The ectopic expression of the gastric inhibitory polypeptide receptor is frequent in adrenocorticotropin-independent bilateral macronodular adrenal hyperplasia, but rare in unilateral tumors.
Control of cortisol secretion by the abnormal expression of the gastric inhibitory polypeptide receptor (GIP-R) have been observed in some rare cases of ACTH-independent, food-dependent Cushing's syndrome (FD-ACS) due to adrenal adenoma (AA) or bilateral macronodular hyperplasia (AIMAH). This study was performed to determine the prevalence of GIP-R ectopic expression in ACS and its correlation with fasting cortisol levels. GIP-R expression was studied by RT-PCR in 30 unilateral adrenal tumors [16 AA and 14 adrenocortical cancer (AC)] and 8 AIMAH tissues. Fasting and postprandial cortisol levels were assayed, respectively, at 0800 and 1200 h in AA, AC, and AIMAH, and 1 h after a morning standard meal in 6 AIMAH patients. Similar expression of 2 GIP-R isoforms was observed in 1 of 16 AA, 0 of 14 AC, and 4 of 8 AIMAH as well as in the 4 insulinomas used as positive controls. In vitro study of the GIP-R-expressing AA showed stimulation of cortisol secretion and cAMP production by GIP. The fasting 0800-h plasma cortisol level was above 276 nmol/liter in all patients except 1 AA case and 1 AIMAH case, both of whom expressed GIP-R. In the 3 additional AIMAH cases that expressed the GIP-R, fasting plasma cortisol levels were above 276 nmol/liter. This study demonstrates that ectopic expression of GIP-R is rare in AA and is usually associated with the low fasting plasma cortisol levels that characterize FD-ACS. In contrast, GIP-R expression is frequent in AIMAH and might not always be associated with a low fasting plasma cortisol level. This suggests that maintenance of hypercortisolemia in GIP-R- expressing AIMAH does not always depend solely on GIP-R, and that simultaneous abnormal expression of other membrane receptors might be present. The expression of GIP-R could not be observed during malignant transformation of the adrenal cortex. This study highlighted the major role of cAMP alterations secondary to GIP-R ectopic expression in the pathophysiology of AIMAH and in some rare cases of well differentiated benign adrenocortical tumors.
Groussin
Lionel
L
Service des Maladies Endocriniennes et Métaboliques, Centre National de la Recherche Scientifique, UPR1524, CHU Cochin, 75014 Paris, France.
Perlemoine
Karine
K
Contesse
Vincent
V
Lefebvre
Hervé
H
Tabarin
Antoine
A
Thieblot
Philippe
P
Schlienger
Jean Louis
JL
Luton
Jean Pierre
JP
Bertagna
Xavier
X
Bertherat
Jérôme
J
D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D000307:Adrenal Gland Diseases / Q000378:metabolism*; D000310:Adrenal Gland Neoplasms / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000502:physiology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006965:Hyperplasia; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution
D012333:RNA, Messenger; D011964:Receptors, Gastrointestinal Hormone; D000324:Adrenocorticotropic Hormone; C041086:gastric inhibitory polypeptide receptor; D006854:Hydrocortisone