A prospective study of the hypothalamic-pituitary-adrenal axis in children with acute lymphoblastic leukemia receiving chemotherapy

Salem, Mona A.; Tantawy, Azza Abdel Gawad; Sedfy, H H El; Laboudy, Mohamed A. El; Toaima, Dalia N.; Mahmoud, Nermine H.; Selim, Dalia

doi:10.1179/1607845414y.0000000208

Cited by 14 publications

(27 citation statements)

References 22 publications

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“…A key issue is time to recovery of the HPA axis following discontinuation of glucocorticoid treatment. The percentage of patients with adrenal insufficiency following oral treatment cessation declines over time, but remains up to 40% six months following cessation (21,22,23,24,25), 20% two years following cessation (26,27,28), and 5% three years following cessation (26). This underscores the potential long-term nature of adrenal insufficiency after glucocorticoid use.…”

Section: Recovery Of the Hpa Axismentioning

confidence: 97%

MANAGEMENT OF ENDOCRINE DISEASE: Glucocorticoid-induced adrenal insufficiency: replace while we wait for evidence?

Laugesen

Broersen

Hansen

et al. 2021

European Journal of Endocrinology

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Glucocorticoids are, besides non-steroidal anti-inflammatory drugs, the most widely used anti-inflammatory medications. Prevalence studies indicate substantial use of both systemic and locally acting agents. A recognized adverse effect of glucocorticoid treatment is adrenal insufficiency, which is highly prevalent based on biochemical testing, but its clinical implications are poorly understood. Current evidence, including randomized trials and observational studies, indicates substantial variation among patients in both risk and course of glucocorticoid-induced adrenal insufficiency, but both are currently unpredictable. Oral and intra-articular formulations, as well as long-term and high-dose treatments, carry the highest risk of glucocorticoid-induced adrenal insufficiency defined by biochemical tests. However, no route of administration, treatment duration, or dose can be considered without risk. More research is needed to estimate the risk and temporal pattern of glucocorticoid-induced adrenal insufficiency, to investigate its clinical implications, and to identify predictors of risk and prognosis. Randomized trials are required to evaluate whether hydrocortisone replacement therapy mitigates risk and symptoms of glucocorticoid-induced adrenal insufficiency in patients discontinuing glucocorticoid treatment. This review aims to provide an overview of available evidence, pointing to knowledge gaps and unmet needs.

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Section: Recovery Of the Hpa Axismentioning

confidence: 97%

MANAGEMENT OF ENDOCRINE DISEASE: Glucocorticoid-induced adrenal insufficiency: replace while we wait for evidence?

Laugesen

Broersen

Hansen

et al. 2021

European Journal of Endocrinology

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“…It may be aggravated by co-administration of fluconazole 122 . Thus, corticosteroid replacement is indicated during the first weeks to months after cessation of corticosteroid therapy, not least during episodes of serious stress unless a stimulation test has shown a normal adrenal response 122, 123 . The duration of adrenal insufficiency has been ascribed to variants of the GR gene 124 , but formal genome-wide association analyses are lacking.…”

Section: Endocrinopathiesmentioning

confidence: 99%

Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

et al. 2017

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During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both), bone toxicities (including osteonecrosis), thromboembolism, sinusoidal obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia), high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall survival rates above 90%, there is a need for strategies for assessing the burden of toxicities in the overall evaluation of anti-leukemic therapy programs.

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“…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 ]. This may be due to higher steroid concentrations.…”

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 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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A prospective study of the hypothalamic-pituitary-adrenal axis in children with acute lymphoblastic leukemia receiving chemotherapy

Abstract: Adrenal suppression is an inevitable consequence of ALL therapy. Monitoring of cortisol levels and steroid coverage during stress is recommended, and gradual steroid tapering is suggested.

Cited by 14 publications

References 22 publications

MANAGEMENT OF ENDOCRINE DISEASE: Glucocorticoid-induced adrenal insufficiency: replace while we wait for evidence?

MANAGEMENT OF ENDOCRINE DISEASE: Glucocorticoid-induced adrenal insufficiency: replace while we wait for evidence?

Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

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

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