High-dose Glucocorticoid Administration Research Articles

Effect of dexamethasone on quality of life in children with acute lymphoblastic leukaemia: a prospective observational study

BackgroundGlucocorticoids are important in the treatment of childhood acute lymphoblastic leukaemia (ALL). However, cyclic administration of high dose glucocorticoids may cause rapid and substantial changes in quality of life (QoL). The maintenance phase of the Dutch ALL-9 protocol consisted of alternating two weeks on and five weeks off dexamethasone (6 mg/m2/day). The present study was performed to assess the effect of dexamethasone on QoL during treatment for ALL according to this protocol.MethodsIn a multicentre prospective cohort study, QoL was assessed halfway (T1) and at the end of the two-year treatment (T2). A generic (Child Health Questionnaire) and disease specific (PedsQL™ cancer version) QoL questionnaire were used to assess QoL in two periods: on and off dexamethasone, respectively.Results41 children (56% males) were evaluated, mean age at diagnosis was 5.6 years. The CHQ physical and psychosocial summary scores were significantly lower than population norms. At T1 and T2, overall QoL showed no significant change. However, regarding specific domains (pain, cognitive functioning, emotion/behaviour and physical functioning) QoL decreased over time. QoL was significantly more impaired during periods on dexamethasone.ConclusionDexamethasone was associated with decreased QoL. At the end of treatment, reported QoL during dexamethasone deteriorated even more on certain scales (pain, cognitive functioning, emotion/behaviour and physical functioning). Knowledge of the specific aspects of QoL is essential to improve counselling and coping in paediatric oncology. Adverse effects of specific drugs on QoL should be taken into account when designing treatment protocols.

Vitamin D insufficiency underlies unexpected hypocalcemia following high dose glucocorticoid therapy

Vitamin D insufficiency is a reemerging and common health problem for skeletal system. Pharmacological application of glucocorticoid inhibits intestinal calcium absorption and stimulates tubular calcium excretion, thus induces severely negative calcium balance. We report a patient presenting symptomatic hypocalcemia following high dose glucocorticoid administration. After a pulse-therapy with methylprednisolone, hypocalcemia with muscle cramp developed in association with hypercalciuria and secondary hyperparathyroidism in the absence of hypomagnesemia. Circulating level of 1,25-dihydroxyvitamin D was in a reference range, while that of 25-hydroxyvitamin D was insufficient. Treatment with alfacalcidol of 1 μg/day promptly improved serum calcium level within a couple of weeks. Vitamin D insufficiency could be a serious problem in patients with high dose glucocorticoid therapy.

Direct suppression of testosterone secretion by single ultra high dose glucocorticoid administration

While it is well established that chronic stress and long-term glucocorticoid administration inhibit the hypothalamo-pituitary gonadal (HPG) axis, predominantly by interfering with the secretion of gonadotropin releasing hormone (GnRH) as well as of luteinizing hormone (LH) and follicle stimulating hormone (FSH), the effects of acute stress/single high dose glucocorticoid administration on the HPG axis are less well understood. To address this issue we analyzed serum testosterone levels in 30 healthy men divided into two age groups (group 1 aged 20 to 40 and group 2 aged 60 to 80) before and 6h after treatment with a single ultra high dose of dexamethasone (40mg orally). We could show that dexamethasone pretreatment resulted in acute downregulation of testosterone by 29% in the combined age group (mean±SD before dexamethasone 4.7±2.7 [µg/l]; mean±SD after dexamethasone 3.3±1.0 [µg/l]; p<0.05). This effect was more pronounced in the younger age group (42% downregulation compared to 16% in the older age group). In contrast, LH and FSH levels did not change significantly in either age group, indicating a direct testicular effect of dexamethasone. We conclude that high doses of glucocorticoids as produced in situations of physiological or pathological stress can inhibit testosterone production/release directly at the testicular level. This stress response seems to be more pronounced in younger than in older men.

Regulation of Macrophage Migration Inhibitory Factor Expression by Glucocorticoids in Vivo

Glucocorticoid hormones are important anti-inflammatory agents because of their anti-inflammatory and proapoptotic action within the immune system. Their clinical usefulness remains limited however by side effects that result in part from their growth inhibitory action on sensitive target tissues. The protein mediator, macrophage migration inhibitory factor (MIF), is an important regulator of the host immune response and exhibits both glucocorticoid-antagonistic and growth-regulatory properties. MIF has been shown to contribute significantly to the development of immunopathology in several models of inflammatory disease. Although there is emerging evidence for a functional interaction between MIF and glucocorticoids in vitro, little is known about their reciprocal influence in vivo. We investigated the expression of MIF in rat tissues after ablation of the hypothalamic-pituitary-adrenal axis and after high-dose glucocorticoid administration. MIF expression is constitutive and independent of the influence of adrenal hormones. Hypophysectomy and the attendent loss of pituitary hormones, by contrast, decreased MIF protein content in the adrenal gland. Administration of dexamethasone was found to increase MIF protein expression in those organs that are considered to be sensitive to the growth inhibitory effects of glucocorticoids (immune and endocrine tissues, skin, and muscle). This increase was most likely because of a posttranscriptional regulatory effect because tissue MIF mRNA levels were not influenced by dexamethasone treatment. Finally, MIF immunoneutralization enhanced lymphocyte egress from blood during stress-induced lymphocyte redistribution, consistent with a functional interaction between MIF and glucocorticoids on immune cell trafficking in vivo. These findings suggest a role for MIF in both the homeostatic and physiological action of glucocorticoids in vivo.