The prevalence of subclinical hypothyroidism at different total plasma cholesterol levels in middle aged men and women: a need for case-finding?

OBJECTIVE: In order to determine whether screening of thyroid function is justified in patients with hypercholesterolaemia, we determined the prevalence of subclinical hypothyroidism at different levels of total plasma cholesterol in middle-aged men and women. DESIGN AND METHODS: 1200 participants were selected from a population based cross sectional study on risk factors for cardiovascular diseases. The participants were divided into three groups: total plasma cholesterol < 5 mmol/l, total plasma cholesterol 5-8 mmol/l, total plasma cholesterol > 8 mmol/l. Each group was comparable in size and sex distribution. Subclinical hypothyroidism was defined as plasma TSH levels higher than 4 mU/l, in the presence of normal free thyroxine (FT4(4)) concentration. RESULTS: Plasma samples of a total of 1191 participants were analyzed. The overall prevalence of subclinical hypothyroidism was 1.9% in men and 7.6% in women of middle age. In women the prevalence of subclinical hypothyroidism increased from 4.0 percent in the lowest, to 10.3 percent in the highest cholesterol stratum (P = 0.02). In men, the mean prevalence was 1.8 percent and roughly similar in the various strata. After age correction, an increase of 1 mU/l TSH in women was associated with an increase of 0.09 mmol/l total plasma cholesterol (95% confidence interval (CI) 0.02-0.16 mmol/l). A similar trend was found in men (0.16 mmol/l, 95% CI -0.02-0.34 mmol/l). CONCLUSIONS: In the population, the prevalence of subclinical hypothyroidism is up to 10 percent in middle aged women with high levels of total plasma cholesterol and may justify case-finding. In these women approximately 0.5 mmol/l of total plasma cholesterol can be attributed to the subclinical thyroid dysfunction. In men a similar correlation between thyroid dysfunction and total plasma cholesterol is seen, but the prevalence of thyroid dysfunction is considerably lower.     

Zufallsbefund: erhöhter TSH-Wert

The use of thyroid-stimulating hormone (TSH) testing in routine laboratory screening and testing of TSH before administration of contrast medium, resulted in an increased number of incidentally detected elevated TSH levels. In the case of slightly increased values in asymptomatic patients, repeated measurement of TSH is recommended for confirmation. Confirmed elevated TSH levels should lead to additional measurements of the peripheral thyroid hormones, determination of thyroid autoantibodies and performance of thyroid gland ultrasound examination. The most common reasons for acquired subclinical and overt hypothyroidism are autoimmune diseases of the thyroid gland and in many cases substitution therapy with levothyroxine is then necessary. In subclinical hypothyroidism it remains unclear at which TSH levels the initiation of substitution therapy makes sense. In the case of simultaneously elevated peripheral thyroid hormones rare diseases, such as secondary hyperthyroidism and thyroid hormone resistance should be considered.     

Low-density lipoprotein cholesterol in subclinical hypothyroidism.

The significance of subclinical hypothyroidism in regard to ensuing hyperlipidemia remains unclear. Because an unfavorable lipid profile would provide a possible explanation for the reported association of coronary-heart disease with this syndrome, we have evaluated the relationship of thyrotropin (TSH) with total cholesterol, low-density-lipoprotein (LDL) cholesterol, and triglycerides in patients with normal thyroid function (n = 4886) as well as subclinical (n = 1055) and manifest (n = 92) hypothyroidism. Serum concentrations of LDL cholesterol were similar in euthyroid persons (134+/-39 mg/dL) and in patients with subclinical hypothyroidism (137+/-40 mg/dL) but were higher (178+/-70 mg/dL, p < 0.01) in overt hypothyroidism. Within the group of subjects with subclinical hypothyroidism there was no apparent relationship between serum concentrations of TSH ranging from 4.0 to 49.0 microU/mL and concentrations of LDL cholesterol. Thus, there is no "threshold value" of TSH in these patients per se necessitating substitution therapy with thyroxine.     

Prolactin and TSH response to TRH and metoclopramide before and after l-thyroxine therapy in subclinical hypothyroidism

The effects of the dopamine (DA) receptor antagonist metoclopramide on the plasma thyroid stimulating hormone (TSH) and prolactin (PRL) levels were studied in 8 patients with subclinical hypothyroidism (defined as absence of clinical signs of hypothyroidism with normal thyroid hormone levels, normal or slightly increased basal plasma TSH levels and increased and long-lasting TSH response to TRH) before and after l-thyroxine replacement therapy. Metoclopramide induced a significant (p less than 0.01) TSH release in the subclinical hypothyroid patients. Two weeks after l-thyroxine replacement therapy (50 micrograms/day), the TSH response to metoclopramide was completely blunted in subclinical hypothyroidism. In these patients a significant (p less than 0.01) inhibition of TSH response to intravenous thyrotropin-releasing hormone (TRH) was also observed after treatment with thyroid hormone. In analogy to the TSH behavior, plasma PRL secretion in response to metoclopramide and TRH administration was significantly (p less than 0.05) inhibited in the subclinical hypothyroid patients after l-thyroxine replacement therapy.     

TSH-controlled L-thyroxine therapy reduces cholesterol levels and clinical symptoms in subclinical hypothyroidism: a double blind, placebo-controlled trial (Basel Thyroid Study)

This study evaluated the effect of physiological, TSH-guided, L-thyroxine treatment on serum lipids and clinical symptoms in patients with subclinical hypothyroidism. Sixty-six women with proven subclinical hypothyroidism (TSH, 11.7 +/- 0.8 mIU/liter) were randomly assigned to receive L-thyroxine or placebo for 48 wk. Individual L-thyroxine replacement (mean dose, 85.5 +/- 4.3 microg/d) was performed based on blinded TSH monitoring, resulting in euthyroid TSH levels (3.1 +/- 0.3 mIU/liter). Lipid concentrations and clinical scores were measured before and after treatment. Sixty-three of 66 patients completed the study. In the L-thyroxine group (n = 31) total cholesterol and low density lipoprotein cholesterol were significantly reduced [-0.24 mmol/liter, 3.8% (P = 0.015) and -0.33 mmol/liter, 8.2% (P = 0.004), respectively]. Low density lipoprotein cholesterol decrease was more pronounced in patients with TSH levels greater than 12 mIU/liter or elevated low density lipoprotein cholesterol levels at baseline. A significant decrease in apolipoprotein B-100 concentrations was observed (P = 0.037), whereas high density lipoprotein cholesterol, triglycerides, apolipoprotein AI, and lipoprotein(a) levels remained unchanged. Two clinical scores assessing symptoms and signs of hypothyroidism (Billewicz and Zulewski scores) improved significantly (P = 0.02). This is the first double blind study to show that physiological L-thyroxine replacement in patients with subclinical hypothyroidism has a beneficial effect on low density lipoprotein cholesterol levels and clinical symptoms of hypothyroidism. An important risk reduction of cardiovascular mortality of 9-31% can be estimated from the observed improvement in low density lipoprotein cholesterol.     

Decreased HDL cholesterol in subclinical hypothyroidism: the effect of L-thyroxine therapy

Thyroid function and lipid tests were measured in 29 premenopausal women with subclinical hypothyroidism. This group was compared with 41 euthyroid women matched for age and metabolic parameters. In basal condition there was no difference in thyroid hormone levels between the two groups except for TSH concentration (P less than 0.01). Total cholesterol, triglycerides and apolipoprotein (apo A1, A2, B) of women with subclinical hypothyroidism were not different from controls. HDL cholesterol was significantly decreased in subclinical hypothyroidism compared to the controls (P less than 0.01). With thyroxine therapy, normalization of serum TSH was associated with (1) no significant change in total cholesterol and triglycerides, (2) an increase of HDL cholesterol (P less than 0.01) and apoprotein A1 (P less than 0.05) levels. Total cholesterol/HDL cholesterol ratio was increased in subclinical hypothyroidism (P less than 0.01). During L-thyroxine therapy this ratio returned to normal value. Decreased HDL cholesterol concentration might cause coronary heart disease reported in women with subclinical hypothyroidism.     

Plasma thyrotropin bioactivity in Down's syndrome children with subclinical hypothyroidism

OBJECTIVE: Subclinical hypothyroidism occurs in a number of children with Down's syndrome (DS). The reason for the mildly elevated plasma thyrotropin (TSH) concentrations is not known. The present study investigated whether decreased TSH bioactivity plays a role in this phenomenon. DESIGN: A retrospective study of plasma specimens from DS children with mildly elevated plasma TSH concentrations and thyroid hormone levels within the reference range, using a TSH receptor-adenylate cyclase mediated bioassay. METHODS: Strain JP26 Chinese hamster ovary (CHO) cells, stable transfected with the human TSH receptor, were incubated with unfractionated plasma (1/10 diluted in hypotonic incubation medium) of 10 DS children with subclinical hypothyroidism and nine euthyroid children with insulin-dependent diabetes mellitus as controls. cAMP released in the incubation medium was measured by RIA. Mock-transfected CHO cells were used to correct for non-specific CHO response. WHO Second International Reference Preparation of human TSH was dissolved and diluted in pooled normal human plasma and simultaneously bioassayed to match patient and control results. RESULTS: Plasma TSH levels were slightly increased in DS (mean +/- S.D., 6.5+/-1.3 mU/l, reference range 0.4-4.0 mU/l). Plasma TSH levels for controls (1.3+/-0.4 mU/l) were within the reference range. Plasma thyroid hormone levels in patients and controls were normal, plasma TSH binding inhibitory immunoglobulin and thyroid peroxidase antibodies were negative. cAMP levels (corrected for non-specific CHO response) in DS patients (18.4+/-3.9 pmol/well) and in controls (14.3+/-1.3 pmol/well) did not significantly differ from cAMP levels generated by patient-TSH equivalent TSH standards (16.3+/-0.9 pmol/well). CONCLUSIONS: The present results demonstrate normal TSH bioactivity in plasma of DS children, indicating that subclinical hypothyroidism in these patients is of primary (thyroidal) origin.     

Does treatment withl-thyroxine influence health status in middle-aged and older adults with subclinical hypothyroidism?

OBJECTIVE: To determine if health-related quality of life (HRQL) in patients of middle age and older with elevated thyroid-stimulating hormone (TSH) and normal total thyroid hormone levels—subclinical hypothyroidism—improves withl-thyroxine replacement therapy. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Outpatient clinic. PATIENTS: Thirty-seven patients with subclinical hypothyroidism, most with symptoms consistent with hypothyroidism, over 55 years of age. INTERVEJVTIOJVS: Placebo or L-thyroxine replacement therapy to achieve normal TSH level. MEASUREMENTS AND MAIN RESULTS: Disease-specific and general HRQL, cognitive function, bone mineral density, lipid levels. The mean daily dose of L-thyroxine replacement in the active group was 68±21 μg. TSH decreased by 8.6 mIU/L (95% confidence interval [CI] 4.1 to 13.1) and T₄ increased by 27.9 nmol/L (95% CI 14.8 to 41.2). There was a statistically significant improvement in a composite psychometric memory score in treated versus control patients; all other outcomes showed similar findings in the two groups. Although confidence intervals for most measures did not exclude an important improvement in HRQL with thyroid replacement, no measure of symptoms or HRQL either showed clinically important trends in favor of treatment, or approached conventional levels of statistical significance. CONCLUSIONS: In middle-aged and older patients with elevated TSH and normal T₄, it may not be harmful to follow biochemical and clinical status even in the presence of nonspecific symptoms potentially associated with hypothyroidism. Supported by a grant from Ontario Ministry of Health and by a grant from Boots Pharmaceuticals. Medication and placebo was provided by Boots Pharmaceuticals.     

Does Treating Subclinical Hypothyroidism Improve Markers of Cardiovascular Risk?

Subclinical hypothyroidism is defined as an elevated serum thyroid-stimulating hormone (TSH) level in the face of normal free thyroid hormone values. The overall prevalence of subclinical hypothyroidism is 4-10% in the general population and up to 20% in women aged >60 years. The potential benefits and risks of therapy for subclinical hypothyroidism have been debated for 2 decades, and a consensus is still lacking. Besides avoiding the progression to overt hypothyroidism, the decision to treat patients with subclinical hypothyroidism relies mainly on the risk of metabolic and cardiovascular alterations. Subclinical hypothyroidism causes changes in cardiovascular function similar to, but less marked than, those occurring in patients with overt hypothyroidism. Diastolic dysfunction both at rest and upon effort is the most consistent cardiac abnormality in patients with subclinical hypothyroidism, and also in those with slightly elevated TSH levels (>6 mIU/L). Moreover, mild thyroid failure may increase diastolic blood pressure as a result of increased systemic vascular resistance. Restoration of euthyroidism by levothyroxine replacement is generally able to improve all these abnormalities. Early clinical and autopsy studies had suggested an association between subclinical hypothyroidism and coronary heart disease, which has been subsequently confirmed by some, but not all, large cross-sectional and prospective studies. Altered coagulation parameters, elevated lipoprotein (a) levels, and low-grade chronic inflammation are regarded to coalesce with the hypercholesterolemia of untreated patients with subclinical hypothyroidism to enhance the ischemic cardiovascular risk. Although a consensus is still lacking, the strongest evidence for a beneficial effect of levothyroxine replacement on markers of cardiovascular risk is the substantial demonstration that restoration of euthyroidism can lower both total and low-density lipoprotein-cholesterol levels in most patients with subclinical hypothyroidism. However, the actual effectiveness of thyroid hormone substitution in reducing the risk of cardiovascular events remains to be elucidated. In conclusion, the multiplicity and the possible reversibility of subclinical hypothyroidism-associated cardiovascular abnormalities suggest that the decision to treat a patient should depend on the presence of risk factors, rather than on a TSH threshold. On the other hand, levothyroxine replacement therapy can always be discontinued if there is no apparent benefit. Levothyroxine replacement therapy is usually safe providing that excessive administration is avoided by monitoring serum TSH levels. However, the possibility that restoring euthyroidism may be harmful in the oldest of the elderly population of hypothyroid patients has been recently raised, and should be taken into account in making the decision to treat patients with subclinical hypothyroidism who are aged >85 years.     

Hypothyreose

An autoimmune thyroiditis represents the main reason of hypothyroidism, defined as a lack of thyroid hormone. This autoimmune process results in destruction of functioning thyroid follicles. While subclinical or latent hypothyroidism is defined on the basis of laboratory values (an elevation of TSH with normal peripheral hormone levels), the typical signs and symptoms are associated with hypothyroidism. In about 80% of cases antibodies against thyroid peroxidase can be measured, but only in about 40–50% of cases antibodies against thyroglobulin are detectable. If hypothyrodism has been diagnosed, substitution with levothyroxine should be initiated, with the therapeutic goal to decrease TSH level to the lower normal range. In cases of subclinical hypothyroidism, levothyroxine medication should be started in patients with a high TSH value, positive antibodies and/or the typical ultrasound of autoimmune thyroiditis. However, substitution with levothyroxine in any case of elevated TSH values should be avoided.     

The immunofluorometric TSH assay as first-line test for suspected thyroid dysfunction

In this study of 103 patients with suspected thyroid dysfunction, the diagnostic value of a single basal immunofluorometric (IFMA) TSH measurement was evaluated and compared with the classical TRH test with RIA-TSH measurements, plasma TT4 concentrations and FT4I. A single basal TSH determination accurately predicted the TRH-stimulated TSH response, making the TRH test redundant in most patients. Because undetectable basal TSH did not always exclude a small rise in TSH, the TRH test could still be indicated in patients receiving thyroxine suppression therapy for thyroid cancer. Basal TSH differentiated accurately between euthyroidism and thyroid dysfunction, especially at the decision values of 0.20 and 4.0 mU/l, as proposed in this study. For diagnosis of clinical and subclinical hypo- and hyperthyroidism, additional measurement of TT4 and/or FT4I is necessary. A 2-yr follow-up of patients with subclinical thyroid dysfunction did not show progression to clinical disease. In some of the patients with subclinical hypothyroidism, substitution therapy with thyroxine had been started after initial testing. Indications for treatment of subclinical thyroid dysfunction are discussed.     

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.     

Thyroid dysfunction and serum lipids: a community-based study

OBJECTIVE: It is uncertain whether subclinical hypothyroidism (SCH) is associated with hypercholesterolaemia, particularly in subjects with SCH and serum TSH < or = 10 mU/l. Design, PATIENTS AND MEASUREMENTS: Cross-sectional study of 2108 participants in a 1981 community health survey in Busselton, Western Australia. Serum total cholesterol and triglycerides were measured in all subjects and high density lipoprotein cholesterol (HDL-C) measured (and low density lipoprotein cholesterol (LDL-C) calculated) in a subgroup of 631 subjects at the time of the survey. In 2001, TSH and free T4 concentrations were measured on archived sera stored at -70 degrees C. Serum lipid concentrations in subjects with thyroid dysfunction and euthyroid subjects were compared using linear regression models. RESULTS: In the group as a whole, serum total cholesterol was higher in subjects with SCH (N = 119) than in euthyroid subjects (N = 1906) (mean +/- SD 6.3 +/- 1.3 mmol/l vs. 5.8 +/- 1.2 mmol/l, P < 0.001 unadjusted, P = 0.061 adjusted for age, age(2) and sex). Serum total cholesterol was similarly elevated in subjects with SCH and TSH < or = 10 mU/l (N = 89) (6.3 +/- 1.3 mmol/l, P < 0.001 unadjusted, P = 0.055 adjusted for age, age(2) and sex). In the subgroup analysis, LDL-C was higher in subjects with SCH (N = 30) than in euthyroid subjects (N = 580) (4.1 +/- 1.2 mmol/l vs. 3.5 +/- 1.0 mmol/l, P < 0.01 unadjusted, P = 0.024 adjusted for age, age(2) and sex). LDL-C was significantly increased in subjects with SCH and TSH < or = 10 mU/l (N = 23) (4.3 +/- 1.3 mmol/l, P < 0.001 unadjusted, P = 0.002 adjusted for age, age(2) and sex). CONCLUSION: SCH is associated with increased serum LDL-C concentrations, which is significant after adjustment for age, age(2) and sex.     

Risk for ischemic heart disease and all-cause mortality in subclinical hypothyroidism

We investigated possible associations between subclinical hypothyroidism and atherosclerotic diseases (ischemic heart disease and cerebrovascular disease) and mortality. Of 2856 participants (mean age 58.5 yr) in a thyroid disease screening between 1984 and 1987, 257 subjects with subclinical hypothyroidism (TSH > 5.0 mU/liter) and 2293 control subjects (TSH range 0.6-5.0 mU/liter) were analyzed. In the baseline cross-sectional analysis, subclinical hypothyroidism was associated with ischemic heart disease independent of age, systolic blood pressure, body mass index, cholesterol, smoking, erythrocyte sedimentation rate, or presence of diabetes mellitus [odds ratio (OR), 2.5; 95% confidence interval (95% CI), 1.1-5.4 in total subjects and OR, 4.0; 95% CI, 1.4-11.5 in men] but not in women. However, there was no association with cerebrovascular disease (OR, 0.9; 95% CI, 0.4-2.4). We were unable to detect an influence of thyroid antibody presence on the association between subclinical hypothyroidism and ischemic heart disease. In a 10-yr follow-up study until 1998, increased mortalities from all causes in yr 3-6 after baseline measurement were apparent in men with subclinical hypothyroidism (hazard ratio, 1.9-2.1) but not in women, although specific causes of death were not determined. Our results indicate that subclinical hypothyroidism is associated with ischemic heart disease and might affect all-cause mortality in men.     

Follow up of thyroid hormone parameters in chronically ill geriatric patients: screening for thyroid disorders at hospital admission justified.

The objective of this study was to investigate if screening of chronically ill geriatric patients for thyroid dysfunction is justified just upon hospital admission. TSH was measured in 124 patients at hospital admission and 11-86 (Median 37) days afterwards. FT4 was measured in cases with subnormal, suppressed or elevated TSH (43 cases). Out of 81 patients with normal (0.5-3.6 mU/l) TSH, the control value was subnormal (0.1-<0.5 mU/l) in 6 and elevated (>3.6 mU/l) in one case, but in none of the patients became suppressed (<0.1 mU/l). In 13/30 patients with subnormal TSH the control value was normal but in none of the patients suppressed or elevated. On the contrary, all cases with suppressed (N=9) or elevated (N=4) TSH remained in the same ranges at follow up. Low (<13 pmol/l, N=3) or elevated (>27 pmol/l, N=5) initial FT4 levels did not change in the follow up as well. Out of 35 patients with normal FT4, one became low and another elevated. Improvement or worsening of the clinical state in the follow up did not correlate to changes of TSH. The prevalence of unsuspected thyroid dysfunctions were 11.3% (hyperthyroidism clinical: 4, subclinical: 5, hypothyroidism clinical: 3, subclinical: 2 cases). All cases except one with subclinical hypothyroidism were detected by the initial screening. Only one patient with clinical hyperthyroidism was initial misinterpreted as having subclinical disease. Conclusions: In chronically ill geriatric patients investigated at hospital admission, a measurable TSH practically excludes hyperthyroidism in the follow up. Suppressed TSH levels remain suppressed but subnormal levels should be controlled because their normalization frequently occur in the follow up. Screening upon hospital admission is sensitive enough to detect cases of thyroid dysfunction and justified by their high prevalence.     

Thyroxine replacement therapy and circulating lipid concentrations

OBJECTIVE Hypothyroidism is a common disorder and while the association of overt hypothyroidism with hyper-cholesterolaemia is clear, the effect upon lipids of the minor abnormalities of thyroid function often found in those receiving T4 replacement therapy is unclear. The aim of the present studies was to define in those with hypothyroidism the effect upon circulating lipids of subtle changes in thyroid status, indicated by serum TSH values below or above the normal range. DESIGN (i) Prospective study of short-term T4 treatment of those with subclinical hypothyroidism, (ii) Cross-sectional study of long-term T4 treatment, comparing non-T4 treated controls and T4 treated patients with serum TSH values either below or within the normal range. PATIENTS Short-term T4 therapy was examined in 11 post-menopausal females with subclinical hypothyroidism (high TSH, normal free T4) studied before therapy and 6 weeks after T4 at incremental doses (50, 100, 150 μg/ day). Long-term T4 treatment for hypothyroidism was investigated in 105 females on therapy for at least 1 year compared with 105 controls matched for age and menopausal status. MEASUREMENTS Fasting levels of total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol and HDL subtractions were determined in patients and controls. RESULTS (i) T4 treatment of subjects with subclinical hypothyroidism resulted in reductions in total and LDL cholesterol with increasing T4 dose (P <0 001). Comparison of lipid results pretreatment with those when TSH was restored to normal revealed no significant difference in lipids; in contrast, comparison of lipids in those with normal TSH compared with the same subjects when TSH was suppressed revealed reductions in total and LDL cholesterol, (ii) Long-term T4 treatment was associated with a reduction in total and LDL cholesterol measurements in those over 55 years receiving suppressive doses of T4 but no significant difference in lipids in those with normal serum TSH compared with non-T4 treated controls. CONCLUSION Effects of T4 upon lipid measurements suggest that patients with subclinical hypothyroidism should receive replacement therapy. Doses of T4 which suppress TSH to below normal may have a more significant influence upon lipids than doses of T4 which restore TSH to the normal range.     

Plasma viscosity, an early cardiovascular risk factor in women with subclinical hypothyroidism

OBJECTIVE: It is controversial, if subclinical hypothyroidism increases cardiovascular risk. Plasma viscosity is a hemorheological parameter, which is accepted as an early cardiovascular risk factor. We investigated the alterations in plasma viscosity in women with subclinical hypothyroidism. DESIGN: 40 female patients with subclinical hypothyroidism and 31 age- and weight-matched healthy women were included. Free thyroxine (FT4), thyroid stimulating hormone (TSH), lipid parameters, fibrinogen, C-reactive protein (CRP) levels, hematocrit and plasma viscosity were measured in all subjects. MAIN OUTCOME: Plasma viscosity, total cholesterol and low density lipoprotein were significantly increased and high density lipoprotein was significantly decreased in patients with subclinical hypothyroidism. No significant correlation was found among the parameters. CONCLUSION: Increased plasma viscosity in patients' group suggests that cardiovascular risk might be increased in patients with subclinical hypothyroidism. As far as we could reach, this is the first study concerning plasma viscosity in subclinical hypothyroidism.     

Circulating lipids and minor abnormalities of thyroid function

OBJECTIVE: We determined the effect of subclinical hyperthyroidism (defined as low circulating TSH with normal serum free T4) and subclinical hypothyroidism (raised serum TSH with normal free T4) on fasting levels of blood lipids. DESIGN: Prospective study of lipid concentrations in patients identified as having abnormal TSH. PATIENTS: Patients were identified in a population screening study of those over 60 years, with persistently low TSH with normal free T4 (n = 27) or high TSH but normal free T4 (n = 57). Patients were matched to controls with normal serum TSH by age, sex and body mass index. MEASUREMENTS: Serum TSH, free T4, free T3, total cholesterol, low density lipoprotein (LDL) cholesterol and high density lipoprotein (HDL) cholesterol. RESULTS: Serum free T4 measurements were significantly higher in those with subclinical hyperthyroidism than in their controls (P < 0.001) and lower in those with subclinical hypothyroidism than in matched controls (P < 0.001). Measurement of fasting lipids in patients and controls revealed a marked (12.2%) reduction in serum total cholesterol in subclinical hyperthyroidism (P < 0.01); no significant difference in fasting lipids between patients with subclinical hypothyroidism and controls was observed. CONCLUSIONS: Differences in free T4 between those with low or high TSH and controls with normal TSH suggest that abnormalities of TSH directly reflect thyroid hormone excess and deficiency. A reduction in cholesterol in those with subclinical hyperthyroidism suggests a direct influence of thyroid hormone excess on lipid metabolism in these patients.     

开展亚临床甲状腺功能减退症的临床研究

亚临床甲状腺功能减退症 (甲减 )是一种常见的内分泌专业亚临床疾病 ,主要诊断依据是血清TSH水平增高 ,而血清FT4正常。亚临床甲减的主要不良后果是发展为临床甲减和促进缺血性心脏病的发生。影响亚临床甲减发展为临床甲减的主要因素有两个 :血清TSH水平和甲状腺自身抗体 ,两个因素有叠加作用。甲状腺激素替代治疗对于阻止亚临床甲减发展为临床甲减的效果尚不确切 ;亚临床甲减与高胆固醇血症、高血压、吸烟和糖尿病一样 ,构成动脉粥样硬化和心肌梗塞的独立危险因素 ,其对此两病的危险度分别为 1.9和 3 .1。甲状腺素纠正亚临床甲减对降低血清胆固醇有一定效果 ;妊娠妇女的亚临床甲减对后代的智力影响已经引起高度关注。我国一组根据对流行病学调查的结果 ,提出了血清TSH、甲状腺自身抗体 (TPOAb、TgAb)的正常值范围 ,以及与疾病相关的甲状腺自身抗体的切割点值 ,可供参考。     

Increased sensitivity to the inhibitory effect of excess iodide on thyroid function in patients with beta-thalassemia major and iron overload and the subsequent development of hypothyroidism

OBJECTIVE: Patients with beta-thalassemia frequently develop primary hypothyroidism and other endocrine disorders due to iron overload. We studied whether administration of excess iodide to patients with apparently normal thyroid function could uncover an underlying thyroid disease. DESIGN AND METHODS: Twenty-five patients, 10 prepubertal (mean age 11+/-3 years) and 15 adults (mean age 23+/-5 years) with normal thyroid hormone and TSH levels, a normal response of TSH to TRH and negative thyroid peroxidase antibodies received 20mg iodide three times daily for three weeks, and thyroid hormone and TSH levels were measured weekly during, and for three weeks after, iodide administration and every 3 months thereafter for the next 5 years. RESULTS: During iodide administration there was a significant decrease in thyroid hormone concentrations which remained within normal levels, and a significant increase in TSH concentrations which in 14 out of 25 (56%) patients reached the hypothyroid level. Baseline TSH values were higher in those patients who developed subclinical hypothyroidism (2.31+/-0.71mU/l vs 1. 34+/-0.64mU/l, P=0.0016). Subclinical hypothyroidism developed in 70% of prepubertal and in 47% of adult patients. Serum ferritin was elevated in all patients. Nine of the fourteen patients (64.3%) who developed subclinical hypothyroidism during iodide administration developed hypothyroidism during the 5-year follow-up compared with only one of the eleven patients with a normal response to iodide (P=0.004). CONCLUSIONS: Patients with beta-thalassemia should not be exposed to excess iodide due to increased sensitivity to its inhibitory effects on thyroid function. The susceptible individuals frequently develop permanent hypothyroidism in the following years.