Thyroid function after subtotal thyroidectomy for hyperthyroidism.

Among 76 patients who had had a subtotal thyroidectomy for hyperthyroidism from one to seven years previously recurrent hyperthyroidism was found in three and hypothyroidism in 13. The remaining 60 subjects were clinically euthyroid but a raised level of serum thyroid-stimulating hormone (TSH; greater than 5-0 mu U/ml) was found in 39. Analysis of the data showed that their serum thyroxine was significantly lower than in the subjects with a normal TSH. The serum triiodothyronine (T-3) was similar in both groups. It is concluded that subjects with a raised TSH remain clinically euthyroid by maintaining a normal serum T-3 concentration. There was no evidence of any long-term progressive deterioration of thyroid function after subtotal thyroidectomy.     

Radioiodine treatment of multinodular non-toxic goitre.

OBJECTIVE--To investigate the long term effect of radioactive iodine on thyroid function and size in patients with non-toxic multinodular goitre. DESIGN--Consecutive patients with multinodular non-toxic goitre selected for radioactive iodine treatment and followed for a minimum of 12 months (median 48 months) after an intended dose of 3.7 MBq/g thyroid tissue corrected to a 100% uptake of iodine-131 in 24 hours. PATIENTS--69 patients with a growing multinodular non-toxic goitre causing local compression symptoms or cosmetic inconveniences. The treatment was chosen because of a high operative risk, previous thyroidectomy, or refusal to be operated on. MAIN OUTCOME MEASUREMENTS--Standard thyroid function variables and ultrasonically determined thyroid volume before treatment as well as 1, 2, 3, 6, and 12 months after treatment and then once a year. RESULTS--56 patients were treated with a single dose of 131I, 12 with two doses, and one with four doses. In 45 patients treated with one dose and remaining euthyroid the median thyroid volume was reduced from 73 (interquartile range 50-106) ml to 29 (23-48) ml at 24 months in the 39 patients in whom this was measured during follow up. The median reduction was 40 (22-48) ml (60% reduction, p < 0.0001), half of which occurred within three months. Patients treated with two doses as well as those developing hypothyroidism and hyperthyroidism had a significant reduction in thyroid volume. Eleven patients developed hypothyroidism (cumulative five year risk 22%, 95% confidence interval 4.8% to 38.4%). Side effects were few: three cases of hyperthyroidism and two cases of radiation thyroiditis. Only one patient was dissatisfied with the result; she was referred for operation six months after treatment. CONCLUSIONS--A substantial reduction in thyroid volume accompanied by a low incidence of hypothyroidism and few side effects makes the use of radioactive iodine an attractive alternative to surgery in selected cases of non-toxic multinodular goitre.     

How often should patients be reviewed after treatment with iodine-131 for thyrotoxicosis?

Six to 18 years after treatment with iodine-131 for thyrotoxicosis 69 euthyroid patients with raised serum thyrotrophin (TSH) concentrations (mean 25.0 +/- SE 2.0 mU/l) and 61 with normal concentrations (mean 4.0 +/- 0.2 mU/l) were included in a prospective five-year follow-up study beginning in 1972. During this period 13 patients from the original group with raised serum TSH concentrations became hypothyroid. In contrast it was five years before hypothyroidism developed in a single patient from the group with normal serum TSH concentrations in 1972, although raised concentrations were recorded in 19 of these patients during the study.     

Diagnosing amyloid goitre with thyroid aspiration biopsy

OBJECTIVE: The aim of the study was to evaluate the value of fine needle aspiration biopsy of the thyroid as a tool for diagnosing amyloid goitre and assess how amyloidosis affects thyroid tissue and thyroid function. METHODS: Clinical and laboratory evaluation of 50 patients with secondary systemic amyloidosis was done, and goitre was found in 38 of them. All 38 patients underwent thyroid aspiration biopsy. Tissue samples were stained with haematoxylin and eosin, May-Grünwald-Giemsa, crystal violet and Congo red. RESULTS: Of the 38 cases of amyloid goitre, 10 showed euthyroid sick syndrome, two showed primary hyperthyroidism, two showed hypothyroidism and one showed subacute thyroiditis. The serum levels of thyroid hormones and thyroid-stimulating hormone were normal in the remaining patients. Thirty-five of the 38 patients (92%) showed amyloidosis after thyroid aspiration. One of these patients had papillary carcinoma in addition to amyloid goitre. Ten patients underwent subtotal thyroidectomy, and one patient underwent total thyroidectomy after aspiration. Microscopic evaluation revealed that the thyroid parenchyma in all patients was largely replaced with amyloid and adipose tissue. CONCLUSION: Fine needle aspiration of the thyroid is a valuable and sensitive method for diagnosing amyloid goitre, especially because it is a safe and easily performed procedure. Further, amyloid goitre has no significant influence on thyroid function even when it causes extensive parenchyma replacement.     

Treatment of Hypothyroidism: A Reappraisal of Thyroxine Therapy

Twenty-two subjects with hypothyroidism have been studied in detail before and during replacement therapy with L-thyroxine (T-4). All subjects were stabilized on the minimum dose of T-4 which was necessary to suppress their serum thyroid-stimulating hormone (TSH) concentration to normal, and on this dose most subjects had a normal or impaired TSH response to thyrotrophin-releasing hormone (TRH). The daily dose of T-4 required to suppress TSH was 0·1 mg (13 subjects), 0·15 mg (six subjects), and 0·2 mg (three subjects). It was shown that all subjects were euthyroid on these doses and, using a range of thyroid function tests, that they were normal in all respects when compared with a group of euthyroid controls, with the exception of a small group who had a marginally raised serum triiodo-L-thyronine (T-3) concentration. It has been shown that those subjects who required the larger doses of T-4 had a more advanced degree of thyroid failure than those who were stabilized on 0·1 mg T-4 daily. It is concluded that conventional doses of T-4 (0·2-0·4 mg daily) are often associated with subclinical hyperthyroidism.     

Fine needle aspiration cytology in non-neoplastic non-toxic recurrent nodular goitre

The aim of the study was to examine whether evaluation of anisokaryosis is helpful in the cytological diagnosis of focal lesions in non-toxic recurrent goitre (NRG) after thyroidectomy for non-malignant goitre. Karyometric analysis was performed in routine cytological smears obtained from 80 females: 40 with focal lesions in non-toxic primary goitre (NPG) and 40 with NRG (postoperative histopathological examination revealed nodular goitre in both groups in all cases). We found that the level of anisokaryosis was significantly (P<0.005) higher in NRG than in NPG. There were no significant differences between the two lesions, in cellular composition or thyroid follicular cell arrangement. Thus, isolated anisokaryosis, a feature of malignancy in patients without a prior thyroidectomy, has limited diagnostic value in recurrent goitre.     

Determination of serum thyroxine enantiomers in patients by liquid chromatography with a chiral mobile phase

A chromatographic method for the separation and determination of D- and L-thyroxine enantiomers (D-, and L-T4) in human serum with a chiral ligand ion-exchange system using a chiral mobile phase additive and a silica column was established. An aqueous eluent containing L-proline (L-pro) sufficiently complexed copper II ions and triethylamine (TEA) was used. It was monitored with a UV detector. The separation was completed in 12 min. The method has acceptable sensitivity, precision and accuracy for analysis. The limit of detection and the limit of quantitation for both D- and L-T4 were 0.1 microg/ml and 0.8 microg/ml, respectively. Calibration curves were linear within 1-100 microg/ml; the mean correlation coefficients were r(D-T4)=0.9986 for D-T4 and r(L-T4)=0.9978 for L-T4. T4 enantiomers were separated on baseline under the optimum condition. L-T4 eluted before D-T4. The concentration of D-T4 and L-T4 in 45 thyroid patients serum (hyperthyroid, hypothyroid, thyroidectomy, goitre or thyroiditis) using HPLC was determined, those results showed that D,L-T4 concentration varied in different thyroid patient. Attention should be paid to this result in treating thyroid disease in the clinic.     

Does prophylactic thyroxine treatment after operation for non-toxic goitre influence thyroid size?

In order to evaluate the influence of thyroxine treatment on thyroid volume after thyroidectomy for non-toxic goitre 110 consecutive patients were randomised to receive thyroxine (150 micrograms daily) or no treatment three months after operation. Thyroid volume determined by ultrasonography did not differ significantly between the two groups one year after operation. Nevertheless, a similar decrease in volume was seen from three to 12 months postoperatively in the thyroxine treated and no treatment groups (median 18 (range 8-70) ml to 16 (range 7-57) ml, and median 20 (range 9-72) ml to 17 (range 8-58) ml, respectively). Three patients (two given thyroxine) had recurrence of goitre within the observation period of one year. In this series thyroid volume decreased during the first postoperative year independently of thyroxine treatment. Hence it seems questionable whether postoperative thyroid function studies can identify patients at risk of recurrence of goitre after operation for non-toxic goitre and whether routine postoperative treatment with thyroxine is justifiable.     

The problem of goitre with particular consideration of goitre resulting from iodine deficiency (II): management of non-toxic nodular goitre and of thyroid nodules

The present opinions on the therapy with L-thyroxine (L-T4) of non-toxic multinodular, as well as of non-toxic thyroid nodules are rather divergent. This treatment is based on the suppression of TSH secretion from the pituitary. There are no doubts that fine-needle aspiration biopsy (FNAB) performance is the first and--at the same time--the most significant diagnostic procedure in the case of thyroid structural lesions (nodules, goitre, thyroiditis). FNAB performance should--by all means--precede the beginning of L-T4 application for the treatment of non-toxic multinodular goitre or thyroid nodules. The simplicity, clearness and high efficacy, with comparable results in each case, are the core of good diagnostic algorithm. Unfortunately, not all diagnostic algorithms concerning thyroid nodules and multinodular goitre fulfil these important criteria.     

Oxidative stress markers during a course of hyperthyroidism

INTRODUCTION: Previous studies have shown the presence of oxidative stress in hyperthyroid patients. The aim of this study was to evaluate the influence of hyperthyroidism on lipid peroxidation, plasma lipoprotein oxidation and antioxidant status. We have estimated the clinical utility of the biochemical parameters analysed as markers of oxidative stress in hyperthyroidism. MATERIAL AND METHODS: Twenty five patients with overt hyperthyroidism because of Graves' disease or toxic multinodular goitre and 20 healthy subjects were included in the study. Lipid peroxidation was evaluated by measurement of peroxides and malondialdehyde with 4-hydroxynonenal (MDA + 4-HNE) concentrations. Autoantibodies against oxidised LDL (anti-oxLDL) were assayed as a marker of lipoprotein oxidation. Changes in the antioxidant defence system were estimated by measurement of total antioxidant status in serum (TAS) and erythrocyte superoxide dismutase activity (SOD). RESULTS: A significant increase in serum concentration of peroxides and MDA + 4-HNE was observed in patients with hyperthyroidism. However, no difference was found in anti-oxLDL concentration and antioxidant status parameters (TAS, SOD) between the control group and the patient group. CONCLUSIONS: Our results indicate an intensification of the oxidative processes caused by an excess of thyroid hormones, which is not accompanied by a response from the antioxidant system. Elevated concentrations of lipid peroxidation products in serum, both peroxides and malondialdehyde with 4-hydroxynonenal, may be useful as markers of oxidative stress during the course of hyperthyroidism.     

Clinical importance of reversibility in primary goitrous hypothyroidism.

Twenty seven hypothyroid patients with a serum concentration of thyroid stimulating hormone (TSH) of over 40 mU/1 were followed up for three to 20 weeks without replacement therapy. The serum thyroid hormone concentrations increased with a dramatic decrease in serum TSH values in 14 patients (reversible group) but there was no significant change in the other 13 (irreversible group). Fourteen out of 19 patients with goitre but none of the eight patients without goitre belonged to the reversible group. All of the 11 patients with a high uptake of iodide by the thyroid, three of the six with a normal uptake, and none of the 10 with a low uptake belonged to the reversible group. These observations indicate that patients with goitrous hypothyroidism with a preserved thyroid uptake of iodide are likely to become euthyroid spontaneously without replacement therapy.     

Radioimmunoassay of Triiodothyronine in Unextracted Human Serum

Serum triiodothyronine (T-3) concentrations have been estimated by radioimmunoassay using unextracted serum. The serum T-3 concentrations have been shown to be similar in two separate European populations (0·76-1·67 ng/ml). Raised T-3 values have been observed in all subjects with hyperthyroidism. Low values are seen in hypothyroidism although there is some overlap with the normal range. There is a good correlation between serum T-3 and serum thyroxine (T-4) concentrations, and estimation of T-3 seems likely to prove a practical and reliable test of thyroid function.     

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.     

Porphyria cutanea tarda: comparison of cases precipitated by alcohol and estrogens.

A group of seven patients with porphyria cutanea tarda (PCT) precipitated by excessive alcohol consumption (A) was compared with a group of nine patients with PCT precipitated by estrogen therapy (B). Comparison was based on clinical signs, biochemical and morphologic evidence of liver disease, results of serum iron studies and response to therapy. Group A patients were men of mean age 57 years; group B patients were women of mean age 39 years who had been taking estrogen orally, either for contraception (in combination with progesterone) or as replacement therapy. Clinical signs were essentially the same in the two groups. Some patients in both groups had biochemical and morphologic evidence of liver disease. Group A patients had elevated values for serum iron and total iron-binding capacity, whereas patients in group B had normal or low values. Cessation of estrogen therapy of less than a year''s duration brought about a spontaneous clinical and biochemical remission in group B patients. Otherwise, phlebotomy seemed to be the therapy of choice in both groups.     

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.     

毒性多结节性甲状腺肿的手术术式探讨

目的:探讨毒性多结节性甲状腺肿的手术切除范围,为临床手术治疗毒性多结节性甲状腺肿提供理论依据。方法:收集2006年12月至2011年12月哈尔滨医科大学附属第一临床医学院普外科确诊且进行手术的52例双侧毒性多结节性甲状腺肿患者的临床资料,并按照术式分为次全切除组(24例)和近全/全切除组(28例)。术后通过病理检查观察其合并甲状腺癌的情况,临床观察其是否出现声音嘶哑(喉返神经损伤)和低钙血症(甲状旁腺损伤)情况,并随访患者甲状腺结节和(或)甲状腺功能亢进的复发情况。结果:次全切除组甲状腺癌的检出率为4.2%(1/24),近全/全切除组检出率为7.1%(2/28),两者比较差异无统计学意义(x2=0.02,P0.05);两组患者术后暂时性声音嘶哑发生率分别为4.2%(1/24)、3.6%(1/28),差异无统计学意义(x2=0.37,P0.05),术后暂时性低钙血症发生率分别为4.2%(1/24)、7.1%(2/28),差异亦无统计学意义(x2=0.02,P0.05)。近全/全切除组患者术后无甲状腺结节和(或)甲状腺功能亢进复发,次全切除组患者有5例复发,复发率为20.8%(5/24),两组比较差异有统计学意义(x2=4.28,P0.05)。结论:甲状腺近全/全切除术比次全切除术更能减少毒性多结节性甲状腺肿的复发。     

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.     

Thyroid function in lung cancer

Thyroid function was assessed at the time of initial diagnosis in 204 patients with lung cancer and compared with that of age and sex-matched patients with non-malignant lung disease. Abnormalities in thyroid function were found in 67 patients (33%). The most prevalent abnormality was a low T3 concentration; this was not associated with other clinical or biochemical evidence of hypothyroidism, but the short-term prognosis of these patients was worse than that of matched patients with lung cancer having normal T3 concentrations. Primary hypothyroidism occurred in three patients, low T4 concentrations and free thyroxine index (FTI) with normal thyrotrophin (TSH) concentrations in four patients, and moderately raised TSH with normal thyroid hormone concentrations in six patients; nine patients had a raised FTI with or without raised T4 concentration as the sole abnormality.Overall, the pattern of thyroid hormone metabolism in lung cancer was a tendency towards reduced T3 concentrations with significantly increased T4/T3 ratios and modestly increased 3,3′,5′-triiodothyronine (rT3) concentrations. The altered T4/T3 ratio was particularly noticeable in patients with anaplastic tumours of small (“oat cell”) and large cell types, but was not apparently related to detectable extrathoracic metastases.These data suggest that thyroid hormone metabolism is altered in patients with lung cancer by decreased 5′-monodeiodination of T4. The resulting low T3 concentrations and altered T4/T3 ratio may be partly responsible for the reduced ratio of androsterone to aetiocholanolone observed in lung cancer, which is known to be a poor prognostic sign.     

Hypercoagulation in glomerulonephritis.

The clotting values of 50 patients with glomerulonephritis were examined. Three different coagulation groups were recognised: those with normal clotting values (group 1); those with high concentrations of factor VIII but otherwise normal clotting results (group 2); and patients who showed the presence of an activator of the intrinsic coagulation pathway, indicated by the presence of a short activated partial thromboplastin time or the ability of patients'' plasma to shorten control clotting time in mixing studies (group 3). Patients in group 2 either had a uniform rise in all three components of the factor VIII molecule or a disproportionately higher concentration of factor-VIII-related antigen. In contrast, the level of VIII clotting activity in patients in group 3 was always higher than concentrations of either VIIIAg or VIIIWF. A significantly high incidence of thrombotic complications was observed in patients with group 3 but in none of the patients in either group 1 or group 2. Impaired renal function was more common in patients in groups 2 and 3, with higher mean serum creatinine concentrations in those with group 3. Patients with glomerulonephritis who have a short partial thromboplastin time with kaolin or who shorten control clotting time form a subgroup in whom hypercoagulation could adversely affect the course of their disease. The value of antiplatelet or anticoagulant treatment in these patients needs to be explored.     

Serum ferritin in colorectal cancer patients and its prognostic evaluation

The aim of this study was to investigate the relationship between preoperative serum ferritin levels, clinico-pathological parameters and survival analysis of patients with colorectal cancer. Ninety-four patients (57 males) with a mean age of 65 years (39-87 years) underwent 63 curative and 31 palliative operations. Follow-up was at least 5 years. Patients were categorized with normal (30-215 ng/mL in men and 11-148 ng/mL in women), low, or high serum ferritin levels. Prognostic evaluation was undertaken with stratified survival analysis and Cox's regression model. Twenty-nine of the patients (30.9%) had raised ferritin levels and 14 (14.9%) had low values. Comparisons of the survival curves showed significant differences in stage C disease; specifically, patients with either low or high ferritin levels had a shorter survival than patients with normal levels. Patients who underwent palliative surgery and had high ferritin serum values also had a shorter survival. In multivariate analysis, the variables with a negative effect on survival were stage, serum ferritin levels and age. Our data suggest that patients with advanced colorectal cancer having normal preoperative serum ferritin levels may have a better prognosis, although the prognostic value related to this association requires further investigation.