Elevated post‐dexamethasone suppression cortisol concentrations correlate with hormonal alterations of the hypothalamo‐pituitary adrenal axis in patients with adrenal incidentalomas
Authors: Tsagarakis S. , Roboti C. , Kokkoris P. , Vasiliou V. , Alevizaki C. , Thalassinos N. 
Published: March 2003

OBJECTIVE

It has recently been suggested that autonomous cortisol production may lead to subclinical glucocorticoid excess in a substantial number of patients with incidentally discovered adrenocortical adenomas. Following a standard low‐dose dexamethasone suppression test (LDDST) cortisol concentrations are frequently incompletely suppressed in patients with adrenal incidentalomas, due to an ACTH‐independent secretion of cortisol by the adrenal mass. Thus, post LDDST cortisol concentrations may provide a measure of the degree of autonomous glucocorticoid secretion, but hormonal alterations in relation to post‐LDDST cortisol concentrations have not been thoroughly investigated.

PATIENTS AND MEASUREMENTS

61 patients with radiological features highly suggestive of adrenal adenomas were studied. These included 43 women, 18 men; mean age 59 ± 1.4, range: 25–76 years; BMI 30.9 ± 0.8 kg/m2; and waist:hip ratio 0.90 ± 0.016. All subjects underwent a standard LDDST, as follows: after a 48‐hr stabilisation period, 24‐hr urine collections for basal urinary free cortisol (UFC) were performed. Basal serum cortisol and plasma ACTH were measured at 8 AM and at midnight the following day, and subjects started dexamethasone 0.5 mg 6 hourly for 2 days. Post‐dexamethasone cortisol and ACTH levels were measured at 8 AM, 6‐hrs after the last dose of dexamethasone. Blood samples for dehydroepiandrosterone sulphate (DHEAS) and serum lipids were obtained on the morning preceding dexamethasone administration.

RESULTS

Post‐LDDST cortisol concentrations correlated positively with the size of the adenoma (r=+0.527, P<0.001). There was a negative rank correlation of post‐LDDST cortisol concentrations and basal ACTH levels at 0900h (rs=−0.426 P<0.001) and DHEAS (rs=−0.380, P=0.006). Moreover, there was a good rank correlation between DHEAS and basal ACTH levels (rs=+0.456,, P<0.001). A positive rank correlation was observed between post‐LDDST cortisol concentrations and midnight cortisol concentrations (rs=+0.317, P=0.020). As recent studies have suggested that post‐LDDST cortisol levels higher than 70 nmol/l may indicate significant hypercortisolism comparisons were also performed between patients divided according to post‐LDDST cortisol values into 3 groups: Group A, >70 nmol/l (19 pts); Group B, 30–70 nmol/l (27 pts); Group C, <30 nmol/l (15 pts). Although there was no difference in basal cortisol and UFC values between these groups, ACTH and DHEAS levels were significantly lower, and midnight cortisol significantly higher in group A compared to group C patients (P=0.030, P=0.017 and P=0.001 respectively). Cholesterol and triglyceride levels were slightly albeit significantly higher in group A compared to group C patients (P<0.05).

CONCLUSIONS

It is concluded that higher post‐low dose dexamethasone cortisol concentrations are associated with lower ACTH and dehydroepiandrosterone sulphate, higher midnight cortisol concentrations and larger adenomas. These findings are consistent with the hypothesis that post‐low dose dexamethasone cortisol concentrations represent a useful index in assessing subtle glucocorticoid autonomy in patients with adrenal adenomas.