Περίληψη:
The role of desmopressin, alone or in combination with CRH, in the
differential diagnosis between Cushing’s disease (CD) and ectopic ACTH
secretion (EAS) still remains uncertain. Based on existing data, the
desmopressin test is regarded as an alternative to the CRH stimulation
test and, when given in combination with CRH, it has been suggested to
completely discriminate between patients with CD and EAS. However,
assessment of these tests has been limited in only a small number of
patients with EAS. Desmopressin is a relatively specific V2 vasopressin
receptor (V2R) agonist. Although expression of V3 vasopressin receptor
(V3R) is common in tumors with EAS, the expression of V2R has not been
extensively investigated. In the present study, we report our findings
of the desmopressin and the combined CRH-desmopressin test in a series
of patients with CD and EAS; also, the expression of V2R and V3R was
investigated in tumors with EAS by a RT-PCR method.
We assessed a cohort of 31 patients with ACTH-dependent Cushing’s
syndrome, including 26 patients with CD and five cases with
histologically confirmed EAS. To avoid bias of predetermined criteria,
univariate curves of the receiver operating characteristics (ROC) were
constructed by plotting the sensitivity against 1-specificity at each
level of the percent cortisol (F) and ACTH responses to these tests.
Following desmopressin administration there was an overlap of the
percent F and ACTH responses among patients with CD and EAS, and the
area under the ROC curve for both these responses was not significantly
different than that occurring by chance. This was also true for the
percent F response following the combined CRH-desmopressin test.
However, the area under the ROC curve for the percent ACTH rise
following the combined test was significantly different; the point of
the ROC curve closest to 1 corresponded to a percent ACTH rise of 218%
(88% sensitivity and 80% specificity). Expression of V2R and V3R mRNA
was investigated in four of the five excised tumors with EAS and
revealed the presence of the V2R in all, whereas the V3R mRNA was
expressed in three of these cases.
In conclusion, in this series the desmopressin test produced a
significant overlap of responses between CD and patients with EAS and,
therefore, is of limited value in the differential diagnosis of the
ACTH-dependent Cushing’s syndrome. This is most probably due to the
expression of the V2R in tumors with EAS. Moreover, following the
combined CRH-desmopressin test only the ACTH but not the F responses
were diagnostically useful, but still far from completely discriminating
patients with CD and EAS.
Συγγραφείς:
Tsagarakis, S
Tsigos, C
Vasiliou, V
Tsiotra, P and
Kaskarelis, J
Sotiropoulou, C
Raptis, SA
Thalassinos, N