Serum thyrotropin response to thyrotropin-releasing hormone and free thyroid hormone indices in patients with familial thyroxine-binding globulin deficiency.

The response in serum thyrotropin (TSH) to synthetic thyrotropin-releasing hormone (TRH) as well as serum free thyroxine index (FT4I) and free triiodothyronine index (FT3I) was investigated in six patients with familial thyroxine-binding-globulin (TBG) deficiency. The total serum thyroxine (T4) and triiodothyronine (T3) concentrations were significantly decreased, compared with those of normal subjects (3.4 +/- 0.9 microgram/dl, mean +/- SD. vs. 9.0 +/- 1.5 microgram/dl, p less than 0.01 and 87 +/- 27 ng/dl vs. 153 +/- 37 ng/dl, p less than 0.01, respectively). FT4I was lower than the normal range in all but one (5.3 +/- 1.5 vs. 8.9 +/- 1.6, p less than 0.01), whereas FT3I was all in the normal range and of no significant difference from the normal control (132 +/- 22 vs. 148 +/- 25). Serum TSH concentrations in TBG deficiency were all in the normal range (1.0-4.2 muU/ml) and the maximum TSH increments following TRH 500 microgram iv were 8.9 +/- 2.0 muU/ml and of no significant difference from the normal control (10.2 +/- 4.5 muU/ml). These results indicate that the euthyroid state in familial TBG deficiency is more clearly defined by TRH-test and the normal response to TRH in familial TBG deficiency is presumably under the control of the serum free T3 level rather than the serum free T4 level.     

Changes in the plasma and urine alpha human atrial natriuretic peptide (alpha hANP) concentration in patients with thyroid disorders

In order to assess the possible involvement of thyroid hormone in alpha human atrial natriuretic peptide (alpha hANP), we investigated the plasma and urine ANP concentration in patients with primary hyperthyroidism and hypothyroidism. Plasma and urine were extracted through Sep-Pak C18 cartridges and the urine ANP concentration was corrected by urine creatinine (cre. mg/dl) and expressed as fmol/mg.cre.. The plasma ANP concentration in patients with untreated hyperthyroidism (32.3 +/- 7.0 fmol/ml; n = 22) was higher than in normal subjects (p less than 0.01 vs control; 6.2 +/- 0.7 fmol/ml). After restoration to euthyroidism, the plasma ANP concentration (patients with treated hyperthyroidism) fell to normal (8.9 +/- 1.9 fmol/ml). The plasma ANP concentration in patients with untreated hypothyroidism (14.1 +/- 3.0 fmol/ml; n = 7) was higher than normal, but in two of them there was mild renal dysfunction and an incomplete right blundle branch block in the electrocardiogram. It was possible that these factors contributed to the observed increase in plasma ANP. However, a significant positive correlation was found between plasma ANP and free thyroxine (n = 40, r = 0.449; p less than 0.01) and free triiodothyronine (n = 40, r = 0.546; p less than 0.01). The urine ANP concentration in patients with untreated hyperthyroidism was markedly higher than in normal subjects (p less than 0.01), but in untreated hypothyroidism not significantly different from normal.     

Changes in plasma fibronectin levels in thyroid diseases

The plasma levels of fibronectin (Fn) have been measured in normal subjects and in patients with thyroid diseases. The mean plasma Fn levels in 62 normal adults was 32.0 +/- 6.0 mg/dl, whereas it was elevated to 62.6 +/- 16.1 mg/dl (mean +/- SD) in 25 patients with hyperthyroidism and decreased to 19.2 +/- 8.0 mg/dl in 9 patients with hypothyroidism. The 9 patients with simple goiter have normal values of 29.1 +/- 8.0 mg/dl. With the administration of anti-thyroid drugs, plasma Fn levels normalized, with a time lag, in parallel with normalization of the thyroid function. Positive correlation was obtained between Fn levels and serum levels of triiodothyronine (T3) and thyroxine (T4). The present findings indicate that measurement of plasma Fn both in the basal state and during treatment provides evidence of altered Fn metabolism in thyroid diseases and serves to follow up the effect of treatment.     

Influence of thyroid function on serum bone Gla protein

The serum BGP level was assayed in patients with hyperthyroidism (untreated and remittent cases) and hypothyroidism. The mean serum BGP concentration was 9.7 +/- 0.90 ng/ml in 30 patients with untreated hyperthyroidism which was significantly higher than the 2.7 +/- 0.38 ng/ml in 15 remittent patients and 1.3 +/- 0.31 ng/ml in 13 patients with hypothyroidism (p less than 0.001, p less than 0.001). Serum BGP had a significant positive correlation with the concentrations of free triiodothyronine and alkaline phosphatase in the serum, while it had a significant negative correlation with serum PTH. In the patients with hypothyroidism, serum BGP increased significantly in parallel with increases in serum free triiodothyronine with thyroxine therapy. In the patients with hyperthyroidism, serum free triiodothyronine decreased significantly after the first month of methimazole treatment, and fluctuated within the normal range after two months. Serum alkaline phosphatase and BGP did not show significant changes during the first six months of treatment, although they were eventually reduced significantly at the end of one year. These results suggest that thyroid hormone directly stimulates the synthesis and secretion of BGP in existent osteoblasts and also acts on the bone remodeling cycle, therapy accelerating the rate of bone formation; the latter action may occur over a long period.     

Insulin secretion and sensitivity in hyperthyroidism

To examine the effect of hyperthyroidism on carbohydrate metabolism, we studied glucose-stimulated insulin secretion and glucose utilization in 8 subjects with Graves' disease before and after treatment for hyperthyroidism and 8 age-, sex- and weight-matched normal subjects. Subjects with Graves' disease had significant elevated serum levels of thyroxine (24.81 +/- 2.44 micrograms/dl, mean +/- SEM) and triiodothyronine (459 +/- 5.5 ng/dl, mean +/- SEM). Simultaneous measurement of plasma glucose, serum insulin and C-peptide levels during fasting and every 30 minutes up to 180 minutes after 75 g oral glucose loading was determined. In addition, plasma glucose, serum insulin and serum C-peptide were measured during euglycemic glucose clamp with insulin infusion of 40 mU/m2 min-1. Mean fasting plasma glucose (P less than 0.05, serum insulin (P less than 0.005) and serum C-peptide (P less than 0.005) levels were significantly higher in the hyperthyroid patients. After glucose loading, the plasma glucose (P less than 0.05), serum insulin (P less than 0.05) and C-peptide (P less than 0.05) responses were significantly higher in hyperthyroid patients at all times up to 180 minutes. During euglycemic clamp studies, the steady-state serum insulin levels were identical in the two groups. The glucose disposal rate was lower in hyperthyroid patients before treatment (P less than 0.01) than in normal subjects. After thyroid function had been normalized for 2 to 4 weeks, the glucose disposal rate increased significantly (P less than 0.05), but was still significantly lower than those of normal subjects (P less than 0.05). Our data show that patients with Graves' hyperthyroidism manifest glucose intolerance, hyperinsulinemia and insulin resistance.     

Response of thyrotropin, prolactin and free thyroid hormones to graded exercise in normal male subjects

Serum levels of thyrotrophin (TSH), prolactin (PRL), free thyroxine (FT4) and free triiodothyronine (FT3) were determined before and after physical exercise in 21 normal male subjects. The subjects were divided into 3 groups as follows: group I--light exercise (exercise on the Mijnhardt bicycle ergometer at 100 Watts for 15 min); group II--moderate exercise (a 5 km marathon); group III--heavy exercise (a 10 km marathon). In group I, TSH level rose from 1.96 +/- 0.42 mu u/ml (mean +/- SEM) to 2.52 +/- 0.30 mu u/ml (p less than 0.01), and PRL levels rose from 11.0 +/- 2.0 ng/ml to 19.0 +/- 5.2 ng/ml (p less than 0.01). In group II, TSH rose from 2.11 +/- 0.51 mu u/ml to 2.62 +/- 0.56 mu u/ml (p less than 0.05), and PRL rose from 11.2 +/- 1.6 ng/ml to 24.0 +/- 5.2 ng/ml (p less than 0.01). In group III, TSH rose from 2.01 +/- 0.41 mu u/ml to 2.36 +/- 0.45 mu u/ml (p less than 0.02), and PRL rose from 12.1 +/- 2.0 ng/ml to 47.7 +/- 9.3 ng/ml (p less than 0.01). The serum levels of FT4 showed different results among the three groups: Group I showed an increased response from 1.60 +/- 0.12 ng/dl to 1.72 +/- 0.12 ng/dl (p less than 0.01); Group II showed no significant difference; and group III demonstrated a diminished response from 1.61 +/- 0.14 ng/dl to 1.45 +/- 0.16 ng/dl (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of growth hormone administration on lipids and lipoproteins in growth hormone-deficient patients

Plasma lipids, lipoproteins, and lipoprotein cholesterol levels were studied in a group (n = 8) of prepubertal growth hormone-deficient patients before and after growth hormone (GH) administration. Determination of plasma lipoproteins by a sensitive agarose gel electrophoretic technique demonstrated: (a) in the patients with two prebeta bands an intensification of the fast prebeta lipoprotein fraction after growth hormone administration; and (b) in the patients with one prebeta band the appearance of a second prebeta band after growth hormone administration. The mean (+/- SD) plasma triglyceride level before GH was 86 +/- 60 mg/dl and 158 +/- 95 mg/dl after GH (P less than 0.01). Mean (+/- SD) plasma cholesterol level before GH was 196 +/- 25 mg/dl and 174 +/- 28 mg/dl after GH (P less than 0.05). High-density lipoprotein cholesterol concentrations decreased significantly (P less than 0.001) from mean (+/- SD) 55 +/- 12 mg/dl before GH to 37 +/- 10 mg/dl after GH. Very-low-density lipoprotein cholesterol concentrations increased significantly (P less than 0.05) from mean (+/- SD) 13 +/- 12 mg/dl before GH to 23 +/- 15 mg/dl after GH. Low-density lipoprotein cholesterol concentrations decreased (N.S.) from mean (+/- SD) 123 +/- 15 mg/dl before GH to 114 +/- 15 mg/dl after GH. These lipid and lipoprotein changes could be mediated through the insulin antagonism, hyperinsulinemia, and a decrease in lipoprotein lipase activity caused by growth hormone.     

Human epidermal growth factor concentrations in urine, but not in saliva and serum, depend on thyroid state

To evaluate the effects of thyroid hormones on the concentration of epidermal growth factor (EGF), we determined values for the immunoreactive EGF concentration in the urine (U-irEGF) of newborn infants with congenital hypothyroidism (N = 19), and in urine, saliva and serum of adult patients with hypothyroidism (N = 11) and hyperthyroidism (N = 8). The values were expressed as SD score (SDS), i.e. deviation in SD units from their mean value of healthy subjects of the same age and sex. The SDS of relative U-irEGF (ng/mg creatinine) was lower (P less than 0.01) in newborn infants with congenital hypothyroidism (-0.8 +/- 0.2; mean +/- SEM) than in healthy infants. Their relative U-irEGF correlated with their serum T4 concentrations (r = 0.59, P less than 0.01). The SDS of relative U-irEGF was lower (P less than 0.01) in adult hypothyroid patients (-1.2 +/- 0.5) and higher (P greater than 0.05) in adult hypothyroid patients (0.9 +/- 0.6) than in healthy adult subjects. When subsequently euthyroid, their SDS of relative U-irEGF increased to -0.5 +/- 0.3 (P less than 0.01), and decreased to -0.7 +/- 1.1 (P less than 0.05), respectively. The irEGF concentrations in saliva and serum were not significantly different between the hypothyroid and hyperthyroid patients. Our results indicate that urinary excretion of irEGF in man is dependent on thyroid hormone.     

Serum free thyroxine and thyroxine-binding globulin concentrations in early phase of subacute thyroiditis

Serum total thyroxine (T4), total triiodothyronine (T3), T4-binding globulin (TBG), free T4(FT4) and free T3(FT3) concentrations and the T3-uptake(T3-U) value were estimated in 11 patients with subacute thyroiditis, and compared with the same parameters in 11 patients with Graves' disease, whose serum T4 concentrations were similar to the former group. Seven patients with subacute thyroiditis, who were treated with dicrofenac sodium alone, were investigated as to the sequential changes in serum parameters during their clinical courses. The mean serum T3-U value and FT4, T3 and FT3 concentrations in patients with subacute thyroiditis were increased, but all were significantly lower than those in patients with Graves' disease (p less than 0.01, p less than 0.001, p less than 0.001 and p less than 0.001, respectively). Three patients with subacute thyroiditis, who showed shorter duration of symptoms than 10 days, had serum TBG excess. Thus the mean (+/- SD) serum TBG concentration (26.5 +/- 8.4 micrograms/ml) was significantly higher than that (18.3 +/- 2.9 micrograms/ml) in patients with Graves' disease (p less than 0.02). The ratios of serum T3 to T4 and FT3 to FT4 in patients with subacute thyroiditis were also significantly lower than those in patients with Graves' disease (p less than 0.001 and p less than 0.001, respectively). The serum FT4 in 7 patients treated with dicrofenac sodium alone decreased to the normal range after 3 to 8 weeks from the onset of the illness. In 3 patients with TBG excess and one patient (TBG; 29.0 micrograms/ml), serum TBG declined in consequence of the serum FT4 normalization.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thyroxine-binding globulin and thyroxine-binding prealbumin in hypothyroid and hyperthyroid developing rats

We present evidence based on equilibrium and non-equilibrium binding studies, as well as on immunological techniques, that of the two rat specific thyroid-hormone-binding proteins, i.e., thyroxine-binding globulin (TBG) and thyroxine-binding prealbumin (TBPA), TBG but not TBPA is regulated by the thyroid hormones (TH). Hypothyroidism, induced from the day of birth by daily treatment with propylthiouracil (PTU-rats), leads to dramatic and sustained increases of the TH-binding abilities of the sera measured at equilibrium, whereas hyperthyroidism, induced by treatment with thyroxine (T4-rats), leads to the decrease of these abilities. Polyacrylamide gel electrophoresis and isoelectrofocalisation of radioiodinated T4-labelled sera, together with immunoassay of TBPA, demonstrate that both effects are due to TBG, the levels of which rise in PTU-rats and decline in T4-rats, while TBPA levels do not respond to either depletion or excess of the thyroid hormones. TBG rather than TBPA appears as the key thyroid-hormone-binding protein of the rat, inasmuch as it alone expresses a regulatory function of the thyroid hormones at protein synthesis level.     

Erythrocyte carbonic anhydrase I concentration in patients receiving thyroxine.

We recently reported that the red blood cell (RBC) carbonic anhydrase I (CAI) concentration in patients with hyperthyroidism is reduced and reflects the patient's mean thyroid hormone level over the preceding months. In this study, RBC CAI concentrations were measured in patients with thyroid nodules who were receiving suppressive doses of thyroxine (group I) and compared with those obtained in patients with primary hypothyroidism receiving replacement doses of thyroxine (group 2). Of the 17 patients in group 1, 16 (94%) had elevated plasma free T4 levels, but all 17 had normal free T3 levels. Of the 17 patients in group 2, 16 (94%) had normal free T4 levels and all 17 had normal free T3 levels. Plasma TSH concentrations in group 1 were all below the lower limit of sensitivity of 0.04 mU/l. In group 2, 11 had normal and 6 had slightly elevated plasma TSH concentrations. The mean (+/- SD) RBC CAI concentration in group 1 (300 +/- 53 nmol/g Hb) was significantly lower than that in group 2 (340 +/- 57 nmol/g Hb). The RBC CAI concentration was significantly correlated with both the concentration of plasma free T4 and free T3. These observations indicate that in patients receiving suppressive doses of thyroxine a slight increase in the plasma free T4 concentration produces a slight but significant decrease in RBC CAI levels.     

A thyroxine-binding globulin of major biological significance in the serum of mice: demonstration and ontogenesis

We demonstrate in the mouse serum a hitherto unrecognized major thyroxine binding globulin (TBG), analogous to human TBG or to the recently discovered rat TBG. Our demonstration is based on equilibrium dialysis, electrophoresis, immunoelectrodiffusion and autoradiography techniques. Mouse TBG displays a remarkable ontogenic pattern, with 2-3 times higher activity in foetal than in maternal serum, and a further dramatic increase after birth. Between 1 and 5 days, the T4 binding to serum reaches peak levels 7-10 times more elevated than those measured in normal or pregnant adults. We also present for the first time the ontogenesis of the thyroxine binding prealbumin (TBPA), considered until now as the only specific T4 carrier of the murine species. We show that throughout development it is the TBG, not the TBPA, which crucially governs the level of the T4-serum interactions.     

Increased erythrocyte catalase activity in patients with hyperthyroidism

Levels of human erythrocyte catalase activity were determined in 38 patients with thyroidal dysfunction. In patients with hyperthyroidism, erythrocyte catalase activities were found to be higher than the levels of normal subjects (P less than 0.001). In hypothyroidism, erythrocyte catalase activities were of the same order as those of normal subjects. Significantly high positive correlation was found between erythrocytes catalase activity and the levels of thyroxine (r = 0.5794, n = 36, P less than 0.001), and slight positive correlation was detected between catalase activity and the levels of triiodothyronine (r = 0.3978, n = 33, P less than 0.05). A decreased erythrocyte catalase activity was observed when erythrocytes lysate was incubated with thyroid hormones. It was suggested that erythrocyte catalase activity had close relationship with thyroid state, however, direct effect of thyroid hormones were not observed on erythrocyte catalase assay system in vitro.     

Serum fructosamine in assessment of diabetic control and relation to thyroid function

Measurement of serum fructosamine using a Roche kit is a simple and reliable method for the estimation of glycated serum proteins. The value of serum fructosamine can be affected by hyperglycemia in diabetics and an abnormal turnover rate of serum protein in patients with thyroid dysfunction. We measured the serum fructosamine level in 18 normal control subjects, 71 diabetics (8 IDDM, 63 NIDDM) and 46 non-diabetic untreated patients with thyroid dysfunction (28 hyperthyroidism, 18 hypothyroidism). The serum fructosamine level was significantly increased in the diabetics compared with the normal control subjects (3.84 +/- 0.15 mmol/l vs 2.58 +/- 0.08; mean +/- SE, P less than 0.01). The serum fructosamine level in the diabetics was positively correlated with the fasting plasma glucose and HbAlc level, showing the highest correlation with fasting plasma glucose at 2 weeks before and with the HbAlc level at 2 weeks after serum fructosamine measurement. In the patients with thyroid dysfunction, the serum fructosamine level in hyperthyroidism (2.08 +/- 0.03 mmol/l) and hypothyroidism (3.11 +/- 0.07 mmol/l) were significantly lower (P less than 0.001) and higher (P less than 0.001) than the normal control subjects (2.58 +/- 0.08 mmol/l), respectively. Furthermore, the serum fructosamine level in these patients was negatively correlated with the level of serum thyroid hormones such as T3 (P less than 0.001) and T4 (P less than 0.001). It is concluded that measurement of serum fructosamine is clinically useful for the evaluation of shorter-term glycemic control in diabetics, but its level for diabetic patients with thyroid dysfunction must be cautiously interpreted.     

Radioimmunoassay without extraction of L-triiodothyronine in human serum]

A radio-immunoassay of L-triiodothyronin is described. Blinding of T3 to TBG is prevented by salicylate (1%--w/v). The rabbit antiserum obtained by injection of a complexe T3-bovine serum albumin is diluted between 1/10000 and 1/20000. Bound and free hormone are separated by polyethylene glycol (17%--w/v). Serum T3-concentration in normal subjects averaged 132 +/- 29 ng/dl (SD). In hyperthyroid and hypothyroid patients, these values were respectively 351 +/- 118 ng/dl and 68 +/- 21 ng/dl.     

Thyroxine-binding globulin, triiodothyronine, thyroxine and thyrotropin in newborn infants and children.

Thyroxine-binding globulin (TBG), triiodothyronine (T3), thyroxine (T4) and thyrotropin (TSH) have been determined by radioimmunoassay in plasma of newborn infants and throughout childhood until puberty. Mean maternal TBG concentration was 1.65 +/- 0.09 mg/100 ml (SEM) and significantly higher (p less than 0.01) than cord blood levels of TBG (1.16 +/- 0.08 mg/100 ml (SEM). Throughout infancy and childhood TBG remained significantly elevated (p less than 0.01) compared to a middle age control group of healthy blood donors. T3, T4 and TSH concentrations behaved postnatally as known from previous studies. The T3 and T4 increase observed immediately after birth was not a secondary phenomenon due to changes in TBG concentration since this globulin did not change significantly during this period.     

Short and long term effects of radioiodine and antithyroid drugs on T4 binding proteins, free T4 and T3, during Graves' disease therapy.

Ninety five patients with Graves' disease were studied before and at three months intervals after antithyroid drugs (ATD) (31 cases) or radioiodine (64 cases) therapy until recovery. Before treatment, the T4 maxima binding capacity of TBPA was significantly decreased 253.5 +/- 11.4 mug/100 ml)(mean + se) (control values: 287 +/- 10.4 mug/100 ml) (alpha = 0.04), especially in 53.7% of patients (m = 177 +/- 8 mug/100 ml). The mean of TBG (m = 20.7 +/- 0.9 mug/100 ml) was not different from euthyroid subjects (m = 19.7 +/- 1.7 mug/100 ml) except in 51.2% of patients who had a low TBG (m = 14.3 +/- 1.1 mug/100 ml). An inverse linear correlation was found between TBG-DFT4 (alpha = 0.05) and DF T 3 (alpha = 0.002), TBPA-log DF T4 (alpha = 0.05) but not between TBG and TBPA. The physiological relationship between DFT3, DFT4, TT3, TBG and TBPA was studied in vitro; after adding increased quantities of T4 to a pool of sera collected from eu, hypo or hyperthyroid patients, DFT4, DFT3, FT3 index increased in linear positive relationship with TT4 concentrations, the kinetic of this phenomena was inversely correlated with T4 maximal binding capacity of TBG or TBPA for T4. Addition of T3 to the same sera did not show any effect on the previous parameters. DFT3 depended on the level of T4 in serum more than T3 concentration and was in inverse relationship with the maximal binding capacity of TBG. This data might explain the paradoxal normal or slightly increased values of DFT3 found in T3 thyrotoxicosis. In patients treated with ATD or radioiodine, TBPA but not TBG increased significantly on year after. However, in subjects with an initial very low TGB or TBPA, this phenomenon occurred on the third month after radioiodine or ATD. During the same period, DF T4 and DF T3 were inversely correlated to TBG and TBPA. In conclusion, important changes in T4 binding proteins and free fractions of thyroid hormones were observed in Graves' disease but were corrected by antithyroid therapy. All these data were in good agreement with the normalisation of thyroid function.     

Binding activities of thyroxine binding globulin versus thyroxine binding prealbumin in rat sera: differential modulation by thyroid hormone ligands, oleic acid and pharmacological drugs

We use gel equilibration and electrophoretic techniques to compare the binding properties of thyroxine binding globulin and thyroxine binding prealbumin in rat sera. The evidence indicates that TBG bears the serum lowest capacity highest affinity sites for thyroxine (T4) and triiodothyronine (T3) (Ka1 greater than or equal to 10(9) M-1) as well as weaker saturable T3 sites (Ka2 approximately 10(8) M-1). TBPA bears for T4 only Ka2 approximately 10(8) M-1 sites and for T3 only Ka approximately 10(6) M-1 sites. Consistent with these parameters are the specific responses of TBG and TBPA binding activities to varying serum concentrations of T4, T3, oleic acid, the drugs diphenylhydantoin or salicylate. The primary attack of these compounds is aimed at TBG. Small T4, oleate or DPH doses chase the TBG-bound T4 to TBPA, high doses of T4 or oleate but not of DPH inhibiting the T4 binding to both proteins. In the T3-serum interactions, all tested compounds displace the TBG-bound hormone without chasing it to TBPA. The high reactivity of TBG sites designates the protein as crucially involved in modulating the free vs bound serum levels of T4 and T3 against physiological or pathological variations of binding competitors.     

Correlation between apolipoprotein A-IV and triglyceride concentrations in human sera

Apolipoprotein A-IV concentration was measured by a newly developed competitive enzyme immunoassay in sera from fasted human subjects (n = 105) whose triglyceride concentrations ranged from 20 to 474 mg/dl (total cholesterol below 260 mg/dl) and in which chylomicrons could not be detected. Mean (+/- SD) apolipoprotein A-IV concentration was 13.0 +/- 2.6 mg/dl in sera with triglyceride levels ranging from 20 to 100 mg/dl, 16.9 +/- 3.7 mg/dl in sera with triglyceride levels ranging from 101 to 250 mg/dl, and 22.7 +/- 6.7 mg/dl in sera with triglyceride levels ranging from 251 to 474 mg/dl. The differences among the three groups were highly significant (P less than 0.001). Moreover, variations of apolipoprotein A-IV concentrations according to the triglyceride levels were noted within the normo-triglyceridemic population. Apolipoprotein A-IV concentration was 12.8 +/- 2.1 mg/dl for triglyceride levels ranging from 20 to 75 mg/dl and 16.4 +/- 3.8 mg/dl for triglyceride levels ranging from 76 to 150 mg/dl (P less than 0.01). In the entire population that was studied there was a significant linear correlation (r = 0.61, P less than 0.001) between the concentrations of serum apolipoprotein A-IV and triglyceride. Although the hypothesis of an unknown factor independently influencing both very low density lipoproteins and apolipoprotein A-IV cannot be ruled out, and although no apolipoprotein A-IV was found in the triglyceride-rich lipoprotein fraction after separation by gel filtration, these data suggest that, in fasting subjects, the secretion of very low density lipoproteins could contribute to the plasma apolipoprotein A-IV level.     

Effects of variations in thyroid hormone serum concentrations on serum ACE-activity

Serum angiotensin converting enzyme activities were significantly increased in 26 untreated hyperthyroid patients (20.3 +/- 5.4 U/ml; P less than 0.001) compared with healthy control subjects (13.1 +/- 2.3 U/ml). In 12 patients a significant fall in enzyme activities was observed after treatment compared with pretreatment serum ACE levels (P less than 0.001). Eight patients with hypothyroidism (15.7 +/- 5.1 U/ml) and 11 athyreotic patients, totally thyroidectomized for well-differentiated thyroid cancer, showed no significant differences in serum ACE activities (14.3 +/- 2.2 U/ml) compared with control subjects. After thyroid hormone supplementation a significant increase in serum ACE activity (P less than 0.05) was found in the athyreotic patients. Addition of increasing amounts of L-thyroxine to a serum sample of an athyreotic patient showed no significant effect on ACE activity in vitro. We suggest that the elevated serum ACE activity in hyperthyroidism is not from the thyroid gland, but represents a direct effect of thyroid hormone on ACE synthesis and/or release from endothelial cells.