Thyroid disease and vascular function.

Altered cardiac function in thyroid disease is well recognized and has been extensively investigated, vascular function has however been less well studied in those with thyroid dysfunction. Thyroid hormones, thyroxine (T(4)) and triiodothyronine (T(3)) are important regulators of cardiac function and cardiovascular hemodynamics. The cardiovascular system responds to minimal but persistent changes in circulating thyroid hormone levels producing changes in vascular reactivity and endothelial function. The detection of endothelial dysfunction and/or arterial stiffness allows early identification of individuals at risk as these occur in both patients with risk factors for coronary artery disease and in those with established disease. This may allow treatment to be targeted at high risk individuals with the aim of slowing the progression of vascular disease. The various methods used to assess arterial function are reviewed and the changes demonstrated in human and animal models of thyroid dysfunction.     

Thyroid disease and increased cardiovascular risk.

The effects of thyroid dysfunction are thought to be reversible on restoration of euthyroidism, but postmortem and epidemiologic data suggest that subclinical or treated thyroid disease is associated with increased vascular risk. In order to determine the extent of this risk, and to explore whether the nature and/or treatment of thyroid disease are critical in this relationship, we used medical record linkage to match patients with treated thyroid disease of various etiologies with routinely collected national inpatient and daycase hospital discharge records and death records, and assessed the number of hospitalizations from cardiovascular or cerebrovascular disease or death in patients with thyroid disease and control patients. Patients treated for Graves' disease had more hospitalizations from cardiovascular disease than controls (relative risk, 1.42; 95% confidence interval, 1.20 to 1.67; p < 0.001). Toxic multinodular goiter was also associated with significantly higher rates of cardiovascular disease (relative risk, 1.50; 95% confidence interval, 1.11 to 2.02; p = 0.008). Patients with Hashimoto's thyroiditis aged over 50 years had a threefold increase in cardiovascular admissions compared to controls (23.5% and 6.5%, respectively; 95% confidence interval for difference, 6.0% to 27.9%; p = 0.003). Thus, different forms of thyroid disease were associated with increased long-term vascular risk despite restoration of euthyroidism. The mechanisms that mediate this risk are unclear but may not involve thyroid hormone abnormality.     

Thyroid involvement in Rosai-Dorfman disease.

Rosai-Dorfman disease (RDD) with thyroid involvement is extremely rare; we herein present the sixth known case with a review of the previously reported five cases and discuss the clinicopathological characteristics of this entity. RDD with thyroid involvement has occurred only in females with a mean age of 56.3 years, which is significantly different from nodal RDD predominantly seen in young males. Besides this, autoimmune thyroiditis is frequently associated in RDD with thyroid involvement, which raises a suspicion of a common pathogenesis of both entities. RDD with thyroid involvement is commonly misdiagnosed preoperatively as thyroid malignancy with lymph node metastasis, which may lead to overtreatment and postoperative complication. Clinical presentations might be helpful for a preoperative differential diagnosis; while thyroid function, sonography, thyroid isotope scan, and fine needle aspiration have been less useful. All six cases were treated by surgery and complete remission was seen. However, two patients with a preoperative diagnosis of benign disease suffered from hypothyroidism due to total thyroidectomy.     

Thyroid hormone transporters in health and disease.

Cellular entry is required for conversion of thyroid hormone by the intracellular deiodinases and for binding of 3,3',5-triiodothyronine (T(3)) to its nuclear receptors. Recently, several transporters capable of thyroid hormone transport have been identified. Functional expression studies using Xenopus laevis oocytes have demonstrated that organic anion transporters (e.g., OATPs), and L-type amino acid transporters (LATs) facilitate thyroid hormone uptake. Among these, OATP1C1 has a high affinity and specificity for thyroxine (T(4)). OATP1C1 is expressed in capillaries throughout the brain, suggesting it is critical for transport of T(4) over the blood-brain barrier. We have also characterized a member of the monocarboxylate transporter family, MCT8, as a very active and specific thyroid hormone transporter. Human MCT8 shows preference for T(3) as the ligand. MCT8 is highly expressed in liver and brain but is also widely distributed in other tissues. The MCT8 gene is located on the X chromosome. Recently, mutations in MCT8 have been found to be associated with severe X-linked psychomotor retardation and strongly elevated serum T(3) levels.     

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.     

Plasma lipids and lipoproteins in liver disease.

There are many changes in the plasma, lipids, and lipoproteins in patients with liver disease. They have proved difficult to study but our understanding of these changes has increased greatly during recent years. In obstructive jaundice hyperlipidaemia is a fairly constant finding and this appears to be due to the regurgitation of phospholipid from the obstructed biliary tree. The plasma lipids tend to fall with parenchymal liver disease. The composition of the lipoproteins depends on the activity of the plasma enzyme lecithin: cholesterol acyl transferase. When LCAT activity is high the individual lipoprotein fractions are normal. When it is reduced all of the lipoprotein fractions are affected but the pattern found with obstruction is quite different from that found with parenchymal disease. The changes in plasma lipoproteins appear to be associated with change in the lipid composition of cellular membranes and this may have important functional implications.     

Thyroid function in chronic liver disease.

There is a recent hypothesis that thyroxine (T4), secreted by the thyroid gland under physiological conditions, is mono-deiodinated in extrathyroidal sites to form the more active 3, 3', 5-tri-iodothyronine (T3) before exerting biological activity at target tissue level. Futhermore, circumstantial evidence suggests that the liver is an important site for the extra-thyroidal conversion of T4 to T3. Thyoid hormone pathophysiology in liver disease is therefore of interest. Patients with hepatic cirrhosis have normal or raised plasma T4 concentration and markedly reduced plasma T3 concentration. Free hormone measurement reflect this pattern and three is kinetic and other evidence to support the concept that extra-thyroidal conversion of T4 to T3 is reduced in patients with liver dysfunction. Comparable finding have however been reported in patients with other non-hepatic chronic systemic diseases but, unlike in hepatic cirrhosis, serum thyrotropin (TSH) is not increased. Increased serum TSH is found in hepatic cirrhois and is often accompanied by an abnormal TSH response to thyrotropin-releasing hormone (TRH) suggesting, in addition, disordered hypothalamic-pituitary control of thyroid function in these patients. Thyroid physiology is clearly markedly disturbed in hepatic cirrhosis but no single hypothesis adequately accounts for all the observed abnormalities. The recent finding of increased plasma 3, 3', 5-tri-iodothyronine (reverse t3; rT3) concentration in hepatic cirrhosis may ulimately clarify our understanding.     

Thyroid disease and pregnancy: degrees of knowledge.

OBJECTIVE: The literature on the impact of thyroid abnormalities on pregnancy and the postpartum has expanded rapidly over the last two decades. The objective of the present study was to determine the level of knowledge of endocrinologists, obstetrician/gynecologists, internists, and family physicians in regard to thyroid disease and pregnancy. DESIGN: A 16-item questionnaire on issues related to thyroid disease and pregnancy was developed. Endocrinologists (n = 116), obstetrician/gynecologists (n = 81), internists (n = 109), and family physicians (n = 99) were asked to complete the questionnaire. Physician self-report of confidence regarding degree of knowledge was obtained through completion of a seven-point Likert scale. MAIN OUTCOME: The percentage of questions answered correctly by all physicians was 63%. Endocrinologists had the highest correct response rate (77%), followed by obstetrician/gynecologists. Hierarchical regression analysis revealed that medical specialty, years of training, confidence level, and whether or not the physician treated pregnant women were significantly related to the overall score. CONCLUSIONS: The present study demonstrates a suboptimal level of knowledge regarding thyroid disease and pregnancy among physicians in four specialties. A comprehensive physician education program is needed.     

Thyroid nodular disease

The thyroid gland is fairly homogeneous but nodules are frequent. Nodules greater than 1.0 cm are usually palpable, but non-palpable nodules, smaller than 1.0 cm are far more frequent. Thyroid nodular disease, the etiology of which is multifactorial, encompasses lesions, from the small incidentaloma to large multinodular intrathoracic goiter. The main diagnostic issues are related to the functional and morphological characterization using TSH measurements and image methods. Fine needle aspiration biopsy is the method of choice to rule out malignancy, the incidence of which is similar in single or multinodular goiter (MNG). MNG treatment can be surgical or radioactive iodine (131I) could be indicated if the 131I uptake is adequate. It is likely that the use of recombinant human TSH (rhTSH) will strongly change the application of 131I in MNG treatment. The benign single thyroid nodule, "cold" or "hot" at scintigraphy, can be treated with percutaneous ethanol injection. The "hot" nodule can also be treated by surgery or 131I.     

Thyroid disease and the heart

The cardiovascular signs and symptoms of thyroid disease are some of the most profound and clinically relevant findings that accompany both hyperthyroidism and hypothyroidism. On the basis of the understanding of the cellular mechanisms of thyroid hormone action on the heart and cardiovascular system, it is possible to explain the changes in cardiac output, cardiac contractility, blood pressure, vascular resistance, and rhythm disturbances that result from thyroid dysfunction. The importance of the recognition of the effects of thyroid disease on the heart also derives from the observation that restoration of normal thyroid function most often reverses the abnormal cardiovascular hemodynamics. In the present review, we discuss the appropriate thyroid function tests to establish a suspected diagnosis as well as the treatment modalities necessary to restore patients to a euthyroid state. We also review the alterations in thyroid hormone metabolism that accompany chronic congestive heart failure and the approach to the management of patients with amiodarone-induced alterations in thyroid function tests.     

关注甲状腺疾病的心血管风险

近年来,对糖尿病伴高血压及心血管并发症的认识已取得共识并出台了相应的诊治指南,但是对于内分泌代谢系统的另一重要疾病--甲状腺疾病与心血管风险的关系和诊治还了解不多,也未引起足够的重视.     

Thyroid disease and female reproduction

The menstrual pattern is influenced by thyroid hormones directly through impact on the ovaries and indirectly through impact on SHBG, PRL and GnRH secretion and coagulation factors. Treating thyroid dysfunction can reverse menstrual abnormalities and thus improve fertility. In infertile women, the prevalence of autoimmune thyroid disease (AITD) is significantly higher compared to parous age-matched women. This is especially the case in women with endometriosis and polycystic ovarian syndrome (PCOS). AITD does not interfere with normal foetal implantation and comparable pregnancy rates have been observed after assisted reproductive technology (ART) in women with and without AITD. During the first trimester, however, pregnant women with AITD carry a significantly increased risk for miscarriage compared to women without AITD, even when euthyroidism was present before pregnancy. It has also been demonstrated that controlled ovarian hyperstimulation (COH) in preparation for ART has a significant impact on thyroid function, particularly in women with AITD. It is therefore advisable to measure thyroid function and detect AITD in infertile women before ART, and to follow-up these parameters after COH and during pregnancy when AITD was initially present. Women with thyroid dysfunction at early gestation stages should be treated with l-thyroxine to avoid pregnancy complications. Whether thyroid hormones should be given prior to or during pregnancy in euthyroid women with AITD remains controversial. To date, there is a lack of well-designed randomized clinical trials to elucidate this controversy.