Oxidative stress in adult growth hormone deficiency: different plasma antioxidant patterns in comparison with metabolic syndrome.

BACKGROUND AND AIMS: Growth hormone deficiency (GHD) is a condition associated with increased cardiovascular risk and insulin-resistance. Oxidative stress (OS) could be a mechanism underlying both these phenomena. In order to investigate plasma antioxidant defenses in such condition, we evaluated adults with GHD, compared with controls and metabolic syndrome patients (MetS), studying plasma total antioxidant capacity (TAC) and coenzyme Q10 (CoQ10, lipophilic antioxidant) levels, both in its oxidized and reduced forms, correlating this data with metabolic and hormonal pattern. MATERIALS AND METHODS: In this case-control study, 51 GHD, 36 controls, and 35 MetS were enrolled. An evaluation of hormonal and metabolic parameters was performed. TAC was measured using the system metmyoglobin -H202 and the chromogen ABTS, whose radical form is spectroscopically revealed; latency time (LAG) in the appearance of ABTS● is proportional to antioxidant in sample. CoQ10 was assayed by electrochemical method. RESULTS: Despite HOMA index was higher in both GHD and MetS (2.2 ± 0.3 and 3.1 ± 0.3 vs. 1.2 ± 0.2 in controls), only in MetS we observed lower LAG levels (64.5 ± 3.1 s vs. 82.8 ± 5.8 in GHD and 80.6 ± 6.6 in controls), suggesting an increased consumption of antioxidants. LAG significantly correlated with uric acid only in MetS (r 2 = 0.65, p < 0.001), suggesting a different pattern of antioxidants. CoQ10 exhibited a trend toward lower levels in GHD, although not significant. CONCLUSIONS: Our data indicate that GHD, although sharing with MetS various metabolic features, including increased HOMA levels, showed a different pattern of plasma antioxidants, suggesting inadequate reactivity toward radical production rather than an antioxidants consumption as in MetS.

Plasmatic and Intracellular Markers of Oxidative Stress in Normal Weight and Obese Patients with Polycystic Ovary Syndrome.

Introduction Insulin resistance (IR) is associated with polycystic ovary syndrome (PCOS). Oxidative stress (OS) is, in turn, related to IR. Studies in PCOS evidenced an increase in OS markers, but they are mainly performed in obese patients, while the complex picture of normal weight PCOS is still poorly investigated. Matherials and Methods To investigate OS in PCOS and relationship with hormonal and metabolic picture, we performed a case-control study in 2 PCOS groups: normal weight (N-PCOS, n=21, age 18-25 ys, mean±SEM BMI 20.7±0.2 kg/m2) and obese (OB-PCOS, n=15, 20-30 ys, BMI 32.8±1.1), compared with control groups matched for BMI: normal (N-C, n=10, 20-30 ys, BMI 21.6±0.9) and obese (OB-C, n=20, 21-31ys, BMI 36.8±1.0). Malondialdehyde (MDA) in blood plasma and peripheral mononuclear cells, obtained by density-gradient centrifugation, was assayed spectrophotometrically by TBARS assay. CoenzymeQ10 (CoQ10) in plasma and cells was assayed by HPLC. Plasma Total Antioxidant Capacity (TAC) was also measured by spectrophotometric method. Results PCOS patients exhibited higher Testosterone levels than controls, but OB-PCOS had highest HOMA (Homeostasis Model Assessment) index, suggesting marked insulin resistance. Despite plasma MDA levels were not significantly different (N-PCOS 3380±346.94 vs. N-C 7 120±541.66; OB-PCOS 5 517.5±853.9 vs. OB. 3 939.66±311.2 pmol/ml), intracellular MDA levels were significantly higher in N-PCOS than controls (mean 3 259±821.5 vs. 458±43.2 pmol/106/cells) and higher than OB-PCOS, although not significantly (1363.1±412.8 pmol/106/cells). Intracellular CoenzymeQ10 was higher in N-PCOS than in N-C, but the highest levels were found in OB-C. Conclusions Our data, while confirming the presence of OS in obese PCOS patients in agreement with literature, suggest that OS could be present also in normal weight PCOS, but it can be revealed in tissue rather than in plasma. The relationship with metabolic status remains to be established, but could be a physiopathological basis for antioxidant treatment in such patients.

Evaluation of an Automated CLIA System for the Determination of Carbohydrate Antigen 19-9.

AIM: To compare analytical characteristics between two different methods, a automated chemiluminescent immunoassay (CLIA) versus a radioimmunometric assay (RIA), for the determination of carbohydrate antigen 19-9 (CA19-9). MATERIALS AND METHODS: One hundred and eighty-five blood samples from consecutively enrolled individuals (87 males and 98 females, aged 22-89 and 29-89 years, respectively) were evaluated. For both assays, a cut-off of 37 U/ml was used. RESULTS: Comparison between assays was analyzed using Passing-Bablok regression, which showed a high inter-assay correlation (r=0.926). The mean intra-assay coefficient of variation was 17.6% (range=6.1-50.7%) for the RIA (n=10 samples) and 5.2% (range=0.4-17.0%) for the CLIA assay (n=26 samples). CONCLUSION: This study showed that CLIA for CA19-9 has a good reliability on all samples analyzed and should be preferred to RIA with the aim of reducing costs, greater standardization and more harmonized results.

The link between metabolic features and TSH levels in polycystic ovary syndrome is modulated by the body weight: an euglycaemic-hyperinsulinaemic clamp study.

OBJECTIVE: To evaluate the link among thyroid function, glucose/insulin metabolism and steroid hormones in women with polycystic ovary syndrome (PCOS), and to verify if the body mass index (BMI) might influence the interplay between PCOS features and subclinical hypothyroidism (SCH). STUDY DESIGN: Case-control study conducted from January to December 2014. METHODS: One-hundred fifty-four young women with PCOS, according to Rotterdam criteria, and 88 controls were enrolled in an academic research environment. Anthropometric evaluation, hormonal and lipid assays, oral glucose tolerance test (OGTT) and euglycaemic-hyperinsulinaemic clamp were performed. Hirsutism was assessed with the Ferriman-Gallwey (FG) score. MAIN RESULTS: SCH was found in 14% of PCOS subjects and in 1% of controls (P < 0.01). In PCOS women, TSH levels were directly correlated with fasting glycaemia, but not with other hormonal and metabolic parameters. When PCOS patients were classified on the basis of BMI, TSH levels significantly correlated with insulin secretion, insulin resistance, DHEAS and cortisol levels in obese PCOS women. Inverse correlations were found between TSH and both oestradiol and SHBG in the same group. In nonobese PCOS patients, only waist-to-hip ratio values were correlated with TSH. The prevalence of SCH was not different between nonobese and obese PCOS groups (14 and 15% respectively). However, SCH was associated with higher levels of insulin, DHEAS, cortisol and FG score only in the obese subgroup. CONCLUSIONS: Our data confirm that the prevalence of SCH is increased in PCOS women. The presence of SCH is associated with endocrine and metabolic imbalances of PCOS, and the excessive body weight seems to promote this interplay.

Thyroid Hormones, Oxidative Stress, and Inflammation.

Inflammation and oxidative stress (OS) are closely related processes, as well exemplified in obesity and cardiovascular diseases. OS is also related to hormonal derangement in a reciprocal way. Among the various hormonal influences that operate on the antioxidant balance, thyroid hormones play particularly important roles, since both hyperthyroidism and hypothyroidism have been shown to be associated with OS in animals and humans. In this context, the nonthyroidal illness syndrome (NTIS) that typically manifests as reduced conversion of thyroxine (T4) to triiodothyronine (T3) in different acute and chronic systemic conditions is still a debated topic. The pathophysiological mechanisms of this syndrome are reviewed, together with the roles of deiodinases, the enzymes responsible for the conversion of T4 to T3, in both physiological and pathological situations. The presence of OS indexes in NTIS supports the hypothesis that it represents a condition of hypothyroidism at the tissue level and not only an adaptive mechanism to diseases.

Thyroid hormones and antioxidant systems: focus on oxidative stress in cardiovascular and pulmonary diseases.

In previous works we demonstrated an inverse correlation between plasma Coenzyme Q10 (CoQ10) and thyroid hormones; in fact, CoQ10 levels in hyperthyroid patients were found among the lowest detected in human diseases. On the contrary, CoQ10 is elevated in hypothyroid subjects, also in subclinical conditions, suggesting the usefulness of this index in assessing metabolic status in thyroid disorders. A Low-T3 syndrome is a condition observed in several chronic diseases: it is considered an adaptation mechanism, where there is a reduction in pro-hormone T4 conversion. Low T3-Syndrome is not usually considered to be corrected with replacement therapy. We review the role of thyroid hormones in regulation of antioxidant systems, also presenting data on total antioxidant capacity and Coenzyme Q10. Published studies suggest that oxidative stress could be involved in the clinical course of different heart diseases; our data could support the rationale of replacement therapy in low-T3 conditions.