No abstract

Increased levels of TSH are associated to a decrease in HL activity, explaining our findings of an LDL particle rich in TG. This qualitative lipoprotein alteration suggests a pro-atherogenic pattern in sH. Treatment with L-T(4), however, did not correct the basal lipid derangement.

In elderly patients with metabolic syndrome, worse metabolic control, represented by higher HbA1c levels, was found associated to increased prevalence of thyroid nodules and larger thyroid volume. Moreover, within the whole metabolic syndrome group, patients with T2DM had the largest thyroid volumes.

It is well known that thyroid hormones are important regulators of energy balance and intermediate metabolism. With regard to glucose homeostasis, hyperthyroidism is associated with a state of insulin resistance due to increased hepatic gluconeogenesis (1). In hypothyroidism however, despite the fact that hepatic gluconeogensis has been described as unchanged (2) or decreased (3,4), experiments in animal models have demonstrated a state of insulin resistance both in the adipocyte and in the skeletal muscle (5,6). In humans the literature referring to the connection between thyroid dysfunction and insulin resistance is not consistent; this is in part due to the complex and redundant mechanisms regulating glucose homeostasis, but also to the use of different methods and indexes to assess the insulin sensitivity (indexes derived by the fasting insulin and glucose levels, intravenous [IV] or oral glucose tolerance test, euglycemic hyperinsulinemic clamps, local infusion of insulin and glucose in isolated limbs, examination in vitro of adipocytes, etc.). Specifically, only few studies have evaluated the insulin sensitivity in hypothyroidism and the results are controversial, some (7-12), but not all (13-16) have found that thyroid hormone deficit leads to insulin resistance secondary to decreased glucose disposal. On the other hand, while overt hyperthyroidism has been clearly associated with insulin resistance (1), the data on insulin action in subclinical hyperthyroidism is limited and controversial (17,18).The use of thyroid hormone suppressive therapy for thyroid cancer and its withdrawal before diagnostic or therapeutic intervention offers a unique model to assess the effects of controlled manipulation of circulating thyroid hormones on target pathways, in this case glucose homeostasis.We hypothesized that the lack of thyroid hormones leads to an insulin-resistant state due to a decrease in glucose disposal in skeletal muscle and adipose tissue. Considering the critical impact of insulin resistance on cardiovascular risk (19), we have explored the changes in insulin sensitivity in relation to changes in thyroid hormone homeostasis both under the subclinical hyperthyroid and overt acute hypothyroid status in thyroid cancer patients undergoing thyroid hormone withdrawal.Six women (age 42 AE 11 years, body mass index [BMI] 24 AE 2 kg=m 2 ) that underwent total thyroidectomy for differentiated thyroid cancer were included in the study group. Eight healthy subjects (six women and two men, age 37 AE 2 years, BMI 23 AE 2 kg=m 2 ) served as controls. The characteristics of the thyroid cancer patients are reported in Table 1. All the volunteers had a normal response to a standard 75 g oral glucose tolerance test. No patient had clinical evidence of metastatic disease as assessed by suppressed thyroglobulin and neck ultrasound. The average dose of levothyroxine taken orally every morning for TSH suppression was 169 AE 34 mg=d. Four patients were studied under TSH suppression with levothyroxine (sub HYPER). Due to the fac...

Euthyroid goiter is usually treated with TSH-inhibitory doses of levo-T(4) (L-T(4)). Because triiodothyroacetic acid (TRIAC) decreases TSH levels, the following study was perfomed: 36 euthyroid goitrous female patients (no cancer or chronic thyroiditis) were randomized to TRIAC (19.6 micro g/kg) (n = 19) or L-T4 (1.7 microg/kg) (n = 17) treatment during 11 months. Goiter volume; lumbar and femoral bone mineral density; serum osteocalcin; deoxypyridinoline; TSH; free T(4); total, high-density lipoprotein, and low-density lipoprotein cholesterol; and triglycerides were measured before and after the study period. Student's t test and chi(2) analysis were performed. TSH values (microunits per milliliter) in the TRIAC and L-T(4) groups were: 1.91 +/- 0.6 (basal) and 0.180 +/- 0.1 (after) and 2.1 +/- 2.5 (basal) and 0.180 +/- 0.3 (after), respectively. Thyroid volume decreased 37.9 +/- 35.4% in the TRIAC patients and 14.5 +/- 39.5% in the L-T(4) group (P = 0.069). Forty-two percent of the goiters with TRIAC reduced more than 50% their initial volume vs. 17.7% with L-T(4) (P = 0.15). With TRIAC, patients experienced fewer side effects. No differences in the changes of bone mineral density, serum deoxypyridinoline, osteocalcin, or the lipid profile were observed between both groups. The present results show that TRIAC is more effective than L-T(4) in the reduction of goiter size, with comparable effects on peripheral parameters.