Aberrant adrenal sensitivity to vasopressin in adrenal tumours associated with subclinical or overt autonomous hypercortisolism: is this explained by an overexpression of vasopressin receptors?
OBJECTIVE
Abnormal responsiveness to arginine vasopressin (AVP) was previously observed in cortisol-producing adrenocortical tumours but the mechanism remains unclear. The aim of this study was to characterize the effect of AVP on cortisol secretion from adrenocortical tumours compared to normal human adrenal gland.


METHODS
A multicentre study based on pharmacological, molecular and immunohistochemical experiments performed in adenomatous and normal adrenal tissues.


METHODS
Twenty patients with adrenocortical adenomas and subclinical Cushing's syndrome (SCCS) or Cushing's syndrome (CS) were compared to six control normal subjects.


METHODS
In vivo and in vitro cortisol response to vasopressin, vasopressin receptor subtype mRNA measurement by real-time polymerase chain reaction (RT-PCR), immunohistochemical localization of AVP and its V1a receptor in tumour and normal adrenal tissues.


RESULTS
Terlipressin in vivo enhanced cortisol plasma levels in 17/20 SCCS and 3/6 CS but in none of the control subjects. In vitro cortisol response to AVP was observed in nine tumours studied, with enhanced efficacy and/or potency of AVP in three SCCS tumours compared to normal tissues. AVP receptor subtype mRNA levels were similar in SCCS, CS cells and normal adrenal cells. Some SCCS tumour steroidogenic cells showed AVP and V1a receptor immunoreactivity.


CONCLUSIONS
SCCS and CS adrenocortical tumours often exhibit in vivo and in vitro hyper-responsiveness to AVP, which is not related to vasopressin receptor overexpression, but may be explained by more efficient coupling pathways or by the indirect action of AVP through an autocrine/paracrine mechanism.
Joubert
Michael
M
Department of Endocrinology, CHU Caen, France.
Louiset
Estelle
E
Rego
Jean-Luc Do
JL
Contesse
Vincent
V
Kong
Ling Chun
LC
Benhaim
Annie
A
Mittre
Hervé
H
Lefebvre
Hervé
H
Reznik
Yves
Y
D000236:Adenoma / Q000188:drug therapy* / Q000503:physiopathology; D000310:Adrenal Gland Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D000328:Adult; D016022:Case-Control Studies; D003480:Cushing Syndrome / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008236:Lypressin / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D017483:Receptors, Vasopressin / Q000096:biosynthesis* / Q000187:drug effects; D012720:Severity of Illness Index; D000077585:Terlipressin; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D017483:Receptors, Vasopressin; D014662:Vasoconstrictor Agents; D008236:Lypressin; D000077585:Terlipressin; D006854:Hydrocortisone