Absence Of Thyroid Autoantibodies Research Articles

Detection of thyroid autoantibodies in patients with chronic urticaria and analysis of clinical features

Objective To investigate clinical and serological characteristics of thyroid autoanti-body-positive patients with chronic urticaria. Methods A total of 70 inpatients with chronic urticaria were enrolled from the Department of Dermatology of Hangzhou Third Hospital between January and December in 2016, and divided into 2 groups according to the presence or absence of thyroid autoantibodies. Clinical manifestations, autologous serum skin test (ASST) results, hospital days, discharge outcome, routine blood test results, antibodies, and total serum IgE and IgG levels were compared between the 2 groups. Results Of 70 patients with chronic urticaria, 26 (37.1%) had positive thyroid autoantibodies, while 44 (62.9%) had negative thyroid autoantibodies. Compared with patients with negative thyroid autoantibodies, patients with positive thyroid autoantibodies showed significantly larger wheals and more severe itching (z= 4.399, P 0.05) . Conclusion Chronic urticaria patients with positive thyroid autoantibodies show more severe urticarial condition, and are commonly complicated by positive ASST and decreased levels of basophilic granulocytes. Key words: Urticaria; Thyroid gland; Autoantibodies; Autoimmunity; Basophils

Thyroid Complications of Cancer Therapy: An Increasing Challenge

Thyroid Complications of Cancer Therapy: An Increasing Challenge

Subacute thyroiditis in a patient with juvenile idiopathic arthritis undergoing etanercept treatment: a case report and review of the literature

We report on a 24-year-old woman with juvenile idiopathic arthritis (JIA) who developed subacute thyroiditis (SAT) while being treated with etanercept. She had suffered from JIA for 12 years, and her arthritis proved refractory to treatment with ibuprofen, prednisolone, and methotrexate. For the past 5 years, the patient had been treated successfully with etanercept at 25 mg/week. The patient more recently complained of high fever and lassitude, and presented with anterior neck swelling and tenderness. Palpation of the thyroid gland revealed it to be warm, erythematous, tender, and diffusely swollen. Laboratory tests revealed an increased erythrocyte sedimentation rate and C-reactive protein level. Thyroid function tests revealed decreased levels of thyrotropin-stimulating hormone, increased levels of free triiodothyronine, free thyroxine, and thyroglobulin, and an absence of thyroid autoantibodies. Sonography showed a diffusely reduced predominantly hypoechoic thyroid gland. Unenhanced computed tomography of the neck showed a homogeneously and mildly reduced thyroid gland. Serum titers of several viruses were not significant and so were considered unlikely to be the pathogens. On the basis of these presented findings, we diagnosed SAT, and etanercept therapy was withdrawn. The patient was treated with antibiotics and an increased prednisolone dose was initiated. She became symptom free and showed improved laboratory test results within 2 weeks, and was euthyroid by 3 months. Three months later, the patient developed hypothyroidism, although 6 months further on, the patient was asymptomatic on prednisolone, methotrexate, and levothyroxine therapy. In conclusion, whether SAT is a specific adverse event in this case in response to etanercept remains unclear. Nevertheless, the possibility of SAT should be considered in such patients on etanercept treatment.

Pathologic features of polycystic thyroid disease: Comparison with benign nodular goiter

Polycystic thyroid disease (PCTD) is characterized by multiple thyroid cysts detected by ultrasonography, the absence of thyroid autoantibodies, and susceptibility to the development of hypothyroidism due to a high iodine intake. It is necessary to obtain histopathological information on PCTD in order to clarify the cause of hypothyroidism. We retrospectively reviewed three patients with PCTD and small papillary thyroid cancer who underwent thyroidectomy. We observed the thyroid tissues pathologically in areas with and without multiple cysts, and compared them with those of multinodular goiter with cysts. In the patients with PCTD, there were multiple enlarged follicles that resembled enlarged normal follicles and differed from those found in multinodular goiter in terms of their shape. Huge follicles corresponded to the cysts that were detected by ultrasonography. Each follicle contained colloid. Follicular cells in enlarged follicles comprised low cuboidal epithelium that appeared normal. These findings were common in the 3 patients with PCTD. In Conclusion the PCTD patients had multiple enlarged follicles that seemed to decrease the total number of follicular cells, and may be a cause of hypothyroidism. We believe that PCTD is a new entity of thyroid disease based on the pathological findings.

Thyroid Function and Human Reproductive Health

Via its interaction in several pathways, normal thyroid function is important to maintain normal reproduction. In both genders, changes in SHBG and sex steroids are a consistent feature associated with hyper- and hypothyroidism and were already reported many years ago. Male reproduction is adversely affected by both thyrotoxicosis and hypothyroidism. Erectile abnormalities have been reported. Thyrotoxicosis induces abnormalities in sperm motility, whereas hypothyroidism is associated with abnormalities in sperm morphology; the latter normalize when euthyroidism is reached. In females, thyrotoxicosis and hypothyroidism can cause menstrual disturbances. Thyrotoxicosis is associated mainly with hypomenorrhea and polymenorrhea, whereas hypothyroidism is associated mainly with oligomenorrhea. Thyroid dysfunction has also been linked to reduced fertility. Controlled ovarian hyperstimulation leads to important increases in estradiol, which in turn may have an adverse effect on thyroid hormones and TSH. When autoimmune thyroid disease is present, the impact of controlled ovarian hyperstimulation may become more severe, depending on preexisting thyroid abnormalities. Autoimmune thyroid disease is present in 5-20% of unselected pregnant women. Isolated hypothyroxinemia has been described in approximately 2% of pregnancies, without serum TSH elevation and in the absence of thyroid autoantibodies. Overt hypothyroidism has been associated with increased rates of spontaneous abortion, premature delivery and/or low birth weight, fetal distress in labor, and perhaps gestation-induced hypertension and placental abruption. The links between such obstetrical complications and subclinical hypothyroidism are less evident. Thyrotoxicosis during pregnancy is due to Graves' disease and gestational transient thyrotoxicosis. All antithyroid drugs cross the placenta and may potentially affect fetal thyroid function.

Other complications and associated conditions with diabetes in children and adolescents

aChildren’s Hospital auf der Bult, Hannover, Germany; bthe Children’s Hospital at Westmead, NSW, Australia; cUniversity of Helsinki, Finland; dMedical University Vienna, Austria; eUniversity of Genova, Italy; fUniversitat Ulm, Uni West, Germany; gUniversity of Sydney, Australia Corresponding author: Prof. Dr. med. Olga Kordonouri Diabetes Center for Children and Adolescents Children’s Hospital auf der Bult Hannover, Germany Tel: +49 511/8115-3340; fax: +49 511/8115-3334; e-mail: kordonouri@hka.de

Thyroid Dysfunction in Genotype 3 Chronic Hepatitis C Patients Treated with Interferon & Ribavirin

Purpose: IFN & RIBA therapy for CHC infection has been associated with thyroid dysfunction. Aim of our study was to determine pattern of thyroid Dysfunction only in Genotype 3 Patients and to assess risk factors and reversibility of thyroid disorders induced by IFN therapy. Methods: Patients with CHC, either biopsy proven and/or tested positive for HCV RNA by PCR and having only genotype 3 (N = 200), (M = 101, F = 99) were treated with IFN alpha 2b 3MIU TIW (N = 150) or PEG IFN alpha2a 180 Mcg (N = 50) along with weight based RIBA were included. TSH, free T3 and T4, Thyroid peroxidase antibodies, Thyroglobulin antibodies and Thyroid Stimulating Immunoglobulins were measured at 0, 3, 6, 9 and then at 12 months of treatment. Thyroid dysfunction was defined as TSH level below or above the normal range (0.2–4.5 MIU/L). Frequency was compared using chi square test with Yate's correction or Fischer exact test. A multiple logistic regression model was used in the statistical analysis of various factors for the development of thyroid dysfunction. Variables which were used included age, gender, type of IFN used, presence or absence of thyroid auto antibodies before starting therapy, impact of RVR and SVR. Type of thyroid disease and its outcome were assessed during and after therapy. Results: Thyroid dysfunction developed in 21 (10.5%) (M = 8, F = 13) of 200 patients. Hypothyroidism was seen in 17 and hyperthyroidism in 4 patients. Dysfunction occurred in 15 (10%) of 150 patients who received standard IFN as compared with 6 (12%) of 50 patients who received Peg IFN (P= 1.0). Pretreatment autoantibodies were seen in 15 of 21 patients who later on developed thyroid dysfunction while they were seen only in 10 of remaining 179 who didn' t develop thyroid disease. (P > 0.05) Amongst 200 patients who completed all 6 months of HCV treatment, overall SVR was achieved in 162 (81%) patients. While out of 21 patients who developed thyroid dysfunction SVR was seen in 16 of 21 (76%) as compared to 179 patients who didn' t have thyroid dysfunction SVR was present in 145 (81%) (P= 0.96). By multivariate analysis female gender and pre-treatment autoantibodies presence were independent predictors of developing thyroid dysfunction (P < 0.01) while age, type of IFN, RVR and SVR were not. These patients were followed for six months after cessation of IFN therapy. Out of 21 patients 19 became euthyroid during six months post IFN therapy, while only two patients had to continue taking therapy after this time period. Both were from Peg IFN group and suffered from Hypothyroidism. Conclusion: Female gender and pretreatment auto-antibodies detection are associated with thyroid dysfunction while type of IFN, age, RVR and SVR have no impact on thyroid disease development in CHC.

Long-term outcome of interferon-alpha-induced thyroid autoimmunity and prognostic influence of thyroid autoantibody pattern at the end of treatment.

Thyroid autoimmunity and dysfunction have been widely reported as side effects of interferon-alpha (IFN-alpha) treatment, but the literature lacks data regarding the long-term course of these complications, clinical observation being limited to 6-12 months off therapy. Our study is the first that has aimed to evaluate the natural history of IFN-related thyroid autoimmunity during a 6.2-yr follow-up after the IFN-alpha withdrawal as well as to investigate the potential role of the autoantibody pattern at the end of treatment to predict the long-term outcome. Our study group included 114 patients (79 males, 35 females), mean age 48 yr (range 23-67 yr) with no preexisting thyroid disease, undergoing a 12-month treatment with recombinant IFN-alpha for C virus-related chronic active hepatitis. Thyroid autoimmunity (serum TgAb and TPOAb) and function (serum FT(4), FT(3), TSH) were retrospectively evaluated at the end of IFN therapy, 6 months after IFN withdrawal and after a median period of 6.2 yr (range 5.5-8.4 yr). At the end of treatment, 78 patients were negative for thyroid autoantibodies (Abs-) and all but one of them remained so for the following evaluations. The remaining 36 patients had thyroid autoantibodies (Abs+) at the end of treatment, and they subsequently showed a heterogeneous behavior: 16 patients remained Abs+ for the whole length of the study (persistent thyroiditis); 10 patients became Abs- 6 months off therapy but were again Abs+ 6.2 yr later (remitting/relapsing thyroiditis); 10 patients reverted to autoantibody negativity at different observation times (transient thyroiditis). The absence of thyroid autoantibodies at the end of treatment was a protective factor for the successive development of thyroiditis (odds ratio: 0.02, confidence interval (CI) 95%: 0-0.1). On the contrary, the positivity for TgAb and/or TPOAb at high titers at the end of IFN treatment was significantly related to the highest risk of having chronic thyroiditis (odds ratio: 17.3, CI 95%: 3.2-91.7 for TgAb levels > 50 degree percentile; odds ratio: 7.3, CI 95%: 1.5-35.2 for TPOAb levels > 50 degree percentile). None of the patients showed overt thyroid dysfunction throughout the study, whereas a subclinical hypothyroidism was found in 12 patients. In all 12 cases, the functional abnormality was accompanied by the presence of thyroid autoantibodies. Eight of these 12 patients belonged to the group with persistent thyroiditis (P < 0.05). The absence of thyroid autoantibodies at the end of treatment was a protective factor for the successive development of thyroid dysfunction (odds ratio: 0.06, CI 95%: 0.01-0.56). On the contrary, the positivity for both TgAb and TPOAb at the end of IFN therapy was significantly correlated with the highest risk of having subclinical hypothyroidism 6.2 yr. later (odds ratio: 38.7; CI 95%: 6.2-242). Our study demonstrates that in patients undergoing an IFN-alpha therapy for chronic hepatitis C and with no evidence of preexisting thyroid disease: 1) the negativity for thyroid autoantibodies after IFN treatment is a protective factor for the developing thyroid autoimmunity and/or dysfunction in following years; 2) the IFN-alpha-related thyroid autoimmunity is not a complete reversible phenomenon because some patients can develop chronic thyroiditis; 3) high autoantibody levels at the end of IFN therapy are related to the risk of having chronic thyroid autoimmunity; and 4) the coexistence of TgAb and TPOAb at the end of treatment is a predictive factor for the presence of thyroid dysfunction, even if subclinical, many years after IFN withdrawal.

Clinical, biochemical and immunological characteristics of relapsers and non-relapsers of thyrotoxicosis treated with anti-thyroid drugs.

This study aims to correlate clinical, biochemical and immunological factors seen at diagnosis of thyrotoxicosis with subsequent relapse within 5 years. Retrospective review of case notes, and biochemical assessment at least 5 years after cessation of treatment. A large general hospital endocrine clinic. Patients presenting with a first episode of thyrotoxicosis between 1988 and 1991 who were treated with antithyroid drugs for at least 18 months. Main outcome measures. Relapse was determined by examination of hospital records, general practice records, patient questionnaire and thyroid function tests. A total of 216 subjects presented for the first time with thyrotoxicosis, of whom 89 (41.2%) suffered a relapse of the disease. On univariate analysis, clinical factors associated with increased relapse include younger age at diagnosis, goitre, marked tachycardia, requirement for higher maintenance dose of carbimazole, higher FT4 levels at diagnosis and smoking. Factors not predictive of relapse include presence of thyroid eye signs, positive family history, atrial fibrillation or congestive cardiac failure, acropachy or pretibial myxoedema, and presence or absence of thyroid autoantibodies. Logistic regression analysis showed relapse was predominantly determined by an FT4 > 56.2 nmol L ', pulse rate > 110, presence of goitre and a positive smoking history (R2 = 0.36, P < 0.001). Presence of these four factors predicted relapse in 76 (85.4%) of the 89 patients who relapsed. Increased 'toxicity' of thyrotoxicosis, goitre and smoking are associated with relapse of thyrotoxicosis, and this may be helpful in determining which patients may be better managed with early ablative therapy.

Immunogenetics and IDDM

Comparison of genetic determinants associated with susceptibility to IDDM in different countries remains important for understanding disease epidemiology and aetiology. The strong association of the human leukocyte antigens (HLA) with IDDM continues to be demonstrated in different populations. Genetic heterogeneity of HLA is always encountered in different ethnic groups and in the patients with varying clinical manifestations. Detailed studies by molecular design help to unify the hypothesis that the structural and functional changes in HLA class 11 molecules leads to autoimmune processes. Our studies in the Chinese living in Taiwan reveal that certain HLA class II alleles confer predisposition to or protection from IDDM. Moreover, some of them contribute to the clinical heterogeneity among IDDM subjects, eg. the presence or absence of thyroid autoantibodies. Although the specific HLA alleles might not be the true pathogenic factor(s) for IDDM or thyroid autoimmunity, the inference from the structural biology of the HLA molecules suggests that the amino acid residue 57 of the HLA DQβ chain might play a role in antigen presentation and T cell recognition. This hypothesis is almost correct through tests so far inmost of the populations except in the Japanese. However, the single HLA-DQB-57 locus is not sufficient to explain the difference in the world-wide incidence of IDDM. In complementation with HLA-DQα chain, HLA-DQα, β heterodimers strongly influence the risk to IDDM in Chinese population as well as in other ethnic groups, suggesting the direct role of HLA-DQ genes in IDDM. There are many genes resided within the MHC region on the short arm of chromosome 6. The presence of the linkage disequilibrium between these loci render it difficult to establish the role of individual genes. We have characterized a diallelic polymorphism of heat shock protein 70 gene on the chromosome 6 (HSP70-2 and HLA loci contribute to IDDM independently although these loci are in linkage disequilibrium. In conclusion, molecular typing of HLA class II genes allows us to re-examine the role of HLA in IDDM. Other genetic and environmental factors also contribute to the pathogenesis of IDDM.

Sequence Analysis of the Thyrotropin (TSH) Receptor Gene in Congenital Primary Hypothyroidism Associated with TSH Unresponsiveness

Congenital primary hypothyroidism due to thyrotropin (TSH) unresponsiveness is a very rare disorder and only a few cases have been documented previously. To elucidate whether structural abnormalities in the TSH receptor (TSHR) could be a primary underlying mechanism of this disorder, we analyzed nucleotide sequence of the entire coding region of the TSHR gene in three patients diagnosed with congenital primary hypothyroidism associated with TSH unresponsiveness. Diagnosis of TSH unresponsiveness was largely made based on the following criteria: (a) congenital primary hypothyroidism with autosomal recessive inheritance, (b) a nongoitrous thyroid gland in a normal position with low thyroidal radioactive iodine uptake, (c) normal in vitro TSH bioactivity or absent in vivo response to exogenous TSH, and (d) absence of thyroid autoantibodies. The TSHR cDNA was successfully obtained from RNA of peripheral mononuclear leukocytes with reverse transcription and polymerase chain reaction, and was sequenced directly. Comparison of these nucleotide sequences with the normal TSHR sequence revealed no difference in the predicted amino acid sequence with a heterozygous polymorphism in codon 601 in one patient, indicating absence of TSHR structural abnormalities in these patients. Our results indicate that congenital primary hypothyroidism associated with TSH unresponsiveness is unlikely to be due to mutations in the TSHR-structure gene.

An Outbreak of Thyrotoxicosis due to Atypical Subacute Thyroiditis*

We describe an epidemic of self-limited (6 weeks) thyrotoxicosis which affected 12 index cases, 5 household contacts, and 6 retrospectively identified cases in July, August, and September, 1987 in the town of Winterswijk (28,011 inhabitants), The Netherlands. A small goiter was present in 9 of the 12 index patients, tender upon palpation in only 2. Signs and symptoms of thyrotoxicosis were accompanied by a low grade fever in combination with fatigue, headache, myalgia, and a fine desquamation of the palms and soles. The apparent incubation time between family members was 6 days. Thyroid technetium uptake was decreased in 10 of 11 tested patients. Laboratory findings included elevated sedimentation rates (up to 68 mm/h), increased liver enzymes, lymphopenia in 2 patients, and absence of thyroid autoantibodies. HLA-B35, associated with classical subacute thyroiditis, was found in 1 patient only. An etiological agent was not identified. No evidence was found for thyrotoxicosis factitia. After 10 months, all patients were euthyroid, without a goiter or thyroid autoantibodies. Thus, a new variant of thyroiditis, atypical subacute thyroiditis, was probably the cause of this unusual outbreak. It is unclear at present if this variant of thyroiditis is common in communities and represents a separate disease entity.