Pythagorean self-awareness intervention: A novel cognitive stress management technique for body weight control.

BACKGROUND: Over the past decades, the prevalence of obesity has markedly increased worldwide. Stress is recognized as a substantial contributor to increased body weight; therefore, stress management interventions, especially cognitive behavioural, are becoming increasingly popular. The impact of stress management on stress- and obesity-related biomarkers (eg blood lipid profile, HBA1c, inflammatory biomarkers, such as CRP) has been scarcely studied. The aim of this study was to assess the effect of a novel cognitive behavioural stress management intervention, called 'Pythagorean Self-Awareness Intervention' (PSAI), in overweight/obese adults. MATERIALS AND METHODS: This was a two-armed 1:1 randomized, nonblind controlled study including overweight/obese individuals. The control group followed a personalized Mediterranean low-calorie diet, and the intervention group followed the same diet in addition to the PSAI intervention for 8 weeks. Measurements included demographic, anthropometric (ie BMI, waist-to-hip ratio), stress (ie perceived stress, salivary cortisol), dietary behaviour (ie emotional eating) and metabolic parameters (ie blood lipid profile, HBA1c, CRP, body composition in fat and water). Outcome per-protocol analysis was performed using mixed linear models adjusted for age and gender. RESULTS: A total of 49 of 62 eligible adults were analysed in the study (there were three dropouts in the intervention group and 10 dropouts in the control group); 28 were assigned to the intervention group (mean age 54.7 ± 11.9 years) and 21 to the control group (mean age 51.8 ± 11.9 years). The intervention group showed a statistically significant decrease in perceived stress, cortisol concentrations 30 minutes after awakening, cortisol's area under the curve, BMI, waist-to-hip ratio, restrained, emotional and external eating behaviour, fasting glucose, LDL, triglycerides, HbA1c and body and trunk fat, compared with the control group. Based on the observed effect sizes, clinically meaningful changes may be more evident in stress perception, restrained and external eating behaviour, Hb1ac and trunk fat. The compliance to the PSAI intervention reached 100%, and there were no adverse effects. CONCLUSIONS: The PSAI technique may be an effective stress management method for overweight/obese adults. Future and larger randomized controlled studies are needed to allow generalization of these findings.

The effect of obesity and dietary habits on oxidative stress in Hashimoto's thyroiditis

Objective: Increased oxidative stress has been described in patients with Hashimoto's thyroiditis (HT). The aim of the present study was to investigate whether high oxidative stress is further influenced by obesity and dietary habits in euthyroid women with HT. Methods: Two hundred eighteen consecutive euthyroid women with HT were studied and separated in two groups; 102 with thyroxine replacement and 114 without. For the evaluation of oxidative stress, total lipid peroxide levels in serum (TOS) were measured and recoded as 'high TOS' vs 'medium/low TOS'. The type of food and consumption frequency were recorded. Two binary variables were considered; normal vs low fruit consumption and daily vs sporadic vegetable consumption. Results: 'High TOS' was more frequent in women under thyroxine replacement (31.4% vs 14.7%, OR = 2.7, 95% CI: 1.4­5.2). The prevalence of 'high TOS' was higher among overweight/obese women compared to women with normal BMI (30.4% vs 12.5%, OR = 3.1, 95% CI: 1.5­6.4). Low fruit consumption was associated with increased 'high TOS' prevalence (30.6% vs 12.9%, OR = 3.0, 95% CI: 1.4­6.2). Sporadic vegetable consumption was associated with increased 'high TOS' prevalence compared to daily consumption (29.9% vs 13.5%, OR = 2.7, 95% CI: 1.3­5.7). The examined risk factors were independent and additive in their effect on TOS. At least three risk factors had to be concomitantly present for the likelihood of 'high TOS' to be significantly elevated. Conclusions: Oxidative stress is increased in women with HT under thyroxine replacement. Nevertheless, normal BMI, daily fruit and vegetable consumption, all contribute in maintaining oxidative stress at low levels.

RAGE polymorphisms and oxidative stress levels in Hashimoto's thyroiditis.

BACKGROUND: Polymorphisms of the receptor for advanced glycation end products (RAGE) gene have been studied in various autoimmune disorders, but not in Hashimoto's thyroiditis. Also, increased oxidative stress has been described in patients with Hashimoto's thyroiditis. The aim of this study was to investigate the possible role of two common RAGE polymorphisms (-429T>C, -374T>A) in Hashimoto's thyroiditis; in parallel, we studied oxidative stress levels. MATERIALS AND METHODS: A total of 300 consecutive euthyroid women were examined and classified into three groups: Hashimoto's thyroiditis with treatment (n = 96), Hashimoto's thyroiditis without treatment (n = 109) and controls (n = 95). For a rough evaluation of oxidative stress, total lipid peroxide levels in serum were measured. The -429T>C AluI and -374T>A MfeI polymorphisms of RAGE were studied in genomic DNA. RESULTS: Significant association of the RAGE system with Hashimoto's thyroiditis was found only with regard to the prevalence of the -429T>C, but not with -374T>A polymorphism. The levels of oxidative stress were significantly elevated in Hashimoto's thyroiditis patients under treatment. Further analysis demonstrated that an oxidative stress cut-off value of 590 µmol/L is associated with an increased risk of progression of Hashimoto's thyroiditis from euthyroidism to hypothyroidism; this risk is further increased in carriers of the RAGE -429T>C polymorphism. CONCLUSIONS: Our findings indicate that both examined risk factors may be implicated in the occurrence of Hashimoto's thyroiditis, but this covers only a fraction of the pathophysiology of the disease.

Effects of recombinant human thyrotropin administration on 24-hour arterial pressure in female undergoing evaluation for differentiated thyroid cancer.

Objective. Thyroid-stimulating-hormone (TSH) receptors are expressed in endothelial cells. We investigated whether elevated TSH levels after acute recombinant TSH (rhTSH) administration may result in alterations in blood pressure (BP) in premenopausal women with well-differentiated thyroid carcinoma (DTC). Designs. Thirty euthyroid DTC female patients were evaluated by rhTSH stimulation test (mean age 40.4 ± 8.6 years). A 24 h ambulatory systolic and diastolic blood pressure (SBP, DBP) monitoring (24 hr ABPM) was performed on days 2-3(D2-3). TSH was measured on day 1(D1), day 3(D3), and day 5(D5). Central blood pressure was evaluated on D3. Twenty-three patients were studied 1-4 weeks earlier (basal measurements). Results. TSH levels were D1: median 0.2 mU/L, D3: median 115.0 mU/L, and D5: median 14.6 mU/L. There were no significant associations between TSH on D1 and D3 and any BP measurements. Median D5 office-SBP and 24 h SBP, DBP, and central SBP were correlated with D5-TSH (P < 0.04). In those where a basal 24 h ABPM had been performed median pulse pressure was higher after rhTSH-test (P = 0.02). Conclusions. TSH, when acutely elevated, may slightly increase SBP, DBP, and central SBP. This agrees with previous reports showing positive associations of BP with TSH.

A study of ERα PvuII polymorphism in female patients with acute stroke: no associations with disease severity and early outcome.

Several studies have examined the association of the PvuII polymorphism of the estrogen receptor alpha gene with the risk of stroke. Data linking the polymorphism with the severity and outcome of cerebrovascular disease are lacking. In this study, we evaluated 285 postmenopausal Caucasian patients suffering an acute stroke, hospitalized in two tertiary hospitals over a period of 2 years, and searched for associations between the PvuII polymorphism and the one-month outcome and the neurological severity on admission. The prevalence of CC genotype was 21%, CT 50% and TT 29%. Estradiol levels were higher with increasing frequencies of the C allele (p = 0.04). There was no difference in the short-term functional outcome and mortality and the neurological severity on admission among the three genotypes. We did not find a significant association of the PvuII polymorphism with intracerebral hemorrhage and classical stroke risk factors. An association of the CC genotype with venous thromboembolism history was recorded (p 0.05). There was no association between the PvuII polymorphism and stroke severity and short-term outcome in the studied female stroke population. It is possible that the long-term estrogenic action, reflected by the genetic polymorphism, is not a major determinant of disease severity and prognosis in older age.

Association of the SHBG gene promoter polymorphism with early markers of atherosclerosis in apparently healthy women.

OBJECTIVE: Androgen may be detrimental in the development of cardiovascular disease in women. We investigated possible associations between the (TAAAA)n polymorphism of sex hormone binding globulin (SHBG) gene promoter, which influences transcriptional efficiency of the SHBG gene - and thus the tissue androgen availability - and early markers of atherosclerosis in apparently healthy women. DESIGN AND METHODS: In this prospective clinical study, 153 consecutive women (mean age 43.9±9 years, 66 of whom postmenopausal, without known diabetes, cardiovascular disease), visiting our internal medicine outpatients were examined for unrecognised features of the metabolic syndrome. Endothelium dependent vasodilatation (FMD) and intima media thickness of the common carotid artery (IMT) were recorded. According to the number of SHBG gene promoter repeats patients were classified as short (≤7), medium (=8) and long repeat (≥9) allele groups. RESULTS: The (TAAAA)n repeat length was an independent predictor of FMD in multivariate analysis (p<0.03). FMD was positively correlated with SHBG levels (p=0.004). Women carriers of two long alleles had increased IMT (p=0.031) although this was not independent in the multivariate analysis. CONCLUSIONS: Longer (TAAAA)n repeats in the SHBG gene promoter are associated with impaired FMD, which is an early marker of atherosclerosis. As this polymorphism has been associated with a more androgenic phenotype in women, this association may reflect the life-long tissue exposure to higher free androgens and indirectly supports the view that androgenic exposure may have adverse cardiovascular effects in women.

Pilot study of circulating prolactin levels and endothelial function in men with hypertension.

BACKGROUND: Hyperprolactinemia has been recently associated with hypertension and endothelial dysfunction in humans, confirming animal studies performed in the 1970s that showed high prolactin levels to exert positive chronotropic and vasoconstrictive effects. Whether prolactin affects endothelial function, in the absence of hyperprolactinemia, remains unknown. Considering that secretion of prolactin presents circadian rhythmicity, we tested the hypothesis that in patients with hypertension, who present diurnal variation in their endothelial function as well, prolactin levels correlate with endothelial function and/or blood pressure. METHODS: Endothelial function, assessed by flow-mediated dilatation (FMD) and serum prolactin were examined successively at 12 PM, 9 PM, and 7 AM in 27 nonhyperprolactinemic men with newly diagnosed, untreated essential hypertension. RESULTS: Both FMD and prolactin presented 24-h variation (P < 0.01). FMD reached its lowest values at 7 AM (2.1 ± 1.8%, mean ± s.d.); concurrently prolactin levels peaked (7.18 ng/ml, median). Across the three time points, prolactin changes inversely interacted with FMD changes (P = 0.002). Systolic and diastolic blood pressure also varied significantly but no interaction with prolactin changes was evident. CONCLUSIONS: Diurnal fluctuations of prolactin levels are associated with decreased endothelial function that occurs early in the morning in men with hypertension, although this study did not assess causality. Additional studies are required to determine whether these responses differ from normotensive individuals.

Endogenous estrogen levels are associated with endothelial function in males independently of lipid levels.

Estrogens and androgens may play an important role in vascular health in both sexes. The aim of this study was to examine the relation of endogenous sex hormone levels with early markers of atherosclerosis in a cohort of apparently healthy males. 124 males (age 46.25 ± 9.56) attending a preventive medicine program were examined for unrecognised features of the metabolic syndrome. Flow-mediated dilatation (FMD) and intima-media thickness (IMT) of the common carotid artery were evaluated. Obesity parameters were recorded; estradiol, testosterone, SHBG, free testosterone, insulin, as well as glucose and lipid levels were measured. FMD was positively correlated with estradiol (r = 0.201, P = 0.041) and negatively with total cholesterol (r = -0.205, P = 0.022), low density lipoproteins (r = -0.232, P = 0.009), and triglyceride levels (r = -0.179, P = 0.046). In multivariate analysis, the association of FMD with estrogen was independent of BMI and lipid levels. No significant association between FMD and testosterone levels was found. Subjects with an increased mean IMT (> 0.73 mm, i.e., > 3rd tertile) had lower levels of free (P = 0.021) and bioavailable (P = 0.016) testosterone. In multivariate logistic regression analysis, this association was no longer significant when age or cholesterol levels were considered. Endogenous estrogen levels are associated with FMD, independently of age and lipid levels, showing a protective effect in middle-age male subjects. Circulating androgens are associated, although not independently, with structural changes such as the IMT of carotid artery; this effect is possibly influenced by lipid levels and age.

Free thyroxine is an independent predictor of subcutaneous fat in euthyroid individuals.

OBJECTIVE: Thyroid function parameters have been associated with obesity, but associations with the type of adiposity have not been examined. We used ultrasound (US) to assess regional adiposity and investigated associations of thyroid function with parameters of central obesity. DESIGN: Cross-sectional study. METHODS: A total of 303 apparently healthy individuals (age 42.9+/-8.8, body mass index (BMI) 19.0-43.3, median 26.2 kg/m(2), 181 women) were examined for indices of the metabolic syndrome. BMI, waist and hip circumference, abdominal subcutaneous fat (SF), and preperitoneal fat (PF) layer was estimated. TSH, free thyroxine (fT(4)), triiodothyronine (T(3)), thyroid autoantibodies, insulin, glucose, and lipid levels were measured. Subjects receiving T(4) (9.2%) were excluded. RESULTS: SF and SF/PF ratio were inversely correlated with fT(4) levels (r=-0.169, P=0.023, r=-0.193, P=0.009 respectively). In multivariate analysis, fT(4) was a predictor of SF and SF/PF, independently of age, sex, and smoking. SF correlated with TSH levels (r=0.149, P=0.037). PF and SF were positively associated with T(3) levels (r=0.245, P=0.004 and r=0.189, P=0.019 respectively). T(3) levels were positively associated with BMI (r=0.257, P=0.0004), waist perimeter (r=0.324, P<0.0001), and waist-to-hip ratio (WHR; r=0.363, P<0.0001). The T(3)/fT(4) ratio was positively correlated with SF (r=0.182, P=0.028), WHR (r=0.267, P=0.0003), and BMI (r=0.146, P=0.043). CONCLUSIONS: Increasing SF accumulation as assessed by US is associated with lower fT(4) and higher TSH levels among euthyroid slightly overweight individuals. These associations indicate that subtle variation in thyroid function may participate in regional adiposity.

Thyroid volume, selenium levels and nutritional habits in a rural region in Albania.

OBJECTIVE: Environmental factors are involved in goiter development. An increased number of goitrous patients were identified among outpatients in Gyrocaster, a mountainous region in Southwestern Albania. We examined possible associations of thyroid enlargement with nutritional factors. DESIGN: 112 consecutive patients, 104 females, aged 52.8 +/-12.1 (mean+/-SD), who either were taking thyroxine (n=27) or were suspected to have thyroid disease were examined. Thyroid parameters and nutritional habits were recorded and serum selenium and urine iodine levels were determined; thyroid ultrasound was performed. RESULTS: The median thyroid volume (TV) was 20.4 ml (range 4.4-97.6). All consumed food was home-produced. TV correlated negatively with the frequency of lamb-goat meat and vegetables consumption (p=0.05 and p=0.03, respectively). Mean TV was significantly lower in those eating lamb-goat >1 times/week (21.4+/-13.3 vs 31.9+/-23 ml, p<0.01). The association of TV with lamb meat consumption was independent of sex, education or occupation (p < 0.009). Selenium levels ranged from 30.6-138 microg/L (reference range 43-190). There was no association between selenium levels and TV. 43% of the subjects had TSH < 0.3 mU/L (those on thyroxine were excluded). Log TSH correlated negatively with TV and fT4 levels (p < 0.007), indicating the presence of autonomy (TSHRab positive in two subjects). Mean urinary iodine excretion was 99.8+/-35.3 microg/gr creatinine (normal >100). CONCLUSIONS: Nutritional factors may be involved in the development of goiter in Southwestern Albania. No role of selenium was found. The higher consumption of lamb-goat meat and vegetables, all non-industrialized, appeared to be protective. This finding may reflect better socioeconomic status, although this was not identified. Unrecognized subclinical hyperthyroidism, probably due to thyroid autonomy, was quite common.

The Pro 12 Ala PPAR gamma gene polymorphism: possible modifier of the activity and severity of thyroid-associated orbitopathy (TAO).

OBJECTIVE: The PPAR gamma transcription factor, is involved in both adipogenesis and inflammation, which have been implicated in the pathogenesis of thyroid-associated orbitopathy (TAO). The aim of this study was to explore the possibility that the Pro(12)Ala polymorphism of the PPAR gamma gene, associated with a modified transcriptional activity, might be affecting the severity of TAO. SUBJECTS AND DESIGN: We studied two cohorts of patients with Graves' disease (GD): Group 1 comprised 172 patients of Dutch ethnic origin with TAO, who attended the outpatients' clinic, Department of Endocrinology and Orbital Centre of the Academic Medical Centre, Amsterdam. Group 2 comprised 93 consecutive patients with GD of Greek ethnic origin, who did not have TAO. In group 1, exophthalmometry measurements, lid oedema, diplopia (n = 172) and clinical activity score (CAS) (n = 110), always assessed by the same group of three investigators, were recorded. Autoantibody levels were measured. RESULTS: Allele frequency was 11.5%. There was no difference in the distribution of the polymorphism between GD patients with and without TAO. Among group 1 patients proptosis was significantly lower in Pro(12)Ala carriers (20.1 +/- 3.3 vs. 22.1 +/- 3.1, P = 0.003, t-test). PPAR gamma polymorphism carriers had lower TSH-Rab levels (mean rank 61.8 vs. 83.2, P = 0.015) and lower CAS (available in 110 patients) (mean rank 38.9 vs. 55.4, P = 0.022, M-W-test). The frequency of the polymorphism decreased with increasing CAS (P = 0.023 linear by linear association). Multivariate analysis (step) showed that the association of either proptosis or CAS with the PPAR gamma gene variant remained significant when age, smoking and TSH-Rab levels were taken into account (P < 0.01). CONCLUSIONS: The distribution of the Pro(12)Ala PPAR gamma gene polymorphism is equally present in patients with GD with or without TAO. Among patients with TAO this polymorphism is associated with less-severe and less-active disease.

Association of thyroid function with arterial pressure in normotensive and hypertensive euthyroid individuals: A cross-sectional study.

BACKGROUND: Overt hypothyroidism has been associated with arterial hypertension and increased arterial stiffness. Results in euthyroid individuals have been conflicting. We investigated associations of thyroid function with systolic (SAP) and diastolic (DAP) arterial pressure in euthyroid subjects. METHODS: 311 euthyroid individuals (185 women, mean age 43.9 +/- 9) without a history of diabetes attending a preventive medicine program were examined. Subjects receiving thyroxine (10.6%) were excluded; 19.3% had hypertension, 43% had a family history for hypertension. TSH, fT4, thyroid autoantibodies, insulin, glucose were measured. The "fT4.TSH product", which has been suggested as a T4 resistance-index, was calculated. RESULTS: TSH range was 0.1-8, median 1.4 mU/L, fT4 range was 11.5-25.2 pmol/L, median 17.4. TSH and the "fT4.TSH product" were positively associated with DAP (p < 0.03, for both associations). In the subgroup of individuals with TSH levels 0.36-2.5 mU/L, both TSH and the "fT4.TSH product" were positively correlated with SAP (r = +0.133 p = 0.044, r = +0.152 p = 0.026) and DAP (r = +0.243 p < 0.001, r = +0.252 p < 0.001 respectively); in multivariate analysis the "fT4.TSH product" was a significant predictor of DAP independently of HOMA-IR and BMI (p < 0.001). Similar associations were found when only the non-hypertensive subjects were analysed (p = 0.004). Hypertensive patients had higher TSH levels (p = 0.02) and belonged more frequently to the subgroup with TSH > 2 mU/L (35.3% vs 21.3%, p = 0.045). CONCLUSION: In euthyroid individuals the association of thyroid function with diastolic arterial pressure remains significant even when a stricter "normal range" for TSH levels is considered. The "freeT4.TSH" product appears to be an even stronger predictor of DAP, independently of HOMA insulin resistance index and obesity.

The importance of the (TAAAA)n alleles at the SHBG gene promoter for the severity of coronary artery disease in postmenopausal women.

OBJECTIVE: Androgen may be detrimental in the development of coronary artery disease (CAD) in women. We investigated possible associations between the (TAAAA)n polymorphism of sex hormone-binding globulin (SHBG) gene promoter, which influences transcriptional efficiency of the SHBG gene and the severity of CAD in women. DESIGN: In this prospective clinical study, 146 postmenopausal women (46-88 y) undergoing coronary angiography were studied. CAD severity, history of angina and myocardial infarction, and reproductive history were recorded and hormonal parameters measured. According to the number of SHBG gene promoter repeat polymorphisms, participants were classified into short (seven or fewer), medium length (eight), and long repeat (nine or more) allele groups. RESULTS: Significant CAD was more prevalent in the long repeat allele carrier group: 65% of the participants with three vessels with severe stenosis belonged to the long repeat allele group, whereas only 37% of participants with mild CAD belonged to this group (P=0.01). A history of angina and prevalence of hyperlipidemia was more frequent in the long repeat allele group (P<0.05). Calculated free testosterone levels were higher in the long repeat allele groups (P<0.05), whereas SHBG levels tended to be lower (P=0.06). SHBG levels correlated inversely with body mass index and waist circumference (P<0.05). CONCLUSIONS: Longer (TAAAA)n repeats in the SHBG gene promoter are associated with more severe CAD in women undergoing coronary angiography, a finding not previously reported. This association may reflect the lifelong tissue exposure to higher free androgens and supports the adverse cardiovascular effect of androgenic exposure in this highly selected group of women.

Thyroid function in patients with Alzheimer disease: implications on response to anticholinesterase treatment.

Increasing evidence supports an extensive interrelationship between thyroid hormones and the cholinergic system, which is selectively and early affected in Alzheimer disease (AD). The aim of the present study was to explore thyroid function in patients with AD before and after acetylcholinesterase inhibition treatment to possibly identify variances in response. Thyroid function tests were evaluated in 28 AD patients and 24 age and sex-matched controls. Nineteen of the patients were reevaluated after (4 mo) treatment with donepezil. Serum thyrotropin (TSH), triiodothyronine (T3), thyroxine (T4), the free fractions (fT3, fT4) and thyroid autoantibodies were determined using standard methods. All subjects were clinically euthyroid. Patients presented with higher fT4 and anti-thyroperoxidase levels, as compared with the controls. Significant reduction in T4, fT3, fT4, and anti-thyroperoxidase levels were observed 4 months after treatment. Responders had higher T4 and fT4, than nonresponders, followed by significant reductions after treatment. The above, within the normal range alterations, may represent a direct effect on hormone release from the thyroid gland and/or increased conversion of T4 to T3 within the brain. Higher T4 and fT4 levels before treatment might predict a favorable response to donepezil treatment.

The adrenal gland may be a target of LH action in postmenopausal women.

OBJECTIVE: LH receptor expression and function have been demonstrated in the human adrenal cortex, but their involvement in normal adrenal function remains elusive. Because cortisol levels have been reported to be higher in postmenopausal women than in age-matched men, the aim of the present study was to investigate a possible association of adrenal function with the elevated LH levels in postmenopausal women. DESIGN AND METHODS: A group of 112 endocrinologically normal postmenopausal women (mean age 67.6, range 50-88 years) was evaluated. A basal fasting morning sample of peripheral blood was taken for the determination of LH, cortisol, dehydroepiandrosterone-sulphate (DHEA-S), oestradiol (E2), testosterone, sex hormone-binding globulin (SHBG), insulin and glucose. Information about reproductive function, anthropometric parameters and arterial blood pressure was recorded. RESULTS: The correlation of LH and cortisol was bimodally distributed, with a significant linear correlation up to the LH level of 41 U/l (n = 78, P<0.01), after which the increase of cortisol levelled off. Significant associations were also found between serum DHEA-S and LH levels (P<0.05), as well as between cortisol and testosterone (P<0.0001), but not between E2 and LH. Multivariate analysis showed that the association of cortisol with LH was independent of age and testosterone; the association of DHEA-S with LH was independent of E2, cortisol and age. Significant associations were also found between E2, testosterone and DHEA-S levels (P<0.001). CONCLUSIONS: These results indicate that adrenal cortisol and DHEA-S production may be stimulated by the highly elevated postmenopausal levels of LH; the physiological significance of this association and plausible contribution to the metabolic syndrome observed after the menopause remain to be evaluated.

Severity of cardiovascular disease in women: relation with exposure to endogenous estrogen.

OBJECTIVES: Coronary artery disease (CAD) is more common in men than in women. Endogenous sex steroids may be the main factor responsible, as long-term estrogen action appears to be protective. The aim of the study was to investigate the predisposing factors responsible for the severity of CAD in women. METHODS: One hundred and eight women (100 menopausal) undergoing coronary angiography were studied. Reproductive function was recorded. The severity of CAD was assessed by the number of arteries with severe stenosis, the presence of angina and myocardial infarctions (MI). RESULTS: The time since menopause (TSM) was significantly longer in women with angina and with MIs compared to those without (20.3+/-8.7 years versus 15.8+/-8.7 years and 22.6+/-8.6 years versus 18.1+/-8.9 years, p<0.05), independently of chronological age. The age at menopause was significantly younger in women who had 2 MIs compared to those with 1 or 0 MI (41.5+/-3.5, 47.5+/-5.3 and 48.4+/-5.4 years, respectively; p=0.04); the total duration of menstrual cyclicity was inversely related to the number of MIs (35.6+/-5.8, 34.2+/-5.3 and 28.3+/-3.3 years, 0, 1 and 2 MIs, respectively; p=0.03). CONCLUSIONS: The severity of CAD in women referred for coronary angiography is correlated with measures of exposure to endogenous estrogen. Both the TSM and the age at menopause are aggravating factors for MI, independently of age. There is an independent protective effect of the duration of estrogen exposure on the number of MIs; this has not been reported before and supports the protective role of the length of exposure to endogenous estrogen, especially for the occurrence of MI in this selected group of women.

TSH may not be a good marker for adequate thyroid hormone replacement therapy.

The objective of this study was to evaluate parameters of thyroid function and indices of peripheral thyroid hormone action (such as SHBG) in patients whose hypothyroidism was considered well controlled under current criteria. Eighty-five patients with T4-treated hypothyroidism, 28 of whom had athyria, were compared with 114 normal individuals with the same TSH levels. T3 levels were significantly lower in hypothyroidism although mean T4 and fT4 levels were significantly higher. Furthermore, mean SHBG levels were significantly lower in hypothyroidism independently of age. The difference remained when stricter criteria for adequate treatment were applied (TSH < 2.5 microgU/ml). Significant negative correlations were found between logTSH and T3. The slopes of the regression lines of T3 to TSH were significantly different in the control group and the hypothyroid group: thus, for the same TSH levels, T3 levels were lower in the hypothyroid group. We conclude that patients with T4-treated hypothyroidism have lower T3 levels, lower T3/T4 ratio and lower SHBG than normal individuals with the same TSH, perhaps indicating relative tissue hypothyroidism in the liver. TSH levels used to monitor substitution, mostly regulated by intracellular T3 in the pituitary, may not be such a good indicator of adequate thyroid hormone action in all tissues. The co-administration of T3 may prove more effective in this respect, provided novel suitable preparations are developed. Until this is accomplished, substitution in hypothyroidism should aim at low normal TSH, to ensure normal T3 levels.

Circulating levels of oxidized low-density lipoprotein in overt and mild hypothyroidism.

The increased low-density lipoprotein cholesterol (LDL-C) levels in hypothyroidism may enhance the formation of oxidized LDL (oxi-LDL) that may consequently generate foam cells by their uptake by the macrophages. The goal of this study was to investigate whether plasma circulating oxi-LDL levels are elevated in mild and in overt hypothyroidism, if the concentration of oxi-LDL is influenced in a short-term treatment period by thyroid hormone, and whether correlations exist between serum concentration of thyrotropin (TSH), thyroid hormone, and cholesterol. Thirty-nine patients with overt hypothyroidism (OH), 41 patients with mild thyroid failure (MTF), and 57 controls (CNTR) were investigated. Serum TSH concentrations were increased in OH (18 +/- 6 mU/L) and in MTF (6 +/- 2 mU/L), whereas in CNTR the levels were 1.6 +/- 0.3 mU/L. Plasma circulating levels of oxi-LDL were measured by a new enzyme-linked immunosorbent assay (ELISA) kit (normal range, 40-75 mU/L) and they were found statistically significantly increased in OH compared to MTF (86 +/- 16 mU/L vs. 73 +/- 13 mU/L; p < 0.01) and to CNTR (62 +/- 11 mU/L; p < 0.001). Smokers in all groups exhibited statistically significant higher plasma oxi-LDL levels compared to nonsmokers. The percentage of increase amounted to 17.7% in OH, to 9.8% in MTF, and to 8% in CNTR. Replacement treatment with levothyroxine over a period of 3 months in 12 of 39 patients with OH and in 14 of 41 patients with MTF resulted in a statistically significant decrease of oxi-LDL only in the OH group. Thus, plasma oxi-LDL decreased in OH from 82 +/- 12 mU/L to 73 +/- 10 mU/L (p < 0.05), to the upper normal level, and in MTF from 68 +/- 5 mU/L to 64 +/- 5 mU/L, respectively. In conclusion, we can state that circulating oxi-LDL levels are elevated in untreated overt hypothyroidism, they tend to be higher in mild thyroid failure, they are severely affected by smoking, however, they need a longer time course to decrease via thyroxine treatment.