Inferior petrosal sinus sampling for ACTH-Dependent Cushing’s Syndrome: More than merely localisation? — ASN Events

Inferior petrosal sinus sampling for ACTH-Dependent Cushing’s Syndrome: More than merely localisation? (#358)

Arianne Sweeting 1 , Julie Hetherington 1 , Geoffrey Parker 2 , Richard Waugh 2 , Nimalie Perera 1 , Elizabeth Chua 1 3
  1. Department of Endocrinology & Metabolism, Royal Prince Alfred Hospital, Sydney
  2. Department of Radiology, Royal Prince Alfred Hospital, Sydney
  3. Sydney Medical School, University of Sydney, Sydney


Inferior petrosal sinus sampling (IPSS) utilising corticotrophic releasing hormone (CRH) is considered gold standard for differentiating between pituitary and ectopic adrenocorticotrophic (ACTH)-dependent Cushing’s syndrome. However, false negative rates of up to 10% have been reported. The aim of this study was to evaluate the utility of IPSS in localisation and lateralisation of a pituitary source of ACTH-overproduction in suspected Cushing's Disease (CD).


Eighteen IPSS procedures were performed in seventeen patients with presumed CD and indeterminate MRI results between 2004 to 2013 at our centre. Four patients were excluded from final analysis - three had surgery elsewhere (outcomes not known) and surgery is pending in one. Four were assessed for recurrent disease. The following parameters were evaluated:Central/Peripheral ACTH gradient (≥ 2.0 at baseline or ≥ 3.0 after CRH) for localisation; Inter-petrosal sinus (IPS) gradient (≥ 1.4) for lateralisation; surgical histopathology; and post-operative clinical course.


Results are summarised in Table 1. A Central/Peripheral ACTH gradient of ≥ 2.0 was found in 11/14 at baseline and a gradient of ≥ 3.0 in 14/14 after CRH stimulation, confirming CD in all. IPS gradient was ≥ 1.4 in 11/14 at baseline and in all patients after CRH stimulation. For those undergoing first resection, IPSS predicted the correct tumour side in 8/10 as evidenced by remission post-surgery. In all patients with recurrent disease, despite surgical approach guided by IPS gradient ≥ 1.4, none achieved remission.


In our experience, IPSS localised a pituitary source of ACTH-dependent Cushing’s syndrome with 100% sensitivity and specificity in first presentation and recurrent CD. In patients undergoing first resection, the source of ACTH excess was correctly lateralised in all but two cases where 2 pituitary lesions were evident on initial MRIs. For patients with recurrent disease, repeat IPSS was limited to localisation, re-confirming pituitary disease. Failure to lateralise in this setting reflects distorted pituitary anatomy post-resection.