Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Journal of Pediatric Endocrinology and Metabolism

Editor-in-Chief: Kiess, Wieland

Ed. by Bereket, Abdullah / Darendeliler, Feyza / Dattani, Mehul / Gustafsson, Jan / Luo, Fei Hong / Mericq, Veronica / Toppari, Jorma


IMPACT FACTOR 2018: 1.239

CiteScore 2018: 1.22

SCImago Journal Rank (SJR) 2018: 0.507
Source Normalized Impact per Paper (SNIP) 2018: 0.562

Online
ISSN
2191-0251
See all formats and pricing
More options …
Volume 32, Issue 1

Issues

Long-acting intramuscular ACTH stimulation test for the diagnosis of secondary adrenal insufficiency in children

Rajni Sharma
  • Corresponding author
  • Division of Pediatric Endocrinology, Room no.3058, Teaching Block, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi 110029, India
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Shamnad Madathil / Vivek Maheshwari / Kakali Roy
  • Division of Pediatric Endocrinology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Brijesh Kumar
  • Division of Pediatric Endocrinology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Vandana Jain
  • Division of Pediatric Endocrinology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2018-12-07 | DOI: https://doi.org/10.1515/jpem-2018-0330

Abstract

Background

The diagnosis of adrenal insufficiency (AI) is based on the basal and stimulated levels of serum cortisol in response to the short Synacthen test (SST). In patients with secondary AI (SAI) due to hypothalamic-pituitary-adrenal (HPA) axis defects, the SST has been validated against the insulin tolerance test (ITT), which is the gold standard. However, injection Synacthen is not easily available in some countries, and endocrinologists often use Acton-Prolongatum (intramuscular [IM] long-acting adrenocorticotropic hormone [ACTH]) in place of Synacthen. There are no studies validating the use of IM-ACTH in children with suspected AI. We evaluated the diagnostic value of the IM-ACTH test against the ITT for the diagnosis of SAI in children.

Methods

All children with suspected growth hormone deficiency (GHD) undergoing a routine ITT were evaluated using the IM-ACTH test within 1 week.

Results

Forty-eight patients (36 boys/12 girls, age range: 5–14 years) were evaluated using both the ITT and the IM-ACTH test. Twenty-eight patients had a normal cortisol response (≥18 μg/dL, 500 nmol/L) in the ITT and 20 had low values. In patients with a normal cortisol response on the ITT, the peak value obtained after the IM-ACTH test was higher than that on the ITT (28.7 μg/dL [± 8.8] vs. 23.8 μg/dL [± 4.54], respectively; p=0.0012). Compared to the ITT, the sensitivity and specificity of the IM-ACTH test for the diagnosis of SAI at cortisol cut-offs <18 μg/dL (500 nmol/L) and <22 μg/dL (600 nmol/L) were 57.1% and 92.8%, and 100% and 73.5%, respectively.

Conclusions

A peak cortisol value <18 μg/dL on the IM-ACTH test is highly suggestive of SAI, whereas a value >22 μg/dL rules out SAI.

Keywords: cortisol; growth hormone deficiency; hypothalamic-pituitary-adrenal axis; insulin tolerance test; multiple pituitary hormone deficiency; short Synacthen test

References

  • 1.

    August GP, Lippe BM, Blethen SL, Rosenfeld RG, Seelig SA, et al. Growth hormone treatment in the United States: demographic and diagnostic features of 2331 children. J Pediatr 1990;116:899–903.CrossrefPubMedGoogle Scholar

  • 2.

    Cerbone M, Dattani MT. Progression from isolated growth hormone deficiency to combined pituitary hormone deficiency. Growth Horm IGF Res 2017;37:19–25.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 3.

    Grinspoon SK, Biller BM. Clinical review 62: laboratory assessment of adrenal insufficiency. J Clin Endocrinol Metab 1994;79:923–31.PubMedGoogle Scholar

  • 4.

    Grossman AB. Clinical Review#: the diagnosis and management of central hypoadrenalism. J Clin Endocrinol Metab 2010;95:4855–63.CrossrefPubMedGoogle Scholar

  • 5.

    Bornstein SR, Allolio B, Arlt W, Barthel A, Don-Wauchope A, et al. Diagnosis and treatment of primary adrenal insufficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2016;101:364–89.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 6.

    McDonough RJ, Alba P, Dileepan K, Cernich JT. Employing a results-based algorithm to reduce laboratory utilization in ACTH stimulation testing. J Pediatr Endocrinol Metab 2018;31:429–33.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 7.

    Weintrob N, Sprecher E, Josefsberg Z, Weininger C, Aurbach-Klipper Y, et al. Standard and low-dose short adrenocorticotropin test compared with insulin-induced hypoglycemia for assessment of the hypothalamic-pituitary-adrenal axis in children with idiopathic multiple pituitary hormone deficiencies. J Clin Endocrinol Metab 1998;83:88–92.CrossrefPubMedGoogle Scholar

  • 8.

    Abdu TA, Elhadd TA, Neary R, Clayton RN. Comparison of the low dose short Synacthen test (1 microg), the conventional dose short Synacthen test (250 microg), and the insulin tolerance test for assessment of the hypothalamo-pituitary-adrenal axis in patients with pituitary disease. J Clin Endocrinol Metab 1999;84:838–43.PubMedGoogle Scholar

  • 9.

    Gonzálbez J, Villabona C, Ramón J, Navarro MA, Giménez O, et al. Establishment of reference values for standard dose short Synacthen test (250 microgram), low dose short Synacthen test (1 microgram) and insulin tolerance test for assessment of the hypothalamo-pituitary-adrenal axis in normal subjects. Clin Endocrinol (Oxf) 2000;53:199–204.CrossrefPubMedGoogle Scholar

  • 10.

    Feldman EC, Stabenfeldt GH, Farver TB, Addiego LA. Comparison of aqueous porcine ACTH with synthetic ACTH in adrenal stimulation tests of the female dog. Am J Vet Res 1982;43:522–4.PubMedGoogle Scholar

  • 11.

    Reimondo G, Bovio S, Allasino B, Terzolo M, Angeli A. Secondary hypoadrenalism. Pituitary 2008;11:147–54.Web of SciencePubMedCrossrefGoogle Scholar

  • 12.

    Erturk E, Jaffe CA, Barkan AL. Evaluation of the integrity of the hypothalamic-pituitary-adrenal axis by insulin hypoglycemia test. J Clin Endocrinol Metab 1998;83:2350–4.PubMedGoogle Scholar

  • 13.

    Maghnie M, Uga E, Temporini F, Di Iorgi N, Secco A, et al. Evaluation of adrenal function in patients with growth hormone deficiency and hypothalamic-pituitary disorders: comparison between insulin-induced hypoglycemia, low-dose ACTH, standard ACTH and CRH stimulation tests. Eur J Endocrinol 2005;152:735–41.CrossrefPubMedGoogle Scholar

  • 14.

    Streeten DH, Anderson GH Jr, Bonaventura MM. The potential for serious consequences from misinterpreting normal responses to the rapid adrenocorticotropin test. J Clin Endocrinol Metab 1996;81:285–90.PubMedGoogle Scholar

  • 15.

    Graybeal ML, Fang VS. Physiological dosing of exogenous ACTH. Acta Endorinologica 1985;108:401–6.CrossrefGoogle Scholar

  • 16.

    Agwu JC, Spoudeas H, Hindmarsh PC, Pringle PJ, Brook CG. Tests of adrenal insufficiency. Arch Dis Child 1999;80:330–3.CrossrefPubMedGoogle Scholar

  • 17.

    Rasmuson S, Olsson T, Hagg E. A low dose ACTH test to assess the function of the hypothalamic-pituitary-adrenal axis. Clin Endocrinol (Oxf) 1996;44:151–6.CrossrefPubMedGoogle Scholar

  • 18.

    Mushtaq T, Shakur F, Wales JK, Wright NP. Reliability of the low dose Synacthen test in children undergoing pituitary function testing. J Pediatr Endocrinol Metab 2008;21:1129–32.PubMedGoogle Scholar

  • 19.

    Ng SM, Agwu JC, Dwan K. A systematic review and meta-analysis of Synacthen tests for assessing hypothalamic-pituitary-adrenal insufficiency in children. Arch Dis Child 2016;101:847–53.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 20.

    Ospina NS, Al Nofal A, Bancos I, Javed A, Benkhadra K, et al. ACTH stimulation tests for the diagnosis of adrenal insufficiency: systematic review and meta-analysis. J Clin Endocrinol Metab 2016;101:427–34.Web of ScienceCrossrefGoogle Scholar

  • 21.

    Hurel SJ, Thompson CJ, Watson MJ, Harries PH, Baylis PH, et al. The short Synacthen and insulin stress tests in the assessment of the hypothalamic-pituitary-adrenal axis. Clin Endocrinol 1996;44:141–6.CrossrefGoogle Scholar

  • 22.

    Gundgurthi A, Garg MK, Dutta MK, Pakhetra R. Intramuscular ACTH stimulation test for assessment of adrenal function. J Assoc Physicians India. 2013;61:320–4.PubMedGoogle Scholar

  • 23.

    Jayakumari C, George GS, Nair A, Jabbar PK, Jessy SJ, et al. ACTH stimulation test with long acting ACTH preparation for the diagnosis of adrenal insufficiency. Abstract presented in the National conference of Endocrine Society of India ESICON 2017. Ind J Endocrin Met 2017;21:S62.Google Scholar

  • 24.

    Kelestimur F, Akgün A, Günay 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;18:823–6.CrossrefPubMedGoogle Scholar

  • 25.

    O’Grady MJ, Hensey C, Fallon M, Hoey H, Murphy N, et al. Requirement for age-specific peak cortisol responses to insulin-induced hypoglycaemia in children. Eur J Endocrinol 2013;169:139–45.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 26.

    Lindholm J, Kehlet H. Re-evaluation of the clinical value of the 30 min ACTH test in assessing the hypothalamic- pituitary-adrenocortical function. Clin Endocrinol (Oxf) 1987;26:53–9.PubMedCrossrefGoogle Scholar

  • 27.

    Ach T, Yosra H, Jihen M, Abdelkarim Asma B, Maha K, et al. Cortisol cut-points for the glucagon stimulation test in the evaluation of hypothalamic pituitary adrenal axis. Endocr J 2018;65:935–42.PubMedCrossrefGoogle Scholar

About the article

Corresponding author: Rajni Sharma, Assistant Professor, Division of Pediatric Endocrinology, Room no.3058, Teaching Block, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi 110029, India, Phone: +919811334144


Received: 2018-07-26

Accepted: 2018-11-11

Published Online: 2018-12-07

Published in Print: 2019-01-28


Author contributions: RS conceived the study, participated in the coordination of the study, carried out the statistical analysis and drafted the manuscript. SM, VM, KR and BJ participated in the study design and collected the data. VJ participated in the coordination of the study, chart review and drafting of the manuscript. All the authors read and approved the final manuscript.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


Citation Information: Journal of Pediatric Endocrinology and Metabolism, Volume 32, Issue 1, Pages 57–63, ISSN (Online) 2191-0251, ISSN (Print) 0334-018X, DOI: https://doi.org/10.1515/jpem-2018-0330.

Export Citation

©2019 Walter de Gruyter GmbH, Berlin/Boston.Get Permission

Comments (0)

Please log in or register to comment.
Log in