Polycystic ovary syndrome (PCOS) and idiopathic hirsutism (IH) are androgen excess disorders requiring the determination of classic androgen levels for diagnosis. 11-oxygenated androgens have high androgenic potential, yet their clinical value in those disorders is not clear. Additionally, the role of endocrine disruptors (EDs), particularly in IH, remains understudied. We analyzed 25 steroids and 18 EDs in plasma samples from women with IH, PCOS, and controls using LC-MS/MS. Cytokine levels and metabolic parameters were assessed. Comparisons included non-obese women with PCOS (n = 10), women with IH (n = 12) and controls (n = 20), and non-obese versus obese women with PCOS (n = 9). Higher levels of 11-oxygenated androgens were observed in women with PCOS compared to those with IH, but not controls. Conversely, 11-oxygenated androgen levels were lower in women with IH compared to controls. Cytokine levels did not differ between women with IH and controls. Bisphenol A (BPA) levels were higher in obese women with PCOS compared to non-obese women with PCOS. Bisphenol S occurrence was higher in women with PCOS (90%) compared to controls (65%) and IH (50%). Significant correlations were found between androgens (11-ketotestosterone, androstenedione, testosterone) and insulin and HOMA-IR, as well as between immunomodulatory 7-oxygenated metabolites of DHEA and nine interleukins. Our data confirms that PCOS is a multiendocrine gland disorder. Higher BPA levels in obese women might exacerbate metabolic abnormalities. IH was not confirmed as an inflammatory state, and no differences in BPA levels suggest BPA does not play a role in IH pathogenesis.

• Klíčová slova
• 11-hydroxytestosterone, 11-ketotestosterone, 11-oxygenated androgen, bisphenol A, bisphenol S, endocrine disruptor, idiopathic hirsutism, polycystic ovary syndrome,
• MeSH
• androgeny * krev   metabolismus   MeSH
• benzhydrylové sloučeniny krev   MeSH
• cytokiny krev   metabolismus   MeSH
• dospělí MeSH
• endokrinní disruptory * krev   MeSH
• fenoly MeSH
• hirzutismus * krev   etiologie   chemicky indukované   MeSH
• hyperandrogenismus krev   MeSH
• lidé MeSH
• mladý dospělý MeSH
• obezita krev   metabolismus   MeSH
• syndrom polycystických ovarií * krev   metabolismus   MeSH
• tandemová hmotnostní spektrometrie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• androgeny * MeSH
• benzhydrylové sloučeniny MeSH
• bisphenol A MeSH Prohlížeč
• cytokiny MeSH
• endokrinní disruptory * MeSH
• fenoly MeSH

Leydig cell tumours of the ovary are rare and represent a diagnostic challenge not only due to their sporadic incidence but also due to the seemingly normal imaging. We present three cases of pre- and postmenopausal women who were presented with severe clinical signs of hyperandogenism where modern imaging modalities (including computed tomography (CT), magnetic resonance imaging (MRI) and positron-emission tomography combined with computed tomography (PET-CT)) failed to identify the tumour. Two patients underwent non-expert ultrasound, CT and MRI examination with uniform conclusion that ovaries are of normal appearance. One of the two patients even had a PET-CT performed, which was inconclusive. Our case reports show the importance of examination by specialists with established skills in gynaecologic ultrasonography in the diagnosis of the Leydig cell tumours. The most useful diagnostic tool seems to be the combination of age (postmenopause), symptoms (onset of hirsutism and virilisation), high total testosterone plasma values and expert sonography. On ultrasound, these tumours are unilateral, usually small, solid intraovarian nodules of a slightly increased echogenicity in contrast to the surrounding ovarian tissue, delineated by abundant perfusion with an enhanced vascularity. The appropriate setting of the sensitive colour Doppler is crucial for the detection of intraovarian Leydig cell tumour. Impact statement What is already known on this subject? A diagnosis of Leydig cell tumours is based on ultrasound performed by a trained examiner or by MRI. CT or PET/CT are not among the primary methods of choice. According to the results of imaging investigations surgical treatment is planned. Because these tumours are usually benign and have a good prognosis the unilateral salpingo-oophorectomy is a standard procedure. What do the results of this study add? Our case series show how difficult it can be to establish the diagnosis of Leydig cell tumours by imaging, including transvaginal ultrasound, the most frequently recommended diagnostic tool. We demonstrate in three cases how easily a small hyperechogenic tumour can be overseen or interchanged for a different gynaecological pathology if transvaginal scan is not performed by an experienced examiner trained in sonographic features of gynaecologic neoplasms. What are the implications of these findings for clinical practice and/or further research? This case series demonstrate how important it is to see the patient in the whole complexity with their medical history, proper clinical symptoms evaluation, laboratory test and not to rely solely just on sophisticated high-end investigations, such as the PET-CT, a CT and an MRI. It also emphasises the importance of specialists with established skills in gynaecologic ultrasonography. Further effort should be made to define the resources for the appropriate training of such sonographers.

• Klíčová slova
• ASN, Leydig cell tumour, androgen, androgen-secreting ovarian tumour, hirsutism, hyperandrogenism, testosterone,
• MeSH
• amenorea etiologie   MeSH
• hirzutismus etiologie   MeSH
• hysterektomie vaginální MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• nádor z Leydigových buněk diagnostické zobrazování   patologie   chirurgie   MeSH
• nádory vaječníků diagnostické zobrazování   patologie   chirurgie   MeSH
• ovarektomie MeSH
• PET/CT MeSH
• testosteron krev   MeSH
• ultrasonografie dopplerovská barevná MeSH
• virilizace etiologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• testosteron MeSH

Hypertestosteronism as part of hyperandrogenic states in women is generally defined as abundance of male hormones (in this case abundance of testosterone). Spectrum of clinical symptoms include menstrual disorders, amenorrhoea, different range of hirsutism and virilization. Statistically, most androgen secreting tumors are ovarian aetiology (testosterone secreting tumors located in suprarenal gland are very rare). This rare tumor may produce excess amounts of testosterone, as well as its precursor androstenedione. The highest incidence is between 20-40 years and in postmenopausal period. The treatment is essentially surgical; with gradual adjustment of the hormones.Key words: androgen secreting ovarian tumors - hyperandrogenic states - testosterone - virilisation.

• MeSH
• hirzutismus * etiologie   MeSH
• lidé MeSH
• nádory vaječníků * komplikace   diagnóza   MeSH
• testosteron metabolismus   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• testosteron MeSH

Children with adrenocortical tumors (ACTs) often present with virilization due to high tumoral androgen production, with dihydrotestosterone (DHT) as most potent androgen. Recent work revealed two pathways for DHT biosynthesis, the classic and the backdoor pathway. Usage of alternate routes for DHT production has been reported in castration-resistant prostate cancer, CAH and PCOS. To assess whether the backdoor pathway may contribute to the virilization of pediatric ACTs, we investigated seven children suffering from androgen producing tumors using steroid profiling and immunohistochemical expression studies. All cases produced large amounts of androgens of the classic and/or backdoor pathway. Variable expression of steroid enzymes was observed in carcinomas and adenomas. We found no discriminative pattern. This suggests that enhanced androgen production in pediatric ACTs is the result of deregulated steroidogenesis through multiple steroid pathways. Thus future treatments of ACTs targeting androgen overproduction should consider these novel steroid production pathways.

• Klíčová slova
• Alternative (backdoor) pathway, Androgen biosynthesis, Classic pathway, Dihydrotestosterone, Pediatric adrenocortical tumors,
• MeSH
• adrenokortikální karcinom metabolismus   patologie   MeSH
• adrenokortikální nádory metabolismus   patologie   MeSH
• androgeny biosyntéza   krev   MeSH
• dihydrotestosteron krev   MeSH
• dítě MeSH
• imunohistochemie MeSH
• kojenec MeSH
• lidé MeSH
• Liův-Fraumeniho syndrom genetika   MeSH
• mladiství MeSH
• nádorový supresorový protein p53 genetika   MeSH
• nádory vaječníků metabolismus   patologie   MeSH
• virilizace metabolismus   patologie   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• androgeny MeSH
• dihydrotestosteron MeSH
• nádorový supresorový protein p53 MeSH
• TP53 protein, human MeSH Prohlížeč

OBJECTIVE: Overview of excessive hair growth in women, hirsutism. Although women with hirsutism typically present because of cosmetic concerns, the majority also have an underlying endocrine disorder. DESIGN: Review article. SETTING: Department of Gynecology and Obstetrics, General Faculty Hospital and 1st Faculty of Medicine of Charles Universtity, Prague. MATERIAL AND METHODS: Hirsutism is a clinical diagnosis defined by the presence of excess terminal hair growth (dark, coarse hairs) in androgen-sensitive areas. It affects between five and ten percent of women of reproductive age. It may be the initial, and possibly only, sign of an underlying androgen disorder. CONCLUSIONS: The most common cause of hirsutism is polycystic ovary syndrome (PCOS). In some cases, hirsutism is mild and requires only reassurance and local (nonsystemic) therapy, while in others it causes significant psychological distress and requires more extensive therapy. In case of rapid progressive hair growth should be first exclude androgen-secerning tumour (ovarian, adrenal) as the most serious condition.

• Klíčová slova
• androgen-secerning neoplasm, androgens, combined oral contraeptives antiandrogens., hirsutism, testosterone,
• MeSH
• hirzutismus * psychologie   MeSH
• lidé MeSH
• syndrom polycystických ovarií * MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Hirsutism is defined as excessive terminal hair growth in distribution typical for postpubertal men. It affects approximately 5-10 % of women and most frequently manifests in puberty. Significant cosmetic stigmatization is the usual complaint that brings patient to the doctor and it is crucial to always rule out any primary underlying disease causing hirsutism - benign or malignant. In this review etiopathogenesis, diagnostic procedures and treatment options are discussed.

• Klíčová slova
• hirsutism, hypertrichosis, polycystic ovary syndrome testosterone.,
• MeSH
• hirzutismus * diagnóza   etiologie   terapie   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND AND AIMS: The CONCERTO study results showing the beneficial effects of conversion from cyclosporine to tacrolimus prolonged-release (tacrolimus PR) in stabilised patients after kidney transplantation, were first published in 2011. This communication describes our first experience of conversion from cyclosporine to tacrolimus PR in stabilised kidney transplant patients. The aim was to determine whether it could be used in routine clinical practice in the Czech and Slovak Republics. METHODS: Evaluation was carried out at five transplantation centres in the Czech Republic and Slovakia. In all participating Centres, the drug conversion was conducted according to the ICH/GCP guidelines. A total of 104 patients stabilised after kidney transplantation were converted from maintenance therapy with cyclosporine to treatment with tacrolimus PR. The data were collected 26 weeks after the switch. The primary endpoint was change in kidney graft function measured from the estimated glomerular filtration rate (GFR). The effect of conversion on blood pressure, metabolic parameters and cosmetic changes was also recorded. Special attention was paid to the safety and tolerability of treatment with tacrolimus PR. RESULTS: GFR increased after six months by 10 % (P = 0.040). In addition a significant decrease in serum creatinine and triglycerides level was found together with major reduction in the incidence and severity of gingival hyperplasia and hirsutism. 3% of patients developed new onset of diabetes mellitus. Otherwise, the switch was very well-tolerated, without serious adverse events or acute rejections. CONCLUSION: Conversion from cyclosporine to tacrolimus PR was shown to be a safe therapeutic alternative with patient benefits.

• Klíčová slova
• cyclosporine, immunosuppressive conversion, kidney transplantation, tacrolimus prolonged-release,
• MeSH
• cyklosporin aplikace a dávkování   MeSH
• diabetické nefropatie patofyziologie   MeSH
• dyslipidemie etiologie   MeSH
• hirzutismus etiologie   MeSH
• hodnoty glomerulární filtrace účinky léků   MeSH
• hyperplazie dásní etiologie   MeSH
• imunosupresiva aplikace a dávkování   MeSH
• léky s prodlouženým účinkem MeSH
• lidé středního věku MeSH
• lidé MeSH
• náhrada léků MeSH
• nemoci ledvin chirurgie   MeSH
• renální hypertenze etiologie   MeSH
• takrolimus aplikace a dávkování   MeSH
• transplantace ledvin * MeSH
• výsledek terapie MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• Názvy látek
• cyklosporin MeSH
• imunosupresiva MeSH
• léky s prodlouženým účinkem MeSH
• takrolimus MeSH

BACKGROUND: The differential diagnosis of the pathogenetic causes of hirsutism in combination with hypertension is a challenge for clinicians. METHODS AND RESULTS: This case report demonstrates a patient suffering from two hormonally active tumors - an adrenal adenoma with primary aldosteronism and a Leydig cell ovarian tumor with hyperandrogenism. The task of the authors was easier due to the perimenopausal age of the proband. Adrenal selective venous sampling was very helpful in the diagnosis of these active endocrine tumors. Both were resolved by a single laparoscopic surgery. CONCLUSION: The combination of the two described tumors is a unique clinical finding. The resolution using laparoscopy in a single procedure provided an elegant and efficient therapeutic approach.

• MeSH
• diferenciální diagnóza MeSH
• hirzutismus diagnóza   etiologie   MeSH
• hypertenze diagnóza   etiologie   MeSH
• lidé MeSH
• nádor z Leydigových buněk komplikace   diagnóza   MeSH
• nádory vaječníků komplikace   diagnóza   MeSH
• počítačová rentgenová tomografie MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH

Primary adrenal insufficiency (PAI) is a rare condition in childhood which is either inherited (mostly) or acquired. It is characterized by glucocorticoid and maybe mineralocorticoid deficiency. The most common form in children is 21-hydroxylase deficiency, which belongs to the steroid biosynthetic defects causing PAI. Newer forms of complex defects of steroid biosynthesis are P450 oxidoreductase deficiency and (apparent) cortisone reductase deficiency. Other forms of PAI include metabolic disorders, autoimmune disorders and adrenal dysgenesis, e.g. the IMAGe syndrome, for which the underlying genetic defect has been recently identified. Newer work has also expanded the genetic causes underlying isolated, familial glucocorticoid deficiency (FGD). Mild mutations of CYP11A1 or StAR have been identified in patients with FGD. MCM4 mutations were found in a variant of FGD in an Irish travelling community manifesting with PAI, short stature, microcephaly and recurrent infections. Finally, mutations in genes involved in the detoxification of reactive oxygen species were identified in patients with unsolved FGD. Most mutations were found in the enzyme nicotinamide nucleotide transhydrogenase, which uses the mitochondrial proton pump gradient to produce NADPH. NADPH is essential in maintaining high levels of reduced forms of antioxidant enzymes for the reduction of hydrogen peroxide. Similarly, mutations in the gene for TXNRD2 involved in this system were found in FGD patients, suggesting that the adrenal cortex is particularly susceptible to oxidative stress.

• MeSH
• 11-beta-hydroxysteroiddehydrogenasy nedostatek   MeSH
• adrenální insuficience diagnóza   etiologie   metabolismus   terapie   MeSH
• dítě MeSH
• glukokortikoidy nedostatek   MeSH
• hirzutismus komplikace   vrozené   terapie   MeSH
• kojenec MeSH
• lidé MeSH
• poruchy sexuálního vývoje s karyotypem 46, XX komplikace   terapie   MeSH
• předškolní dítě MeSH
• steroidy biosyntéza   MeSH
• vrozené poruchy metabolismu steroidů komplikace   terapie   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• 11-beta-hydroxysteroiddehydrogenasy MeSH
• glukokortikoidy MeSH
• steroidy MeSH

Hyperandrogenic states in pregnancy are almost always the result of a condition that arises during pregnancy. The onset of virilization symptoms is often very fast. The mother is protected against hyperandrogenism by a high level of SHBG, by placental aromatase and a high level of progesterone. The fetus is protected from the mother's hyperandrogenism partly by the placental aromatase, that transforms the androgens into estrogens, and partly by SHGB. Nevertheless there is a significant risk of virilization of the female fetus if the mother's hyperandrogenic state is serious. The most frequent cause of hyperandrogenic states during pregnancy are pregnancy luteoma and hyperreactio luteinalis. Hormonal production is evident in a third of all luteomas, which corresponds to virilization in 25-35 % of mothers with luteoma. The female fetus is afflicted with virilization with two thirds of virilized mothers. Hyperreactio luteinalis is created in connection with a high level of hCG, e.g. during multi-fetus pregnancies. This condition most frequently arises in the third trimester, virilization of the mother occurs in a third of cases. Virilization of the fetus has not yet been described. The most serious cause of hyperandrogenism is represented by ovarian tumors, which are fortunately rare.

• MeSH
• adenom kůry nadledvin diagnostické zobrazování   metabolismus   MeSH
• adrenokortikální karcinom diagnostické zobrazování   metabolismus   MeSH
• androgeny biosyntéza   fyziologie   MeSH
• aromatasa nedostatek   MeSH
• dospělí MeSH
• hyperandrogenismus komplikace   diagnostické zobrazování   metabolismus   MeSH
• komplikace těhotenství diagnostické zobrazování   metabolismus   MeSH
• lidé MeSH
• luteom diagnostické zobrazování   metabolismus   MeSH
• nadledviny diagnostické zobrazování   metabolismus   MeSH
• nádory nadledvin metabolismus   MeSH
• nádory vaječníků diagnostické zobrazování   metabolismus   MeSH
• ovarium diagnostické zobrazování   metabolismus   MeSH
• placenta enzymologie   MeSH
• plod metabolismus   MeSH
• těhotenství MeSH
• ultrasonografie prenatální MeSH
• virilizace diagnostické zobrazování   etiologie   metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• androgeny MeSH
• aromatasa MeSH