Niamh Phelan

Evidence for a Specific Defect in Hippocampal Memory in Overt and Subclinical Hypothyroidism

CONTEXT Declarative memory largely depends upon normal functioning temporal lobes (hippocampal complex) and prefrontal cortex. Animal studies suggest abnormal hippocampal function in hypothyroidism. OBJECTIVE The aim of the study was to assess declarative memory in overt and subclinical (SCH) hypothyroid patients before and after l-T(4) (LT4) replacement and in matched normal subjects. DESIGN AND SETTING A prospective, open-labeled interventional study was conducted at a teaching hospital. PARTICIPANTS AND INTERVENTION Hypothyroid (n = 21) and SCH (n = 17) patients underwent neuropsychological tests at baseline and 3 and 6 months after LT4 replacement. Normal subjects were studied at the same time-points. MAIN OUTCOME Tests of spatial, verbal, associative, and working memory; attention; and response inhibition and the Hospital Anxiety and Depression Scale were administered. RESULTS Baseline deficits in spatial, associative, and verbal memory, which rely upon the integrity of the hippocampal and frontal areas, were identified in patients with overt hypothyroidism. Spatial and verbal memory were impaired in SCH patients (P < 0.05). TSH levels correlated negatively (P < 0.05) with these deficits. After LT4 replacement, verbal memory normalized. Spatial memory normalized in the SCH group but remained impaired in the hypothyroid group. Associative memory deficits persisted in the overt hypothyroid group. Hospital Anxiety and Depression Scale scores did not correlate with cognitive function. Measures of attention and response inhibition did not differ from control subjects. CONCLUSION Cognitive impairment occurs in SCH and more markedly in overt hypothyroidism. These impairments appear predominantly mnemonic in nature, suggesting that the etiology is not indicative of general cognitive slowing. We propose that these deficits may reflect an underlying disruption of normal hippocampal function and/or connectivity.

Measurement of selected androgens using liquid chromatography–tandem mass spectrometry in reproductive-age women with Type 1 diabetes

STUDY QUESTION What information does androgen profiling using liquid chromatography tandem mass spectrometry (LC-MS/MS) provide in reproductive-age women with Type 1 diabetes (T1D)? SUMMARY ANSWER In T1D women, androstenedione proved most useful of the measured androgens in differentiating subgroups based on clinical phenotypes of hyperandrogenism (HA) and polycystic ovary syndrome (PCOS). WHAT IS KNOWN ALREADY The prevalence of HA and PCOS are increased in women with T1D. These observations are based on measurement of serum androgens using immunoassays, to-date no studies using LC-MS/MS have been reported in reproductive-age women with T1D. STUDY DESIGN, SIZE, DURATION This was a cross-sectional study with recruitment of three groups of reproductive-age women: women with T1D (n = 87), non-diabetic women with (N = 97) and without PCOS (N = 101). PARTICIPANTS/MATERIALS, SETTING, METHODS Using LC-MS/MS, we aimed to characterize androgen profiles and PCOS status in women with T1D, and interpret findings in relation to cohorts of non-diabetic women with and without PCOS. MAIN RESULTS AND THE ROLE OF CHANCE Compared to non-diabetic women, dehydroepiandrosterone/dehydroepiandrosterone sulphate (DHEA/DHEAS) ratio was lower (P < 0.05) in women with T1D. Testosterone levels were greater in T1D women with clinical HA and anovulation compared to those without clinical HA and with regular cycles, while androstenedione levels were greater in T1D women with HA and anovulation compared to those with HA and regular cycles and also those without HA and with regular cycles (P < 0.05 for all). Compared to T1D women without PCOS, the 18% of T1D women who had PCOS were younger with lower BMI, an older age of menarche, and were more likely to have a positive family history of PCOS (P < 0.05 for all). Androgen levels did not differ between women with T1D and PCOS compared to BMI-matched non-diabetic women with PCOS, but androstenedione levels were greater in T1D women with PCOS compared to obese women with PCOS (P < 0.05). LIMITATIONS, REASONS FOR CAUTION Relatively small subgroups of patients were studied, reducing the power to detect small differences. Free testosterone levels were not measured using equilibrium dialysis, and were not calculated - commonly used formulae have not been validated in T1D. WIDER IMPLICATIONS OF THE FINDINGS Androstenedione is a sensitive biochemical marker of clinical hyperandrogenism and PCOS in T1D. T1D women with PCOS are leaner than those without PCOS but are more likely to have a family history of PCOS. Women with T1D and PCOS have a similar biochemical phenotype to lean non-diabetic women with PCOS but differ from obese women with PCOS. The mechanisms underlying PCOS in T1D and its clinical significance require further investigation. STUDY FUNDING/COMPETING INTEREST(S) The study was part-funded by the Meath Foundation. The authors have no competing interests.

What is the potential role of polyunsaturated fatty acids in controlling dyslipidemia in patients with polycystic ovary syndrome

Abstract “There is much evidence of [polyunsaturated fatty acids] effect in lowering fasting and postprandial triglycerides in diabetic as well as normal subjects and recent evidence suggests its potential for women with polycystic ovary syndrome, particularly those with increased liver fat content.”