Effects of Levothyroxine Treatment on Fertility and Pregnancy Outcomes in Subclinical Hypothyroidism: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Subclinical hypothyroidism, defined by elevated thyrotropin (TSH) and normal free thyroxine levels, is associated with adverse pregnancy outcomes, including preterm birth, pre-eclampsia, and small for gestational age. Despite the uncertainty regarding the effectiveness of levothyroxine (LT4) treatment on pregnancy outcomes in subclinical hypothyroidism, LT4 is widely administered with a pre-treatment threshold TSH level of 2.5 mU/L. The aim of this study is to investigate the efficacy of periconceptional LT4 treatment for subclinical hypothyroidism, including TSH levels >2.5 mU/L, and identify the characteristics of subclinical hypothyroidism that can benefit from LT4 treatment. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials from inception to February 2023. We analyzed the pooled effects of LT4 on subclinical hypothyroidism before and during pregnancy. The main outcomes before pregnancy were live birth, pregnancy, and miscarriage. The main outcomes during pregnancy were live birth, miscarriage, and preterm birth. We conducted subgroup analyses to compare the effects of LT4 on subclinical hypothyroidism with TSH levels of 2.5-4.0 and >4.0 mU/L. Results: Of the 888 studies identified, 27 full-text articles were screened for eligibility. Five studies on pre-conception treatment with 768 participants and eight studies on treatment during early pregnancy with 2622 participants were analyzed. One of the two studies on pre-conception treatment in subclinical hypothyroidism with TSH >4.0 mU/L had high risk of bias and the other was composed of 64 participants. Pre-conception LT4 treatment had no significant effect in improving rates of live births and pregnancies, or reducing miscarriages (risk ratio [RR], 95% confidence interval): 1.41 (0.84-2.36), 1.73 (0.88-3.39), and 0.46 (0.11-2.00), respectively. LT4 treatment during pregnancy was not significantly associated with higher rates of live births (RR 1.03, 0.98-1.09) nor decreased miscarriage rates (RR 1.01, 0.66-1.53). The effect of LT4 treatment on preterm birth during pregnancy was significantly different depending on the TSH values (p = 0.04); a positive effect was shown in the subclinical hypothyroidism subgroup with TSH >4.0 mU/L (RR 0.47, 0.20-1.10), while no significant effect was observed in the subgroup with TSH 2.5-4.0 mU/L (RR 1.35, 0.79-2.31). Conclusions: Pre-conceptional LT4 treatment for subclinical hypothyroidism does not improve fertility or decrease the incidence of miscarriages. However, further well-designed studies are needed for pre-conceptional treatment, especially in TSH >4.0 mU/L. LT4 treatment during pregnancy had a positive effect on preterm birth; nevertheless, this was only applicable to subclinical hypothyroidism with TSH >4.0 mU/L.

Effect of L-thyroxine replacement on apolipoprotein B-48 in overt and subclinical hypothyroid patients.

Apolipoprotein B-48 (ApoB-48) is a constituent of chylomicrons and chylomicron remnants, and is thought to be one of the risk factors for atherosclerosis. We evaluated the effect of L-thyroxine (L-T(4)) replacement on serum ApoB-48 levels in patients with primary hypothyroidism. Eighteen patients with overt hypothyroidism (OH) and 18 patients with subclinical hypothyroidism (SH) participated in the study. The lipid profiles, including ApoB-48, were measured in patients with hypothyroidism before and 3 months after L-T(4) replacement. After L-T(4) replacement, the serum concentrations of all lipoproteins, exclusive of lipoprotein(a) (Lp(a)), were significantly decreased in patients with OH. In patents with SH, the serum levels of total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C), remnant-like particle cholesterol (RLP-C), apolipoprotein B (ApoB), and ApoB-48 decreased significantly after L-T(4) replacement. The serum levels of triglycerides (TG), HDL-C, low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA-1), and Lp(a) did not change significantly. In all 36 patients, the reduction in the ApoB-48 levels correlated significantly with the reduction in TSH levels (r = 0.39, P<0.05). This study showed clearly that L-T(4) replacement might reduce serum levels of ApoB-48 in both OH and SH patients. Such altered serum levels of ApoB-48 in patients with OH and SH may be related to the disturbed metabolism of chylomicron remnants in patients with hypothyroidism.

Graves' Disease with Thymic Hyperplasia: The Response of the Thyroid Function, Thyrotropin Receptor Autoantibody, and Thymic Size to Thiamazole Treatment.

We treated a 22-year-old woman suffering from Graves' disease and thymic hyperplasia. She was referred to our institution for a close investigation of thyrotoxicosis and thymic mass. Thyroid tests and magnetic resonance imaging resulted in a diagnosis of Graves' disease and thymic hyperplasia. The thyroid function and thyroid-stimulating hormone receptor antibody (TRAb) were normalized one and five months after thiamazole initiation, respectively. The thymic size began to decrease after 1 month and was further decreased after 5 months; it was normalized after 12 months. The correlation between TRAb titers and the thymic size (R2=0.99) suggested that the patient's autoimmunity might have contributed to the thymic hyperplasia.

Identification of independent risk loci for Graves' disease within the MHC in the Japanese population.

To identify genetic variants that confer the risk of Graves' disease (GD) in the Japanese population, we conducted a two-stage genome-wide association study (GWAS) using 1119 Japanese individuals with GD and 2718 unrelated controls, and a subsequent replication study using independent 432 GD cases and 1157 controls. We identified 34 single nucleotide polymorphisms (SNPs) to be significantly associated with GD in the GWAS phase. Twenty-two out of 34 SNPs remained positive in the replication study. All 22 SNPs were located within the major histocompatibility complex (MHC) locus on chromosome 6p21. No strong long-range linkage disequilibrium (LD) was observed among the 22 SNPs, indicating independent involvement of multiple loci within the MHC with the risk of GD. Multivariate stepwise logistic regression analysis selected rs3893464, rs4313034, rs3132613, rs4248154, rs2273017, rs9394159 and rs4713693, as markers for independent risk loci for GD. The analysis of LD between these seven SNPs and tagging SNPs for GD-associated human leukocyte antigen (HLA) alleles in the Japanese population (HLA-DPB1(*)0501 and HLA-A(*)0206) demonstrated that all of and five of seven SNPs were not in strong LD with HLA-DPB1(*)0501 and HLA-A(*)0206, respectively. Although causal variants remain to be identified, our results demonstrate the existence of multiple GD susceptibility loci within the MHC region.

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.

Benefit of short-term iodide supplementation to antithyroid drug treatment of thyrotoxicosis due to Graves' disease.

OBJECTIVE: Combined treatment with anti-thyroid drugs (ATDs) and potassium iodide (KI) has been used only for severe thyrotoxicosis or as a pretreatment before urgent thyroidectomy in patients with Graves' disease. We compared methimazole (MMI) treatment with MMI + KI treatment in terms of rapid normalization of thyroid hormones during the early phase and examined the later induction of disease remission. DESIGN AND PATIENTS: A total of 134 untreated patients with Graves' disease were randomly assigned to one of four regimens: Group 1, MMI 30 mg; Group 2, MMI 30 mg + KI; Group 3, MMI 15 mg and Group 4, MMI 15 mg + KI. For easy handling, KI tablets were used instead of saturated solution of KI. KI was discontinued when patients showed normal free thyroxine (FT4) levels but MMI was continued with a tapering dosage until remission. Remission rate was examined during a 4- to 5-year observation. MEASUREMENTS: Serum FT4, FT3 and TSH were measured by chemiluminescent immunoassays. TSH receptor antibody (TRAb) was assayed with TRAb-ELISA. Goitre size was estimated by ultrasonography. RESULTS: After 2 weeks of treatment, normal FT4 was observed in 29% of patients in Group 1 and 59% (P < 0.05) of patients in Group 2. Furthermore, normal FT4 after 2 weeks of treatment was observed in 27% of patients in Group 3 and 54% (P < 0.05) of patients in Group 4. Similarly, FT3 normalized more rapidly in Groups 2 and 4 than in Groups 1 and 3. None of the patients showed an increase in thyroid hormones or aggravation of disease during combined treatment with MMI and KI. The remission rates in Groups 1, 2, 3 and 4 were 34%, 44%, 33% and 51%, respectively, and were higher in the groups receiving combined therapy but differences among four groups did not reach significance. CONCLUSIONS: Combined treatment with MMI and KI improved the short-term control of Graves' hyperthyroidism and was not associated with worsening hyperthyroidism or induction of thionamide resistance.

Menstrual disturbances in various thyroid diseases.

The prevalence of menstrual disturbances, including secondary amenorrhea, hypomenorrhea, oligomenorrhea, hypermenorrhea, polymenorrhea and irregular menstrual cycle were prospectively examined in 586 patients with hyperthyroidism due to Graves' disease, 111 with hypothyroidism, 558 with euthyroid chronic thyroiditis, 202 with painless thyroiditis and 595 with thyroid tumor. In the overall patient group, the prevalence did not different from that in 105 healthy controls. However, patients with severe hyperthyroidism showed a higher prevalence of secondary amenorrhea (2.5%) and hypomenorrhea (3.7%) than those (0.2% and 0.9%, respectively) with mild or moderate hyperthyroidism. Moreover, patients with severe hypothyroidism had a higher prevalence (34.8%) of menstrual disturbances than mild-moderate cases (10.2%). Menstrual disturbances in thyroid dysfunction were less frequent than previously thought.

Prevalence of TSH receptor and Gsalpha mutations in 45 autonomously functioning thyroid nodules in Japan.

Somatic mutations of the thyrotropin receptor (TSHR) gene and the gene encoding the alpha subunit of the stimulatory GTP-binding protein (Gsalpha) are the main cause for autonomously functioning thyroid nodules (AFTN) in iodine-deficient regions of the world. In iodine-sufficient regions, including Japan, the genetic relevance of AFTN is unclear. In a series of 45 Japanese subjects with AFTN, exons 9 and 10 of the TSHR and exons 7-10 of Gsalpha , where the activating mutations have been found, were analyzed using direct sequencing. We found 29 somatic mutations: 22 in the TSHR gene and 7 in the Gsalpha gene. The most frequent mutation in TSHR was Met453Thr (10 cases), followed by clustered residues from codons 630 through 633 on TSHR (7 cases). Mutations of Gsalpha were detected at codon 201 in 5 cases and at codon 227 in 2 cases. No patients had coexistent TSHR and Gsalpha mutations in the same nodule. All mutated residues but one, which was deleted at codon 403 on the TSHR gene, are constitutively active. The prevalences of a germline polymorphism of Asp727Glu on the TSHR gene and incidental papillary thyroid carcinoma in thyroid surgical specimens were similar to those reported in other studies. In the present study, more than half of the cases with AFTN had a somatic activating mutation either of the TSHR or Gsalpha gene, despite their high iodine intake.

The prevalence of transient thyrotoxicosis after antithyroid drug therapy in patients with Graves' disease.

BACKGROUND: Although transient thyrotoxicosis occurring after antithyroid drug (ATD) withdrawal in patients with Graves' hyperthyroidism has been reported, the prevalence of transient thyrotoxicosis after ATD therapy is as yet unknown. When patients with transient hyperthyroidism are mistakenly regarded as recurrences, they receive unnecessary therapy. The aim of this study was to investigate the prevalence of transient thyrotoxicosis after ATD withdrawal. METHODS: We selected 110 consecutive patients with Graves' disease whose ATD therapy was stopped from December 2002 to September 2004 prospectively. Patients were observed for more than 1 year after ATD withdrawal, and 12 patients dropped out. Serum levels of free thyroxine (FT(4)), thyrotropin, and thyrotropin-binding inhibitor immunoglobulin were measured at ATD withdrawal, and 3, 6, and 12 months after withdrawal. When the patients showed mild thyrotoxicosis (serum FT(4) level of less than 3.00 ng/dL), we followed them up for 1 month without medication. RESULTS: The remission rate of the study group was 61.8% (68/110). Twenty-eight patients became euthyroid after transient thyrotoxicosis, equivalent to 41.2% of the remission patients. Eight of 28 patients showed overt thyrotoxicosis, and the rest subclinical thyrotoxicosis. Transient thyrotoxicosis occurred mostly 3-6 months after ATD withdrawal. CONCLUSIONS: Transient thyrotoxicosis after ATD withdrawal in patients with Graves' disease is not a rare phenomenon. Clinicians should be aware that the recurrence of Graves' disease after the withdrawal of ATD may be transient.

A novel homozygous missense mutation of the dual oxidase 2 (DUOX2) gene in an adult patient with large goiter.

OBJECTIVE: To describe the first adult case of large goiter associated with a novel R1110Q mutation in the dual oxidase 2 (DUOX2) gene. She was initially euthyroid, and developed hypothyroidism later in her forties. DUOX2 is an essential enzyme in iodine organification of thyroid hormone biosynthesis. Only infant cases of congenital hypothyroidism due to mutations of the DUOX2 gene have been reported. Biallelic mutation of DUOX2 is thought to lead to total iodine organification defect. PATIENTS AND MEASUREMENT: This 57-year-old woman became first aware of goiter around the age of 20 years. Since the goiter had enlarged gradually, she consulted us at the age of 32 years. Goiter was soft, and thyroid function was normal. Antithyroid antibodies were negative. Both physical and mental development was normal. Three of her nine siblings and her mother had large goiters. At the age of 44 years, thyroid function demonstrated subclinical hypothyroidism. She started to take levo-thyroxine at a dose of 100 mug/day to reduce goiter. At the age of 56 years, goiter size remained the same. The perchlorate discharge rate was 72.8%, suggesting partial iodine organification defect. Thus, thyroid peroxidase (TPO) gene and DUOX2 gene were analyzed. RESULTS: There was no mutation in the TPO gene, but a novel homozygous mutation (R1110Q) in the DUOX2 gene was identified. The same heterozygous mutation was detected in her two sons and two grandchildren. This mutation was not detected in 104 control alleles and was located at a site differing from any other reported mutations in the DUOX2 gene. CONCLUSIONS: This homozygous missense mutation can be associated with thyroid dysfunction and goiter formation of an enlarged thyroid gland.

Serial changes in liver function tests in patients with thyrotoxicosis induced by Graves' disease and painless thyroiditis.

CONTEXT: When the liver function tests are aggravated after starting antithyroid drugs (ATDs) in Graves' hyperthyroidism, discontinuation of ATDs is generally considered. However, a question arises whether such aggravation constitutes an adverse effect of the drugs or not. OBJECTIVE: The aim of this study was to clarify the influence of thyrotoxicosis on liver function tests, comparing the results with those in thyrotoxicosis induced by painless thyroiditis. DESIGN: We prospectively studied liver biochemical tests in 30 patients with Graves' disease and in 27 patients with painless thyroiditis. MAIN OUTCOMES: Twenty-three (76.7%) untreated Graves' disease patients and 14 (51.9%) untreated painless thyroiditis patients were found to have at least one liver function test abnormality. One month after starting ATD therapy in patients with Graves' disease, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) elevations from initial values were observed in 16 (53.3%). Similar elevations of AST and ALT from initial values at 1 month were observed in 10 (37.0%) and 7 (25.9%) patients with painless thyroiditis, respectively. Alkaline phosphatase (ALP) increased gradually after starting ATD therapy and maintained an elevated value for 3-5 months in Graves' disease. In painless thyroiditis, ALP also increased gradually, similarly to that in Graves' disease, but changes were mild. Elevation of ALT after 1 month of ATD therapy in Graves' disease was significantly higher in patients whose estimated disease duration was 6 months or more compared to those with duration of less than 6 months. Elevated AST and ALT at 1 month after ATD therapy decreased to normal ranges, even though patients were receiving the same ATDs in Graves' disease. CONCLUSION: Similar serial changes in liver function tests in both Graves' disease and painless thyroiditis strongly suggest that increases of AST and ALT after starting ATD therapy may not be due to ATD side effects but may be induced by changes in thyroid function.

Effect of levo-thyroxine replacement on non-high-density lipoprotein cholesterol in hypothyroid patients.

CONTEXT: Recently, non-high-density lipoprotein cholesterol (non-HDL-C), a measure of total cholesterol minus HDL-C, has emerged as a predictor of cardiovascular disease. OBJECTIVE: We evaluated the effect of L-T4 replacement on non-HDL-C levels in patients with primary hypothyroidism. METHODS: Thirteen patients with overt hypothyroidism and 26 patients with subclinical hypothyroidism participated in the study. The lipid profiles, including non-HDL-C, were measured in patients with hypothyroidism before and 3 months after L-T4 replacement was started. RESULTS: After L-T4 replacement, the serum concentrations of all lipoproteins, exclusive of lipoprotein (a) [Lp(a)], were significantly decreased in patients with overt hypothyroidism. In patients with subclinical hypothyroidism, the serum concentrations of total cholesterol, non-HDL-C, remnant-like particle cholesterol, and apolipoprotein B (Apo B) were significantly decreased, whereas no significant changes in the serum concentrations of low-density lipoprotein cholesterol, HDL-C, triglycerides, apolipoprotein A-I, and Lp(a) were observed. In all 39 patients, the reduction in the non-HDL-C levels correlated with the reduction in the low-density lipoprotein cholesterol, remnant-like particle cholesterol, and Apo B levels. However, the reduction in the non-HDL-C levels did not correlate with the reduction in the HDL-C, Lp(a), and apolipoprotein A-I levels. CONCLUSIONS: This study is the first to show that L-T4 replacement may reduce serum concentrations of non-HDL-C in patients with hypothyroidism. The study also suggests that such altered serum concentrations of non-HDL-C in hypothyroidism may be related to the disturbed metabolism of low-density lipoprotein, remnant lipoprotein, and Apo B.

A novel thyrotropin receptor germline mutation (Asp617Tyr) causing hereditary hyperthyroidism.

Constitutively activating germline mutations of the thyrotropin receptor (TSHR) gene have been identified as a molecular cause of hereditary nonautoimmune hyperthyroidism. We describe here a Japanese kindred with two affected individuals who showed overt hyperthyroidism and mild goiter in the absence of TSHR antibodies. A novel heterozygous germline point mutation, identified in both individuals, resulted in an amino acid substitution of aspartic acid for tyrosine at codon 617 (Asp617Tyr) in the third intracellular loop of the TSHR. Screening of 7 additional family members led to the identification of the same mutation in 4 relatives: 1 had undergone thyroidectomy due to hyperthyroidism but 3 were asymptomatic with subclinical hyperthyroidism. In vitro functional studies of the Asp617Tyr TSHR demonstrated a constitutive activation of the cyclic adenosine monophosphate pathway, but not of the inositol phosphate cascade, with data similar to those of Asp619Gly, the first constitutively activating mutant TSHR identified. Treatment with inorganic iodine for 7 months successfully relieved all symptoms of hyperthyroidism in both patients.

HLA-DPB1*0202 is associated with a predictor of good prognosis of Graves' disease in the Japanese.

Whereas most patients with Graves' disease (GD) have antibodies against the thyrotropin receptor, which are measured as thyrotropin-binding inhibitory immunoglobulin (TBII), the TBII of 10% or less of Japanese patients with GD is undetectable at the first visit and throughout the entire clinical course, and these patients tend to respond well to medications and follow the better clinical course. Therefore, the absence of TBII at the first visit may be a predictor of good prognosis. Ninety-seven patients with GD who had remained TBII negative for at least 2 years from the onset, as well as 142 typical TBII-positive GD patients, were examined to reveal the HLA-linked immunogenetic background for this predictor. Compared with a healthy control population, the frequencies of HLA-A*0206 (OR=2.17, p=9.73x10(-4)) and DPB1*0501 (OR=3.26, p=3.31x10(-7)) carriers were increased in the typical patients, whereas those of HLA-A*0201 (OR=2.16, p=1.92x10(-3)), A*0207 (OR=3.19, p=7.17x10(-4)), and DPB1*0202 (OR=3.13, p=3.97x10(-4)) were increased in the TBII-negative group. These two patient groups were associated with similar HLA-A alleles and different HLA-DPB1 alleles, suggesting the presence of two genetic factors for GD within the HLA region; one is HLA-A linked and may be related to thyroid organ specificity, the other is HLA-DP linked and may control the severity of autoimmunity.

Thyrotoxicosis caused by weight-reducing herbal medicines.

The weight-reducing herbal medicines "Dream Shape" and "Ever Youth" became available in Japan in 2000. Herein, we describe 12 patients who developed thyrotoxicosis after taking them. The thyroid hormone content of 1 capsule or tablet of herbal medicine, measured following Pronase digestion and ethanol extraction, was approximately 1 mug of triiodothyronine and 3 to 4 mug of thyroxine. Two of us took 10 capsules or tablets of Dream Shape or Ever Youth, and changes in thyroid hormone levels were observed during the first 24 hours. Serum free triiodothyronine levels began to rise 2 hours after ingestion and reached peak levels at 4 to 8 hours; changes in free thyroxine and thyrotropin levels were small during the first 24 hours. Similar herbal medicines may have been distributed to other countries via the Internet. Resultant factitious thyrotoxicosis can create diagnostic and therapeutic confusion, particularly in patients with thyroid disease.

Successful Re-administration of Low-dose of Methimazole (MMI) in Graves' Disease Patients Who Experienced Allergic Cutaneous Reactions to MMI at Initial Treatment and Had Received Long-term Propylthiouracil (PTU).

Objective When patients with Graves' disease show severe allergic cutaneous reactions, physicians often suggest that they undergo radioiodine therapy instead of receiving propylthiouracil (PTU), another antithyroid drug, because anti-neutrophil cytoplasmic antibody (ANCA) -related vasculitis can occur with PTU, especially with long-term use. However, some patients refuse radioiodine therapy and chose PTU. Sometimes PTU treatment may be prolonged. Since the frequency of adverse effects of methimazole (MMI) is dose-related, there is a possibility that we can re-administer a low dose without adverse effects to patients well-controlled with PTU who once experienced an allergic reaction to MMI. Methods I prospectively re-administered a low dose of MMI to patients who previously experienced an allergic reaction to MMI at initial treatment. The dose of re-administered MMI ranged from 5 mg twice a week to 5 mg daily. Patients Nine patients with Graves' disease who developed urticaria at initial treatment with MMI and had been treated with PTU for 6 to 21 years were recruited. Results Eight of the 9 patients were successfully controlled with MMI without allergic cutaneous reactions. Only one patient felt itchiness 2 days after switching to MMI. However, skin change was not observed. Conclusion If the patients show allergic cutaneous reactions as a side effect of MMI at the initial treatment for Graves' disease, then there is a strong possibility that such patients can tolerate a low dose of MMI without adverse effects after the disease activity has subsided.

Successful use of iodine and levothyroxine to treat Graves' disease in a pregnant patient with allergy to antithyroid drugs and high thyrotropin-binding inhibitor immunoglobulin after radioiodine therapy.

High titer of thyrotropin-binding inhibitor immunoglobulin (TBII) in patients with Graves' disease can cause fetal hyperthyroidism during pregnancy. Prevention of fetal hyperthyroidism by administration of antithyroid drug (ATD) and levothyroxine (LT(4)) to pregnant patients who previously received ablative therapy has been reported. We administered iodine and LT(4) to a patient during gestation, because she had a severe adverse reaction to ATD. Although gestation proceeded normally, the infant showed transient neonatal hyperthyroidism right after birth. We believe that the fetus would have developed hyperthyroidism if we had not administered iodine to the mother. Administration of iodine and LT(4) to a pregnant patient with Graves' disease showing a high TBII after ablative therapy should be considered in rare patients with allergy to ATD.

Acute suppurative thyroiditis after fine-needle aspiration causing thyrotoxicosis.

A case of thyrotoxicosis caused by acute suppurative thyroiditis after repeated fine-needle aspiration (FNA) is described. A 39-year-old woman with atopic dermatitis showed rapid enlargement of a left thyroid cyst after a third FNA. She had a high fever, painful swelling of the left thyroid, and elevated thyroid hormone levels. Ultrasonography revealed abscess formation in the left thyroid cyst. The cytologic examination of an FNA specimen showed abundant neutrophils, and culture of the aspirate yielded Staphylococcus aureus. Because antibiotic treatment for 1 month failed to improve the inflammatory findings, the patient subsequently underwent left thyroid lobectomy, which resulted in the normalization of thyroid function and the resolution of inflammation. Thyroid infection had possibly been induced by needle-track seeding, because atopic skin favors colonization by S. aureus because of local immunologic deficiency. FNA is a useful and safe technique for aspirating fluid from thyroid cysts, but special care is required in patients with atopic dermatatis to avoid bacterial infection.

Successful treatment for recurrent painful Hashimoto's thyroiditis by total thyroidectomy.

Painful Hashimoto's thyroiditis is an atypical variant of Hashimoto's thyroiditis characterized by thyroid pain and fever. In patients with this condition, anti-inflammatory agents are not always effective as in those with subacute thyroiditis. Therefore, long-term pain management is an important issue. We report herein four cases of painful Hashimoto's thyroiditis requiring total thyroidectomy to relieve thyroid pain and histologic findings of the thyroid gland. All patients had high titers of anti-thyroperoxidase (TPO) and thyroglobulin antibodies. Three were hypothyroid, and the other was euthyroid. During the first visit, four patients had fever and/or thyroid pain with elevated C-reactive protein or erythrocyte sedimentation rate, and they were treated with oral corticosteroids given continuously or intermittently for 9 to 48 months. Because a reduction or discontinuation of corticosteroids caused recurrent painful attacks, the decision was made to perform surgery. After total thyroidectomy, their symptoms disappeared. The histopathologic characteristics of these hypothyroid cases were advanced fibrosis and destructive thyroid architecture. One euthyroid case showed a mild fibrous change and the presence of foreign body type giant cells. In conclusion, total thyroidectomy is the effective and reliable treatment for patients with recurrent painful Hashimoto's thyroiditis. Pathologic characteristics include advanced fibrosis and destructive thyroid architecture.