Abstract
The aim of this study was to further elucidate the activity of the hypothalamo–pituitary–adrenal (HPA) axis in patients with malignancy and to correlate this with the size of the adrenal glands. Fourteen patients with a variety of malignancies were studied prior to receiving cytotoxic chemotherapy. During routine staging computerized tomographic (CT) scans, the size of the body, medial and lateral limbs of the adrenal glands were measured and compared with those of a normal group of patients studied previously. Measurements of 09:00 h serum cortisol and plasma adrenocorticotropic hormone (ACTH) levels were made before and after the administration of dexamethasone (0.5 mg 6-hourly for 48 h) in addition to the peak cortisol response to i.v corticotropin releasing hormone (CRH). Overall, patients with malignancy had significantly larger adrenal glands than patients without malignancy; those with non-haematological malignancies had larger glands than patients with haematological malignancies. Following dexamethasone to suppress circulating cortisol levels, nine patients (64%) demonstrated abnormal resistance with cortisol levels > 50 nmol l−1: mean value 294 nmol l−1 (range 67–1147). Those patients who failed to suppress after dexamethasone had significantly larger adrenal glands than those that did suppress and tended to have non-haematological malignancies. ACTH levels were undetectable or low in three patients in whom it was measured and who did not suppress with dexamethasone. Following CRH, the cortisol levels were highest (823 and 853 nmol l−1) in two of these patients. Malignancy is associated with diffuse enlargement of the adrenal glands and resistance to dexamethasone-induced suppression of the HPA axis, which is not due to ectopic ACTH secretion. This disturbance of the normal control of the HPA axis is unexplained and its functional significance remains uncertain. © 1999 Cancer Research Campaign
Full Text
The Full Text of this article is available as a PDF (122.3 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Besser G. M., Landon J. Plasma levels of immunoreactive corticotrophin in patients with Cushing's syndrome. Br Med J. 1968 Nov 30;4(5630):552–554. doi: 10.1136/bmj.4.5630.552. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dimopoulos M. A., Fernandez J. F., Samaan N. A., Holoye P. Y., Vassilopoulou-Sellin R. Paraneoplastic Cushing's syndrome as an adverse prognostic factor in patients who die early with small cell lung cancer. Cancer. 1992 Jan 1;69(1):66–71. doi: 10.1002/1097-0142(19920101)69:1<66::aid-cncr2820690113>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]
- Grossman A. B., Howlett T. A., Perry L., Coy D. H., Savage M. O., Lavender P., Rees L. H., Besser G. M. CRF in the differential diagnosis of Cushing's syndrome: a comparison with the dexamethasone suppression test. Clin Endocrinol (Oxf) 1988 Aug;29(2):167–178. doi: 10.1111/j.1365-2265.1988.tb00258.x. [DOI] [PubMed] [Google Scholar]
- HYMES A. C., DOE R. P. Adrenal function in cancer of the lung, with and without Cushing's syndrome. Am J Med. 1962 Sep;33:398–407. doi: 10.1016/0002-9343(62)90236-x. [DOI] [PubMed] [Google Scholar]
- Howlett T. A., Drury P. L., Perry L., Doniach I., Rees L. H., Besser G. M. Diagnosis and management of ACTH-dependent Cushing's syndrome: comparison of the features in ectopic and pituitary ACTH production. Clin Endocrinol (Oxf) 1986 Jun;24(6):699–713. doi: 10.1111/j.1365-2265.1986.tb01667.x. [DOI] [PubMed] [Google Scholar]
- Merz H., Fliedner A., Orscheschek K., Binder T., Sebald W., Müller-Hermelink H. K., Feller A. C. Cytokine expression in T-cell lymphomas and Hodgkin's disease. Its possible implication in autocrine or paracrine production as a potential basis for neoplastic growth. Am J Pathol. 1991 Nov;139(5):1173–1180. [PMC free article] [PubMed] [Google Scholar]
- Normann S., Besedovsky H., Schardt M., del Ray A. Interactions between endogenous glucocorticoids and inflammatory responses in normal and tumor-bearing mice: role of T cells. J Leukoc Biol. 1988 Dec;44(6):551–558. doi: 10.1002/jlb.44.6.551. [DOI] [PubMed] [Google Scholar]
- Normann S., Besedovsky H., Schardt M., del Rey A. Hormonal changes following tumor transplantation: factors increasing corticosterone and the relationship of corticosterone to tumor-induced anti-inflammation. Int J Cancer. 1988 Jun 15;41(6):850–854. doi: 10.1002/ijc.2910410613. [DOI] [PubMed] [Google Scholar]
- O'Connell N. A., Kumar A., Chatzipanteli K., Mohan A., Agarwal R. K., Head C., Bornstein S. R., Abou-Samra A. B., Gwosdow A. R. Interleukin-1 regulates corticosterone secretion from the rat adrenal gland through a catecholamine-dependent and prostaglandin E2-independent mechanism. Endocrinology. 1994 Jul;135(1):460–467. doi: 10.1210/endo.135.1.8013385. [DOI] [PubMed] [Google Scholar]
- Pullan P. T., Clement-Jones V., Corder R., Lowry P. J., Besser G. M., Rees L. H. ACTH LPH and related peptides in the ectopic ACTH syndrome. Clin Endocrinol (Oxf) 1980 Nov;13(5):437–445. doi: 10.1111/j.1365-2265.1980.tb03409.x. [DOI] [PubMed] [Google Scholar]
- Ratcliffe J. G., Knight R. A., Besser G. M., Landon J., Stansfeld A. G. Tumor and plasma ACTH concentrations in patients with and without the ectopic ACTH syndrome. Clin Endocrinol (Oxf) 1972 Jan;1(1):27–44. doi: 10.1111/j.1365-2265.1972.tb00375.x. [DOI] [PubMed] [Google Scholar]
- Roh M. S., Drazenovich K. A., Barbose J. J., Dinarello C. A., Cobb C. F. Direct stimulation of the adrenal cortex by interleukin-1. Surgery. 1987 Aug;102(2):140–146. [PubMed] [Google Scholar]
- Salas M. A., Evans S. W., Levell M. J., Whicher J. T. Interleukin-6 and ACTH act synergistically to stimulate the release of corticosterone from adrenal gland cells. Clin Exp Immunol. 1990 Mar;79(3):470–473. doi: 10.1111/j.1365-2249.1990.tb08114.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Seymour J. F., Talpaz M., Cabanillas F., Wetzler M., Kurzrock R. Serum interleukin-6 levels correlate with prognosis in diffuse large-cell lymphoma. J Clin Oncol. 1995 Mar;13(3):575–582. doi: 10.1200/JCO.1995.13.3.575. [DOI] [PubMed] [Google Scholar]
- Shepherd F. A., Laskey J., Evans W. K., Goss P. E., Johansen E., Khamsi F. Cushing's syndrome associated with ectopic corticotropin production and small-cell lung cancer. J Clin Oncol. 1992 Jan;10(1):21–27. doi: 10.1200/JCO.1992.10.1.21. [DOI] [PubMed] [Google Scholar]
- Tominaga T., Fukata J., Naito Y., Usui T., Murakami N., Fukushima M., Nakai Y., Hirai Y., Imura H. Prostaglandin-dependent in vitro stimulation of adrenocortical steroidogenesis by interleukins. Endocrinology. 1991 Jan;128(1):526–531. doi: 10.1210/endo-128-1-526. [DOI] [PubMed] [Google Scholar]
- Trainer P. J., Faria M., Newell-Price J., Browne P., Kopelman P., Coy D. H., Besser G. M., Grossman A. B. A comparison of the effects of human and ovine corticotropin-releasing hormone on the pituitary-adrenal axis. J Clin Endocrinol Metab. 1995 Feb;80(2):412–417. doi: 10.1210/jcem.80.2.7852498. [DOI] [PubMed] [Google Scholar]
- Vincent J. M., Morrison I. D., Armstrong P., Reznek R. H. Computed tomography of diffuse, non-metastatic enlargement of the adrenal glands in patients with malignant disease. Clin Radiol. 1994 Jul;49(7):456–460. doi: 10.1016/s0009-9260(05)81740-4. [DOI] [PubMed] [Google Scholar]
- Vincent J. M., Morrison I. D., Armstrong P., Reznek R. H. The size of normal adrenal glands on computed tomography. Clin Radiol. 1994 Jul;49(7):453–455. doi: 10.1016/s0009-9260(05)81739-8. [DOI] [PubMed] [Google Scholar]
- Whitcomb R. W., Linehan W. M., Wahl L. M., Knazek R. A. Monocytes stimulate cortisol production by cultured human adrenocortical cells. J Clin Endocrinol Metab. 1988 Jan;66(1):33–38. doi: 10.1210/jcem-66-1-33. [DOI] [PubMed] [Google Scholar]
- Winter J. S., Gow K. W., Perry Y. S., Greenberg A. H. A stimulatory effect of interleukin-1 on adrenocortical cortisol secretion mediated by prostaglandins. Endocrinology. 1990 Oct;127(4):1904–1909. doi: 10.1210/endo-127-4-1904. [DOI] [PubMed] [Google Scholar]
- de Castro M., Elliot S., Kino T., Bamberger C., Karl M., Webster E., Chrousos G. P. The non-ligand binding beta-isoform of the human glucocorticoid receptor (hGR beta): tissue levels, mechanism of action, and potential physiologic role. Mol Med. 1996 Sep;2(5):597–607. [PMC free article] [PubMed] [Google Scholar]
