title: Elevated post-dexamethasone suppression cortisol concentrations correlate with hormonal alterations of the hypothalamo-pituitary adrenal axis in patients with adrenal incidentalomas.
abstract: 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.
  
  
  METHODS
  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 0900 h (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.
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Evangelismos' Hospital, Athens, Greece.
authors.forename: S
authors.initials: S
authors.lastname: Tsagarakis
authors.forename: C
authors.initials: C
authors.lastname: Roboti
authors.forename: P
authors.initials: P
authors.lastname: Kokkoris
authors.forename: V
authors.initials: V
authors.lastname: Vasiliou
authors.forename: C
authors.initials: C
authors.lastname: Alevizaki
authors.forename: N
authors.initials: N
authors.lastname: Thalassinos
mesh_terms: D000236:Adenoma / Q000175:diagnosis* / Q000378:metabolism / Q000503:physiopathology; D000304:Adrenal Cortex Function Tests; D000306:Adrenal Cortex Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000503:physiopathology; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000368:Aged; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D003907:Dexamethasone; D005260:Female; D005938:Glucocorticoids; D006801:Humans; D006854:Hydrocortisone / Q000097:blood* / Q000652:urine; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000503:physiopathology*
chemical_list: D005938:Glucocorticoids; D008055:Lipids; D019314:Dehydroepiandrosterone Sulfate; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone