Serum TSH, T4, T3, FT4, FT3, rT3, and TBG in youngsters with non-ketotic insulin-dependent diabetes mellitus

Several parameters of thyroid function were studied in 112 non-ketoacidotic youngsters with insulin-dependent diabetes mellitus (IDDM). Levels of thyroxine (T4), reverse triiodothyronine (rT3), thyroxine-binding globulin (TBG) and T3 were lower than in controls, whereas FT4, and FT3 were normal. T4 levels in IDDM patients were positively related to T3, rT3 and TBG, and inversely related to haemoglobin A1 (HbA1). However, only 4 patients showed biochemical hypothyroidism (T4 less than 5 micrograms/100 ml), whereas their FT4, FT3 and thyroid-stimulating hormone (TSH) levels were normal. Concurrent variations of T3 and rT3 levels were found in IDDM patients; thus, their T3/rT3 ratios were stable or higher than in controls, indicating that peripheral deiodination of T4 is preferentially oriented to production of rT3 only during ketoacidosis. Although changes in thyroid function may reflect the degree of metabolic control of diabetes in a large population, the clinical usefulness of serum thyroid hormone measurements in an individual case still appears to be limited.     

Apparent increase in type I 5'-deiodinase activity induced by antiepileptic medication in mentally retarded subjects

BACKGROUND/OBJECTIVES: Thyroid function measurements in 3 mentally retarded patients treated with antiepileptic drugs (phenytoin or carbamazepine) showed normal thyroid-stimulating hormone (TSH) responses in spite of markedly low levels of total thyroxine (T(4)), triiodothyronine (T(3)), and free thyroxine (FT(4)) concentrations; free triiodothyronine (FT(3)), as well as mean thyroxine-binding globulin (TBG) concentrations were normal. The objective of the present investigations was to determine if antiepileptic medication in these patients contributed to the disparate TSH and thyroid hormone (TH) levels. METHODS: Thyroid tests and other laboratory parameters were measured by conventional techniques. RESULTS: Circulating TH changes noted in retarded patients were similar to those observed in control subjects receiving carbamazepine alone. Reverse T(3) (rT(3)) levels in all patients were either undetectable or below the normal range. CONCLUSIONS: As type I 5'-deiodinase has a higher affinity for rT(3) than T(4), an increased activity of this enzyme would enhance rT(3) deiodination and reduce serum rT(3) concentration whereas enhanced T(4) deiodination would aid in normalizing intracellular FT(3) concentration. The finding of normal serum FT(3) concentration was consistent with normal TSH response and clinical euthyroidism in both retarded and control subjects. While phenytoin-induced increase in type I 5'-deiodinase has been previously noted, the present studies demonstrate a similar effect of carbamazepine on 5'-deiodinase.     

The pituitary-thyroid axis in patients with pituitary disorders

The pituitary-thyroid axis of 12 patients, exposed to transsphenoidal pituitary microsurgery because of nonfunctioning adenomas (6), prolactinomas (3) and craniopharyngioma (1), or to major pituitary injury (1 apoplexy, 1 accidental injury), was controlled more than 6 months following the incidents. The patients did not receive thyroid replacement therapy and were evaluated by measurement of the serum concentration of thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3), T3-resin uptake test and thyrotropin (TSH, IRMA method) before and after 200 micrograms thyrotropin releasing hormone (TRH) iv. The examination also included measurement of prolactin (PRL) and cortisol (C) in serum. Apart from 1 patient with pituitary apoplexy all had normal basal TSH levels and 9 showed a significant TSH response to TRH. Compared to 40 normal control subjects the 12 patients had significantly decreased levels of T4, T3 and rT3 (expressed in free indices), while the TSH levels showed no change. Five of the patients, studied before and following surgery, had all decreased and subnormal FT4I (free T4 index) after surgery, but unchanged FT3I and TSH. The levels of FT4I were positively correlated to both those of FT3I and FrT3I, but not to TSH. The TSH and thyroid hormone values showed no relationship to the levels of PRL or C of the patients exposed to surgery. It is concluded that the risk of hypothyroidism in patients exposed to pituitary microsurgery is not appearing from the TSH response to TRH, but from the thyroid hormone levels.     

Thyroid function tests in children with congenital hypothyroidism on L-thyroxine treatment

The plasma levels of thyroxine (T4), triiodothyronine (T3), free T4 (FT4), free T3 (FT3), reverse T3 (rT3) and immunoradiometrically assayed thyrotropin (IRMA TSH) have been measured in 28 L-T4-treated children with congenital hypothyroidism as well as in a control group (group C). The patients were subdivided into 2 groups according to the nonsuppressed (group A) or suppressed (group B) TSH response to TSH-releasing hormone (TRH). Basal IRMA TSH correlated with the TSH increment after TRH and it was significantly lower in group B vs. groups A and C, while no difference was present between groups A and B in regard to T4, FT4 and rT3, all higher than in group C. FT3 levels were similar in the 3 groups. In children, as in adults, basal IRMA TSH seems to be a reliable index in monitoring overtreatment.     

Thyroid functions in patients with various chronic liver diseases

In order to clarify an alteration in thyroid functions in patients with chronic liver diseases, serum total and free thyroxine (T4, FT4), total and free triiodothyronine (T3, FT3), total reverse T3 (rT3), thyrotropin (TSH), thyroxine-binding globulin (TBG) concentrations, and T3 uptake (T3U) were measured by radioimmunoassays in 53 patients with chronic hepatitis (CH), 24 patients with compensated liver cirrhosis (LC), 17 patients with hepatocellular carcinoma associated with LC (HCC), and 40 normal subjects. Serum T4, T3, and rT3 in CH, and serum rT3 in HCC were significantly increased, while serum T4 in LC and serum T3 in HCC were significantly decreased. Serum TBG was increased and T3U was decreased in these patients. Serum TBG in CH and LC correlated positively with transaminase, and inversely with prothrombin time. FT4 and T4/TBG ratios in CH and LC and FT3 and T3/TBG ratios in LC and HCC were significantly decreased. Although T4/TBG ratios in HCC and T3/TBG ratios in CH were significantly decreased, FT4 in HCC and FT3 in CH were not decreased. The ratio of rT3/T3 in CH and LC correlated with various liver function tests. FT3 in LC and HCC correlated inversely with BSP (45') and positively with KICG. No differences in serum TSH values were found between chronic liver diseases and normal subjects. From these results, it was concluded that the thyroid functions in patients with chronic liver diseases were affected by the decrease in serum thyroxine, elevated serum TBG, the degree of which is in proportion to that of the liver cell damage, and impaired peripheral conversion of T4 to T3, the degree of which is in proportion to that of the hepatic dysfunction.     

Selenium Status Is Positively Associated with Bone Mineral Density in Healthy Aging European Men

ObjectiveIt is still a matter of debate if subtle changes in selenium (Se) status affect thyroid function tests (TFTs) and bone mineral density (BMD). This is particularly relevant for the elderly, whose nutritional status is more vulnerable.ResultsThe overall Se status in our population was low normal with only 0.5% (2/387) of subjects meeting the criteria for Se deficiency. SePP and Se levels were not associated with thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroxine (T4), triiodothyronine (T3) or reverse triiodothyronine (rT3) levels. The T3/T4 and T3/rT3 ratios, reflecting peripheral metabolism of thyroid hormone, were not associated with Se status either. SePP and Se were positively associated with total BMD and femoral trochanter BMD. Se, but not SePP, was positively associated with femoral neck and ward''s BMD. Multivariate linear analyses showed that these associations remain statistically significant in a model including TSH, FT4, body mass index, physical performance score, age, smoking, diabetes mellitus and number of medication use.ConclusionOur study demonstrates that Se status, within the normal European marginally supplied range, is positively associated with BMD in healthy aging men, independent of thyroid function. Thyroid function tests appear unaffected by Se status in this population.     

Thyroid function and plasma selenium in chronic uremic patients on hemodialysis treatment

It has been shown recently that Selenium (Se), an essential trace element for humans, is involved in the regulation of thyroid function, since the enzyme that catalyzes the liver conversion of the thyroid hormone T4 to the more active form T3 is a selenoenzyme. In chronic uremic patients, low blood Se levels as well as thyroid function abnormalities are often found. The present study was carried out to verify whether any correlation exists between Se levels and thyroid function, and to evaluate possible changes in hormonal pattern during Se supplementation in 10 chronic uremic patients on hemodialysis (HD) treatment. Se was supplemented orally as sodium selenite over six consecutive months. Basic plasma Se levels were significantly lower in patients than in normal controls. Right from the start of Se supplementation, plasma Se concentration promptly normalized and leveled off in the normal range throughout the study. Significant increase of FT3 and reduction of TSH levels were detected during Se supplementation. In Se-supplemented patients, a significant direct correlation was also found between reverse T3 (rT3) and TSH, and a significant inverse correlation was found between Se and TSH. Our results suggest that Se deficiency in chronic uremic patients represents a factor influencing the thyroid function and that the Se status should be determined in the evaluation of thyroid metabolism in these patients.     

Changes in the hypothalamic-pituitary-thyroid axis during acute starvation in non-obese patients

We investigated changes in the hypothalamic-pituitary-thyroid axis before, during, and after fasting in twenty-one non-obese euthyroid patients with psychosomatic diseases. Blood samples for free T3 (FT3), T3, free T4 (FT4), T4, reverse T3 (rT3), and TSH were obtained from all patients before and on the 5th day of fasting, and in 11 of the same individuals on the 5th day of refeeding. Serum TSH and T3 responses to TRH were also evaluated in 10 patients before and on the 5th day of fasting. During the fast, FT3, T3 and TSH levels decreased significantly and rT3 levels increased significantly whereas FT4 and T4 levels remained within the normal range. Maximal delta TSH, peak TSH levels, max delta T3, peak T3 levels, and net secretory responses to TRH decreased significantly. Peak TSH levels and max delta TSH to TRH correlated well with basal levels of TSH. A statistically significant negative correlation between basal levels of FT4 and TSH was observed. After refeeding, there was a significant increase only in TSH which returned to prefasting values. These results demonstrated that in a state of "low T3" during acute starvation a reduction in serum T3 might depend partly on TSH-mediated thyroidal secretion.     

Behaviour of serum T3, rT3, TT4, FT4 and TSH levels after exercise on a bicycle ergometer in healthy euthyroid male young subjects

In order to know thyroid function during physical activity, just studied by several authors without univocal findings, we have submitted 10 young subjects, non athletes, aged 22-25 years (mean age 23, 6 +/- 1, 43) to a biologically maximal exercise on a bicycle ergometer. We have also examined the change of TSH serum levels during exercise. Our data show an evident increase of T4 (18, 60% at 10'), p less than 0.025, an increment of FT4 (28, 49 soon after the strain), and no relevant change of T3 and rT3 serum levels. Moreover TSH values show a reduction at 30' (-26, 15%) in comparison with the basal level. Our findings confirm the known increment of T4 and FT4 serum level after physical activity. It can be due, more than an hemoconcentration supported by others, to a real rise of thyroid incretion as in our opinion TSH levels reduction suggests. Concluding we think that the increase of T4 and decrease of TSH could be due to a direct influence of the physical activity on the system interested in their production.     

Behavior of thyroid hormones and TSH in chronic active hepatitis

The authors studied total and free circulating thyroid hormones, rT3, TBG and TSH behaviour on chronic liver disease in 11 subjects with cirrhosis of the liver with ascites(C.E.) and in 6 subjects with chronic active hepatitis (E.C.A.) in comparison with 15 healthy and euthyroid controls. Serum T3,FT3,T4 and FT4 levels were decreased significantly and serum rT3 values increased significantly both in the subjects with C.E. and in patients with E.C.A. Moreover no significantly changes of TSH and TBG levels has been found in 3 groups studied. These data suggest that the alteration of circulating thyroid hormones in chronic liver disease, may represent a compensatory way of reducing the patient's metabolic requirements.     

Effects of ketoacidosis and puberty on basal and TRH-stimulated thyroid hormones and TSH in children with diabetes mellitus

Basal and TRH-stimulated thyroid hormones and TSH were evaluated in two groups of prepubertal and pubertal diabetics: group B - 45 children without ketoacidosis; group C - 16 children with ketoacidosis. The diabetic patients showed no signs of diabetic microangiopathy. Fifty-three healthy subjects served as controls (group A). T4, T3, FT4 and FT3 serum levels were reduced in diabetics, particularly in ketotic ones; T4 and T3 values were lower in pubertal than in prepubertal non-ketotic diabetics and in pubertal than in prepubertal controls, while no significant difference was observed between pubertal and prepubertal ketotic patients. Moreover, no difference in rT3 serum concentrations was found between group A, B and C, but non-ketotic and ketotic pubertals showed a significant rT3 reduction if compared with non-ketotic and ketotic prepubertals and with healthy pubertals. TBG was lower in group B and group C diabetics than in controls. After TRH stimulus, T3 levels showed a significant increase both in controls and in non-ketotic diabetics, while no variation was observed in ketotic children; furthermore, at 120 minutes T3 values were lower in diabetic than in healthy children, particularly in ketotic ones. Basal TSH serum concentrations were reduced in ketotic diabetics, while no difference was found between nonketotic and control subjects. After TRH stimulus, TSH peak was higher in pubertal non-ketotic diabetics than in pubertal controls, while no difference was found between prepubertal and pubertal diabetics, both in non-ketotic and in ketotic status.(ABSTRACT TRUNCATED AT 250 WORDS)     

肝病患者血清甲状腺相关物质的检测与意义

目的探讨不同程度肝病患者血清甲状腺激素水平的变化及其意义。方法应用放射免疫法分别检测114例慢性肝炎、130例肝硬化、96例重型肝炎、120例健康体检者的血清甲状腺激素水平(T3、T4、FT3、FT4、rT3、TSH),抗甲状腺过氧化物酶抗体(抗TPO)、抗甲状腺球蛋白抗体(抗TG)的含量变化。结果肝病患者较正常人血清甲状腺素水平(T3、T4、FT3、FT4)显著降低,而抗TPO、抗TG、rT3含量显著升高,差异有统计学意义;随着肝功能受损程度的加重,血清甲状腺素水平(T3、T4、FT3、FT4)降低程度差异有统计学意义。结论肝病患者血清甲状腺激素水平的检测对评估肝功能、判断病程及预测预后有一定的临床意义。     

Serum thyroid hormone profile and trace elements in children receiving valproic acid therapy: A longitudinal and controlled study

Valproic acid (VPA) may affect thyroid hormone profile, causing alteration in serum trace elements concentrations. The aim of this study was to prospectively investigate this relationship in children receiving VPA monotherapy for a period up to 6 months. Serum thyrotropin (TSH), free thyroxine (FT4), free triiodothyronine (FT3), thyroxine (T4), triiodothyronine (T3), thyroglobuline (TG), selenium (Se), zinc (Zn), and copper (Cu) levels were evaluated at baseline and at the 6th month in all the patients and in the control group. The mean Cu concentration in the 6th months of VPA therapy was significantly lower than that of the control group. TSH level was significantly increased in the patient group whereas FT4 was significantly decreased. The mean TSH level in the 6th month of VPA therapy was significantly higher than that of the control group, whereas mean T4 level was significantly lower. The Cu level in the 6th months of VPA therapy was positively correlated with T4 level. Δlog Cu and ΔTSH were negatively correlated. This study suggests that the alteration in the serum thyroid hormone profile during VPA therapy may result from the reduction in serum Cu levels.     

Thyroid function and trisomy 21. TSH increase and rT3 deficiency

An excess of thyrotropin (TSH) with normal levels of tetraiodothyronine (T4) and of 3,5,3'-triiodothyronine (T3) was confirmed in the serum of 78 trisomy 21 children. A severe deficiency of 3,3',5'-triiodo-thyronine (rT3 or reverse T3) was observed and the decrease of the rT3/TSH ratio was highly significant. These new facts suggest that the rT3 deficiency plays a peculiar role in trisomy 21 (maybe through the regulation of one or few steps of monocarbons' metabolism). A systematic control of thyroid function (including the patient's rT3 level) is mandatory for the follow-up of every trisomy 21 patient.     

Cardiopulmonary bypass: a low T4 and T3 syndrome with blunted thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH)

Thyroid hormone serum concentrations, the thyrotropin (TSH) and prolactin (PRL) response to thyrotropin-releasing hormone (TRH) were evaluated in patients undergoing cardiopulmonary bypass (CPB) conducted in hypothermia. During CPB a marked decrease of thyroxine (T4) and triiodothyronine (T3) concentration with a concomitant increase of reverse T3 (rT3) were observed similarly to other clinical states associated with the 'low T3 syndrome'. Furthermore, in the present study elevated FT4 and FT3 concentrations were observed. In a group of patients, TRH administered during CPB at 26 degrees C elicited a markedly blunted TSH response. In these patients, PRL concentration was elevated but did not significantly increase after TRH. The increased concentrations of FT4 and FT3 were probably due to the large doses of heparin administered to these patients. Thus, the blunted response of TSH to TRH might be the consequence of the elevation of FT4 and FT3 in serum, however, other factors might play a role since also the PRL response to TRH was blocked.     

Screening of geriatric patients for thyroid dysfunction with thyrotropin-releasing-hormone test, sensitive thyrotropin and free thyroxine estimation

Hospitalized geriatric patients (N = 354) from an iodine-deficient area were screened with sensitive thyrotropin (TSH), free and total thyroxine (FT4, T4) and total triiodothyronine (T3) to determine the occurrence rate of clinical and subclinical thyroid dysfunction. The diagnostic value of the tests was compared to each other and to that of the thyrotropin-releasing-hormone test (TRH-test) in order to find the optimal first line screening test in geriatric patients. Clinical hyperthyroidism was found in 13, subclinical hyperthyroidism in 10, overt hypothyroidism in 6 and subclinical hypothyroidism in 8 cases. 20.6% of the patients were euthyroid but had subnormal TSH response to TRH, as a sign of possible thyroid autonomy. The low occurrence rate of clinical thyroid disorders (4.8%) does not justify the screening of geriatric patients in general, but the high probability of thyroid autonomy makes reasonable the investigation of every geriatric patient before iodine administration. Suppressed basal TSH and high FT4 were found to be both sensitive and specific in diagnosing clinical hyperthyroidism, but the predictive value was insufficient; elevated T4 and T3 are specific, but not sensitive. Basal TSH is sensitive, specific and has a good predictive value in diagnosing euthyroidism, whereas normal T4, FT4 or T3 are not specific enough for euthyroidism. Basal TSH is better as a first line test of thyroid function than FT4. A normal basal TSH confirms euthyroidism by itself. Other tests (TRH test, T4, FT4, T3) are necessary to elucidate the clinical importance of a subnormal or suppressed basal TSH.     

The effect of propylthiouracil on thyroid-stimulating hormone-induced alterations in iodothyronine secretion from perfused dog thyroids

The aim of this study was to see whether the inhibitory effect of propylthiouracil on thyroidal secretion of 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine (rT3) could be reproduced in intensively stimulated thyroids, and to elucidate whether an increase in the fractional deiodination of thyroxine (T4) to T3 and rT3 during iodothyronine secretion might be responsible for the transient fall in the T4/T3 and T4/rT3 ratios in thyroid secretion seen in the early phase after stimulation of thyroid secretion. For this purpose T4, T3 and rT3 were measured in effluent from isolated dog thyroid lobes perfused in a non-recirculation system using a synthetic hormone free medium. 1 mmol/1 propylthiouracil induced a significant reduction in thyroid-stimulating hormone (TSH) stimulated T3 and rT3 release while the release of T4 was unaffected. This supports our previous conclusion that T4 is partially monodeiodinated to T3 and rT3 during thyroid secretion. Infusion of 1 mmol/l propylthiouracil for 30 min or 3 mmol/l propylthiouracil for 120 min did not abolish the transient fall in effluent T4/T3 and T4/rT3 induced by TSH stimulation. Thus, this phenomenon seems not to depend on intrathyroidal iodothyronine deiodinating processes.     

Relationship between the thyroidal and gonadal axes during the estrous cycle of ewes of different breeds and ages

In order to define the patterns of TSH, T4, T3, rT3, GH and cortisol during the estrous cycle of sheep, pluriparous and primiparous ewes were synchronized with progestagen-impregnated pessaries (Veramix) at the start of the normal breeding season. After the pessaries were removed (day 0), daily blood sampling was carried out in cannulated ewes during the ovulatory cycle. Hormonal analyses of TSH, T4, T3, rT3, GH, cortisol, LH and progesterone (P) were performed by RIA. P and LH levels during the cycle were conform to the literature and were not different between the primiparous and pluriparous ewes of different breeds used in this study. Neither age nor breed influenced the hormone patterns. A significant negative correlation was found between TSH and P during the cycle, although the correlation between P and T4 was not significant; during the estrous period, low P levels were paralleled by high T4 levels, whereas the reverse was observed during the luteal phase. Higher T3 levels and T3/T4 ratios were observed during the luteal phase. No obvious pattern of rT3 and cortisol during the cycle was found. The GH concentration increased during the 17 days of the cycle. A positive correlation with P was calculated. During the estrous cycle obvious changes in thyroid hormones, GH and TSH occurred. However, this study shows no causal relationship between the thyroid and the gonadal axes.     

A case of hypothyroidism with simultaneous presence of stimulating type anti-thyrotropin (TSH) receptor antibodies and anti-thyroxine (T4) autoantibodies.

We have examined a hypothyroid patient with stimulating type anti-thyrotropin (TSH) receptor antibodies and without blocking type anti-TSH receptor antibodies. Although she had high serum TSH (240 microU/ml) and low free triiodothyronine (FT3, 0.49 pg/ml) concentrations, which agree with physical findings of hypothyroidism, she had an unusually high free thyroxine (FT4) concentration (3.56 ng/dl). Incubation of her serum with 125I-T4, followed by precipitation with 12.5% polyethylene glycol (PEG) disclosed a higher binding of 125I-T4 (34.4%) than in normal controls, being 5-7%. In addition, binding of 125I-T4 to her serum gamma-globulin was completely displaced by the addition of unlabelled T4. From these results it was concluded that her serum contained anti-T4 autoantibodies. Treatment with synthetic T4 was begun and her thyroid function was monitored by sensitive TSH radioimmunoassay (RIA) and RIA of FT4 after PEG treatment. Since both sensitive TSH RIA and FT4 RIA results after PEG treatment give results concordant with the physical findings, it was concluded that both of the RIA results are useful for the evaluation of thyroid function in patients with thyroid hormone autoantibodies.     

Euthyroid hyperthyrotropinemia secondary to hyperestrogenemia in a male with congenital adrenal hyperplasia.

A 10-year-old boy with congenital adrenal hyperplasia and associated hyperplastic testicular adrenal rests had high serum concentrations of 17-OH progesterone (17-OHP), estradiol (E2), testosterone (T), and basal and TRH-stimulated TSH and PRL, but normal thyroid hormones (T3, T4, FT3, FT4) and thyroxine-binding globulin (TBG). Upon dexamethasone therapy, steroid hormones returned progressively toward normal as did both PRL and TSH; PRL declined faster than TSH. Serum E2 correlated better with PRL than with TSH. Therefore, the responsiveness of the thyrotrophs to the ambient concentration of E2 is lower and slower than that of the lactotrophs. In the context of the inconclusive data on the role of estrogens in controlling the secretion of TSH in humans, our case suggests that E2 does stimulate the secretion of basal and TRH-elicited both TSH and PRL, and that this positive action is unopposed by T. In contrast, T antagonizes the estrogen-induced increase in serum TBG. We also postulate that E2 might impair the bioactivity of TSH, in order to explain (i) the approximate 3-fold increase in serum TSH coexisting with a normally sized (rather than enlarged) thyroid and normal (rather than increased) serum thyroid hormones, and (ii) the inability of TRH-stimulated TSH to acutely raise FT3 serum levels.