NAFLD in Some Common Endocrine Diseases: Prevalence, Pathophysiology, and Principles of Diagnosis and Management.

Secondary nonalcoholic fatty liver disease (NAFLD) defines those complex pathophysiological and clinical consequences that ensue when the liver becomes an ectopic site of lipid storage owing to reasons other than its mutual association with the metabolic syndrome. Disorders affecting gonadal hormones, thyroid hormones, or growth hormones (GH) may cause secondary forms of NAFLD, which exhibit specific pathophysiologic features and, in theory, the possibility to receive an effective treatment. Here, we critically discuss epidemiological and pathophysiological features, as well as principles of diagnosis and management of some common endocrine diseases, such as polycystic ovary syndrome (PCOS), hypothyroidism, hypogonadism, and GH deficiency. Collectively, these forms of NAFLD secondary to specific endocrine derangements may be envisaged as a naturally occurring disease model of NAFLD in humans. Improved understanding of such endocrine secondary forms of NAFLD promises to disclose novel clinical associations and innovative therapeutic approaches, which may potentially be applied also to selected cases of primary NAFLD.

Assessment of growth and metabolism characteristics in offspring of dehydroepiandrosterone-induced polycystic ovary syndrome adults.

Polycystic ovary syndrome (PCOS) is a common reproductive disorder that has many characteristic features including hyperandrogenemia, insulin resistance and obesity, which may have significant implications for pregnancy outcomes and long-term health of women. Daughters born to PCOS mothers constitute a high-risk group for metabolic and reproductive derangements, but no report has described potential growth and metabolic risk factors for such female offspring. Hence, we used a mouse model of dehydroepiandrosterone (DHEA)-induced PCOS to study the mechanisms underlying the pathology of PCOS by investigating the growth, developmental characteristics, metabolic indexes and expression profiles of key genes of offspring born to the models. We found that the average litter size was significantly smaller in the DHEA group, and female offspring had sustained higher body weight, increased body fat and triglyceride content in serum and liver; they also exhibited decreased energy expenditure, oxygen consumption and impaired glucose tolerance. Genes related to glucolipid metabolism such as Pparγ, Acot1/2, Fgf21, Pdk4 and Inhbb were upregulated in the liver of the offspring in DHEA group compared with those in controls, whereas Cyp17a1 expression was significantly decreased. However, the expression of these genes was not detected in male offspring. Our results show that female offspring in DHEA group exhibit perturbed growth and glucolipid metabolism that were not observed in male offspring.

Letrozole vs estradiol valerate induced PCOS in rats: glycemic, oxidative and inflammatory status assessment.

The objective of our study was to investigate glycemic, oxidative/antioxidative and inflammatory status in letrozole and estradiol valerate induced polycystic ovarian syndrome (PCOS) models. Sixty adult female Wistar rats were divided into four groups: L (0.2 mg letrozole/0.5 ml carboxymethyl cellulose (CMC), daily for 30 days), the control group CL, EV (one i.m. injection of 5 mg EV/0.5 ml sesame oil) and its corresponding control group CEV. After 30 days, ovarian morphology was assessed through ultrasound, serum free testosterone was determined, and an oral glucose tolerance test was performed. Blood, muscle, liver and periovarian adipose tissue (POAT) were collected for oxidative/antioxidative and inflammatory status evaluation. Free testosterone was increased only in the L group, while fasting glycemia was higher in the EV group. Both L and EV led to a significantly decreased level of muscle malondialehyde (MDA) and liver glutathione peroxidase (GPx) activity, while in POAT, MDA level diminished and GPx activity increased. The only difference between the two protocols was in muscle, where after L administration, GPx activity was significantly lower. Implementation of both protocols resulted in an increased expression of pNFKB in muscle, liver and POAT. The expression of monocyte chemoattractant protein 1 (MCP1) increased in liver and POAT after L administration, while in the EV group, MCP1 and STAT3 decreased in POAT. Our study shows that both protocols are characterized by an inflammatory environment in the usually insulin resistant tissues of human PCOS, without generating oxidative stress. In addition, EV has mild metabolic effects and unexpected interference with MCP1 expression in POAT, which require further investigation.

An assessment of the elastic properties of the aorta in nonobese women with polycystic ovary syndrome.

In this study, we determined that aortic stiffness was lower and aortic distensibility was higher in nonobese women with polycystic ovary syndrome (PCOS) who had similar characteristics with the control group in terms of lipid profile and insulin resistance. In the absence of traditional cardiovascular risk factors, it seems that there is no predisposition to atherosclerosis in nonobese women with PCOS.

Assessment of ovarian vascularization in the polycystic ovary by three-dimensional power Doppler ultrasonography.

OBJECTIVE: To assess whether there are differences in ovarian echogenicity and vascularization as assessed by three-dimensional power Doppler angiography (3D-PDA) between women with polycystic ovaries (PCO) and women with normal ovaries (NO). METHODS: Eighty-three women were classified into two groups according to the 2003 Rotterdam consensus criteria. The NO group comprised women (n = 45) with regular menstrual cycles and proven fertility, whereas the PCO group comprised women (n = 38) with oligo-anovulation, clinical and/or biochemical features of hyperandrogenism, and polycystic ovary morphology at two-dimensional ultrasound. All women were evaluated by means of 3D-PDA. The parameters studied in both groups were follicle number per ovary (FNPO), ovarian volume (OV), mean gray value (MG) and three vascular indices: vascularization index (VI), flow index (FI) and vascularization flow index (VFI). RESULTS: The PCO group showed a higher mean OV as well as FNPO. No differences in MG, VI, FI and VFI were found between the groups. CONCLUSIONS: 3D-PDA indices are not useful for discriminating between normal and polycystic ovaries.

Homeostasis model assessment-insulin resistance (HOMA-IR), a key role for assessing the ovulation function in polycystic ovary syndrome (PCOS) patients with insulin resistance.

According to our research, we evaluated that for the ovulation function in polycystic ovary syndrome (PCOS) with IR, Homeostasis model assessment-insulin resistance (HOMA-IR) is a clinic , simple and practical and sensitive Index for assessing the ovualtion failure. Meanwhile, after anti-IR treatment, HOMA-IR is also a reliable and simple for accessing the recoverying ovulation function.

Morphological assessment of polycystic ovary using transvaginal ultrasound.

A total of 104 patients with bilateral polycystic ovaries (PCO) diagnosed by transvaginal ultrasound were classified into four groups (A < 5 cysts, B 5-10 cysts, C > 10 cysts located under ovarian capsule, D numerous cysts distributed all over the ovary) according to the number of microcysts. Ovarian volume, clinical features (menstrual disturbance, obesity and hirsutism), endocrine levels [luteinizing hormone (LH), LH/follicle stimulating hormone ratio, testosterone, androstenedione and dehydroepiandrosterone-sulphate] and response to clomiphene were compared for each group and 17 control subjects with normal ovulatory cycles. Ovarian volume in PCO subjects was significantly larger than that in control subjects. As the number of microcysts increased, the ovarian volume enlarged and the endocrine abnormality worsened. All endocrine parameters in PCO subjects with menstrual disturbances were significantly higher than those in PCO subjects without menstrual disturbances and controls. In PCO subjects without menstrual disturbances only androstenedione was significantly higher than in controls. Among PCO subjects, the frequency of menstrual disturbances, the percentage of response to clomiphene and the pregnancy rate in groups C and D were significantly higher than in groups A and B. Therefore, screening the ovaries in infertile patients by means of transvaginal ultrasound and subsequent assessment of morphology in PCO may suggest endocrine abnormality and help in selecting the proper treatment.

Assessment of ovaries by magnetic resonance imaging in patients presenting with polycystic ovarian syndrome.

The demonstration of bilaterally enlarged ovaries with multiple small cysts at ultrasound is the morphological hallmark of polycystic ovarian syndrome (PCOS). However, a number of patients with clinical and biochemical diagnosis of PCOS have ovaries that are without sonographically visible discrete cysts. A better contrast resolution is obtained with magnetic resonance imaging (MRI) and enables visualization of organ structure not seen with other techniques. The purpose of the study was to relate the clinical and biochemical features of 10 patients presenting with a PCOS profile to magnetic resonance imaging and to compare these findings with those observed at ultrasound. With MRI, at least one ovary typical of PCOS could be visualized in eight patients, while this was the case in only three patients with ultrasound. The ultrasound examinations were indeed equivocal in the majority of patients (seven cases). No apparent relationship could be found between the clinical and biochemical parameters and ovarian morphology assessed by MRI or ultrasound. In summary, the present study supports the superiority of MRI technique to assess ovarian morphology over the ultrasound technology used in our study. However, the recent technological advances in ultrasound, and specifically the advent of high frequency transvaginal sonography, will be of particular interest in the study of PCOS.