Endocrine Abstracts

Introduction: To assess the demographic data, etiological distribution, methods of diagnosis in patients with clinical (CS) and subclinical Cushing’s (SCC) syndrome.

Methods: Forty-seven patients, 35 with CS and 12 with SCC patients were evaluated retrospectively.

Results: Of the 35 patients with CS, 55% were classified as ACTH-dependent and 43% as ACTH-independent. Pituitary adenoma constituted 54% of cases, adrenal adenoma 34%, adrenal carcinoma 9% and ectopic ACTH syndrome 3%. ACTH independent macronodular adrenal Hyperplasia (AIMAH) was determined in 50% of the 12 patients with SCC, adrenal adenoma in 33.3%, adrenal carcinoma in 8.3% and pituitary adenoma in 8.3%. At 1 mg DST and 2-day 2 mg DST tests used for endogenous hypercortisolism screening and diagnosis, 1.8 μg/dl cortisol threshold value sensitivities were 100 and 97.9%, respectively. When a 7.5 μg/dl threshold value was used for overnight cortisol, test sensitivity was 81.8% in clinical syndrome patients and 50% in subclinical syndrome patients. While plasma ACTH levels were above a threshold value of 15 pg/ml in all (100%) ACTH-dependent Cushing’s syndrome patients, ACTH was below this threshold in all adrenal Cushing’s syndrome patients. IPSS performed with CRH stimulation had 100% sensitivity and specificity in differentiating Cushing’s disease from ectopic ACTH syndrome. No positive receptor response was determined in any test included in the standard screening protocol recommended for the detection of aberrant receptors in AIMAH patients.

Discussion: AIMAH was the most common cause of subclinical Cushing’s syndrome in our study. Since 5–10% of incidental adrenal masses are bilateral, the number of AIMAH cases with subclinical Cushing’s syndrome is expected to rise increasingly. The absence of positive response in any test in the standard protocol recommended for aberrant receptors, supports the idea that there may be other aberrant receptors. While a 1.8 μg/dl cortisol threshold value following overnight 1 mg DST and 2-day 2 mg DST had high sensitivity for detecting endogenous hypercortisolemia, a 7.5 mcg/dl threshold value for overnight serum cortisol had low sensitivity. Plasma ACTH levels above 15 pg/ml are compatible with ACTH-dependent Cushing’s syndrome, while ACTH levels below 15 pg/ml are compatible with ACTH-independent Cushing’s syndrome. Plasma ACTH may be between 5 and 15 pg/ml in AIMAH cases with mild hypercortisolemia and adrenal adenomas in particular. IPSS is the most reliable means for discriminating between pituitary and non-pituitary sources of ACTH.