Comparison of PCOS phenotypes in adolescent and young adult Mediterranean women with possible PCOS.

PURPOSE: During adolescence, PCOS features are supposed to be in evolution. Because of this, the diagnosis of PCOS in adolescence is often unclear and few studies have compared adolescent and adult PCOS phenotype distribution and features. The aim is to compare phenotypes in adolescents and young adults with PCOS. METHODS: 109 girls aged from 13 to 19 years were retrospectively studied. All patients had a gynecological age > 2 years. 63 patients were adolescents (3-5 years beyond menarche) while 46 patients were young adults (6-9 years beyond menarche). Diagnosis of different PCOS phenotypes (A, B, C, D) was made according to the Rotterdam criteria. Clinical data (menstrual cycles, BMI, presence of hirsutism), androgen circulating levels (total testosterone, androstenedione, dehydroepiandrosterone sulphate) and ovarian morphology by ultrasound were assessed. RESULTS: 109 patients presented PCOS according to the Rotterdam criteria. Phenotype A was by far the most common phenotype (73.4%) followed by phenotype B (21.1%). Only few patients had phenotype C (4.6%) or phenotype D (0.9%). When patients were divided in two groups (adolescent and young adult patients), no significant difference in prevalence and features of the different phenotypes was observed. CONCLUSION: In this cohort of adolescent and young adult women with PCOS, the progression of age does not change the prevalence and the features of main PCOS phenotypes. It suggests that the Rotterdam criteria might be used also in adolescents, at least in those with 2 or more years of gynecological age, for the diagnosis of PCOS.

PPAR-γ signalling as a key mediator of human hair follicle physiology and pathology.

Peroxisome proliferator-activated receptors (PPARs) are abundantly expressed in human skin, with PPAR-γ being the most intensively investigated isoform. In various ex vivo and in vivo models, PPAR-γ-mediated signalling has recently surfaced as an essential element of hair follicle (HF) development, growth and stem cell biology. Moreover, the availability of novel, topically applicable PPAR-γ modulators with a favourable toxicological profile has extended the range of potential applications in clinical dermatology. In this review, we synthesize where this field currently stands and sketch promising future research avenues, focussing on the role of PPAR-γ-mediated signalling in the biology and pathology of human scalp HFs, with special emphasis on scarring alopecias such as lichen planopilaris and frontal fibrosing alopecia as model human epithelial stem cell diseases. In particular, we discuss whether and how pharmacological modulation of PPAR-γ signalling may be employed for the management of hair growth disorders, for example, in scarring alopecia (by reducing HF inflammation as well as by promoting the survival and suppressing pathological epithelial-mesenchymal transition of keratin 15 + epithelial stem cells in the bulge) and in hirsutism/hypertrichosis (by promoting catagen development). Moreover, we explore the potential role of PPAR-γ in androgenetic alopecia, HF energy metabolism and HF ageing, and consider clinical perspectives that emanate from the limited data available on this so far. As this field of translational human hair research is still in its infancy, many open questions exist, for which we briefly delineate selected experimental approaches that promise to generate instructive answers in the near future.

Genetic, hormonal and metabolic aspects of PCOS: an update.

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder affecting 5-10 % of women of reproductive age. It generally manifests with oligo/anovulatory cycles, hirsutism and polycystic ovaries, together with a considerable prevalence of insulin resistance. Although the aetiology of the syndrome is not completely understood yet, PCOS is considered a multifactorial disorder with various genetic, endocrine and environmental abnormalities. Moreover, PCOS patients have a higher risk of metabolic and cardiovascular diseases and their related morbidity, if compared to the general population.

Hormonal and psychosocial correlates of psychological well-being and negative affectivity in young gynecological-endocrinological patients.

To study the relationship between hormones, psychosocial factors and psychological well-being or negative affectivity (NA), 102 women (aged 15-31) responded to the 12-item well-being questionnaire (W-BQ12), with subscales for positive well-being (PWB), negative well-being (NWB) and energy (ENE); the Hospital Anxiety and Depression Scale (HADS), consisting of depression (HADS-D) and anxiety (HADS-A) subscales; the Beck Depression Inventory (BDI), and the Hamilton Depression Scale (HAMD). The univariate analysis revealed significant negative correlations between luteinizing hormone (LH) and HADS-T, HADS-D and HADS-A, and between follicle stimulating hormone (FSH) and HADS-A. Positive correlations were shown for thyroid stimulating hormone (TSH), HADS-T, and HADS-A. Cortisol and prolactin levels strongly correlated with BDI and HAMD scores, respectively. In a multivariate analysis, TSH significantly predicted the mood impairment in HADS-T (ß = 0.68) and HADS-A (ß = 0.68), while economic status predicted the general well-being (ß = 0.75), NWB (ß = -0.83), ENE (ß = 0.89), and HADS-A (ß = -0.63). We could not detect any significant differences in NA or well-being in patients with versus without PCOS or with versus without hirsutism, but almost all psychometric parameters differed significantly according to the economic status. In conclusion, TSH was the only hormonal predictor of overall NA and anxiety, and low-economic status overtrumped the impact of hormones on the psychological well-being.

PCOS in adolescence and type 2 diabetes.

Polycystic ovary syndrome is a frequent disorder in women of reproductive age that consists of a heterogeneous combination of hyperandrogenism, chronic anovulation, and polycystic ovaries. Hyperandrogenism and anovulation are clearly linked to insulin resistance and compensatory hyperinsulinism, with an ovarian androgenic hyperresponsiveness to circulating insulin. Evidence is increasing that suggests that lipotoxicity, which is a key mechanism in the development of insulin resistance and type 2 diabetes, could also explain the androgen overproduction. During adolescence, diagnosis of polycystic ovarian syndrome (PCOS) may be difficult but is of importance because PCOS increases future risk of type 2 diabetes and metabolic complications. Metabolic perturbations begin early in adolescence and also exist in adolescent relatives of women with PCOS, even before clinical signs of PCOS. Screening for impaired glucose tolerance or type 2 diabetes is also important in this population, and treatment should focus on PCOS clinical manifestations as well as long-term metabolic risk.

Should insulin resistance be screened in lean hirsute women?

The role of insulin resistance (IR) is well-documented in obese women with polycystic ovary syndrome (PCOS). Controversies exist concerning the presence of IR in idiopathic hirsutism (IH) or if it is a manifestation of high body mass index (BMI). We aimed to investigate the presence/absence of IR in lean hirsute women. One-hundred fifty-one lean women with hirsutism [96 PCOS (group 1) and 55 IH (group 2)] and 58 age-and BMI-matched healthy controls (group 3) were recruited in the study (mean age 25.21 ± 6.1 versus 26.26 ± 4.6years; BMI 21.79 ± 1.7 versus 22.02 ± 2.2 kg/m(2), respectively). Significantly higher insulin and HOMA-IR, and significantly lower fasting glucose insulin ratio (FGIR), quantitative insulin sensitivity check index (QUICKI), reciprocal insulin, and Raynaud index were detected in groups 1 and 2 than in group 3 (p < 0.05). These IR indices were similar between groups 1 and 2. The number of patients with IR (HOMA-IR > 2, FGIR < 7.2, or QUICKI < 0.357) was significantly higher in groups 1 and 2 than in group 3, but was similar between groups 1 and 2. A higher frequency of IR occurs in lean hirsute women regardless of they having PCOS or IH. IR may contribute to aetiopathogenesis of IH, or may cause some metabolic abnormalities in these patients.

[The importance of putrescine in the human body]. / Znaczenie putrescyny w organizmie czlowieka.

Putrescine plays a very important role in the regulation of division, differentiation and maturation of cells as well as apoptosis. As the polycationic molecule it stabilizes the structure of DNA and participates in the functioning of cell membranes. It is able to interact with series of ion channels and has affinity for many receptors. The article presents the participation of putrescine in the metabolism of iron and mechanism of its transport across biological membranes. Especially important for the homeostasis of putrescine has ornithine decarboxylase and availability of its substrate--ornithine. Affecting to this enzyme is the simplest and widely used method of controlling the concentration of putrescine. For this purpose its inhibitor-eflornithine is applied. There was also a number of other enzymes involved in the metabolism of putrescine that was presented. Current information about the clinical relevance of putrescine in infertility, embryonic development, hirsutism, epilepsy, Alzheimer's disease, Parkinson's disease, prevention of metastases and hemostasis was also described. These processes were presented, in which putrescine plays a major role and focused on the latest reports. Attention was drawn to the situations where it has beneficial effects and those in which it is the cause of the pathology. Some of the cited reports are in phase of speculation on the possible use of it, but a significant part is already confirmed and used in clinical practice. The facts presented in this article show how great is the meaning of putrescine and how important role this simple specimen plays in the metabolic processes of living organisms.

Ovarian SAHA syndrome is associated with a more insulin-resistant profile and represents an independent risk factor for glucose abnormalities in women with polycystic ovary syndrome: a prospective controlled study.

BACKGROUND: SAHA syndrome is characterized by the tetrad: seborrhea, acne, hirsutism, and androgenetic alopecia. No previous study has examined the prevalence of glucose abnormalities in ovarian SAHA and explored whether it may be an independent risk factor for glucose abnormalities. OBJECTIVE: In a prospective controlled study, we investigated the spectrum of glucose abnormalities in ovarian SAHA and explored whether it is associated with a more insulin-resistant profile. METHODS: In all, 316 patients with a diagnosis of polycystic ovary syndrome (PCOS) (56 with SAHA) and 102 age-matched healthy women were examined and underwent a 2-hour oral glucose tolerance test. Serum glucose homeostasis parameters, hormones, and adipokines were determined. RESULTS: SAHA prevalence was 17.7% in patients with PCOS and predominance of the severe PCOS phenotype. Ovarian SAHA was independently associated with a more insulin-resistant profile (higher homeostatic model assessment of insulin resistance score, lower quantitative insulin sensitivity check index [QUICKI] and MATSUDA indices, and relative hypoadiponectinemia), and represented an independent risk factor for glucose abnormalities regardless of anthropometric features, age, and PCOS phenotype. LIMITATION: There was no performance of skin biopsies. CONCLUSION: The prompt recognition of SAHA syndrome in women with PCOS permits an earlier diagnosis and surveillance of metabolic abnormalities, especially in Mediterranean PCOS population exhibiting a lower prevalence of glucose abnormalities.

The lack of association between idiopathic hirsutism and metabolic disturbances: Iranian PCOS Prevalence Study.

BACKGROUND: Idiopathic hirsutism (IH) is a condition diagnosed after other hirsutism related is ruled out. Its definition diagnosis had a dynamic process along with improving the understanding of the various androgen excess disorders. There is uncertainty regarding its health impact and its long-term metabolic consequences. We aimed to compare metabolic syndrome (Mets) and insulin resistance (IR) of Iranian women with IH and a group of healthy controls in a large community-based study. METHODS: Anthropometric measurements, biochemical parameters, Mets (using Joint Interim Statement criteria) and IR (estimated by the homeostasis model assessment), were compared between 101 women with IH and 423 healthy controls recruited from among 1126 reproductive aged women. RESULTS: There was a statistically significant difference between the BMI of women with IH in comparison to normal control (27.7 versus 26.7 kg/m(2), p = 0.02); however, the prevalence of android adiposity was similar (26.7% and 24.3%, respectively). The age and BMI adjusted prevalence of Mets and IR are similar in women with IH and controls (30% versus 23.9 and 25.7 % versus 22.5%, respectively). CONCLUSION: There will be no need for additional cardiometabolic evaluations for women with IH, later in life.

Clinical, hormonal and metabolic characteristics of polycystic ovary syndrome among obese and nonobese women in the Croatian population.

Obesity has a deteriorating impact on women with PCOS, although prevalence and the impact of specific traits of PCOS remain inconstant in different populations. Therefore, the aim of this study was to explore the differences in clinical, hormonal and metabolic features between obese and nonobese Croatian women diagnosed as having PCOS according to Rotterdam consensus criteria. The study included 74 obese and 208 nonobese women with PCOS. Clinical, biochemical and metabolic variables were compared among those PCOS subgroups. Obese subjects with PCOS had a higher risk of developing oligo-amenorrhea (OR 3.7; 95% CI, 1.1-12.5) and lower risk for developing hirsutism and acne (OR 0.2; 95% CI, 0.1-0.3 and OR 0.8; 95% CI 0.5-1.4, respectively). Obese PCOS subjects also had a higher risk of developing hyperandrogenemia (OR 2.5; CI 95% 0.9-6.7), insulin resistance (OR 4.5; CI 95%, 2.6-7.9), hypercholesterolemia (OR 5.0, CI 95% 2.5-10.2), hypertriglyceridemia (OR 5.2; 95% CI, 2.9-9.2) as well as elevated serum CRP levels (OR 4.1; 95% CI 1.4-12.2) compared to nonobese PCOS women. In conclusion, nonobese Croatian women with PCOS are more inclined to cosmetic problems associated with PCOS then metabolic ones. This is the first study to report the impact of obesity on acne and irregular menses as a study outcome. Obesity deteriorates menstrual regularity, insulin sensitivity and lipid profile in Croatian women with PCOS; therefore one of the fundamental treatment strategies of PCOS should be obesity prevention.

[Hirsutism and multinodular goiter in a 40-year-old female watchmaker]. / Hirsutismus und Struma multinodosa bei einer 40-jährigen Uhrmacherin.

This article presents the case of a female patient with acromegaly caused by ectopic production of growth hormone-releasing hormone (GHRH) secretion. In the presence of typical clinical features of acromegaly but a lack of evidence for a pituitary adenoma the results of somatostatin receptor scintigraphy were indicative of a typical carcinoid of the lungs as the cause of the ectopic secretion of GHRH and the stimulation of pituitary gland growth hormone secretion resulting in acromegaly. Finally, the patient underwent curative surgical treatment.

Hirsutism, virilism, polycystic ovarian disease, and the steroid-gonadotropin-feedback system: a career retrospective.

This career retrospective describes how the initial work on the mechanism of hormone action provided the tools for the study of hirsutism, virilism, and polycystic ovarian disease. After excessive ovarian and or adrenal androgen secretion in polycystic ovarian disease had been established, the question whether the disease was genetic or acquired, methods to manage hirsutism and methods for the induction of ovulation were addressed. Recognizing that steroid gonadotropin feedback was an important regulatory factor, initial studies were done on the secretion of LH and FSH in the ovulatory cycle. This was followed by the study of basic mechanisms of steroid-gonadotropin feedback system, using castration and steroid replacement and the events surrounding the natural onset of puberty. Studies in ovariectomized rats showed that progesterone was a pivotal enhancer of estrogen-induced gonadotropin release, thus accounting for the preovulatory gonadotropin surge. The effects of progesterone were manifested by depletion of the occupied estrogen receptors of the anterior pituitary, release of hypothalamic LHRH, and inhibition of enzymes that degrade LHRH. Progesterone also promoted the synthesis of FSH in the pituitary. The 3α,5α-reduced metabolite of progesterone brought about selective LH release and acted using the GABA(A) receptor system. The 5α-reduced metabolite of progesterone brought about selective FSH release; the ability of progesterone to bring about FSH release was dependent on its 5α-reduction. The GnRH neuron does not have steroid receptors; the steroid effect was shown to be mediated through the excitatory amino acid glutamate, which in turn stimulated nitric oxide. These observations led to the replacement of the long-accepted belief that ovarian steroids acted directly on the GnRH neuron by the novel concept that the steroid feedback effect was exerted at the glutamatergic neuron, which in turn regulated the GnRH neuron. The neuroprotective effects of estrogens on brain neurons are of considerable interest.

Clinical and biochemical characteristics of polycystic ovary syndrome in Croatian population.

Polycystic ovary syndrome (PCOS) is a common endocrine condition affecting women of reproductive age. There are many typical signs and symptoms that allow for the diagnosis of PCOS depending on the criteria used. Interestingly, ethnicity influences the extent of these signs and symptoms; therefore, the frequency of symptoms varies between different countries and ethnic groups. The prevalence of this syndrome in Croatia is unknown, and it's clinical and biochemical characteristics have not yet been reported. During this study, we used the Rotterdam criteria to evaluate 365 Croatian women with PCOS, and compared them to 304 age matched controls to assess the clinical and biochemical abnormalities that occur in PCOS patients. The mean age of PCOS patients at presentation was 26.1 +/- 5.9 years and of controls were 28.0 +/- 4.2 years. Women with PCOS has significantly higher body mass index (BMI) than the control group, although in both groups most patients had normal weight (76.2% vs. 87.8%). Abdominal distribution of fat tissue was similar in both groups. Menstrual cycle abnormalities were observed in 90.7% of PCOS patients, and ultrasonographic appearance of polycystic ovaries was reported in 97.3% of PCOS cases. Nearly 75% of patients with PCOS had hirsutism and 49.6% had acne. We recorded significantly higher serum levels of luteinizing hormone (LH), total testosterone (TT), free testosterone (fT) and insulin, while the serum levels of sex hormone binding globuline (SHBG) and follicular stimulating hormone (FSH) were significantly lower than in the control group. Serum glucose values were not significantly different between the groups. In conclusion, chronic anovulation, hirsutism and ultrasound appearance of polycystic ovaries are the dominant features of PCOS in Croatian population. The majority of patients with PCOS had normal body weight. The incidence of insulin resistance in this group of patients is less than the previously described frequency in other populations of patients with PCOS and normal weight.

[Diagnosis and management of hirsutism]. / Diagnostyka i leczenie hirsutyzmu.

Apart from being a source of great distress and social embarrassment, hirsutism may be also a sign of an underlying endocrine or malignant disease. The diagnosis should be always methodical and adjusted to the nature of the clinical presentation. The clinical evaluation of the potentially hirsute patient first involves confirming the presence of hirsutism by hormonal assessment and then excluding underlying disorders or associated abnormalities. There is no uniform treatment approach for the management of hirsutism and the therapy is directed at suppressing ovarian or adrenal androgen production, inhibiting the conversion of testosterone to dihydrotestosterone, or antagonizing the effects of androgens at the receptor level. All these tratment options are reviewed. In this paper, we provide the recommended approach to the diagnosis and treatment of hirsute patient.

Assessment of hirsutism among Korean women: results of a randomly selected sample of women seeking pre-employment physical check-up.

BACKGROUND: The objectives of this study were to define the distribution of the modified Ferriman-Gallwey (mF-G) score in a random group of Korean women and to study any association(s) between hirsutism and endocrine/metabolic markers. METHODS: A single investigator assessed the mF-G score prospectively in 1010 Korean women, who consulted a health-care center as part of a group check-up for employment. Logistic regression models were utilized to test the relationships between the presence of hirsutism and levels of endocrine/metabolic markers. RESULTS: Subjects had mF-G scores ranging from 0 to 19, and 505 subjects (50.0%) had an mF-G score of zero. Of the 1010 subjects, 95.1% had a score at or below six; thus, a score of six or greater represented hirsute women in our population. The most frequently affected site was the upper back, but the most densely affected area was found to be the lower abdomen. Hirsutism was significantly and positively associated with serum levels of total testosterone (T) and hemoglobin A1(c), but negatively associated with those of sex hormone binding globulin (SHBG). In addition, the odds of a woman developing hirsutism were higher for increased total T and HbA1(c), and lower for decreased SHBG. Hirsutism and homeostatic model assessment for insulin resistance were positively associated, but the relationship was not significant after adjusting for age and BMI. CONCLUSIONS: mF-G scores greater that six represent the appropriate diagnostic cutoff for the detection of hirsutism in Korean women. Increased serum total T and HbA1(c,) and decreased SHBG concentrations were associated with the presence of hirsutism.

[Correlations between clinical signs and hormonal parameters in young women with hirsutism].

Hyperandrogenism is the pathological condition, which clinical signs are "androgendependent dermopathies" (seborrhea, acne, hirsutism, alopecia) and not in every cases evidence with hyperandrogenemia. Free testosterone is the most frequent marker of hyperandrogenism, but its determination routinely not feasible in all laboratories. Therefore, some models for calculating free and bioavailable testosterone have been developed. In women the testosterone sources are not only ovaries and adrenal glands, but also abdominal and peripheral fat. There are many investigations to definite correlations between body mass index, androgens and sex hormone binding globulin. The aim of this study was to define the correlations between clinical, biochemical markers of hyperandrogenism and body mass index, with regard of abdominal obesity in young women with hirsutism. 83 female adolescents (14-20 year) with hirsutism and 20 female adolescents in control group were included. C-peptide, estradiol, total testosterone, sex hormone binding globulin (SHBG) were measured. Free androgen index (FAI), free (cFT) and bioavailable (Bio-T) testosterone were calculated. The levels of C-peptide and glucose were used to compute Homa-IR (homeostasis model assessment for insulin resistance). There were detected significant high levels by all hormonal parameters of hyperandrogenism in women with hirsutism, than in control group. In patients with abdominal obesity were also found significant high levels by all calculated parameters of hyperandrogenism and significant low level of steroid-bind globulin, than in patients with central obesity. In two groups by hirsutism degree were not detected any differences between androgen markers. The findigs of this research suggest, that android obesity in female adolescents with hirsutism can cause harder hyperandrogenism and elevate free androgen index, free and bioavailable testosterone levels. The prophylactic reduction of body mass index may prevent complications.

Endocrinology of Hirsutism: From Androgens to Androgen Excess Disorders.

Unwanted sexual hair growth has a considerable negative impact on a woman's self-esteem and quality of life. Excessive growth of terminal hair in women in a man-like pattern is defined as hirsutism and affects up to 1 in 7 women. Androgens secreted by the ovary and adrenal are the main regulator of physiological and pathological alterations of skin hair. Hirsutism is the result of the interaction between circulating serum androgens and hair follicles. Hirsutism is the most commonly used clinical diagnostic criterion of hyperandrogenism and majority of hirsutism cases are due to androgen excess. Over 80% of women with hirsutism will have polycystic ovary syndrome, about 10% will have idiopathic hirsutism, and the remaining will have rare disorders including non-classical congenital adrenal hyperplasia, hyperandrogenism with insulin resistance and acanthosis nigricans, and androgen-secreting neoplasms. Cushing's syndrome, acromegaly, thyroid dysfunction and hyperprolactinemia might be associated with hirsutism as well as the use of androgens, anabolic steroids and valproate. This paper provides an overview of the principal endocrinological aspects of hirsutism including the role of androgens in excessive hair growth and associated androgen excess disorders. Clinical evaluation and management of hirsutism are also discussed.

Steroid biomarkers and genetic studies reveal inactivating mutations in hexose-6-phosphate dehydrogenase in patients with cortisone reductase deficiency.

CONTEXT: Cortisone reductase deficiency (CRD) is characterized by a failure to regenerate cortisol from cortisone via 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), resulting in increased cortisol clearance, activation of the hypothalamic-pituitary-axis (HPA) and ACTH-mediated adrenal androgen excess. 11beta-HSD1 oxoreductase activity requires the reduced nicotinamide adenine dinucleotide phosphate-generating enzyme hexose-6-phosphate dehydrogenase (H6PDH) within the endoplasmic reticulum. CRD manifests with hyperandrogenism resulting in hirsutism, oligo-amenorrhea, and infertility in females and premature pseudopuberty in males. Recent association studies have failed to corroborate findings that polymorphisms in the genes encoding H6PDH (R453Q) and 11beta-HSD1 (Intron 3 inserted adenine) interact to cause CRD. OBJECTIVE: Our objective was to reevaluate the genetics and steroid biochemistry of patients with CRD. DESIGN: We analyzed 24-h urine collection for steroid biomarkers by gas chromatography/mass spectrometry and sequenced the HSD11B1 and H6PD genes in our CRD cohort. PATIENTS: Patients included four cases presenting with hyperandrogenism and biochemical features clearly indicative of CRD. RESULTS: Gas chromatography/mass spectrometry identified steroid biomarkers that correlated with CRD in each case. Three cases were identified as homozygous (R109AfsX3, Y316X, and G359D) and one case identified as compound heterozygous (c.960G-->A and D620fsX3) for mutations in H6PD. No mutations affecting enzyme activity were identified in the HSD11B1 gene. Expression and activity assays demonstrate loss of function for all reported H6PDH mutations. CONCLUSIONS: CRD is caused by inactivating mutations in the H6PD gene, rendering the 11beta-HSD1 enzyme unable to operate as an oxoreductase, preventing local glucocorticoid regeneration. These data highlight the importance of the redox control of cortisol metabolism and the 11beta-HSD1-H6PDH pathway in regulating hypothalamic-pituitary-adrenal axis activity.

Disruption of chromodomain helicase DNA binding protein 2 (CHD2) causes scoliosis.

Herein we characterize an apparently balanced de novo translocation, t(X;15)(p22.2;q26.1)dn, in a female patient with scoliosis, hirsutism, learning problems, and developmental delay (DGAP025). Other clinical findings include a high-arched palate, 2-3 syndactyly of the toes, and mildly elevated serum testosterone. No known or predicted genes are disrupted by the Xp22.2 breakpoint. The 15q26.1 breakpoint disrupts chromodomain helicase DNA binding protein 2 (CHD2). Another member of the chromatin-remodeling gene family, CHD7, has been associated with a defined constellation of congenital anomalies known as coloboma, heart anomaly, choanal atresia, mental retardation, genital and ear anomalies syndrome (CHARGE) and idiopathic scoliosis. Monosomy of 15q26 also has been associated with a spectrum of congenital abnormalities and growth retardation that overlaps with those of DGAP025. To provide a biological correlate, we characterized a mutant mouse model with Chd2 disruption that is associated with embryonic and perinatal lethality. Expression analysis indicated that Chd2 is expressed in the heart, forebrain, extremities, facial and dorsal regions during specific times of embryonic development. Chd2(+/m) mice showed pronounced lordokyphosis, reduced body fat, postnatal runting, and growth retardation. These data suggest that haploinsufficiency for CHD2 could result in a complex of abnormal human phenotypes that includes scoliosis and possibly features similar to CHARGE syndrome.

Metabolic syndrome.

Hirsutism is a finding that can lead to subsequent metabolic diagnoses such as the metabolic syndrome. Metabolic syndrome describes a cluster of cardiometabolic risk factors associated with overweight and obesity. Although it has been the subject of some controversy, perhaps due to the many definitions proposed by different health organizations, metabolic syndrome is clinically relevant in that it is a predictor of vascular risk, even independent of any associated type 2 diabetes. While various definitions may differ in precise cut-off points, they uniformly emphasize key pathophysiologic processes: visceral obesity, dyslipidemia, insulin resistance, and hypertension. Management of metabolic syndrome focuses on methods of reducing the component risk factors, and therapies thus target the above processes as well as controlling inflammation and the prothrombotic state. Treatments can include not only pharmacologic approaches but behavior modification as well.