Biochemical screening for subclinical cortisol-secreting adenomas amongst adrenal incidentalomas

Abstract

Objective: Biochemistry and 131 I-6b-iodomethyl norcholesterol scintigraphy (IMS) have both been used to assess cortisol secretion by adrenocortical incidentalomas. However, which biochemical abnormalities indicate subclinical corticoid excess is still debatable whilst IMS is expensive and cumbersome. The aim of the study was to evaluate prospectively patients with adrenal incidentalomas using both IMS and biochemical methods to examine whether the IMS pattern is associated with biochemical abnormalities and, if this is so, to find a biochemical parameter that could be used as a screening test to identify a subset of patients on whom IMS could subsequently be performed. Methods: Thirty-one patients with benign cortical adenomas were recruited from 43 consecutive patients with adrenal incidentalomas. All 31 patients underwent IMS and measurement of (i) 0800 h serum cortisol, ACTH, dehydroepiandrosterone and 17-hydroxyprogesterone; (ii) midnight serum cortisol; (iii) 2400 h excretion of urinary free cortisol; (iv) cortisol after the overnight 1 mg dexamethasone (DEX) suppression test; (v) cortisol after an i.v. 4 mg DEX test; (vi) determination of the diurnal variation in serum cortisol. Results: Sixty-one per cent of patients displayed unilateral uptake during IMS and 39% showed bilateral uptake. Patients with unilateral uptake exhibited significantly lower ACTH concentrations P 0X0005Y higher midnight cortisol concentrations P 0X02Y disrupted diurnal variation of serum cortisol P 0X02 and higher cortisol concentrations after DEX suppression tests P 0X01X Cortisol concentrations following the two DEX suppression tests correlated closely r 0X80Y P 0X0001X The i.v. 4 mg DEX test was clearly more sensitive for the diagnosis of unilateral uptake than the overnight 1 mg DEX test (76 vs 52%). Using various thresholds of cortisol concentration following the overnight 1 mg DEX test, it was found that the sensitivity of the test could be improved to 100% if the threshold was set at 60 nmol/l rather than the classical value of 138 nmol/l. All patients but one with post-test serum cortisol concentrations above 60 nmol/l as against none of patients with cortisol below 60 nmol/l exhibited at least one associated biochemical abnormality indicating subclinical glucocorticoid excess. Conclusion: In adrenocortical incidentalomas, unilateral uptake during IMS suggests subclinically excessive and/or autonomous cortisol secretion. A cortisol concentration above 60 nmol/l following the overnight 1 mg DEX test is highly correlated with unilateral uptake and is associated with biochemical abnormalities indicating subclinical glucocorticoid excess. Our results favour the use of the 1 mg overnight DEX test with revised criteria of interpretation as a screening test for subclinical hypercortisolism among patients with adrenocortical incidentalomas.

Adrenal incidentalomas — a continuing management dilemma

“…Bardet et al (1996) found that low 8 am dehydroepiandrosterone sulfate, low 8 am ACTH, basal urinary free cortisol, unsuppressed 8 am serum cortisol after overnight 1 mg dexamethasone suppression, unsuppressed day 2 serum cortisol, and unsuppressed day 2 urinary free cortisol after low-dose dexamethasone suppression had low sensitivity (0-50%) and moderate specificity (79-94%) to differentiate unilateral from bilateral scintigraphy uptake. In contrast, Valli et al (2001) found that unsuppressed 8 am cortisol after overnight dexamethasone suppression had 100% sensitivity and 67% specificity to predict unilateral uptake. Studies of diagnosis of catecholamine excess and primary hyperaldosteronism reveal similar problems in sensitivity and specificity.…”

Prevalence and natural history of adrenal incidentalomas

“…Since adrenal scintiscan may not be available in all centers, the 1 mg overnight dexamethasone suppression test may be a rapid and convenient tool to identify patients at risk for disease progression. With revised cut-off levels for a normal response, this test shows a good correlation with scintigraphic patterns and a high sensitivity in the detection of mild subclinical hypercortisolism (92,93).…”

“…As to the role of adrenocortical scintigraphy as a predictive factor for adrenal hyperfunction, findings of an increased risk of adrenal hyperfunction in patients showing exclusive uptake by the adrenal mass indicate that this scintigraphic pattern may represent an early phase of functional autonomy of the adrenal adenomas also in the case of apparently normal hormone function (42,52,67,92,127). Indeed, a mild degree of autonomy is demonstrated by lack of complete suppression after low-dose dexamethasone (92,93).…”

“…Indeed, a mild degree of autonomy is demonstrated by lack of complete suppression after low-dose dexamethasone (92,93). Since adrenal scintiscan may not be available in all centers, the 1 mg overnight dexamethasone suppression test may be a rapid and convenient tool to identify patients at risk for disease progression.…”

Adrenal incidentalomas: ‘the rule of four'

“…For this reason, the terms subclinical Cushing's syndrome or subclinical autonomous glucocorticoid hypersecretion (SAGH) have been used. 8,9 There is evidence for an increased prevalence of certain of the problems associated with Cushing's syndrome in patients with SAGH, such as increased cardiovascular risk factors (hypertension, central obesity, diabetes, impaired glucose tolerance, hyperlipoproteinaemia) and an increased risk of osteoporosis, supporting the significance of their early recognition and appropriate management. 10,11 …”