Neary R., Clayton R.N. Comparison of the low dose short Synacthen test (1 μg), the conventional dose short Synacthen test (250 μg) and the insulin tolerance test for assessment of the hypothalamo-pituitary-adrenal axis in patients with pituitary disease. J. Clin. Endocrinol. Metab. 1999, 84: 838–843.

    CAS  PubMed  Google Scholar 

  21. Clayton R.N. Short Synacthen test versus insulin stress test for assessment of the hypothalamo-pituitary- adrenal axis: controversy revisited. Clin. Endocrinol. (Oxf.) 1996, 44: 147–149.

    Article  CAS  Google Scholar 

  22. Streeten D.H. Shortcomings in the low-dose (1 μg) ACTH test for the diagnosis of ACTH deficiency states. J. Clin. Endocrinol. Metab. 1999, 84: 835–837.

    CAS  PubMed  Google Scholar 

  23. Mayenknecht J., Diederich S., Bahr V., Plockinger U., Oelkers W. Comparison of low and high dose corticotropin stimulation test in patients with pituitary disease. J. Clin. Endocrinol. Metab. 1998, 83: 1558–1562.

    Article  CAS  PubMed  Google Scholar 

  24. Huang T.S., Chang C.C., Chang Y.C., Shun C.T. Primary antiphospholipid-antibody syndrome with pituitary apoplexy and adrenal insufficiency: a case report. Endocrinologist 1999, 9: 317–321.

    Article  Google Scholar 

  25. Blevins L.S. Serum cortisol is not an accurate predictor of the integrity of the hypothalamo-pituitary-adrenal axis. Clin. Endocrinol. (Oxf.) 1995, 42: 101–102.

    Article  Google Scholar 

  26. Oelkers W., Boelke T., Bahr V. Dose-response relationships between plasma adrenocorticotropin, cortisol, aldosterone, and 18-OH-hydroxycorticosterone after injection of ACTH (1-39) or human CRH in man. J. Clin. Endocrinol. Metab. 1988, 66: 181–186.

    Article  CAS  PubMed  Google Scholar 

  27. Jackson R.S., Carter G.D., Wise P.H., Alaghband-Zadeh J. Comparison of paired short synacthen and insulin tolerance test soon after pituitary surgery. Ann. Clin. Biochem. 1994, 31: 46–49.

    Article  PubMed  Google Scholar 

  28. Kane K.F., Emery P., Sheppard M.C., Stewart P.M. Assessing the hypothalamo-pituitary-adrenal axis in patients on long-term glucocorticoid therapy: the short synacthen versus the insulin tolerance test. Q. J. Med. 1995, 88: 263–267.

    CAS  Google Scholar 

  29. Ammari F., Issa B.G., Millward E., Scanion M.F. A comparison between short ACTH and insulin stress tests for assessing hypothalamo-pituitary-adrenal function. Clin. Endocrinol. 1996, 44: 473–476.

    Article  CAS  Google Scholar 

  30. Livanou T., Ferriman D., James V.H.T. Recovery of hypothalamo-pituitary-adrenal function after corticosteroid therapy. Lancet 1967, ii: 856–859.

    Article  Google Scholar 

  31. Naito Y., Fukta J., Tamai S., Seo N., Makai Y., Mori K., Imura H. Biphasic changes in hypothalamo-pituitary-adrenal function during the early recovery period after major abdominal surgery. J. Clin. Endocrinol. Metab. 1991, 73: 111–117.

    Article  CAS  PubMed  Google Scholar 

  32. Munabi A.K., Feuillan P., Staton R.C., Rodbard D., Chrousos G.P., Anderson R.E., Strober M.D., Lynn Loriaux D., Cutler G.B. Adrenal steroid responses to continuous intravenous adrenocorticotropin infusion compared to bolus injection in normal volunteers. J. Clin. Endocrinol. Metab. 1986, 63: 1036–1039.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine, College of Medicine, National Taiwan University, 7 Chung-Shan South Road, Taipei, Taiwan

    Tien-Shang Huang M.D. & Y. -D. Jiang

Authors
  1. Tien-Shang Huang M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y. -D. Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tien-Shang Huang M.D..

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huang, TS., Jiang, Y.D. Repetitive graded ACTH stimulation test for adrenal insufficiency. J Endocrinol Invest 23, 163–169 (2000). https://doi.org/10.1007/BF03343700

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03343700

Key-words

Search

Navigation