A critical analysis of the value of simultaneous inferior petrosal sinus sampling in Cushing's disease and the occult ectopic adrenocorticotropin syndrome

The clinical, biochemical, and radiological features of pituitary ACTH-depe ndent Gushing's syndrome(CS) [Cushing's disease (CD)] are often indistingui shable from those of occult ectopic ACTH-dependent CS (oEAS). We have evalu ated, retrospectively, the results of simultaneous bilateral inferior petro sal sinus (IPS) ACTH sampling before and after CRH stimulation in 128 patie nts with ACTH-dependent CS: 107 patients with CD, 6 with oEAS, 1 with an ad renal adenoma, 1 with a pituitary gangliocytoma, and 1 with Nelson's syndro me; while, in the remaining 12, the source remains unclear. One hundred sev en patients received human-sequence CRH (hCRH), and II received ovine CRH; another 6 patients underwent stimulation with desmopressin and hCRH, and 4 with desmopressin alone. A successful bilateral IFS catheterization and sam pling (IPSCS) rate of 87.5% was obtained only after considerable experience had been gained. Sixty-nine patients with CD underwent successful bilatera l IPSCS: the IFS-to-peripheral ratio of plasmaACTH value (IPS/P) rose from 9.5 +/- 1.4 to a maximum ratio of 55.8 +/- 7.5 in 67 patients, after CRH st imulation. The maximum ratio was obtained at 5 min in 60 of the 69 patients with CD; however, all 69 patients obtained a ratio of more than 2, at that time. In contrast, the 6 patients with occult ACTH-secreting neoplasms had a maximal IPS/P ratio of 1.3 +/- 0.16, and this did not change after CRH s timulation. A bilateral IPS/P ratio more than 2, obtained 5 min after CRH s timulation, had a sensitivity of 97% and a specificity of 100% in diagnosin g CD. Two patients with proven active CD had an IPS/P ratio of less than 2. After successful bilateral IPSCS, the gradients between the IFS ACTH conce ntrations [IPS ACTH gradient (IPSG)] of more than 1.4, at 5 min after CRH s timulation, had a sensitivity of 83% in correctly lateralizing the pituitar y microadenoma, compared with 72% sensitivity for magnetic resonance imagin g (MRI) scanning. Furthermore, when IPSG and MRI findings were contradictor y, IPSG was more often correct than MRI scanning. Although oEAS is a relati vely uncommon cause of ACTH-dependent hypercortisolism (5.5% in our series) , the accurate diagnosis of ACTH-dependent CS and localization of an intrap ituitary microadenoma requires bilateral IPSCS with CRH stimulation, provid ed that the appropriate technical experience is available. hCRH is as effec tive a secretagogue as ovine CRH, and either maybe used. The value of the c ombination of CRH and desmopressin stimulation requires more detailed inves tigation.