Total and free thyroid hormone concentrations in patients receiving maintenance replacement treatment with thyroxine

Total and free serum concentrations of thyroxine and triiodothyronine were measured in 122 subjects with hypothyroidism who were clinically well while receiving conventional replacement treatment with thyroxine. In a third of patients concentrations of total and free thyroxine were raised, often considerably; nevertheless concentrations of total and free triiodothyronine were usually normal. Though significant correlations were obtained between total triiodothyronine concentrations and total thyroxine concentrations (p less than 0.001) and between the triiodothyronine concentrations and free thyroxine concentrations (p less than 0.001) the slope of the line of the regression equation describing these correlations was small, hence large increases in both total and free thyroxine concentrations were accompanied by only modest increases in total and free triiodothyronine concentrations. The presence of total or free thyroxine concentrations above normal in patients taking thyroxine therefore are not necessarily of clinical consequence. In the assessment of adequacy of replacement treatment with thyroxine the most logical combination of in vitro thyroid function test results may be a normal thyrotrophin concentration and normal free triiodothyronine concentration.     

Relevance of increased serum thyroxine concentrations associated with normal serum triiodothyronine values in hypothyroid patients receiving thyroxine: a case for "tissue thyrotoxicosis"

Fifteen patients receiving standard thyroxine replacement therapy (100-200 micrograms daily) for primary hypothyroidism and who had persistently raised free thyroxine concentrations in their serum were investigated to see whether the dose being given was too high. In addition to the usual thyroid hormone assays systolic time intervals (which indicate left ventricular contractility) were calculated as accurate reflectors of tissue thyroid activity. All patients showed the expected increased free and total thyroxine concentrations; but mean total and free concentrations of triiodothyronine were normal, while reverse triiodothyronine values were raised. Mean systolic time intervals were significantly reduced as compared with normal and fell within the thyrotoxic range. Seven patients subsequently had their doses of thyroxine reduced by 50 micrograms daily and were reinvestigated one month later. All showed significant falls in circulating thyroxine and triiodothyronine concentrations and an increase in mean systolic time intervals to the normal range. In patients receiving thyroxine replacement therapy for primary hypothyroidism a raised serum thyroxine concentration may indicate tissue thyrotoxicosis and should prompt a reduction of the thyroxine dose.     

Abnormalities of thyroid function tests in hospital inpatients

Results of thyroid function tests were analysed in 199 clinically euthyroid inpatients with normal serum thyroid stimulating hormone values. Serum total triiodothyronine was less than 1.25 nmol/l in 61.8% of samples, free triiodothyronine less than 3.9 pmol/l in 57.8%, total thyroxine less than 63 nmol/l in 21.1% and free thyroxine less than 9.5 pmol/l in 17.6%. In contrast, thyroxine binding globulin ratio was below normal (less than 5) in only 5 samples. A significant positive correlation (P less than 0.001) of serum free thyroxine with total thyroxine, thyroxine/thyroxine binding globulin ratio and free triiodothyronine was present as well as a significant negative correlation (P less than 0.001) with serum thyroid stimulating hormone. There was no correlation of free thyroxine measurements with serum albumin or non-esterified fatty acid concentrations. Although serum free thyroxine is low in a number of patients with non-thyroidal illnesses, this does not appear to be due to a rise in non-esterified fatty acids or a fall in albumin as has been proposed. Serum thyroid stimulating hormone measurements are essential to confirm the diagnosis of hypothyroidism in such subjects.     

Transient neonatal hyperthyrotrophinaemia: a serum abnormality due to transplacentally acquired antibody to thyroid stimulating hormone

In a screening programme for neonatal hypothyroidism an otherwise healthy female infant was found to have a high concentration of thyroid stimulating hormone in a filter paper blood spot and in serum. A high concentration was also found in the maternal serum. Mother and baby were both biochemically euthyroid with normal serum thyroxine concentrations. The apparently high concentration of thyroid stimulating hormone in the mother was due to the presence of an IgG antibody that bound to human but not bovine thyroid stimulating hormone. Maternal serum inhibited the action of human thyroid stimulating hormone in an in vitro bioassay for the hormone. It is suggested that the baby acquired the antibody transplacentally, especially as the concentration of thyroid stimulating hormone subsequently fell. It is concluded that maternal serum should be assayed for thyroid stimulating hormone when a neonate is found to have a high concentration of the hormone and a normal concentration of thyroxine to establish the incidence of this finding and to avoid inappropriate replacement treatment.     

Raised plasma glutathione S-transferase values in hyperthyroidism and in hypothyroid patients receiving thyroxine replacement: evidence for hepatic damage

Using plasma glutathione S-transferase measurements hepatocellular integrity was assessed in groups of hyperthyroid and hypothyroid patients before and after treatment. Ten of 14 hyperthyroid patients had clearly raised plasma glutathione S-transferase values at presentation and in each patient treatment with either iodine-131 or carbimazole resulted in a significant fall in glutathione S-transferase. The eight hypothyroid patients had normal glutathione S-transferase values at presentation and all showed a significant increase in these after thyroxine replacement therapy. In three of these patients in whom standard doses of replacement therapy were associated with a raised free thyroxine (T4) concentration but normal total and free triiodothyronine (T3) values glutathione S-transferase was increased. Similar though less consistent changes were seen in the results of standard chemical tests of liver function. It is concluded that hyperthyroidism may produce subclinical liver damage in a high proportion of patients and that this resolves with effective treatment. More important, the data suggest that hypothyroid patients receiving thyroxine replacement therapy may have similar subclinical liver damage. Patients receiving thyroxine should be monitored by the measurement of free, not total hormone concentrations, and in those in whom free T4 is raised the dose of thyroxine should be reduced. It would also be expedient to include periodic biochemical assessment of liver function in patients receiving thyroxine.     

Management and outcome of children with congenital hypothyroidism detected on neonatal screening in South Australia

Thirty-eight congenitally hypothyroid children who were detected in a neonatal screening programme have been treated for a mean period of 3.8 years (range, 0.5-8.5 years) by the maintenance of the free thyroxine index in the upper normal range as the main determinant of the dose of thyroxine. Only excessive elevation of, or serial rises in, thyroid stimulating hormone (TSH) level influenced the dose of thyroxine. This treatment strategy, which aims to avoid the potentially adverse effects of thyroxine overdosage, has often resulted in delayed return of TSH levels to normal, especially in athyrotic children (mean TSH +/- SD at one year of age in athyrotic children, 72 +/- 90 mU/L; in children with ectopic thyroid glands, 24 +/- 16 mU/L; normal range, 0-7 mU/L). The mean thyroxine dose of about 100 micrograms/m2 did not change significantly with age, and is lower than the doses that are sometimes quoted in the literature; athyrotic children require significantly more thyroxine (P less than 0.05) than those with ectopic thyroid glands. Symptoms and signs of congenital hypothyroidism, although subtle, were significantly more common (P less than 0.05 for symptoms and P less than 0.001 for signs) in athyrotic children compared with those with ectopic glands. No physical or developmental abnormality related to congenital hypothyroidism has been demonstrated on follow-up; mean height and weight percentiles approximate the 50th percentile at ages one to six years and mean developmental scores +/- SD at about two years of age by the Griffiths Mental Development Scale and at 4.5-6.5 years by the Wechsler Preschool and Primary Scale are 102.4 +/- 10.4 and 111.2 +/- 12.2, respectively. Long-term follow-up studies are necessary to exclude more subtle developmental and neurological abnormalities.     

On the relation of dystonic movements to serum thyroxine levels

A patient with psychomotor retardation secondary to delayed treatment of cretinism developed abnormal dystonic movements in the absence of other signs of toxicity during levothyroxine replacement therapy at a serum thyroxine level of 16 μg./100 ml. The dystonic movements disappeared when the serum thyroxine level fell. The abnormal movements were considered to be related to high thyroxine levels in this patient with pre-existing central nervous system dysfunction.     

Heart rate variability and its response to thyroxine replacement therapy in patients with hypothyroidism

目的　测定甲状腺功能减退 (甲减 )患者心率变异 (HRV)及观察甲状腺素替代治疗后的变化。方法　记录 38例甲减患者与 2 1例正常者 2 4小时动态心电图 ,并进行HRV分析。 18例甲减患者治疗 3月后重复HRV测定。结果　甲减时 ,HRV的时阈指标较对照组明显降低 ;频阈指标中 ,高频功率 (HF)较对照组明显增高 ,而低频 (LF)与HF比值较对照组显著减低。甲减患者经甲状腺素替代治疗后 ,HRV时阈指标和频阈指标均明显改善 ,且与FT3和FT4 的恢复程度相一致。结论　甲减时 ,自主神经活动明显改变 ,且以迷走神经兴奋性增加占优势。这种自主神经异常在甲状腺素替代治疗后可部分改善。     

Thyroxine, methimazole, and thyroid microsomal autoantibody titres in hypothyroid Hashimoto's thyroiditis

Ten hypothyroid patients with Hashimoto's thyroiditis were treated with methimazole 30 mg in addition to thyroxine 0.15 mg daily. Another 10 hypothyroid patients with Hashimoto's thyroiditis were given thyroxine 0.15 mg alone. After 22 weeks of treatment significant decreases in thyroid microsomal autoantibody titres were observed in both groups (p less than 0.01). There was no difference in the mean change in titre between the two groups. When the patients treated with methimazole were subsequently given thyroxine 0.15 mg alone for a further 22 weeks no additional change in titre was observed. The data suggest that thyroxine, by normalising serum thyroid stimulating hormone concentrations, may reduce the autoantigenic properties of the thyrocytes with a subsequent decrease in autoantibody titres.     

Cyclosporin treatment of IgA nephropathy: a short term controlled trial

Cyclosporin's known regulatory effects on the immune system suggest that it may be useful in treating patients with IgA nephropathy. A randomised prospective single blind study of 19 patients with IgA nephropathy and proteinuria (greater than 1.5 g/day) was conducted to determine the therapeutic value of cyclosporin. The patients were divided into two groups: nine patients were given oral cyclosporin (5 mg/kg/day) for 12 weeks and 10 patients a placebo. The two groups were comparable in age of presentation, ratio of men to women, plasma creatinine and serum IgA concentrations, creatinine clearance, daily urinary protein excretion, severity of renal histopathological changes, and prevalence of hypertension. A significant reduction of proteinuria and an increase of plasma albumin concentration was observed with treatment with cyclosporin. Nevertheless, a significant rise of plasma creatinine concentration and a fall in creatinine clearance was found in patients after six weeks' treatment with cyclosporin, although the plasma cyclosporin concentrations were maintained within a narrow therapeutic range. Serum IgA concentrations were reduced in seven patients. Renal function improved within eight weeks after treatment was stopped. Three months after treatment was stopped proteinuria remained less than half of the pretreatment values in three patients. No similar biochemical changes were observed in the controls. Short term cyclosporin therapy may be beneficial in reducing proteinuria in some patients with IgA nephropathy. As transient renal impairment was seen, despite cyclosporin concentrations being maintained within a narrow therapeutic range, indiscriminate use of cyclosporin in glomerulonephritis should be discouraged.     

甲状腺素对非酒精性脂肪肝大鼠ANGPTL3表达的影响

目的 探讨甲状腺激素(TH)对非酒精性脂肪肝(NAFLD)大鼠血管生成素样蛋白3(ANGPTL3)表达的影响,明确TH是否通过ANGPTL3途径影响NAFLD大鼠肝脏脂肪变性。方法健康3周初断乳SD雄性大鼠30只,随机分为5组:正常组、高脂组、甲状腺素预防组、甲状腺素治疗组、吉非罗齐组;所有大鼠除正常组外均以高脂饮食喂养,分别于0、4、8、12周断尾取血,12周末处死大鼠,取肝脏。苏木精-伊红法(HE)染色,进行肝脂肪变性程度评分,采用酶联免疫吸附实验(ELISA法)检测血清ANGPTL3含量,逆转录聚合酶链式反应(RT-PCR)检测肝脏中ANGPTL3 mRNA的表达水平。结果甲状腺素预防组及吉非罗齐组大鼠肝组织脂肪变性程度均低于高脂组及甲状腺素治疗组(P<0.01)。高脂组血清ANGPTL3水平在第8周后出现增高,呈时间依赖性,其肝组织中的ANGPTL3 mRNA表达亦较正常对照组明显升高(P<0.01)。甲状腺预防组大鼠在8、12周均出现血清ANGPTL3浓度降低,并可下调肝脏ANGPTL3 mRNA水平,与高脂组及甲状腺素治疗组相比较,差异均具有统计学意义(P<0.05)。甲状腺素治疗组与吉非罗齐组亦可一定程度下调血清ANGPTL3水平及肝组织中ANGPTL3 mRNA 表达(P<0.05),但其降低的程度少于甲状腺素预防组(P<0.05)。结论NAFLD形成过程中伴有ANGPTL3进行性增高,早期给予小剂量TH可通过ANGPTL3途径而改善NAFLD大鼠肝脂肪变性程度。     

Effect of propranolol on thyroid homeostasis of healthy volunteers.

The effect of propranolol on thyroid status was investigated by administering the drug in 2 therapeutic doses (80 mg b.d. and 120 mg b.d.) to 8 healthy volunteers and serially measuring total and free thyroid hormones and their major binding protein. Mean free T3 fell by 1.2 pmol/l (P less than 0.05) whilst mean free T4 and mean rT3 rose by 3.3 pmol/l (P less than 0.01) and 0.16 nmol/l (P less than 0.01) respectively. Mean thyroxine binding globulin (TBG) fell by 1.2 mg/l (P less than 0.001). Despite the change in free hormone levels there was no significant change in TSH. For the first time the effect of propranolol on circulating thyroid hormones and binding proteins in healthy subjects is apparent within one study. The biological significance of the change in free hormone levels is discussed.     

Sequential defunctionalization followed by thyroxine supple- mentation as preoperative preparation of hyperthyroid patients undergoing thyroidectomy

Background Preparing hyperthyroid patients for thyroid surgery with a combination of antithyroid drugs and thyroxine has long been controversial because this combination usually results in only partial inhibition of thyroid function. We therefore used large doses of antithyroid drugs to completely inhibit the synthesis of thyroxine and render the thyroid gland defunctionalized. We then administered physiologic doses of thyroxine to inhibit thyroid-stimulating hormone secretion. We have named this treatment “sequential thyroid defunctionalization followed by thyroxine supplementation.”
Methods Four hundred and seventy-one hyperthyroid patients seen at our hospital were divided into experimental and control groups. The control group was treated preoperatively with antithyroid drugs and iodine preparation. The experimental group was further divided into four subgroups and treated with “sequential thyroid defunctionalization followed by thyroxine supplementation”. Each of the four subgroups received different doses of antithyroid drugs and thyroxine for differing time periods. Thyroid function was assessed at each stage of treatment, as were operative blood loss volumes and postoperative complications.
Results Compared to the control group, the four experimental groups showed less thyroid congestion and surface varices at surgery. Patients in subgroup A also had thyroid glands that were almost histologically normal. The mean operative blood loss volume of the experimental group was less than that of the control group （（326±163） ml in the control group; （196±57） ml in subgroup A; （230±71） ml in subgroup B; （240±80） ml in subgroup C; and （312±97） ml in subgroup D）. The postoperative complication rate of the experimental group was 8.64% （21/243） whereas that of the control group was 17.54% （40/228）.
Conclusions Sequential thyroid defunctionalization followed by thyroxine supplementation is effective in reducing the bleeding volume and postoperative complication rate in     

Beta-adrenoreceptor blocking drugs and thyroid hormones in hyperthyroid subjects.

Serum thyroid hormone concentrations were measured before and during 10 days'' treatment with atenolol (200 mg/day), acebutolol (400 mg/day), oxprenolol (160 mg/day) and propranolol (160 mg/day) in 24 hyperthyroid patients. During propranolol treatment serum triiodothyronine (T3) concentrations fell significantly (P less than 0.05) but there was no change in thyroid hormone concentrations in the other groups although all patients reported a symptomatic improvement.     

Effect of captopril on kidney function in insulin-dependent diabetic patients with nephropathy

The influence of angiotensin II on kidney function in diabetic nephropathy was assessed by studying the effect of 12 weeks' monotherapy with captopril (25-50 mg twice a day) in 16 hypertensive insulin dependent diabetic patients with persistent albuminuria. In an initial one week randomised single blind trial of captopril versus placebo, captopril (for nine patients) reduced arterial blood pressure from 148/94 (SD11/6) to 135/88 (8/7) mm Hg (p less than 0.05) and albuminuria from 1549 (range 352-2238) to 1170 (297-2198) micrograms/min (p less than 0.05), while glomerular filtration rate remained stable. No significant changes occurred in seven patients treated with placebo. During the 12 weeks of captopril treatment arterial blood pressure in all patients fell from 147/94 (11/6) to 135/86 (13/7) mm Hg (p less than 0.01), albuminuria fell from 1589 (range 168-2588) to 1075 (35-2647) micrograms/min (p less than 0.01), and glomerular filtration rate fell from 99 (SD19) to 93 (25) ml/min/1.73 m2 (p less than 0.01). The renin-angiotensin system showed suppressed plasma concentrations of angiotensin II and increased concentrations of angiotensin I and renin. The study showed that glomerular filtration rate is not dependent on angiotensin II, that captopril reduces albuminuria, probably by lowering glomerular hypertension, and that captopril represents a valuable new drug for treating hypertension in diabetics dependent on insulin with nephropathy.     

前列腺炎患者前列腺液免疫球蛋白G、A和M测定

本文采用SRID对83例前列腺炎及27例正常对照组EPS中IgG、A、M含量进行了测定。结果表明前列腺炎患者EPS中IgG、IgA和IgM均明显高于对照组（P＜0.005），IgG/IgA显著低于对照组（P＜0.005）。并对25例前列腺炎患者治疗前、后进行了观察，治疗前EPS中三种Ig高于对照组（P＜0.01）和治疗后（P＜0.01），治疗后的三种Ig仍高于对照组（P＜O.01）。治疗前、后的IgG/IgA明显低于对照组（P＜0.01），而治疗前、后无显著区别（P＞0.05）。因此，应将EPS中三种Ig增高及IgG/IgA降低作为前列腺炎的诊断标准，并将EPS中三种Ig及IgG/IgA达到正常水平视为治愈的标准。     

甲状腺机能亢进症红细胞微量元素锌、铜、铁缺陷研究

采用原子吸收分光光谱技术建立了一种适合临床应用的重复性及准确性良好的红细胞微量元素测定法。作者检测４０例正常人及５０例甲亢病人的血浆及红细胞锌、铜、铁含量，结果发现甲亢者存在红细胞锌、铜缺陷。红细胞锌与甲状腺激素呈负相关关系；红细胞铜与甲状腺激素呈正相关关系；红细胞锌显著降低（Ｐ＜０．００１），与Ｔ４、Ｔ３呈负相关（Ｐ＜０．０１）；红细胞铜显著增加（Ｐ＜０．０１），与Ｔ４呈正相关（Ｐ＜０．０５）。初诊甲亢患者治疗后红细胞锌明显增加（Ｐ＜０．０５），红细胞铜明显降低（Ｐ＜０．０５），提示甲状腺激素干扰红细胞锌、铜代谢。     

American Thyroid Association guidelines for use of laboratory tests in thyroid disorders

Selection of appropriate laboratory determinations will enable the clinician to diagnose thyroid dysfunction readily in the majority of patients. At the present time, estimation of free thyroxine and a "sensitive" thyrotropin assay are recommended as the principal laboratory tests for thyroid disease. A decrease in serum free thyroxine estimate and a raised level of serum thyrotropin confirm the diagnosis of hypothyroidism caused by thyroid gland failure. An increase in free thyroxine estimate combined with a serum sensitive thyrotropin level suppressed to less than 0.1 mU/L establishes the diagnosis of thyrotoxicosis. In sick patients, a normal or raised serum free thyroxine estimate together with a normal level of serum thyrotropin suggests that the patient has neither hypothyroidism nor thyrotoxicosis. Patients with severe illnesses, generally in the intensive care unit, and those treated with certain drugs, as well as individuals with unusual thyroid disorders, may present with confusing laboratory findings. An understanding of the regulation of the thyroid hormone system and/or judicious consultation with an endocrinologist should enable the clinician to diagnose thyroid disease, if present, in such patients.     

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.     

抑郁症患者甲状腺激素水平变化的临床探讨

目的探讨血清甲状腺激素水平与抑郁症的关系。方法采用放射免疫法(RIA)分别测定32例正常对照组、56例精神抑郁症患者(其中单相抑郁症25例,双相抑郁症31例)治疗前后TT3、TT4、FT3、FT4、TSH浓度。结果患者治疗前TT3水平明显高于对照组(P<0.01),FT3明显低于对照组(P<0.01);经过治疗,TT4低于治疗前(P<0.05),且恢复到正常范围;双相抑郁症患者血清FT3明显低于单相抑郁症患者(P<0.05)。结论提示抑郁症患者甲状腺激素水平变化与症状的消失有关,甲状腺激素水平异常是继发于情绪障碍;FT3水平降低可能是双相抑郁症的一个生物学指标。