Serum thyrotropin is a better predictor of future thyroid dysfunction than thyroid autoantibody status in biochemically euthyroid patients with diabetes: implications for screening.

AIM: To ascertain the predictive values of thyroid autoantibodies and thyrotropin (TSH) levels for subsequent thyroid dysfunction in patients with diabetes. METHODS: Review of records of 467 patients who had attended diabetes clinics for a mean of 6.1 years. Baseline autoantibody and TSH results and thyroid status at annual review were determined. RESULTS: Thyroid disorders were known in 29 patients (6.2%), and newly identified in 32 (6.9%), at presentation. Of 406 patients with normal baseline thyroid status, 24 (5.9%) developed thyroid dysfunction during 6.1 years of mean follow-up. Higher baseline TSH concentration was associated with subsequent hypothyroidism; a threshold of 1.53 mU/L, approximately defining the top quartile, provided 75% sensitivity and specificity. Both TSH greater than 1.53 mU/L and positive autoantibody status predicted thyroid dysfunction, but only TSH was significant in multivariable analysis (odds ratio, 7.74, p < 0.001). No overt thyroid dysfunction developed in 293 patients with baseline TSH levels less than 1.53 mU/l. CONCLUSIONS: Baseline TSH level may be a better predictor of thyroid dysfunction than thyroid autoantibodies in people with diabetes. Patients with TSH levels below the top quartile have a risk of thyroid dysfunction similar to the general population. It may be appropriate to stop annual thyroid screening in this group, although confirmation is required.     

Ovarian function after hysterectomy in an Irish hospital population.

A group of 52 women following hysterectomy with conservation of one or both ovaries was compared with an age-matched control group attending with menstrual irregularity/menorrhagia, in terms of proportions of women with postmenopausal endocrine profiles, and climacteric symptoms. The mean age for the groups was 42 years, and the mean interval between hysterectomy and the time of the study was 3.5 years. Endocrine levels were postmenopausal in six study and two control patients, and this difference was not significant. Vasomotor symptoms were a complaint of 28 (54%) of the study group and 18 (35%) of the control group, while 30 (58%) and 18 (35%) respectively had at least two other non-specific symptoms. In the absence of prospective studies elucidating the effect of hysterectomy on ovarian function, endocrine profiles should be performed in hysterectomised women complaining of symptoms.     

Glucocorticoid exposure in late gestation permanently programs rat hepatic phosphoenolpyruvate carboxykinase and glucocorticoid receptor expression and causes glucose intolerance in adult offspring.

Low birth weight in humans is predictive of insulin resistance and diabetes in adult life. The molecular mechanisms underlying this link are unknown but fetal exposure to excess glucocorticoids has been implicated. The fetus is normally protected from the higher maternal levels of glucocorticoids by feto-placental 11beta-hydroxysteroid dehydrogenase type-2 (11beta-HSD2) which inactivates glucocorticoids. We have shown previously that inhibiting 11beta-HSD2 throughout pregnancy in rats reduces birth weight and causes hyperglycemia in the adult offspring. We now show that dexamethasone (a poor substrate for 11beta-HSD2) administered to pregnant rats selectively in the last week of pregnancy reduces birth weight by 10% (P < 0.05), and produces adult fasting hyperglycemia (treated 5.3+/-0.3; control 4.3+/-0.2 mmol/ liter, P = 0.04), reactive hyperglycemia (treated 8.7+/-0.4; control 7.5+/-0.2 mmol/liter, P = 0.03), and hyperinsulinemia (treated 6.1+/-0.4; control 3.8+/-0.5 ng/ml, P = 0.01) on oral glucose loading. In the adult offspring of rats exposed to dexamethasone in late pregnancy, hepatic expression of glucocorticoid receptor (GR) mRNA and phosphoenolpyruvate carboxykinase (PEPCK) mRNA (and activity) are increased by 25% (P = 0.01) and 60% (P < 0.01), respectively, while other liver enzymes (glucose-6-phosphatase, glucokinase, and 11beta-hydroxysteroid dehydrogenase type-1) are unaltered. In contrast dexamethasone, when given in the first or second week of gestation, has no effect on offspring insulin/glucose responses or hepatic PEPCK and GR expression. The increased hepatic GR expression may be crucial, since rats exposed to dexamethasone in utero showed potentiated glucose responses to exogenous corticosterone. These observations suggest that excessive glucocorticoid exposure late in pregnancy predisposes the offspring to glucose intolerance in adulthood. Programmed hepatic PEPCK overexpression, perhaps mediated by increased GR, may promote this process by increasing gluconeogenesis.     

Prevention of mother-to-child transmission of HIV infection: Views and perceptions about swallowing nevirapine in rural Lilongwe,Malawi

Background  

In 2006 the World Health Organization described the status of prevention of mother to child transmission (PMTCT) service implementation as unacceptable, with an urgent need for a renewed public health approach to improve access. For PMTCT to be effective it needs to be accessible, acceptable and affordable; however research in Africa into accessibility, uptake and acceptability of PMTCT services has been predominately urban based and usually focusing on women who deliver in hospitals. The importance of involving other community members to strengthen both PMTCT uptake and adherence, and to support women emotionally, has been advocated. Urban men's and rural traditional birth attendants' (TBAs) involvement have improved uptake of HIV testing and of nevirapine.     

Perspectives of normal child development in rural Malawi – a qualitative analysis to create a more culturally appropriate developmental assessment tool

Background Child development in developing countries is often evaluated using assessment tools created for ‘Western’ settings. Recent work has demonstrated that, for certain developmental milestones, ‘Western’ tools may be inaccurate as they include items unfamiliar to children of different cultural settings. Methods We used qualitative methods to gather information about normal development in an African setting. Ten village and two professional focus group discussions (FGDs) were conducted. We used purposive sampling methods to recruit groups of mothers, grandmothers and men in four areas of Southern Malawi for village FGDs. Separate FGDs were carried out with professionals working in areas relating to child development. A thematic content analysis established main patterns and themes and dissemination of results and continued feedback allowed for respondent validation and reflection of results. The information then gathered was used to create questions for a revised Malawian developmental assessment tool. Results Social and gross motor milestones were the main focus of interest for village and professional FGDs with the latter creating new language and fine motor concepts. Social milestones highlighted included ‘duties and chores’, ‘sharing’ and ‘taking up leadership roles’. Language milestones included ‘reporting events’ and ‘shrugging to indicate no’ and fine motor milestones included ‘peeling bananas’, ‘sorting maize’ and ‘making patterns with bottle tops’. Intelligence was described in relation to social and community integrity rather than ‘Western’ concepts of numeracy and literacy. Conclusions Concepts, ideas and language relating to normal development in a sub‐Saharan African setting have been gathered in this study. These have been used to create items for a more culturally appropriate developmental assessment tool.     

Efficacy of anastrozole in the treatment of hypogonadal,subfertile men with body mass index ≥25 kg/m2

BackgroundAnastrozole is a non-steroidal fourth generation aromatase inhibitor that stops the conversion of testosterone to estradiol and has been used as empiric medical therapy for the treatment of male infertility in men with an abnormal testosterone-to-estradiol ratio <10 in order to increase endogenous testosterone levels. This study sought to evaluate the efficacy of anastrozole in the treatment of hypogonadal, subfertile men with body mass index greater than 25 mg/kg² with respect to hormonal profile, semen parameters and overall fertility status.MethodsRetrospective chart review was performed of hypogonadal, subfertile men with body mass index ≥25 kg/m² who were treated with anastrozole (1 mg daily). Hormonal measurements and semen analysis prior to and after treatment was analyzed in 30 men. Total motile count was calculated from semen analysis. Clinical pregnancy rates were recorded.ResultsMen treated with anastrozole had increases in follicle stimulating hormone (4.8 versus 7.6 IU/L, P<0.0001), luteinizing hormone (3.4 versus 5.4 IU/L, P<0.0001), testosterone (270.6 versus 412 ng/dL, P<0.0001) and testosterone-to-estradiol ratio (9 versus 26.5, P<0.0001) and decrease in estradiol level (32 versus 15.9 pg/mL, P<0.01) after 5 months of therapy. Increases in sperm concentration (7.8 versus 14.2 million/mL, P<0.001), total motile count (12.6 versus 17.7 million, P<0.01) and strict morphology (3.0% versus 3.5%, P<0.05) was appreciated. Clinical pregnancy rate for our cohort was 46.6% (14 of 30), with 71.4% (10 of 14) conceiving through in vitro fertilization, 14.2% (2 of 14) through intrauterine insemination and 14.2% (2 of 14) through natural intercourse.ConclusionsAnastrozole improves hormonal profiles and semen parameters in hypogonadal, subfertile men with body mass index over 25 kg/m² and may aid in achieving pregnancy especially in conjunction with assisted reproductive techniques.