Heterogeneity of responses of dynamic tests in patients with ectopic cushing

Aleksandra Gamrat; Mari Minasyan; Komisarz-Calik Maria Aleksandra; Alicja Hubalewska-Dydejczyk; Aleksandra Gilis-Januszewska

doi:10.1530/endoabs.99.EP342

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Endocrine Abstracts (2024) 99 EP342 | DOI: 10.1530/endoabs.99.EP342

ECE2024 Eposter Presentations Endocrine-Related Cancer (90 abstracts)

Heterogeneity of responses of dynamic tests in patients with ectopic cushing’s syndrome (ECS). the half of patients with ECS have an increase in ACTH in the CRH/desmopressin test, nearly 1/3 have complete or some inhibition of cortisol in HDDST

Aleksandra Gamrat ^1,2 , Mari Minasyan ¹ , Maria Aleksandra Komisarz-Calik ¹ , Alicja Hubalewska-Dydejczyk ¹ & Aleksandra Gilis-Januszewska ¹

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¹Jagiellonian University Medical College, Chair and Department of Endocrinology, Kraków, Poland; ²Jagiellonian University Medical College, Doctoral School of Medical and Health Science

Introduction: According to the literature, the CRH test has the highest specificity in excluding ECS (ACTH 93.9%, cortisol 89.4%). A combination of the high dose dexamethasone test (HDDST) and CRH/desmopressin test (CRH/desmopressinT) is used to increase the discriminatory capacity in ACTH-dependent CS.

Objectives: This study aims to investigate the response to dynamic tests in ECS patients.

Methods: 35 consecutive ECS patients were analyzed (3 SCLC patients were excluded from further analysis). Neuroendocrine tumor (NET) constituted 47% of all EAS (60% gastroenteropancreatic, 40% thoracic (1 thymic and 5 pulmonary carcinoids (PC)), 4 cases were occult. The cut-off points for CRH/desmopressinT was >20% increase in cortisol concentration (Δcortisol%), >35% increase in ACTH (ΔACTH%) and for HDDST >50% decrease of cortisol (-Δcortisol%). The CRH/desmopressinT was performed in 18/32 (16 CRH/2desmopressin), HDDST in 25/32 patients.

Results: All patients responded to CRH/desmopressin (ACTH surge range: 12-197%), with average increase of cortisol and ACTH by 25.5% and 63%. The CRH/desmopressinT ΔACTH% and Δcortisol% were observed in 50% patients, in all PC and in 35.7% of other ECSs (P=0.02). The average percentage increase of ACTH in the CRH/desmopressinT was higher in the PC compared to other ECSs (98% vs 32% P=0.08). In HDDST -Δcortisol% was observed in 3 patients/12% (uterus clear cell carcinoma, PC and occult origin), 28% of the patients responded with a >30% decrease in cortisol. Positive results in both tests, indicative of Cushing’s disease was observed in two ECSs (PC, occult). Patients with ΔACTH%, compared to the remaining ECSs, were characterized by a significantly higher potassium concentration (3.69 vs 2.51 mmol P=0.02) and a higher baseline ACTH concentration (281 vs 214 pg/ml). Patients with -Δcortisol% in HDDST also had higher potassium concentration compared to the non-inhibition group (4.3 mmol/l vs 2.91 mmol/l, P=0.04). There were no significant differences in response to dynamic tests between men and women. There was a strong correlation between the increase in cortisol in the CRH/desmopressinT and the decrease in cortisol in the HDDST (Spearman’s correlation coefficient -0.89 P<0.05).

Conclusion: Half of ECS patients have Δcortisol% and ΔACTH% in CRH/desmopressinT and nearly one third in HDDST have cortisol decrease >30%. Our results also suggest that an increase in cortisol in the CRH/desmopressinT is associated with a decrease in cortisol in the HDDST. Further, multicenter studies are needed to understand the response of ECS patients to dynamic tests and to establish/improve diagnostic differential criteria.