Inherited adrenocorticotropin-independent macronodular adrenal hyperplasia with abnormal cortisol secretion by vasopressin and catecholamines: detection of the aberrant hormone receptors on adrenal gland.
ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a rare disorder and an unusual cause of Cushing s syndrome, of which familial transmission has rarely been reported. In this study, a mother and her son, the former affected with definite AIMAH and the latter with possible AIMAH, are described. Although the mother manifested overt Cushing s syndrome, her son remained with no stigmata of Cushing s syndrome except for bilateral adrenal tumor and mild hypertension, and a full suppression of plasma cortisol by lowdose dexamethasone was observed in him. Recently, aberrant expression of adrenal receptors for various ligands has been noted in AIMAH patients. In our cases, provocation tests in vivo suggested that AVP and catecholamines promoted cortisol production through V1a and/or V1b receptors and via beta-adrenergic receptor, respectively. Reverse transcriptional-PCR analysis of the operated adrenal tissues of mother revealed the abnormal expression of mRNA of receptors for V1b, V2, and LH/hCG, none of which was observed in a normal control. Inherited AIMAH is very rare, and the son might be at the earliest developmental stage of AIMAH among the cases reported so far. An intervention could be tried to prevent the development of overt Cushing s syndrome by suppression of the possible endogenous ligands or by blockade of the receptors that may be aberrantly expressed in his adrenal glands.
Miyamura
Nobuhiro
N
Department of Metabolic Medicine, Kumamoto University School of Medicine, Japan. miyamura@kaiju.medic.kumamoto-u.ac.jp
Taguchi
Tetsuya
T
Murata
Yusuke
Y
Taketa
Kayo
K
Iwashita
Shinsuke
S
Matsumoto
Kazuya
K
Nishikawa
Takeshi
T
Toyonaga
Tetsushi
T
Sakakida
Michiharu
M
Araki
Eiichi
E
D000307:Adrenal Gland Diseases / Q000235:genetics* / Q000503:physiopathology; D000310:Adrenal Gland Neoplasms / Q000150:complications; D000311:Adrenal Glands / Q000473:pathology*; D000318:Adrenergic beta-Agonists; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000328:Adult; D000368:Aged; D001127:Arginine Vasopressin; D002395:Catecholamines; D006063:Chorionic Gonadotropin / Q000235:genetics; D003346:Corticotropin-Releasing Hormone; D003480:Cushing Syndrome / Q000209:etiology; D003907:Dexamethasone; D005260:Female; D005938:Glucocorticoids; D007987:Gonadotropin-Releasing Hormone; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D006965:Hyperplasia; D006973:Hypertension / Q000150:complications; D007545:Isoproterenol; D007986:Luteinizing Hormone / Q000235:genetics; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D017483:Receptors, Vasopressin / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000318:Adrenergic beta-Agonists; D002395:Catecholamines; D006063:Chorionic Gonadotropin; D005938:Glucocorticoids; D012333:RNA, Messenger; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D007987:Gonadotropin-Releasing Hormone; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D007986:Luteinizing Hormone; D003346:Corticotropin-Releasing Hormone; D007545:Isoproterenol; D006854:Hydrocortisone