TSH Receptor Antibody Levels Research Articles

Chorea, convulsive seizures and cognitive impairment in a patient with autoimmune thyroid disease

Chorea and convulsive seizures are rare consequences of hyperthyroidism [1, 2]. We describe the case of such manifestation of autoimmune thyroid disease. In 2003, a 23-year-old woman presented with the first symptoms of hyperthyroidism—palpitations, weight loss and exercise intolerance. TSH and fT4 concentrations were 0.01 μIU/ml and 43 pmol/l, respectively (norm: TSH 0.35–4.9 μIU/ml, fT4 11.5–23.2 pmol/l). The patient was treated with thiamazole in tapering doses (from 60 to 10 mg per day). After 2 months, hypothyreosis was observed and thiamazole was withdrawn. 2 weeks later, the signs of thyrotoxicosis and involuntary movements of the left extremities appeared. Hyperthyreosis was verified (fT4 87.3 pmol/l) and treatment with propylothiouracil (600 mg per day) was initiated. Neurological examination confirmed left-sided hemichorea. Elevated levels of TSH receptor antibodies (TRAb) and thyroperoxidase autoantibodies (TPO Ab) were documented: 16.7 and 257.5 IU/ml, respectively (norm: 0.1–1.22 IU/ml and <60 IU/ml, respectively). Biopsy specimen of the thyroid showed lymphocytic infiltration, typical of lymphocytic thyroiditis. The patient had no family history of neurological disorders or dementia syndromes. Ceruloplasmin and copper concentrations were normal, similar to anticardiolipin, antistreptolysin O, and anti-neutrophil cytoplasm antibodies. Antinuclear and anti-double-stranded DNA antibodies were negative. Cerebrospinal fluid examination and MRI of the brain were normal, and borreliosis and toxoplasmosis were ruled out based on immunological examination of serum and cerebrospinal fluid. EEG revealed slight changes in the posterior temporal and occipital leads: theta waves and isolated sharp waves, predominantly in the right hemisphere, along with slight changes of paroxysmal character in the frontal and anterior temporal leads. Haloperidol (6 mg per day) and thioridazin (50 mg per day) were administered. fT4 concentrations diminished (28.7 pmol/l) and choreic movements considerably subsided. Treatment with a maintenance dose of thiamazole was continued. Prednisone (60 mg per day, with 5 mg reduction every week) was administered. The dosages of neuroleptics were reduced and finally withdrawn. Choreic movements diminished gradually to disappear completely within 6 weeks. The return of chorea has not been observed so far. For over a year, during treatment with thiamazole (2.5 mg per day), the patient was euthyroid. In October 2005, in the first trimester of pregnancy, symptoms of thyreotoxicosis were once again reported. TSH and fT4 concentrations were 0.02 μIU/ml and 51.73 pmol/l, respectively. Thiamazole was withdrawn and propylothiouracil (initially 150 mg per day) was administered. It was withdrawn in the third trimester, when serum fT4 decreased to 14.7 pmol/l. 3 months after the delivery, signs of hyperthyreosis were observed (fT4 = 41.7 pmol/l), and treatment with propylothiouracil (150 mg/day) was reinstated. In October 2006, the patient presented with generalized tonic–clonic convulsive seizures, loss of consciousness and retrograde amnesia. fT3 and fT4 concentrations were elevated (20.11 pg/ml and 5.19 ng/dl, respectively; norm: 1.71–3.71 pg/ml and 0.71–1.85 ng/dl, respectively). Laboratory tests and MRI of the brain were normal. Antithyroid treatment was intensified and the patient became euthyroid in December 2006. TPO Ab and anti-thyroglobulin antibodies (Tg Ab) were elevated (872.7 and 194.8 IU/ml, respectively; norm <60 IU/ml). In June 2008, the patient underwent treatment with radioactive iodine 131I (150 MBq). Between January 2009 and August 2010, the patient was euthyroid and did not receive any pharmacotherapy. During this period of time, she started to suffer from depression, difficulties with her memory, and sleep disturbances. Psychological examination confirmed mild cognitive impairment and mood disorder. Single-photon emission computed tomography of the brain showed slight global hypoperfusion in both cerebral hemispheres, and an unilateral reduction in the regional blood flow of the left parietal lobe, left temporal lobe and left insula. MRI of the brain was normal. EEG revealed slight changes in frontal and temporal leads in the form of theta waves and isolated sharp waves, accompanied by minor paroxysmal features observed in the posterior temporal and occipital leads. In January 2010, levels of TPO Ab were still elevated (324 IU/ml), while TG Ab and TRAb were normal. In August 2010, subclinical hypothyreosis was diagnosed (TSH 6.13 μIU/ml, fT4 1.36 ng/dl) and treatment with l-thyroxin (25 μg/day) was initiated. Cognitive function deterioration has not been observed thus far. The pathophysiological mechanism underlying hyperthyroidism-induced chorea is unclear. In most reported cases, choreoathetosis was observed during thyreotoxic states, and one cannot exclude autoimmune mechanisms underlying the chorea [2, 3]. Morphological changes in the basal ganglia are another potential cause of chorea in patients with hyperthyroidism [3]. Seizures are one of the clinical features of encephalopathy associated with autoimmune thyroiditis, often termed Hashimoto’s encephalopathy. The exact pathomechanism of this disease is still not fully understood. Its neurological symptoms can result from autoimmune inflammation of minute cerebral vessels, with the involvement of anti-TPO antibodies [4]. Hereby, presented case illustrates that cognitive impairment may be an unusual consequence of autoimmune thyroid disease, and thyroid function should be examined in subjects with encephalopathy, chorea and seizures.

Is the measurement of inferior thyroid artery blood flow velocity by color-flow Doppler ultrasonography useful for differential diagnosis between gestational transient thyrotoxicosis and Graves' disease? A prospective study

OBJECTIVE:To determine the role of peak systolic velocity, end-diastolic velocity and resistance indices of both the right and left inferior thyroid arteries measured by color-flow Doppler ultrasonography for a differential diagnosis between gestational transient thyrotoxicosis and Graves' disease during pregnancy.METHODS:The right and left inferior thyroid artery-peak systolic velocity, end-diastolic velocity and resistance indices of 96 patients with thyrotoxicosis (41 with gestational transient thyrotoxicosis, 31 age-matched pregnant patients with Graves' disease and 24 age- and sex-matched non-pregnant patients with Graves' disease) and 25 age- and sex-matched healthy euthyroid subjects were assessed with color-flow Doppler ultrasonography.RESULTS:The right and left inferior thyroid artery-peak systolic and end-diastolic velocities in patients with gestational transient thyrotoxicosis were found to be significantly lower than those of pregnant patients with Graves' disease and higher than those of healthy euthyroid subjects. However, the right and left inferior thyroid artery peak systolic and end-diastolic velocities in pregnant patients with Graves' disease were significantly lower than those of non-pregnant patients with Graves' disease. The right and left inferior thyroid artery peak systolic and end-diastolic velocities were positively correlated with TSH-receptor antibody levels. We found an overlap between the inferior thyroid artery-blood flow velocities in a considerable number of patients with gestational transient thyrotoxicosis and pregnant patients with Graves' disease.CONCLUSIONS:This study suggests that the measurement of inferior thyroid artery-blood flow velocities with color-flow Doppler ultrasonography does not have sufficient sensitivity and specificity to be recommended as an initial diagnostic test for a differential diagnosis between gestational transient thyrotoxicosis and Graves' disease during pregnancy.

Severe Graves' Ophthalmopathy After Percutaneous Ethanol Injection in a Nontoxic Thyroid Nodule

Percutaneous ethanol injection (PEI) is used to treat cystic or mixed benign thyroid nodules. This treatment can result in rare complications, and three cases of Graves' disease (GD) without Graves' ophthalmopathy (GO) have been reported after PEI treatment of toxic thyroid adenomas. Here we present a 55-year-old male patient who developed GD and severe GO after PEI treatment of a mixed cystic-solid, nontoxic thyroid nodule. Six months after PEI, the nodule volume had decreased from 8.9 to 3.0 mL, but we observed severe hyperthyroidism with elevated serum free triiodothyronine, free thyroxine, and thyrotropin receptor antibody levels. We also observed ophthalmopathy with symmetrical orbit and soft tissue involvement (grade b/c) and a clinical activity score of 4/7. The diagnosis of GO was confirmed by bilateral corneal damage, increased intraocular pressure on upgaze, and inconstant diplopia. A computed tomography scan showed that the inferior, medial, and superior extraocular muscles were bilaterally enlarged, the perineural space at the orbital cone was slightly reduced and the ophthalmic vein was congested. A cause-effect relationship between PEI and GD/GO was likely in this patient because of the temporal sequence. Although the mechanism was unknown, we speculated that the thyroid tissue damage caused by PEI released a large amount of antigenic materials from follicular thyroid cells, including thyrotropin receptor protein, which triggered the autoimmune inflammatory response against the thyroid itself and the orbital soft tissues. The patient did not have any risk factors for either GD or GO. This observation raises the concern, therefore, that unpredictable and severe complications, such as GD and GO, may occur in a few patients treated with PEI.

Development of Thyroid Dysfunction and Autoantibodies in Graves' Multiplex Families: An Eight-Year Follow-Up Study in Chinese Han Pedigrees

This 8-year follow-up study is aimed at determining the relapse and development of Graves' disease (GD) and the potential risk factors that could be associated with the development of thyroid dysfunction and autoantibodies in Chinese pedigrees. Fifty-four Chinese Han GD pedigrees (322 members) were recruited in 2000. Forty-five pedigrees (263 members) were followed up. Their clinical and laboratory characteristics and fasting urinary iodine were measured with the same method at the two time points. We found that the mean age for onset of GD in offspring was much younger than that of their parents (p=0.013). At baseline, the prevalence of hyperthyroidism, hypothyroidism, and subclinical hypothyroidism in first-degree relatives were 5.5%, 1.6%, and 1.1%, respectively. Individuals with thyroid dysfunction were positive for thyroid autoantibodies. The prevalence of positive thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), or TSH receptor antibody (TRAb) in the first-degree relatives with euthyroidism in these pedigrees was 18.6%, 17.4%, or 56.9%, respectively. At follow-up, individuals with positive TPOAb were at risk of developing thyroid dysfunction, whereas patients with positive TRAb had increased risk for relapse even after drug treatment. The percentage of nonsmokers with positive TPOAb and TgAb was significantly higher than that of smokers (p<0.05), but the levels of serum TRAb were significantly higher in smokers at follow-up than baseline (p<0.01). Genetic factors are crucial for the development of autoimmune thyroid disease (AITD), thyroid dysfunction, and the outcomes of Graves' patients following treatment with medicines. Although smoking was negatively associated with the presence of thyroid antibodies (TPOAb/TgAb), smoking may induce or aggravate GD.

Immune effect of propylthiouracil and methimazole in the treatment of Graves' disease

Objective To observe the changes in TSH receptor antibody (TRAb) and soluble intercellular adhesion molecule-1 ( sICAM-1 ) levels after treatment of propylthiouracil ( PTU ) and methimazole( MMI ) in patients with Graves' disease (GD). Methods One hundred and six cases of clinically diagnosed patients with GD were divided into PTU and MMI groups( each group, n =53 ). The patients in two groups were regularly followed for 36 months. TRAb and sICAM-1 were measured with ELISA method. Results( 1 ) The general data of two groups were not significantly different before treatment( all P＞0. 05 ). ( 2 ) There was no difference in TRAb positive rates between two groups before treatment. The clinical remission rates between PTU and MMI groups showed no difference (83.02％ vs88.68％ ). The cure rate was higher in MMI group than in PTU group( 58.49％ vs 37.74％, P＜ 0. 05 ). (3) There existed significant differences in TRAb levels determined before and 6, 12, 24,30, and 36 months after treatment( all P＜0. 01 ), being gradually decreased with time( F=275.48 ,P＜0.01 ). TRAb levels between two groups were significantly different( F=5.86, P＜0. 05 ). (4) sICAM-1 levels at 36 months after treatment compared with the baseline in both groups were statistically different (P＜0. 01 ), but no difference was found between two groups. ConclusionsBoth PTU and MMI improve the immune status of patients with GD, and the immunosuppressive effect of methimazole is more evident. Key words: Propylthiouracil; Methimazole; TSH receptor antibody ; Soluble intercellular adhesion molecule-1

Thyroid dermopathy and acropachy

Graves’ disease is an autoimmune condition with extrathyroidal immune-mediated manifestations, including ophthalmopathy and dermopathy. Dermopathy, or pretibial myxedema, typically occurs in patients with ophthalmopathy. The presence of high levels of thyrotropin receptor antibodies indicates a more severe autoimmune process. Diagnosis is on recognition of clinical features; skin biopsy may be needed in some cases. One in four patients with thyroid dermopathy, usually occurring in the pretibial area, has acropachy and digital clubbing. Localization to the pretibial area is most likely due to dependency and mechanical factors. Rarely, upper body involvement occurs, usually triggered by trauma. Mild cases resolve over time. Moderate or severe cases require local corticosteroid therapy. Severe cases, including elephantiasis, are usually persistent and mimic lymphedema.

Observing pretibial myxedema in patients with Graves' disease using digital infrared thermal imaging and high-resolution ultrasonography: for better records, early detection, and further investigation

Pretibial myxedema (PM) is a manifestation of Graves' disease (GD). Currently, its diagnosis depends on physicians' observation and biopsy. No satisfactory, objective, and non-invasive tool is available to record and investigate lesions. Digital infrared thermal imaging (DITI) detects surface temperature, and sonography reflects composition changes in soft tissue. This study was aimed to observe changes in DITI and sonography in PM, and to evaluate their clinical usefulness. Nineteen GD patients with PM, 22 GD patients with mild diffuse non-pitting edema over lower legs, 46 GD patients with normal appearance of lower legs, and 14 normal volunteers were recruited for observation with DITI; 8, 21, 21, and 11 of them respectively also received soft tissue sonography for investigating the pathogenesis of DITI change. Lower leg temperatures of normal volunteers decreased gradually from proximal to distal parts. In all 19 patients with PM, DITI showed abnormally low focal temperatures over the lesions. In GD patients with mild diffuse non-pitting edema and GD patients with normal appearance of lower legs, DITI showed abnormally low focal temperature in 90.9 and 65.2% of the patients respectively. Areas of clinically visible PM and low focal temperature detected by DITI were sonographically characterized with increased skin thickness, hypoechoic substance deposition in the cutaneous tissue, and blurred boundary lines between dermis and subcutaneous tissue. TSH receptor antibody level correlated positively and significantly with skin thickness change and adjusted temperature difference between the center of temperature defect and the surrounding skin (P=0.046 and 0.033 respectively). By using DITI and sonography, we detected characteristic changes in PM. These techniques are helpful in recording and may be useful tools to detect early changes of PM.

Persistent high TRAb values during pregnancy predict increased risk of neonatal hyperthyroidism following radioiodine therapy for refractory hyperthyroidism

Serum levels of TSH receptor antibody (TRAb) often increase after radioiodine treatment for Graves' disease, and high-serum levels of maternal TRAb in late pregnancy indicate a risk of neonatal hyperthyroidism. The aim of this retrospective study is to investigate the characteristics of Graves' women who had a history of radioiodine treatment for intractable Graves' disease, and whose neonates suffered from hyperthyroidism. The subjects of this study were 45 patients with Graves' disease who became pregnant during the period from 1988 to 1998 after receiving radioiodine treatment at Ito Hospital. 25 of the 45 subjects had had a relapse of hyperthyroidism after surgical treatment for Graves' disease. 19 pregnancies were excluded because of artificial or spontaneous abortion. In the remaining 44 pregnancies of 35 patients, neonatal hyperthyroidism developed in 5 (11.3%) pregnancies of 4 patients. Serum levels of TRAb at delivery were higher in patients whose neonates suffered from hyperthyroidism (NH mother) than those of patients who delivered normal infants (N mother). Furthermore, serum levels of TRAb in NH mother did not change during pregnancy, although those of 4 patients of N mother, in which serum levels of TRAb before radioiodine treatment were as high as in NH mother, decreased significantly during pregnancy. In conclusion, women who delivered neonates with hyperthyroidism following radioiodine treatment seem to have very severe and intractable Graves' disease. Persistent high TRAb values during pregnancy observed in those patients may be a cause of neonatal hyperthyroidism.

Isotretinoin Influences Pituitary Hormone Levels in Acne Patients

Besides suppressing sebum production, the exact mechanism of action of isotretinoin in acne vulgaris is not known. Several hormones have been linked to the pathogenesis of acne. In this study, we investigated the effects of isotretinoin on the pituitary-adrenal axis, whose activity may be increased in acne. Various hormone systems were evaluated before and after 3 months of isotretinoin treatment in 47 acne patients. Free triiodothyronine (T3), thyroid-stimulating hormone and thyroid-stimulating hormone receptor antibody levels decreased significantly during isotretinoin treatment (p < 0.001, p < 0.02 and p < 0.02, respectively), as did those of luteinising hormone, prolactin and total testosterone (p < 0.005), as well as morning cortisol and adrenocorticotropic hormone (p < 0.005 and p < 0.05, respectively). We conclude that isotretinoin causes mild suppression of pituitary hormone levels, which may be beneficial for tackling the pathogenesis of acne.

Drug discontinuation after treatment with minimum maintenance dose of an antithyroid drug in Graves' disease: a retrospective study on effects of treatment duration with minimum maintenance dose on lasting remission

According to the guideline issued by the Japan Thyroid Association in 2006 for treatment of Graves' disease, discontinuing antithyroid drug (ATD) therapy is recommended when serum free thyroxine (FT4) and thyroid stimulating hormone (TSH) concentrations have been maintained within the reference range for a certain period after treatment with one ATD tablet every other day (minimum maintenance dose therapy, MMDT). In this retrospective study, the relationship between MMDT duration and remission rate was investigated. The participants were 107 consecutive patients with Graves' disease whose ATD therapy was stopped according to the guideline. Serum FT4, TSH, and TSH receptor antibody (TRAb) levels were measured when ATD was discontinued and every 3 months thereafter. The percentage of patients in remission was 86.9% at 6 months, 73.8% at 1 year, and 68.2% at 2 years after ATD discontinuation. The remission rate increased with MMDT duration, being significantly higher in patients with MMDT durations of 19 months or more than those with MMDT durations of 6 months or less. In patients with MMDT durations of 6 months or less, the remission rate was significantly lower in TRAb-positive patients than in TRAb-negative patients at the time of withdrawal of ATD; however, this was not observed in patients with MMDT durations of 7 months or more. These findings suggest that in patients who discontinue ATD after a certain MMDT duration, the remission rate increases as the MMDT duration increases, and ATD should not be discontinued in TRAb-positive patients with MMDT durations of 6 months or less.

Qualitative and Quantitative Impact of Protective Glucocorticoid Therapy on the Effective 131I Half-Life in Radioiodine Therapy for Graves Disease

This aim of this retrospective study was to determine the impact of glucocorticoid therapy on the effective (131)I half-life in radioiodine therapy for Graves disease. Three hundred fifteen consecutive Graves disease patients undergoing radioiodine therapy at our institution between August 2004 and January 2009 were enrolled. We investigated the influences of thyroid state (hypothyroidism, euthyroidism, hyperthyroidism), antithyroid drug dose before (131)I therapy, thyroid-stimulating hormone receptor antibody (TRAb) level, and qualitative and quantitative factors of prednisolone therapy on the effective (131)I half-life, applying univariate (paired t test) and multivariate (multiple-regression) analyses. Multivariate analyses revealed independent significant effects of the thyroid metabolic state (P = 0.004), antithyroid drugs (P < 0.001), presence of TRAb (P = 0.004), and glucocorticoids (P = 0.046) on thyroidal radioiodine half-life. Compared with euthyroidism, thyrotoxicosis and hypothyroidism reduced the effective half-life; high doses of antithyroid drugs and high TRAb levels had the same effect. Also, glucocorticoid therapy shortened the effective thyroidal radioiodine half-life in a dose-dependent manner. Pharmacologically, this effect is attributable to the prednisolone-induced increase of renal plasma (131)I clearance and the resulting reduction of plasma (131)I available for reuptake into the thyroid during radioiodine therapy. Oral treatment with prednisolone results in a reduction of effective thyroidal (131)I half-life in Graves disease, especially at higher doses.

The significance of changes in thyrotropin receptor antibody and soluble intercellular adhesion molecule-1 levels in patients with thyroid-associated ophthalmopathy during intravenous methylprednisolone pulse treatment

Objective To explore the relationship of thyrotropin receptor antibody (TRAb) and soluble intercellular adhesion molecule-1 ( sICAM-1 ) in patients with thyroid-associated ophthalmopathy ( TAO), and the role played by TRAb and sICAM-1 in the pathogenesis of TAO. Method Twenty-three TAO patients were assigned to groups according to the clinical activity score and EUGOGO. All patients were treated with intravenous methylprednisolone pulse. The levels of serum TRAb and sICAM-1 were evaluated by a competitive radioimmunoassay and enzyme-linked immunosorbent assay respectively before treatment and by the end of each methylprednisolone pulse. Results The differernce in serum TRAb levels was associated with activity scores of TAO (P=0. 020). The change in serum sICAM-1 was associated with durations of TAO ( P = 0.015). During methylprednisolone treatment in active TAO patients, the levels of TRAb kept on decreasing gradually and markedly declined after the third methylprednisolone pulse in active TAO patients (P＜0.05). The trends of changes in serum TRAb and sICAM-1 levels were both different in active and inactive TAO patients by tendency analysis. Conclusion TRAb level was related to the activity of TAO and might serve as a significant predictor of response to methylprednisolone therapy. The negative correlation between sICAM-1 levels and duration of TAO corroborates the role played by ICAM-1 during the early stage of TAO. Higher sICAM-1 levels are not expected to be specific to TAO and may not predict a response to methylprednisolone therapy. Key words: Thyroid-associated ophthalmopathy; Thyrotropin receptor antibody; Soluble intercellular adhesion molecule-1

Risk Factors for Development or Deterioration of Graves' Ophthalmopathy

Graves' ophthalmopathy (GO) significantly impairs the quality of life of affected individuals and the most severe cases can be sight threatening. Given the limited therapeutic options, a strong emphasis should be placed on disease prevention to diminish the significant morbidity associated with this disease. GO is most prevalent in women and most severe in men. Although some genetic differences between GO patients and Graves' disease patients without ophthalmopathy have been identified, none of the polymorphisms identified to date impart a high enough risk of GO to justify genetic testing to guide therapy or preventive strategies. Poorly defined mechanical factors that appear also to play a role in GO susceptibility will likely be better elucidated with advances in imaging techniques. Tobacco smoking has been consistently linked to development or deterioration of GO. Smokers who receive radioactive iodine have the highest incidence of unfavorable GO outcome, which is proportional to the number of cigarettes smoked per day. Several studies have reported an association between radioactive iodine treatment for Graves' disease and worsening or development of GO. Observational studies suggest that the same appears to be true for thyroid dysfunction, including both hyper- and hypothyroidism. While thyrotropin receptor antibody levels appear to be useful in predicting the course of disease and response to therapy, it is not known whether they are predictive of GO development. The puzzling scenarios of euthyroid or clinically unilateral GO, the large number of nonsmoking GO patients, and the occasional development of GO years after thyroid dysfunction has been treated all underline the multifactorial etiology of this disorder in which no single factor determines the clinical outcome. GO appears to have a complex genetic basis with multiple susceptibility alleles that act in combination with nongenetic factors to contribute to disease expression.

Color-Flow Doppler Sonography in Patients with Subclinical Thyroid Dysfunction

To assess the value of color-flow Doppler sonography (CFDS) in evaluating intrathyroidal blood flow and velocity in patients with subclinical thyroid dysfunction. In this prospective study, patients with subclinical hypothyroidism, patients with subclinical hyperthyroidism, and euthyroid patients without known thyroid autoimmune disease who served as controls were included. Subclinical thyroid dysfunction was defined as normal se-rum free thyroxine (FT4) and free triiodothyronine (FT3) in the presence of high (subclinical hypothyroidism), or low-suppressed (subclinical hyperthyroidism) serum thyrotropin (TSH) levels. Serum FT4, FT3, TSH, and antibodies to thyroid peroxidase and thyroglobulin were measured in all participants. In addition, TSH receptor antibody levels were determined in patients with subclinical hyperthyroid-ism. All participants underwent conventional sonography and CFDS. Mean peak systolic velocity (PSV) and resistive index were obtained from multiple extranodular thyroid parenchyma samplings and inferior thyroid artery measurements. The study population included 27 patients with subclinical hypothyroidism, 15 patients with subclinical hyperthyroidism, and 20 euthyroid patients. Patients with subclinical hypothyroidism had significantly higher mean intrathyroidal PSV values than control patients (19.9 +/- 5.6 cm/s vs 15.7 +/- 4.4 cm/s; P = .008), whereas patients with subclinical hyperthyroidism had significantly higher mean PSV values than control patients at the inferior thyroid artery level (29.7 +/- 10.7 cm/s vs 21.9 +/- 6.8 cm/s; P = .014). Compared with control patients, a greater proportion of patients with subclinical hypothyroidism and patients with subclinical hyperthyroidism had marked CFDS patterns (78% vs 15% [P<.001] and 53% vs 15%; [P<.001], respectively). A significant association was found between positivity for thyroid autoantibodies and intense CFDS patterns. No correlation was found between TSH or thyroid hormone levels and CFDS pattern or blood flow velocity. We have demonstrated that significantly increased thyroid blood flow velocity and vascularity are already present in patients with mild thyroid dysfunction.

Different fetal-neonatal outcomes in siblings born to a mother with Graves-Basedow disease after total thyroidectomy: a case series

IntroductionWe describe three different fetal or neonatal outcomes in the offspring of a mother who had persistent circulating thyrotropin receptor antibodies despite having undergone a total thyroidectomy several years before.Case presentationThe three different outcomes were an intrauterine death, a mild and transient fetal and neonatal hyperthyroidism and a severe fetal and neonatal hyperthyroidism that required specific therapy.ConclusionsThe three cases are interesting because of the different outcomes, the absence of a direct correlation between thyrotropin receptor antibody levels and clinical signs, and the persistence of thyrotropin receptor antibodies several years after a total thyroidectomy.

Association Between Thyroid Associated Ophthalmopath and Thyroid Autoantibody

Purpose: The same autoimmune process is thought to cause thyroid associated ophthalmopathy (TAO) and Graves disease. The aim of this study is to determine whether thyroid autoantibody is related to the development of thyroid associated ophthalmopathy. Methods: A retrospective chart analysis was performed on patients with a newly diagnosed Graves' disease, who presented to our ophthalmology clinic between January 2006 and December 2009. Thyroid autoantibody titers were obtained at the time of diagnosis and were used to determine the presence or absence of TAO. In addition, any correlations between thyroid autoantibodies were analyzed in patients with TAO. Results: Thyroid autoantibody levels correlated with the development of TAO. Fifty-eight (69%) out of 84 patients with positive thyroid-stimulating hormone receptor antibody (TRAB) levels at the time of diagnosis had TAO. Only 50 (51%) of the 99 patients with negative TRAB levels had TAO. This difference between the two groups was statistically significant (odds ratio, OR=2.2, p=0.013). A statistically significant correlation with the development of TAO was also found in thyroid peroxidase antibody (TPOAb) and anti-thyroglobulin antibody (TgAb), respectively (OR=0.5, p=0.317; OR=0.3, p=

Prevention of Relapse of Graves’ Disease by Treatment with an Intrathyroid Injection of Dexamethasone

Antithyroid drugs are widely used in the treatment of Graves' disease (GD), but the relapse rate is very high after therapy withdrawal. We evaluated the reduction effects of intrathyroid injection of dexamethasone (IID) on the relapse rate of hyperthyroidism in patients with newly diagnosed GD. A total of 191 patients with GD completed the study. After 6 months of treatment with methimazole (MMI), the patients were randomly assigned to receive either MMI (96 patients) alone or MMI combined with IID (MMI+IID; 95 patients) treatment for 3 months, followed by continuing a dose of MMI that would maintain euthyroidism for the next 9 months in all of the patients. After withdrawal of the medical therapy, patients were followed for 24 months, and the relapse rate of hyperthyroidism was evaluated. No statistical difference was observed in the levels of serum FT(4), TSH, or TSH receptor antibodies (TR-Ab), the thyroid volume, or the TR-Ab positive rate between the two groups at month 6. After the next 3 months of treatment with MMI+IID or MMI alone, the levels of TSH increased significantly, and the levels of serum TR-Ab, the TR-Ab positive rate, and thyroid volume decreased significantly in the MMI+IID group compared with the MMI group. Seven patients (7.4%) experienced a relapse of overt hyperthyroidism in the MMI+IID group and 49 patients (51%) in MMI group during the 2-yr follow-up period (P < 0.001). MMI+IID treatment is helpful to prevent relapse of hyperthyroidism in GD after medical therapy withdrawal.

Thyroid blood flow as a useful predictor of relapse of Graves’ disease after normal delivery in patients with Graves’ disease

Objective Measurement of the peak systolic velocity (PSV) in the inferior thyroid artery (ITA) before withdrawal of an anti-thyroid drug (ATD) is useful for predicting relapse of Graves’ disease (GD). We further investigated whether the ITA–PSV can be used for prediction of GD relapse after delivery in euthyroid women with GD who stopped ATD administration during mid- to late pregnancy. Patients and methods ITA–PSV was monitored monthly for three months after delivery in 42 women with GD aged from 24 to 45 years old (mean ± SE: 34.7 ± 0.92 years old) who met the above criteria. To confirm the stability of the measurement, ITA–PSV was also measured monthly in 32 age-matched non-pregnant normal women and for three months after delivery in 10 age-matched women. Results ITA–PSV and thyroid volume were higher in women with GD immediately after delivery compared to normal women, but the levels of TSH receptor antibody (TRAb) and thyroid-stimulating antibody (TSAb) did not differ significantly between the two groups. Of the 42 patients, 23 had relapse of GD and the smoker/non-smoker ratio and thyroid volume in these patients immediately after delivery were significantly higher than those in the 19 patients who did not undergo relapse (10/23 vs. 0/19, p < 0.0001; 24280.3 ± 2280.9 vs. 19670.0 ± 2103.7 mm 3, p = 0.046), while ITA–PSV, TRAb and TSAb did not differ between the two groups of patients. The ITA–PSV ratio was calculated by dividing each value in the follow-up period by that obtained immediately after delivery. A significant increase in the mean ITA–PSV ratio occurred at least one month before the time of relapse (1.00 ± 0.00 at –3 months before relapse vs. 1.46 ± 0.12 at –1 month, p = 0.010; 1.00 ± 0.00 at –3 months vs. 1.77 ± 0.13 at the time of relapse, p = 0.0048). In contrast, there were no significant changes in this ratio during the follow-up period in non-relapse patients. Conclusion Monthly measurement of ITA–PSV after delivery in remitted euthyroid women with GD may assist in early prediction of GD relapse.

Lymphocytes resided in the thyroid are the main source of TSH-receptor antibodies in Basedow's-Graves' disease?

The source of TSH-receptor antibodies (TRAb) in Basedow's-Graves' disease is still under debate. Previous studies by other groups had found TRAb levels in the thyroid vein higher than or equal to that in the peripheral vein. The aim of the present work was to investigate the suspected presence of this TRAb gradient in 14 Graves' patients who underwent surgery. Interestingly, in 6 patients higher levels of TRAb were measured in the antecubital vein when compared to the thyroid vein, in another 6 there was no gradient and 2 exhibited higher TRAb levels in their thyroid veins. A clear gradient of thyroid hormones in favour of the thyroid vein was also present, while no gradient of TSH, anti-thyreoglobulin and anti-microsomal antibodies, total IgG, IgA and IgM levels and no differences of the CD4+/CD8+ cell ratios were found between the two sampling sites. We conclude that cells other than lymphocytes residing in the thyroid gland must also be involved in TRAb production.

A Case of Euthyroid Graves Disease Which Developed Into Graves Disease With Thyrotoxicosis After Subacute Thyroiditis

The presence of stimulating TSH receptor antibody (TRAb) results in Graves disease with thyrotoxicosis. However, some patients with Graves disease are euthyroid despite the presence of this antibody. Patient: A 42-year-old Japanese woman had suffered from diplopia. Thyroid function, however, was normal. Serum TRAb levels were elevated at 1.7 U/L (normal range: under 1.0 U/L). The working diagnosis was euthyroid Graves disease. Eighteen months later, she noticed pain and tumor in the anterior region of the neck. Physical examination revealed 3.2-cm diameter, firm tumor in the left lobe of thyroid accompanied by exquisite tenderness. The serum free plasma free thyroxin, free triiodethyronine, and TSH was 1.60 ng/dL, 3.62 pg/mL, and below 0.01 mU/L, respectively. The erythrocyte sedimentation rate was 64 mm/h, TRAb values had increased to 3.52 U/L. Three months later, the serum levels of FT4 and TRAb increased and the diagnosis of Graves disease with thyrotoxicosis was made. To our best knowledge, this is the first case report of euthyroid Graves disease being connected to hyperthyroid Graves disease by subacute thyroiditis.