Home Risk of adrenal insufficiency following intra-articular or periarticular corticosteroid injections among children with chronic arthritis
Article
Licensed
Unlicensed Requires Authentication

Risk of adrenal insufficiency following intra-articular or periarticular corticosteroid injections among children with chronic arthritis

  • Justine Turmel-Roy , Marc-Antoine Bédard , Maude Millette , David Simonyan , Jean-Philippe Proulx-Gauthier EMAIL logo and Isabelle Rousseau-Nepton EMAIL logo
Published/Copyright: August 26, 2020

Abstract

Objectives

Intra-articular and/or periarticular corticosteroid injection (IACI) is a common procedure in pediatric rheumatology. Despite many adult studies demonstrating a significant risk of adrenal insufficiency (AI) following the procedure, very little evidence is available in the pediatric literature regarding this risk. The main goal of this study is to evaluate the prevalence of AI in children with chronic arthritis following IACI.

Methods

This is a retrospective study including children aged 0-18 years who had an IACI from June 2017 to July 2019. An 8:00 morning cortisol (8MC) sample was drawn around two weeks after the injection, and an ACTH 1mcg stimulation test was performed if morning cortisol level was low. AI was defined as an 8MC under 50 nmol/L or an abnormal ACTH stimulation test. Risks factors for AI and its duration were assessed.

Results

Sixty patients were included in this study. AI prevalence was 30% with 18 of 60 affected patients. The corticosteroid dose injected was statistically associated with the development of AI. Median duration of AI was 181 days for the nine patients who were followed up until resolution of AI. Four patients developed symptoms of AI, namely fatigue (2 of 4), nausea (2 of 4) and abdominal pain (3 of 4). None were hospitalized or died.

Conclusions

In this cohort of children with chronic arthritis who had an IACI, we found a high prevalence of AI. Monitoring and counseling of such complication is warranted until further evidence is available.


Corresponding authors: Isabelle Rousseau-Nepton, Department of Pediatrics, Division of Pediatric Endocrinology, CHU de Québec – Université Laval, 2705 Boulevard Laurier, Quebec, G1V4G2, Canada, E-mail: ; and Jean-Philippe Proulx-Gauthier, Department of Pediatrics, Division of Pediatric Rheumatology, CHU de Québec – Université Laval, 2705 Boulevard Laurier, Quebec, G1V4G2, Canada, E-mail:
Dr. Rousseau-Nepton and Dr. Proulx-Gauthier: are co-senior authors.
  1. Research funding: No external funding was secured for this study.

  2. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  3. Competing interests: The authors have no conflict of interests to disclose.

  4. Informed consent: Informed consent was waived given the retrospective nature of this study.

  5. Ethical approval: Research involving human subjects complied with all relevant national regulations, institutional policies and is in accordance with the tenets of the Helsinki Declaration (as revised in 2013), and has been approved by the authors' Institutional Review Board. Patient/parent consent was waived given the retrospective nature of this study.

References

1. Kliegman, RSB, St-Geme, JW, Schor, NF, Behrman, RE. Nelson textbook of pediatrics. Philadelphia, PA: Elsevier; 2016.Search in Google Scholar

2. Prakken, B, Albani, S, Martini, A. Juvenile idiopathic arthritis. Lancet 2011;377:2138–49. https://doi.org/10.1016/s0140-6736(11)60244-4.Search in Google Scholar

3. Habib, GS, Saliba, W, Nashashibi, M. Local effects of intra-articular corticosteroids. Clin Rheumatol 2010;29:347–56. https://doi.org/10.1007/s10067-009-1357-y.Search in Google Scholar PubMed

4. Cardone, DA, Tallia, AF. Joint and soft tissue injection. Am Fam Physician 2002;66:283–8.Search in Google Scholar

5. Habib, GS. Systemic effects of intra-articular corticosteroids. Clin Rheumatol 2009;28:749–56. https://doi.org/10.1007/s10067-009-1135-x.Search in Google Scholar PubMed

6. Berthelot, JM, Le Goff, B, Maugars, Y. Side effects of corticosteroid injections: what’s new?. Joint Bone Spine 2013;80:363–7. https://doi.org/10.1016/j.jbspin.2012.12.001.Search in Google Scholar PubMed

7. Koehler, BE, Urowitz, MB, Killinger, DW. The systemic effects of intra-articular corticosteroid. J Rheumatol 1974;1:117–25.Search in Google Scholar

8. Olivier, C, LJC, MD, d’Omezon, Y, Vague, P, Hawthorn, E. Retentissement de la corticothérapie intra-articulaire et intra-rachidienne sur l’axe hypophyso-surrenal. Rhumatologie 1971;23:323–30.Search in Google Scholar

9. Younes, M, Neffati, F, Touzi, M, Hassen-Zrour, S, Fendri, Y, Bejia, I, et al.. Systemic effects of epidural and intra-articular glucocorticoid injections in diabetic and non-diabetic patients. Joint Bone Spine 2007;74:472–6. https://doi.org/10.1016/j.jbspin.2006.10.009.Search in Google Scholar PubMed

10. Reeback, JS, Chakraborty, J, English, J, Gibson, T, Marks, V. Plasma steroid levels after intra-articular injection of prednisolone acetate in patients with rheumatoid arthritis. Ann Rheum Dis 1980;39:22–4. https://doi.org/10.1136/ard.39.1.22.Search in Google Scholar PubMed PubMed Central

11. Armstrong, RD, English, J, Gibson, T, Chakraborty, J, Marks, V. Serum methylprednisolone levels following intra-articular injection of methylprednisolone acetate. Ann Rheum Dis 1981;40:571–4. https://doi.org/10.1136/ard.40.6.571.Search in Google Scholar PubMed PubMed Central

12. Habib, G, Khazin, F, Jabbour, A, Chernin, M, Badarny, S, Hakim, J, et al.. Simultaneous bilateral knee injection of methylprednisolone acetate and the hypothalamic-pituitary adrenal axis. A Single-Blind Case-Control Study 2014;62:621–6. https://doi.org/10.2310/jim.0000000000000048.Search in Google Scholar PubMed

13. Habib, G, Zahran, R, Najjar, R, Badarny, S, Jabbour, A, Artul, S, et al.. The effect of intra-articular injection of Diprospan at the knee joint on the hypothalamic-pituitary-adrenal axis. Swiss Med Wkly 2015;145:w14134.10.4414/smw.2015.14134Search in Google Scholar PubMed

14. Mader, R, Lavi, I, Luboshitzky, R. Evaluation of the pituitary–adrenal axis function following single intraarticular injection of methylprednisolone. Arthritis Rheum 2005;52:924–8. https://doi.org/10.1002/art.20884.Search in Google Scholar PubMed

15. Reid, DM, Eastmond, C, Rennie, JA. Hypothalamic-pituitary-adrenal axis suppression after repeated intra-articular steroid injections. Ann Rheum Dis 1986;45:87. https://doi.org/10.1136/ard.45.1.87.Search in Google Scholar

16. Duclos, M, Guinot, M, Colsy, M, Merle, F, Baudot, C, Corcuff, JB, et al.. High risk of adrenal insufficiency after a single articular steroid injection in athletes. Med Sci Sports Exerc 2007;39:1036–43. https://doi.org/10.1249/mss.0b013e31805468d6.Search in Google Scholar

17. Weitoft, T, Ronnblom, L. Glucocorticoid resorption and influence on the hypothalamic-pituitary-adrenal axis after intra-articular treatment of the knee in resting and mobile patients. Ann Rheum Dis 2006;65:955–7.10.1136/ard.2005.041525Search in Google Scholar

18. O’Sullivan, MM, Rumfeld, WR, Jones, MK, Williams, BD. Cushing’s syndrome with suppression of the hypothalamic-pituitary-adrenal axis after intra-articular steroid injections. Ann Rheum Dis 1985;44:561–3. https://doi.org/10.1136/ard.44.8.561.Search in Google Scholar

19. Shuster, S, Williams, IA. Adrenal suppression due to intra-articular corticosteroid therapy. Lancet 1961;278:171–2. https://doi.org/10.1016/s0140-6736(61)90461-5.Search in Google Scholar

20. Habib, G, Elias, S, Abu-Elhaija, M, Sakas, F, Khazin, F, Artul, S, et al.. The effect of local injection of methylprednisolone acetate on the hypothalamic-pituitary-adrenal axis among patients with greater trochanteric pain syndrome. Clin Rheumatol 2017;36:959–63. https://doi.org/10.1007/s10067-016-3517-1.Search in Google Scholar

21. Habib, G, Jabbour, A, Artul, S, Hakim, G. Intra-articular methylprednisolone acetate injection at the knee joint and the hypothalamic-pituitary-adrenal axis: a randomized controlled study. Clin Rheumatol 2014;33:99–103. https://doi.org/10.1007/s10067-013-2374-4.Search in Google Scholar

22. Lazarevic, MB, Skosey, JL, Djordjevic-Denic, G, Swedler, WI, Zgradic, I, Myones, BL. Reduction of cortisol levels after single intra-articular and intramuscular steroid injection. Am J Med 1995;99:370–3. https://doi.org/10.1016/s0002-9343(99)80183-1.Search in Google Scholar

23. Broersen, LH, Pereira, AM, Jorgensen, JO, Dekkers, OM. Adrenal insufficiency in corticosteroids use: systematic review and meta-analysis. J Clin Endocrinol Metab 2015;100:2171–80. https://doi.org/10.1210/jc.2015-1218.Search in Google Scholar PubMed

24. Weiss, S, Fischel, B, Kisch, ES. Systemic effects of intra-articular steroid preparations. Ann Rheum Dis 1980;39:413–4. https://doi.org/10.1136/ard.39.4.413.Search in Google Scholar PubMed PubMed Central

25. Bancos, I, Hahner, S, Tomlinson, J, Arlt, W. Diagnosis and management of adrenal insufficiency. Lancet Diabetes Endocrinol 2015;3:216–26. https://doi.org/10.1016/s2213-8587(14)70142-1.Search in Google Scholar

26. Shulman, DI, Palmert, MR, Kemp, SF. Lawson Wilkins, D, Therapeutics, C. Adrenal insufficiency: still a cause of morbidity and death in childhood. Pediatrics 2007;119:e484–94. https://doi.org/10.1542/peds.2006-1612.Search in Google Scholar PubMed

27. Bornstein, SR, Allolio, B, Arlt, W, Barthel, A, Don-Wauchope, A, Hammer, GD, et al.. Diagnosis and treatment of primary adrenal insufficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2016;101:364–89. https://doi.org/10.1210/jc.2015-1710.Search in Google Scholar PubMed PubMed Central

28. Huppertz, HI, Pfüller, H. Transient suppression of endogenous cortisol production after intraarticular steroid therapy for chronic arthritis in children. J Rheumatol 1997;24:1833–7.Search in Google Scholar

29. Laaksonen, AL, Sunell, JE, Westerén, H, Mulder, J. Adrenocortical function in children with juvenile rheumatoid arthritis and other connective tissue disorders. Scand J Rheumatol 1974;3:137–42. https://doi.org/10.3109/03009747409097139.Search in Google Scholar PubMed

30. Derendorf, H, Möllmann, H, Grüner, A, Haack, D, Gyselby, G. Pharmacokinetics and pharmacodynamics of glucocorticoid suspensions after intra-articular administration. Clin Pharmacol Ther 1986;39:313–7. https://doi.org/10.1038/clpt.1986.45.Search in Google Scholar PubMed

31. Kumar, S, Singh, RJ, Reed, AM, Lteif, AN. Cushing’s syndrome after intra-articular and intradermal administration of triamcinolone acetonide in three pediatric patients. Pediatrics 2004;113:1820–4. https://doi.org/10.1542/peds.113.6.1820.Search in Google Scholar PubMed

32. Habib, G, Artul, S, Chernin, M, Hakim, G, Jabbour, A. The effect of intra-articular injection of betamethasone acetate/betamethasone sodium phosphate at the knee joint on the hypothalamic-pituitary-adrenal axis: a case-controlled study. J Investig Med 2013;61:1104–7. https://doi.org/10.2310/jim.0b013e3182a67871.Search in Google Scholar PubMed

33. Esselinckx, W, Kolanowski, J, Nagant de Deuxchaisnes, C. Adrenocortical function and responsiveness to tetracosactrin infusions after intra-articular treatment with triamcinolone acetonide and hydrocortisone acetate. Clin Rheumatol 1982;1:176–84. https://doi.org/10.1007/bf02042771.Search in Google Scholar PubMed

34. Wicki, J, Droz, M, Cirafici, L, Vallotton, MB. Acute adrenal crisis in a patient treated with intraarticular steroid therapy. J Rheumatol 2000;27:510–1.Search in Google Scholar

35. Kazlauskaite, R, Evans, AT, Villabona, CV, Abdu, TA, Ambrosi, B, Atkinson, AB, et al.. Corticotropin tests for hypothalamic-pituitary- adrenal insufficiency: a metaanalysis. J Clin Endocrinol Metab 2008;93:4245–53. https://doi.org/10.1210/jc.2008-0710.Search in Google Scholar PubMed

36. Mager, DE, Lin, SX, Blum, RA, Lates, CD, Jusko, WJ. Dose equivalency evaluation of major corticosteroids: pharmacokinetics and cell trafficking and cortisol dynamics. J Clin Pharmacol 2003;43:1216–27. https://doi.org/10.1177/0091270003258651.Search in Google Scholar PubMed

37. Ahmet, A, Brienza, V, Tran, A, Lemieux, J, Aglipay, M, Barrowman, N, et al.. Frequency and duration of adrenal suppression following glucocorticoid therapy in children with rheumatic diseases. Arthritis Care Res 2017;69:1224–30. https://doi.org/10.1002/acr.23123.Search in Google Scholar

38. Charmandari, E, Nicolaides, NC, Chrousos, GP. Adrenal insufficiency. Lancet 2014;383:2152–67. https://doi.org/10.1016/s0140-6736(13)61684-0.Search in Google Scholar

Received: 2020-04-26
Accepted: 2020-07-13
Published Online: 2020-08-26

© 2020 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Research Articles
  3. Analysis of the alpha galactosidase gene: mutation profile and description of two novel mutations with extensive literature review in Turkish population
  4. Cascade screening and treatment of children with familial hypercholesterolemia in Turkey
  5. Risk of adrenal insufficiency following intra-articular or periarticular corticosteroid injections among children with chronic arthritis
  6. Vitamin D status is related to severity at onset of diabetes and worse glycemic control
  7. Reassessing vitamin D supplementation in preterm infants: a prospective study and review of the literature
  8. Mutations in PMM2 gene in four unrelated Spanish families with polycystic kidney disease and hyperinsulinemic hypoglycemia
  9. Liraglutide pharmacokinetics and exposure-response in pediatric patients with type 2 diabetes
  10. Identification of nucleotide polymorphism within the NeuroD1 candidate gene and its association with type 1 diabetes susceptibility in Iranian people by polymerase chain reaction-restriction fragment length polymorphism
  11. Prevalence of autoantibodies in type 1 diabetes mellitus pediatrics in Mazandaran, North of Iran
  12. Clinical features of the diabetes eating problem survey–revised Turkish version in children and adolescent with type 1 diabetes
  13. Ambulatory blood pressure profile in office normotensive obese children: prevalence of masked hypertension and impact of parental hypertension
  14. Glycogen storage disease type VI can progress to cirrhosis: ten Chinese patients with GSD VI and a literature review
  15. Short Communication
  16. Screening for imprinting disorders in 58 patients with clinically diagnosed idiopathic short stature
  17. Case Reports
  18. ROHHAD syndrome – A still unrecognized cause of childhood obesity: report of three cases
  19. Carbonic anhydrase VA deficiency: a very rare case of hyperammonemic encephalopathy
  20. Idiopathic infantile hypercalcemia: mutations in SLC34A1 and CYP24A1 in two siblings and fathers
  21. GCK-MODY in a child with cystic fibrosis: the doubt of the treatment plan
Downloaded on 14.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/jpem-2020-0219/html
Scroll to top button