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High prevalence of acquired von Willebrand's syndrome in patients with thyroid diseases undergoing thyroid surgery.

BACKGROUND AND OBJECTIVES: Various coagulation abnormalities occur in patients with thyroid diseases. These abnormalities range from subclinical laboratory findings to hemorrhage or thromboembolism. However, the prevalence of hemostatic abnormalities in patients with thyroid diseases is still unclear. DESIGN AND METHODS: Between January 1999 and December 2003, 1342 consecutive patients with various thyroid diseases who were candidates for thyroid surgery underwent preoperative screening of hemostatic parameters including prothrombin time, activated partial thromboplastin time and platelet-related hemostasis with the PFA-100 platelet-function analyzer. RESULTS: Thirty-nine patients (2.9%) had abnormalities of the coagulation screening tests. Of these, 35 patients had von Willebrand's disease (type 1 in 33 cases and type 2A in 2 cases), 2 patients had decreased platelet aggregability, and 2 patients had coagulation factor XI deficiency. As all patients with coagulation abnormalities responded to subcutaneous desmopressin injection (0.3 microg/Kg BW), this drug was successfully used as surgical prophylaxis. INTERPRETATION AND CONCLUSIONS: Up to 3% of patients with thyroid diseases undergoing thyroid surgery have coagulation abnormalities, in most cases resembling von Willebrand's disease. Coagulation screening tests are needed in order to identify those patients at increased risk of bleeding.

Adolescent↗

Selective embolization of thyroid arteries (SETA) as a palliative treatment of inoperable anaplastic thyroid carcinoma (ATC).

OBJECTIVES: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive solid tumors in humans. Despite intense application of multimodality of treatment with surgery and/or external beam radiotherapy and chemotherapy, the survival rates remain low--generally the mean survival is about six (6) months after diagnosis. Rapid development--particularly over the last decade--of interventional radiology, provides methodology that allows examining thyroid arterial embolization as an alternative approach to ablating thyroid tissue. The aim of the present study was to evaluate selective embolization of the thyroid arteries (SETA) as a possible alternative for the palliative treatment of advanced, inoperable ATC. PATIENTS AND METHODS: The study group comprised five (5) patients with advanced stage of inoperable ATC. All the patients underwent SETA of the superior and/or inferior thyroid arteries. SETA was performed using polyvinyl alcohol particles, ranging from 500-710 microm in diameter. After SETA, selective angiography of thyroid arteries was performed to ensure that the targeted arteries were completely occluded. CONCLUSIONS: The results of the present study suggest that SETA is minimally invasive and save method of palliative treatment of ATC and, as such, may be recommended in cases of intractable hemorrhage and pain caused by ATC progression.

Aged↗

Flow cytometry phenotypization of thyroidal lymphoid infiltrate and functional status in Hashimoto's thyroiditis.

OBJECTIVE: To evaluate the thyroidal lymphoid infiltrate (TLI) in thyroidal functional status (TFS) for differences among patients with Hashimoto's thyroiditis (HT). STUDY DESIGN: Flow-cytometry (FC) was applied to thyroidal fine-needle cytology samples in 57 patients. TLI was analyzed using a fluorescence-activated cell sorter (FACS) scan and fluorescence antibodies CD3, CD4, CD5, CD8, CD10, and CD19 and kappa and lambda light chains. TFS was determined by serum thyroid-stimulating hormone (TSH), FT3 and FT4 immunoassays, in specific clinical settings, to classify the cases as hyperthyroid, euthyroid and hypothyroid. FC assessment was then compared with the corresponding TFS. RESULTS: B-lymphocytes were present in 44 cases (77%). T-lymphocytes were present in all the cases; CD4/CD8 = 2:1 ratio was observed in 16 euthyroid, 1 hyperthyroid and 3 hypothyroid; CD4/CD8 > or = 3:1 ratio in 22 euthyroid, 2 hyperthyroid and 2 hypothyroid cases; CD4/CD8 < or = 1:1 ratio in 1 euthyroid, 3 hyperthyroid and in 7 hypothyroid cases. Grouping hyperthyroid and hypothyroid cases, a significant association was observed with the CD4/CD8 < or = 1:1 ratio (p < 0.01). CONCLUSION: Intrathyroidal CD4/CD8 < 1:1 ratio might be the expression of intense apoptosis in the early phases of HT, generally followed by the restoration of CD4/CD8 balance; persistence of increased intrathyroidal CD8 might be related to intense thyroidal damage and thus an increasing risk of hypothyroidism.

Adult↗

[Study of hormone replacement therapy following total thyroidectomy in thyroid cancer--with special reference to the analysis of thyroid hormone peripheral effects, using indirect calorimetry].

Peripheral effects of thyroid hormones were examined using an indirect calorimetry in 18 patients with thyroid cancer before and after total thyroidectomy. Peripheral effects of exogenous thyroid hormones in TSH-suppression therapy after thyroidectomy were also studied. The subjects were maintained without hormone replacement for 3 weeks after total thyroidectomy. The ratio of resting energy expenditure to basal energy expenditure (REE/BEE) was determined before operation, before hormone replacement, and 1 and 5 weeks after the beginning of replacement, and the values were compared with changes in the blood thyroid hormone levels. Positive correlations were observed between the changes in endogenous thyroid hormone levels before and after total thyroidectomy and those in REE/BEE (free T3 vs. REE/BEE; r = 0.756, p less than 0.01), suggesting that evaluation of REE/BEE is clinically useful as an index of peripheral effects of thyroid hormones. Five weeks after the beginning of hormone replacement, T4 and free T4 were slightly range, and no enhancement of energy metabolism was noted. From these findings, the post-operative TSH suppression therapy carried out at our department is considered to be justifiable also from the viewpoint of energy metabolism.

Adult↗

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.

Female↗

[Thyroid microsomal autoantibodies in thyroid disease: their value as an antigenic marker].

An autoimmune disease can be the cause of thyroid disfunction. Determination of autoantibodies titers is the best way of demonstrating its existence. We studied 172 thyroid patients (146 females, 26 males) with ages ranging from 15 to 81 years. Thyroid microsomal autoantibodies (TMA) were detected by a modified agglutination test (SERA-TEK kit, Ames Div); a dilution greater than or equal to 1/1600 was considered as diagnostic of autoimmune disease. Patients were classified according to morphological and functional status in 3 groups: GI = non toxic goiter, n = 98 (71 diffuse, 20 multi and 7 uninodular); GII = toxic goiter, n = 62 (52 diffuse, 4 multi, 2 uninodular and 4 subacute thyroiditis); G III = hypothyroidism, n = 12 (5 primary hypothyroidism and 7 chronic thyroiditis). A control group of 30 normal individuals, ages ranging from 19 to 85 years was also studied. Diagnostic titers of TMA were found in 30.8% of group I, 88.5% of group II, 91.6% of group III and only in 6.6% of controls. The high incidence of positive TMA in toxic diffuse goiter (96.1%) as well as in hypothyroid patients was expected since these are typical examples of thyroid autoimmune disease. In the non toxic goiter group, positive TMA were present in 50% of multinodular, 28% of uninodular and 25% of diffuse goiters and the incidence of positive TMA varied according to age, being higher over the age of 40 years and lower under the age of 20 years. We postulate that this unexpected high incidence of positive TMA in non toxic goiter is due to amelioration of chronic iodine deficiency inducing the expression of latent autoimmune disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

c-myc expression in the thyroid. I: Normal, adenomatous, and cancerous thyroid tissue.

Recent investigations have suggested that myc oncogene expression may be important in the development or progression of thyroid tumors. The purposes of the present study were to assess cellular (c)-myc expression in thyroid adenomas (n = 5), as well as in thyroid cancer (n = 4) and in normal thyrocytes (n = 7). Total RNA was prepared by extraction with guanididium thiocyanate and ultracentrifugation through a CsCl2 cushion. 30 micrograms total RNA was size fractionated on a 1% (w/v) agarose/formaldehyde gel and transferred to nylon membranes. These membranes were hybridized to a 32P-labelled third exon c-myc DNA. Following hybridization, blots were washed under high stringency and subjected to autoradiography; radioautographic bands were assessed visually or were quantitated by scanning densitometry. Nodular tissue had approximately the same degree of expression of the 2.4 Kb c-myc message as the surrounding normal tissue from the same gland (0.66 +/- 0.09 vs. 1.0 +/- 0.26, respectively); normal thyrocytes were capable in every instance of expressing the 2.4 Kb c-myc message. Thyroid cancer tissue expressed this message (0.91 +/- 0.17) but only at a level comparable to normal tissue. No other bands of hybridization were detected in any samples. We conclude that c-myc oncogene expression is comparable in normal thyrocytes and in thyroid nodules or thyroid cancer samples. These findings support a role for c-myc in both normal and neoplastic thyrocyte growth.

Adenoma↗

[Congenital piriformo-thyroid fistula as a cause of recurrent suppurative thyroiditis].

A previously healthy five year old boy presented with suppurative, febrile thyroiditis of the left lobe with pronounced general and local signs of inflammation, normal thyroid function and lack of thyroid antibodies. Intravenous antibiotic therapy improved the condition quickly. Six and nine months later however recurrent left lobe thyroiditis occurred. Endoscopic examination showed an internal fistula from the left piriform sinus to the left thyroidal lobe which was cut out. The case report confirms previous communications, that recurrent suppurative thyroiditis is nearly always caused by a piriform sinus fistula, probably a fourth pharyngeal pouch remnant which can be cured surgically.

Child, Preschool↗

[Physiopathological studies of thyroid function in the calf. 1. Diagnosis of thyroid function in the calf].

Clinico-chemical and radiometric methods, common in routine diagnosis in human medicine for in-vitro assessment of thyroid function, were tested for their applicability to calf. The assessment of protein-fixed iodine and of iodine extractable from stock, the thyroxine test, the tri-iodothyronine test, the tri-iodothyronine radio-immuno assay, and the effective thyroxine ratio test, basically, were applicable to diagnosis of thyroid function in calf. The thyrotrophin releasing hormone test, in conjunction with efforts to determine peripheral thyroid gland hormone concentration (in particular tri-iodothyronine), was also applicable to calf, although thyroid stimulation hormone with radio-immuno assay, another procedure in human medicine (specificity of thyroid stimulation hormone antibody), proved unsuitable for the determination of bovine thyroid stimulation hormone.

Animals↗

In vitro and in vivo reversal of thyroid epithelial polarity: its relevance for autoimmune thyroid disease.

A method is described for culturing intact human thyroid follicles, based on the study of 40 thyroidectomy specimens from normal (n = 18) and diseased glands (n = 22). Reversal of the normal polarity of thyrocytes, whereby the microvilli move from the colloid edge to the vascular pole of the cells, occurs gradually when the amount of fetal calf serum (FCS) is changed from 0.5% to 10%. The translocation of thyroid 'microvillar' antigens, (surface expression of 'microsomal' and a separate surface antigen) from the follicular to the vascular pole of thyrocytes was assessed by indirect immunofluorescence with human sera containing microsomal antibodies, as well as by electron microscopy. In normal and diseased thyroid glands up to 80% of follicles became reversed after 5-10 days in high FCS and the microsomal/microvillar antigen persisted for about twice as long as in monolayer cultures. Spontaneous reversal of polarity was observed in six of eight glands from patients with Graves' thyrotoxicosis or toxic nodular goitre in freshly dispersed tissues or after 2 days in 0.5% FCS, unlike normal tissues where only a trace of reversal appeared after 7 days of culture under these conditions. It is postulated that polarity reversal may play a role in human thyroid autoimmunity as the normally secluded 'microvillar' antigens becomes transposed to the vascular pole of thyroid follicles where they are in direct contact with cytotoxic antibodies or sensitized immunocytes. This could initiate lesions in intact follicles. Inappropriate HLA-DR expression on thyrocytes, either stimulated by phytohaemagglutinin (PHA) or appearing spontaneously as an early marker of thyroiditis, did not correlate with reversal of polarity.

Antigens, Surface↗

Incidence of thyroid cancer in women in relation to previous exposure to radiation therapy and history of thyroid disease.

Female residents of 13 counties of Western Washington, in whom papillary, follicular, or mixed papillary-follicular thyroid carcinomas had been diagnosed between 1974 and 1979 were interviewed regarding their medical and reproductive histories and past exposure to radiation treatments. For comparison, a random sample of women from the same population was interviewed. Women who had received radiation treatments to the head or neck prior to 5 years before interview were 16.5 times (95% confidence interval = 8.1-33.5) more likely than unexposed women to develop cancer. The relative risk (RR) was highest for papillary cancer (19.4) but also was elevated substantially for follicular and mixed papillary-follicular tumors. Women first irradiated at age 19 years or younger had a much higher RR than did women irradiated at age 20 or older. Regardless of prior radiation exposure, women who ever had had a goiter were at increased risk of developing thyroid cancer. Women who had ever developed a goiter had 17 times the risk of developing follicular cancer and almost 7 times the risk of developing papillary cancer as compared with women who never had had a goiter. Risk of thyroid cancer was elevated even among women who had had a history of goiter many years prior to diagnosis. A history of thyroid nodules was also a risk factor for papillary and mixed thyroid cancer. Neither a history of hypothyroidism nor hyperthyroidism was found to increase the risk of thyroid cancer.

Adolescent↗

Natural cytotoxicity of blood mononuclear cells from normal subjects and patients with Hashimoto's thyroiditis against normal thyroid cells.

Natural cytotoxicity of human blood mononuclear cells against dog thyroid cells grown in monolayer was investigated. Cytotoxicity was assessed as specific release of 51Cr from Na51CrO4 labelled thyroid cells. The effector cells were unfractionated blood mononuclear cells prepared by Hypaque-Ficoll gradient centrifugation. Killing of dog thyroid cells by peripheral blood mononuclear cells from normal subjects was demonstrated. This was time and effector: target cell ratio dependent. Killing by peripheral blood mononuclear cells from patients with Hashimoto's thyroiditis was similar to that for normal subjects although increased killing was demonstrated in 2 patients and decreased killing in 2 patients. A possible role of natural cytotoxicity against thyroid cells in thyroid autoimmunity is discussed.

Adult↗

Microparticle-enhanced nephelometric immunoassay of anti-thyroid peroxidase autoantibodies in thyroid disorders.

Crude thyroid peroxidase extracted from human thyroid microsomes was covalently bound onto polyacrylic and polyfunctional copolymerized microparticles. We observed agglutination of the thyroid peroxidase-microparticle conjugate with 13 monoclonal antibodies (mAbs) specific for epitopes on four different antigenic domains of human thyroid peroxidase (TPO; EC 1.11.1.7), after addition of anti-mouse immunoglobulins. We quantified agglutination by measuring with a specially designed nephelometer the light scattered by the conjugates. This allowed us to develop a microparticle-enhanced nephelometric immunoassay for human anti-TPO autoantibodies (aAbs) with defined epitopic specificity, based on the ability of aAbs to inhibit mAb-induced agglutination. Applied to patients with autoimmune thyroid diseases, this assay confirmed the polyclonality of anti-TPO aAbs and their preferential reactivity toward epitopes located on the A and B antigenic domains of the TPO molecule. The same specificities seem to be present in patients with Hashimoto thyroiditis or Graves disease.

Autoantibodies↗

[Postpartum thyroiditis and the contribution of ultrasonographic examination of the thyroid gland in its diagnosis during the first half-year after delivery].

Changes which take place in the thyroid parenchyma of the mother from postpartum thyroiditis and which lead to a change of echogenicity can be detected by ultrasonographic examination of the thyroid gland before clinical manifestation of impaired thyroid function caused by inflammation. The authors evaluated the echogenicity of the thyroid gland in 60 women three months after delivery. From the whole group of women 47 (78.4%) had a homogenous and adequate echogenicity, 13 (21.6%) had a reduced echogenicity. A positive cytological finding, i.e. lymphocytic infiltration was found in 9 women and concurrently positive antithyroglobulin antibodies in 5 of them. During the first six months after childbirth impaired thyroid function was recorded in 4, i.e. 6.6%: 1x hyperthyroidism and 3x hypothyroidism.

Female↗

Thyroid hormones and autoantibodies in pregnant patients with thyroid diseases.

Serum concentrations of thyroid stimulating hormone (TSH) and thyroid autoantibodies in pregnant patients with thyroid disease at various stages of pregnancy were determined by in-house ELISAs. In normal pregnancy, serum TSH levels were significantly elevated (p < 0.05) from 13 weeks of gestation. The normal reference ranges for TSH for the second (0.6-5.0 mIU/l) and third trimester (0.6-5.6 mIU/l) were significantly higher (p < 0.05; p < 0.01 respectively) compared to 0.4-4.5 mIU/l for the first trimester. In pregnant thyroid patients, serum TSH levels correlated highly (p < 0.001) to T4 (r = 0.740), FT4I (r = 0.683) and MicAb (microsomal antibodies) (r = 0.825) but weaker (p < 0.01) to T3 (r = -0.512), FT3I (r = 0.520) and TgAb (thyroglobulin antibodies) (r = 0.618). Thus, measurement of TSH with the highly sensitive ELISA (enzyme linked immunosorbent assay) would form a useful first line test for thyroid dysfunction in pregnancy while measurement of thyroid autoantibodies would aid in the diagnosis of autoimmune hypothyroidism.

Adult↗

Thyroid surgery in untreated severe hyperthyroidism: perioperative kinetics of free thyroid hormones in the glandular venous effluent and peripheral blood.

BACKGROUND AND METHODS: It is generally believed that thyroid surgery in Graves' disease requires a euthyroid state to avoid thyrotoxic reactions. We carried out a prospective study on 23 patients who had severe hyperthyroidism with free thyroid hormone concentrations (fT3 or fT4) exceeding the upper normal boundary by 300% or more and who were not pretreated with thyrostatic agents. We determined hormone levels during operation in the thyroid venous effluent before and after surgical trauma and monitored their postoperative elimination kinetics. RESULTS: The concentration of fT3 and fT4 in the venous effluent of the hyperactive gland did not exceed the peripheral levels. Surgery did not induce any intraoperative or postoperative increase in fT4 or fT3, whereas thyroglobulin concentrations rose sharply. Both fT4 and fT3 followed biphasic elimination kinetics, and a significant decline of circulating free hormone concentrations was measurable within the first postoperative hour. CONCLUSIONS: Contrary to widely held assumptions, the surgical trauma does not stimulate the release of thyroid hormones. Hence this mechanism cannot account for the postoperative development of thyroid storm. Our observations imply that immediate operation should generally be considered for the emergency treatment of an imminent thyroid storm.

Adult↗

[A case of postpartum silent thyroiditis misapprehended as malignant lymphoma of the thyroid].

A case of postpartum silent thyroiditis misapprehended as malignant lymphoma of the thyroid is reported. The patient was a 30-year-old female who had received irradiation therapy to the neck for malignant lymphoma 9 years ago. She was referred to our department owing to a struma accompanying rapid aggravation of chronic thyroiditis after delivery. The mechanism of this case was possible to be explained by immune rebound theory. It was difficult to make differential diagnosis of this case from malignant lymphoma of the thyroid clinically and cytologically when immune rebound phenomena with invasion of lymphocyte and appearance of lymph follicle were the strongest. Immune state of the patients with chronic thyroiditis accompanied by morphological change should be taken into consideration in the process of making diagnosis of malignant lymphoma of the thyroid.

Adult↗

[Quantitative image feature analysis of echographic textures using the normalized first moment of the power spectra: comparison of normal thyroid with chronic thyroiditis].

In order to evaluate the coarseness of echographic textures objectively, ultrasonic B-mode data from the thyroid glands in 10 normal subjects and 10 patients with chronic thyroiditis were digitized. The normalized first moment of the power spectra in the digitized matrix data that were obtained was calculated by computer processing of a Fourier transformation algorithm. On phantom study, when the location of the region to be analyzed or the gray scale level of the images was changed, the normalized first moment of the power spectra in the low frequency region of less than 1.0 cycle/mm varied significantly, and noise components in the high frequency region of more than 2.5 cycles/mm exceeded the signal components. Thus we attempted to calculate the normalized first moment of the power spectra from 1.0 to 2.5 cycles/mm in human thyroid glands. The values of the normalized first moment of the power spectra in the thyroid glands with normal (n = 20) and chronic thyroiditis (n = 20) were 0.989 +/- 0.036 and 1.065 +/- 0.063, respectively. These values were significantly different between the two groups (p < 0.01). It is concluded that the normalized first moment of the power spectra calculated within the limited frequency is useful in characterizing the echographic texture of chronic thyroiditis.

Chronic Disease↗