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


OBJECTIVE
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 microg) 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 microg/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.


CONCLUSIONS
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.
Bilgir
O
O
Internal Medicine Department, Bozyaka Training and Research Hospital, Izmir, Turkey.
Kebapcilar
L
L
Bilgir
F
F
Sarì
I
I
Oner
P
P
Karaca
B
B
Alacacioglu
I
I
D000324:Adrenocorticotropic Hormone; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects; D001549:Benzamides; D003366:Cosyntropin; D004700:Endocrine System Diseases / Q000139:chemically induced* / Q000378:metabolism; D005260:Female; D005934:Glucagon; D005938:Glucocorticoids / Q000172:deficiency; D006728:Hormones; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects*; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011743:Pyrimidines / Q000009:adverse effects*
D000970:Antineoplastic Agents; D001549:Benzamides; D005938:Glucocorticoids; D006728:Hormones; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D003366:Cosyntropin; C006418:adrenocorticotropin zinc; D000068877:Imatinib Mesylate; D000324:Adrenocorticotropic Hormone; D005934:Glucagon; D006854:Hydrocortisone