Subclinical hypothyroidism and lipid abnormalities in older women attending a vascular disease prevention clinic: effect of thyroid replacement therapy

The authors evaluated the frequency and type of lipid disorders associated with subclinical hypothyroidism (SH) in older women referred to their university vascular disease prevention clinic. They also assessed the results of thyroid replacement therapy. Fasting serum lipid profiles and thyroid function tests were measured in 333 apparently healthy women (mean age: 71.8 +/- 7 years). These women were divided into 3 groups: group I: 60-69 years old (n = 132); group II: 70-79 years old (n = 153); group III: 80-89 years old (n = 48). SH was defined as a serum thyrotropin concentration higher than 3.20 mlU/mL with a normal free thyroxine concentration. The prevalence of SH was 7.5%. Thyrotropin was higher than 3.20 mU/mL in 25 women; 7 (5.3%), 14 (9.2%), and 4 (8.3%) in groups I, II, and III, respectively. Low-density lipoprotein cholesterol (LDL-C) concentrations were higher in the women with SH (p = 0.037). The mean values of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), TC/HDL-C ratio, lipoprotein (a) (Lp[a]), apolipoprotein A-I (apo AI) apolipoprotein B100 (apo B) and apo B/apo A ratio were higher and triglycerides (TG) were lower, compared with those with normal levels of thyrotropin. However, none of these differences reached significance. Restoration of euthyroid status (thyroxine: 50-100 microg/day) in 17 SH women significantly improved TC (p = 0.017), LDL-C (p = 0.014), TC/HDL-C (p = 0.05), LDL-C/HDL-C (p = 0.03), apo B (p = 0.013), and Lp(a) (p = 0.0005) values. SH is relatively common in older women attending a vascular disease prevention clinic. Thyroid hormone replacement therapy significantly improved serum lipids. In particular, the reduction in LDL-C and Lp(a) concentrations may be of clinical benefit.     

Leptin and the pituitary-thyroid axis: a comparative study in lean, obese, hypothyroid and hyperthyroid subjects

OBJECTIVE: To study interactions between leptin and the pituitary-thyroid axis, both in euthyroid and dysthyroid states. SUBJECTS AND MEASUREMENTS: We investigated the relationships of plasma leptin to levels of free thyroid hormones and TSH in 18 patients with newly diagnosed hyperthyroidism, 22 with newly diagnosed primary hypothyroidism, and 32 lean (body mass index [BMI] < 30) and 37 obese (BMI > 30 kg/m2) euthyroid subjects. Hypothyroid patients were restudied during thyroxine replacement treatment. RESULTS: Median [interquartile range] plasma leptin concentrations were highest in obese euthyroid subjects (31.5 [19.0-48.0] and in untreated hypothyroid patients (19.2 [11.5-31.5]), and lowest levels in untreated hyperthyroid patients (8.9 [5.5-11.1]) and lean euthyroid control subjects (6.6 [3.9-14.4] micrograms/l (Kruskall-Wallis one-way analysis of variance; P < 0.0001). In euthyroid subjects, plasma leptin levels were higher in obese than in lean subjects (P < 0.00001). In obese subjects plasma levels of TSH correlated with percentage body fat (r = 0.67; P < 0.001) and plasma leptin (r = 0.61; P < 0.001). In untreated hyperthyroid subjects plasma leptin was unrelated to free T3, and in untreated hypothyroidism plasma leptin was unrelated to either free T3 or TSH concentrations (all P = NS). In untreated hyperthyroid, but not hypothyroid, patients plasma leptin concentrations correlated with BMI (r = 0.57; P = 0.02). Treatment of hypothyroidism with thyroxine resulted in a significant reduction in plasma leptin concentrations from 20.8 (11.8 to 31.6) to 12.9 (4.6-21.2) micrograms/l (P = 0.005), but BMI did not change significantly in the hypothyroid subjects being studied prospectively. CONCLUSIONS: (i) In euthyroid subjects, plasma leptin and TSH levels correlate, and both are positively correlated with adiposity. (ii) Plasma leptin was significantly elevated in hypothyroid subjects, to levels similar to those seen in obese euthyroid subjects. (iii) Treatment of hypothyroidism resulted in a reduction in the raised plasma leptin levels. The data are consistent with the hypothesis that leptin and the pituitary-thyroid axis interact in the euthyroid state, and that hypothyroidism reversibly increases leptin concentrations.     

Adiponectin levels and cardiovascular risk factors in hypothyroidism and hyperthyroidism

OBJECTIVE: Adiponectin, an adipose tissue-derived hormone, has been reported to have anti-inflammatory and anti-atherogenic effects. The physiological effect of adiponectin on the metabolic changes and its relation with cardiovascular risk factors in thyroid dysfunction states is still not clear. The aim of the study was to evaluate plasma adiponectin level and its relation to cardiovascular risk factors in patients with thyroid dysfunction. PATIENTS AND MEASUREMENTS: Sixty-seven patients with hypothyroidism, 56 patients with hyperthyroidism and 52 age- and sex-matched euthyroid subjects were enrolled in the study. Adiponectin, C-reactive protein (CRP), homocysteine (Hcy), lipid parameters, Lipoprotein(a) [Lp (a)], Apolipoprotein (Apo) A, Apo B and fibrinogen levels were measured in all subjects. Insulin sensitivity was determined using the Homeostasis Model Assessment (HOMA-IR). RESULTS: Circulating adiponectin levels were not different between the groups (16.2 +/- 5.0, 15.1 +/- 3.7, 15.9 +/- 4.8 ng/ml; hypothyroid, hyperthyroid, euthyroid group, respectively). Plasma adiponectin levels correlated negatively with body mass index (BMI) and HOMA-IR index and positively with high-density lipoprotein cholesterol (HDL-C) in all groups. There was a significant correlation between adiponectin and CRP levels in both hypothyroid and hyperthyroid groups. In all groups, adiponectin levels did not correlate with age, systolic blood pressure, diastolic blood pressure and thyroid hormones. Multiple regression analysis revealed BMI and HDL-C levels to be the most important predictors of circulating adiponectin levels. CONCLUSIONS: Plasma adiponectin levels are associated with BMI and HDL-C levels in patients with hypothyroidism and hyperthyroidism. But there is not a direct relation of adiponectin with thyroid hormones in these patients.     

Changes in plasma low-density lipoprotein (LDL)- and high-density lipoprotein cholesterol in hypo- and hyperthyroid patients are related to changes in free thyroxine, not to polymorphisms in LDL receptor or cholesterol ester transfer protein genes

Thyroid function disorders lead to changes in lipoprotein metabolism. Both plasma low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) increase in hypothyroidism and decrease in hyperthyroidism. Changes in LDL-C relate to altered clearance of LDL particles caused by changes in expression of LDL receptors on liver cell surfaces. Changes in cholesterol ester transfer activity partly explain changes in HDL-C. It has been suggested that the magnitude of these changes is related to polymorphisms of involved genes. The aim of the present study is to investigate whether the polymorphic AvaII restriction site in exon 13 of the LDL receptor gene and the polymorphic TaqIB site in intron 1 of the cholesterol ester transfer protein are associated with the magnitude of the changes in plasma LDL-C and HDL-C, respectively, in the transition from the hypo- or hyperthyroid to the euthyroid state. From a consecutive group of 66 untreated hypothyroid and 60 hyperthyroid patients, 47 Caucasians in each group were analyzed. Fasting LDL-C and HDL-C were measured at baseline and 3 months after restoration of the euthyroid state. Genotype was determined by means of PCR techniques. The homozygous presence of a restriction site was designated as +/+, heterozygous as +/-, and absence as -/-. Trend analysis was done with ANOVA. Among hypo- or hyperthyroid patients, subgroups with different genotypes did not differ in thyroid function pre- or post treatment. The mean decrease in LDL-C (mmol/L +/- SD) in hypothyroid patients with different AvaII genotypes did not differ: - 1.07 +/- 1.44 (-/-, N = 15), -1.25 +/- 1.53 (+/-, N = 19), and -1.18 +/- 1.01 (+/+, N = 13) mmol/L [not significant (NS)]; neither did the mean increase in hyperthyroid patients: 1.07 +/- 0.90 (-/-, N = 18), 0.92 +/- 1.00 (+/-, N = 21), and 1.20 +/- 0.45 (+/+, N = 6) (NS). The mean decrease in HDL-C (mmol/L +/- SD) in hypothyroid patients with different TaqIB genotypes did not differ: -0.22 +/- 0.26 (-/-, N = 13), -0.15 +/- 0.23 (+/-, N = 21), and -0.12 +/- 0.22 (+/+, N = 9) (NS); neither did the mean increase in hyperthyroid patients: 0.29 +/- 0.39 (-/-, N = 7), 0.26 +/- 0.23 (+/-, N = 22), and 0.19 +/- 0.31 (+/+, N = 18) (NS). Changes in LDL-C and HDL-C correlated with the logarithm of the change in free T4 (fT4), expressed as the fT4 posttreatment/fT4 pretreatment ratio (r = -0.81, P < 0.001; and r = -0.62, P < 0.001, respectively). In conclusion, in the transition from hypo- or hyperthyroidism to euthyroidism, no association is found between AvaII genotype and changes in plasma LDL-C nor between TaqIB genotype and changes in HDL-C. Changes in LDL-C and HDL-C correlate with changes in fT4.     

Serum Ghrelin Levels in patients with Hashimoto's thyroiditis.

OBJECTIVE: Hypothyroidism is associated with changes in appetite and body weight. Ghrelin is an orexigenic peptide, and it stimulates appetite and increases food intake. However, the potential relationship between circulating ghrelin levels, hypothyroidism, and thyroid antibodies has not been adequately studied. DESIGN: Forty-seven patients with hypothyroidism due to Hashimoto's thyroiditis and 48 euthyroid subjects were enrolled in the study. Thyroid hormones and antibodies, insulin, glucose, ghrelin levels, and lipid parameters were measured in all the subjects. MAIN OUTCOME: Hypothyroid group showed significantly decreased serum levels of ghrelin and ghrelin=body mass index (BMI) compared to euthyroid group (31.9 +/- 21.5 pg/mL vs. 50.5 +/- 34.8 pg/mL, p < 0.001; and 1.24 +/- 0.93 vs. 2.12 +/- 1.53, p < 0.0001). In hypothyroid group, 6 months after treatment, ghrelin levels and ghrelin/BMI remained lower than euthyroid group (33.2 +/- 21.1 pg/mL vs. 50.5 +/- 34.8 pg/mL, p < 0.001; and 1.27 +/- 0.86 vs. 2.12 +/- 1.53, p < 0.0001). Ghrelin levels were decreased in hypothyroid patients with high thyroid peroxidase antibody (TPOAb) titre compared to hypothyroid patients with low TPOAb titre (19.1 +/- 23.1 pg/ mL vs. 35.3 +/- 17.4 pg/mL, p < 0.01). Ghrelin levels correlated positively with free triiodothyronine (FT3) and free thyroxine (FT4), and negatively with age, thyroglobulin antibody (TAb), TPOAb, total cholesterol (T-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and triglycerides (TG) in hypothyroid group. In euthyroid group, circulating ghrelin levels correlated negatively with age, FT3, FT4, TG, and VLDL-C levels. No significant correlation was observed between ghrelin and homeostasis model assessment for insulin resistance (HOMA-IR) and between ghrelin and quantitative insulin sensitivity check index (QUICKI) in both groups. Regression analysis revealed that FT3 level is the most important predictor of ghrelin levels. CONCLUSION: Thyroid hormones and antibodies seem to have a potential effect on serum ghrelin levels in patients with hypothyroidism.     

Clinical studies on lipid metabolism in hyperthyroidism and hypothyroidism--evaluation of serum apolipoprotein levels before and after treatment

The present study was undertaken to assess lipid metabolism in patients with thyroid dysfunction with special reference to serum apolipoprotein levels. Serum lipid, lipoprotein and apolipoprotein levels were determined in 28 hyperthyroid and 16 hypothyroid female patients while untreated and euthyroid. Apolipoproteins were measured by the method of single radial immuno-diffusion (SRID). These results were compared with the values of 28 female controls. In the untreated hyperthyroid group, the serum levels of total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were significantly decreased compared to the controls and increased after treatment. In hypothyroidism, these values before treatment were higher than those in the controls and decreased after treatment. Serum apo A-I, A-II, B and C-III levels were significantly decreased in the untreated hyperthyroid group compared to the control values. Apo C-II and E levels in hyperthyroidism were identical both before and after treatment compared with the control values, respectively. In the untreated hypothyroidism, apo B, C-II, C-III and E levels were significantly elevated compared to the controls, and these changes in apolipoproteins except apo C-II were restored after treatment. Apo A-I and A-II levels in the untreated hypothyroidism were not statistically different from the values after treatment or those in the control group. Serum thyroid hormone (T3, T4) levels inversely correlated apo B and C-III in all subjects. In hypothyroidism, serum TSH positively correlated with apo B, C-II and C-III. The increase in relative body weight (%RBW) in hyperthyroidism during treatment correlated with the changes of TC and LDL-C. In conclusion, these results indicate that thyroid hormones have a substantial influence on the serum apolipoprotein levels, and that measurement of apolipoproteins as well as lipids and lipoproteins in patients with thyroid dysfunction may be useful to evaluate the lipid metabolism and the effect of therapy.     

Concentrations of somatomedin-C and triiodothyronine in patients with thyroid dysfunction and nonthyroidal illnesses

We studied the possibility of an association between serum somatomedin-C (Sm-C) and thyroid hormone concentrations. For this purpose 34 hyperthyroid patients, 39 patients with primary hypothyroidism, 36 patients with severe nonthyroidal illnesses (NTI), and 63 euthyroid healthy control subjects were examined. The mean concentration of serum dialyzable free triiodothyronine (FT3) was 26.6 +/- 15.4 pmol/l (+/- SD) in hyperthyroidism, 2.8 +/- 1.2 in hypothyroidism, 4.2 +/- 1.1 in NTI, and 5.3 +/- 0.7 in controls. The lowest mean concentration of serum Sm-C (10.1 +/- 3.0 nmol/l) was found in the NTI group and the highest in the hyperthyroid group (16.8 +/- 3.2): these concentrations differed significantly from the mean control level (12.2 +/- 2.2). In NTI patients the serum FT3 and T3 levels correlated significantly with the serum Sm-C levels (r = 0.63; p less than 0.001, r = 0.65; p less than 0.001, respectively). In hypothyroid patients there was a weak correlation between the serum FT3 and Sm-C levels (r = 0.36; p less than 0.05), but no correlations were found in hyperthyroid and healthy subjects. We conclude that the lowered Sm-C levels in NTI do not reflect a hypothyroid state, as normal Sm-C levels were found in hypothyroidism, and that impaired nutritional state of the patients is the most likely explanation for the association between Sm-C and FT3 (and T3) in NTI.     

Role of surrogate markers in assessment of insulin resistance in females with thyroid disorders

IntroductionThyroid status is known to affect insulin sensitivity although conflicting data have been reported regarding hypothyroid and hyperthyroid states. Assessment of insulin resistance is difficult, therefore we compared homeostasis model assessment (HOMA), glucose to insulin (G:I) ratio, glucose to C-peptide (G:C) ratio and ferritin of hypothyroid and hyperthyroid subjects with euthyroid, euglycemic subjects.MethodsThe study group comprised of 40 hypothyroid, 25 hyperthyroid female subjects and 40 euthyroid controls. Serum samples of all the patients were assayed for thyroid profile, glucose, Insulin, C-peptide and ferritin. Homeostasis model of assessment (HOMA-IR), (G:I), (G:C) and ferritin were employed as surrogate measures to assess the level of insulin resistance. The area under the curves for the surrogate markers was determined from the receiver operating characteristics (ROC) curves for the hypothyroid and hyperthyroid patients.ResultsPatients with hypothyroidism demonstrated insulin resistance as observed by the higher HOMA-IR and G:I ratio as compared to the controls whereas insulin resistance was not detected in the hyperthyroid patients in our study.ConclusionThyroid dysfunction attributes to deranged glucose metabolism. Assessment of the surrogate markers might prove to be beneficial in detecting insulin resistance at the incipient stages and subsequent management.     

Plasma atriopeptin concentrations in hyperthyroidism, euthyroidism, and hypothyroidism: studies in man and rat

Atriopeptin (AP) is a polypeptide produced by atrial myocytes that is capable of inducing diuresis, natriuresis, and vasodilatation. Because thyroid dysfunction is known to be associated with alterations in both renal function and vasomotor control, we investigate the possible effects of varying thyroid function on AP in humans and rats. Plasma AP concentrations were determined in hyperthyroid and hypothyroid patients and normal subjects. Plasma AP was also measured in some patients after the iv infusion of 1 L 150 mmol/L NaCl and after treatment of hyperthyroidism or hypothyroidism. Plasma and atrial AP concentrations were measured in hyperthyroid, euthyroid, and hypothyroid rats. Plasma AP concentrations did not differ in the hyperthyroid (n = 22), euthyroid (n = 45), and hypothyroid (n = 16) subjects [47.1 +/- 18.2 (mean +/- SD), 45.1 +/- 28.9, and 42.4 +/- 20.0 pg/mL, respectively]. After NaCl infusion, mean plasma AP concentrations did not increase significantly in any of the three groups. Treatment of hyperthyroidism and hypothyroidism did not result in a significant change in plasma AP levels. In contrast, plasma AP concentrations were significantly higher in T4-treated (hyperthyroid) rats than in either euthyroid or propylthiouracil-treated (hypothyroid) rats [621 +/- 17 vs. 266 +/- 41 (P less than 0.01) and 210 +/- 28 pg/mL (P less than 0.001), respectively], whereas atrial AP contents were similar in the three groups of rats. We conclude that hyperthyroidism and hypothyroidism in man are not associated with significantly altered plasma AP concentrations. The higher plasma AP levels in T4-treated rats may reflect the relatively shorter duration or greater severity of thyroid dysfunction or thyroid hormone-induced myocardial hypertrophy in the animals.     

Effect of thyroid function on LDL oxidation in hypothyroidism and hyperthyroidism

Oxidized low-density lipoproteins (LDL) are highly suspected of initiating the atherosclerosis process. Hypothyroidism is frequently associated with hypercholesterolemia and carries increased risk for atherosclerosis. In contrast to hypothyroidism, hyperthyroidism is not associated with increased LDL cholesterol, but is associated with increased oxidized LDL. This study was designed to evaluate the changes in LDL oxidation in subjects with hypothyroidism or hyperthyroidism, and to reveal the effects of treatment in hypothyroidism and hyperthyroidism on LDL oxidation and lipid profiles. Thirty-two patients with hypothyroidism and 16 patients with hyperthyroidism were studied before the therapy and thereafter, when they were euthyroid with appropriate treatment. Plasma lipids and lipoproteins, and the oxidizability of LDL by determining the levels of malonaldehyde bis (dimethyacetyl) (MDA) and diene conjugation, were determined at baseline and after the patients were rendered euthyroid. The actual content of dienes in LDL particles was increased in hypothyroidism, with a decrease after T4 supplementation (p < .001). Dienes in LDL particles were increased in hyperthyroidism, with a decrease after treatment (p < .05). In hypothyroid patients, the lag phase was shorter in the pretreatment period than in the euthyroid period (p > .05). The lag phase of hyperthyroid patients was shorter in the pretreatment period than in the euthyroid period and hypothyroid state (p < .001). The Cu2+-catalyzed dienes of LDL and MDA oxidation in the hypothyroid state and the subsequent euthyroid states were decreased (p < .001). The Cu2+-catalyzed dienes of LDL (p < .01) and MDA oxidation (p < .001) in hyperthyroid patients after treatment were decreased. The enhanced LDL oxidation may play a role in the cardiac disease process in both hypothyroidism and hyperthyroidism.     

Low density lipoprotein cholesterol, lipoprotein(a), and apo(a) isoforms in the elderly: relationship to fasting insulin. Associazione Medica Sabin

BACKGROUND AND AIM: Insulin resistance/hyperinsulinemia are often associated with aging and could play an important role in the development of glucose intolerance and dyslipidemia in the elderly. We investigated the relationship between plasma fasting insulin with total cholesterol (TC) and low density lipoprotein LDL cholesterol (LDL-C), triglycerides (TG), lipoprotein(a) [Lp(a)] levels apolipoprotein (a) [apo (a)] isoforms in 100 free-living "healthy" octo-nonagenarians. METHODS AND RESULTS: Fasting insulin was positively correlated with TG, whereas a negative relation was found with TC and LDL-C (r = -0.29 and r = -0.28 respectively; p < 0.01), LDL-C/apo B, HDL-C and apo A-I levels. Fasting insulin was also inversely correlated with Lp(a) levels (r = -0.22; p < 0.03), whereas the latter were significantly related with TC and LDL-C (r = 0.30 and r = 0.31; p < 0.005), TG (r = 0.21; p < 0.05) and apo B (r = 0.26; p < 0.02). There was a negative relation between Lp(a) levels and apo(a) isoforms: the greater the apo(a) molecular weight, the lower the Lp(a) level (p < 0.0001). Fasting insulin increased with apo(a) size, though the difference in insulin levels among apo(a) isoforms was not significant (p = 0.4). Multiple regression analysis showed that fasting insulin was the best predictor of LDL-C (R2 = 0.14; p = 0.002) irrespective of age, gender, BMI, waist circumference and TG, while apo(a) isoform size, BMI and waist circumference were related with Lp(a) irrespective of TC and LDL-C, TG and apo B (R2 = 0.35 to 0.37; p < 0.0001). CONCLUSIONS: These results suggest that fasting insulin levels significantly influence LDL-C metabolism in old age. Lp(a) levels seem to be very strongly related to genetic background, although an indirect relation with insulin through adiposity and/or other associated lipid abnormalities cannot be ruled out.     

Effect of -thyroxine therapy on lipoprotein fractions in overt and subclinical hypothyroidism, with special reference to lipoprotein(a)

The effect of -thyroxine therapy on lipoprotein fractions was assessed in 15 patients with overt hypothyroidism (14 women and one man aged 45 ± 3.9 years; thyrotropin [TSH]: mean ± SEM, 42 ± 6.5 mIU/L; range, 20.5 to 106.5) and 14 patients with subclinical hypothyroidism (13 women and one man aged 41 ± 4 years; TSH: mean ± SEM, 9.1 ± 1 mIU/L; range, 5.1 to 17.3). Fasting serum lipid levels were measured initially and 4 months after achievement of a euthyroid state with incremental -thyroxine therapy (TSH: mean ± SEM, 1.8 ± 0.4 mIU/L; range, 0.3 to 4.9 for both groups). In the ovartly hypothyroid group, restoration of a euthyroid state was associated with a significant reduction in total cholesterol, and apo B. In the subclinically hypothyroid group, there was a significant reduction of only total cholesterol (199.6 ± 13.2 v 183.4 ± 11.6 mg/dL) and LDL-C (131.6 ± 8.4 v 114 ± 9.25 mg/dL). In contrast, lipoprotein(s) [Lp(a)] was unaffected by the incremental adjustment of -thyroxine therapy in both groups (overt, 34.3 ± 8.8 v 35.6 ± 6.7 mg/dL; subclinical, 23.0 ± 8.6 v 29.4 ± 9.5 mg/dL). We conclude that restoration of a euthyroid state in patients with overt hypothyroidism has no significant effect on Lp(a) levels, and confirm that subclinical hypothyroidism is associated with a significant increase in LDL-C, known to have an atherogenic effect.     

Serum N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) levels in hyperthyroidism and hypothyroidism

E Natriuretic peptides represent a novel diagnostic tool in the assessment of heart failure. N-terminal-pro-B-type natriuretic peptide (NT-proBNP), a member of the natriuretic peptid family, is produced and released from cardiac ventricles. Changes in cardiac functions are observed in thyroid dysfunctions. The aim of this study was to assess the changes in serum NT-proBNP levels and to evaluate impact of thyroid hormones on serum NT-proBNP in patients with hyperthyroidism and hypothyroidism. Serum NT-proBNP levels were measured in 21 patients with hyperthyroidism and in 24 patients with hypothyroidism and compared with 20 healthy control subjects. Patients without cardiac disease were included into the study as well. Serum NT-proBNP levels were measured by electrochemiluminescence immunoassay. Serum NT-proBNP levels were higher in hyperthyroid patients than in hypothyroid patients and in control subjects, with mean values of 239.03 +/- 47.33, 45.97 +/- 13.48, 55.57 +/- 13.01 pg/ml, respectively (p < 0.0001). Serum NT-proBNP and thyroid hormones were correlated in all patients. Moreover, there was a significant positive correlation between serum NT-proBNP and serum free T4 (FT4) levels (r = 0.549, p = 0.012) in hyperthyroidic patients. Multiple regression analyses demonstrated that increasing FT4 was independently associated with a high serum NT-proBNP levels, whereas heart rate was not in hyperthyroid patients. Serum NT-proBNP levels are higher in the hyperthyroid state as compared with the hypothyroid and euthyroid state. Thyroid dysfunction affects serum NT-proBNP levels, possibly influencing the secretion of the peptide. Therefore, thyroid function has to be considered when evaluating high serum NT-proBNP levels in patients without cardiac dysfunction.     

The effect of L-thyroxine replacement therapy on lipid based cardiovascular risk in subclinical hypothyroidism

The aim of our study was to assess the changes in serum lipid profiles after replacement therapy with L-T4 in patients with subclinical hypothyroidism (SCH), and to see whether there is an improvement in dyslipidemia based cardiovascular risk. Thirty non-smoker pre-menopausal women with newly diagnosed SCH (TSH between 4 and 10 microIU/ml) were involved in our study; twenty-six euthyroid healthy subjects were used as control group. TSH, free T3 (FT3), free T4 (FT4), total cholesterol (TC), triglyceride (TG), HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) levels were measured before and after 6 months of L-T4 (50-100 microg/ day) therapy. TSH levels were targeted as < 2.0 microIU/ml. LDL-C was calculated using the Friedewald formula, while the cardiovascular risk was assessed with the TC/HDL-C ratio. Pre-treatment serum TC and LDL-C concentrations in SCH patients were significantly higher than those of euthyroid subjects (199.8 +/- 22.2 vs 181.5 +/- 24.6 mg/dl, p < 0.01; 146.3 +/- 26.1 vs 124.8 +/- 12 mg/dl, p < 0.001, respectively). TC, LDL-C levels and the TC/HDL-C ratio were reduced significantly after 6-month replacement therapy (-21.1 +/- 34.4 mg/dl or -10.5%, p < 0.01; -21.5 +/- 30.3 mg/dl or -14.7%, p < 0.001, respectively; and TC/HDL-C from 4.8 +/- 0.6 to 4.1 +/- 0.5 mg/dl, p < 0.01), while body mass index (BMI) values did not change. In conclusion, even mild elevations of TSH are associated with changes in lipid profile significant enough to raise the cardiovascular risk ratio, and these changes are corrected once the patients have been rendered euthyroid.     

Plasma high density lipoprotein cholesterol in thyroid disease.

The plasma levels of high density lipoprotein cholesterol (HDL-C) were reduced in 16 hyperthyroid female patients compared to 37 euthyroid women (33.5 +/- 8 vs. 51.5 +/- 13 mg/dl (mean +/- SD); P less than 0.001). When 5 patients were restudied after restoration of the euthyroid state, plasma HDL-C increased from 29 +/- 5 to 43 +/- 11.5 mg/dl (P less than 0.05). In addition, in 22 hypothyroid women, HDL-C levels were also diminished compared to the euthyroid group (43.4 +/- 15.5 vs. 51.5 +/- 13 mg/dl; P less than 0.05). Nine patients were restudied after L-T4 replacement therapy; their levels of HDL-C increased but not to a statistically significant degree. The daily administration of 0.3 mg L-T4 to eight normal male volunteers for 1 month did not significantly affect HDL-C levels.     

Lipid profile in subclinical hypothyroidism: is L-thyroxine substitution beneficial?

OBJECTIVE: The significance of dyslipidemia in subclinical hypothyroidism (SH) and the effect of thyroid substitution on lipids remain controversial. The present study aimed to assess the association of SH with lipid abnormalities and to quantify the effect of L-thyroxine therapy on serum lipid profiles. DESIGN: Serum lipid parameters of 66 patients with SH and 75 age- and sex-matched euthyroid controls were evaluated in a cross-sectional study. RESULTS: Patients with SH had higher total cholesterol (TC) (222+/-45 (s.d.) vs 190+/- 32 mg/dl), low-density lipoprotein cholesterol (LDL-C) (139+/-28 vs 118+/-39 mg/dl), apolipoprotein B (149+/-21 vs 139+/-18 mg/dl) and lipoprotein (a) (Lp(a)) (median 12.5 (0.8-101) mg/dl vs 7 (0.8-44) mg/dl) levels compared with euthyroid controls (P<0.05 for all comparisons). In a follow-up study including 37 patients with SH, all measurements were repeated after restoration of a euthyroid state with incremental doses of l-thyroxine. No significant changes in serum lipid profiles were observed except for a decrease in high-density lipoprotein cholesterol (59+/-15 to 55+/-14 mg/dl, P<0.05). However, patients with high pre-treatment TC (> or =240 mg/dl) showed a significant reduction in both TC (278+/-28 vs 257+/-36 mg/dl, P<0.05) and LDL-C (192+/-23 vs 173+/-28 mg/dl, P<0.01) levels. Similar but more pronounced changes were observed in a subgroup of patients with pre-treatment levels of TSH > or =10 microU/ml. Thyroid autoimmunity had no effect on either the baseline or the post-treatment lipid profile. CONCLUSION: Although patients with subclinical hypothyroidism exhibit increased levels of the atherogenic parameters (mainly LDL-C and Lp(a)), thyroid substitution therapy does not seem to significantly improve dyslipidemia in the whole group of patients.     

Elevated serum lipoprotein(a) in subclinical hypothyroidism

OBJECTIVES Asymptomatic lymphocytic thyroiditis and subclinical hypothyroidism are associated with increased risk for coronary artery disease. The present study aimed at evaluating serum lipoprotein(a)(Lp(a), measured as apo(a), and other lipid parameters In 32 subjects with asymptomatic subclinical hypothyroidism. SUBJECTS Thirty-two Chinese subjects with asymptomatic subclinical hypothyroidism were compared to 96 age and sex-matched healthy controls. RESULTS Subclinical hypothyroid patients had higher (P < 0.005) apo(a), total triglyceride (TG), total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) but lower (P < 0.05) high density lipoprotein cholesterol (HDL-C) levels compared with sex and age-matched controls (apo(a) 296 (48–1650) vs 182 (19–1952 U/I), geometric mean (range); TG 1.86 ± 0.94 vs 1.33±0.74mmol/l (mean ± SD); TC 6.10 ±1.17 vs 5.42 ±1.13 mmol/l; LDL-C 410 ± 1.00 vs 3.49 ± 0.96 mmol/l; HDL-C 1.15 ± 0.40 vs 1.34 ± 0.40 mmol/l, respectlvely). Apo A-I and apo B were also higher than controls (1.96 ± 048 vs 1.48 ± 029 g/l and 1.44 ± 042 vs 1.05±029 g/l, respectively). Total cholesterol/HDL ratio and LDL/HDL ratio were also elevated in these subjects (577 ± 1.96 vs 428 ±1.19 and 389 ± 1.41 vs 2.79 ± 0.97, respectively, both P < 0.0005). Individual analysis revealed that 16 (50%) subjects had hyperlipoprotelnaemia (TC > 5.2 mmol/l in 10;TC > 52 mmol/l and TG > 2.3mmol in six) as compared to 21(208%) in the control group (P < 0.005). Subjects with TSH ± 11.0mlU/l had significantly higher TC/HDL and LDL/HDL ratios. A significant correlation was observed between TSH levels and TC/HDL ratios (r = 0.455, P < 001). CONCLUSIONS Subclinical hypothyroidism Is associated not only with elevated LDL-cholesterol levels and low HDL-cholesterol levels but also with elevated lipoprotein (a). This may further Increase the risk development of atheroscierosis.     

Tyrosine and glutamic acid in plasma and urine of patients with altered thyroid function

The plasma concentrations of glutamic acid and tyrosine were measured in euthyroid, hyperthyroid, and hypothyroid patients. In the group of normal individuals, plasma concentrations of glutamic acid were more variable than were those of tyrosine. Levels of glutamic acid in plasma were elevated proportionately more than were those of tyrosine in hyperthyroidism, but were normal in hypothyroidism. Oral sodium glutamate tolerance in hyperthyroid patients did not differ from that of normal subjects in the mean increments attained from fasting to peak levels. This contrasts with altered tyrosine tolerance previously reported in hyperthyroidism. In hypothyroid patients, after ingestion of a load of sodium glutamate the mean increments from fasting to peak levels were slightly greater than normal. Daily variations in the plasma concentrations of glutamic acid were undemonstrable in normal individuals and were not modified by either hyperthyroidism or hypothyroidism. An unexplained elevation in the plasma concentration of glutamic acid at 2 a.m. was observed in several hyperthyroid patients. The urinary excretion of glutamic acid in a 24-hr period was increased nearly tnefold in hyperthyroid patients compared to results obtained in normal subjects. A similar percentage of the total glutamic acid (31–37%) was excreted during the period from 8 a.m. to 4 p.m. in both normal and hyperthyroid patients. The urinary excretion of tyrosine was also increased in hyperthyroidism; the magnitude of the increase (nearly twofold) was less than that of glutamic acid. These data provide further evidence that in hyperthyroid patients increases in the concentrations of tyrosine and glutamic acid in plasma are consistent findings and demonstrate that the urinary excretion of both of these amino acids is also markedly increased.     

Effects of thyroid hormone on plasma adenosine 3',5'-monophosphate production in man.

Thyroid hormone may nonspecifically modulate cAMP production and end-organ responsiveness to diverse hormonal stimuli. This hypothesis was tested in 18 hyperthyroid, 16 euthyroid, and 8 hypothyroid human subjects by measurement of cAMP in plasma and urine both in the basal state and following stimulation by epinephrine, parathyroid hormone, and glucagon—hormones known to act through cAMP. Supine fasting plasma cAMP (PcAMP) concentrations (mean ± SEM) were minimally elevated in the hyperthyroid patients (23.5 ± 1.3 nM, p < 0.001) when compared with the euthyroid (17.1 ± 0.6 nM) or hypothyroid (20.5 ± 1.7 nM) groups. Infusion of propranolol over 45 min failed to lower basal PcAMP concentrations in 5 hyperthyroid subjects. Epinephrine infusions (0.05 μg/kg/min) caused an exaggerated peak PcAMP response (58.7 ± 5.7 nM) in 5 hyperthyroid patients and a diminished response (27.3 ± 3.2 nM) in 5 hypothyroid patients when compared with 5 euthyroid subjects (42.3 ± 2.6 nM, p < 0.05). Administration of parathyroid hormone, 200 units intravenously, also caused significant differences in urinary cAMP excretion (μmole/hr) in the hyperthyroid (11.37 ± 0.96, p < 0.005) and hypothyroid patients (2.4 ± 0.58, p < 0.001) when compared to the euthyroid group (6.59 ± 0.74). Glucagon (1 mg intravenously) caused an enhanced peak PcAMP response in the hyperthyroid patients (514 ± 34 nM) compared with the euthyroid (240 ± 29 nM) or hypothyroid (223 ± 28 nM) groups (p < 0.005). The PcAMP disappearance half-time following the peak response to glucagon was similar in all three groups, indicating that plasma sampling is probably a valid indicator of cAMP production. These studies demonstrate that thyroid hormone may modulate the response of multiple hormonal effects mediated by cAMP. The findings suggest a further cellular mode of action of thyroid hormone which may account for a number of the metabolic disturbances observed in patients with thyroid disease.     

Effectiveness of radioiodine (131-I) as definitive therapy in patients with autoimmune and non-autoimmune hyperthyroidism

We evaluated the outcome of radioiodine (RAI) therapy in 100 consecutive patients treated in the period 2000-2001 for hyperthyroidism due to Graves' disease (GD), toxic adenoma (TA) and toxic multinodular goiter (TMG). Thyroid function was measured before and after therapy every 3-6 months up to 3 yr. Three years after therapy, 75% of TA patients were euthyroid, 18.7% were hypothyroid and 6.3% hyperthyroid. Of the TMG patients, 62.2% were euthyroid, 18.9% were hypothyroid and 18.9% hyperthyroid. In GD patients euthyroidism was achieved in 12.9% of the patients, hypothyroidism in 74.2% and hyperthyroidism persisted in 12.9%. Definitive hypothyroidism was significantly higher in GD (p<0.0001) than in TA and TMG patients. Overall, positive effect of RAI (definitive hypothyroidism or euthyroidism) was very high: 93.7% in TA, 81.1% in TMG and 87.1% in GD patients. Thyroid volume reduction was observed in all patients, but was higher in GD patients (mean reduction of 76%) and in TA patients (mean nodule reduction of 69%). In TMG, mean reduction was of 32%. The median activity of RAI received by the 86 cured patients was 555 MBq (15 mCi) compared to 407 Mbq (11 mCi) received by the 14 patients who remained hyperthyroid. No influence was found between outcome and clinical parameters at the moment of 131-I therapy. In conclusion, our results indicate that RAI therapy is highly effective and safe for the control of hyperthyroidism.