Abstract
Objective:
Potent glucocorticoids (GC) cause iatrogenic Cushing’s syndrome (ICS) due to suppression of hypothalamo-pituitary-adrenal (HPA) axis and may progress to adrenal insufficiency (AI). The aim was to review the clinical and laboratory findings of patients with ICS and to investigate other serious side effects.
Methods:
The possibility of AI was investigated by low-dose adrenocorticotrophic hormone test. Hydrocortisone was started in patients with adrenal failure.
Results:
Fourteen patients (five boys) with ages ranging from 0.19 to 11.89 years were included. The duration of GC exposure ranged from 1 to 72 months. Ten patients were prescribed topical GC and the rest had oral exposure. Moon face and abdominal obesity were detected in all patients. At presentation, 12 of 14 had AI and two infants had hypercalcemia and nephrocalcinosis. Of 11 patients, ultrasonography revealed hepatosteatosis in five. A cream for diaper dermatitis was used in one infant and the active ingredient was listed as panthenol. However, blood and urine steroid analyses revealed that all endogenous steroids were suppressed. Median (range) time to normalization of HPA axis function was 60 (30-780) days.
Conclusion:
The majority (85%) of patients had life-threatening AI and two patients had hypercalcemia. These results highlight the serious side-effects of inappropriate use of potent GCs, especially in infants. The recovery of the HPA axis in children might take as long as three years. Parents should be informed regarding the possibility of some products containing unlisted synthetic GC and to be aware of their side effects.
Keywords: Cushing’s syndrome, adrenal insufficiency, glucocorticoids, adverse effect, hypercalcemia, non-alcoholic fatty liver disease
Read the full text
6 sections · 2 figures · PDF
Create your free account to read the full text.
- Full text with figures and tables
- PDF and supplementary files
- Access on every Galenos journal
One Galenos account works on every Galenos journal site.
References
Stratakis CA. An update on cushing syndrome in pediatrics. Ann Endocrinol (Paris) 2018;79:125-131. Epub 2018 Apr 9
Paragliola RM, Papi G, Pontecorvi A, Corsello SM. Treatment with synthetic glucocorticoids and the hypothalamus-pituitary-adrenal axis. Int J Mol Sci 2017;18:2201.
Crowley RK, Argese N, Tomlinson JW, Stewart PM. Central hypoadrenalism. J Clin Endocrinol Metab 2014;99:4027-4036.
Broersen LH, Pereira AM, Jørgensen JO, Dekkers OM. Adrenal insufficiency in corticosteroids use: systematic review and meta-analysis. J Clin Endocrinol Metab 2015;100:2171-2180. Epub 2015 Apr 6
Güven A, Gülümser O, Ozgen T. Cushing’s syndrome and adrenocortical insufficiency caused by topical steroids: misuse or abuse? J Pediatr Endocrinol Metab 2007;20:1173-1182.
Guven A, Karadeniz S, Aydin O, Akbalik M, Aydin M. Fatal disseminated cytomegalovirus infection in an infant with Cushing’s syndrome caused by topical steroid. Horm Res 2006;64:35-38. Epub 2005 Aug 2
Joseph RM, Hunter AL, Ray DW, Dixon WG. Systemic glucocorticoid therapy and adrenal insufficiency in adults: a systematic review. Semin Arthritis Rheum 2016;46:133-141. Epub 2016 Mar 9
Barillas JE, Eichner D, Van Wagoner R, Speiser PW. Iatrogenic cushing syndrome in a child with congenital adrenal hyperplasia: erroneous compounding of hydrocortisone. J Clin Endocrinol Metab 2018;103:7-11.
Demir K, Konakçı E, Özkaya G, Kasap Demir B, Özen S, Aydın M, Darendeliler F. New features for child metrics: further growth references and blood pressure calculations. J Clin Res Pediatr Endocrinol 2020;12:125-129. Epub 2019 Sep 2
Weintrob N, Sprecher E, Josefsberg Z, Weininger C, Aurbach-Klipper Y, Lazard D, Karp M, Pertzelan A. 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.
Axelrod L. Perioperative management of patients treated with glucocorticoids. Endocrinol Metab Clin North Am 2003;32:367-383.
Henzen C, Suter A, Lerch E, Urbinelli R, Schorno XH, Briner VA. Suppression and recovery of adrenal response after short-term, high-dose glucocorticoid treatment. Lancet 2000;355:542-545.
Zora JA, Zimmerman D, Carey TL, O’Connell EJ, Yunginger JW. Hypothalamic-pituitary-adrenal axis suppression after short-term, high-dose glucocorticoid therapy in children with asthma. J Allergy Clin Immunol 1986;77:9-13.
Mendoza-Cruz AC, Wargon O, Adams S, Tran H, Verge CF. Hypothalamic-pituitary-adrenal axis recovery following prolonged prednisolone therapy in infants. J Clin Endocrinol Metab 2013;98:E1936-E1940. Epub 2013 Sep 30
Morris HG, Jorgensen JR. Recovery of endogenous pituitary-adrenal function in corticosteroid-treated children. J Pediatr 1971;79:480-488.
Turpeinen M, Salo OP, Leisti S. Effect of percutaneous absorption of hydrocortisone on adrenocortical responsiveness in infants with severe skin disease. Br J Dermatol 1986;115:475-484.
Ellison JA, Patel L, Ray DW, David TJ, Clayton PE. Hypothalamic-pituitary-adrenal function and glucocorticoid sensitivity in atopic dermatitis. Pediatrics 2000;105:794-799.
Turpeinen M. Adrenocortical response to adrenocorticotropic hormone in relation to duration of topical therapy and percutaneous absorption of hydrocortisone in children with dermatitis. Eur J Ped 1989;148:729-731.
Cortet C, Barat P, Zenaty D, Guignat L, Chanson P. Group 5: Acute adrenal insufficiency in adults and pediatric patients. Ann Endocrinol (Paris) 2017;78:535-543. Epub 2017 Nov 23
Bowden SA, Henry R. Pediatric Adrenal Insufficiency: Diagnosis, Management, and New Therapies. Int J Pediatr 2018;2018:1-8.
Gonc EN, Kandemir N, Kinik ST. Significance of low-dose and standard-dose ACTH tests compared to overnight metyrapone test in the diagnosis of adrenal insufficiency in childhood. Horm Res 2003;60:191-197.
Rose SR, Lustig RH, Burstein S, Pitukcheewanont P, Broome DC, Burghen GA. Diagnosis of ACTH deficiency. Comparison of overnight metyrapone test to either low-dose or high-dose ACTH test. Horm Res 1999;52:73-79.
Mongioì LM, Condorelli RA, Barbagallo F, Cannarella R, La Vignera S, Calogero AE. Accuracy of the low-dose ACTH Stimulation test for adrenal insufficiency diagnosis: a re-assessment of the cut-off value. J Clin Med 2019;8:806.
Glenny HP, Brindley DN. The effects of cortisol, corticotropin and thyroxine on the synthesis of glycerolipids and on the phosphatidate phosphohydrolase activity in rat liver. Biochem J 1978;176:777-784.
Magomedova L, Cummins CL. Glucocorticoids and metabolic control. Handb Exp Pharmacol 2016;233:73-93.
Woods CP, Hazlehurst JM, Tomlinson JW. Glucocorticoids and non-alcoholic fatty liver disease. J Steroid Biochem Mol Biol 2015;154:94-103. Epub 2015 Aug 1
Temple JL, Cordero P, Li J, Nguyen V, Oben JA. A Guide to non-alcoholic fatty liver disease in childhood and adolescence. Int J Mol Sci 2016;17:947.
Nerup J. Addison’s disease-clinical studies. a report of 108 cases. Acta Endocrinol 1974;76:127-141.
Wong RK, Gregory R, Lo TC. A case of isolated ACTH deficiency presenting with hypercalcaemia. Int J Clin Pract 2000;54:623-624.
Harano Y, Kitano A, Akiyama Y, Kotajima L, Honda K, Arioka H. A case of isolated adrenocorticotropic hormone deficiency: a rare but possible cause of hypercalcemia. Int Med Case Rep J 2015;8:77-79.
Bhatti RS, Flynn MD. Adrenal insufficiency secondary to inappropriate oral administration of topical exogenous steroids presenting with hypercalcaemia. BMJ Case Rep 2012;2012:bcr0320125983.
Sakao Y, Sugiura T, Tsuji T, Ohashi N, Yasuda H, Fujigaki Y, Kato A. Clinical manifestation of hypercalcemia caused by adrenal insufficiency in hemodialysis patients: a case-series study. Intern Med 2014;53:1485-1490.
Ahn SW, Kim TY, Lee S, Jeong JY, Shim H, Han YM, Choi KE, Shin SJ, Yoon HE. Adrenal insufficiency presenting as hypercalcemia and acute kidney injury. Int Med Case Rep J 2016;9:223-226.
Muls E, Bouillon R, Boelaert J, Lamberigts G, Van Imschoot S, Daneels R, De Moor P. Etiology of hypercalcemia in a patient with Addison’s disease. Calcif Tissue Int 1982;34:523-526.
Miura W, Mizunashi K, Kimura N, Koide Y, Noshiro T, Miura Y, Furukawa Y, Nagura H. Expression of stanniocalcin in zona glomerulosa and medulla of normal human adrenal glands, and some adrenal tumors and cell lines. APMIS 2000;108:367-372.
Cosman F, Nieves J, Herbert J, Shen V, Lindsay R. High-dose glucocorticoids in multiple sclerosis patients exert direct effects on the kidney and skeleton. J Bone Miner Res 1994;9:1097-1105.
Walker DA, Davies M. Addison’s disease presenting as a hypercalcemic crisis in a patient with idiopathic hypoparathyroidism. Clin Endocrinol (Oxf) 1981;14:419-423.
