Renato Pasquali

Tissue-specific dysregulation of 11β-hydroxysteroid dehydrogenase type 1 in overweight/obese women with polycystic ovary syndrome compared with weight-matched controls

CONTEXTnAbnormal cortisol metabolism in polycystic ovary syndrome (PCOS) has been invoked as a cause of secondary activation of the hypothalamic-pituitary-adrenal axis and hence androgen excess. However, this is based on urinary excretion of cortisol metabolites, which cannot detect tissue-specific changes in metabolism and may be confounded by obesity.nnnOBJECTIVEnTo assess cortisol clearance and whole-body and tissue-specific activities of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 (HSD11B1)) in PCOS.nnnDESIGNnCase-control study.nnnSETTINGnMedical center.nnnPATIENTSnA total of 20 overweight-obese unmedicated Caucasian women with PCOS, aged 18-45 years, and 20 Caucasian controls matched for age, BMI, body fat distribution, and HSD11B1 genotypes (rs846910 and rs12086634).nnnMAIN OUTCOME MEASURESnCortisol metabolites were measured in 24u200ah urine. During steady-state 9,11,12,12-[(2)H]4-cortisol infusion, cortisol clearance was calculated and whole-body HSD11B1 activity was assessed as the rate of appearance of 9,12,12-(2)H3-cortisol (d3-cortisol). Hepatic HSD11B1 activity was quantified as the generation of plasma cortisol following an oral dose of cortisone. Subcutaneous adipose HSD11B1 activity and HSD11B1 mRNA were measured, ex vivo, in biopsies.nnnRESULTSnUrinary cortisol metabolite excretion, deuterated cortisol clearance, and the rate of appearance of d3-cortisol did not differ between patients with PCOS and controls. However, hepatic HSD11B1 conversion of oral cortisone to cortisol was impaired (P<0.05), whereas subcutaneous abdominal adipose tissue HSD11B1 mRNA levels and activity were increased (P<0.05) in women with PCOS when compared with controls.nnnCONCLUSIONSnTissue-specific dysregulation of HSD11B1 is a feature of PCOS, over and above obesity, whereas increased clearance of cortisol may result from obesity rather than PCOS.

Adrenal adenomas, subclinical hypercortisolism, and cardiovascular outcomes.

Purpose of reviewRecent evidence has highlighted the link between cardiovascular outcomes and incidentally discovered adrenal masses. The purpose of this review is to summarize the most recent findings on the cardiovascular profile of patients with nonfunctional adrenal adenomas. Recent findingsNonsecreting adrenal tumors, defined mostly by cortisol levels after dexamethasone suppression test below 1.8u200a&mgr;g/dl, are associated with impairment of markers of subclinical atherosclerosis such as intima-media thickness and flow-mediated vasodilation. The presence of impaired indices of insulin resistance could represent an additional factor that contributes to the worsening of the cardiovascular profile of those patients. No evidence of increased cardiovascular outcomes was found in this group of patients. On the contrary, according to the findings of recent long-term retrospective studies, patients with subclinical hypercortisolism have an increased incidence of cardiovascular outcomes and related mortality with respect to nonsecreting adrenal masses and to the general population. SummaryAn impaired cardiovascular profile is a common finding in patients with apparently nonfunctional adrenal masses. However, the incidence of cardiovascular outcomes and related mortality seems to be increased only in patients with mild cortisol hypersecretion.

Cross-talk between adipose tissue and the HPA axis in obesity and overt hypercortisolemic states.

Abstract In addition to its roles in providing insulation and mechanical support, adipose tissue (AT) has been recognised as the major site for storage of surplus fuel. Since leptin was discovered, white AT (WAT) has been recognised as an endocrine organ and an important source of biologically active substances with local and/or systemic action called adipokines. The metabolic and endocrine activities of AT are under the control of several hormones: a particular role has been played by glucocorticoids (GC), which able to participate, along with other hormones, both in recruitment of progenitor cells and in differentiation and secretive activities. AT is also able to generate cortisol from cortisone through 11β-hydroxysteroid-dehydrogenase (11β-HSD). There are controversial reports in the literature, showing a hyperactivity of 11β-HSD in obesity. It has been postulated that obesity, particularly the visceral body fat distribution (V-BFD), may be considered a maladaptation to stress exposure, thus leading to hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis, and higher-than-normal cortisol levels. In this review, we will examine the cross-talk between the HPA axis and AT, their relationship under stressful events, depending on steroid hormones and different adipokine secretions.

The Endocrine Impact of Obesity and Body Habitus in the Polycystic Ovary Syndrome

Obesity, particularly the abdominal type, is associated with several abnormalities of sex steroid balance in women, including an increased androgen production rate and decreased serum levels of sex hormone-binding globulin. It is hypothesized that the increasing epidemic of obesity worldwide may also favor the high prevalence of obesity among women with polycystic ovary syndrome (PCOS). Obesity has a profound impact on the PCOS phenotype, being associated with more severe hyperandrogenism and insulin-resistant state and fertility disorders.