Adrenal insufficiency during treatment for childhood acute lymphoblastic leukemia is associated with glucocorticoid receptor polymorphisms ER22/23EK and BclI

Ruiter, Ruben D. de; Gordijn, Maartje S.; Gemke, Reinoud J. B. J.; Bos, Cor van den; Bierings, Marc; Rotteveel, Joost; Koper, Jan W.; Rossum, Elisabeth F.C. van; Kaspers, Gertjan J. L.

doi:10.3324/haematol.2014.105056

Cited by 10 publications

(6 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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

View full text Add to dashboard Cite

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.

show abstract

Section: Endocrinopathiesmentioning

confidence: 99%

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

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Inter-individual variability in the sensitivity of the HPAA to exogenous glucocorticoids has been observed 44128129. For example, higher cortisol after administration of dexamethasone was associated with an inadequate response to the low dose ACTH stimulation test after a 14 day course of prednisolone in healthy volunteers 44.…”

Section: Factors Affecting Likelihood Of Glucocorticoid Induced Adrenal Insufficiencymentioning

confidence: 99%

“…For example, higher cortisol after administration of dexamethasone was associated with an inadequate response to the low dose ACTH stimulation test after a 14 day course of prednisolone in healthy volunteers 44. This variation is possibly linked—among other factors—to polymorphisms of the genes encoding the glucocorticoid and mineralocorticoid receptors 14129130131132. Glucocorticoid receptor polymorphisms were reported to be associated with increased sensitivity to glucocorticoids, leading to a higher prevalence of features associated with hypercortisolism and efficacy of glucocorticoids or, by contrast, a relative glucocorticoid resistance with lower rates of development of features suggestive of iatrogenic Cushing’s syndrome 133134135136137138139140141142.…”

Section: Factors Affecting Likelihood Of Glucocorticoid Induced Adrenal Insufficiencymentioning

confidence: 99%

Glucocorticoid induced adrenal insufficiency

Prete

Bancos

2021

BMJ

View full text Add to dashboard Cite

Synthetic glucocorticoids are widely used for their anti-inflammatory and immunosuppressive actions. A possible unwanted effect of glucocorticoid treatment is suppression of the hypothalamic-pituitary-adrenal axis, which can lead to adrenal insufficiency. Factors affecting the risk of glucocorticoid induced adrenal insufficiency (GI-AI) include the duration of glucocorticoid therapy, mode of administration, glucocorticoid dose and potency, concomitant drugs that interfere with glucocorticoid metabolism, and individual susceptibility. Patients with exogenous glucocorticoid use may develop features of Cushing’s syndrome and, subsequently, glucocorticoid withdrawal syndrome when the treatment is tapered down. Symptoms of glucocorticoid withdrawal can overlap with those of the underlying disorder, as well as of GI-AI. A careful approach to the glucocorticoid taper and appropriate patient counseling are needed to assure a successful taper. Glucocorticoid therapy should not be completely stopped until recovery of adrenal function is achieved. In this review, we discuss the factors affecting the risk of GI-AI, propose a regimen for the glucocorticoid taper, and make suggestions for assessment of adrenal function recovery. We also describe current gaps in the management of patients with GI-AI and make suggestions for an approach to the glucocorticoid withdrawal syndrome, chronic management of glucocorticoid therapy, and education on GI-AI for patients and providers.

show abstract

“…Interestingly, Eipel and colleagues previously observed that pediatric patients harboring the N363S polymorphism more often developed GC-related hepatotoxicity and glucose abnormalities in the course of acute lymphoblastic leukemia (ALL) treatment [16]. Moreover, previous studies also with pediatric ALL patients showed that Bcl I carriers were also more likely to develop Cushingoid-like symptoms (e.g., adiposity, hypertension, and diabetes) and depression during treatment with systemic corticosteroids [17], as well as a longer period of adrenal insufficiency after high-dose corticosteroid therapy in homozygous Bcl I carriers [18].…”

Section: Discussionmentioning

confidence: 99%

Anthropometrics and Metabolic Syndrome in Relation to Glucocorticoid Receptor Polymorphisms in Corticosteroid Users

et al. 2020

View full text Add to dashboard Cite

Introduction: Corticosteroids are widely prescribed and their use has been linked to adverse cardiometabolic outcomes. A pivotal role in the action of corticosteroids is reserved for the glucocorticoid receptor (GR). Here, we assessed the relationship of glucocorticoid (GC) sensitivity altering GR polymorphisms with anthropometrics and metabolic syndrome (MetS) in corticosteroid users. Methods: In this population-based cohort study (Lifelines) we genotyped 10,621 adult participants for GR hypersensitive (1/2 copies BclI and/or N363S) and GR resistant (1/2 copies ER22/23EK and/or 9β) variants. We assessed the relationship between functional GR polymorphisms with body mass index (BMI), waist circumference (WC), and MetS in users of corticosteroids. Results: Overall corticosteroid use was associated with a significantly higher BMI and WC in GR wild-type users (BMI: +0.63 kg/m2 [0.09-1.16], P=.022; WC: +2.03 cm [0.61-3.44], P=.005) and GR hypersensitive (BMI: mean difference +0.66 kg/m2 [95% CI, 0.31-1.01); WC: +2.06 cm (1.13-2.98), both P<.001), but not in GR resistant users. Significantly higher WC in GR resistant carriers was observed only for inhaled corticosteroid users. With respect to MetS, again only GR wild-type users (OR 1.44 [1.07-1.94], P=.017) and GR hypersensitives (odds ratio (OR) 1.23 [95% CI, 1.00-1.50], P=.046) were more likely to have MetS; even more pronounced in only inhaled corticosteroid users (GR wild-type users, OR 1.64 [1.06-2.55], P=.027; GR hypersensitive users, OR 1.43 [1.08-1.91], P=.013). Conclusions: Polymorphisms associated with increased GR sensitivity and wild-type GR are related to increased BMI, WC and an increased MetS presence in corticosteroid users, especially of the inhaled types, when compared to nonusers. The adverse effects of corticosteroid use are less pronounced in users harboring GR resistant polymorphisms.

show abstract

Adrenal insufficiency during treatment for childhood acute lymphoblastic leukemia is associated with glucocorticoid receptor polymorphisms ER22/23EK and BclI

Cited by 10 publications

References 14 publications

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

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

Glucocorticoid induced adrenal insufficiency

Anthropometrics and Metabolic Syndrome in Relation to Glucocorticoid Receptor Polymorphisms in Corticosteroid Users

Contact Info

Product

Resources

About