Selective Venous Sampling in the Differential Diagnosis of ACTH-Dependent Cushing’s Syndrome

Abstract

Bilateral simultaneous inferior petrosal sinus sampling, associated with the oCRH stimulation test (100 µg i.v. as a bolus) was performed in 22 patients with Cushing’s syndrome and no signs of pituitary abnormalities. Catheters were inserted into both femoral veins. More than one site in the superior and inferior vena cava was sampled before reaching the inferior petrosal sinuses. Blood samples for ACTH and β-endorphin were gently aspirated from both petrosal sinuses and from a peripheral vein simultaneously. Blood was drawn at 0, 5, 10 and 15 min after oCRH injection. Seventeen of 22 patients showed an ipsilateral to peripheral vein ratio higher than 1.5, and 12 patients showed a lateralization of ACTH levels after oCRH stimulation. Seventeen patients underwent transsphenoidal pituitary surgery. Nine patients had a pituitary adenoma at the expected side; 1 at the contralateral side, while in 2 it was central. Three of 4 patients in whom the ipsilateral/peripheral ratio was less than 1.5 had the highest ACTH levels at the superior or inferior vena cava, not responsive to oCRH stimulation. One of these had a mediastinal and one a pulmonary mass. The third one, with an occult ectopic source, is still under investigation. At immunohistochemical and biological in vitro studies, both tumors were shown to secrete ACTH. In 13 patients in whom both β-endorphin and ACTH measurements were performed, these hormones showed similar patterns of response. In conclusion, simultaneous bilateral petrosal sinus catheterization is a useful tool in the differential diagnosis of Cushing’s syndrome as concerning pituitary and ectopic forms. The finding of a ratio <1.5, especially after oCRH stimulation, between pituitary/peripheral sites strongly suggests the existence of an ectopic ACTH-secreting tumor. In the pituitary forms, an oCRH stimulation test performed during the procedure may clearly indicate the site of ACTH hypersecretion.

Simultaneous and Bilateral Inferior Petrosal Sinus Sampling for the Diagnosis of Cushing&rsquo;s Syndrome: Comparison of Multihormonal Assay, Baseline Multiple Sampling and ACTH-Releasing Hormone Test

“…Moreover, this study shows, for the first time to our knowledge, the lack of ISG for GH, PRL, TSH, FSH and LH as well as of p-endorphin in patients with EAS. These data, although obtained in only 4 cases are in agreement with the report of p-endorphin ISG in 2 other cases of EAS [24] and indicate that the multiple hormone evalua tion might improve the diagnostic accuracy of IPSS. Finally, the question of whether IPSS can be confirmed in clinical practice as a reliable tool to localize the site of the pituitary microadenoma in CD is still unresolved.…”

“…Al though it has been suggested that corticotroph microade nomas preferentially arise in the central mucoid core of the anterior lobe [25,26], these tumors can arise any where in the sella including the intermediate lobe [20][21][22]27]. In our series the correct localization of the side of the adenoma was obtained in 87% of cases and in only a minority of patients was the adenoma falsely localized (21 %): the percentage of cases was, however, comparable to the findings of other authors [4,5,24], Furthermore, no patient with poststimulation gradient reversal was found [28].…”

A role for life events in the pathogenesis of Cushing's disease

“…Morphological assessment was performed by pituitary and adrenal computerized tomography and/or magnetic resonance imaging, and adrenal scintiscan with 6-methyl-75Se-seleniomethyl-19-norcholesterol. When indicated, bilateral petrosal sinus sampling was also employed (Boscaro et al, 1992). All patients were interviewed while on remission after surgery, pituitary irradiation or pharmacological treatment with inhibitors of steroid production (Sonino et al, 1988(Sonino et al, , 1991, and therefore not in the hypercortisolaemic state.…”

Patterns of ACTH Response to oCRH in Cushing’s Disease: Correlation with Histological/Immunocytochemical Findings

“…Morpho logical assessment was performed by pituitary and adrenal computer ized tomography (CT) and/or magnetic resonance imaging (MRI), and adrenal scintiscan with 6-methyl-75-scleniomcthyl-19-norcholesterol. When indicated, bilateral petrosal sinus sampling was also employed [18][19][20][21]. Patients of both groups all showed good cortisol suppression with high-dose dexamethasone test (table 1).…”