Is there any relationship between imatinib mesylate medication and hypothalamic-pituitary-adrenal axis dysfunction?

• Published in: International journal of clinical practice (Esher) Vol. 64; no. 1; pp. 45 - 50
• Main Authors: Bilgir, O., Kebapcilar, L., Bilgir, F., Sarì, I., Oner, P., Karaca, B., Alacacioglu, I.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.01.2010; John Wiley & Sons, Inc
• Subjects: Adrenocorticotropic Hormone; Adult; Aged; Antineoplastic Agents - adverse effects; Benzamides; Cosyntropin; Endocrine System Diseases - chemically induced; Endocrine System Diseases - metabolism; Endocrinology; Female; Glucagon; Glucocorticoids - deficiency; Hormones; Humans; Hydrocortisone - metabolism; Hypothalamo-Hypophyseal System - drug effects; Imatinib Mesylate; Inhibitor drugs; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - metabolism; Male; Middle Aged; Pharmacology; Piperazines - adverse effects; Pituitary-Adrenal System - drug effects; Protein Kinase Inhibitors - adverse effects; Pyrimidines - adverse effects
• ISSN: 1368-5031; 1742-1241; 1742-1241
• DOI: 10.1111/j.1742-1241.2008.01856.x

Summary Background:  Imatinib mesylate [tyrosine kinase (TK) inhibitor] is a novel medication in the treatment of chronic myelogenous leukaemia (CML). TK is also essential in hypothalamo‐pituitary‐adrenal (HPA) axis. Purpose:  The aim of this study was to evaluate HPA axis in patients treated with imatinib. Twenty‐five patients were included in this study. Methods:  Glucagon stimulation test (GST) and low‐dose (1 μg) adrenocorticotropin test (LDSST) were used to assess the HPA gland axis. Results:  Seventeen (68%) subjects had impaired peak response when a cortisol cut‐off value is accepted as 500 nmol/L. Twelve (48%) out of 17 subjects also failed to show a response to LDSST. Therefore, 12 patients (48%) were defined as HPA deficient. Only two of these 25 patients had morning serum cortisol < 200 nmol/l (7.22 μg/dl), and failed the GST and/or LDSST, indicating that the majority had partial glucocorticoid deficiency. If the cut‐off presume for LDSST is from 500 to 600 nmol/l, 16 patients (64%) would have failed both the GST and LDSST. Conclusion:  Our results indicate an increased prevalence of subclinical glucocorticoid deficiency in patients receiving imatinib mesylate for CML. Therefore under stressed conditions, such as intercurrent illness state, overt and untreated partial glucocorticoid deficiency in CML patients become life threatening.