The role of inferior petrosal sinus sampling in ACTH-dependent Cushing's syndrome: review and joint opinion statement by members of the Italian Society for Endocrinology, Italian Society for Neurosurgery, and Italian Society for Neuroradiology

Abstract

<jats:p>In the management of adrenocorticotropic hormone (ACTH)–dependent Cushing's syndrome, inferior petrosal sinus sampling (IPSS) provides information for the endocrinologist, the neurosurgeon, and the neuroradiologist. To the endocrinologist who performs the etiological diagnosis, results of IPSS confirm or exclude the diagnosis of Cushing's disease with 80%–100% sensitivity and over 95% specificity. Baseline central-peripheral gradients have suboptimal accuracy, and stimulation with corticotropin-releasing hormone (CRH), possibly desmopressin, has to be performed. The rationale for the use of IPSS in this context depends on other diagnostic means, taking availability of CRH and reliability of dynamic testing and pituitary imaging into account. As regards the other specialists, the neuroradiologist may collate results of IPSS with findings at imaging, while IPSS may prove useful to the neurosurgeon to chart a surgical course. The present review illustrates the current standpoint of these 3 specialists on the role of IPSS.</jats:p>

Latest diagnostic approaches to determine the cause of ACTH-dependent Cushing’s syndrome, in the South African setting

“…By using a ratio of greater than 3:1 with CRH stimulation during IPSS, most studies report an increased accuracy, especially with regard to an improvement in the sensitivity to 81-100%. 5 However, as discussed earlier, CRH is largely unobtainable in South Africa.…”

“…5 Sensitivity of IPSS for PC has been reported with much greater variability (54-96%), but most studies report sensitivities well above 80%. 5 Our patient had a ratio of 12:1 from the right IPS, which far exceeds this diagnostic threshold and confirms PC. Of note, samples taken from the left IPS showed ACTH concentrations equal to peripheral blood, at a ratio of 1:1 (see below).…”

“…19,20 Although side effects are rare, DDAVP administration does have the potential for vasoconstriction, hyponatraemia and haemostatic effects for which patients should be observed after the procedure. 5 Due to the invasive nature of IPSS, diagnostic accuracy should be enhanced in every feasible way and, as such, DDAVP is a suitable alternative to CRH in the South African setting during IPSS. In our patient the central to peripheral ACTH ratio in the right catheter doubled to 24:1 after 10 mcg DDAVP IV administration.…”

“…5,19 It has, however, been shown that correction of ACTH ratios for prolactin improves the accuracy of localisation. 27,28 Right and left ACTH levels are corrected for prolactin levels by dividing the ACTH level by the ipsilateral and concurrent prolactin value.…”

“…Inferior petrosal sinus sampling (IPSS) remains the most accurate method to localise the source of ACTH excess. 5,6 However, IPSS is invasive with a risk of adverse events and requires expertise that is not readily available, especially in South Africa. Unfortunately no non-invasive test, when used in isolation, can improve on the aforementioned pretest probability for PC.…”