[Aberrant expression of the GIP (Gastric Inhibitory Polypeptide) receptor in an adrenal cortical adenoma responsible for a case of food-dependent Cushing's syndrome].
A 33 year old woman was investigated for an atypical case of Cushing's syndrome with suppressed early morning plasma cortisols. Chronic hypercortisolism was confirmed by classical biological criteria (24 h urinary cortisol excretion, dexamethasone suppression tests); more detailed dynamic and pharmacological tests revealed unanticipated features: spontaneous circadian plasma cortisol variations showed post prandial peaks; they could be induced by oral--but not intravenous--glucose tolerance tests, and were inhibited by the concomitant administration of Sandostatin (a somatostatin analog). Adrenal CT scan identified a 2 cm unilateral adenoma with ipsilateral and contralateral atrophy. Surgical removal of the tumor cured the hypercortisolism with hypocortisolism. Comparative analysis of the tumoral and normal tissues showed that only the former responded in vitro to GIP (Gastric Inhibitory Polypeptide) and contained the specific mRNA of the GIP receptor. This case illustrates a new pathophysiological mechanism of tumorigenesis due to the aberrant expression of a seven transmembrane domain receptor in a tumoral tissue. The nature of the given receptor induced a particular clinical phenotype related to food intake.
Luton
J P
JP
Clinique des Maladies Endocriniennes et Métaboliques, CNRS UPR 1524, Hôpital Cochin, Paris.
Bertherat
J
J
Kuhn
J M
JM
Bertagna
X
X
D000306:Adrenal Cortex Neoplasms / Q000150:complications / Q000378:metabolism*; D000328:Adult; D003480:Cushing Syndrome / Q000209:etiology / Q000378:metabolism*; D005260:Female; D005749:Gastric Inhibitory Polypeptide; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D019518:Postprandial Period; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics*
D011964:Receptors, Gastrointestinal Hormone; D005749:Gastric Inhibitory Polypeptide; C041086:gastric inhibitory polypeptide receptor