1: Clin Endocrinol (Oxf)  1996 Aug;45(2):147-56 

Petrosal sinus sampling for diagnosis of Cushing's disease: evidence of false
negative results.

Lopez J, Barcelo B, Lucas T, Salame F, Alameda C, Boronat M, Salto L, Estrada J.

Department of Endocrinology, Universidad Autonoma de Madrid, Spain.

OBJECTIVE: While inferior petrosal sinus (IPS) sampling correctly diagnoses
pituitary-dependent Cushing's syndrome if a significant ratio of plasma ACTH
between the IPS and the peripheral blood is demonstrated, little has been said
about the significance of a negative ratio in Cushing's disease (e.g. a
false-negative result). This study evaluates the results of IPS sampling in
patients with Cushing's disease, and compares them with both imaging findings
and transsphenoidal examination. DESIGN: The results of IPS sampling were
retrospectively compared with both imaging findings and transsphenoidal
examination. IPS samples were obtained before and 2, 5 and 10 minutes after
intravenous administration of 100 micrograms of CRH. PATIENTS: Thirty-two
patients with Cushing's disease were evaluated. All subsequently underwent
transphenoidal examination of the pituitary gland. MEASUREMENTS: The ratio of
the ACTH concentrations at the IPS and in the peripheral blood (IPS:P ratio),
and the ratio of the ACTH concentrations between the IPSs (interpetrosal ratio)
were calculated. Radiographic evaluation of the pituitary gland was performed
with magnetic resonance imaging (MRI, 29 cases) or computed tomography imaging
(CT, 3 cases). RESULTS: Transsphenoidal examination of the pituitary gland
revealed a microadenoma in 27 cases. Radiological imaging showed a signal
compatible with a microadenoma in 22 cases (68.8%), and correctly located the
tumour at the side found at surgery in 14 of the 22 cases with positive
transsphenoidal findings (MRI 13 cases, CT 1 case, overall 63.6%). Successful
bilateral catheterization was accomplished in 30 patients (93.8%). Samples
before and after CRH stimulation were drawn in 24 cases. No major complications
were observed with the technique. IPS catheterization correctly predicted
Cushing's disease (by means of a significant IPS: P ACTH ratio) in 27 of the 30
patients (90%) with basal sampling, and in 23 of the 24 cases with samples drawn
before and after CRH administration (95.8%). Taking into account the 12 patients
with a lateral microadenoma shown at transsphenoidal examination, IP sinus ACTH
ratio was in agreement with the side recorded by the neurosurgeon in 8/12 cases
(66.7%). MRI correctly located the tumour in 8/12 patients (66.7%). One patient
showed no significant IPS: P ACTH ratio in any set of samples. His MRI showed no
sign of a microadenoma. Two years later, another pituitary MRI evaluation showed
a midline hypodense signal. The transsphenoidal examination revealed a
microadenoma and the post-operative plasma cortisol and urinary free cortisol
fell to 293 nmol/l and 100 nmol/24 h, respectively. CONCLUSIONS: Only when a
significant IPS:P ACTH ratio is present can Cushing's disease be established by
IPS sampling. The absence of a significant IPS: P ACTH ratio does not
necessarily imply ectopic secretion of ACTH, nor does it exclude Cushing's
disease. The results of lateralization by IPS sampling do not remove the need
for a thorough transsphenoidal examination of the contents of the sella turcica.

PMID: 8881446 [PubMed - indexed for MEDLINE]