Selected CNR1 polymorphisms and hyperandrogenemia as well as fat mass and fat distribution in women with polycystic ovary syndrome.

The endocannabinoid system is postulated to play an important role in the etiology of obesity, insulin resistance, fat distribution and metabolic disorders. Insulin resistance associated with abdominal obesity plays a leading role in the etiology of hyperandrogenism and other clinical features of the polycystic ovary syndrome (PCOS). A total of 174 women 16-38 years old, diagnosed with PCOS according to the Rotterdam criteria are recruited. Control group consisted of 125 healthy women 18-45 years old. Medical history, physical examination, anthropometric parameters and metabolic parameters were carried out. Six CNR1 gene polymorphisms were diagnosed. We observed a significantly three times higher risk of GG genotype in the polymorphism rs12720071 in women with PCOS versus the control group (p = 0.0344, OR = 3.01). A similar, significant 8-fold higher risk (p = 0.0176, OR = 8.81) was demonstrated for genotype CC polymorphism rs806368 associated with PCOS. We observed a 3.6-fold increased risk of hyperandrogenemia (free androgen index - FAI > 7) in patients with GG genotype in the rs12720071 polymorphism and AA genotype in the polymorphism rs1049353 (OR = 2.7). Our study may indicate a role of the endocannabinoid system in the occurrence of a specific hyperandrogenemia phenotype of PCOS.

PPAR-gamma2 Pro12Ala polymorphism in the population of obese and non-obese men of the city of Wroclaw.

INTRODUCTION: The aim of this study was to examine the association of Pro12Ala PPARgamma2 polymorphism with anthropometric and biochemical parameters defining the risk for the development of metabolic syndrome in a healthy population of men. MATERIAL AND METHODS: The study group consisted of 176 healthy men, aged 25-65 years (average 54.16 years). Polymorphisms of the PPAR-g gene (Pro12Ala, Ala12Ala, Pro12Pro) were explored using the PCR-RFLP method. Plasma glucose, insulin, total cholesterol, LDL, HDL and TG were measured using commercially available kits. RESULTS: The genotypic distribution of the Pro12Ala polymorphism was as follows: Pro/Ala 69.8% (n = 123), Ala/Ala 28.4% (n = 50) and Pro/Pro 1.8% (n = 3). The Pro12Ala and Ala12Ala subjects did not differ in any of the measured variables. The non-obese (BMI < 30 kg/m(2), n = 117) and obese subpopulations (BMI > 30 kg/m(2), n = 56) did not significantly differ in the distribution of the genotypes. In the nonobese subpopulation, the homozygous Ala12 carriers (n = 38, 32.4%) had higher systolic blood pressure, plasma triglycerides, insulin levels and HOMA-IR. CONCLUSIONS: We conclude that despite the high frequency of the Ala allele at the PPAR-gamma2 gene in our population of Polish men, the Ala12 allele does not appear to improve insulin sensitivity or have an influence on the occurrence of obesity. It remains to be explained by larger studies if this polymorphism carries any risk of the development of metabolic abnormalities in non-obese men.

Use of body weight and insulin resistance to select obese patients for echocardiographic assessment of subclinical left ventricular dysfunction.

Obesity is associated with heart failure. Recognition of subclinical left ventricular (LV) dysfunction may permit the initiation of therapy to prevent the development of heart failure. In this study of anthropometric, biochemical, and echocardiographic measurements in 295 healthy overweight subjects, we sought to investigate the effect of insulin resistance and severity of obesity on LV function and to establish a strategy for detection of LV dysfunction using metabolic and echocardiographic measurements. Correlates of subclinical dysfunction (defined from myocardial deformation in a matched group of 98 slim controls) were sought, and receiver operator characteristic curves for clinical and laboratory parameters were performed to identify optimal cutoffs to permit an effective diagnostic strategy. Subclinical impairment of LV function (average strain<18%) was present in 124 subjects (42%), and 52% of severely obese patients (body mass index [BMI]>35 kg/m2). Independent correlates of strain were BMI (beta=-0.25, p<0.0001), fasting insulin (beta=-0.22, p<0.001), and age (beta=-0.18, p<0.003). In patients with a BMI<35 kg/m2, subclinical impairment was uncommon in the absence of hyperinsulinemia. Using a BMI<35 kg/m2 and an insulin level<13 mIU/L to select patients for further testing allowed echocardiography to be avoided in 35% of subjects in whom the prevalence of LV dysfunction was low. In conclusion, obesity and insulin resistance are important contributors to LV dysfunction, a deleterious effect of hyperinsulinemia on LV performance is particularly seen in overweight and moderately obese subjects, and the combination of BMI, fasting insulin, and echocardiography appears optimal for efficient identification of subclinical LV dysfunction in overweight and obese subjects.

[A case of primary hypoparathyroidism and hypothyroidism co-existing with chronic renal failure]. / Rzadki przypadek wspólistnienia pierwotnej niedoczynnosci przytarczyc i tarczycy z przewlekla niewydolnoscia nerek.

A case of 24-year old woman with chronic renal failure and primary hypoparathyroidism is presented. Primary hypothyroidism and bilateral hypoacousis were also found. Typically concomitant with chronic renal failure is development of secondary hyperparathyroidism and its co-morbidities, i.e. renal osteodystrophy that consists of osteomalacia, osteoporosis and pathological fractures. In case of some patients with very high concentration of parathormone (PTH) and with signs of renal osteodystrophy, which is the case of tertiary hyperparathyroidism, subtotal parathyroidectomy is the optimal treatment. Reduction of PTH concentration protects bones from further destruction and from accumulation of calcium phosphate in tissues. The accompanying primary parathyroid failure would probably protect from the further consequences of PTH over-production--renal osteodystrophy. The case is reported in view of a rare occurrence of such co-existence, lack of its description in Polish literature as well as diagnostic difficulties.

[Evaluation of the influence of sex hormones on homocysteine concentration in pre- and postmenopausal women]. / Ocena wplywu wybranych hormonów na stezenie homocysteiny u kobiet przed menopauza i po menopauzie.

The aim of study was to evaluate the influence of sex hormones: estradiol (E), follicle-stimulating hormone (FSH), progesterone (P), testosterone (T), dehydroepiandrosterone (DHEA-S) and cortisol (F) on the serum homocysteine concentration (HCY) in 40 premenopausal (group M) and 80 postmenopausal (group K) women. The influence of E2 therapy (ET) on the serum HCY level in the women with surgical menopause was also estimated. The plasma HCY concentration in the group M was significantly higher that in group K. After ET serum HCY level decreased significantly. No correlations were found between serum HCY and E2 concentrations in the all groups. No correlations were observed between HCY and FSH, P, T and F concentrations in pre-and postmenopausal groups. There was a significant negative correlation between serum HCY and DHEA-S concentration in group K. This result may indicate, that high level of DHEA decreases HCY concentration. There was no correlation in group M, where the mean concentration of DHEA was lower than in group K. The results of study indicate, that menopause increases and ET decreases plasma HCY concentration. DHEA-S may inhibit plasma HCY concentration in premenopausal women. More studies are needed to elucidate these hypotheses.

[The effect of estrogen deficiency, estrogen and estro-progestagene therapy on total plasma homocysteine and serum lipid peroxide levels in postmenopausal women]. / Wplyw niedoboru estrogenów, leczenia estrogenowego i estro-progestagienowego na stezenie homocysteiny i nadtlenków lipidów u kobiet po menopauzie.

OBJECTIVES: Elevated plasma homocysteine (Hcy) concentration is a risk factor for atherosclerosis and venous thrombosis. DESIGN: an observational study. MATERIALS AND METHODS: 120 healthy women were recruited and divided in two subgroups--postmenopausal women (M-80 women) and premenopausal women (40 women) with normal menstruation as control group. 26 women with surgical menopause were treated with percutaneous estrogen therapy and remaining 54 women were treated with estro-progestagen replacement therapy. Measurements of FSH and estradiol was made using radioimmunoassay. HCY was assessed using enzymatic conversion method. RESULTS: Concentrations of Hcy and lipid peroxides (LPO) in postmenopausal study group were higher than in the premenopausal. Treatment with estradiol (E2) alone or in combination with medroxyprogesterone acetate decreased LPO and Hcy concentrations to levels observed in premenopausal group. CONCLUSIONS: Our results suggest that estrogens have a profound influence on Hcy and LPO levels. Reduction in Hcy levels after treatment lowers the production of free radicals and thus contributes to lipid peroxidation decrease and LPO levels reduction after therapy. A practical conclusion may be proposed: in postmenopausal women with elevated Hcy levels who require hormonal replacement therapy, Hcy level control is indicated in order to administer such a therapy, which decreases Hcy concentrations.

[Amiodarone and the thyroid gland]. / Amiodaron a tarczyca.

Amiodarone is an iodine-rich drug. Its chronic administration may lead to disturbances in thyroid hormone metabolism and/or overt gland dysfunction. It causes an increased in serum fT4, rT3, and TSH concentrations and a decreased serum level of fT3 without thyroid dysfunction. Amiodarone may induce thyrotoxicosis (AIT--Amiodarone-induced thyrotoxicosis) or hypothyroidism (AIH--Amiodarone-induced hypothyroidism) in some persons. AIT occurs more frequently in areas with low iodine intake. The excess iodine contributes to excessive thyroid hormone synthesis-type I AIT or may lead to thyroiditis and a destructive process of thyroid follicular cells, resulting in excess thyroid hormone release-type II AIT. The mixed form of AIT also occurs. Type I AIT should be treated with antithyroid drugs alone or in association with potassium perchlorate, type II AIT benefits from treatment with glucocorticoids, whereas the mixed form of AIT is most effectively treated with a combination of thionamides, potassium perchlorate, and glucocorticoids. AIT often requires thyroidectomy after restoration of euthyroidism or radioiodine therapy, provided that 24-h thyroid radioactive iodine uptake values permit. AIH prevails in areas with high dietary iodine intake. It requires a discontinuation of amiodarone therapy and thyroid hormone (levothyroxine) replacement. It can remit spontaneously. Amiodarone and L-thyroxine therapy is also possible. Baseline thyroid function tests, thyroid antibodies, and imaging examinations such as thyroid ultrasound on initial evaluation and follow-ups every 6 months must be carefully monitored before starting amiodarone therapy.