Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia

Rensen, Niki; Gemke, Reinoud J. B. J.; Dalen, Elvira C. van; Rotteveel, Joost; Kaspers, Gertjan J. L.

doi:10.1002/14651858.cd008727.pub4

Cited by 55 publications

(53 citation statements)

References 51 publications

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“…In addition, Petersen et al showed that 40% of patients suffer from adrenal insufficiency for over 8 weeks [7]. Cochrane review including 10 studies concluded that impaired adrenal function is common after the induction treatment of childhood ALL and that it usually occurs a few days after tapering of prednisolone [10]. We showed that the earlier the adrenal stimulation test was done, the more likely it showed insufficient response.…”

Section: Discussionmentioning

confidence: 71%

“…CYP3A4 plays an important role in the metabolism of corticosteroids. The Cochrane review also suggests that clinicians should pay special attention to patients who have received fluconazole during their induction therapy [10]. Earlier studies have shown that fluconazole has a delaying effect on the adrenal recovery with fluconazole doses over 10 mg/kg/day [11].…”

Section: Discussionmentioning

confidence: 99%

“…The median time to normal adrenal function in group 1 was 31 days (95% CI 28-34), 24 days in group 2 (95% CI 18-30) and 12 days in group 3 (95% CI [10][11][12][13][14]. The probability for recovery changed between days 20 and 30 for group 3, but for the other two groups the recovery was more linear with time ( Supplementary Fig.…”

Section: Factors Contributing To Full Recovery Of Hpa Axismentioning

confidence: 95%

“…Adrenal insufficiency is a known consequence of a highdose glucocorticoid treatment during induction therapy of ALL treatment in children. Earlier studies have shown a varying incidence and duration of adrenal insufficiency as well as a controversy regarding the need of hydrocortisone substitution [10]. The ideal time point of testing of the adrenal function during intensive ALL therapy, interpretation of the results and length of hydrocortisone substitution, need further evaluation.…”

Section: Introductionmentioning

confidence: 99%

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Adrenal function after induction therapy for acute lymphoblastic leukemia in children short: adrenal function in ALL

2020

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Prednisolone used in the induction phase of the treatment of acute lymphoblastic leukemia (ALL) may suppress hypothalamic-pituitary-adrenal axis and require hydrocortisone substitution. In this retrospective analysis, we reviewed altogether 371 ACTH stimulation tests of 352 children after a uniform NOPHO (Nordic Society of Pediatric Hematology and Oncology) ALL induction. Both low-and standard-dose ACTH tests were used. Full recovery of adrenal function was defined by both normal basal and stimulated cortisol levels. Sixty-two percent of patients were detected with normal adrenal function in median of 15 days after tapering of prednisolone. Both low basal and stimulated cortisol levels were detected in 13% of patients. The median time to normal adrenal function was 31 days (95% CI 28-34), 24 days (95% CI 18-30), and 12 days (95% CI 10-14) for those with basal cortisol <107, 107-183, and >183 nmol/L at first ACTH testing, respectively. Patients with fluconazole prophylaxis had higher median baseline cortisol levels compared to patients without prophylaxis (207 nmol/L, range 21-839 nmol/L vs. 153 nmol/L, range 22-832 nmol/L, P = 0.003).Conclusion: These data can be used to reduce unnecessary substitution or testing, but also to guarantee hydrocortisone substitution for those at risk. What is Known:•These data can be used to reduce unnecessary hydrocortisone substitution or ACTH testing. •Our data helps to guarantee hydrocortisone substitution for those at risk of adrenal insufficiency. What is New:•Full recovery of adrenal function after ALL induction is detected in 62% of patients already at 15 days after tapering of prednisolone.•Both basal and stimulated cortisol testing are required for detection of full adrenal recovery.•Recovery time of adrenal function is extended over 3-4 weeks after tapering of prednisolone in patients with low basal cortisol levels (<107 nmol/L) at first testing.

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Section: Factors Contributing To Full Recovery Of Hpa Axismentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Adrenal function after induction therapy for acute lymphoblastic leukemia in children short: adrenal function in ALL

2020

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“…High-dose fluconazole was suggested as a risk factor for prolonged adrenal insufficiency. The relationship between the presence of infection or stress and adrenal insufficiency were not consistent (Rensen et al 2017).…”

Section: Figurementioning

confidence: 97%

The hypothalamic–pituitary–adrenal axis in childhood cancer survivors

Wei¹,

Crowne²

2018

Endocrine-Related Cancer

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Endocrine abnormalities are common among childhood cancer survivors. Abnormalities of the hypothalamic-pituitary-adrenal axis (HPAA) are relatively less common, but the consequences are severe if missed. Patients with tumours located and/or had surgery performed near the hypothalamic-pituitary region and those treated with an accumulative cranial radiotherapy dose of over 30 Gy are most at risk of adrenocorticotrophic hormone (ACTH) deficiency. Primary adrenal insufficiency may occur in patients with tumours located in or involving one or both adrenals. The effects of adjunct therapies also need to be considered, particularly, new immunotherapies. High-dose and/or prolonged courses of glucocorticoid treatment can result in secondary adrenal insufficiency, which may take months to resolve and hence reassessment is important to ensure patients are not left on long-term replacement steroids inappropriately. The prevalence and cumulative incidences of HPAA dysfunction are difficult to quantify because of its non-specific presentation and lack of consensus regarding its investigations. The insulin tolerance test remains the gold standard for the diagnosis of central cortisol deficiency, but due to its risks, alternative methods with reduced diagnostic sensitivities are often used and must be interpreted with caution. ACTH deficiency may develop many years after the completion of oncological treatment alongside other pituitary hormone deficiencies. It is essential that health professionals involved in the long-term follow-up of childhood cancer survivors are aware of individuals at risk of developing HPAA dysfunction and implement appropriate monitoring and treatment.

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