title: Irregular and frequent cortisol secretory episodes with preserved diurnal rhythmicity in primary adrenal Cushing's syndrome.
abstract: To evaluate the pathophysiology of altered cortisol secretion in patients with primary adrenal hypercortisolism, cortisol secretion was investigated in 12 patients, seven with a unilateral adenoma and five with ACTH-independent macronodular adrenal hyperplasia compared with age- and gender-matched controls and with patients with pituitary-dependent hypercortisolism. Pulsatile secretion was increased 2-fold (P = 0.04), attributable to increased event frequency (P = 0.002). All patients showed a significant diurnal rhythm with a delay in phase shift of 3 h (P = 0.01). Approximate entropy ratio, a feedback-sensitive measure, was increased compared with controls (P = 0.00003) but similar to that of pituitary-dependent hypercortisolism (P = 0.77), denoting loss of autoregulation. Cortisol burst-mass tended to be smaller in patients with ACTH-independent macronodular adrenal hyperplasia than in unilateral adenoma (P = 0.06). In conclusion, increased cortisol secretion in patients with primary adrenal Cushing's syndrome is caused by amplified pulsatile secretion via event frequency modulation. We speculate that partial preservation of secretory regularity and diurnal rhythmicity point to incomplete autonomy of these tumors.
authors.affiliation: Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
authors.forename: M O
authors.initials: MO
authors.lastname: van Aken
authors.forename: A M
authors.initials: AM
authors.lastname: Pereira
authors.forename: S W
authors.initials: SW
authors.lastname: van Thiel
authors.forename: G
authors.initials: G
authors.lastname: van den Berg
authors.forename: M
authors.initials: M
authors.lastname: Frölich
authors.forename: J D
authors.initials: JD
authors.lastname: Veldhuis
authors.forename: J A
authors.initials: JA
authors.lastname: Romijn
authors.forename: F
authors.initials: F
authors.lastname: Roelfsema
mesh_terms: D000236:Adenoma / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000310:Adrenal Gland Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000311:Adrenal Glands / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D002940:Circadian Rhythm; D003480:Cushing Syndrome / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D019277:Entropy; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
chemical_list: D006854:Hydrocortisone