Eftihios Trakakis

Augmentation of cortical bone mineral density in women with polycystic ovary syndrome: a peripheral quantitative computed tomography (pQCT) study

BACKGROUND Women with polycystic ovary syndrome (PCOS) may have increased cortical bone mineral density (BMD) and probably higher bone material quality as well as better resistance in the compression strength of the tibia, measured by peripheral quantitative computed tomography (pQCT), in comparison with that of age-matched healthy subjects. METHODS Thirty women with PCOS, (15 lean and 15 obese) and 15 age-matched healthy controls were enrolled in this study. The clinical, biochemical and ultrasound characteristics of the two groups were evaluated. Using pQCT, the following parameters were measured: volumetric cortical density (CBD) and volumetric trabecular density (TBD) BMD, total bone cross-sectional area (ToA), cortical area (CoA), cortical thickness (CRT-THK-C) and finally the strength-strain index (SSI). RESULTS The geometrical parameters (CoA, ToA, CRT-THK-C), the SSI as well as the TBD were increased in the PCOS women; however, these differences did not achieve statistical significance between lean PCOS women, obese PCOS women, and controls. Conversely, CBD was significantly higher in PCOS women compared with controls (P < 0.000) and furthermore in lean PCOS women compared with obese ones (P < 0.01040). CONCLUSIONS The PCOS women of our study seem to have a higher quality of bone material in the distal tibia and probably a better resistance of bone in the compression strength without alterations in bone mass and geometry (especially the lean PCOS women), indicating that our oligomenorrheic and hyperandrogonemic PCOS women may be protected from the development of osteoporosis and fracture risk later in life.

Congenital adrenal hyperplasia because of 21-hydroxylase deficiency. A genetic disorder of interest to obstetricians and gynecologists.

Congenital adrenal hyperplasia (CAH) due to deficiency of the enzyme 21-hydroxylase (21-OH), is distinguished in its classical and nonclassical form and is one of the most common autosomal recessive inherited diseases in humans. The classical form appears between 1:5000 and 1:15000 among the live neonates of North America and Europe, whereas the nonclassical form occurs in approximately 0.2% of the general white populations. Three alleles are associated with the 21-OH locus and can be combined in various ways to individuals who are either unaffected, heterozygote carriers, or affected with the classical or nonclassical disease. Variable signs and symptoms of hyperandrogenism are common to both types of the disorder. In women with CAH, hyperandrogenism may be present, extending from virilization of external genitalia and salt-wasting in classical (C)-CAH cases, to menstrual irregularity, obesity, short stature, infertility or subfertility and skin disorders such as hirsutism, in nonclassical (NC)-CAH cases. These clinical characteristics of NC-CAH cases do not differ unmarkedly from those shown in patients with polycystic ovary syndrome, idiopathic hirsutism, or hyperinsulinemia. The significant advances in molecular biology and gene analysis over the past 2 decades have led to the development of novel sensitive methods of DNA analysis and study, including polymerase chain reaction and Southern blot analysis. Thus it has been revealed that the 21-OH gene (CYP21A2) and its nonfunctional pseudogene (CYP21A1P) are located on chromosome 6 (6p21.3), sharing a high homology of about 98%. Inactivating mutations occur as complete gene deletions, large gene conversions and pseudogene-derived mutations. Target Audience: Obstetricians & Gynecologists, Family Physicians Leaning Objectives: After completion of this article, the reader should be able to recall the epidemiology of carrier status for 21-hydroxylase deficiency, identify phenotypic characteristics for classic and non-classic congenital adrenal hyperplasia, and describe the consequences of 21-hydroxylase block with respect to production of other hormones and enzymes.

An update to 21-hydroxylase deficient congenital adrenal hyperplasia

Congenital adrenal hyperplasia (CAH) due to deficiency of the enzyme 21-hydroxylase (21-OH) is distinguished in classical (C-CAH) and non-classical form (NC-CAH), and it is also one of the most common autosomal recessive inherited disorders in humans. The prevalence of C-CAH is between 1:10,000 and 1:15,000 among the live neonates of North America and Europe while the NC-CAH occurs in approximately 0.2% of the general white population. The highest incidence of CAH (1:282 and 1:2141, respectively) has been evaluated in Yupik Eskimos in Alaska and in the populations of the island La Reunion (France), while the lower was detected in New Zealand newborns (0.3%). Nowadays, it has been established that except for the adrenal cortex in CAH cases, the adrenal medulla was also affected. In human 21-OH deficient adrenal gland it has been discovered that not only the chromaffin cells formed extensive neurites, expanding between adrenocortical cells, but also that the adrenal androgens promote outgrowth, whereas glucocorticoids preserve neuroendocrine cells. It seems that normal cortisol secretion by the adrenal cortex is necessary for adrenomedullary organogenesis. The synthesis of 21-OH is controlled by the active CYP21A2 gene located at a distance of 30 kb from a highly homologous pseudogene designated CYP21A1P.

21-hydroxylase deficiency: From molecular genetics to clinical presentation

Congenital adrenal hyperplasia due to deficiency of the enzyme 21-hydroxylase (21-OH), a cytochrome P450 enzyme located in the endoplasmic reticulum and which catalyzes the conversion of 17-hydroxyprogesterone to 11-deoxycortisol and progestene to deoxycorticosterone, is distinguished in its classical and non-classical form and is also one of the most common autosomal recessive inherited diseases in humans. The classical form appears in a rate between 1:5000 and 1:15,000 among the live neonates of North America and Europe, while the non-classical form occurs in approximately 0.2% of the general white population. This rate is especially high between the Ahskenazi Jews and a part (ie Italians, Hispanics) of the Mediterranean populations. Three alleles are associated with the 21-OH locus and can be combined in several ways in individuals who are either unaffected, heterozygote carriers, or affected with classical or non-classical disease. Variable signs and symptoms of hyperandrogenism, such as hirsutism, acne, virilization of the external genitalia and/or the body, short stature, menstrual irregularities, are common to both types of the disorder. Among the genes responsible for the synthesis of the enzyme 21-OH and the antigens of HLA system, exist both a proven genetic linkage and a proven genetic linkage disequilibrium. HLA-Bw47, HLAB5 and HLA-B35 are the most common haplotypes usually met in the classical form, while the haplotype HLA-B14DR1 is the most recurrent in the non-classical form of the disease. The significant advances in molecular biology and gene analysis over the past two decades have led to the development of novel sensitive methods of DNA analysis and study, such as polymerase chain reaction and southern blot analysis. Thus, it has been revealed that the synthesis of enzyme 21-OH is controlled by two genes, the active CYP21B gene and the CYP21A pseudogene. All three forms of the disease have a known sequence of gene changes owing to mutations in isolated proteins or whole series of genes due to translocations or deletions of genetic material.

Hemodynamic alterations and wall properties in large arteries of young, normotensive, and non-obese women with polycystic ovary syndrome.

Young, normotensive, and non-obese women with polycystic ovary syndrome (PCOS) may present abnormal hemodynamic alterations (HA). The purpose of this study was to investigate heart rate (HR), intima-media thickness (IMT), and diameter (DCCA) in the common carotid arteries (CCA), flow velocities, and resistance index in both extracranial carotid and vertebral arteries (VA), in the abdominal aorta (AO) and in the renal arteries (RA) in PCOS women and matched controls. This was a case-control study conducted at a tertiary University Hospital. We studied 53 PCOS women and 53 healthy matched volunteers as controls. The previously reported parameters were assessed using color Doppler ultrasonography. HR, IMT in the CCA, and peak systolic velocity in all examined arteries were significantly increased in PCOS women compared to controls. On the contrary, DCCA was significantly decreased in PCOS women compared to controls. End diastolic velocity (EDV) in both VA and RA, in the AO and in the left extracranial carotid system was significantly increased in the PCOS group compared to controls. Furthermore, the peripheral resistance (PR) of AO and right external carotid artery was also found to be increased while in both RA and in left VA, PR was decreased. No further statistical significant HA in EDV and PR were noted. The results of this study provide evidence for a mild hyperdynamic circulation in young, normotensive, non-obese women with PCOS compared to controls, indicating a mild sympathetic activation at an early age, which may be an underlying cause of hypertension and cardiovascular risk.

Predictive value of increased nuchal translucency as a screening test for the detection of fetal chromosomal abnormalities

Objective. The study aimed to estimate the incidence of increased nuchal translucency in the first trimester ultrasound scan results (cut-off limit 2.5 mm) and to evaluate the predictive value of increased nuchal translucency as a screening test for the detection of fetal chromosomal abnormalities. Methods. We used the ultrasound scan results of nuchal translucency evaluation and the results of chromosomal analysis of the invasive prenatal control performed as a result of increased nuchal translucency. Results. We collected 2183 nuchal translucency ultrasound scans in which we detected 21 embryos with a pathologic value (0.96%). We collected the data of 168 cases of invasive prenatal control due to increased nuchal translucency from which 122 cases were found. A total of 122 cases of pregnant women undergone an invasive prenatal diagnostic method due to increased nuchal translucency, of which 11 fetuses were found with trisomy 21 (Down syndrome) (9%), 3 fetuses with trisomy 13 (Patau syndrome) (2.45%), 3 fetuses with monosomy 45XO (Turner syndrome) (2.45%) and 1 fetus with translocation (0.8%). Conclusions. The positive predictive value of the increased fetal nuchal translucency as a screening test for the detection of fetal chromosomal abnormalities based on the results of the chromosomal-genetic analysis of the invasive prenatal diagnostic procedures is 14.8%.

Comparing classic and newer phenotypes in Greek PCOS women: the prevalence of metabolic syndrome and their association with insulin resistance.

Objective: Recently, it has been debated whether the new polycystic ovary syndrome (PCOS) phenotypes, according to the Rotterdam criteria, share the same metabolic risk with the classic ones (National Institutes of Health 1990). Our study sought to compare the prevalence of metabolic syndrome (MS) and glucose homeostasis disorders in Greek women with classic and new PCOS phenotypes. Materials and methods: Two hundred and sixty-six Greek PCOS women were recruited and divided into groups according to two of the three Rotterdam criteria that they fulfilled. Two subgroups were formed; the first represented the classic phenotypes and the second the new phenotypes. The clinical, biochemical, and ultrasound characteristics of both groups were explored. All subjects were evaluated for MS and underwent a 2-h glucose tolerance test to assess insulin resistance (IR) as measured by the homeostasis model assessment (HOMA-IR), quantitative insulin sensitivity check index (QUIC-KI), and MATSUDA indices. Results: 62.4% of PCOS women were classified as classic NIH phenotypes of which 32 women had MS (prevalence 19.6%). Only 4 patients categorized in the newer phenotypic groups had MS (prevalence 4.1%). Among the subjects with classic phenotypes, 11.7% exhibited impaired glucose tolerance (3-fold higher percentage compared to patients with newer phenotypes). Regarding IR indices, HOMA-IR was significantly higher and QUICKI significantly lower for classic phenotypes. Conclusions: Greek PCOS women with classic phenotypes are at increased risk for MS and impaired glucose homeostasis compared to women with newer phenotypes. A subclassification of PCOS permits the earlier recognition and closer surveillance of women whose metabolic profile indicates potential risks for adverse health outcomes.

The prevalence of glucose metabolism abnormalities in Greek women with polycystic ovary syndrome

The prevalence of glucose metabolism abnormalities in PCOS women worldwide varies between 10 and 40% but there are no data in Greek PCOS women. In this retrospective study the prevalence of glucose abnormalities and the indices of insulin resistance (IR) and whole-body insulin sensitivity were estimated in a Greek population with PCOS. Impaired glucose tolerance (IGT), impaired fasting glucose (IFG) and type 2 diabetes mellitus (t2DM) were calculated. The prevalence of IGT, IFG and t2DM in our PCOS population was 7.6, 5.1 and 1.7%, respectively. The total prevalence of glucose abnormalities was estimated as 14.1%. The prevalence of t2DM was three- to four-fold higher than in the general Greek female population of the same age as this was estimated by 2, recently published studies. PCOS women with increased BMI and waist circumference and age greater than 30 years, present more severe IR and decreased whole-body insulin sensitivity. Our data indicates a relatively high prevalence of glucose intolerance and t2DM in a Greek population with PCOS. Obese women with PCOS are in higher risk to develop glucose abnormalities and probably t2DM later in life and therefore every woman diagnosed with PCOS should undergo a 2-h post load OGTT.

The Incidence of 21α-Hydroxylase Deficiency in Greek Hyperandrogenic Women: Screening and Diagnosis

The purpose of this prospective study was to determine the incidence of any form of 21α.-hydroxylase deficiency among Greek women with hyperandrogenic symptoms, and to test the predictive value of basal serum 17-hydroxyprogesterone (17-OHP) in the early follicular phase as a screening index for patient preselection to adrenocorticotropic hormone (ACTH) testing. Eighty-eight unselected women with hyperandrogenic symptoms were examined in the Gynecological Endocrinology Unit of the Second Department of Obstetrics and Gynecology of Athens University. Using the ACTH-stimulated 17-OHP values at 60 minutes (17-OHP60) the study population was divided into four groups (A, B, C and D). Clinical and basal hormonal parameters as well as serum 17-OHP60 values and human leukocyte antigens were studied. Both clinical and basal hormonal parameters could be used to distinguish only patients with severe 21α-hydroxylase deficiency (group A). In contrast, patients with moderate non-classical congenital adrenal hyperplasia (...

Prevalence of non classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency in Greek women with acne: a hospital-based cross-sectional study

Aim  To determine the prevalence and frequency of non classical congenital adrenal hyperplasia (NC‐CAH) due to 21‐OHD at the time of clinical presentation and at the peripubertal period in a substantial sample of Greek women with acne and to investigate the correlation of serum T, 17‐OHP and DHEA‐S with acne appearance at the time of clinical presentation.