• Nani Wijayanti Dn Department of Pharmacy, Hang Tuah University, Surabaya, Java, Indonesia.
  • Nun Zairina Department of Pharmacy, Installation of Dr. Soetomo Teaching Hospital Surabaya, Surabaya, Java, Indonesia.
  • Ninik Asmaningsih Department of Pediatrics, Nephrology Division, Dr. Soetomo Teaching Hospital Surabaya, Surabaya, Java, Indonesia.
  • Yulistiani Department of Pharmacy, Hang Tuah University, Surabaya, Java, Indonesia.


Objective: The objective of this study is to analyze the cortisol levels in induction and alternate phases associated with the clinical manifestation in the developing of adrenal suppression.

Methods: An observational, longitudinal study which had been approved by the ethical committee of Dr. Soetomo Teaching Hospital Surabaya was conducted from June to October 2016. The cortisol levels were measured before induction phase (t=0), after induction phase (t=1), and after alternate phase (t=2). The venous blood samples were obtained in the morning at 08.00–09.00 am. The data were analyzed using student's t-test.

Results: A total of 15 patients were included, but 6 patients were excluded because of cross-reactivity with prednisone when using ADVIA Centaur Cortisol Assay. 9 patients (55.56% boys) had a mean age 6–< 12 years old and 33.33% were initial attack and dependent steroid nephrotic syndrome. 8 of 9 patients had a normal cortisol level at baseline (t=0). The cortisol level decrement in the induction phase was 72.92% (11.79±10.66 mcg/dL–1.75±1.08 mcg/dL) (*p=0.024). After alternate phase, the cortisol levels increased 417.60% (1.75±1.08 mcg/dL to 5.95±3.33 mcg/dL (*p=0.007). The clinical manifestation as nausea/vomiting and abdominal distension only appeared in 11.11% of patients in the induction phase but not in the alternate phase.

Conclusions: Hypothalamus-pituitary-adrenal (HPA) axis suppression could develop after induction phase which was indicated by low cortisol levels. High-dose and long-term prednisone exposure decreased the cortisol levels reversibly. The clinical manifestation of adrenal suppression as weakness, nausea/vomiting, acute dehydration, and abdominal distension almost did not manifest in all patients.

Keywords: Cortisol, Nephrotic syndrome, Sensitive steroid nephrotic syndrome, Prednisone, High-dose prednisone, Long-term prednisone, Hypothalamus-pituitary-adrenal axis suppression, Children.


1. Alatas H, Taralan T, Partini P, Sudung OP. Konsesus Tata Laksana Sindrom Nefrotik Idiopatik pada Anak. Jakarta: Ikatan Dokter Anak Indonesia; 2008. p. 1-18.
2. Lennon R, Watson L, Webb NJ. Nephrotic syndrome in children. Paediatr Child Health 2009;20:36-42.
3. Krishnan RG. Nephronic Syndrome. Paediatr Child Health 2009;22:337-40.
4. Trihono PP, Alatas H, Tambunan T, Pardede SO. Tata Laksana Sindrom Nefrotik Idiopatik pada Anak Edisi Kedua. Jakarta: Unit Kerja Koordinasi Nefrologi IDAI; 2012. p. 1-32.
5. Niaudet P. Treatment of Idiopathic Nephrotic Syndrome in Children. Netherland: UpToDate Wolters Kluwer; 2015. p. 1-20.
6. Niaudet P, Boyer O. Idiopathic nephrotic syndrome in children: Clinical aspects. In Avner ED, Harmon WE, Niaudet P, Yoshikawa N, Emma F, Goldstein S, editors. Pediatric Nephrology. 7th ed. New York: Springer; 2016. p. 841-3.
7. Lombel RM, Gipson DS, Hodson EM. Treatment of steroid-sensitive nephrotic syndrome: New guidelines from KDIGO. Pediatr Nephrol 2012;2:1-17.
8. Gupta P, Bhatia V. Corticosteroid physiology and principles of therapy. Indian J Pediatr 2008;75:1-8.
9. Hilal-Dandan R, Brunton LL, editors. Modulation of cardiovascular function. Goodman and Gilman’s Manual of Pharmacology and Therapeutics. 2nd ed, New York: McGraw Hill; 2014. p. 770-9.
10. Chrousos GP. Physiology of Corticotropin-Releasing Hormone. Netherland: UpToDate Wolters Kluwer; 2015. p. 1-15.
11. Shulman DL, Palmert MR, Kemp SF. Adrenal insufficiency: Still a cause of morbidity and death in childhood. Pediatrics 2007;119:e484-94.
12. Liu D, Ahmet A, Ward L, Krshnamoorthy P, Mandelcom E, Leigh R, et al. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin Immunol J 2013;30:1-25.
13. Miller WL, Fluck CE. Adrenal cortex and its disorder. In Sperling MA, editor, Pediatric Endocrinology 4th ed. Philadelphia,PA: Saunders Elsivier; 2014. p. 537-8.
14. Einaudi S, Bertorello N, Masera N, Farinasso L, Borisone E, Rizzari C, et al. Adrenal axis function after high-dose steroid therapy for childhood acute lymphoblastic leukemia. Pediart Blood Cancer 2008;50:537-41.
15. Soyka LF, Saxena KM. Alternate-day steroid therapy for nephrotic children. JAMA 1965;192:125-30.
16. Leisti S, Koskimies O. Risk of relapse in steroid-sensitive nephrotic syndrome: Effect of stage of post-prednisone adrenocortical suppression. J Pediatr 1983;103:553-8.
17. Sumboonnanonda A, Vingjirad A, Suntorpoch V, Petrarat S. Adrenal function after prednisolone treatment in childhood nephrotic syndrome. J Med Assoc Thai 1994;77:126-9.
18. Abeyagunawardena AS, Hindamarsh P, Trompeter R. Adrenocortical suppression increase the risk of relapse in nephrotic syndrome. Arch Dis Child 2007;92:585-8.
19. Ramachandran R, Jairam A, Bhansali A, Jha V, Gupta K, Sakhuja V, et al. Study of hypothalamic pituitary adrenal axis in patients of membranous nephropathy receiving modified ponticelli regimen. Indian J Nephrol 2015;1:1-5.
20. Krasowski MD, Dress D, Morris CS, Maaskestad J, Blau JL, Ekins S, et al. Cross-reactivity of steroid hormone immunoassays: Clinical significance and two-dimensional molecular similarity prediction. BMC Clin Pathol 2014;33:1-13.
21. Bartels M, De Geus E, Kirschbaum C, Sluyter F, Boomsma DI. Heritability of daytime cortisol levels in children. Behav Genet 2003;33:421-33.
22. Furst DF, Saag K G. Glucocorticoid Withdrawal. Ohio: UpToDate Wolters Kluwer; 2015. p. 1-19.
23. Gunnar MR, Donzella B. Social regulation of cortisol levels in early human development. Psychoneuroendocrinology 2002;27:199-220.
24. Barrett EJ. The adrenal gland. In Boron WF, Boulpeb EL, editors, Medical Physiology, A Cellular and Molecular Approach. Philadelphia, PA: Elsevier Saunders; 2012. p. 1057-73.
25. Bancos I, Hahner S, Tomlinson J, Arlt W. Diagnosis and management of adrenal insufficiency. Lancet 2014;14:70142-1.
26. Taketomo C, Hodding J, Kraus, D. Pediatric Dosage Handbook. 17th ed. Ohio: Lexicomp; 2002, 2013. p. 1569.
27. Lexicomp. Pediatric Drug Information Prednisone. Ohio: UpToDate Wolters Kluwer; 2015. p. 1-14.
28. Donohoue PA. Diagnosis of Adrenal Insuffiency in Children. Ohio: UpToDate Wolters Kluwer; 2014. p. 1-21.
232 Views | 205 Downloads
How to Cite
Dn, N. W., N. Zairina, N. Asmaningsih, and Yulistiani. “ANALYSIS OF CORTISOL LEVEL AFTER HIGH-DOSE AND LONG-TERM PREDNISONE EXPOSURE IN CHILDREN WITH STEROID-SENSITIVE NEPHROTIC SYNDROME”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 11, no. 15, Oct. 2018, pp. 56-60, doi:10.22159/ajpcr.2018.v11s3.30031.
Original Article(s)