Postpartum thyroiditis and familial dysalbuminemic hyperthyroxinemia.

Familial dysalbuminemic hyperthyroxinemia (FDH) is a syndrome associated with euthyroidism and increased binding of T4 to serum albumin. The combined occurrence of FDH and postpartum hyperthyroidism due to Graves' disease has only been reported in one patient. We now describe the first case of FDH and thyrotoxicosis due to postpartum silent thyroiditis. In a 19-yr-old woman, FDH, suspected on the basis of strikingly elevated analog free T4 (fT4) and total T4 values, but normal two-step fT4 and serum TSH values, was confirmed by [125I]T4 agarose-gel electrophoresis. When FDH and thyrotoxicosis, characterized by markedly elevated analog fT4, total T4, and two-step fT4 values and undetectable TSH values, coexist, the differential diagnosis may be confusing.

Methimazole has no dose-related effect on the intensity of the intrathyroidal autoimmune process in relapsing Graves' disease.

Declining thyroid autoantibodies during treatment and decreased lymphocytic infiltration after treatment of patients with Graves' disease suggest immunosuppressive actions of antithyroid drugs. However, the recent report of similar relapse rates after low and high dose carbimazole treatment of Graves' disease seems to contradict the immunosuppression thesis. We therefore determined the intrathyroidal methimazole concentrations with a high performance liquid chromatography method in 17 patients undergoing subtotal thyroid resection for relapsing Graves' disease. The intensity of the intrathyroidal infiltration by immunoglobulin G-producing plasma cells, activated T cells, and antigen presenting cells, and the total number of lymphocytes were identified immunohistologically with monoclonal antibodies for kappa- and lambda-immunoglobulin light chains, UCHL1, and the S100 antibody, respectively, followed by morphometry. The intrathyroidal methimazole concentration and the cumulative preoperative methimazole doses did not correlate with the intensity of the intrathyroidal infiltration by any of these immunocompetent cells. Comparison of groups with significantly different intrathyroidal methimazole concentrations (134 ng/g, n = 8 vs. 993 ng/g, n = 7) showed no significant differences for any of the intrathyroidal immunocompetent cells. These findings suggest that there is no dose-related effect of methimazole on the intensity of the intrathyroidal autoimmune process of patients with relapsing Graves' disease. They provide an explanation for why it does not seem justifiable to recommend higher methimazole doses than those required for the control of hyperthyroidism with the goal of immunosuppression.

Chromatographically purified immunoglobulin G of endemic and sporadic goiter patients stimulates FRTL5 cell growth in a mitotic arrest assay.

A strain of differentiated rat thyroid cells (FRTL5) in continuous culture was used to study the presence of thyroid growth-promoting immunoglobulins (TGI) in the serum of patients with endemic and sporadic euthyroid goiters. To identify true in vitro cell proliferation a microscopic mitotic arrest assay was used. Immunoglobulins G (IgGs) were prepared with QAE-Sephadex A-50 or protein-A-Sepharose. A positive growth stimulation index was found in IgG preparations of 65 of 71 patients with endemic goiter and in 9 of 14 IgG preparations of patients with sporadic goiter. IgG preparations of 15 control subjects from an area where endemic goiter due to iodine deficiency does not occur and of 18 subjects without iodine deficiency and without thyroid enlargement living in the endemic area did not stimulate FRTL5 cell growth. FRTL5 cell growth stimulation with IgGs of these euthyroid goiter patients could only be detected when IgG was tested in combination with a small dose of TSH. Immunoprecipitation with polyclonal and monoclonal antihuman IgG was able to abolish the growth-promoting effects. In 32 blinded samples the Feulgen cytobiochemical assay, formerly used to detect TGI, was compared with the FRTL5 mitotic arrest assay. The two methods showed similar results. Our observations of chromatographically purified IgG promoting thyroid cell proliferation in vitro provide good evidence that IgG was responsible for thyroid cell growth in vitro and suggest that autoimmune growth mechanisms may be involved in the pathogenesis of both endemic and sporadic goiters.

The impact of geographical, clinical, dietary and radiation-induced features in epidemiology of thyroid cancer.

Cancer of the thyroid accounts for less than 1% of all cancers recognised each year, but the incidence is rising. Much of the early work of the epidemiology and aetiology of thyroid cancer was based on the assumption that thyroid cancer can be treated as an entity. The recognition that two distinct types of endocrine cell occur within the thyroid has made it clear that any discussion of the aetiology and epidemiology of thyroid malignancies must take into account the histological classification of these tumours. Moreover, there are difficult problems to be considered when comparing thyroid cancer incidence across tumour registries, because of a lack of standardisation or morbidity data collection, difficulties in histological diagnosis, varying rates of diagnosis of occult papillary carcinoma, and prevalence and techniques of autopsies. So far only a relatively small proportion of thyroid cancer cases can be explained with adequate certainty as regards epidemiology and aetiology. As in cancer in general, the aetiology and epidemiology of thyroid cancer in detail remains unknown in the majority of cases.

Subclinical hyperthyroidism as a risk factor for atrial fibrillation.

OBJECTIVES: Atrial fibrillation is a well-known manifestation of hyperthyroidism. We studied whether subclinical hyperthyroidism with low serum thyrotropin concentrations and free thyroid hormone concentrations within the normal range in clinically euthyroid persons is a risk factor for subsequent atrial fibrillation. METHODS: We studied 23,638 persons. The subjects were classified according to their serum thyrotropin concentrations: group 1 comprised those with normal values of serum thyrotropin concentration (>0.4-5.0 mU/L) and free tri-iodothyronine and free thyroxine concentrations were within the normal range (22,300 subjects), group 2 comprised those with both low serum thyrotropin values (5-fold higher likelihood for the presence of atrial fibrillation with no significant difference between subclinical and overt hyperthyroidism.

Immunoscintigraphy of inflammatory processes with a technetium-99m-labeled monoclonal antigranulocyte antibody (MAb BW 250/183).

Antigranulocyte immunoscintigraphy with a technetium-99m- (99mTc) labeled monoclonal antigranulocyte antibody (MAb BW 250/183) was performed in 34 in-patients of the departments of accident surgery and internal medicine in order to prove or exclude inflammatory processes. After labeling with 99mTc, 555 MBq, 99mTc-MAb (0.5 mg antibody) were slowly injected intravenously over a period of 5 min. A whole-body scan was done 4-6 hr postinjection, and planar or SPECT images were performed 6, 18, and 24 hr postinjection. Leukocyte immunoscintigraphy proved inflammatory suppurating processes in 20 cases (true-positive) and excluded them in 11 cases (true-negative). The findings were false-positive in two patients (hematoma without signs of infection, pseudoarthrosis) and false-negative in one patient (encapsulated lung abscess with pleural fibrosis). Anti-idiotypic human anti-mouse antibodies (HAMA) were found only in one out of 20 patients. According to our experiences, immunoscintigraphy with 99mTc-MAb BW 250/183 has a sensitivity of 95%, and is, therefore, well suited for the identification of leukocytic inflammations.

Anti-carcinoembryonic antigen immunoscintigraphy (technetium-99m-monoclonal antibody BW 431/26) and serum CEA levels in patients with suspected primary and recurrent colorectal carcinoma.

This study comprises a total of 141 patients with suspected primary and recurrent colorectal carcinomas, in whom immunoscintigraphy with 99mTc-Mab BW 431/26 was performed. Whole-body scans were done 5.5 hr and SPECT imaging of the abdominal region was done at 6 and 24 hr postinjection of 1100 MBq 99mTc-labeled Mab (1 mg). In the course of primary tumor identification (n = 65), sensitivity of anti-CEA immunoscintigraphy was 95%, specificity 91%. In the diagnosis of early recurrences (n = 76), immunoscintigraphy was the method of choice to clarify the problem (sensitivity 94%; specificity 86%). Overall sensitivity of immunoscintigraphy in patients with suspected colorectal carcinomas and early recurrences was 95%, specificity 88%. Human anti-mouse antibodies were found in 29% (80% predominantly anti-isotypic, 20% predominantly anti-idiotypic). In contrast to anti-CEA immunoscintigraphy, the results of serum CEA levels were rather disappointing. Only 18 out of the 43 surgically verified primary colorectal carcinomas and 17 out of 32 patients with recurrences showed elevated serum CEA levels. In our clinical experience with this 99mTc-labeled anti-CEA antibody, immunoscintigraphy can play an important role in the identification of early colorectal recurrences and in postoperative colorectal cancer patients it should be performed in cases with unclear transmission computed tomography.

Thyroid volume and urinary iodine in European schoolchildren: standardization of values for assessment of iodine deficiency.

Up to 1992, most European countries used to be moderately to severely iodine deficient. The present study aimed at evaluating possible changes in the status of iodine nutrition in 12 European countries during the past few years. Thyroid volume was measured by ultrasonography in 7599 schoolchildren aged 7-15 years in one to fifteen sites in The Netherlands. Belgium, Luxemburg, France, Germany, Austria, Italy, Poland, the Czech and Slovak Republics, Hungary and Romania. The concentrations of urinary iodine were measured in 5709 of them. A mobile unit (ThyroMobil van) equipped with a sonographic device and facilities for the collection of urine samples visited all sites in the 12 countries. All ultrasounds and all urinary iodine assays were performed by the same investigators. The status of iodine nutrition in schoolchildren has markedly improved in many European countries and is presently normal in The Netherlands, France and Slovakia. It remains unchanged in other countries such as Belgium. There is an inverse relationship between urinary iodine and thyroid volume in schoolchildren in Europe. Goiter occurs as soon as the urinary iodine is below a critical threshold of 10 micrograms/dl. Its prevalence is up to 10 to 40% in some remote European areas. This work produced updated recommendations for the normal volume of the thyroid measured by ultrasonography as a function of age, sex and body surface area in iodine-replete schoolchildren in Europe. This study proposes a method for a standardized evaluation of iodine nutrition on a continental basis, which could be used in other continents.

The influence of iodine on the intensity of the intrathyroidal autoimmune process in Graves' disease.

Several lines of evidence support an etiological role of iodine for the initiation and perpetuation of autoimmune thyroid disease. However, varying relapse rates after increased iodine supplementation have been reported for Graves' disease. Furthermore the effects of iodine on the intensity of human autoimmune thyroiditis have previously only been investigated by indirect parameters and actions of iodine on thyroid function and a possible enhancement of the intrathyroidal autoimmune process in Graves' disease are difficult to separate in previous studies. Moreover lymphocytic thyroiditis in animal models has always been induced by considerably higher iodine doses as those used in in vivo studies. Therefore we investigated the effect of low and high iodine concentrations on the intensity of the intrathyroidal autoimmune process in Graves' disease. The intensity of intrathyroidal infiltration by lymphocytes, memory T cells, plasma cells and antigen presenting cells was determined by quantitative immunohistologic methods in 38 Graves' disease patients. 12 patients received additional preoperative iodine (group II) and 26 were treated with thiourelene antithyroid drugs only (group I). Urinary and intrathyroidal iodine concentrations were determined by a modified cer arsenite method in both groups. Application of high iodine doses in group II induced a significant increase of kappa and lambda positive plasma cells and interdigitating reticulum cells. This was not observed for activated T cells. There was no correlation between the extent of intrathyroidal infiltration by activated T cells, plasma cells and antigen presenting cells, and intrathyroidal or urinary iodine or intrathyroidal iodine concentrations in group I.(ABSTRACT TRUNCATED AT 250 WORDS)

Misinterpretation of iodine uptake in papillary thyroid carcinoma and primary lung adenocarcinoma.

This is the first case report of an iodine-storing metastasising carcinoma of extrathyroidal origin and the simultaneous presence of a papillary thyroid carcinoma. In the course of the disease, an increase in pathological iodine uptake was observed after repeated iodine-131 ablation, so that the original tentative diagnosis of a metastasising, differentiated thyroid carcinoma appeared to be confirmed; moreover, the histological work-up of a femur metastasis--without adequate immunohistochemical assessment--was misinterpreted. What is also remarkable about this case report is a pathological iodine-131 uptake both in the extrathyroidal primary tumor and the metastases.

Thyrotropin and thyroglobulin as an index of optimal iodine intake: correlation with iodine excretion of 39,913 euthyroid patients.

The recommendations for the dietary allowance of iodine are 150 micrograms per day for adolescents and adults. Thyrotropin (TSH) and thyroglobulin (Tg) can be used as surveillance indicators for assessing iodine deficiency disorders. We compared the relation between TSH and Tg, free triiodothyronine, and thyroxine serum levels with urinary iodine excretion in 2311 untreated euthyroid patients using our modified cericarsenite method. An adequate iodine intake may be assumed when TSH and Tg values are at the lower end of the normal range. Patients were grouped according to urinary iodine excretion and goiter size. In the group with an iodine excretion between 201 and 300 micrograms of iodine per gram of creatinine, the lowest TSH values and even low Tg levels could be shown. We conclude that an iodine intake of approximately 250 micrograms/day is associated with the lowest TSH stimulation to thyrocytes. In the groups separated according to thyroid size, significantly higher Tg levels were found in the patients with uninodular and multinodular goiter as a result of longstanding iodine deficiency, whereas actual urinary iodine excretion did not differ significantly. Additionally, iodine excretion of 39,913 euthyroid patients between 1984 was 1996 was examined. In Austria iodized salt (10 mg KI/kg) was introduced by law in 1963 and increased to 20 mg KI/kg salt in 1990. An initial increase of iodine excretion until 1993 was followed by a decrease in 1994 and 1995 without further changes in 1996. These results show that iodine intake has improved since 1984; however, in 1996 iodine excretion in one-third of the investigated patients was under 100 micrograms per gram of creatinine and more than 80% had less than 200 micrograms per gram of creatinine.

Impact of stress and triiodothyronine on plasma magnesium fractions.

The differential regulation of free and bound plasma magnesium was studied in healthy volunteers exposed to various forms of stress, and patients screened for thyroid disorder. Both ergometric (7 min) and psychological (45 min) stress had no effect on free plasma magnesium, but increased the bound fraction. Before combined physical and psychological stress (45 min aerobatics) there was no correlation between the plasma fractions of magnesium; thereafter, there was a strong negative correlation between increased free and decreased bound magnesium. Three days of training in ground combat increased significantly the plasma levels of both magnesium fractions. Patients screened for thyroid disorder had a significant, positive correlation between both plasma fractions of magnesium, and a highly significant negative correlation between plasma T3 and the two magnesium fractions. No clear correlation between plasma catecholamines and magnesium levels was seen under any of the above conditions. Overall, the data show that the evaluation of the functions of circulating magnesium requires the specific measurement of the free and bound fractions.

Hypervolemic haemodilution and completed stroke: how important is the application time for its effect?

In 75 patients with completed stroke hypervolemic haemodilution was performed for 1 day with 500 ml 6% HES 200.000/0.6-0.66 (Elohäst) to test the acute influence of application time for haemorheological changes. The patients were divided into 3 groups randomly selected: group A received the infusion for 2 hours, group B for 4 hours and group C for 6 hours. Haematocrit (HCT), whole blood viscosity (VI-VB), blood elasticity (EL-VB) and plasma viscosity (VI-PL) were determined before onset of infusion, after 6 and 18 hours subsequently. The values obtained were compared with the onset results. In all groups and parameters after 6 hours there was a significant decrease. After 18 hours group A showed a significant higher value of HCT and increasing trends for VI-VB and EL-VB. In group B after 18 hours a significant decrease of VI-VB could be observed. In group C all values remained significantly below the onset. The results show, that one important haemorheological argument for an effective form of haemodilution should also be a long application time. This might be one of the reasons, why in some studies with hypervolemic haemodilution no positive results could be obtained.

3,5,3'-Triiodothyroacetic acid (TRIAC) effects on pituitary thyroid regulation and on peripheral tissue parameters.

The effects of TRIAC on peripheral thyroid hormones, TSH incretion and peripheral tissue parameters were investigated in 13 mildly obese patients (group I) and 10 volunteers of normal body weight (group II). TRIAC was administered 3 x 1 mg daily over a period of 8 days to both groups. In group I (on a 400 kcal low caloric diet) bTSH and fT4 decreased significantly whereas TT4 decreased only insignificantly. TT3 and fT3 rose significantly due to the cross-reactivity of the employed antibody. The peripheral tissue parameters cholesterol, ankle jerk and systolic time interval did not reveal any changes suggesting an increase in metabolic rate. The increase in heart frequency was not significant either. The significant rise in sex-hormone binding globulin was most probably associated with the weight reduction of 3.1 +/- 1.2 kg per week. In group II (on normal diet) bTSH and fT4 decreased significantly whereas TT4 decreased only insignificantly. As in group I, TT3 and fT3 rose significantly. Also in group II TRIAC did not cause alterations in the peripheral tissue parameters. In contrast to the obese group the volunteers in group II showed no significant rise in sex-hormone binding globulin and no reduction of body weight. Side effects such as nervousness, tremor or palpitations were not observed. Thus, TRIAC does not induce an increase in peripheral metabolic rate, not even under a TSH-suppressive dose as high as 3 x 1 mg per day.

201Tl myocardial SPECT and beta-endorphin levels in patients with suspected silent ischemia.

Today silent myocardial ischemia (SMI) is a well-recognized phenomenon. However, in the absence of clinical signs suggesting coronary artery disease (CAD), a streamlined diagnostic approach for precise clarification has proved to be difficult. Sensitivity and specificity of ergometric results are rather poor in symptom-free patients. Thus the question arises, whether the necessity of coronary angiography can be established more precisely by 201Tl myocardial SPECT in these patients. Treadmill exercise according to the Bruce protocol, 201Tl myocardial SPECT and coronary angiography were performed in a total of 106 patients with suspected SMI. In group I (high probability of ischemia; n = 46), reversible defects detected by SPECT correlated well with significant stenoses and irreversible defects with subtotal stenoses or complete occlusions. SPECT sensitivity in the detection of ischemia was 91%, its specificity 96%. In group II (low probability of ischemia; n = 60), SPECT sensitivity was as high as in group I (94%) but due to a high number of false-positive results (e.g. cardiomyopathy) specificity was only 75%. However, SPECT was superior to exercise ECG (sensitivity 70%; specificity 56%) in the detection of SMI. In addition, beta-endorphin levels were determined in 180 healthy subjects, 37 patients with symptomatic CAD and in 34 patients with SMI before and during maximum exercise. Exercise values in patients with SMI were significantly higher than in healthy subjects or in patients with symptomatic CAD.

Transient prealbumin-associated hyperthyroxinemia in TSH-producing pituitary adenoma.

This case report describes a 38-year-old male who was hospitalized for further clarification of clinically mild hyperthyroidism. His increased total hormone levels, the elevated free thyroid hormones and the elevated basal TSH with blunted response to TRH strongly suggested a pituitary adenoma with inappropriate TSH incretion. Transmission computed tomography showed an intrasellar expansion, 16 mm in diameter. The neoplastic TSH production was confirmed by an elevated alpha-subunit and a raised molar alpha-sub/TSH ratio. However, T4 distribution on prealbumin (PA, TTR), albumin (A) and thyroxine binding globulin (TBG) showed a clearly increased binding to PA (39%), indicating additional prealbumin-associated hyperthyroxinemia. The absolute values of PA, A and TBG were within the normal range. After removal of the TSH-producing adenoma, basal TSH, the free thyroid hormones and T4 binding to prealbumin returned to normal. Therefore, the prealbumin-associated hyperthyroxinemia had to be interpreted as a transitory phenomenon related to secondary hyperthyroidism (T4 shift from thyroxine binding globulin to prealbumin) rather than a genetically conditioned anomaly of protein binding.

Differentiation of lymph-node metastases by anti-CEA immunoscintigraphy in a patient with follicular thyroid and breast cancer.

Supraclavicular lymph node metastases appeared in a female patient six years after thyroidectomy, radioiodine therapy and external radiation for a follicular thyroid carcinoma and four years after mastectomy and lymphadenectomy for an invasive ductal breast cancer. It was not possible either by conventional imaging methods or by serological methods, to assign the metastases to one of the two primary tumors. Anti-CEA immunoscintigraphy and SPECT of the cervicothoracic region showed a circumscribed pathological uptake of 99mTc-labeled anti-CEA antibodies in the area of the supraclavicular lymph nodes. The preoperative suspicion of lymph-node infiltration by CEA-expressing breast cancer cells was confirmed histologically after surgical removal of the lymph nodes.

[Changes in zinc level in the serum, whole blood and erythrocytes in disorders of thyroid function]. / Veränderungen des Zinkspiegels im Serum, Vollblut und im Erythrozyten bei Schilddrüsen-Stoffwechselstörungen.

The zinc level in serum and whole blood was determined in a series of 121 patients, 20 suffering from overt hyperthyroidism, 34 with manifest hypothyroidism and a control group of 67 euthyroid subjects. The zinc content per deciliter of erythrocytes was calculated from the haematocrit. The hyperthyroid group revealed a highly significantly elevated serum zinc level (p less than 0.01), but a most significantly reduced zinc content in whole blood (p less than 0.001) in comparison with the euthyroid group. On the other hand, the reverse changes were observed in the hypothyroid group, i.e. a most significantly reduced serum zinc content (p less than 0.001) and a highly significantly increased zinc content in whole blood (p less than 0.01). These results suggest that the determination of zinc levels both in serum and in whole blood may be a useful additional parameter of peripheral thyroid hormone effect.

[Microcirculation in parenteral Ginkgo biloba extract therapy]. / Die Mikrozirkulation unter parenteraler Ginkgo-biloba-Extrakt-Therapie.

15 patients with arteriosclerotic lesions in the extracranial brain arteries, randomly selected, were treated with an infusion of 250 ml physiological NaCl and 25 ml Ginkgo biloba extract (Tebonin). A second group (n = 15) received 250 ml NaCl without drugs stimulating blood flow. The skin microcirculation was measured in vivo by means of a helium-neon laser at one of the 4 extremities. Perfusion increased significantly (p less than or equal to 0.01) in response to Ginkgo biloba extract als composed with the response in the control group. The results justify the administration of Ginkgo biloba extract in vascular diseases.

[Tl-201 myocardial SPECT in silent myocardial ischemia and angiographically proven coronary heart disease]. / Tl-201-Myokard-SPECT bei stummer Myokardischämie und angiographisch gesicherter koronarer Herzkrankheit.

Silent myocardial ischemia is defined as true myocardial ischemia without angina pectoris in patients with angiographically detected coronary artery disease. In this study 52 patients (46 male, 8 female: mean age 53 years) with a pathological exercise test but no symptoms were investigated. They showed stenosis of 75% or more of the diameter in at least one coronary segment on angiography. Prior to or after catheterization (within 14 days) Tl-201 SPECT was done and evaluated independently of angiography. A clear correlation between angiographically confirmed stenosis and reversible perfusion defects with Tl-201 SPECT was established (62 out of 76 lesions). Furthermore, there was a significant relation between angiographically detected subtotal or total occlusions of coronary vessels and irreversible perfusion defects using Tl-201 SPECT (35 in 44 lesions) (p less than 0.001). In patients with ST depression but without angina pectoris during the exercise test, the Tl-201 SPECT is highly suited to determine the hemodynamic effect of coronary stenoses.