Analysis of the value of bilateral inferior petrosal Sinus sampling (BIPSS) in Cushing's syndrome. Can BIPSS be employed to guide surgical resection?

Objective: Diagnosis and treatment of ACTH- dependent hypercortisolism are challenging. We are confronted with two major problems: The distinguishment of ACTH overproduction due to pituitary lesion from ectopic production is not always obvious in conventional biochemical tests. Localization of pituitary lesions is the second problem as microadenomas are often missed in MRIs. To define the diagnosis we performed bilateral ACTH sampling in BIPSS and evaluated its predictive value for tumor lateralization.

Methods: Prior to BIPSS standard biochemical tests were performed. All the patients received sella MRI. During catheterization timing of the ACTH sampling before and after CRH stimulation was – 5, 0, 5, 10, 15 min. Prolactin was measured as index of pituitary venous drainage. Diagnostic criteria included the central vs. peripheral ACTH ratio (IPS: P) and right vs. left ratio.

Results: 14 of 21 patients with hypercortisolism showed no clear sella MRI findings. These patients underwent BIPSS. 11 patients obtained an IPS: P ratio 3 – 83 suggesting Cushing's disease.2 patient showed ectopic ACTH secretion,1 patient Nelson's syndrome,1 patient remained with unclear hypercortisolism.10 patients showed right to left ACTH gradient of 3 – 78.1 patient showed no side gradient.11 patients underwent surgery. In only 2 cases tumor lateralization in IPS was 'incorrect' – a microadenoma was found on the other side. In 1 of these 2 cases cavernosus sinus thrombosis caused restricted venous drainage and thus low ACTH level on the ipsilateral side. In this case BIPSS cannot be used to guide surgical resection. The accuracy for lateralization was 82%.8 of 11 patients showed remission after surgery.

Conclusions: IPS Sampling is an invasive investigation in the diagnosis of Cushing's syndrome. It's a powerful tool to distinguish central ACTH overproduction from etopic secretion. Despite early controversy, we believe that BIPSS can be applied for the preoperative tumor localization when MRI studies are not clear.