Assessment of Early Markers of Cardiovascular Risk in Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a heterogeneous syndrome, with long-term sequelae from birth to senescence. The long-term effects of PCOS are attributed to several metabolic aberrations ensuing the syndrome. In a systematic review of literature regarding the cardiovascular risk factors that accompany PCOS, we found that macrovascular function has been assessed by flow-mediated dilatation (FMD), microvascular function by venous occlusion plethysmography (VOP), and arterial structure by ultrasonographic assessment of intima-media thickness (IMT) usually of the carotid artery. Contradictory results have been reported; however, in most studies, endothelial dysfunction, an early marker of atherosclerosis assessed either by haemodynamic methods such as FMD or by biochemical methods such as endothelin-1 levels, was found to be impaired. VOP is a less-studied method, with few indices altered. IMT was found to be altered in most of the included studies, but the population was more heterogeneous. Inflammatory markers, including C-reactive protein, were also found to be altered in most studies. On the other hand, a number of interventions have been shown beneficial for the markers of cardiovascular risk, in the context of insulin-sensitizers. However, other interventions such as oral contraceptive pills or statins did not consistently show a similar beneficial effect. In summary, the early identification and eventual treatment of cardiovascular clinical and biochemical risk factors may be used in clinical practice to prevent potential 'silent' triggers of cardiovascular disease.

Magnetic Resonance Imaging or Endoscopic Ultrasonography for Detection and Surveillance of Pancreatic Neuroendocrine Neoplasms in Patients with Multiple Endocrine Neoplasia Type 1?

Our aim was to compare the clinical utility of Magnetic Resonance Imaging (MRI) and Endoscopic Ultrasonography (EUS) in identifying Pancreatic Neurondocrine Neoplasms (PanNENs) and monitoring size alterations in Multiple Endocrine Neoplasia type 1 (MEN1) patients. Thirty-one MEN1 patients with PanNENs and concurrent screening by EUS and abdominal MRI were included and 129 pancreatic lesions were detected in total. MRI detected fewer lesions than EUS (n=73 vs. 110, p=0.006). MRI sensitivity and specificity compared to EUS at 20 and 10 mm cut-offs of maximal lesion diameter were 96 and 88% (20 mm cut-off) and 90 and 82%(10 mm cut-off), respectively (concordance rates of 97 and 87% and Cohen's kappa=0.912 and 0.718, respectively). Lesions<1 cm were more often detected with EUS (p=0.025). Data from sequential concurrent imaging on lesion growth rate [n=7 (mean±SD: 2 mm/year±3.4 mm vs. 1.9 mm/year±3.6 mm)] over a period of at least two years as well as pathology data in connection to preoperative concurrent imaging were available in a small number of patients (n=7, p=0.933 for mean differences in maximal lesion diameter). MRI of the pancreas was more readily available and less expensive than EUS in an outpatient setting. In conclusion, MRI performs well compared to EUS for the detection and subsequent surveillance of MEN1-related panNENs larger than 10 mm and seems to be cost-effective. Both modalities could be used at initial assessment and MRI alone could be utilized thereafter in patient surveillance. EUS retains its value in surgical planning and the detection of small mostly functional PanNENs.

Assessment of serum-free cortisol levels in patients with adrenocortical carcinoma treated with mitotane: a pilot study.

OBJECTIVE: Mitotane treatment in adrenocortical carcinoma (ACC) results in unreliable measurement of serum total cortisol (TC) levels because of an elevation in corticosteroid-binding globulin (CBG). DESIGN: The use of a newly-developed serum-free cortisol (FC) assay was assessed to investigate the characteristics of a more valid measure of cortisol status. PATIENTS: Sixty-two serum samples from patients with ACC treated with mitotane were studied. Different subgroups were studied according to mitotane levels (<14, 14-20 and >20 mg/dl), hydrocortisone replacement treatment, presence of Cushing's syndrome (CS) and adrenocorticotrophin (ACTH) levels. MEASUREMENTS: Serum FC was measured using a newly-developed assay, TC, CBG and plasma ACTH using conventional laboratory kits; TC-to-CBG (Free cortisol index, FCI, nmol/mg) and TC-to-FC (TFR) ratios were calculated. RESULTS: CBG levels were elevated and positively correlated to mitotane levels. FC was positively related to TC and FCI in nearly all subgroups studied. Plasma ACTH was negatively related to parameters of cortisol levels in the total samples studied. In the 'target' subgroup with normal ACTH levels and mitotane levels 14-20 mg/dl, no correlation of plasma ACTH with any parameter studied was seen, and FC suggested over-replacement with hydrocortisone treatment in the subgroup with CS. CONCLUSIONS: FC measurement may offer additional information in the follow-up of patients on mitotane, especially when there is a history of CS which invalidates the use of acute changes in plasma ACTH as a parameter of hydrocortisone replacement. These preliminary data suggest that it may prove useful as a biochemical marker when TC or FCI are invalidated by mitotane treatment or plasma ACTH is suppressed by hypercortisolaemia. Larger studies are needed to substantiate the clinical utility of FC measurement in specific groups of patients.