Michael Fanta

Prevalence of nonclassic adrenal hyperplasia (NCAH) in hyperandrogenic women.

Objective. The clinical symptoms of nonclassic adrenal hyperplasia (NCAH) are identical with polycystic ovary syndrome (PCOS). The aim of our study was to determine the prevalence of nonclassic adrenal hyperplasia (21-hydroxylase-deficiency) in hyperandrogenic women, its biochemical, endocrine and clinical characteristics and to compare them with parameters of patients with ovarian hyperandrogenism. Methods. Since 1999, 298 patients with elevation of at least one androgen and manifestation of one of the clinical androgenic symptoms (oligo/amenorrhea, hirsutism or acne) have been identified in our database. A diagnosis of NCAH was considered when the basal or stimulated 17-hydroxyprogesterone was elevated. Results. Only eight patients were identified as having 21- hydroxylase deficient NCAH in the whole group of 298 hyperandrogenic women. Hirsutism and acne were found only in three, two patients, five of them had oligo/amenorrhea. Seven patients had both elevated basal and stimulated 17-hydroxyprogesterone, while in one case only elevation of stimulated level was found. All of the NCAH patients had elevated concentrations of testosterone, six DHEA, lower SHBG was found in four patients. Surprisingly, none of the NCAH patients had increased DHEAS. Conclusion. In our study, the prevalence of NCAH in hyperandrogenic women was 2.68%. Their leading symptom was oligomenorrhea, skin androgenic disorders were a minor clinical problem. None of the NCAH patients had an elevated DHEAS, the androgen dominantly produced by the adrenal glands.

Comparison of corticoid substitution versus combined oral contraception administration in the treatment of non-classic adrenal hyperplasia: A prospective study

Objective.The clinical symptoms of non-classic adrenal hyperplasia (NCAH) are the same as those in patients with polycystic ovary syndrome (PCOS). The aim of our study was to compare conventional corticoid treatment of NCAH with the effect of combined oral contraception (COC) administration (used in treatment of PCOS) on clinical and laboratory parameters of NCAH. Design.A prospective clinical study, cross-over design. Material and methods.Since 1999 from 298 hyperandrogenic women, eight patients having 21-hydroxylase deficient NCAH have been identified. They were divided equally into two groups according to the order of application treatment modality (hydrocortison vs. COC). Effect of treatment of both modalities on clinical symptoms (hirsutism – FG score, acne, menstrual cycle) and laboratory parameters (testosterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulphate, sex hormone binding globulin (SHBG)) were evaluated. Results.We observed the decrease of plasma androgens in both groups, which did not differ significantly. Significant increase of SHBG (i.e. decrease of free androgens) was, however, documented in each period with COC administration. Not surprisingly, improvement of the most frequent clinical symptom of NCAH in our study group, oligomenorrhea, was also more apparent in COC. Hirsutism was only a minor problem in our group that did not allow to evaluate treatment effect of both the modalities Conclusion.Our results indicate that ovarian suppression by COC administration can effectively suppress androgen production and improve the most frequent clinical symptom (irregular cycle) in patients with NCAH, so can be successfully used for the treatment at least under basal conditions. Whether corticosteroid substitution can be limited to patients with inadequate response to COC on plasma androgen levels or with signs of adrenal insufficiency requires further data.

High-risk human papillomavirus DNA in paraaortic lymph nodes in advanced stages of cervical carcinoma

BACKGROUND Paraaortic lymph nodes represent the second level in the lymphatic spread of cervical cancer. Recent studies have confirmed the association of HPV DNA in pelvic lymph nodes in early-stage disease with metastatic involvement and a less favourable prognosis. OBJECTIVE The aim of our study was to detect 13 high-risk genotypes of HPV in paraaortic nodes harvested from patients with FIGO IB2-IIIB tumours and correlate findings with histopathology. STUDY DESIGN The study involved patients with advanced cervical cancer who had undergone low paraaortic lymphadenectomy. The cytobrush technique was used for perioperative sample collection from the tumour and fresh lymphatic tissue. Patients with non-HPV related cancers were used as a control group. RESULTS The study involved 24 cervical cancer patients. High-risk HPV DNA was found in the primary tumour of all cases and in PALN in 16 (67%) cases. The most frequent genotype was HPV 16, both in the tumour and in the paraaortic lymph nodes (83% and 54%, respectively). Metastatic involvement of paraaortic lymph nodes was identified in 8 cases (33%), which all were also HPV DNA positive. No HPV DNA was detected in PALN in any of 22 control group cases. CONCLUSIONS Using the cytobrush technique, the presence of at least one HR HPV genotype in the primary tumour was identified in all the patients. The metastatically involved paraaortic lymph nodes always contained the DNA of at least one HPV genotype present in the primary tumour. Determination of clinical significance of HR HPV DNA presence in histologically negative lymph nodes requires further follow-up of the cohort.

The utility of fasting plasma glucose to identify impaired glucose metabolism in women with polycystic ovary syndrome.

Abstract We evaluated the utility of impaired fasting plasma glucose as defined by ADA to identify women with polycystic ovary syndrome (PCOS) affected by impaired glucose metabolism (i.e. impaired fasting glucose, impaired glucose tolerance and diabetes mellitus). In 330 women with PCOS, according to ESHRE criteria, an oral glucose tolerance test was done. Impaired fasting glucose was present in 36 women (12%), impaired glucose tolerance in 29 women (8.8%) and diabetes mellitus in 10 women (3%), 4 of them have fasting glucose higher than 7 mmol/l. The combination of impaired fasting glucose and impaired glucose tolerance was seen in 5 women (1.5%). The sensitivity of impaired fasting glucose for the detection of impaired glucose tolerance was 24% and specificity 91.8%. When fasting glucose above 5.6 mmol/l was used as the screening criterion, 28/35 subjects (80%) would have been missed. We conclude that fasting plasma glucose is not sufficiently sensitive for the detection of impaired glucose tolerance and diabetes mellitus type 2 in women with PCOS. Chinese abstract 评价ADA（美国糖尿病协会）定义的空腹血糖受损检测多囊卵巢综合征女性糖代谢受损（例如空腹血糖受损、糖耐量异常以及糖尿病）的有效性。对ESHER（欧洲人类生殖与胚胎学会）标准诊断的330名多囊卵巢综合征患者实施口服糖耐量试验。36名女性（12%）表现空腹血糖受损，29名女性（8.8%）表现糖耐量异常，10名女性（3%）表现为糖尿病，其中4名女性空腹血糖大于7mmol/L。5名女性（1.5%）同时具有空腹血糖受损及糖耐量异常。空腹血糖受损检测出糖耐量异常的敏感度及特异度分别为24%、91.8%。如果以空腹血糖大于5.6mmol/L作为筛查标准，28/35（80%）的患者将会被漏诊。我们推断：空腹血糖检测多囊卵巢综合征女性糖耐量受损及2型糖尿病的敏感性不足。

Prediction of insulin sensitivity in non-obese women with polycystic ovary syndrome

UNLABELLED Insulin resistance is a frequent (although not constant) abnormality in both obese and nonobese women with polycystic ovary syndrome (PCOS). It plays a key role in the predisposition to type 2 diabetes, which is the most important health consequence of the syndrome. Identification of patients with insulin resistance is significant both for follow-up and for therapeutic reasons. The aim of the study was to evaluate the relationships between insulin sensitivity, measured by euglycemic clamp, and both endocrine and metabolic indices and to identify the best model for predicting insulin sensitivity. A total of 41 nonobese women fulfilling the diagnostic criteria for PCOS were enrolled in the study. None of the androgens correlated with the insulin sensitivity index. All clamp parameters correlated with SHBG, triglycerides, and body mass index, although no correlation was found with waist to hip ratio or waist circumference. The close relationship between insulin sensitivity and SHBG was documented by factor analysis and by its presence in all prediction models as the most significant (or even the single) predictor of the insulin sensitivity index. IN CONCLUSION 1) a decreased level of SHBG can be used as a single reliable parameter in the prediction of insulin sensitivity in nonobese women with PCOS; and 2) waist to hip ratio, waist circumference, and androgen concentrations have no predictive value.