Alteration of hypothalamus-pituitary-adrenal glands axis in colorectal cancer patients.
OBJECTIVE
in advanced cancer patients a cell-mediated immunological impairment, both at baseline and during postoperative period (surgical trauma response) is often found and is associated with poor prognosis. Furthermore it is well known that cortisol is strictly involved in the response to major surgical stress, has an important immunosuppression activity and causes a redistribution of immunological population cells in different tissues. The aim of the study was to verify serum levels and circadian rhythm of cortisol and ACTH in patients with colorectal cancer at baseline before surgery and in the postoperative period, and relate it to the immune status.


METHODS
40 patients (22 female, 18 male with a median age of 66 yrs) with histologically proven colorectal cancer undergoing to surgery were enrolled in the study. Assessment of total lymphocyte, CD4+, cortisol level, circadian rhythm of cortisol (11 pm and 8 am) was performed at baseline and in 3rd and 7th postoperative days. ACTH levels (11 pm and 8 am) were studied in 18 patients.


RESULTS
increase of cortisol serum level in the post-operative period vs baseline was statistically significant both in 3rd and 7th days. A significant decrease of total and CD4+ lymphocytes count was found on both 3rd and 7th postoperative days compared to baseline and to normal values. The rate of patients with an altered circadian rhythm was 68% and 53% at 3rd and 7th postoperative days respectively. At baseline 28% of patients had an altered cortisol circadian rhythm and it was significantly more frequent in patients with nodal involvement (P<0.005) and with metastatic spread (P<0.004). 44% of 18 patients evaluated for ACTH circadian rhythm displayed an alteration and it was significantly higher in patients with nodal involvement and metastatic disease (P<0.05). No relations between lymphocytopenia and alteration of night-cortisolemy, day-cortisolemy and cortisol and ACTH circadian rhythm were found, neither at baseline, 3rd and 7th postoperative days.


CONCLUSIONS
it is known that lymphocytopenia, both at baseline and in the postoperative period, is associated with a poor prognosis in cancer patients and that cortisol plays an important role in the immune response. Our data show that lymphocytopenia often present in cancer patients, poor prognostic factor, seems not to be associated with ACTH and cortisol level and circadian rhythm alteration, both at baseline and after surgical stress. Otherwise even if paraneoplastic syndromes seems not to be related to colorectal cancer and no patient showed adrenocortical metastasis, an impairment of circadian rhythm of cortisol and ACTH was found at baseline in 28% and 44% respectively. It was significantly associated with the presence of metastatic disease. These preliminary results suggest further investigations on relation between cancer and endocrine system.
Mussi
Chiara
C
Department of Surgery, San Gerardo Hospital, University of Milan-Bicocca.
Angelini
Carlo
C
Crippa
Stefano
S
Caprotti
Roberto
R
Fumagalli
Luca
L
Motta
Vittorio
V
Uggeri
Franco
F
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000368:Aged; D002940:Circadian Rhythm / Q000502:physiology*; D015179:Colorectal Neoplasms / Q000097:blood* / Q000601:surgery; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008207:Lymphatic Metastasis; D018655:Lymphocyte Count; D008297:Male; D011184:Postoperative Period; D011300:Preoperative Care; D012016:Reference Values
D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone