The importance of thyroid microsomal antibodies in the development of elevated serum TSH in middle-aged women: associations with serum lipids.

OBJECTIVE: We assessed the relative risk of both serum TSH and antithyroid antibody concentrations with regard to progression of thyroid failure and studied the lipid profiles of individuals with elevated TSH levels. DESIGN, PATIENTS AND MEASUREMENTS: In a randomly selected group of 427 women aged 40-60 (mean 55) years volunteering in an epidemiological survey in Zoetermeer, TSH and thyroid microsomal antibodies (TMA) were determined. Ten years after the initial survey only TSH was measured and the lipid profiles of the individuals with elevated serum TSH levels were studied and compared with a reference group. RESULTS: During follow-up, four of 427 women were treated with thyroxine. Seventeen of 423 women initially had elevated serum concentrations of TSH (> 4.2 mU/l), 11 of whom were TMA positive. In the group of 406 women with initially a normal TSH, nine out of 37 (24%) TMA-positive women developed elevated serum levels of TSH over 10 years. In contrast only 10 of 369 (3%) TMA-negative women had elevated serum TSH levels 10 years after the initial survey (P < 0.001). Altogether, at the end of the observation period, 40% of TMA-positive subjects had elevated serum TSH concentrations, compared to 3% in the TMA-negative group (P < 0.01). TSH levels in the upper part of the normal range also appeared to have a predictive value: if those both with TSH levels between 2.0 and 4.2 and with a positive TMA status were contrasted with those without antibodies and low TSH, the crude relative risk was 71.5 (31.0-164.3), whereas the crude relative risk of presence versus absence of TMA was only 36.3 (18.8-70.3). Women with elevated TSH levels did not show changes in serum concentrations of total cholesterol (7.4 +/- 1.1 mmol/l), apo-A, (4.7 +/- 1.0 mmol/l) and apo-B (3.1 +/- 0.7 mmol/l) lipoproteins, compared with control individuals (7.2 +/- 1.3, 4.7 +/- 0.8 and 3.0 +/- 0.7 mmol/l, respectively). CONCLUSIONS: The determination of serum TMA in middle-aged women can identify an important group of women at risk of developing an elevated serum TSH. TMA measurement is of potential use in the prevention of cardiovascular disease. An elevated serum TSH, however, in our study-group does not seem to be accompanied by an abnormal lipid profile, as reported by others.

Isolated systolic hypertension and vessel wall thickness of the carotid artery. The Rotterdam Elderly Study.

We studied the association between isolated systolic hypertension (ISH) and generalized atherosclerosis as indicated by intima-media wall thickness (IMT) of the distal common carotid artery. The Rotterdam Elderly Study is a single-center study of a cohort of 11,854 elderly persons > or = 55 years old. Baseline measurements included ultrasonic evaluation of plaques and vessel wall thickness of both carotid arteries and extensive measurements of cardiovascular risk factors. Mean IMT and lumen diameter of subjects with ISH (systolic pressure > or = 160 mm Hg and diastolic pressure < 90 mm Hg) among the first 1,000 participants (n = 33) and 66 age- and sex-matched control subjects were compared. None of the subjects were using antihypertensive drug treatment, and all were free of cardiovascular disease. Mean IMT of the right common carotid artery was significantly higher in those with ISH than in normotensive subjects, with a mean difference of 0.07 mm (95% confidence interval [CI], 0.01, 0.14). Results for the left carotid artery were similar (mean difference, 0.06 mm; 95% CI, -0.01, 0.13). The end-diastolic mean lumen diameter was significantly larger in subjects with ISH than in control subjects for both right and left sides, with a mean difference of 0.70 mm (95% CI, 0.38, 1.01) and 0.48 mm (95% CI, 0.17, 0.80), respectively. Adjustment for differences in body mass index, serum lipids, smoking, and fibrinogen did not materially change the findings. Furthermore, atherosclerotic plaques were more frequently observed among those with ISH compared with control subjects, with a mean difference of 12% (95% CI, -1, 25).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular determinants of carotid artery disease. The Rotterdam Elderly Study.

The objective of the present study was to assess the prevalence of moderate and severe stenosis of the right carotid artery in the elderly and its associations with smoking, blood pressure, serum lipid levels, and hemostatic factors. The Rotterdam Elderly Study is a recently started single-center prospective follow-up study of a cohort of 11,854 elderly people aged 55 years or more. In 1990, 954 participants of the Rotterdam Elderly Study underwent ultrasonic duplex examination of the right internal carotid artery. A reduction of the lumen diameter of 16-49% was found in 29 people (3.0%). Severe stenosis (50% or more) was observed in 13 people (1.4%). With differences in age, sex, and body mass index taken into account, subjects with moderate-to-severe carotid artery disease had, compared with participants without stenosis, lower mean high density lipoprotein cholesterol levels (mean difference, 0.10 mmol/l; 95% confidence interval, 0, 0.20) and higher mean fibrinogen levels (difference, 0.24 g/l; 0.04, 0.45). Among them were more people with hypertension (mean difference, 16%) and more current smokers (mean difference, 13%). Factor VIIc and factor VIIIc activity was higher in subjects with carotid artery disease, without, however, reaching statistical significance (mean difference, 0.06 IU/ml [-0.01, 0.12] and 0.21 IU/ml [-0.05, 0.47], respectively). Our data suggest that hypertension, smoking, and reduced serum high density lipoprotein cholesterol levels, combined with unfavorable increases in hemostatic factors, may be related to carotid artery disease in the elderly.

Ten-year follow-up study of islet-cell antibodies and childhood diabetes mellitus.

To find out whether subclinical autoimmunity precedes onset of nonfamilial insulin-dependent diabetes mellitus (IDDM), 4806 schoolchildren aged 5-19 years from a township in Holland were followed-up for at least ten years after blood was sampled for measurement of islet-cell antibodies (ICA). ICA positivity conferred a relative risk of IDDM of 533 (95% CI 145-1955). In the 10 years of follow-up 4 of the 8 ICA-positive subjects became insulin dependent, whereas the probability of being free of IDDM was 99.9% for those who were ICA-negative at the start of the study. The findings suggest that, although chronic autoimmunity involving the pancreatic beta-cells may precede non-familial IDDM by many years, a positive ICA test on a single occasion predicts the development of IDDM in only 4 out of 8 subjects over a period of 10 years.

Monomeric (7S) IgM in primary biliary cirrhosis.

Monomeric (7S) IgM was measured in 25 patients with primary biliary cirrhosis and 25 age- and sex-matched controls by simple double immunodiffusion in the polyacrylamide gel. 7S IgM was detected in a quarter of the patients and in none of the controls. The presence of 7S IgM was related to the elevation of total IgM as measured by radial immunodiffusion techniques. Patients with 7S IgM had significantly higher levels of cryoglobulins and immune complexes in their sera than 7S IgM-negative patients. In addition, serum alkaline phosphatase concentrations were more elevated in the 7S IgM-positive patients than in the 7S IgM-negative patients, reflecting more extensive bile duct damage. The presence of monomeric (7S) IgM and other differences in the IgM molecule may be significant for the pathogenesis of primary biliary cirrhosis.

The absolute quantification of human IgM and IgG: standardization and normal values.

Nephelometric, turbidimetric and radial immunodiffusion methods are described, which permit valid, reproducible determination of human IgM and IgG by weight. Subgroups of IgM, 7S-IgM and subclasses of IgG did not interfere with these methods. For IgG the International Unit represented a constant weight quantity in agreement with official WHO estimations. For IgM the IU was not constant and much lower values are found. It is therefore suggested that the IU should be abolished for human IgM and IgG. Absolute values for IgM levels are presented for both sexes and for age groups in the range of 5-80 years. The figures showed significant variation with sex and age.

Serum IgM in primary biliary cirrhosis.

Serum IgM concentrations were measured in 25 patients with primary biliary cirrhosis (PBC) and 25 age- and sex-matched controls by the classical Mancini technique and by a modified method, which included reduction to 7 S monomers. Standards calibrated against the WHO standard, as well as a serum standard with an absolute value calibrated by immunological and non-immunological techniques, were used. All patients had an elevated IgM level; measurement of serum IgM is therefore a simple and sensitive screening test for patients with cholestasis. When measured with the standard calibrated against the WHO standard, the average IgM levels for PBC patients and controls agreed with results previously reported; the average IgM levels were much lower when a serum standard with an absolute IgM value was used; further standardization in needed. The differences in the ratio of the IgM measured by the classical method (pentameric IgM) to that measured by the alternative method (monomeric IgM) support the existence of different IgM subgroups or the in vivo presence of monomeric IgM in some patients with PBC.

Cholesterol determinations. A comparative study of methods with special reference to enzymatic procedures.

Two enzymatic methods for the determination of cholesterol in serum have been modified for automatic use. These methods utilize the colour reactions according to Kageyama or Trinder to measure the hydrogen peroxide resulting from the enzymatic reaction. The procedures have been compared with the classical methods according to Abell and to Huang. Details regarding the procedures are given. Comparisons made during routine analysis of a large number of different sera have been expressed in the form of regression equations. The standard errors of the methods are given along with the standard deviations for differences between methods. Some conversions of values from one method into another are also given. It appears that the automated Kageyama method can be used for large scale practice. The manual Kageyama method is not very satisfactory because of its large experimental error. A disadvantage of the Kageyama methods is the necessity of having blank corrections for haemolytic sera. The Trinder method avoids the problem and has some additional advantages.

The validity of the radial immunodiffusion method for the quantitative determination of human IgM. Evaluation of a modified method.

Three subgroups of human IgM can be distinguished on the basis of differences of slopes of the D2 versus absolute concentration plot in the radial immunodiffusion technique (Klein et al., 1973). Individual IgM fractions, whether mono- or polyclonal, always belong to only one of these groups. The differences between the subgroups disappear after reduction of the IgM to 7S subunits. These findings provide an explanation for the large discrepancies between absolute IgM determinations in different laboratories. It follows that most of the readings of individual IgM values in the Mancini technique must be wrong by any standard, including WHO reference preparations. The insertion of a simple reduction step in the assay abolishes the differences in quantitative reactivity between IgM subgroups as well as between natural 7S and 19S IgM. This allows an absolute determination of both forms together. The values thus obtained differ considerably from the estimates given by Humphrey and Batty (1974). It also appears that the International Units of the WHO do not represent the same quantity of IgM in different reference sera. The modified method allows the determination of total monoclonal as well as polyclonal human IgM by weight.