[Show abstract][Hide abstract] ABSTRACT: Polycystic ovary syndrome (PCOS) is characterised by increased frequency of hypothalamic GnRH pulses leading to a relative increase in LH synthesis by the pituitary. As GnRH stimulation can reveal a relative LH excess, we have endeavoured to assess whether GnRH test might be useful in the diagnosis of PCOS.
The study involved 185 subjects: a PCOS group, n = 151, all with oligo- or amenorrhoea, aged (mean ± SD) 24.8 ± ± 5.4 years, BMI 24.5 ± 6.0 kg/m²; and regularly menstruating controls, n = 34, aged 26.6 ± 5.0 years, BMI 24.6 ± 5.5 kg/m². In 121 subjects with PCOS and in 32 controls, serum LH and FSH were measured before (0 minutes) and 30 and 60 minutes after GnRH stimulation (100 μg i.v.). Insulin resistance was assessed by HOMA and Insulin Resistance Index derived from glucose and insulin concentrations during 75 gram oral glucose tolerance test.
Women with PCOS had higher testosterone (p = 0.0002), androstendione (p = 0.0021), 17OH-progesterone (p < 0.0001) and were more insulin resistant. Raised concentrations of at least one androgen were, however, found only in 58.1% of women with PCOS. Baseline and stimulated LH concentrations were higher in PCOS (9.09 ± 5.56 vs 4.83 ± 1.71 IU/L, 35.48 ± 31.4 vs 16.30 ± 6.68 IU/L, 33.86 ± 31.8 vs 13.45 ± 5.2 IU/L, at 0, 30 and 60 mins post GnRH, respectively, p < 0.0001). There was no difference in baseline or stimulated FSH concentrations between groups. Relative increases of LH or FSH in comparison to respective baseline values were similar in both groups. There was, however, a marked increase in LH/FSH ratio in PCOS in comparison to controls (LH0 min/FSH(₀ min) 1.59 ± 0.95 vs 0.76 ± 0.2, LH(₃₀ min) /FSH(₃₀ min) 4.07 ± 3.0 vs 1.89 ± 0.79, LH(₆₀ min)/FSH(₆₀ min) 3.56 ± 2.58 vs 1.55 ± 0.63, p < 0.0001 at all time points). Further analysis revealed that LH30 min/FSH(₃₀ min) > 2.11 or LH(₆₀ min)/FSH(₆₀ min) > 1.72 had 78.3% and 87.5% sensitivity and 81.7% and 81.3% specificity for the diagnosis of PCOS, respectively.
Women with PCOS have higher baseline and GnRH-stimulated LH concentrations. GnRH stimulation results in an increase in LH/FSH ratio in women with PCOS. Therefore we postulate that this phenomenon might be potentially useful as an additional tool in the diagnosis of PCOS.
Endokrynologia Polska 03/2011; 62(2):120-8. · 0.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 32-year-old Caucasian was admitted at 14 weeks of gestation with hypotension and weight loss. Family members noted that she appeared "tired" prior to pregnancy Past medical history included primary hypothyroidism treated with thyroxine (100 microg/day). She had a healthy daughter aged 2.5 years who had been born small for gestational age. At about 8 weeks of gestation she started to vomit several times a day. She was treated with antiemetics and intravenous fluids. Following discharge she remained nauseated, weak and lightheaded and lost about 8 kg of weight. After readmission she appeared ill and dehydrated, BMI 16.6 kg/m2, BP 90/60 mmHg supine, 70/50 mmHg upright (with faint-like sensation), normal heart sounds, chest clinically clear, abdomen soft and not tender Investigations revealed severe hyponatraemia (sodium 112 mmol/L), normal potassium level 4.3 mmol/L, normal renal function, TSH 1.31 microIU/mL (reference range (RR): 0.27-4.2), freeT4 1.99 ng/dL (RR: 0.93-1.7), freeT3 3.29 pg/mL (RR: 2.57-4.43), anti-TPO antibodies 467 IU/mL (RR: <34)). She was hyperpigmented, hypotensive and hyponatraemic despite rehydration. Cortisol & ACTH, followed by a 250 microg short Synacthen test were requested and revealed peak cortisol response of 17 nmol/L (RR: above 550 nmol/l) as well as high baseline ACTH (969 pg/mL, RR: 0-46 pg/mL). She was started on hydrocortisone and felt tremendously better A diagnosis of Addisons disease was made (in view of hypothyroidism as a part of Autoimmune Polyglandular Syndrome type II). She was discharged on hydrocortisone and fludrocortisone replacement. Further during her pregnancy there was about two-week foetal growth delay. She, however delivered a healthy female infant at 36 weeks of gestation. CONCLUSIONS: New onset Addison's disease is rare in pregnancy but may present with prolonged vomiting and weight loss. Therefore adrenal failure should be included in the differential diagnosis of hyperemesis gravidarum.
Ginekologia polska 07/2010; 81(7):537-40. · 0.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Matrix metalloprotenases (MMPs) are proteolytic enzymes active in inflammatory states. We have examined MMP-9, MMP-2, and their respective tissue inhibitors: TIMP-1 and TIMP-2 in sera of women with gestational diabetes mellitus (GDM) and various degrees of insulin resistance (IR) in the third trimester of pregnancy.
Fasting serum levels of MMP-9, MMP-2, TIMP-1 and TIMP-2 were measured in 26th-28th week of gestation in 51 women divided according to their response to a 50-g glucose challenge test (GCT) and a 75-g OGTT: controls (n = 20): both tests normal; the GDM group (n = 16) both tests abnormal; the intermediate group (IG; n = 15) abnormal GCT and normal OGTT. MMPs and TIMPs were correlated with the parameters of IR: homeostasis model assessment (HOMA) and insulin resistance index (IRI).
MMP-9, MMP-2, TIMP-1 and MMP-9/TIMP-1 ratio were not different among the groups. TIMP-2 levels were significantly higher in the GDM and IG groups than in controls (p < 0.01). MMP-2/TIMP-2 ratio was lower in the GDM group than in the other groups (p < 0.01) and was correlated to HOMA and IRI (r = -0.465 and r = -0.43 respectively, p < 0.01).
Serum MMP levels do not reflect inflammation in GDM. Elevated TIMP-2 and consequently lower MMP-2/TIMP-2 levels in GDM need to be clarified, but are unlikely to be a consequence of inflammation.
[Show abstract][Hide abstract] ABSTRACT: Endometriosis is a highly prevalent gynecological condition, where the formation of endometriotic foci is linked with locally increased activity of matrix metalloproteinases (MMPs). In the present study, we tested the hypothesis that raised serum levels of MMPs might reflect the severity of endometriosis. We compared serum levels of MMP-2 and MMP-9, and of their tissue inhibitors TIMP-1 and TIMP-2, in infertile women, matched for age and body mass index, with either mild (stage I, END-I; n = 15) or severe endometriosis (stage IV, END-IV; n = 22). There was no difference in the concentrations of MMP-2, MMP-9, TIMP-1 and TIMP-2 between the analyzed groups. There was, however, a correlation between MMP-9 and TIMP-1 for the combined group (n = 37) (r = 0.48; p = 0.0032) and in women with END-IV (r = 0.51; p = 0.0163), as well as a highly significant correlation between MMP-2 and TIMP-2 for the combined group (r = 0.69; p = 0.0001), END-I (r = 0.51; p = 0.0406) and END-IV groups (r = 0.77; p = 0.0001). There was also a significant correlation between TIMP-1 and TIMP-2 in the combined and END-IV groups (r = 0.39; p = 0.0182 and r = 0.5450; p = 0.0099, respectively). The balance between MMPs and their inhibitors is preserved in the serum of women with endometriosis, but serum concentrations of MMP-2, MMP-9, TIMP-1 and TIMP-2 cannot be considered to represent a valid measure of the severity of endometriosis.
[Show abstract][Hide abstract] ABSTRACT: INTRODUCTION, MATERIAL AND METHODS: Visfatin is a cytokine, mainly expressed in visceral fat, that exerts insulin-mimicking effects in rodents through activation of an insulin receptor, although the binding-site is distinct from that of insulin. However, the mechanisms that regulate visfatin synthesis are still not fully understood. In particular, it is not clear whether short-term glucose-induced hyperglycaemia and hyperinsulinaemia as well as a glucocorticoid-induced increase in insulin resistance are reflected in appreciable alterations in serum visfatin levels in humans. In order to investigate this we measured serum visfatin, glucose and insulin concentrations during a 75.0 gram oral glucose tolerance test (OGTT) [Study 1], as well as before and after oral administration of dexamethasone [Study 2]. Study 1 included 17 subjects (2 males), aged 35.7 +/- 15.6 (mean +/- SD) years of BMI 35.2 +/- 9.3 kg/m(2). Blood samples were taken before (0 minutes) and at 60 and 120 minutes after glucose administration. Study 2 included 20 subjects (4 males, 5 subjects with type 2 diabetes), aged 42.1 +/- 17.2 years of BMI 36.7 +/- 8.38 kg/m(2) who underwent screening for Cushing's disease/syndrome. Dexamethasone was administered at a dose of 0.5 mg every 6 hours for 48 hours. Fasting serum concentrations of visfatin, glucose and insulin were assessed before (D0) and after 48 hours of dexamethasone administration (D2). Insulin resistance was assessed according to the HOMA method in non-diabetic individuals (n = 15). RESULTS: In Study 1 two subjects were found to have impaired glucose tolerance and one subject was found to have diabetes mellitus. Glucose administration resulted in a highly significant increase in insulin (from 11.4 +/- 7.2 microU/mL at 0 min to 98.9 +/- 68.6 microU/mL at 60 min and 72.6 +/- 45.1 microU/mL at 120 minute of OGTT, p < 0.001 for 60 and 120 minutes in comparison to baseline). However, there was no change in serum visfatin concentrations (84.6 +/- 11.6 ng/mL at 0 minutes, 82.6 +/- 12.7 ng/mL at 60 minutes and 81.1 +/- 14.5 ng/mL at 120 minutes of OGTT, p = ns). All subjects in Study 2 achieved suppression of cortisol concentrations below 50 nmo/l. Dexamethasone administration resulted in an increase in fasting insulin (from 11.5 +/- 6.9 to 16.9 +/- 7.6 microU/mL; p = 0.011) and an increase in HOMA (from 2.73 +/- 1.74 to 4.02 +/- 2.27; p = 0.015), albeit without a significant change in serum visfatin concentrations (61.1 +/- 19.8 vs. 68.3 +/- 19.4 ng/mL, p = ns). In neither Study 1 nor Study 2 was there any significant correlation between serum visfatin and age, BMI or HOMA. CONCLUSIONS: There is a striking difference between the marked rise in insulin concentrations and the lack of change in visfatin concentrations during the oral glucose tolerance test. This implies that it is highly unlikely that visfatin is involved in the short-term regulation of glucose homeostasis in human subjects. Dexamethasone administration (4 mg/48 hours) induces an increase in insulin resistance, although without significant change in serum visfatin concentrations. Therefore in contrast to the in vitro data, short term glucocorticoid administration does not result in appreciable changes in serum levels of this adipocytokine. Furthermore, the results of our study do not support the notion that glucocorticoid-induced insulin resistance is likely to be related to changes in serum concentrations of visfatin.
Endokrynologia Polska 01/2007; 58(3):188-94. · 0.99 Impact Factor