Cushing's syndrome in a patient with bilateral macronodular adrenal hyperplasia responding to cisapride: an in vivo and in vitro study.
Cortisol secretion in adrenal Cushing's syndrome can be regulated by aberrant hormone receptors, such as gastric inhibitory polypeptide, V1 vasopressin, catecholamines, LH/human chorionic gonadotropin, and serotonin receptors. We report the case of a patient with Cushing's syndrome due to bilateral adrenal macronodular hyperplasia. Extensive in vivo testing for the presence of aberrant receptors revealed a 5-fold increase of plasma cortisol after the administration of cisapride, an agonist of the serotonin 4 (5-HT(4)) receptor. Primary cell cultures were established from adrenocortical specimens obtained at surgery, and in vitro studies also showed that cisapride determined an increase [133.7 +/- 5.5% (mean +/- SE) of baseline, considered 100%) of cortisol secretion from cultured cells. The presence of 5-HT(4) receptor transcript, and in particular of isoforms c, g, and n, was confirmed by RT-PCR, and the determination of the mRNA levels by real-time RT-PCR revealed a higher expression than in normal adrenal glands. To our knowledge, this is one of the first reports of Cushing's syndrome in which cortisol secretion is regulated mainly by the 5-HT(4) receptor, among known aberrant receptors. In addition, it is noteworthy that hypocortisolism ensued after the removal of the most enlarged adrenal gland, but the in vivo response to cisapride persisted.
Mannelli
Massimo
M
Endocrine Unit, Department of Clinical Physiopathology, University of Florence, 50139 Florence, Italy. m.mannelli@dfc.unifi.it
Ferruzzi
Pietro
P
Luciani
Paola
P
Crescioli
Clara
C
Buci
Lisa
L
Corona
Giovanni
G
Serio
Mario
M
Peri
Alessandro
A
D000311:Adrenal Glands / Q000473:pathology*; D000324:Adrenocorticotropic Hormone; D020117:Cisapride / Q000627:therapeutic use*; D003480:Cushing Syndrome / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism; D006965:Hyperplasia; D066298:In Vitro Techniques; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D044140:Receptor, Angiotensin, Type 1; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics; D011945:Receptors, Angiotensin / Q000235:genetics; D011985:Receptors, Serotonin / Q000235:genetics; D044422:Receptors, Serotonin, 5-HT4; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use*
D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D018342:Receptors, Adrenergic, beta-1; D011945:Receptors, Angiotensin; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D044422:Receptors, Serotonin, 5-HT4; D000324:Adrenocorticotropic Hormone; D020117:Cisapride; D006854:Hydrocortisone