Role of thyroid on testicular lipids in prepubertal, pubertal and adult rats. I. Hyperthyroidism

The influence of thyroxine-induced hyperthyroidism on testicular neutral and phospholipids was studied in prepubertal, pubertal and adult rats. Thyroxine treatment (25 micrograms/100 g body weight) for 1 month decreased testicular total lipids, total glyceride glycerols, total cholesterol and total phospholipids. Different classes of glyceride glycerol, cholesterol and phospholipid were also diminished due to thyroxine treatment. All classes of lipids returned to the euthyroid level after the withdrawal of thyroxine treatment. The data obtained in the present study suggest that thyroid hormones have a definite influence on testicular lipid metabolism in rats.     

甲状腺癌术后短期甲状腺功能低下对骨代谢的影响

目的:观察分化型甲状腺癌(DTC)患者手术后、碘131(131I)清甲治疗前停用甲状腺素造成的短期甲减对骨代谢的影响。方法:选择DTC术后患者53例作为试验组,50例健康人作为对照组,试验组于停服甲状腺素第二天空腹采血行游离甲状腺素(FT4)、游离三碘甲状腺原氨酸(FT3)、促甲状腺激素(TSH)、血钙(Ca)、血磷(P)、血清碱性磷酸酶(ALP)、血清骨钙素(BGP),I型前胶原羧基末端前肽(PICP)、I型胶原交联羧基末端肽(ICTP)等各项检查,停服甲状腺素4周后于131I治疗前再行上述检查,对照组于体检当日采空腹血测相同项目。结果:试验组患者停药前血清FT3、FT4水平明显高于对照组,差异有统计学意义(P0.05)。停服甲状腺素后,试验组患者血清TSH升高,T3、T4水平降低,血BGP、血Ca、PICP、ICTP水平降低,与停药前及对照组的检验结果相比均有明显差异(P0.05)。停药后,骨密度与停药前比较差异无统计学意义(P0.05)。停服甲状腺素前后血磷水平无明显变化,与对照组相比也没有明显差异(P0.05)。结论:甲状腺癌术后造成甲状腺功能低下可明显影响患者骨代谢,应于131I后及时给予甲状腺激素,及时纠正甲低状态,同时也可适量补充钙剂。     

Thyroid suppression test with serum thyroxine concentration as index of suppression

A thyroid suppression test is suggested which relies on the change in concentration of serum thyroxine as the index of thyroid response to the administration of triiodothyronine. The test has been carried out in 16 healthy volunteers and in 27 patients referred for routine suppression tests. This index appears to be sensitive and safe and results in a reduction in the required dosage of triiodothyronine. The test can be carried out in fewer patient-visits than the commonly used suppression test; moreover, in remote areas the patient need not attend the specialist centre because the course of triiodothyronine can be given (and the serum samples obtained) locally, the samples then being sent to the appropriate laboratory for assay.     

Effect of thyroid hormone on epidermal growth factor-like immunoreactivity and growth velocity in cynomolgus monkeys

To examine the potential role of epidermal growth factor (EGF) in mediating the effects of thyroid hormone on linear growth, we measured serum EGF levels by RIA in cynomolgus monkeys before and during methimazole-induced hypothyroidism, and after 9 weeks of T4 replacement at different doses. Ten castrated prepubertal monkeys were rendered hypothyroid by methimazole (0.0125% in drinking water for 12 weeks). Methimazole was continued, and T4 was then administered for 9-week intervals. Six weeks elapsed between successive T4 doses. The sequence of different T4 doses for each animal was random. Serum EGF level was measured at baseline and at the end of each treatment period with a newly developed RIA using a polyclonal antiserum against human recombinant EGF. Serum EGF level correlated significantly with the level of serum thyroxine but not with serum triiodothyronine, over the thyroxine dosage range of 1-4 micrograms/kg/day (r = 0.41, p less than 0.005). Lower-leg growth rate correlated significantly with serum EGF level over this same thyroxine dosage range (r = 0.41, p less than 0.005). These data are consistent with the hypothesis that EGF may mediate some of the effects of thyroid hormone on skeletal growth.     

Thyroid function and polyamines. III. Changes in ornithine decarboxylase activity and polyamine contents in the rat thyroid during hyperplasia and involution

Changes in ornithine decarboxylase (ODC) activity and in polyamine contents of the rat thyroid were studied under various experimental conditions. Methylthiouracil (MTU) treatment produced several-fold increases in the thyroid ODC activity and in the content of putrescine, spermidine and spermine within a week. While serum thyrotropin (TSH) levels increased gradually up to 3 weeks, the content of both putrescine and spermidine tended to reach a plateau after 2 weeks of the goitrogen treatment; spermine content continued to increase progressively for 3 weeks. Discontinuance of MTU at 7 days resulted in a rapid decline in the elevated thyroid ODC activity, followed by a diminution of putrescine, spermidine and RNA contents. Thyroidal putrescine, spermidine and RNA responded more sensitively to both introduction and withdrawal of TSH stimulation than thyroidal spermine and DNA. Excess iodide, having no effect on the basal level of thyroid ODC, suppressed the MTU-induced increase in this enzyme activity without affecting circulating TSH, thyroxine (T4) and triiodothyronine (T3) levels. There was a significant negative correlation between the ODC activity and intrathyroidal concentration of iodine in MTU-pretreated rats. Theophylline increased the thyroid weight and ODC activity when given to rats fed with a subeffective dose of MTU. Analyses of serum TSH, T4, T3 and of thyroidal iodine revealed that TSH-induced thyroid ODC activity was suppressed by increased circulating thyroid hormones and/or intrathyroidal iodine. Furthermore, it was suggested that thyroid hormones and excess iodide acted directly on the thyroid to alter polyamine biosynthesis, possibly by changing the responsiveness of the gland to TSH.     

Ablative radioiodine therapy for hyperthyroidism: long term follow up study.

A total of 225 patients were treated for hyperthyroidism with 555 MBq (15 mCi) radioiodine to ablate the thyroid and induce early hypothyroidism. The efficacy of this treatment in eradicating hyperthyroidism and problems of follow up were assessed one to six years later from case records and questionnaires. Information was received from 197 out of 219 live patients (90%) and from 160 doctors concerning 207 patients (92%). Only three patients were not traced and six had died since treatment. The modal time to hypothyroidism was three months, and 64% of patients were hypothyroid at one year; 5.6% had failed to become euthyroid within one year. Ninety five per cent of patients had been seen by the doctor and 82% had had a thyroid test done within the past two years. Most doctors preferred patients to be returned to their care once thyroxine treatment was stabilised. An ablative dose of 131I is recommended as an effective means of treatment which has clear advantages over conventional methods. Good communications and effective follow up should ensure success.     

Neonatal screening for congenital hypothyroidism by measurement of plasma thyroxine and thyroid stimulating hormone concentrations.

Neonatal screening for congenital hypothyroidism was introduced in the City of Birmingham in 1980 by measuring concentrations of both thyroid stimulating hormone and thyroxine in plasma. Over two years 30 108 babies were tested. Thirty one babies were recalled because of thyroid stimulating hormone concentrations greater than 40 mU/l, of whom 12 were treated with replacement thyroxine. Six babies were found to have low thyroxine concentrations because of reduced thyroxine binding globulin and five raised thyroxine values because of increased thyroxine binding globulin. As a result of this study screening was continued with measurement of thyroid stimulating hormone only as the primary test for congenital hypothyroidism, the thyroxine value being measured only when the concentration of thyroid stimulating hormone exceeded 20 mU/l.     

Growth,development, and reassessment of hypothyroid infants diagnosed by screening.

Thirty]six neonates in whom hypothyroidism was diagnosed after thyroid stimulating hormone screening were reassessed at 1 year. All had grown satisfactorily and the mental development scores were normal in all except two. Treatment was withdrawn in 32 and persistent hypothyroidism was confirmed in 31 cases. Thyroid stimulating hormone concentrations were raised in one-third of cases before the withdrawal of treatment and this was associated with generally lower concentrations of serum thyroxine (T4) and smaller doses of L-thyroxine than in those cases with normal concentrations of thyroid stimulating hormone. In treating congenital hypothyroidism, serum T4 concentrations should be monitored regularly and the dose of thyroxine adjusted to maintain serum T4 in the upper part of the reference range.     

甲状腺激素对豚鼠卡那霉素中毒性耳聋的预防作用

卡那霉素、庆大霉素等抗生素常引起耳聋,目前尚无较好的防治方法。卡那霉素对内耳的毒性作用,主要先影响有关的酶功能,继而破坏毛细胞而致聋。甲状腺激素具有促进蛋白质合成、增强细胞生物氧化的功能。因此可能具有减轻卡那霉素耳毒性的作用。本实验以耳廓反射、内耳生物电及耳蜗铺片为指标,观察甲状腺激素对卡那霉素耳中毒的预防。实验豚鼠分两组,各13只,对照组每天注射卡那霉素300mg/kg,共10天;甲状腺素组先隔天服甲状腺片20mg共四次,以后给予与对照组相同剂量卡那霉素,同时仍隔天服甲状腺片20mg直至停药后16天,前后总共服17次。结果:(1)耳廓反射阈变化,对8、4、2KHz三个频率听力均下降的耳,对照组为11只耳,甲状腺素组为3只耳,两者差异显著。听力下降的频率范围及程度,对照组比甲状腺素组更大。对照组听力下降开始出现的时间明显早于甲状腺素组;(2)内耳生物电,0～80dβ不同程度短声引起的耳蜗微音器电位与听神经动作电位幅值甲状腺素组动物均高于对照组;(8)耳蜗铺片,对照组大部分动物耳蜗各回的毛细胞严重变性缺损,甲状腺素组耳蜗病变仅局限在底回。以上结果表明甲状腺激素能减轻卡那霉素的耳毒性,为耳毒性抗生素致聋的防治提供了一条新的研究途径。     

Reduced serum free thyroxine concentration in postmenopausal women receiving oestrogen treatment.

Thyroid hormone state was assessed in a group of postmenopausal women who had received long term treatment with oestrogen. Serum concentrations of total thyroxine, triiodothyronine, and thyroxine binding globulin were raised compared with those in a control group given placebo; serum concentrations of thyroid stimulating hormone did not differ between the groups. Oestrogen treatment resulted in a significant decrease in the serum free thyroxine concentration and in the ratio of thyroxine to thyroxine binding globulin, which supports the view that oestrogen is the causative factor of the physiological reduction in free thyroid hormone during pregnancy.     

SMS 201-995 and thyroid function in acromegaly: acute, intermediate and long-term effects.

The acute (TRH-stimulation test), intermediate (0-6 days administration), and long-term (0-30 months administration) effects of SMS 201-995 (octreotide) treatment on thyroid function were studied. Subcutaneous injection of 100 micrograms SMS 201-995 one hour before 200 micrograms TRH intravenously reduced serum TSH response area by more than 50% in 8 healthy volunteers. After 3 days of continuous subcutaneous infusion (CSI) of SMS 201-995 in 9 acromegalic patients (100 micrograms/24 h) a slight but significant decrease in serum total triiodothyronine (TT3) and a concomitant increase in serum TSH were demonstrated, indicating an initial inhibitory effect on peripheral deiodination of thyroxine. After a further 3 days treatment serum T3 and TSH had returned to prevalues. Six of the nine acromegalics were treated with SMS 201-995 (100-1500 micrograms/24 h) and admitted for diurnal hormone profiles on 13 occasions over 30 months. Apart from a barely significant increase in serum TSH, no changes in thyroid function were noted. The study was especially designed to detect minute changes over time in thyroid hormones. The only long-term effect of SMS 201-995 was the barely significant clinically irrelevant increase in serum TSH, possibly caused by a slight inhibition of peripheral deiodination of thyroxine.     

Screening for thyroid disease in a primary care unit with a thyroid stimulating hormone assay with a low detection limit.

In a study at a primary care centre in a predominantly rural area of Sweden the records of all patients with established thyroid disease were scrutinised and 2000 consecutive adult patients screened with an immunoenzymometric thyroid stimulating hormone assay. The aims of the study were fourfold: firstly, to assess the total burden of thyroid disease in primary care centres in Sweden; secondly, to assess the efficacy of clinical diagnosis of the disease in unselected populations of patients; thirdly, to assess the efficacy of clinical evaluation of treatment with thyroxine; and, lastly, to see whether a single analysis of the serum thyroid stimulating hormone concentration by recent methods would be enough to identify an abnormality of thyroid function. Of the roughly 17,400 adults in the study community, 111 women and 10 men were being treated for thyroid disease. Screening detected 68 patients (3.5%) not receiving thyroxine who had a serum thyroid stimulating hormone concentration of 0.20 mU/l or less, all of whom were followed up clinically. Fifty of these patients were also studied biochemically during follow up. Only nine of the 68 patients had thyroid disease (three with thyrotoxicosis requiring treatment), no evidence of the disease being found in the remainder. Sixteen patients had spontaneous hypothyroidism requiring treatment, and neither these nor three patients with thyrotoxicosis had been detected at the preceding clinical examination. Of 35 patients in whom thyroid disease was suspected clinically at screening, none had laboratory evidence of thyroid dysfunction. In this series 1.3% of all women in the study community (2.6% of all 50-59 year olds) and 0.1% of the men were being treated for thyroid disease at the primary care centre, roughly 1.0% of adults subjected to screening were found to have thyroid disease requiring treatment, and most patients with a thyroid stimulating hormone concentration of 0.20 mU/l or less did not have thyroid dysfunction. It is concluded that measuring the basal serum thyroid stimulating hormone concentration by present methods is insufficient for the biochemical assessment of thyroid dysfunction in unselected populations.     

Therapy of endemic goitre: controlled study on the effect of iodine and thyroxine

Two kinds of medical treatment of endemic goitre (400 microgram of iodine, n=11, and 150 microgram of L-thyroxine, n=12) were compared in a double blind study with a placebo group (n=12) during a period of 12 months and an observation time of three months after cessation of therapy. The means of the neck circumference and of the estimated thyroid volume decreased significantly during treatment in both groups, whereas no significant difference was observed in the placebo group. The results in both therapy groups did not differ significantly from each other. No side effects or symptoms of hyperthyroidism were observed. During treatment the index of free thyroxine (FT4I) increased significantly in both the iodine and the thyroxine group and delta TSH after TRH decreased significantly. Total triiodothyronine (TT3) did not show significant alterations. Three months after cessation of therapy in the thyroxine treated group the mean FT4I dropped into the range before treatment, whereas it remained slightly elevated in the iodine group. In the thyroxine treated group the mean delta TSH was higher than its value before therapy. After withdrawal of iodine, however, the mean delta TSH remained decreased for three months. The study indicates that 400 micrograms of iodine per day may be at least as effective as a standard dose of 150 micrograms of thyroxine to treat endemic goitre in an iodine deficient area.     

Optimization of 131I ablation in patients with differentiated thyroid carcinoma: comparison of early outcomes of treatment with 100 mCi versus 60 mCi

INTRODUCTION: The aim of this study was to compare the early outcomes between two groups of patients with differentiated thyroid carcinoma (DTC) who received 60 or 100 mCi of (131)I for remnant ablation. MATERIAL AND METHODS: 224 DTC patients with primary tumor > 1 cm of diameter or multifocal were randomised into prospective clinical trial. Patients with extrathyroideal extension of primary tumor and nodal metastases or M1 were not enrolled. 99 patients received 60 mCi, and 125--100 mCi of radioiodine as the first ablative dose. RESULTS: The effectiveness of thyroid ablation was evaluated after one year, during endogenous TSH (thyroid stimulating hormone) stimulation, and after two years during Lthyroxine therapy. Whole body scintigraphy (WBS) was performed under thyroxine withdrawal and thyroglobulin serum level was assessed. Distant micrometastases were detected in 9.8% of patients by post-therapy WBS, 11 patients in group A treated with 60 mCi and 11 in group B treated with 100 mCi. In other patients no symptoms of persistent disease were detected. At one year follow up full remission was diagnosed in 176 patients: 76 in group A and 100 in group B. The remaining ones, 13.3% and 11.2% respectively, received the second course of (131)I for remnant ablation. There were no statistically significant differences in Tg (thyroglobulin) serum level either 12 or 24 months after 131I treatment. CONCLUSIONS: Our evaluation of early efficacy of adjuvant radioiodine treatment in low risk DTC patients shows no differences between two radioiodine activities - 60 and 100 mCi in relation to thyroid ablation. Thus, the activity of 60 mCi is recommended.     

Is steroid therapy needed in the treatment of destructive thyrotoxicosis induced by alpha-interferon in chronic hepatitis C?

OBJECTIVE: Treatment with interferon (IFN) of patients affected by chronic hepatitis C (CH-C) may produce alterations in thyroid function, such as hypothyroidism, Graves'-like hyperthyroidism and destructive thyrotoxicosis (DT). IFN-induced DT is characterized by suppressed serum TSH levels, normal or elevated FT4 and FT3 concentrations, with the presence or absence of thyroid peroxidase antibodies and antithyroglobulin antibodies, the absence of thyroid receptor antibodies and radioactive iodine uptake suppressed or <5%. DESIGN: IFN-induced DT is a mild clinical disease, because thyroid-destructive processes last for a short time and involve a small portion of the gland. At present, the therapeutic approach in DT suggests IFN withdrawal and 1-2 months of methylprednisolone treatment. METHODS: In consideration of possible untoward side effects of steroid treatment in patients with CH-C, we studied two groups of patients with CH-C who developed DT after treatments with various preparations of recombinant IFN (with or without ribavirin). Patients sequentially entered the study during a 4-year period, at the time of DT diagnosis, when IFN therapy was discontinued. The first 12 subjects (group A) were treated with 8-16 mg/day methylprednisolone for 30-40 days after IFN withdrawal; in the following 15 patients (group B), IFN withdrawal was not followed by any additional treatment. All patients underwent clinical and laboratory controls of thyroid function at 1, 2, 3 and 6 months after DT diagnosis. RESULTS: The results showed restoration of euthyroidism in both group A and group B patients at 6 months after DT diagnosis, regardless of steroid treatment. CONCLUSIONS: The simple withdrawal of IFN therapy in patients with CH-C, who had developed DT, appears to be effective in the treatment of the thyroid disease. This therapeutic approach should be preferred in order to avoid possible undesired side effects of steroid therapy in patients with CH-C.     

Effects of feeding high dosages of vitamin E to laying hens on thyroid hormone concentrations of hatching chicks.

Long-term experimental feeding of 20,000 ppm alpha-tocopheryl acetate to laying hens caused a significant (P < 0.05) decrease in hatching rates as compared to the control group, which was fed a diet containing 19 ppm alpha-tocopherol. When the thyroid hormones in the developing chicks were checked on incubation days 16, 19, 21, and 22, the following results were ascertained: During the latter part of incubation, increases in plasma concentrations of thyroxine and triiodothyronine were observed. No significant differences in hormone concentrations (P > 0.05) between the control and the treatment group were observed during incubation days 16, 19, and 22. However, on the day of hatching (day 21 of incubation) significantly lower (P < 0.05) triiodothyronine concentrations in chick embryos of piped eggs were found in the treatment group. Moreover, thyroxine concentrations in non-piped eggs and in hatched chicks were found to be significantly higher as compared to the control group. Given these results, one concludes that extremely high dosages of vitamin E may affect thyroid hormone concentrations of hatching chicks, and therefore, the chicks might be inhibited in pipping the egg shell. Hypothetically, the hepatic enzyme 5'-monodeiodinase is involved in the mechanism of inhibition.     

Prevalence of coeliac disease in patients with thyroid autoimmunity.

The occurrence of autoimmune thyroid disorders among patients with coeliac disease (CD) is well documented, but the exact prevalence of CD among patients with autoimmune thyroid diseases (ATD) is as yet unclear. We screened 150 newly diagnosed patients with ATD by serum endomysial antibody detection (EmA). In 5 subjects (3.3%) EmA positivity was found; all underwent jejunal biopsy. On gluten-free diet an excellent clinical and histological response was recorded with an improvement of hypothyroidism and reduction of the thyroxine dosage. Our data suggest a significant high prevalence (3.3%) of CD in patients with ATD, in particular with Hashimoto's thyroiditis.     

Developmental plasticity in thyroid function primed by maternal hyperleptinemia in early lactation: a time-course study in rats

Pups whose mothers were leptin-treated during the last 3 days of lactation have thyroid dysfunction at adulthood. However, there was no report about leptin treatment in the first days of life or about its action on thyroid function during development. Here, we evaluated the effects of maternal leptin treatment on the first 10 days of lactation upon thyroid function of the offspring at 21, 30, and 180 days old. At birth, lactating Wistar rats were divided into: Leptin (Lep) - leptin-treated (8 μg/100 g of body weight, s.c.) for the first 10 days of lactation and Control (C, saline-treated). Mothers were killed at the end of lactation and their offspring at 21, 30, and 180 days old. Triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH), and leptin levels in serum and milk were measured. Liver mitochondrial glycerolphosphate dehydrogenase (mGPD) activity was determined. Significant differences had p<0.05. At the end of lactation, Lep mothers had higher milk T3 (+ 30%), while their offspring had higher serum T3 (+ 20%) and TSH (+ 84%). At 30 days-old, Lep offspring showed lower TSH ( - 48%), T3 ( - 20%), and mGPDm ( - 42%). At 180 days-old, Lep group presented hyperleptinemia (1.4-fold increase), higher serum T3 (+ 22%), and lower mGPD activity ( - 57%). Maternal hyperleptinemia on lactation causes hypothyroidism in the pups at 30 days, which may program for higher serum T3 at adulthood. In conclusion, maternal hyperleptinemia during lactation, that is common in obese mothers, may have an impact in future disease development, such as thyroid dysfunction.     

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.     

Predicting a relapse of Graves' hyperthyroidism in adults during the early phase of treatment with anti-thyroid drugs

INTRODUCTION: The long-term effectiveness of anti-thyroid drugs (ATD) in the treatment of Graves' hyperthyroidism (GH) is still unsatisfactory and difficult to predict. The aim of this study was to evaluate the usefulness of a determination of serum level of thyrotropin-binding inhibiting immunoglobulins (second generation TBII assay) in predicting the possibility of relapse in the early phase of pharmacological treatment. MATERIAL AND METHODS: We investigated 37 patients within the 20-60 age range with the first occurrence of GH. All patients were treated with thiamazole for 12 months. Clinical assessment, ultrasound estimation of thyroid volume and determination of serum thyrotropin, free thyroxine, free triiodothyronine, thyroid autoantibodies and TBII levels were carried out at the onset and after 1, 3, 6, 9 and 12 months of ATD treatment. RESULTS: The mean follow-up period after ATD withdrawal was 27.24 +/- 5.81 months. Of 37 patients 12 (32%) had a relapse of hyperthyroidism (mean time 8.17 +/- 6.91 months after drug withdrawal). The difference in TBII levels between the relapse and the remission group was found to be significant after the first month of therapy until the end of ATD treatment. We observed that patients with TBII above 14 IU/L after 3 months and above 8 IU/L after 6 months of therapy relapsed more frequently than patients with lower levels (sensitivity 50% and specificity 92 and 96%, respectively). CONCLUSIONS: The study confirmed that TBII estimation in the early phase of ATD could be useful in the proper planning of GH therapy and early qualification to more radical treatment (radioiodine or surgery).