Second-Line Tests in the Diagnosis of Adrenocorticotropic Hormone-Dependent Hypercortisolism.

Cushing's syndrome (CS) is a rare disease caused by chronic and excessive cortisol secretion. When adrenocorticotropin hormone (ACTH) is measurable, autonomous adrenal cortisol secretion could be reasonably ruled out in a differential diagnosis of CS. ACTH-dependent CS accounts for 80%-85% of cases and involves cortisol production stimulated by uncontrolled pituitary or ectopic ACTH secretion. Pituitary adenoma is not detected in up to one-third of cases with pituitary ACTH secretion, whereas cases of CS due to ectopic ACTH secretion may be associated with either malignant neoplasia (such as small cell lung carcinoma) or less aggressive neuroendocrine tumors, exhibiting only the typical symptoms and signs of CS. Since the differential diagnosis of ACTH-dependent CS may be a challenge, many strategies have been proposed. Since none of the available tests show 100% diagnostic accuracy, a step-by-step approach combining several diagnostic tools and a multidisciplinary evaluation in a referral center is suggested. In this review, we present a clinical case to demonstrate the diagnostic work-up of ACTH-dependent CS. We describe the most commonly used dynamic tests, as well as the applications of conventional or nuclear imaging and invasive procedures.

Activation profiles of monocyte-macrophages and HDL function in healthy women in relation to menstrual cycle and in polycystic ovary syndrome patients.

PURPOSE: Hormonal status and menopause affect human macrophage function and cardiometabolic risk. In polycystic ovary syndrome (PCOS) patients the cardiometabolic risk increases through mechanisms that are largely unknown. We tested the hypotheses that macrophage activation is influenced by menstrual cycle and that ovarian dysfunction in PCOS patients is associated with altered macrophage inflammatory responses and cholesterol efflux capacity of serum HDL. METHODS: Blood samples were obtained in the follicular and luteal phases from cycling women (n = 10) and on a single visit from PCOS patients with ovarian dysfunction (n = 11). Monocyte-derived macrophage activation and monocyte subsets were characterized ex vivo using flow cytometry. The capacity of HDL to promote cell cholesterol efflux through the main efflux pathways, namely aqueous diffusion, ATP-binding cassette A1 and G1, was also evaluated. RESULTS: Hormone and metabolic profiles differed as expected in relation to menstrual cycle and ovulatory dysfunction. Overall, macrophage responses to activating stimuli in PCOS patients were blunted compared with cycling women. Macrophages in the follicular phase were endowed with enhanced responsiveness to LPS/interferon-γ compared with the luteal phase and PCOS. These changes were not related to baseline differences in monocytes. HDL cholesterol efflux capacity through multiple pathways was significantly impaired in PCOS patients compared to healthy women, at least in part independent from lower HDL-cholesterol levels. CONCLUSIONS: Regular menstrual cycles entailed fluctuations in macrophage activation. Such dynamic pattern was attenuated in PCOS. Along with impaired HDL function, this may contribute to the increased cardiometabolic risk associated with PCOS.