We examined insulin sensitivity and secretion, together with the levels of selected glucoregulatory hormones, in 15 female patients with severe hypothyroidism (H) and during subsequent thyroid hormone replacement therapy (HRT) using the euglycaemic hyperinsulinaemic clamp technique. Insulin action, as evaluated by glucose disposal, the insulin sensitivity index, and fasting post-hepatic insulin delivery rate were established. The basal levels of insulin, C-peptide and counter-regulatory hormones were measured in basal condition. In H, glucose disposal (p<0.01), the insulin sensitivity index (p<0.01) and post-hepatic insulin delivery rate (p<0.05) were significantly lower than during HRT. No significant changes in the levels of fasting insulin and C-peptide were observed. The levels of counter-regulatory hormones in patients with H were significantly higher than during HRT (glucagon, p<0.05; epinephrine, p<0.01; cortisol, p<0.05; growth hormone, p<0.05). In H, an inverse correlation between insulin sensitivity and insulin secretion was observed (p<0.05). Cortisol was the most important factor affecting the variability of insulin sensitivity values, regardless of thyroid function (p=0.0012). In conclusion, H altered both insulin sensitivity and the levels of selected counter-regulatory hormones. The situation was restored by HRT, as manifested not only by normalisation of insulin sensitivity, secretion and levels of glucoregulatory hormones, but also by improvement of their relationships.

Objective: Polycystic ovary syndrome (PCOS) has been linked to a high risk of type 2 diabetes mellitus. Disturbances in the secretion of the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) have been observed in states with impaired glucose regulation. This paper considers the secretion of GIP and GLP-1 after oral glucose load in a group of lean, glucose-tolerant PCOS women in comparison with age-and body mass index (BMI)-matched healthy women. Design: Case control. Methods: PCOS (nZ21, 25.8G4.1 years, BMI 21.6G1.7 kg/m 2 ) and control healthy women (CT, nZ13, 28.5G7.2 years, BMI 20.3G2.5 kg/m 2 ) underwent oral glucose tolerance test (OGTT) with blood sampling for glucose, insulin, C-peptide, total GIP, and active GLP-1. Insulin sensitivity was determined both at fasting and during the test. Statistics: Repeated measures ANOVA. Results: Glucose levels and insulin sensitivity did not differ between PCOS and CT. PCOS had significantly higher levels of C-peptide (P!0.05) and tended to have higher insulin levels. The levels of total GIP were significantly higher in PCOS than in CT (P!0.001). Active GLP-1 levels exhibited a significantly different time-dependent pattern in PCOS (P!0.002 for PCOS versus time interaction). GLP-1 concentrations were similar in PCOS and CT in the early phase of OGTT and then reached significantly lower levels in PCOS than in CT at 180 min (P!0.05). Conclusions: Increased total GIP and lower late phase active GLP-1 concentrations during OGTT characterize PCOS women with higher C-peptide secretion in comparison with healthy controls, and may be the early markers of a pre-diabetic state.

The aim of our study was to compare insulin sensitivity in lean and obese European polycystic ovary syndrome (PCOS) women with lean healthy women. We performed the euglycemic hyperinsulinemic clamp in 83 women with PCOS [53 lean with body mass index (BMI) of 21.5 ؎ 1.8 kg/m 2 and 30 obese with BMI of 29.6 ؎ 3.7 kg/m 2 ] and in 15 healthy women with BMI of 21.6 ؎ 1.8 kg/m 2 to determine glucose disposal (M) and the insulin sensitivity index (ISI). Statistical evaluation was done using Kruskal-Wallis ANOVA followed by Kruskal-Wallis multiple-comparison z-value test. The basal blood glucose was significantly higher in lean and obese PCOS women than in controls (P < 0.02). Fasting insulin was significantly higher in both lean and obese PCOS women than in controls (P < 0.000001). Obese PCOS women were more insulin resistant than controls (P < 0.02 for M and P < 0.0008 for ISI); lean PCOS women did not differ from controls in M or ISI. Posthepatic insulin delivery was significantly higher in both lean and obese PCOS women compared with controls (P < 0.000008). We conclude that lean PCOS women are not more insulin resistant than healthy controls. Insulin hypersecretion, on the other hand, is present even in lean PCOS women. IT IS GENERALLY accepted that women with polycystic ovary syndrome (PCOS) have a high prevalence of insulin resistance, with a consequent increased risk of metabolic diseases later in life. It is well established that obese PCOS women are insulin-resistant in excess of their adiposity (1, 2). In lean PCOS women, however, the situation is not so clear. To date, there have been two studies using the euglycemic hyperinsulinemic clamp that were not able to demonstrate a difference in insulin sensitivity between lean PCOS women and healthy controls in Europe (3, 4), whereas a study in the United States described significantly impaired insulin action in lean PCOS in comparison with healthy women matched for body fat and fat-free mass (2). Similar results were obtained by another group in Turkey (5). All these studies were conducted on small groups of lean women with PCOS (from 7-11 patients). These discrepancies are not easy to explain; ethnic origin of the patients could probably account for part of the differences.In the present study, we thus examined large groups of both lean and obese women fulfilling the generally accepted diagnostic criteria of PCOS, using an euglycemic clamp, which is considered the gold standard in evaluating insulin sensitivity. The aim of our study was to compare insulin sensitivity in lean and obese European PCOS women with lean controls. Subjects and MethodsThe study group consisted of 83 oligo/amenorrheic women with PCOS matching the National Institutes of Health criteria (6). All had clinical manifestation of hyperandrogenemia presenting as hirsutism and/or acne and with the elevation of the free testosterone (T) index more than six and/or androstenedione (A) above the upper limit of the normal range. Women were in good health condition, without any other serious disorder....

Objective: To evaluate adrenal and ovarian steroidogenesis before and after long-term treatment with metformin in women with polycystic ovary syndrome (PCOS). Design and Methods: Twenty-four women with PCOS were evaluated before and after treatment (27^4 weeks) with metformin (1000 mg/day) using adrenocorticotrophin (ACTH), GnRH analogue and oral glucose tolerance (oGTT) tests. For statistical evaluation, ANOVA and Wilcoxon's test were used. Results: In 58% of the women a significant improvement in menstrual cyclicity was observed. No significant change in basal steroid levels was found. After ACTH stimulation, a significant decrease in the activity of 3b-hydroxysteroid dehydrogenase in C 21 steroids P , 0X05 and in 17b-hydroxysteroid dehydrogenase P , 0X01 was observed, as was an increase in the activity of C17,20-lyase in the D 4 pathway P , 0X01X A significant growth in the dehydroepiandrosterone (DHEA)/DHEA-sulfate ratio P , 0X05 was detected. With regard to ovarian steroidogenesis, a significant decrease in the stimulated levels of testosterone P , 0X05Y index of free testosterone P , 0X01Y LH P , 0X05 and oestradiol P , 0X01Y and an increase in the levels of 17-hydroxypregnenolone P , 0X05 were detected. In the indices of ovarian enzyme activities, we observed a significant decrease in 3b-hydroxysteroid dehydrogenase in C 21 steroids P , 0X01Y in C17,20-lyase in the D5 pathway P , 0X01Y in 17b-hydroxysteroid dehydrogenase P , 0X05 and in aromatase. In glucose metabolism, a tendency towards reduction in the homeostasis model assessment (HOMA)-R (for insulin resistance) and HOMA-F (for b cell function) was detected. In addition, an increase in the levels of C peptide during oGTT was observed P , 0X01X Conclusions: Long-term metformin treatment reduced various steroid enzymatic activities both in the ovary and the adrenal glands, without apparent changes in basal steroid levels and in insulin sensitivity.

In this review we summarize recent opinions on the possible role of vitamin D in the risk of thyroid diseases development. It may be concluded from the available data that vitamin D deficiency, particularly levels below 12.5 ng/ml should be considered as an additional, but important risk factor for development of thyroid autoimmunity, both chronic autoimmune thyroiditis and Graves´ disease. A higher risk of Graves´ disease development is also associated with several polymorphisms in the gene encoding for vitamin D binding protein and for the specific receptor of active form of vitamin D -1,25-(OH) 2 D 3 in the respective target cells. Important for development of thyroid cancer appeared polymorphisms of genes encoding for vitamin D receptors and of genes encoding for the participating hydroxylating enzymes in thyroid tissue, leading to a diminished local 1,25-(OH) 2 D 3 formation capacity with following alteration of antiproliferatory, antiapoptotic and prodifferentiating efficacy of the latter.Whether supplementation with high doses of vitamin D or its analogues possesses preventive or therapeutic effect is an object of intensive studies.