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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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).</p> <p>Conclusion</p> <p>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.</p

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 ( &lt; 0.04). In those where a basal 24 h ABPM had been performed median pulse pressure was higher after rhTSH-test ( = 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

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: 1.4–5.2). 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: 1.5–6.4). Low fruit consumption was associated with increased ‘high TOS’ prevalence (30.6% vs 12.9%, OR = 3.0, 95% CI: 1.4–6.2). Sporadic vegetable consumption was associated with increased ‘high TOS’ prevalence compared to daily consumption (29.9% vs 13.5%, OR = 2.7, 95% CI: 1.3–5.7). 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

Coronary artery disease in postmenopausal women - the role of endogenous sex hormones and their receptors

Objectives: Long term estrogen action appears to be protective, while androgen may be detrimental for vascular health in women. The sensitivity to sex hormones is influenced by variants in estrogen and androgen receptor genes (ERα, ERβ, AR). The aim of this study was to investigate the role of the sex hormones and of common ERα, ERβ and AR gene polymorphisms in the severity of CAD in postmenopausal women. Methods: We studied 174 postmenopausal women undergoing coronary angiography (age 45-88 yrs). The severity of CAD was assessed by the number of arteries with >50% stenosis, as well as with the presence of angina and myocardial infarctions (MI). ERα polymorphisms PvuII, XbaI and ERβ polymorphisms AluΙ and RsaΙ were investigated. The length of (CAG)n repeats of the AR was genotyped. Reproductive parameters, predisposing risk factors for CAD were recorded; biochemical and hormonal parameters were measured. Results: 75 women had 0, 39 had one, 37 had two and 23 had three vessels with severe stenosis. The time since menopause was significantly longer in women with angina and MIs compared to those without (20.3±8.7 vs 15.8±8.7yrs, 22.6±8.6, vs 18.1±8.9yrs respectively, p50% στένωση), το ιστορικό ΣΝ, το γυναικολογικό ιστορικό και ελέγχθηκαν ορμονικές και βιοχημικές παράμετροι. Μελετήθηκαν οι πολυμορφισμοί του ERα PvuII (c.454-397T>C) και XbaI (c.454-351A>G), του ERβ AluI (1730G>A) και RsaI (1082G>A) καθώς και οι πολυμορφισμοί του ΑR που προκύπτουν από το μήκος (CAG)n των επαναλαμβανόμενων αλληλουχιών (ΕΑ) του γονιδίου του AR. Αποτελέσματα: 75 γυναίκες είχαν 0, 39 είχαν 1, 37 είχαν 2 και 23 είχαν 3 αγγεία με σοβαρή στένωση στην αγγειογραφία. Η χρονική απόσταση από την εμμηνόπαυση ήταν σημαντικά μεγαλύτερη και ανεξάρτητη της χρονολογικής ηλικίας στις γυναίκες με ιστορικό στηθάγχης ή ΟΕΜ (p19 ΕΑ (18.2 και 1.45% αντίστοιχα, p=0.019). Τα επίπεδα ολικής χοληστερόλης και LDL παρουσίαζαν αρνητική συσχέτιση με τον αριθμό (CAG)n ΕΑ (p<0.04). Τα μέσα επίπεδα της SHBG ήταν χαμηλότερα στις γυναίκες που έφεραν βραχύτερα αλλήλια (p=0.03). Συμπεράσματα: Στην ομάδα των μετεμμηνοπαυσιακών γυναικών που μελετήσαμε, η βαρύτητα της ΣΝ, σχετίζεται με μειωμένη έκθεση σε ενδογενή οιστρογόνα κατά τη διάρκεια της ζωής τους. Συχνοί πολυμορφισμοί των οιστρογονικών υποδοχέων (ERα και ERβ) και του AR, οι οποίοι ενδεχομένως τροποποιούν δια βίου την ευαισθησία των ιστών στις ορμόνες του φύλου επηρεάζουν τη βαρύτητα της ΣΝ ή/και παράγοντες κινδύνου για ΣΝ και μπορεί ενδεχομένως να χρησιμοποιηθούν ως προγνωστικοί δείκτες για την εξέλιξη της ΣΝ

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

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. 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. 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 &lt; 0.01). 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

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 &lt; 0.01). after which the increase of cortisol levelled off. Significant associations were also found between serum DHEA-S and LH levels (P &lt; 0.05). as well as between cortisol and testosterone (P &lt; 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 &lt; 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