ACTH-independent
Cushing's syndrome may be due to the development of
ectopic hormone receptors in adrenal tissue. Thus, in food-dependent
Cushing's syndrome the adrenals aberrantly express receptors for
gastric inhibitory polypeptide (GIP). We present the case of a 60-year-old woman with food-dependent
Cushing's syndrome whose
cortisol levels increased after stimulation with CRH. In this patient with
Cushing's syndrome the finding of low basal plasma
cortisol levels in the late night and early morning as well as a paradoxical rise of plasma
cortisol during a 7-h infusion with
dexamethasone (carried out without any restriction in food intake), suggested that
cortisol production was stimulated at times of food intake. Hourly measurements of plasma
cortisol for 48 h revealed prominent meal-related peaks. A plasma
cortisol response, elicited by oral
glucose administration, could be prevented by
octreotide. Plasma
ACTH was low or undetectable. CRH administration was followed by a
ACTH response from 3 to 16 ng/l and a plasma
cortisol response from 230 to 680 nmol/l.
Octreotide treatment for nearly five months induced a partial clinical and biochemical remission. Total bilateral
adrenalectomy was performed. The left adrenal was grossly enlarged (7 x 5.5 x 4 cm) and the right adrenal was slightly enlarged (6 x 4 x 1.8 cm). Microscopy revealed bilateral nodular
hyperplasia. Cell
suspensions of adrenal tissue from the patient did respond in a dose-dependent fashion to stimulation with GIP and were very sensitive to stimulation with synthetic ACTH1-24. However, CRH had no significant effect on
cortisol production in vitro. Using RT-PCR amplification and
cDNA hybridization,
GIP receptor was found to be overexpressed in the left and right adrenal tissues from this patient as compared to adrenal tissues from a normal individual or from non GIP-dependent adrenal
Cushing's syndrome. There was no evidence of presence of adrenal
CRH receptors. Thus, in this patient with food-dependent
Cushing's syndrome, the CRH-induced plasma
ACTH and
cortisol response is probably mediated by an incomplete suppression of the HPA axis as a result of the intermittent food-dependent nature of
Cushing's syndrome.