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.     

Serum T3 level in the patients with hyperthyroidism after therapy.

Serum T3 level in various thyroid diseases was determined in unextracted serum with the Dainabot kit for T3 RIA. The serum T3 level in 33 normal subjects was 0.8-1.6 ng/ml. It was 5.7 +/- 3.5 ng/ml (mean +/- S.D.) in 36 hyperthyroid patients, and undetectable to 0.8 ng/ml in 21 hypothyroid patients. Generally the serum T4 and serum T3 decreased in parallel after radioiodine therapy for hyperthyroidism. However, in some cases the serum T3 level remained high in spite of normalized serum T4 after radioiodine therapy. This state indicated "T3-toxicosis", and hyperthyroidism was apt to recur. When thyroid function was observed for 2 years following radioiodine treatment, the ratio of serum T3 (T3 level before treatment/T3 level after treatment) decreased more significantly as compared with the ratio of serum T4 in euthyroid cases. Serum T3 provides a more sensitive index of thyroid function than serum T4 in euthyroid states after radioiodine or anti-thyroid drug therapy. The present data indicate that the serum T3 level and the T4/T3 ratio are valuable aids in the estimation of prognosis of hyperthyroid patients after various treatments.     

Iodide-induced hypothyroidism in a patient with anorexia nervosa

A 39-year-old woman who had been suffering from anorexia nervosa was found to have hypothyroidism. Serum T4, free T4, T3, free T3 and TSH were 3.19 micrograms/dl, 0.5 ng/dl, 15.3 ng/dl, 1.2 pg/ml and 162.1 microU/ml, respectively. On careful questioning, she was found to have taken an iodine-rich diet. The serum iodine concentration was 122 micrograms/dl (normal: 4-9 micrograms/dl) and urinary iodide excretion was 13.05 mg/day (normal: less than 2 mg). After withdrawal of the iodine-rich diet, her serum T4 gradually increased and TSH returned to the normal range. She was diagnosed as having iodide-induced hypothyroidism. However, no significant elevation of serum T3 or free T3 was observed. Serum T4, free T4, T3, free T3 and TSH were 7.85 micrograms/dl, 0.8 ng/dl, 13.6 ng/dl, 4.3 pg/ml and 6.02 microU/ml, respectively. The iodide-perchlorate discharge test result was negative. These findings suggest that there exists some unknown mechanism by which a patient with anorexia nervosa may be sensitive to excess iodide. Furthermore, it is of interest to note that in a recovery phase from the hypothyroid state, normalization of serum T4 rather than T3 is well-correlated to TSH secretion.     

Serum thyroxine and triiodothyronine radioimmunoassay values in the normal ferret

The European ferret, Mustela putorius furo, has become increasingly popular as an animal model in biomedical research. However, certain important normal clinical data have not been established for the ferret. In this study, serum thyroxine (T4) and 3,3',5-triiodothyronine (T3) values were obtained from ferrets by the use of commercial radioimmunoassays. Sera from 44 animals, 31 males (27 intact and 4 castrated) and 13 females (10 intact and 3 spayed) were assayed. Serum T4 values ranged from 1.01-8.29 micrograms/dl for males (mean = 3.24 +/- 1.65 micrograms/dl), and 0.71-3.43 micrograms/dl for females (mean = 1.87 +/- 0.79 micrograms/dl). Serum T4 values of adult female ferrets, juvenile ferrets (less than 1 year old) of either sex, and castrated males were similar to the normal T4 values of the cat, 1.20-3.80 micrograms/dl. Intact adult male ferrets had higher serum T4 values which were more comparable to those of the normal dog 1.52-3.60 micrograms/dl. Serum T3 values ranged from 0.45-0.78 ng/ml for males (mean = 0.58 +/- 0.09 ng/ml), and 0.29-0.73 ng/ml for females (mean = 0.53 +/- 0.13 ng/ml). These values are comparable to those of dogs and cats which are 0.50-1.50 ng/ml.     

Serum concentrations of 3, 3'-diiodothyronine, 3', 5'-diiodothyronine, and 3, 5-diiodothyronine in altered thyroid states

To investigate the thyroid hormone metabolism in altered states of thyroid function, serum concentrations of 3, 3'-diiodothyronine (3, 3'-T2), 3', 5'-T2 and 3, 5-T2 as well as T4, T3 and rT3 were determined by specific radioimmunoassays in 17 hyperthyroid and 10 hypothyroid patients, before and during the treatment. Serum T4, T3, rT3, 3, 3'-T2 and 3', 5'-T2 concentrations were all higher in the hyperthyroid patients than in age-matched controls and decreased to the normal ranges within 3 to 4 months following treatment with antithyroid drugs. In the hypothyroid patients, these iodothyronine concentrations were lower than in age-matched controls and returned to the normal ranges after 2 to 3 months treatment with T4. In contrast, serum 3, 5-T2 concentrations in hyperthyroid patients (mean +/- SE : 4.0 +/- 0.5 ng/dl) were not significantly different from those in controls (3.9 +/ 0.4 ng/dl), although they tended to decrease in 3 of 6 patients after the antithyroid drug therapy. Serum 3, 5-T2 levels in the hypothyroid patients (3.8 +/- 0.6 ng/dl) were also within the normal range and showed no significant change following the T4 replacement therapy. However, serum 3, 5-T2 as well as 3, 3'T2 concentrations rose significantly with a marked rise in serum T3 following T3 administration, 75 micrograms/day for 7 days, in Graves' patients in euthyroid state.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thyroid function and antimicrosomal antibody during the course of silent thyroiditis

The thyroid function and antithyroidal antibody were studied in 17 patients with silent thyroiditis unrelated to pregnancy. The antimicrosomal hemagglutination antibody (MCHA) was negative in ten of them (group I) and was positive in seven (group II). At one month after the thyrotoxicosis, thyroid function became normal in both groups. At two months after the onset of thyrotoxicosis, in group I T4 (8.1 +/- 1.8 micrograms/dl, Mean +/- SD), T3 (113 +/- 25 ng/dl) and TSH were normal. At that time T4 (2.8 +/- 2.2 micrograms/dl) was significantly decreased (p less than 0.001) compared with those of group I and the levels of TSH were strikingly increased in 6 patients in group II. The level of T3 (96 +/- 29 ng/dl) in group II was not different from that of group I. Therefore MCHA was negative in patients who did not develop hypothyroidism and MCHA was positive in patients who developed hypothyroidism. The development of hypothyroidism two months after thyrotoxicosis and positive MCHA are correlated. The Tg was elevated in 7 out of 13 patients (54%) with negative antithyroglobulin hemagglutination antibody and in the remainder was normal during thyrotoxicosis. The discrepancy between the level of Tg and thyroid hormones was discussed.     

Effects of thyroid status and fasting on hepatic metabolism of apolipoprotein A-I

Metabolism of apolipoprotein (apo)A-I was studied in normal and chow-fed hyperthyroid rats, in 24-h fasted untreated male rats, and in rats after thyroparathyroidectomy (TXPTX). Rats were made hyperthyroid by administration of T3 (9.6 micrograms/day) or T4 (30 micrograms/day) with an Alzet osmotic minipump. Hyperthyroidism produced a similar two- to threefold elevation in plasma levels of apoA-I in male or female animals. During treatment with T3, plasma levels of T3 ranged from 200 to 400 ng/dl and did not correlate with plasma apoA-I levels. The net mass secretion and synthesis ([3H]leucine incorporation) of apoA-I by perfused livers from male hyperthyroid rats was elevated, while secretion of albumin was not different than that of euthyroid rats. Furthermore, the incorporation of [3H]leucine into total perfusate and hepatic protein was not altered by hyperthyroidism. The effect of thyroid hormone on apoA-I synthesis, therefore, does not appear to be a general effect on protein synthesis. After longer periods of treatment (28 days) with T3 (9.6 micrograms/day), hepatic apoA-I production decreased from that observed after 7 or 14 days of treatment, yet plasma apoA-I concentrations remained elevated. Plasma T3 decreased from 100 ng/dl to 40 ng/dl, in the hypothyroid rat resulting from TXPTX, but the plasma concentration of apoA-I did not change during the 2-week experimental period. The net secretion of apoA-I by livers from hypothyroid animals was depressed and albumin was uneffected compared to the euthyroid. Overnight fasting of euthyroid rats did not alter hepatic apoA-I secretion or plasma apoA-I levels, although under fasting conditions we had reported that hepatic output of apoB and E of VLDL is depressed. The addition of oleic acid to the perfusion medium, sufficient to stimulate VLDL production, did not affect net hepatic secretion of apoA-I by livers from euthyroid, hyperthyroid, or hypothyroid rats. In summary, hepatic synthesis of apoA-I appears to be controlled independently of other apo-lipoproteins and secretory proteins (albumin). Hepatic apoA-I synthesis is sensitive to thyroid status, increased in the hyperthyroid and decreased in the hypothyroid state. The specific stimulation of hepatic synthesis and secretion of apoA-I in the hyperthyroid state, however, tends to normalize over an extended period, perhaps from compensatory effects of a hormonal nature.     

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.     

Gamma-glutamyltranspeptidase and alkaline phosphatase serum activities: their relation to the outcome of Graves' disease

Gamma-glutamyltranspeptidase (GGT) and alkaline phosphatase (ALP) were assayed in the sera of 27 patients affected with Graves' disease prior to conventional (12-18 months) methimazole (30-5 mg/day) treatment, who were subsequently followed up over 36 +/- 1.5 months (m +/- SEM). Twelve patients underwent recurrence of thyrotoxicosis (relapsers) at variable intervals from withdrawal of treatment, whereas the remaining 12 remained euthyroid (nonrelapsers). In the study group as a whole, both GGT and ALP serum levels were significantly (p less than 0.001) increased with respect to 24 sex- and age-matched euthyroid controls (31.8 +/- 3.6 vs. 11.5 +/- 1.2 U/l and 203 +/- 13.8 vs. 110 +/- 7.3 U/l, m +/- SEM). Prevalence of GGT and ALP elevations was 56% (15/27) and 58% (15/26), respectively. Serum GGT activity was age dependent (r = 0.466, p less than 0.05) and inversely related to log2 microsomal antibody initial titer (r = 0.499, p less than 0.05) in the whole series. There was no difference in mean pretreatment thyroxine (T4) or triiodothyronine (T3) between the groups with supranormal enzyme and normal enzyme levels. However, in the group with enhanced enzyme levels, relapsed patients had higher initial T4 (20.3 +/- 0.8 vs. 17.1 +/- 0.7 micrograms/dl, p less than 0.01) and lower both initial T3 (452 +/- 31.1 vs. 551 +/- 57.8 ng/dl, p less than 0.02) than the nonrelapsed patients. Only in this group, initial T3:T4 ratio was a valuable indicator of the outcome of the disease, since it was below 30 in 7/7 (100%) relapsers vs. 2/8 (25%) nonrelapsers, but above 30 only in 6 subjects who remitted.     

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)     

Studies on the T3 suppression test by the 24-hour thyroidal 131I uptake in patients with Graves' disease: comparison of the effects of propylthiouracil and methylmercaptoimidazole

The T3 suppression test by the 24-hr thyroidal 131I uptake was reevaluated in patients with Graves' disease before and after withdrawal of antithyroid drug. Fifty patients had been treated with propylthiouracil (PTU) or methylmercaptoimidazole (MMI) for 12 to 70 months. They were prescribed a maintenance dose of antithyroid drug (PTU, 50 mg/day; MMI, 5 mg/day) at the time of investigation and regarded as euthyroid on the basis of serum T3, T4 and TSH levels. Each patient was given 75 micrograms T3 daily for 8 days in conjunction with PTU or MMI. The 24-hr thyroidal 131I uptake was then measured (post T3 uptake). In 30 patients whose post T3 uptake was below 35%, treatment was stopped and the T3 suppression test was repeated at one and 3 months later. During the two-year follow up, 24 remained well, while 6 relapsed within 4 to 12 months. In patients with sustained remission, the post T3 uptake was significantly lower in the MMI-treated group (13 cases, 7.7 +/- 1.0%) than in the PTU-treated group (11 cases, 18.6 +/- 1.9%). MMI withdrawal produced a marked rebound in the post T3 uptake, whereas none of the patients showed the rebound after PTU withdrawal. In patients who relapsed later, there was no difference in the post T3 uptake during treatment and the rebound occurred in the both groups following goitrogen withdrawal. Serum T3, T4 and TSH levels were within normal ranges at one and 3 months after cessation of antithyroid drug. From the results of the present study, it is concluded that criteria for T3 suppressibility by the 24-hr uptake should be determined by the antithyroid drug employed and by the time of investigation. There is a dissociation in the post T3 uptake values following withdrawal of the two different antithyroid drugs.     

Effect of intravenous methimazole on serum levels of thyroid hormones in patients with hyperthyroidism resistant to oral thyrostatic drugs

The effectiveness of therapy involving intravenous administration of methimazole applied in patients with hyperthyroidism resistant to oral thyrostatic drugs has been investigated. Methimazole (Favistan, Asta) was administered intravenously to 3 patients (two women and one man, of ages 21, 24 and 67 years, respectively) in whom there was no remission of the disease after oral methimazole therapy lasting at least two months. Blood serum concentrations of thyroxine (T4), triiodothyronine (T3), reverse++ triiodothyronine (rT3) and triiodothyronine binding index (T3I) have been measured and free thyroxine index (FT4I) calculated before the treatment and on the 4-th, 7-th, 11-th, 14-th and 17-th day of the treatment. The mean value of T4 concentration decreased from 17.0 micrograms/dl before the treatment to 9.7 micrograms/dl after the treatment. T3 from 352 to 177 ng/dl, rT3 from 114 to 103ng/dl the value of T3I from 183 to 161%, and that of FT4I from 30 to 17, respectively. A significant fall of T3 level was observed on the 11-th day of the therapy, that of rT3 on the 14-th day, and that of FT4I on the seventh day. It was concluded that the resistance of some patients with hyperthyroidism to the oral thyreostatic therapy may be caused by the defective absorption of these drugs from the intestinal tract.     

Clinical study on increased serum thyroxine-binding globulin in cancerous state

Serum thyroxine-binding globulin (TBG) in 169 patients with various cancers was determined by radioimmunoassay (RIA). Eleven patients showed a high serum TBG level (greater than 35 micrograms/ml). Two of them had been treated with estrogen for prostate cancer. One patient had high serum TBG with serum hepatitis. Another 8 cases had normal liver function and also normal levels serum estrogen. Thus, about 4.7% (8/169) of the cancer patients had high serum TBG and mild hyperthyroxinemia caused by unknown mechanisms. The high TBG level in these patients continued until just before death, or in some cases decreased to normal after removal of cancer tumors by operation. Cancer is occasionally associated with an increase in serum TBG. Although the mechanism is not clear, the increased TBG in the cancerous state in interesting and has significance as a tumor marker.     

TBG-dependency of age related variations of thyroxine and triiodothyronine.

Thyroxine (T4), triiodothyronine (T3) and thyroxine-binding globulin (TBG) were determined in healthy individuals ranging in age from newborn to 95 years. T4: 10.25 +/- 1.62 microng/100 ml, T3: 1.62 +/- 0.35 ng/ml and TBG: 1.34 +/- 0.15 mg/100 ml, were found elevated until puberty compared to a middle age group with T4: 7.27 +/- 2.26 microng/100 ml, T3: 1.15 +/- 0.24 ng/ml and TBG: 0.98 +/- 14 mg/100 ml. T4 and T3 followed almost TBG concentration. In old age is dissociation between T4: 5.79 +/- 1.56 microng/100 ml, T3: 0.79 +/- 0.21 ng/ml and TBG: 1.28 +/- 0.15 mg/100 ml was found. Except for old age the ratio T4/TBG and T3/TBG minimized the age dependent variation of T4 and T3 and reduced the coefficient of variance from 26% to 17.7% for T4 and from 26.5 to 25% for T3. Age reduction of T4/TBG is 15% and of T3/TBG 13% respectively more pronounced than for T4 and T3 alone. These data indicate: 1) age related variations of T4 and T3 due to age dependency of TBG, 2) deviation of T4 and T3 values in old age from that expected by their TBG levels and 3) the importance of the routine use of hormone/TBG ratio.     

The renin-angiotensin system in hypothyroidism of short duration

In six hypothyroid patients (2 male, 4 females, ages 22 through 59 years), plasma renin activity (PRA) and aldosterone (Aldo) were measured when the patients were euthyroid on levothyroxine therapy and one month after the therapy was stopped. Colonic mucosal potential differences were measured during the hypothyroid and euthyroid stages, and catecholamine sensitivity was determined by the blood pressure response to infused norepinephrine. Significant differences were observed in the PRA and aldosterone concentrations which were 4.1 +/- 2.5 ng/ml/h and 9.4 +/- 5.9 ng/dl, respectively in the hypothyroid stage and 6.9 +/- 2.3 ng/ml/h and 15.2 +/- 7.3 ng/dl, respectively when the patients were made euthyroid. The colonic mucosal potential differences (which reflect increased endogenous mineralocorticoid activity), became more electronegative after correction of hypothyroidism (-16.8 +/- 7.5 mV vs -32 +/- 18.2 mV; P less than 0.04) concentrations. Statistically significant decreases in norepinephrine pressor effects were observed in hypothyroid patients when compared to the euthyroid state (7.4 +/- 2.3 vs 10.9 +/- 1.9 micrograms/ng/min; P less than 0.01). It is concluded that patients with hypothyroidism have a hormonal pattern reminiscent of "low renin hypertension", and exhibit decreased sensitivity to catecholamines. Such changes are corrected when the patients become euthyroid on levothyroxine therapy.     

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.     

Long-term intramuscular administration of thyrotropin-releasing hormone tartrate in patients with cerebrovascular disease: effects on the pituitary-thyroid axis.

We studied the effects of long-term (30 days) refracted daily intramuscular administration of 4 mg TRH tartrate (TRH-T) on the pituitary-thyroid axis in 20 euthyroid patients affected by cerebrovascular disease (CVD). All subjects were assayed for T4, T3, FT4, FT3, TSH and TBG plasma levels before treatment (D0), after 15 and 30 treatment days (D15, D30), and after a 15-day washout (D45). In addition, TSH response to 200 micrograms intravenous TRH was assessed at D0, D30 and D45. We observed a significant increase in T4, FT4 and FT3 levels in the face of decreased TSH concentrations. A blunted TSH response to TRH bolus persisted at D30. These data demonstrate that the down-regulation mechanism may be partially overcome in vivo when thyrotrophs are chronically exposed to pharmacological TRH-T doses and that TSH pattern is mainly due to the negative feedback of thyroid hormones, even though pituitary TSH reserves may become depleted. Furthermore, prolonged TRH-T administration does not produce hyperthyroidism in euthyroid CVD patients.     

Measurement of serum thyroxine binding prealbumin in various thyroidal states by radioimmunoassay

Serum thyroxine binding prealbumin (TBPA) levels in various thyroidal states were examined by radioimmunoassay (RIA). This technique is highly sensitive, accurate and reproducible. The normal mean (+/- 2SD) level of serum TBPA is 26.9 +/- 8.0 mg/dl (29.4 +/- 5.2 in men and 24.9 +/- 7.6 mg/dl in women). Serum TBPA levels in pregnant women were significantly lower than in normal females (P less than 0.05). Serum TBPA levels in patients with untreated hyperthyroidism were 12.9 +/- 4.0 mg/dl (mean +/- SD) and in patients with untreated hypothyroidism were 25.2 +/- 4.7 mg/dl (mean +/- SD). The mean TBPA concentrations in untreated hyperthyroidism were significantly lower than that for normal population (P less than 0.01), but untreated hypothyroidism was almost within normal range. The changes in TBPA levels in hyperthyroidism and hypothyroidism were similar to those in TBG levels. In untreated hyper- and hypothyroidism, restoration to euthyroidism by treatment was uniformly accompanied by a normalization of serum TBPA and TBG levels. A negative correlation between serum thyroid hormone binding protein (TBG and TBPA) and free thyroxine was observed in patients with hyperthyroidism. The coefficient of correlation between TBPA and free thyroxine was -0.80 (P less than 0.01) and between TBG and free thyroxine -0.58 (P less than 0.01). From these experiments it appears that not only TBG but also TBPA may play an important role in the regulation of the free thyroxine concentration in response to various thyroidal states.     

Angiotensin-converting enzyme activity decreases during fasting

Serum angiotensin-converting enzyme (ACE) activity varies directly with thyroid hormone levels in states of altered thyroid function. Because T3 levels decrease during fasting, ACE activity was examined to ascertain if it was reduced in this low T3 condition. Eighteen obese euthyroid subjects were hospitalized and placed on a weight-maintaining diet for 4 days. Nine subjects (Group 1) underwent a fast (50 kcal/day) for 8 days. Nine (Group 2) subjects received T3 (5 micrograms q 3 h) during an identical fast. Weight loss was identical in both groups (-4.4 kg). Serum T3 fell in Group 1 from 104 +/- 8 to 50 +/- 4 ng/d/(p less than .05) but was unchanged in Group 2 (114 +/- 11 ng/dl fed vs. 120 +/- 14 ng/dl fasted). Blood pressures fell significantly in Group 1 (mean systolic: 112----104 mmHg; diastolic: 71----65 mmHg, p less than 0.05), but not in Group 2 subjects. ACE activity fell progressively in Group 1 subjects during fasting (14.4 +/- 1.6 U/ml fed vs. 12.8 +/- 1.4 U/ml fasted p less than 0.05). ACE activity was not decreased significantly early in the fast in patients given T3, but by late fast (days 6-8) was reduced to the same degree as in Group 1 subjects. Glucose and insulin levels fell similarly in both groups. Conclusions: (1) ACE activity is reduced during starvation. This effect is not mediated by T3. (2) Blood pressure reduction during fasting may result from the low T3 levels, but not from decreased ACE activity. Interpretation of serum ACE activity must be viewed in the context of a patient's diet.     

Pituitary resistance to thyroid hormone--a case report

Pituitary resistance to thyroid hormone is a very rare cause of hyperthyroidism. It is characterized by normal, or elevated TSH concentration with high concentration of T3 and T4. Here, we present a case of a 24-year-old woman who suffered from mild thyrotoxicosis and diffuse goiter for several years. She had elevated fT3 and fT4 with slightly elevated TSH concentration. Pituitary adenoma was excluded as magnetic resonance imaging showed normal pituitary gland, alpha subunit was within normal range and TSH concentration increased after TRH administration. Sonography revealed normoechogenic, slightly enlarged thyroid gland. Previously, she was given thiamazole, but without any significant amelioration. Thus, the diagnosis of the syndrome of pituitary resistance to thyroid hormone was established. The patient was given bromocriptine at a dose of 10 mg per day. After 2 months of treatment she achieved a state of constant euthyrosis and following next few months thyroid volume diminished.