Changes in circulating thyroid hormone levels and systolic time intervals in acute hypothyroidism

OBJECTIVE: We have previously reported that, in thyrotoxic patients treated with carbimazole, serum T4 and T3 levels are the first parameters to return to normal, followed by the systolic time interval (STI, a marker of thyroid function at tissue level) and then the serum TSH. The aim of this study was to compare the rate of change of thyroid hormones, TSH and STI in treated hypothyroid patients after the sudden withdrawal of thyroxine. DESIGN AND PATIENTS: Serum T4, T3 (free and total) and TSH were measured in 12 patients taking thyroxine for primary hypothyroidism; seven were biochemically euthyroid and five were over-replaced, as defined by an elevated free T4 and a sub-normal TSH. Thyroxine was withdrawn and the measurements repeated three times a week until the STI rose above the euthyroid range (0.26-0.32). RESULTS: After stopping thyroxine, the serum TSH and STI left the normal range, in advance of the free T4 and T3, after 9.5 +/- 0.95 and 12.2 +/- 1.5 days respectively (mean +/- SEM). The TSH was the first parameter to leave the euthyroid range in all subjects except one in whom the serum TSH was fully suppressed (less than 0.05 mU/l) initially. In the euthyroid group the TSH and STI increased rapidly after stopping thyroxine (time to leave euthyroid range 7.4 +/- 0.8 and 9.4 +/- 0.7 days respectively). In contrast, in the over-replaced group serum TSH and STI became elevated after 12.4 +/- 1.0 days (P less than 0.005 vs euthyroid group) and 16.0 +/- 2.7 days (P less than 0.05 vs euthyroid group) respectively. There was no delay in the fall in serum T4 or T3 in the over-replaced group when compared with the euthyroid group. CONCLUSIONS: In the evolution of primary hypothyroidism, markers of thyroid function at a tissue level (TSH and STI) become abnormal in advance of thyroid hormones. After stopping thyroxine therapy in treated hypothyroid patients, there is a delayed rise in STI and serum TSH levels in subjects with a subnormal TSH level, as compared with those with a normal TSH on treatment. This suggests mild tissue thyrotoxicosis in these individuals.     

Sex hormone-binding globulin in the diagnosis of peripheral tissue resistance to thyroid hormone: the value of changes after short term triiodothyronine administration

Thyroid hormone is one of several factors that modulate the level of sex hormone-binding globulin (SHBG) in serum. SHBG levels are usually elevated in thyrotoxicosis and have been reported to be normal in a few patients with generalized resistance to thyroid hormone (GRTH). This study was designed to determine whether basal serum SHBG levels or the SHBG response to short term T3 administration could be used as an index of thyroid hormone action and thus serve as a test for the evaluation of patients suspected of having peripheral tissue resistance to thyroid hormone. Serum SHBG, total T4, free T4 index (FT4I), total T3, and TSH levels were measured in 21 normal subjects, 28 hypothyroid patients, 20 thyrotoxic patients, and 10 patients with GRTH. Excluding patients with GRTH, serum basal SHBG values were correlated with FT4I values (r = 0.66; P less than 0.0001). Mean SHBG levels in the patients with GRTH [37.6 +/- 16.2 (+/- SD) nmol/L] were not significantly different from those in the normal subjects (35.1 +/- 19.3 nmol/L) or hypothyroid patients (26.3 +/- 17.1 nmol/L), but were significantly lower than those in the thyrotoxic group (64.7 +/- 19.2 nmol/L; P less than 0.001). All 10 patients with GRTH had basal SHBG values in the normal range, but 7 of 20 (35%) thyrotoxic patients also had normal basal SHBG values. T3 was given orally for three sequential 3-day periods at doses of 50, 100, and 200 micrograms daily to 7 normal subjects, 11 hypothyroid and 3 thyrotoxic patients, and all 10 patients with GRTH. The serum SHBG concentration was measured on the last day at each dosage level. During T3 administration, SHBG levels increased in all individuals with normal tissue responsiveness. The increase above the basal value (delta SHBG) at each T3 dose was similar in normal, hypothyroid, and thyrotoxic individuals (non-resistant subjects). After administration of 50 micrograms T3 daily, the mean delta SHBG level was decreased [-2.9 +/- 5.3 (+/- SD) nmol/L] in the resistant patients and increased (4.0 +/- 4.9 nmol/L; P less than 0.005) in the nonresistant subjects. After administration of 100 micrograms T3 daily, the mean delta SHBG was -4.5 +/- 6.8 nmol/L in the resistant patients and 8.6 +/- 5.1 nmol/L (P less than 0.0001) in the nonresistant subjects. Serum SHBG decreased by more than 2 nmol/L in 6 of 10 (60%) resistant patients, but in no nonresistant subject.(ABSTRACT TRUNCATED AT 400 WORDS)     

ERYTHROCYTE OUABAIN BINDING IN PATIENTS RECEIVING THYROXINE

Thyroid hormone action at the cellular level was investigated in euthyroid women who were receiving replacement thyroxine, and whose plasma T4 levels were above the upper reference limit for healthy subjects. There is evidence that erythrocyte sodium pump sites are reduced in number in patients with hyperthyroidism. These sites were measured by the ouabain binding capacity. Plasma T4, free T3 and TSH were also measured, the latter by a high sensitivity fluoroimmunoassay. Three groups of women were investigated; 30 patients receiving T4 with elevated plasma T4 concentrations, 30 age-matched healthy women, and 10 untreated thyrotoxic patients. Erythrocyte ouabain binding was significantly reduced in the thyroxine treated patients, although not to the degree observed in the thyrotoxic patients. Plasma free T3 concentration was increased in 12 of 30 treated patients. TSH was undetectable in 23 of 30 treated patients. The ouabain binding results provide some evidence for increased thyroid hormone action at cellular level in thyroxine treated patients.     

Sex hormone-binding protein in hyperthyroxinemic patients: a discriminator for thyroid status in thyroid hormone resistance and familial dysalbuminemic hyperthyroxinemia

Sex hormone-binding globulin (SHBG) levels in serum are affected by thyroid status; hyperthyroidism is associated with high SHBG levels, whereas hypothyroid patients have low or normal SHBG levels. This study was undertaken to test the usefulness of SHBG determinations to define the thyroid status in two hyperthyroxinemic states: thyroid hormone resistance (THR) and familial dysalbuminemic hyperthyroxinemia (FDH). Serum SHBG levels were determined in 193 patients and 26 normal subjects using an IRMA-type RIA. In the control group, the mean values in women (58.9 nmol/liter) and men (32.7 nmol/liter) were significantly different (P less than 0.001). In adult subjects with THR, SHBG levels were within the normal range, with mean values of 54.8 nmol/liter (range, 28.7-82.5 nmol/liter) in women and 18 and 20 nmol/liter in two men. In FDH subjects, the mean SHBG levels did not differ from the normal values; they averaged 60.7 nmol/liter in women and 42.3 nmol/liter in men. From these data we conclude that in THR and FDH, free T4 levels elicit an appropriate hepatic response corresponding to the euthyroid status of these subjects. SHBG determination may, therefore, serve as an in vitro test for end-organ sensitivity to thyroid hormones.     

Effect of D-thyroxine on serum sex hormone binding globulin (SHBG), testosterone, and pituitary-thyroid function in euthyroid subjects

Concentrations of serum sex hormone binding globulin (SHBG) and free testosterone (T) were examined in 10 euthyroid subjects (5 men and 5 women) before, during and after 30 days of the daily ingestion of 1 or 4 mg D-thyroxine (D-T4), the thyroxine analog that has only 1-15% of the calorigenic effect of L-thyroxine (L-T4). No changes in serum L-T4 or triiodothyronine (T3), serum cholesterol, SHBG, T, progesterone, estradiol-17 beta, or free T concentrations were observed in response to the 1 mg dose, but there was a slight elevation in the free thyroxine index (FTI) and a significant (p less than 0.02) suppression of the thyrotropin (TSH) response to thyrotropin releasing hormone (TRH). The 4 mg dose of D-T4 induced an increase in SHBG levels in all but one man. There was a significant negative correlation between the SHBG and percent free T (p less than 0.05) although the mass of free T did not change. As a group, the women responded with a greater increase in SHBG and decrease in percent free T than the men. Serum cholesterol decreased (p less than 0.01), all serum thyroid hormone values measured by RIA were increased (p less than 0.01), and the TSH response to TRH was completely suppressed. Despite these changes, the subjects remained clinically euthyroid. Concentrations of testosterone, progesterone and estradiol-17 beta remained unchanged. Serum luteinizing hormone (LH), which was evaluated in the men only, also did not change during the daily administration of 4 mg D-T4.     

Thyroid abnormalities in the McCune-Albright syndrome: ultrasonography and hormonal studies

Hyperthyroidism and goiter have been reported frequently in association with the McCune-Albright syndrome (MAS). To assess the prevalence and extent of thyroid abnormalities in girls with MAS, we studied 19 patients [mean age, 6.6 +/- 1 (+/- SE) yr; mean bone age, 9.5 +/- 1 yr] and 18 normal control girls (mean age, 10.3 +/- 0.5 yr). All patients appeared euthyroid when examined; 1 was taking antithyroid medication. Ultrasonography revealed thyroid abnormalities in 7 patients, including generalized inhomogeneity, small (2-4 mm) and large (greater than 10 mm) hypoechoic regions, and echogenic nodule-like regions. Repeat ultrasonography after intervals of 9-18 months showed enlargement of large hypoechoic regions in 2 patients. In the patients with abnormal ultrasound findings, serum TSH was uniformly low or suppressed both at baseline and after administration of 7 micrograms/kg TRH. The mean serum T3 level in this group was significantly higher than that in controls (2.9 +/- 0.2 vs. 2.3 +/- 0.1 nmol/L; P less than 0.05), whereas mean serum T4, free T4, and T4-binding globulin levels did not differ from those of controls. In the remaining 11 patients, thyroid ultrasonography was normal, and the serum levels of T3, T4, free T4, and TSH were normal. Bioassay showed no detectable thyroid-stimulating activity in the plasma of the MAS patients with suppressed TSH levels. None of the patients became overtly thyrotoxic over 3-6 yr of observation, and their serum iodothyronine levels remained stable. We conclude that thyroid dysfunction is common in girls with MAS, but that it may be clinically occult and not rapidly progressive. The thyroid dysfunction, like that of the ovaries, is associated with structural abnormalities in the gland itself, together with suppressed levels of the respective stimulating hormones.     

Androgens and estrogens in postmenopausal insulin-treated diabetic women

Diabetic women may have an increased risk of developing endometrial carcinoma. Ovarian and adrenal activity seem to be factors in the genesis of this cancer. We have measured serum sex hormone-binding globulin (SHBG), free and bound fractions of estrogens and androgens, and gonadotropins in 20 consecutive postmenopausal insulin-treated diabetic women and 16 normal postmenopausal women. The diabetics were nonketoacidotic, without nephropathy and without proliferative retinopathy. The groups were comparable regarding age and percent ideal body weight. The diabetic group had significantly increased serum levels of estrone (P less than 0.001), estrone sulfate (P less than 0.05), 17 beta-estradiol (P less than 0.02), and SHBG (P less than 0.001). Levels of testosterone, delta 4-androstenedione, and dehydroepiandrosterone sulfate tended to be higher (not significantly) in the diabetics. FSH and LH levels were similar in the two groups, while serum PRL was significantly lower in the diabetic group (P less than 0.02). The hormonal changes in the diabetics were not related to control of the diabetes. We conclude that total estrogen levels are increased in postmenopausal women with insulin-treated diabetes mellitus. High SHBG levels in these patients tend to keep the free fractions of sex hormones within normal limits.     

血清TSH水平与血脂异常的相关性研究

目的 探讨亚临床甲状腺功能减退(甲减)以及甲状腺功能正常的人群中TSH水平与血脂谱之间的关系.方法 2007年在沈阳市大东区进行糖尿病及甲状腺疾病的整群抽样调查,其中包括亚临床甲减110例和1 240名甲状腺功能正常者进入研究,研究对象既往无甲状腺病史,未服用影响甲状腺功能和调节血脂的药物.检查项目包括甲状腺功能、血脂、空腹血糖、胰岛素等.结果 (1)亚临床甲减患者高密度脂蛋白胆固醇(HDL-C)水平低于甲状腺功能正常组.(2)按照<中国成人血脂异常诊治指南>将人群分组,在超重的人群中(体重指数≥24.0 kg/m2),高低密度脂蛋白胆固醇(LDL-C)组的TSH水平明显升高[(3.07±0.27对2.41±0.11)mU/L,P=0.027],这种差异在超重女性组中更加明显.甲状腺功能正常且超重的人群中,TSH与总胆固醇呈正相关,且这种相关性不受稳态模型评估的胰岛素抵抗指数(HOMA-IR)的影响.(3)在女性中,TSH与甘油三酯呈正相关,与HDL-C呈负相关.在超重的女性组中,TSH与总胆固醇、LDL-C呈正相关,且经过年龄、性别、体重指数等因素的校正后相关性仍然存在.结论在甲状腺功能正常及亚临床甲状腺功能减退症人群中,TSH升高为血脂异常的危险因素,且独立于胰岛素抵抗.

Abstract：

Objective To investigate the relationship between serum thyrotrophin(TSH)and dyslipidemia in subclinical hypothyroid and euthyroid subjects. Methods An epidemiological study on diabetes and thyroid diseases was performed in Dadong community, Shenyang city, in 2007. 110 subjects with subclinical hypothyroidism(SCH)and 1 240 euthyroid subjects were enrolled in the study. Neither history of thyroid diseases nor administration of thyroid-related and lipid-regulating medicines were reported in these subjects. The levels of serum thyroid hormones, lipids, fasting plasma glucose(FPG), and insulin were determined. Results (1)Patients with SCH had significantly lower HDL-C levels than those who were euthyroid.(2)According to the guideline of treatment of adult dyslipidemia in China, the lipid profiles were each categorized. Mean TSH levels were higher in subjects in the dyslipidemia subclass than subjects in the normal subclass. The differences were significant in high LDL-C subclass in overweight individuals. In euthyroid overweight women, mean TSH levels were significantly higher in high LDL-C subclass. In the euthyroid population, TSH was positively associated with total cholesterol in overweight population. The association was not modified by the homestasis model assessment for insulin resistance(HOMA-IR)values.(3)TSH was associated positively with serum triglycerides and negatively with serum HDL-C in women. TSH was positively associated with total cholesterol in overweight population and positively associated with total cholesterol and LDL-C in overweight women after adjustment for age, sex, and body mass index. Conclusion Raised serum TSH seems to be a risk factor of dyslipidemia in subclinical hypothyroid and euthyroid subjects, which is independent of insulin sensitivity.     

The effects of dopaminergic blockade on serum TSH and prolactin levels in thyrotoxicosis

In the first part of this study, we have demonstrated that, in 7 patients with untreated thyrotoxicosis, a 7 day regime of the long acting dopamine antagonist metoclopramide (10 mg orally 8 hourly) produces more adequate dopaminergic blockade at pituitary level than a single oral 10 mg dose of the compound as assessed by serum prolactin responses. Subsequently, we have employed this protracted oral metoclopramide regime to evaluate the contribution of dopaminergic tone to the abnormal TSH and prolactin responsiveness of thyrotoxicosis. Serum TSH and prolactin responses to iv TRH (200 micrograms) were measured in 10 untreated thyrotoxic patients before and after a 7 day period of metoclopramide 10 mg orally 8 hourly. Ten euthyroid individuals were studied in similar fashion, their serum samples being analysed for prolactin levels alone, thus providing a control group for prolactin responsiveness to TRH, before and after metoclopramide. In the thyrotoxic patients basal TSH levels did not change as a consequence of metoclopramide therapy and the TSH response to TRH remained flat. Basal prolactin levels were similar in thyrotoxic and euthyroid individuals and the increase in prolactin, seen in both groups after metoclopramide, was smaller in the thyrotoxic group than in the euthyroid group. Prolactin responsiveness to TRH was significantly impaired in the thyrotoxic subjects as compared to euthyroid subjects. After metoclopramide there was a significant decline in prolactin responsiveness in the euthyroid group, and a similar, though insignificant, trend in the thyrotoxic patients. We conclude that in thyrotoxicosis dopaminergic tone plays no major part in the suppression of TSH levels, nor in the impaired prolactin responsiveness to TRH.     

PROTEIN-A PURIFIED HUMAN IMMUNOGLOBULINS: A COMPARISON OF THYROID STIMULATING AND THYROTROPHIN RECEPTOR BINDING ACTIVITIES IN THYROTOXICOSIS

Protein-A purified human thyroid stimulating immunoglobulins (TSIg) and thyrotrophin binding inhibiting immunoglobulins (TBIIg) were measured in euthyroid subjects and thyrotoxic patients by bioassay and TSH radioligand receptor assay respectively. Unextracted sera from euthyroid and thyrotoxic subjects inhibited both basal and TSH stimulated iodide uptake in the bioassay, which was based on iodide uptake in porcine thyrocytes. Similar effects were seen with Ig and TSIg extracted from sera using either polyethylene glycol or ammonium sulphate. However IgG and TSIg prepared using Protein-A Sepharose CL-4B from sera of euthyroid subjects had little effect in this system. The majority of Protein-A purified TSIg preparations from sera of thyrotoxic patients stimulated iodide uptake in procine thyrocytes in a dose-dependent manner and most (85%) diluted parallel to both bovine and human TSH. TSIg and TBIIg from 73 patients with thyrotoxicosis were assessed using the bioassay and receptor assay and compared to a control group of 35 euthyroid subjects. The median (and range) values for TSIg and TBIIg in the euthyroid group were 4.35 (0.8 to 7.5, % stimulation over control) and 2.7 (-9.3 to 8.6, TBII index) for the bioassay and radioreceptor assay respectively. A value of greater than 10.0 in both assays was taken as a positive result. Of the thyrotoxic patients 61 out of 73 were positive in the bioassay (83.6%) compared to 60 in the radioreceptor assay (82.2%). There was a positive correlation between the two assays (r = 0.821, P less than 0.001). Of the 73 thyrotoxic patients 40 were untreated, 18 had received carbimazole and 15 had been previously treated with iodine-131. TSIg levels in the untreated thyrotoxics were similar to those in either group of treated patients. However they were higher (P less than 0.05) in the iodine-131 group than in the patients treated with carbimazole. Similar results were obtained for TBIIg. The coupling of a specific extraction method for human serum IgG with a bioassay for TSIg has demonstrated a high prevalence of these immunoglobulins in patients with thyrotoxicosis. The agreement between this assay and a radioreceptor assay was good, indicating that TSH displacing and thyroid stimulating activities of these immunoglobulins are closely related.     

Deceptively high thyroid hormone levels in a neonate due to autoantibodies against thyroid hormones transferred from a mother with Graves' disease.

At birth, a clinically euthyroid male neonate was found to have unexpectedly high levels of free T3 and T4 concurrent with a high TSH level. The mother was treated with propylthiouracil for Graves' disease during and after pregnancy. The neonate also had an extremely high titer of TSH receptor antibodies. He soon became clinically thyrotoxic as TSH levels were suppressed and thyroid hormone levels rose. After instituting antithyroid therapy, TSH levels became elevated again, while thyroid hormone levels decreased but were still above normal. Around 3 months after birth, both TSH receptor antibodies and discordance, between the levels of thyroid hormones and TSH, disappeared. Because of high maternal TSH levels in conjunction with an elevated free T3 level at 7 months postpartum, we suspected the presence of autoantibodies against thyroid hormones (AAb). Maternal and infant blood samples were then examined retrospectively for AAb and were detected in all the samples except those of the infant taken more than 3 months after birth. The authors, therefore, suggest that physicians be aware of the presence of AAb in pregnant women with Graves' disease, in order to avoid inappropriate treatment which could lead to fetal and neonatal hypothyroidism.     

Subtle changes in serum thyrotrophin (TSH) and sex-hormone-binding globulin (SHBG) levels during long-term follow-up after radioactive iodine in multinodular non-toxic goitre.

OBJECTIVE: We investigated possible changes in the pituitary-thyroid axis after radioactive iodine (RAI) treatment of multinodular non-toxic goitre. DESIGN: Consecutive patients with multinodular non-toxic goitre, who remained euthyroid after radioactive iodine (RAI) treatment. PATIENTS: Twenty-three women with multinodular non-toxic goitre were followed after treatment with RAI. MEASUREMENTS: Free T4 index (FT4I), FT3I, free T4, SHBG (immunoradiometric assay), and a third-generation TSH assay (chemiluminetric assay) TSH were measured. RESULTS: Three weeks after RAI treatment TSH had decreased and SHBG increased (P < 0.05). Only 2/18 patients actually had suppressed TSH values, while 12/18 had values in between euthyroid and toxic levels. Trend analysis from 1.5 to 24 months after RAI treatment demonstrated a progressive increase in TSH (P < 0.01) and gradual decrease in SHBG (P < 0.02). No changes in FT4I, FT3I, or free T4 were found. CONCLUSION: A third-generation TSH assay gave detailed information about changes in thyroid status when TSH was below normal values. FT4I, FT3I, and free T4 seem to be less sensitive parameters than TSH and SHBG for recording subtle changes in thyroid status after RAI treatment of nodular non-toxic goitre. We demonstrated that changes in the pituitary-thyroid axis continue for a long time after RAI treatment of multinodular non-toxic goitre. These patients should be followed up in order to detect possible late hypothyroidism.     

THE CIRCADIAN VARIATION OF THYROTROPHIN IN PATIENTS WITH PRIMARY THYROIDAL DISEASE

We have used a highly sensitive immunochemiluminometric assay (ICMA) for human TSH to study the effect of thyroid status on the circadian variation in TSH levels. Three subjects with Graves' disease, three with toxic multinodular goitre and three with euthyroid multinodular goitre were sampled every hour for 24 h. The results obtained were compared to those from five euthyroid control subjects. It was found that some patients with hyperthyroidism and suppressed basal TSH levels exhibited a 24 h secretory pattern similar to that seen in normal subjects with peak TSH levels occurring at night. In addition two subjects with a euthyroid multinodular goitre demonstrated levels of TSH below the normal range despite being clinically and biochemically euthyroid. TSH suppression in these subjects is probably related to some degree of thyroid autonomy and possible development of hyperthyroidism in the future.     

Adrenal abnormalities in polycystic ovary syndrome

This study was undertaken to examine the role of adrenal androgen excess in the pathogenesis of polycystic ovary syndrome (PCOS) and, if such was present, to assess its reversibility using dexamethasone given in physiological dosage at night. Mean plasma testosterone (T), T/sex-hormone binding globulin (T/SHBG) ratio, androstenedione, and 17-OH-progesterone levels were elevated in the 19 patients studied. Plasma estrone values were elevated, whereas estradiol levels were normal. Plasma FSH was decreased and LH responsiveness to LHRH was exaggerated. Metyrapone, an 11-hydroxylase inhibitor, was administered at 2400 h to induce hypocortisolemia and compensatory ACTH secretion so that adrenal androgen and glucocorticoid responsiveness to endogenous stimulation could be examined. Plasma T, androstenedione, and 11-deoxycortisol responses to metyrapone were excessive in PCOS patients, thus indicating a specific adrenal abnormality. After 3 months treatment with dexamethasone, 0.5 mg at night, mean plasma T/SHBG and androstenedione declined to normal, and mean plasma dehydroepiandrosterone and dehydroepiandrosterone sulfate declined to below normal. The mean estrone value was slightly lower during dexamethasone. Plasma LH responsiveness to LHRH was no longer significantly different from normal, but FSH was suppressed. During treatment androgen responsiveness to metyrapone stimulation was normal, whereas 11-deoxycortisol responsiveness was suppressed. Fifteen patients completed 3 months of treatment with dexamethasone. Of these, 10 resumed regular menstruation. The latter group had suppression of plasma T, T/SHBG, androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate. Only plasma androstenedione fell significantly in the remainder. These observations support the hypothesis that, in at least some patients, PCOS develops in response to abnormal gonadotropin secretion induced by hyperestronemia occurring as a consequence of excessive adrenal androgen secretion.     

Low serum thyrotropin is associated with high plasma fibrinogen

BACKGROUND: Elevated plasma fibrinogen levels are associated with an increased risk of cardiovascular events. Decreased serum TSH predicts vascular mortality, which hypothetically could be explained in part by alterations in the blood coagulation system. OBJECTIVE: The objective of this study was to investigate the association between thyroid function and plasma fibrinogen levels in a general population. DESIGN: The population-based Study of Health in Pomerania was performed in a previously iodine-deficient area in Germany, including 4310 subjects, aged 20-79 yr. Data for 3804 individuals without thyroid disease were analyzed. Analysis revealed an association between thyroid function status and plasma fibrinogen concentration. RESULTS: Elevated fibrinogen levels (>3.25 g/liter) were observed in 14 subjects with increased serum TSH levels (32.6%), 973 euthyroid subjects (28.9%), 158 subjects with decreased serum TSH levels (40.7%), and six individuals with overt hyperthyroidism (54.4%). Logistic regression analysis revealed decreased serum TSH as an independent risk factor for elevated fibrinogen levels (odds ratio, 1.42; 95% confidence interval, 1.12-1.80). CONCLUSIONS: Thyroid function is associated with plasma fibrinogen. Decreased serum TSH is an independent risk factor for elevated plasma fibrinogen levels as a possible explanation for the high cardiovascular mortality among affected subjects.     

Bone Gla protein and sex hormone-binding globulin in nontoxic goiter: parameters for metabolic status at the tissue level

Several patients with nontoxic goiter have reduced serum TSH levels, as measured with new sensitive assays. Whether this is a sign of subclinical hyperthyroidism, thus having the potential of adverse effects on different organs with time, is not known. We have measured serum levels of 2 markers of thyrometabolic status at the tissue level, bone gamma-carboxyglutamic acid-containing protein (BGP), reflecting the function of osteoblasts, and sex hormone-binding globulin (SHBG), reflecting the function of hepatocytes, in 44 patients (41 women and 3 men) with nontoxic goiter (11 diffuse and 33 nodular goiters; serum T4, T3, free T4, and free T3 levels had been normal and stable for at least 0.5 yr). Serum TSH levels ranged from normal to unmeasurably low values (less than 0.05 mU/L). Serum TSH levels correlated negatively to serum BGP levels (r = -0.60; P less than 0.001). Due to the postmenopausal surge in serum BGP levels, premenopausal women (n = 21) were tested separately without changing the significance (r = -0.53; P less than 0.02). Expressing serum BGP values as a percentage of the mean value in control subjects of the same age and sex did not change the correlation (r = -0.63; P less than 0.001). Six patients had serum BGP levels above the normal range, and patients with reduced serum TSH levels (less than 0.45 mU/L; n = 12) had significantly enhanced serum BGP levels [median, 1.53 nmol/L (range, 1.02-4.24) vs. 1.23 nmol/L (0.62-3.71); P less than 0.05]. Serum TSH also correlated negatively to serum SHBG levels (r = -0.56; P less than 0.001; women alone: r = -0.58; P less than 0.001). Eight patients had serum SHBG levels above the normal range, and patients with reduced serum TSH levels had significantly enhanced serum SHBG levels, expressed as a percentage of the mean control value for the relevant sex [203% (range, 75-288) vs. 120% (42-317); P less than 0.01]. It is concluded that the lower serum TSH levels in patients with nontoxic goiter, the higher are serum BGP and SHBG levels. This suggests a progressively generalized (not only pituitary) tissue overexposure to thyroid hormones, the lower the serum TSH levels. Therefore, the finding of a reduced serum TSH level in patients with nontoxic goiter might reflect supraphysiological levels of T4 and/or T3, which could possibly be harmful.     

SHBG levels correlate with insulin resistance in postmenopausal women

BackgroundOverweight or central obesity is generally associated with increases in fasting insulin levels, insulin resistance, and glucose intolerance and has been identified as a target for new therapeutic strategies, including early change in lifestyle. Early biochemical markers for identifying at-risk patients will be useful for prevention studies. The aim of this study is to investigate whether or not SHBG level is a useful index of hyperinsulinemia and/or insulin resistance in pre- and postmenopausal obese women. At the same time, the relationship between SHBG concentrations and features of the metabolic syndrome were evaluated.Methods229 women were eligible for this study. MetS was defined by using a modification of the ATP III guidelines. All patients were euthyroid, obese and overweight, 25 to 69 years of age. Subjects were divided into groups of premenopausal women (n = 125) and postmenopausal women (n = 104). Various fatness and fat distribution parameters, SHBG, sex hormones, FSH, LH, thyroid hormones, serum levels of fasting and postprandial glucose, lipid profile, uric acid and serum insulin, and blood pressure were measured.ResultsNo significant difference was found in mean SHBG levels between pre- and postmenopausal obese women in this study (p = 0.866).In premenopausal obese women, SHBG correlated negatively with BMI, waist circumference, fasting glucose, uric acid levels and FAI.In postmenopausal obese women, SHBG correlated negatively with fasting glucose, postprandial plasma glucose, fasting insulin, HOMA-IR and FAI and positively with HDL.SHBG had a significant inverse association with MetS parameters only in postmenopausal women, also after adjusting for BMI, age and estradiol.ConclusionsObesity may influence the levels of endogenous sex steroid, especially after menopause. SHBG concentrations are correlated with features of the metabolic syndrome, particularly in postmenopausal obese women.These results suggest that SHBG may be an index of insulin resistance in postmenopausal obese women.     

Circulating levels of plasma adrenocorticotropin in polycystic ovary disease

Excessive adrenal androgen production contributes to hyperandrogenism in polycystic ovarian disease (PCO). This study was performed to determine the concentration of basal plasma ACTH in PCO patients and normal women and correlate its level with that of circulating adrenal androgen. In PCO patients, significant increases in serum testosterone, androstenedione, and dehydroepiandrosterone sulfate were noted compared to levels in normal women. The mean circulating plasma ACTH in PCO patients (22 +/- 2 pg/ml) was not different from that in normal controls (20 +/- 2 pg/ml). The mean ratio of dehydroepiandrosterone sulfate to ACTH in individual PCO patients was significantly greater than that in normal subjects, whereas the cortisol to ACTH ratio was similar in both groups. These results suggest that increased adrenal androgen production in PCO patients is not due to abnormal ACTH secretion but arises from either altered adrenal responsiveness to ACTH or abnormal adrenal stimulation by a factor(s) other than ACTH.     

A comparison of plasma TSH levels in patients with diffuse and nodular non-toxic goiter.

Plasma TSH levels were measured in 115 euthyroid patients with simple goiter, of whom 52 had diffuse and 63 nodular enlargement of the thyroid gland, and in 191 euthyroid patients without goiter. There was no significant difference between the plasma TSH levels in the patients with diffuse goiter and the non-goitrous controls, implying that the maintenance of diffuse hyperplasia is not dependent upon a raised level of plasma TSH. On the other hand, plasma TSH levels in the patients with nodular goiter were significantly lower than those recorded in either the patients with diffuse goiter (P less than 0.01) or in the patients without goiter (P less than 0.0001), supporting the view that thyroid function may be autonomous in nodular goiters.     

TRH-induced TSH and prolactin responses in the elderly

Since there are divergencies in the thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) in old age, and since a hypothalamopituitary dysfunction has been suggested in the elderly, we have studied the thyroid function and the TRH responsiveness of TSH and prolactin (PRL) in 56 euthyroid patients over 70 years old, grouped according to age (70-79, 80-89, 90 or more years) and sex. Results were compared to those of 15 postmenopausal women and 11 men. In the elderly patients there was a decrease in plasma tri-iodothyronine (T3) and an increase in reverse T3 (rT3) levels while thyroxine (T4), basal TSH and PRL levels remained normal. The mean TSH and PRL responses to TRH (250 micrograms i.v.) were reduced but there was no age effect within the elderly. Only a sex effect was detected, TSH and PRL responses being appreciably lowered in men. In eight patients without severe disease or malnutrition, the response of TSH was not significant. We conclude that despite an apparent euthyroid status, TSH and PRL responses are blunted in elderly patients, and more in men than in women. These data, consistent with a hypothetical hypothalamopituitary dysfunction, indicate the difficulties of thyroid status assessment in the elderly.