Adrenal enlargement and failure of suppression of circulating cortisol by dexamethasone in patients with malignancy

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

The Hypothalamic–Pituitary–Adrenal Axis in Women with Differentiated Thyroid Cancer

“…In contrast to previous findings suggesting HPA abnormalities in patients with malignancies other than thyroid cancer (1,2), the results of this study suggest that abnormalities of HPA-axis function are not common, at least in female patients with a favorable malignancy, such as DTC.…”

“…Activation and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been observed in some cancer patients, characterized by enlarged adrenal glands and abnormal cortisol dynamics demonstrated as non-suppressible hypercortisolism (1,2). This disturbance is not fully explained and its functional significance remains uncertain.…”

Bilateral adrenal enlargement and non-suppressible hypercortisolism as a presenting feature of gastric cancer

“…Irrespective of the exact cause of adrenal enlargement in the present case, both adrenal metastases and hyperplasia are associated with overactivity of the HPA axis. 2,3 Functional disturbances in the HPA axis associated with malignant disease are in some ways similar to those that occur in critical illness. Although it is well established that patients with critical illness on the intensive care unit (ICU) are hypercortisolaemic, there is also evidence of altered glucocorticoid feedback control.…”

“…6 However, although we cannot completely exclude the possibility of pituitary-dependent Cushing's syndrome, we feel that this latter diagnosis was less likely due to the following reasons: ACTH concentrations were low (510 ng/L); pituitary MRI was normal; and similar responses to CRH have been reported in cancer patients with bilateral di¡use adrenal enlargement. 2 Only after progression of the patient's symptoms did it become clear that the primary cause for the clinical picture was a di¡usely in¢ltrative gastric carcinoma, which was identi¢ed after a second gastroscopy. Although gastric pathology was originally considered, initial gastroscopy was reported as normal.…”

“…the ectopic ACTH syndrome, in most cases its aetiology and functional signi¢cance are uncertain. 2 Functional disturbances in the activity of the hypothalamic^pituitary^adrenal (HPA) axis may also occur in malignant disease. It is well documented that metastatic disease a¡ecting the adrenal glands may lead to adrenal insu⁄ciency, yet it is far less well appreciated that hypercortisolaemia is more commonly observed.…”