Non-alcoholic fatty liver disease through the female lifespan: the role of sex hormones.

The prevalence of non-alcoholic fatty liver disease (NAFLD) differs between various stages of the female lifespan. The aim of this review is to summarize current evidence on the association of NAFLD and circulating sex hormones and to explore the pathogenesis of NAFLD within the context of (1) sex hormone changes during the reproductive, post-reproductive female life and beyond and (2) the in vitro and in vivo evidence on pharmacological modulation in women on menopausal hormone treatment (MHT) or endocrine therapy after breast cancer. The fluctuation in estrogen concentrations, the relative androgen excess, and the age-related reduction in sex hormone-binding globulin are related to increased NAFLD risk. Moreover, the peri-menopausal changes in body composition and insulin resistance might contribute to the increased NAFLD risk. Whether MHT prevents or improves NAFLD in this population remains an open question. Studies in women with breast cancer treated with tamoxifen or non-steroidal aromatase inhibitors point to their adverse effects on NAFLD development, although a more pronounced effect of tamoxifen is reported. Future studies focusing on the underlying pathogenesis should identify subgroups with the highest risk of NAFLD development and progression into more aggressive forms, as well as elucidate the role of hormone therapies, such as MHT.

Ovarian tissue cryopreservation and transplantation to delay menopause: facts and fiction.

Ovarian tissue cryopreservation and transplantation (OTCT) is increasingly being used in young cancer patients for fertility restoration and prevention of premature ovarian insufficiency (POI) and has recently been advocated as a method to delay menopause. This is accomplished by cryopreserving ovarian tissue that is excised laparoscopically in thin pieces at a young age. Cryopreserved tissue will be transplanted at menopause, when ovarian function is no longer present. Transplantation may need to be repeated several times to achieve long-term restoration of ovarian function. However, it is unknown whether ovarian grafts result in a normal steroid pulsatile secretion, similar to that present during reproductive years. In addition, it is not known whether the need to restore ovarian activity appears earlier in women who undergo OTCT to delay menopause, although indirect data suggest that this is likely to be true. Until today, no cohort or comparative studies evaluating OTCT as a potential alternative to hormone replacement therapy (HRT) have been published and, thus, there is no evidence to suggest that OTCT is superior to HRT in terms of both efficacy and safety. Given the availability of alternative, established treatments for managing menopausal symptoms, as well as the multiple unanswered questions regarding the method, it is imperative that, before OTCT is regarded as a mainstream technique for management of menopausal symptoms, further evaluation and clinical investigation are undertaken.

EAA clinical practice guidelines-gynecomastia evaluation and management.

BACKGROUND: Gynecomastia (GM) is a benign proliferation of the glandular tissue of the breast in men. It is a frequent condition with a reported prevalence of 32-65%, depending on the age and the criteria used for definition. GM of infancy and puberty are common, benign conditions resolving spontaneously in the majority of cases. GM of adulthood is more prevalent among the elderly and proper investigation may reveal an underlying pathology in 45-50% of cases. OBJECTIVES: The aim was to provide clinical practice guidelines for the evaluation and management of GM. MATERIALS AND METHODS: A literature search of articles in English for the term 'gynecomastia' was conducted. Evidence-based recommendations were developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. RESULTS: A set of five statements and fifteen clinical recommendations was formulated. CONCLUSIONS: The purpose of GM assessment should be the detection of underlying pathological conditions, reversible causes (administration/abuse of aggravating substances), and the discrimination from other breast lumps, particularly breast cancer. Assessment should comprise a thorough medical history and physical examination of the breast and genitalia (including testicular ultrasound). A set of laboratory investigations may integrate the evaluation: testosterone (T), estradiol (E2), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicular stimulating hormone (FSH), thyroid stimulating hormone (TSH), prolactin, human chorionic gonadotropin (hCG), alpha-fetal protein (AFP), liver and renal function tests. Breast imaging may be used whenever the clinical examination is equivocal. In suspicious lesions, core needle biopsy should be sought directly instead. Watchful waiting is recommended after treatment of underlying pathology or discontinuation of substances associated with GM. T treatment should be offered to men with proven T deficiency. The use of selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs) and non-aromatizable androgens is not justified in general. Surgical treatment is the therapy of choice for patients with long-lasting GM. SUMMARY OF STATEMENTS (S) AND RECOMMENDATIONS (R): S1. Gynecomastia (GM) is a benign proliferation of glandular tissue of the breast in males. S2. GM of infancy is a common condition that usually resolves spontaneously, typically within the first year of life. S3. GM of puberty is a common condition, affecting approximately 50% of mid-pubertal boys; in more than 90% of cases, it resolves spontaneously within 24 months. S4. The prevalence of GM in adulthood increases with increasing age; proper investigation may reveal an underlying pathology in approximately 45-50% of the cases. S5. Male breast cancer is rare; GM should not be considered a premalignant condition. The following recommendations are divided into 'strong', denoted by the number 1 and associated with the terminology 'we recommend', and 'weak' denoted by the number 2 and associated with the phrase 'we suggest'. The grading of the quality of evidence is denoted as follows: ⊕○○○ for very low-quality evidence; ⊕⊕○○ for low quality; ⊕⊕⊕○ for moderate quality; and ⊕⊕⊕⊕ for high quality. R1. The presence of an underlying pathology should be considered in GM of adulthood. We recommend that the identification of an apparent reason for GM in adulthood, including the use of medication known to be associated with GM, should not preclude a detailed investigation (1 ⊕⊕⊕○). R2. We suggest that the initial screening to rule out lipomastia, obvious breast cancer, or testicular cancer might be performed by a general practitioner or another non-specialist (2 ⊕○○○). R3. We recommend that in those cases where a thorough diagnostic workup is warranted, it should be performed by a specialist (1 ⊕○○○). R4. We recommend that the medical history should include information on the onset and duration of GM, sexual development and function, and administration or abuse of substances associated with GM (1 ⊕⊕⊕○). R5. We recommend that the physical examination should detect signs of under-virilization or systemic disease (1 ⊕⊕⊕⊕). R6. We recommend that breast examination should confirm the presence of palpable glandular tissue to discriminate GM from lipomastia (pseudo-gynecomastia) and rule out the suspicion of malignant breast tumor (1 ⊕⊕⊕⊕). R7. We recommend that the physical examination should include the examination of the genitalia to rule out the presence of a palpable testicular tumor and to detect testicular atrophy (1 ⊕⊕⊕⊕). R8. We recommend that genitalia examination is aided by a testicular ultrasound, as the detection of a testicular tumor by palpation has low sensitivity (1 ⊕⊕○○). R9. We suggest that a set of evaluations may include T, E2 , SHBG, LH, FSH, TSH, prolactin, hCG, AFP, and liver and renal function tests (2 ⊕⊕○○). R10. We suggest that breast imaging may offer assistance, where the clinical examination is equivocal (2 ⊕⊕○○). R11. We suggest that, if the clinical picture is suspicious for a malignant lesion, core needle biopsy should be performed (2 ⊕⊕○○). R12. We recommend watchful waiting after treatment of underlying pathology or discontinuation of the administration/abuse of substances associated with GM (1 ⊕⊕○○). R13. We recommend that T treatment should be offered only to men with proven testosterone deficiency (1 ⊕⊕⊕○). R14. We do not recommend the use of selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs), or non-aromatizable androgens in the treatment of GM in general (1 ⊕⊕○○). R15. We suggest surgical treatment only for patients with long-lasting GM, which does not regress spontaneously or following medical therapy. The extent and type of surgery depend on the size of breast enlargement, and the amount of adipose tissue (2 ⊕⊕○○).

European Academy of Andrology guideline Management of oligo-astheno-teratozoospermia.

BACKGROUND: Oligo-astheno-teratozoospermia is frequently reported in men from infertile couples. Its etiology remains, in the majority of cases, unknown with a variety of factors to contribute to its pathogenesis. The aim of this European Academy of Andrology guideline was to provide an overview of these factors and to discuss available management options. MATERIALS AND METHODS: PubMed was searched for papers in English for articles with search terms: male infertility and oligo-astheno-teratozoospermia. For evidence-based recommendations, the GRADE system was applied. Issues related to urogenital infections/inflammations have not been included in this document as they will be covered by separate guidelines. RESULTS: For men with oligo-astheno-teratozoospermia, the European Academy of Andrology recommends: A general physical examination to assess signs of hypogonadism. A scrotal physical examination to assess (i) the testes and epididymes for volume and consistency, (ii) deferent ducts for total or partial absence, and (iii) occurrence of varicocoele. Performing two semen analyses, according to World Health Organization guidelines to define an oligo-astheno-teratozoospermia. An endocrine evaluation. A scrotal ultrasound as part of routine investigation. Karyotype analysis and assessment of Yq microdeletions in infertile men with a sperm concentration ≤5 × 106 /mL. Cystic fibrosis transmembrane conductance regulator gene evaluation in case of suspicion for incomplete congenital obstruction of the genital tract. Against quitting physical activity to improve the chance of achieving pregnancy. Against androgen replacement therapy to improve the chance of achieving pregnancy. Assisted reproduction techniques to improve the chance of achieving pregnancy, in case other treatment options are not available or not efficient. Androgen replacement therapy in patients with biochemical/clinical signs of hypogonadism, after completion of the fertility treatment. CONCLUSION: These guidelines can be applied in clinical work and indicate future research needs.

Effects of treatment for psoriasis on circulating levels of leptin, adiponectin and resistin: a systematic review and meta-analysis.

BACKGROUND: Metabolic syndrome, a risk factor of cardiovascular disease, is more common in patients with psoriasis than in the general population. Circulating adipokine concentrations are altered in patients with psoriasis and are suggested to represent the pathophysiological link between psoriatic lesions and metabolic alterations. OBJECTIVES: To perform a systematic review of the literature for studies that investigated possible differences in circulating levels of leptin, adiponectin or resistin in patients with psoriasis before and after any treatment intervention, and to meta-analyse the best evidence available. METHODS: A search was conducted in three databases (PubMed, Central and Embase). Eligible for the review were studies that assessed leptin, adiponectin or resistin concentrations in patients with psoriasis before and after any topical or systemic treatment. RESULTS: After treatment, blood concentrations of leptin were similar to those before treatment [standardized mean difference (SMD) 0·06, 95% confidence interval (CI) -0·09 to 0·20], with no heterogeneity among studies (I2 = 0%, P = 0·88). After treatment, blood concentrations of adiponectin were similar to those before treatment (SMD -0·14, 95% CI -0·34 to 0·05), with significant heterogeneity among studies (I2 = 36·8%, P = 0·032). After treatment, blood concentrations of resistin were significantly lower than those before treatment (SMD 0·50, 95% CI 0·20-0·79), with significant heterogeneity among studies (I2 = 61·4%, P < 0·001). CONCLUSIONS: There is no evidence that treatment for psoriasis modifies leptin and adiponectin concentrations. However, treatment intervention reduces resistin concentrations, a finding that is expected to be of clinical importance.

Ultraviolet radiation and effects on humans: the paradigm of maternal vitamin D production during pregnancy.

Current evidence indicates that neonates born of mothers with vitamin D deficiency during pregnancy have greater risk for developing hypocalcemia, rickets and extra-skeletal disorders. Despite the classic knowledge that ultraviolet-B (UVB) exposure is the most efficient way for a future mother to obtain optimal vitamin D concentrations, no current consensus or clinical recommendations exist regarding the duration and timing of UVB exposure for pregnant women. This article offers a narrative review of available data regarding how UVB exposure affects maternal vitamin D production during pregnancy, along with a discourse on clinical implications of this public health issue. Future studies would benefit from adopting UVB exposure estimates to recommend appropriate UVB exposure to pregnant women. Doing so could provide a more holistic and practical approach in managing maternal hypovitaminosis D during pregnancy.

Hypovitaminosis D in pregnancy in the Mediterranean region: a systematic review.

Despite high levels of sunshine, maternal hypovitaminosis D during pregnancy is prevalent in the Mediterranean region. The aim of this study is to systematically review trials that investigated vitamin D concentrations during pregnancy in this region, in order to determine predictors of hypovitaminosis D and explain this phenomenon. After applying inclusion/exclusion criteria, 15 studies were entered into the systematic review involving 2649 pregnant women and 820 neonates. The main outcome was maternal vitamin D status, assessed by serum 25-hydroxy-vitamin D (25(OH)D) concentrations. Possible predictors of the outcome included maternal age, body mass index (BMI), race, socioeconomic status, skin type, gestational age, sun exposure, calcium and vitamin D intake and supplementation, smoking status, parity and season of delivery. Studies differed widely in vitamin D deficiency criteria, method of measurement and outcomes. The prevalence of vitamin D insufficiency ranges from 9.3 to 41.4%, whereas that of vitamin D deficiency from 22.7 to 90.3%. A positive association with 25(OH)D concentrations exists for light skin color, white race, uncovered dressing pattern, maternal vitamin D supplementation and season of gestation (spring/summer). An inverse association exists for BMI and gestational age, whereas data for smoking and socioeconomic status are controversial. We concluded that vitamin D deficiency in pregnancy seems to be quite common, even in the Mediterranean region. Racial, social and cultural habits, as well as the absence of preventive supplementation/dietary strategies, seem to negate the benefits of sun exposure.

Obesity in the ageing man.

As the population is ageing globally, both ageing and obesity are recognized as major public health challenges. The aim of this narrative review is to present and discuss the current evidence on the changes in body composition, energy balance and endocrine environment that occur in the ageing man. Obesity in the ageing man is related to changes in both body weight and composition due to alterations in energy intake and total energy expenditure. In addition, somatopenia (decreased GH secretion), late-onset hypogonadism (LOH), changes in thyroid and adrenal function, as well as changes in appetite-related peptides (leptin, ghrelin) and, most importantly, insulin action are related to obesity, abnormal energy balance, redistribution of the adipose tissue and sarcopenia (decreased muscle mass). A better understanding of the complex relationship of ageing-related endocrine changes and obesity could lead to more effective interventions for elderly men.

Selenomethionine treatment in patients with autoimmune thyroiditis: a prospective, quasi-randomised trial.

AIMS: To test whether selenium administration affects autoantibodies to thyroid peroxidase (anti-TPO) and thyroglobulin (anti-TG) titres in chronic autoimmune (Hashimoto's - HT) thyroiditis. METHODS: A prospective, open-label, quasi-randomised study in 86 HT patients (n = 86) assigned to either selenomethionine (Seme) 200µg daily for 3 months (Se3, n = 15) or 6 months (Se6, n = 46) or placebo (Control, n = 25). Serum Se, anti-TPO, anti-TG and thyroid hormones were measured in all patients at baseline, 3 and 6 months. A subgroup of 18 patients (twelve on Se6 and six controls) were subjected in thyroid fine-needle biopsy at baseline and 6 months to detect changes in lymphocyte infiltration. RESULTS: No significant difference in anti-TPO levels was recorded after 3 (p = 0.88) or 6 months (p = 0.62) on Seme. Anti-TG levels decreased both at 3 months (p = 0.001) and 6 months (p = 0.001). No significant changes in thyroid stimulating hormone, free thyroxine and free triiodothyronine levels or in the lymphocytes' number in thyroid cytology specimens were detected. Age, gender, duration of disease, baseline anti-TPO levels and per cent change in Se levels could not predict the response of anti-TPO levels to Seme administration. CONCLUSION: Our data suggest that Seme administration in pharmacological doses for a period of 6 months seems to have no significant effect on serum thyroid auto-antibodies' levels or lymphocyte infiltration of the thyroid gland.

Hormone therapy for postmenopausal endometrial cancer survivors: a survey among Greek obstetricians-gynaecologists.

PURPOSE OF INVESTIGATION: In this study we evaluated the prescription attitude of Greek obstetricians-gynaecologists towards hormone replacement therapy (HRT) for endometrial cancer survivors. METHODS: An anonymous questionnaire was sent to 900 members of the Hellenic Society of Obstetrics and Gynaecology, presenting a hypothetical case of an endometrial cancer survivor with indications for HRT, followed by a series of relevant questions. RESULTS: Three hundred and three valid responses were received and analysed according to age, gender and practice setting. HRT would be prescribed by 30.4% of gynaecologists; as far as type of regimen is concerned, 67.4% would prescribe tibolone, 22.8% estrogen-only and 9.8% estrogen plus progestagen. In contrast, 69.6% would not prescribe HRT due to the fear of endometrial cancer recurrence (88.2%), development of breast cancer (2.8%) or both (4.7%); among them, 28.4% would prescribe central nervous system (CNS) medications, selective estrogen receptor modulators (SERMs), phyto-oestrogens or biphosphonates, as alternates. CONCLUSIONS: One out of three Greek gynaecologists would prescribe HRT to endometrial cancer survivors. Alternative therapies, mainly CNS medications, would be suggested by the opposers.

Gabapentin and pregabalin in the treatment of fibromyalgia: a systematic review and a meta-analysis.

WHAT IS KNOWN AND OBJECTIVES: Fibromyalgia (FBM) is a common chronic pain disorder affecting up to 2% of the general population. Current treatment options are mostly symptom-based and limited both in efficacy and number. Two promising alternatives are gabapentin (GP) and pregabalin (PB). We aimed to estimate the efficacy and safety/tolerability of the two compounds in FBM through a systematic review and a meta-analysis of relevant randomized double-blind placebo-controlled (RCT) were performed. DATA SOURCES, EXTRACTION AND ANALYSIS: A literature search was conducted through MEDLINE, EMBASE, Cochrane CENTRAL and the reference lists of relevant studies. Responders to treatment (>30% reduction in mean pain score) and dropouts due to lack of efficacy were used as primary outcome measures. Dropout rates and incidence of common adverse outcomes were also investigated. Four RCTs, reporting data on 2040 patients, were reviewed and three of them using PG were included in the meta-analysis. RESULTS: Pregabalin at a dose of 600, 450 and 300 mg per day is effective in FBM compared to placebo (NNT: 7, upper 95% CI: 12, 450 mg). A number of adverse events (AE), such as dizziness, somnolence, dry mouth, weight gain, peripheral oedema, is consistently associated with treatment at any dose and could lead one out of four patients to quit treatment (NNH: 6, lower 95% CI: 4, 600 mg). Indirect comparison meta-analysis suggests that PB at a dose of 450 mg per day could result in more responders than at 300 mg, but this result needs to be interpreted with caution as there were no significant differences between 600 and 300 mg or between 600 and 450 mg. Data on GP is limited. WHAT IS NEW AND CONCLUSIONS: The analysis indicates that PB at a dose of 450 mg per day is most likely effective in treating FBM, although AE are not negligible. Further evidence is necessary for more conclusive inferences.

Efficacy and safety of denosumab in postmenopausal women with osteopenia or osteoporosis: a systematic review and a meta-analysis.

Receptor activator of nuclear factor-kappaB ligand (RANKL) is a cytokine essential for osteoclast differentiation, activation, and survival. Denosumab, a human monoclonal antibody against RANKL, constitutes a promising antiresorptive agent for osteoporosis. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), and other trial registries through January 2009. We selected randomized controlled trials (RCTs) of denosumab in women with low bone mass that described the changes on bone markers and bone mineral density (BMD) as well as the adverse events including fracture risk. We analyzed data from nine RCTs involving 10 329 participants. Although denosumab universally decreased bone markers and increased lumbar and hip BMD, the efficacy evaluation based on percentage (%) mean change from the baseline was not possible due to missing data. Denosumab was not associated with a significant reduction in fracture risk [OR (95% CI) 0.74 (0.33 to 1.64), p=0.45]. Increased risk of serious adverse events [OR (95% CI) 1.83 (1.10 to 3.04), p=0.02] and serious infections [OR (95% CI) 4.45 (1.15 to 17.14), p=0.03] were evident. In conclusion, although effective as an antiresorptive agent, denosumab has not yet proved its efficacy on fracture risk reduction while increased infection risk questions its safety.

Adiponectin levels in women with polycystic ovary syndrome: a systematic review and a meta-analysis.

BACKGROUND: Conflicting results regarding adiponectin levels in women with polycystic ovary syndrome (PCOS) have been reported. To evaluate adiponectin levels in PCOS, a systematic review of all studies comparing adiponectin levels in women with PCOS with healthy controls and a meta-analysis of those involving women with similar body mass index (BMI) were performed. The influence of possible effect modifiers, such as insulin resistance (IR) and testosterone, was investigated. The influence of obesity was investigated through a 'nested' meta-analysis after within-study BMI stratification and appropriate pooling. METHODS: Literature search was conducted through MEDLINE, EMBASE, Cochrane CENTRAL (through June 2008), references from relevant studies and personal contact with the authors. Thirty-one studies, reporting data on 3469 subjects, were reviewed and 16 included in the main meta-analysis. RESULTS: Women with PCOS demonstrated significantly lower adiponectin values [weighted mean difference (95% confidence interval) -1.71 (-2.82 to -0.6), P < 10(-4)], yet with significant between-study heterogeneity. Lower adiponectin levels are associated with the IR observed in women with PCOS, compared with controls. IR, but not total testosterone, was found significant among biological parameters explored in the meta-regression model. Hypoadiponectinaemia was present in both lean and obese women with PCOS when compared with non-PCOS counterparts. Data on high molecular weight (HMW) adiponectin are limited (three studies). CONCLUSIONS: After controlling for BMI-related effects, adiponectin levels seem to be lower in women with PCOS compared with non-PCOS controls. Low levels of adiponectin in PCOS are probably related to IR but not to testosterone. Total adiponectin should not be used as a biomarker of PCOS severity. Further investigation is needed for HMW adiponectin levels in PCOS.

Hormone therapy for postmenopausal breast cancer survivors: a survey among obstetrician-gynaecologists.

PURPOSE OF INVESTIGATION: To investigate the attitude of Greek obstetrician-gynaecologists towards prescription of hormone therapy to postmenopausal breast cancer survivors. METHODS: An anonymous questionnaire was sent to members of the Hellenic Society of Obstetrics and Gynaecology with a hypothetical case and a series of relevant questions. RESULTS: Three hundred valid answers were received. Hormone therapy would be prescribed to a breast cancer survivor by only 8%; 80% of these would prefer tibolone. In contrast, 92% would not prescribe hormone therapy; 97% would do so due to the risk of disease recurrence; 70% would not prescribe any alternative therapy, 21% would prescribe CNS-active compounds and 7% SERMs. CONCLUSIONS: The vast majority of Greek obstetrician-gynaecologists would not prescribe hormone therapy for menopausal symptoms in breast cancer survivors due to the theoretical risk of disease recurrence. Among those who would not prescribe hormone therapy, 21% would opt to CNS-active compounds.

The use of demographic, ultrasonographic and scintigraphic data in the diagnostic approach of thyroid nodules.

INTRODUCTION: Thyroid nodules are a common diagnostic challenge mainly because of the need to exclude thyroid malignancy. The aim of this study was to evaluate the usefulness of demographic, ultrasonographic and scintigraphic findings in differentiating benign from malignant thyroid lesions in patients presenting with thyroid nodules. MATERIALS AND METHODS: 941 patients, who presented with palpable thyroid nodules and underwent at least one fine-needle aspiration biopsy (FNAB), were retrospectively evaluated. RESULTS: The thyroid was assessed by ultrasonography (US) in 796 patients and by scintigraphy (SC) in 774 patients. The final diagnostic outcome was established after surgery (n=183) or after a minimum of one-year clinical follow-up period. Higher rates of malignancy were observed in male gender (p<0.001), in patients presenting with a solitary nodule in US (p<0.001), in nodules with maximum diameter > or =4.5 cm in US (p=0.024) and in nodules detectable by SC (p=0.006). There were no statistical differences in the rates of malignancy among cystic, solid or mixed nodules in US or among "hot", "warm" or "cold" nodules in SC. CONCLUSIONS: Male gender, solitary nodule and nodule diameter > or =4.5 cm can serve as adjuncts to FNAB in predicting the risk of thyroid malignancy in patients presenting with thyroid nodules.

Epidemiologic analysis of thyroid fine needle aspiration biopsies over a period of 18 years (1987-2004).

INTRODUCTION: Fine Needle Aspiration Biopsy (FNA) is a method widely used in the assessment of thyroid nodules. The main aim of this 18-year retrospective study was the investigation of the diagnostic value of FNA cytology in thyroid malignancy. SUBJECTS AND METHODS: We retrospectively reviewed 1376 patients who underwent 1938 FNAs from 1987 to 2004 in the Department of Endocrinology, "Hippokration" General Hospital, Thessaloniki, Greece. Of them 178 subsequently underwent total or subtotal thyroid resection and a pathology report was available. RESULTS: FNA cytology shows a sensitivity of 76.2% and a specificity of 90.5% for thyroid malignancy, with a significant agreement between FNA cytology and the histology following resection surgery (Cohen's method, p<0.05). There was a considerable improvement in the diagnostic value of FNA cytology during the sub-period 1996-2004 as compared to the sub-period 1987-1995. CONCLUSIONS: 1) FNA is a reliable diagnostic method in the assessment of thyroid malignancy, 2) a non-diagnostic FNA should always be repeated, 3) meticulous follow-up is mandatory, even after a cytological result of benign hyperplasia and 4) increased experience can improve the diagnostic value of FNA in thyroid malignancy.

Serum osteoprotegerin and RANKL are not specifically altered in women with postmenopausal osteoporosis treated with teriparatide or risedronate: a randomized, controlled trial.

Risedronate and teriparatide have opposite actions on the osteoblast-osteoclast dipole and are expected to influence the RANK/RANKL/osteoprotegerin (OPG) system. We aimed to evaluate changes in serum OPG and RANKL after risedronate or teriparatide administration in postmenopausal osteoporotic women. Seventy-four postmenopausal Caucasian women (age 64.1+/-1.0 years) were studied. Women with osteopenia served as controls (group 1, n=30). Women with osteoporosis were randomly assigned to either risedronate 35 mg once weekly (group 2, n=21) or teriparatide 20 microg once daily (group 3, n=23) for six months. Blood samples for serum RANKL, OPG, N-terminal propeptide of type 1 collagen (P1NP), and C-terminal telopeptide of type 1 collagen (CTx) were obtained before treatment and three and six months after treatment. P1NP and CTx levels remained unchanged in group 1, decreased in group 2 (p<0.001), and increased in group 3 women (p<0.001) throughout the treatment. OPG levels remained unchanged while RANKL decreased gradually in all groups (p<0.001). There was no correlation between OPG or RANKL and P1NP or CTx. Our data suggest that neither antiresorptive nor osteoanabolic therapy causes specific alterations of serum OPG/RANKL levels; therefore, these cytokines cannot substitute for the established markers of bone turnover in the monitoring of response to osteoporosis treatment.

Post-partum thyroiditis in a mediterranean population: a prospective study of a large cohort of thyroid antibody positive women at the time of delivery.

Post-partum thyroiditis (PPT) is a common disease with important clinical sequelae. Its clinical features, association with antimicrosomal antibodies (TPOAb) and long-term prognosis are not thoroughly described in Mediterranean populations. The aims of this study were: 1) to describe clinical features of PPT in a Greek population, 2) to associate TPOAb with PPT presence, and 3) to identify long-term prognosis of PPT. 1,594 consecutive post-partum women were studied within 3 days of their delivery. Women with positive TPOAb were followed-up for one yr for clinical and biochemical evidence of PPT. Incidence of positive TPOAb was 5.2% whereas incidence of PPT was 2.4%. PPT was presented as hyperthyroidism alone (18%), hypothyroidism alone (40%) and hyperthyroidism followed by hypothyroidism (42%). A titer of 1:1600, immediately post-partum, could predict PPT with 97% sensitivity and 91% specificity. History of PPT in previous pregnancies was associated with PPT in the current pregnancy. This association did not exist with maternal age, gestation duration, parity, abortions, sex of the newborn, birth-weight or smoking. Long-term hypothyroidism developed in 21% of women. Observation and post-partum thyroid function testing, where PPT is suspected, seems to constitute the best clinical approach. There is need for long-term follow-up in PPT patients.

Interleukin-1 beta and tumor necrosis factor-alpha in normal/infertile men.

Cytokines play an important role in intercellular communications. Human sperm contains a wide spectrum of cytokines. such as interleukin-1 beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha). Their effects on semen quality are subject to debate. The aim of this study was to determine concentrations of IL-1beta and TNF-alpha in normal fertile men and in different groups of male infertility in an attempt to clarify the physiology and suggest possible clinical uses. Sixty-six subfertile male patients with varicocele (n = 22). infection of accessory genital glands (n = 14), varicocele plus infection (n = 4), chronic epididymitis (n = 8). post-renal transplantation status (n = 5), idiopathic oligoasthenoteratospermia (n = 9), cryptorchidism (n = 1), and homozygous beta-thalassemia (n = 3) as well as 5 male controls were studied through history, physical examination, spermiograms, plasma basal hormonal levels, and IL-1beta and TNF-alpha levels in seminal fluid. There was no significant statistical difference regarding IL-1beta and TNF-alpha among fertile men and subfertile patients of any cause. 1L-1beta and TNF-alpha were in tight positive correlation (p<.001). Determination of IL-1beta and TNF-alpha does not provide useful information in male routine infertility workup. Nevertheless, a better understanding of these mediators in semen of normal men and infertile patients may contribute to a new approach to the management of male infertility.

Ambiguous genitalia, 45,X/46,XY mosaic karyotype, and Y chromosome microdeletions in a 17-year-old man.

OBJECTIVE: To describe clinical and laboratory features of a patient with 45,X/46,XY mosaic karyotype and Y chromosome microdeletions and to discuss the diagnostic problems in his management. DESIGN: Case report. SETTING: University department. PATIENT(S): A 17-year-old man with ambiguous genitalia, 45,X/46,XY mosaic karyotype, and Y chromosome microdeletions. INTERVENTION(S): Testicular ultrasonography, karyotype, open testicular biopsy, polymerase chain reaction (PCR) screening for cystic fibrosis, PCR screening for Y chromosome microdeletions in peripheral blood and testicular tissue, and reverse transcriptase PCR in testicular tissue for Y chromosome microdeletions. MAIN OUTCOME MEASURE(S): Avoidance of dissemination of testicular cancer. RESULT(S): The patient was referred for bilateral orchiectomy. CONCLUSION(S): 45,X/46,XY mosaic karyotype is associated with a broad spectrum of phenotypes that includes female with Turner syndrome, male with mixed gonadal dysgenesis, male pseudohermaphroditism, and apparently normal male. Microdeletions of the long arm of the Y chromosome may be associated with Y chromosomal instability, leading to formation of 45,X cell lines. 45,X/46,XY males carry an increased risk for gonadal tumors and must be followed closely.