title: Cushing's syndrome in a patient with bilateral macronodular adrenal hyperplasia responding to cisapride: an in vivo and in vitro study.
abstract: 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.
authors.affiliation: Endocrine Unit, Department of Clinical Physiopathology, University of Florence, 50139 Florence, Italy. m.mannelli@dfc.unifi.it
authors.forename: Massimo
authors.initials: M
authors.lastname: Mannelli
authors.forename: Pietro
authors.initials: P
authors.lastname: Ferruzzi
authors.forename: Paola
authors.initials: P
authors.lastname: Luciani
authors.forename: Clara
authors.initials: C
authors.lastname: Crescioli
authors.forename: Lisa
authors.initials: L
authors.lastname: Buci
authors.forename: Giovanni
authors.initials: G
authors.lastname: Corona
authors.forename: Mario
authors.initials: M
authors.lastname: Serio
authors.forename: Alessandro
authors.initials: A
authors.lastname: Peri
mesh_terms: 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*
chemical_list: 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