Endocrine Abstracts

Background: Diagnostic work-up for Cushing ’s syndrome (CS) can be challenging, with variable performance characteristics on screening tests. We were recently referred a young female patient with Cushing’s disease (CD) due to a microadenoma. She presented with a seizure and initial biochemical work-up included a Synacthen stimulation test (SST). Her peak cortisol rose to over 1,000 nmol/l. Exaggerated response during SST is expected in hyperestrogenic states due to elevation in cortisol-binding globulin concentrations, for e.g. pregnancy and those taking estrogen-containing pills. However, overstimulation of the adrenal cortex by increased ACTH, as in ACTH-driven CS, is physiologically expected to result in hypertrophy of the zona fasciculata and therefore produce a heightened cortisol response during SST.

Aim: We retrospectively compared the difference in peak cortisol concentrations, after 250 µg tetracosactide administration during SST, in patients with active CD and those without CS but intact steroid axis.

Methods: In our unit, all patients with CD undergoing Transphenoidal Sugery (TSS) are started on steroid replacement post-operatively. SST is performed, after a standard steroid weaning, at 6-8 weeks post-operatively and if normal, standard biochemical work-up for steroid excess takes place again. We included all patients who were not in biochemical remission after TSS. Our comparator cohort includes all patients with a normal SST result after pituitary surgery for non-Cushing tumours. Roche I and Roche II Cortisol assays were used, with a normal SST response defined as peak serum cortisol level of >550 nmol/l or >420 nmol/l, respectively. Conversion of peak cortisol level from Roche I to Roche II equivalent concentration was done using validated regression equation. Mann-Whitney U test and Fisher’s exact test were used for statistical analysis for continuous and categorical variables respectively. Results are expressed as mean (±SD).

Results: 13 patients with active CD and 210 patients with normal SST results were included in our CD and control cohort. Mean peak cortisol in our CD cohort was higher at 1020 (±305) nmol/l compared to 677 (±144) nmol/l (P<0.01). 62% of SSTs in the CD cohort had a peak cortisol of >850 nmol/l compared to 9% in the control cohort (P<0.01).

Conclusion: Patients with active CD demonstrate a higher than average cortisol response during SST. Clinicians should keep a high index of suspicion for ACTH-driven CS in patients with an exaggerated cortisol response on SST, especially in the context of initial biochemical work-up for pituitary incidentalomas.