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

Introduction:

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).

Methodology:

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:

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.

Conclusion:

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. 

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