To evaluate whether patients with subclinical hypothyroidism have a disturbance in lipid metabolism, and whether supplemental L-thyroxine (L-T4) therapy would improve their lipid parameters, we measured serum levels of thyroid hormones, TSHand lipid parameters in 34 patients with subclinical hypothyroidism before and 2 months after treatment with L-T4. Before treatment, patients with subclinical hypothyroidism had elevated serum low density lipoprotein cholesterol (LDL-C) concentrations compared with control subjects (P<0.05). Overall, L-T4 therapy significantly decreased the serum level of TSH (P<0.01), total cholesterol (TC; P<0.02), high density lipoprotein cholesterol (P<0.02), LDL-C (P<0.05), and the ratio of apolipoprotein B to apolipoprotein Al (P<0.05). Lipid values in patients with basal serum TSHlevels below 10 mU/ 1 were not affected by L-T4 therapy, whereas serum levels ofTC and LDL-Cdecreases significantly (P<0.01) in patients with serum TSH levels above 10 mU/1. Thus, the L-T4 treatment appears to have a preventive effect on the disturbance of lipid metabolism in patients with subclinical hypothyroidism, especially in patients with serum TSHlevels above 10 mU/1. (Internal Medicien 33: 413-417, 1994)

Abstract. The aim of this study was to evaluate the relationship between subclinical hypothyroidism and/or autoimmune thyroid disease and coronary heart disease (CHD). Ninety seven patients diagnosed as having CHD by a coronary angiography (CHD group) and 103 healthy subjects matched for age, sex and body mass index (control group) were included in the study. Thyroid function, thyroid autoantibodies and serum lipid concentrations were measured in the CHD and control groups. The CHD group exhibited significantly decreased serum free T3 (FT3) and free T4 (FT4) levels, and significantly increased serum TSH levels as compared with the control group, indicating a significant decrease in thyroid function in the CHD patients. Serum high density lipoprotein cholesterol (HDL-C) levels were significantly decreased in the CHD group. The incidence of subclinical hypothyroidism and thyroid autoantibodies was similar in both two groups. These observations were also true of women even after those who had diabetes mellitus (DM), hypertension (HT) and a smoking habit were excluded. This was not the case, however, in men without DM, HT, or a smoking habit. Patients with CHD had significantly lower serum levels of HDL-C than the control subjects, regardless of gender (P<0.01). In the group with CHD, there was no difference between the serum lipid levels in patients with subclinical hypothyroidism and those with normal thyroid function. Female patients with CHD had significantly lower serum levels of thyroid hormone and HDL-C, but their subclinical hypothyroidism or thyroid autoimmunity did not seem to be related to the development of CHD.

Serum thyroglobulin levels were serially measured in 25 normal pregnant women to evaluate thyroidal activity during normal pregnancy. Measurements included serum T3, T4, free T4, TBG, and TSH.Tg and FT4 levels were found to be decreased in the third trimester when compared with those of the first trimester and with those of normal non-pregnant individuals (P < 0.01). TSH levels were higher than normal in pregnant women at all stages of pregnancy, with a significant rise at the third trimester. These findings suggest the presence of a subclinical hypothyroid state in the late stage of normal pregnancy.It has been reported that the levels of serum free thyroxine (FT4) and free 3,5,3'-triiodothyronine (FT3), measured by the classic equilibrium dialysis method (Sterling & Brenner 1966;Weeke et al. 1982) and the recent analog-type radioimmuno¬ assay (RIA, Franklyn et al. 1983a,b;Smith & Bold 1983), are decreased in the late stage of normal pregnancy. However, the clinical significance of these findings has not been clarified, since preg¬ nant women show none of the clinical features of hypothyroidism, and the results of these RIAs have been shown to be influenced by serum albu¬ min levels (Stockigt et al. 1982;Amino et al. 1983; Midgley & Wilkins 1983), which to some extent may change during pregnancy. It is thus import¬ ant to study other indexes of thyroid status which are not influenced by TBG or albumin. As serum thyroglobulin (Tg) levels have been reported to correlate with thyroid status , 1975Madeddu et al. 1984), we followed the serum Tg levels during normal pregnancy in order to see whether they would decrease with the FT4 levels or not. Materials and MethodsTwenty-live normal pregnant women with no previous history of thyroid diseases and no anti-thyroid anti¬ bodies in their sera were followed for the entire period of pregnancy. Blood was drawn at the first trimester (5-19 weeks), the second trimester (26-29 weeks), and the third trimester (35 -37 weeks). The sera were stored at -20°C.

We tested the claim that uni- and multinodular goiter (UNG and MNG) and papillary carcinoma (PC) of the thyroid are autoimmune thyroid diseases (AITD) similar to Graves' disease (GD) and Hashimoto's thyroiditis (HT). The expression of HLA-DR on cultured thyroid epithelial cells (thyrocytes) from UNG, MNG, and PC after coculture with autologous peripheral blood mononuclear cells (PBMC) was compared with that on GD and HT cells. The thyrocytes also were cultured with interferon-gamma (IFN gamma) alone. A cytotoxicity assay involving 51Cr-labeled thyrocytes, anti-HLA-DR, and complement was used to determine HLA-DR expression. Stimulation of thyrocytes with 200 U/mL IFN gamma induced HLA-DR (expressed as a cytotoxicity index) equally well on all thyrocytes [AITD (n = 6): IFN gamma, 23.8 +/- 7.7 (+/- SD); unstimulated, 3.6 +/- 2.0; UNG (n = 6), MNG (n = 9), and PC (n = 5): IFN gamma, 22.5 +/- 4.7; unstimulated, 4.0 +/- 3.0]. When cocultured with autologous PBMC, the values were: AITD, 24.9 +/- 10.1; UNG, MNG, and PC, 3.8 +/- 3.7 (P less than 0.001). The supernatants from the AITD cocultures had higher IFN gamma concentrations (by RIA) than those from the other cocultures. We conclude that in UNG, MNG, and PC, the peripheral blood helper T-lymphocytes are not sensitized to thyrocyte membrane antigen(s); consequently, little if any IFN gamma is produced in cocultures, and hence, there is no increase in thyrocyte HLA-DR expression, unlike the situation in AITD (GD and HT). Thus, UNG, MNG, and PC are not primarily autoimmune in nature, as defined by a lack of sensitization of the PBMC of such patients to thyroid antigen(s).