İntravenöz yolla yüksek dozda ve orta-uzun süreli verilen deksametazon ve metilprednizolon tedavilerinin hipotalamus-hipofiz-adrenal (HHA) aksa etkisi

Doğuş Vurallı; Ayfer Alikaşifoğlu

doi:10.12956/tchd.644700

Research Article

İntravenöz yolla yüksek dozda ve orta-uzun süreli verilen deksametazon ve metilprednizolon tedavilerinin hipotalamus-hipofiz-adrenal (HHA) aksa etkisi

Year 2020, Volume: 14 Issue: 4, 333 - 338, 26.06.2020

Doğuş Vurallı , Ayfer Alikaşifoğlu

https://doi.org/10.12956/tchd.644700

Abstract

Amaç: Uzun etkili ve potent bir
glukortikoid olan deksametazon ve orta etkili ve orta etki gücü
olan metilprednizolonun intravenöz puşe olarak verilmesinin adrenal
yetmezliğe neden olup olmadığını ve veriliş şeklinin adrenal
yetmezlik riskini değiştirip değiştirmediğini değerlendirmektir.

Gereç ve Yöntemler: Yaşları 2
ay ve 18 yaş arası değişen ve son 3 yılda çeşitli sebeplerle
on günden daha uzun süre intravenöz deksametazon veya
metilprednizolon tedavisi alan ve steroid tedavisinin kesilmesi
açısından Çocuk Endokrinoloji bölümüne yönlendirilen 46 olgu
(24 kız, 22 erkek) çalışmaya dahil edildi. Olguların yaşı,
kortikosteroid tedavisi alma süreleri (gün), hidrokortizon eşdeğeri
olarak ortalama tedavi dozu (mg/m²/gün),
tedavi alırken değerlendirilen bazal ACTH ve kortizol düzeyleri,
düşük doz ACTH testi zirve kortizol yanıtı kaydedildi. Serumda
bazal sabah kortizol düzeyi 3 μg/dl'nin
(85 nmol/L) altında olması kortikosteroid kullanımına bağlı
adrenal
yetmezlik lehine değerlendirilirken 20 μg/dl'nin
üzerinde olması
normal
kabul edildi. Düşük
doz ACTH testinde zirve kortizol düzeyinin ≥18
μg/dl (500 nmol/L) olması normal olarak değerlendirildi.

Bulgular: Olguların ortalama
yaşları 7.9±5.8
yıl (aralık 2 ay-18 yıl), ortalama kortikosteroid kullanma
süreleri 26.2±11.8
(aralık 12-75) gün, ortalama günlük doz sayısı 2.2±1.2
(aralık 1-4), ortalama hidrokortizon eşdeğeri kortikosteroid
dozları 235.6±114.6
(aralık 86-428) mg/m²/gün
idi. Olguların ortalama bazal kortizol düzeyi 9.9±4.0
(aralık 4.2-16.8) μg/dl,
ortalama bazal ACTH
düzeyi 30.4±18.6
(aralık 8.6-72.5) pg/ml idi. Olguların hepsinin zirve kortizol
yanıtı ≥
18 μg/dl idi.

Tartışma/Sonuç: Çalışmamızda
suprafizyolojik dozlarda ortalama 26 gün gibi uzun bir sürede
deksametazon ve metilprednizolon gibi güçlü glukokortikoidlerin
intravenöz yolla verilmesine rağmen olguların hiçbirinde adrenal
supresyon gelişmemiş olması adrenal supresyon gelişiminde tedavi
süresi ve tedavi dozu kadar ilacın veriliş şeklinin de önemli
olduğunu göstermektedir. Glukortikoidlerin hızlı intravenöz
infüzyon/intravenöz puşe yolu ile verilmesi adrenal supresyon
açısından daha az riskli olabilir. Bu konu ile ilgili daha çok
sayıda vaka içeren çalışmalara ihtiyaç vardır.

Keywords

Adrenal yetmezlik, deksametazon, hipotalamo-hipofizer sistem, metilprednizolon

References

1. Spiegel RJ, Vigersky RA, Oliff AI, Echelberger CK, Bruton J, Poplack DG. Adrenal suppression after short-term corticosteroid therapy. Lancet. 1979 Mar 24;1(8117):630-3.
2. Arlt W, Allolio B. Adrenal insufficiency. Lancet. [Research Support, Non-U.S. Gov't]. 2003 May 31;361(9372):1881-93.
3. Axelrod L. Perioperative management of patients treated with glucocorticoids. Endocrinol Metab Clin North Am. [Review]. 2003 Jun;32(2):367-83.
4. LaRochelle GE, Jr., LaRochelle AG, Ratner RE, Borenstein DG. Recovery of the hypothalamic-pituitary-adrenal (HPA) axis in patients with rheumatic diseases receiving low-dose prednisone. Am J Med. [Review]. 1993 Sep;95(3):258-64.
5. Harter JG, Reddy WJ, Thorn GW. Studies on an Intermittent Corticosteroid Dosage Regimen. N Engl J Med. 1963 Sep 19;269:591-6.
6. Fauci AS. Alternate-day corticosteroid therapy. Am J Med. 1978 May;64(5):729-31.
7. Ackerman GL, Nolsn CM. Adrenocortical responsiveness after alternate-day corticosteroid therapy. N Engl J Med. [Clinical Trial Controlled Clinical Trial]. 1968 Feb 22;278(8):405-9.
8. Cooper MS, Stewart PM. Corticosteroid insufficiency in acutely ill patients. N Engl J Med. [Review]. 2003 Feb 20;348(8):727-34.
9. Westerhof L, Van Ditmars MJ, Der Kinderen PJ, Thijssen JH, Schwarz F. Recovery of adrenocortical function during long-term treatment with corticosteroids. BMJ. 1972 Apr 22;2(5807):195-7.
10. Graber AL, Ney RL, Nicholson WE, Island DP, Liddle GW. Natural History of Pituitary-Adrenal Recovery Following Long-Term Suppression with Corticosteroids. J Clin Endocrinol Metab. 1965 Jan;25:11-6.
11. Schlaghecke R, Kornely E, Santen RT, Ridderskamp P. The effect of long-term glucocorticoid therapy on pituitary-adrenal responses to exogenous corticotropin-releasing hormone. N Engl J Med. 1992 Jan 23;326(4):226-30.
12. Walther FJ, Findlay RD, Durand M. Adrenal suppression and extubation rate after moderately early low-dose dexamethasone therapy in very preterm infants. Early Hum Dev. [Clinical Trial Randomized Controlled Trial Research Support, U.S. Gov't, P.H.S.]. 2003 Oct;74(1):37-45.
13. Brundage KL, Mohsini KG, Froese AB, Walker CR, Fisher JT. Dexamethasone therapy for bronchopulmonary dysplasia: improved respiratory mechanics without adrenal suppression. Pediatr Pulmonol. [Research Support, Non-U.S. Gov't]. 1992 Mar;12(3):162-9.
14. Deutschbein T, Unger N, Mann K, Petersenn S. Diagnosis of secondary adrenal insufficiency: unstimulated early morning cortisol in saliva and serum in comparison with the insulin tolerance test. Horm Metabolic Res. 2009 Nov;41(11):834-9.
15. Endert E, Ouwehand A, Fliers E, Prummel MF, Wiersinga WM. Establishment of reference values for endocrine tests. Part IV: Adrenal insufficiency. Neth J Med. 2005 Dec;63(11):435-43.
16. Krasner AS. Glucocorticoid-induced adrenal insufficiency. JAMA. [Case Reports Clinical Conference]. 1999 Aug 18;282(7):671-6.
17. Grinspoon SK, Biller BM. Clinical review 62: Laboratory assessment of adrenal insufficiency. J Clin Endocrinol Metab. [Research Support, U.S. Gov't, P.H.S. Review]. 1994 Oct;79(4):923-31.
18. Zollner EW. Hypothalamic-pituitary-adrenal axis suppression in asthmatic children on inhaled corticosteroids: part 1. Which test should be used? Pediatr Allergy Immunol. [Review]. 2007 Aug;18(5):401-9.
19. 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. [Clinical Trial Controlled Clinical Trial Research Support, Non-U.S. Gov't]. 2003;60(4):191-7.
20. Tordjman K, Jaffe A, Grazas N, Apter C, Stern N. The role of the low dose (1 microgram) adrenocorticotropin test in the evaluation of patients with pituitary diseases. J Clin Endocrinol Metab. 1995 Apr;80(4):1301-5.
21. Laxer RM. Pharmacology and drug therapy. In: Cassidy JT PR, Laxer RM, Lindsley CB, editor. Textbook of pediatric rheumatology. 5 ed. Philadelphia: Elsevier; 2005. p. 76-141.
22. Nichols T, Nugent CA, Tyler FH. Diurnal Variation in Suppression of Adrenal Function by Glucocorticoids. J Clin Endocrinol Metab.1965 Mar;25:343-9.
23. Wenning GK, Wietholter H, Schnauder G, Muller PH, Kanduth S, Renn W. Recovery of the hypothalamic-pituitary-adrenal axis from suppression by short-term, high-dose intravenous prednisolone therapy in patients with MS. Acta Neurol Scand. 1994 Apr;89(4):270-3.
24. Brophy T, Chalk JB, Ridgeway K, Tyrer JH, Eadie MJ. Cortisol production during high dose dexamethasone therapy in neurological and neurosurgical patients. Journal Neurol Neurosurg Psychiatry. 1984 Oct;47(10):1081-6.
25. Faical S, Uehara MH. [Systemic effects and withdrawal syndrome in chronic users of corticosteroids]. Rev Assoc Med Bras. [Review]. 1998 Jan-Mar;44(1):69-74.
26. Kozower M, Veatch L, Kaplan MM. Decreased clearance of prednisolone, a factor in the development of corticosteroid side effects. J Clin Endocrinol Metab 1974 Mar;38(3):407-12.
27. Da Silva AN, Schiff D. Adrenal insufficiency secondary to glucocorticoid withdrawal in patients with brain tumor. Surg Neurol. 2007 May;67(5):508-10.
28. Goichot B, Vinzio S, Luca F, Schlienger JL. [Do we still have glucocorticoid-induced adrenal insufficiency?]. Presse Med. [Review]. 2007 Jul-Aug;36(7-8):1065-71.

Year 2020, Volume: 14 Issue: 4, 333 - 338, 26.06.2020

Doğuş Vurallı , Ayfer Alikaşifoğlu

https://doi.org/10.12956/tchd.644700

Abstract

References

1. Spiegel RJ, Vigersky RA, Oliff AI, Echelberger CK, Bruton J, Poplack DG. Adrenal suppression after short-term corticosteroid therapy. Lancet. 1979 Mar 24;1(8117):630-3.
2. Arlt W, Allolio B. Adrenal insufficiency. Lancet. [Research Support, Non-U.S. Gov't]. 2003 May 31;361(9372):1881-93.
3. Axelrod L. Perioperative management of patients treated with glucocorticoids. Endocrinol Metab Clin North Am. [Review]. 2003 Jun;32(2):367-83.
4. LaRochelle GE, Jr., LaRochelle AG, Ratner RE, Borenstein DG. Recovery of the hypothalamic-pituitary-adrenal (HPA) axis in patients with rheumatic diseases receiving low-dose prednisone. Am J Med. [Review]. 1993 Sep;95(3):258-64.
5. Harter JG, Reddy WJ, Thorn GW. Studies on an Intermittent Corticosteroid Dosage Regimen. N Engl J Med. 1963 Sep 19;269:591-6.
6. Fauci AS. Alternate-day corticosteroid therapy. Am J Med. 1978 May;64(5):729-31.
7. Ackerman GL, Nolsn CM. Adrenocortical responsiveness after alternate-day corticosteroid therapy. N Engl J Med. [Clinical Trial Controlled Clinical Trial]. 1968 Feb 22;278(8):405-9.
8. Cooper MS, Stewart PM. Corticosteroid insufficiency in acutely ill patients. N Engl J Med. [Review]. 2003 Feb 20;348(8):727-34.
9. Westerhof L, Van Ditmars MJ, Der Kinderen PJ, Thijssen JH, Schwarz F. Recovery of adrenocortical function during long-term treatment with corticosteroids. BMJ. 1972 Apr 22;2(5807):195-7.
10. Graber AL, Ney RL, Nicholson WE, Island DP, Liddle GW. Natural History of Pituitary-Adrenal Recovery Following Long-Term Suppression with Corticosteroids. J Clin Endocrinol Metab. 1965 Jan;25:11-6.
11. Schlaghecke R, Kornely E, Santen RT, Ridderskamp P. The effect of long-term glucocorticoid therapy on pituitary-adrenal responses to exogenous corticotropin-releasing hormone. N Engl J Med. 1992 Jan 23;326(4):226-30.
12. Walther FJ, Findlay RD, Durand M. Adrenal suppression and extubation rate after moderately early low-dose dexamethasone therapy in very preterm infants. Early Hum Dev. [Clinical Trial Randomized Controlled Trial Research Support, U.S. Gov't, P.H.S.]. 2003 Oct;74(1):37-45.
13. Brundage KL, Mohsini KG, Froese AB, Walker CR, Fisher JT. Dexamethasone therapy for bronchopulmonary dysplasia: improved respiratory mechanics without adrenal suppression. Pediatr Pulmonol. [Research Support, Non-U.S. Gov't]. 1992 Mar;12(3):162-9.
14. Deutschbein T, Unger N, Mann K, Petersenn S. Diagnosis of secondary adrenal insufficiency: unstimulated early morning cortisol in saliva and serum in comparison with the insulin tolerance test. Horm Metabolic Res. 2009 Nov;41(11):834-9.
15. Endert E, Ouwehand A, Fliers E, Prummel MF, Wiersinga WM. Establishment of reference values for endocrine tests. Part IV: Adrenal insufficiency. Neth J Med. 2005 Dec;63(11):435-43.
16. Krasner AS. Glucocorticoid-induced adrenal insufficiency. JAMA. [Case Reports Clinical Conference]. 1999 Aug 18;282(7):671-6.
17. Grinspoon SK, Biller BM. Clinical review 62: Laboratory assessment of adrenal insufficiency. J Clin Endocrinol Metab. [Research Support, U.S. Gov't, P.H.S. Review]. 1994 Oct;79(4):923-31.
18. Zollner EW. Hypothalamic-pituitary-adrenal axis suppression in asthmatic children on inhaled corticosteroids: part 1. Which test should be used? Pediatr Allergy Immunol. [Review]. 2007 Aug;18(5):401-9.
19. 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. [Clinical Trial Controlled Clinical Trial Research Support, Non-U.S. Gov't]. 2003;60(4):191-7.
20. Tordjman K, Jaffe A, Grazas N, Apter C, Stern N. The role of the low dose (1 microgram) adrenocorticotropin test in the evaluation of patients with pituitary diseases. J Clin Endocrinol Metab. 1995 Apr;80(4):1301-5.
21. Laxer RM. Pharmacology and drug therapy. In: Cassidy JT PR, Laxer RM, Lindsley CB, editor. Textbook of pediatric rheumatology. 5 ed. Philadelphia: Elsevier; 2005. p. 76-141.
22. Nichols T, Nugent CA, Tyler FH. Diurnal Variation in Suppression of Adrenal Function by Glucocorticoids. J Clin Endocrinol Metab.1965 Mar;25:343-9.
23. Wenning GK, Wietholter H, Schnauder G, Muller PH, Kanduth S, Renn W. Recovery of the hypothalamic-pituitary-adrenal axis from suppression by short-term, high-dose intravenous prednisolone therapy in patients with MS. Acta Neurol Scand. 1994 Apr;89(4):270-3.
24. Brophy T, Chalk JB, Ridgeway K, Tyrer JH, Eadie MJ. Cortisol production during high dose dexamethasone therapy in neurological and neurosurgical patients. Journal Neurol Neurosurg Psychiatry. 1984 Oct;47(10):1081-6.
25. Faical S, Uehara MH. [Systemic effects and withdrawal syndrome in chronic users of corticosteroids]. Rev Assoc Med Bras. [Review]. 1998 Jan-Mar;44(1):69-74.
26. Kozower M, Veatch L, Kaplan MM. Decreased clearance of prednisolone, a factor in the development of corticosteroid side effects. J Clin Endocrinol Metab 1974 Mar;38(3):407-12.
27. Da Silva AN, Schiff D. Adrenal insufficiency secondary to glucocorticoid withdrawal in patients with brain tumor. Surg Neurol. 2007 May;67(5):508-10.
28. Goichot B, Vinzio S, Luca F, Schlienger JL. [Do we still have glucocorticoid-induced adrenal insufficiency?]. Presse Med. [Review]. 2007 Jul-Aug;36(7-8):1065-71.

There are 28 citations in total.

Details

Primary Language	Turkish
Subjects	Internal Diseases
Journal Section	ORIGINAL ARTICLES
Authors	Doğuş Vurallı 0000-0002-4011-2299 Ayfer Alikaşifoğlu 0000-0003-3379-6407
Publication Date	June 26, 2020
Submission Date	November 9, 2019
Published in Issue	Year 2020 Volume: 14 Issue: 4

Cite

Vancouver	Vurallı D, Alikaşifoğlu A. İntravenöz yolla yüksek dozda ve orta-uzun süreli verilen deksametazon ve metilprednizolon tedavilerinin hipotalamus-hipofiz-adrenal (HHA) aksa etkisi. Türkiye Çocuk Hast Derg. 2020;14(4):333-8.

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