PETROSAL SINUS SAMPLING FOR DIAGNOSIS OF CUSHINGS-DISEASE - EVIDENCE OF FALSE-NEGATIVE RESULTS

OBJECTIVE While inferior petrosal sinus (IPS) sampling correctly diagn oses 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 Cus hing's disease (e.g. a false-negative result). This study evaluates th e results of IPS sampling in patients with Cushing's disease, and comp ares 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 wer e obtained before and 2, 5 and 10 minutes after intravenous administra tion of 100 mu g of CRH.PATIENTS Thirty-two patients with Cushing's di sease were evaluated. All subsequently underwent transsphenoidal exami nation of the pituitary gland. MEASUREMENTS The ratio of the ACTH conc entrations at the IPS and in the peripheral blood (IPS:P ratio), and t he ratio of the ACTH concentrations between the IPSs (interpetrosal ra tio) were calculated. Radiographic evaluation of the pituitary gland w as performed with magnetic resonance imaging (MRI, 29 cases) or comput ed tomography imaging (CT, 3 cases). RESULTS Transsphenoidal examinati on of the pituitary gland revealed a microadenoma in 27 cases. Radiolo gical imaging showed a signal compatible with a microadenoma in 22 cas es (68.8%), and correctly located the tumour at the side found at surg ery in 14 of the 22 cases with positive transsphenoidal findings (MRI 13 cases, CT 1 case, overall 63.6%). Successful bilateral catheterizat ion was accomplished in 30 patients (93.8%). Samples before and after CRH stimulation were drawn in 24 cases. No major complications were ob served with the technique, IPS catheterization correctly predicted Cus hing's disease (by means of a significant IPS:P ACTH ratio) in 27 of t he 30 patients (90%) with basal sampling, and in 23 of the 24 cases wi th samples drawn before and after CRH administration (95.8%). Taking i nto account the 12 patients with a lateral microadenoma shown at trans sphenoidal 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 si gnificant IPS:P ACTH ratio in any set of samples. His MRI showed no si gn of a microadenoma. Two years later, another pituitary MRI evaluatio n showed a midline hypodense signal. The transsphenoidal examination r evealed a microadenoma and the post-operative plasma cortisol and urin ary 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 Cu shing's disease be established by IPS sampling. The absence of a signi ficant IPS:P ACTH ratio does not necessarily imply ectopic secretion o f ACTH, nor does it exclude Cushing's disease. The results of laterali zation by IPS sampling do not remove the need for a thorough transsphe noidal examination of the contents of the sella turcica.