Usefulness of inferior petrosal sinus venous endocrine markers in Cushing's disease

Bilateral and simultaneous sampling of the inferior petrosal sinuses in patients with Cushing's disease has been used to establish the presence and laterality of adrenocorticotropic hormone (ACTH)-producing microadenomas prior to transsphenoidal surgery. Successful preoperative lateralization depends upon equivalent dilution of pituitary venous blood on the two sides since samples which are diluted by unequal amounts of non-pituitary blood may lead to erroneous results. To assure valid sampling results, the use of other pituitary hormones, measured simultaneously, has been proposed to correct the ACTH concentrations from the inferior petrosal sinuses against unequal dilution by non-pituitary venous blood. This proposal presumes that ACTH-secreting microadenomas will not cause unequal delivery of the other pituitary hormones into the two inferior petrosal sinuses. The inferior petrosal sinus concentrations of prolactin (PRL), thyrotropin (TSH), and the alpha subunit of human chorionic gonadotropin (α-HCG) were evaluated as indicators of pituitary venous blood dilution in 11 patients with Cushing's disease. Four patients with ectopic ACTH syndrome served as controls. Blood was withdrawn simultaneously from catheters in both inferior petrosal sinuses and from a peripheral vein for measurement of ACTH, PRL, TSH, and α-HCG. The ACTH concentrations were then corrected for dilution by non-pituitary blood by dividing the ACTH concentration from each side by the ratio of the inferior petrosal sinus to peripheral blood concentrations of PRL, TSH, and α-HCG for that side. At surgery, all 11 patients had ACTH-secreting microadenomas on the side predicted by the uncorrected ACTH concentrations. However, in three patients the corrected ACTH values would have led to erroneous results. Among the 18 sets of corrected inferior petrosal sinus measurements in these three patients, the corrected ACTH values failed to show an inferior petrosal sinus gradient in six and localized the tumor to the side opposite the adenoma in four. Incorrect lateralization was obtained with each of the hormones (PRL, TSH, and α-HCG) used for correction. Furthermore, the ipsilateral (side of tumor)-to-contralateral inferior petrosal sinus gradient of ACTH in patients with Cushing's disease was generally paralleled by a significant inferior petrosal sinus gradient of PRL, TSH, and α-HCG to the side of the tumor, whereas patients with the ectopic ACTH syndrome tended not to exhibit lateralizing (side-to-side) gradients. These findings indicate that the simultaneous measurement of inferior petrosal sinus concentrations of PRL or TSH or of the glycoprotein hormone α subunit does not improve preoperative localization of ACTH-secreting microadenomas and may lead to incorrect lateralization of the tumor. The results also suggest that ACTH-secreting microadenomas cause enhanced delivery of PRL, TSH, and α subunit into the inferior petrosal sinus ipsilateral to the tumor which, in turn, may reflect paracrine stimulation of hormone secretion in the anterior pituitary gland surrounding ACTH-secreting microadenomas.