Painless giant cell thyroiditis diagnosed by fine needle aspiration and associated with intense thyroidal uptake of gallium

A 52-year-old woman presented with fever, goiter, and no evidence of pain or tenderness in the thyroid. A diagnosis of silent thyroiditis was made after obtaining evidence of biochemical thyrotoxicosis, intense gallium-67 citrate thyroidal localization, and cytologic thyroiditis. Fine needle aspiration biopsy of the thyroid revealed numerous giant cells in all areas of the thyroid, typical of subacute thyroiditis. This is believed to be the first time painless thyroiditis is reported with the classic cytologic feature of painful subacute thyroiditis.     

Carcinomatous involvement of the thyroid presenting as subacute thyroiditis

Carcinomatous involvement of the thyroid is a most unusual cause of hyperthyroidism and thyroiditis, with only a few cases reported in the literature. The authors present a 35-year-old woman with signs, symptoms, and laboratory findings of hyperthyroidism, and subacute thyroiditis that was due to extensive replacement of the thyroid gland by adenocarcinoma (shown by fine needle aspiration). After chemotherapy with vincristine and cisplatin, the swelling of the thyroid resolved, thyroidal uptake of radioactive iodine increased, and mild hypothyroidism developed. Despite the improvement in her thyroid status, she died from progressive malignancy. This case illustrates the value of fine needle aspiration cytology where doubt exists in the diagnosis of thyroid disorders.     

Occult parathyroid carcinoma in a patient with papillary thyroid carcinoma and Hashimoto's thyroiditis

A 47-year-old female patient with a previous history of right thyroid lobectomy was admitted to the hospital because of a 3 cm nodule in the thyroid gland. Hormonal evaluation showed subclinical hypothyroidism with serum levels of thyroid stimulating hormone slightly elevated to 4.4 microg/dl (normal: 0.4-4 microg/dl). Thyroid ultrasound showed diffuse irregularity of the gland and the presence of a solitary nodule (30x18 mm in diameter) localized in the left lobe. A fine needle aspiration biopsy was performed. Cytological analysis revealed papillary thyroid carcinoma and Hashimoto's thyroiditis. Total thyroidectomy was performed. During the operation, two of the parathyroid glands were detected to be hyperplastic. Histopathological examination of the thyroid and parathyroid glands revealed Hashimoto's thyroiditis with papillary thyroid carcinoma and synchronous carcinoma of the parathyroid gland. To our knowledge, this association of occult parathyroid carcinoma in a patient with papillary thyroid carcinoma and Hashimoto's thyroiditis has not been reported in the literature. Given the high prevalence of autoimmune diseases in elderly women, a random occurrence of this triad represents the most likely explanation.     

Inhibition by immunoglobulin G of synthesis of thyroid hormone in thyroid cultures from hypothyroid patients with goitrous Hashimoto's thyroiditis

Recently, thyroid microsomal antigen was identified as thyroid peroxidase, and thyroid microsomal antibody was found to inhibit thyroid peroxidase activity in vitro. We investigated the possibility that anti-microsomal antibody inhibits the iodination of tyrosine, in vivo. Immunoglobulin G with or without anti-microsomal antibody from hypothyroid patients with goitrous Hashimoto's thyroiditis inhibited thyroid hormone synthesis in cultured slices of normal human thyroid tissue. IgGs with anti-microsomal antibody inhibited 125I thyroidal uptake and thyroid hormone synthesis stimulated by TSH more than normal IgG did. However, the same results were obtained with IgGs without anti-microsomal antibody. This effect did not involve anti-microsomal antibody, anti-thyroglobulin antibody, TSH-binding inhibitor immunoglobulin, thyroid stimulation-blocking immunoglobulin, or the cAMP level of the thyroid tissue. The ratio of organic I to inorganic I with stimulation by TSH in slices incubated with IgG from hypothyroid patients with goitrous Hashimoto's thyroiditis or normal IgG was not significantly different, but was significantly higher in slices incubated with methylmercaptoimidazole. Therefore, IgG from hypothyroid patients with goitrous Hashimoto's thyroiditis mainly suppressed 125I thyroidal uptake, rather than inhibiting thyroid peroxidase activity. In addition, this IgG was present in the serum of 11 of the 12 hypothyroid patients with Hashimoto's thyroiditis studied. This IgG may be involved in the mechanism that causes hypothyroidism in some patients with goitrous Hashimoto's disease.     

Development of severe aplastic anemia in a girl with Hashimoto's thyroiditis and papillary thyroid carcinoma

A 14-year-old girl was admitted because of general fatigue and cervical lymphadenopathy. She showed bilateral struma (IInd degree) and enlargement of her left cervical lymph nodes. Laboratory data revealed neutropenia (219/microliter) and thrombocytopenia (Plt 5.1 x 10(4)/microliter) with mild anemia (Hb 11.1 g/dl), and the bone marrow aspirate and biopsy specimens showed hypocellularity. In addition, auto-antibodies against thyroid peroxidase (TPO) and thyroglobulin (TG) were highly elevated. Computed tomography of the neck showed a nodule in the left thyroid lobe with marked lymphadenopathy, and fine needle aspiration biopsy demonstrated papillary thyroid carcinoma with Hashimoto's thyroiditis and metastasis to the lymph nodes. One month after left thyroid lobectomy and cervical lymphadenectomy, the patient's condition progressed to very severe aplastic anemia, and she received immunosuppressive therapy consisting of cyclosporin A and anti-thymocyte globulin. Hematologically, partial and complete responses were obtained three and six months later, respectively. Of interest, anti-TPO and TG antibody titers remarkably decreased after immunosuppressive therapy. The patient had HLA-DR 2(DRB 1*1501) and DR 8(DRB 1*0802). The former is frequently found in patients with cyclosporin A-dependent aplastic anemia, and the latter is frequently found in Asian patients with Hashimoto's thyroiditis, suggesting an underlying autoimmune background for the simultaneous outbreak of aplastic anemia and Hashimoto's thyroiditis complicated by thyroid carcinoma.     

Multiple branchial cleft-like cysts in a female patient with Hashimoto's thyroiditis

We report a case of branchial cleft-like cysts (intrathyroidal lymphoepithelial cysts) associated with Hashimoto's thyroiditis. Palpation did not detect any nodules. Multiple cystic lesions were detected in the lateral side of the thyroid bilateral lobes by imagings of an I-123 scintigram, Tl-201 scintigram, sonography, and computerized tomography. Sonography displayed multiple cysts with strong echogenic spots in the cystic fluid. Repeated fine needle aspiration biopsies of the cysts consistently revealed only normal lymphocytes. Although these lesions could not be given diagnosis, subtotal thyroidectomy leaving the intact isthmus was performed. Microscopic findings revealed multiple branchial cleft-like cysts lined by flattened epithelial cells. Surrounding the epithelial lining were dense lymphoid follicles with large, reactive germinal centers. The remaining thyroid parenchyma showed Hashimoto's thyroiditis. Multiple branchial cleft-like cysts should be considered when sonographic examination reveals multiple cysts in the lateral side of the bilateral lobes, and fine needle aspiration biopsy displays only normal lymphocytes. To our knowledge, this is the first case of branchial cleft-like cysts associated with Hashimoto's thyroiditis reported in Japan.     

Thyroid cytology and histology

Fine needle aspiration (FNA) is an economical procedure that allows prompt evaluation of a thyroidal mass. Careful attention to each step of the aspiration will allow good specimens to be obtained. The cytopathologist should obtain the aspirates or else should accompany the clinician performing the aspirations. Unsatisfactory specimens should constitute less than 5% of the total. Reliable diagnoses can be made of papillary carcinoma, medullary carcinoma, anaplastic carcinoma, chronic lymphocytic thyroiditis, benign cystic lesions and the usual colloid-rich adenomatoid nodules. The diagnosis of follicular neoplasms and some cellular adenomatoid nodules remains problematical. Therefore, some thyroid operations inevitably yield benign follicular lesions.     

Diagnosis of thyroid malignant lymphoma by reverse transcription-polymerase chain reaction detecting the monoclonality of immunoglobulin heavy chain messenger ribonucleic acid

Distinguishing between thyroid malignant lymphoma and lymphocytic thyroiditis (Hashimoto's thyroiditis) is quite difficult and problematic. Molecular techniques to detect clonal lymphoid proliferation based on Ig heavy chain (IgH) gene rearrangement may be used to facilitate more accurate diagnosis of malignant lymphoma. We recently established a method for diagnosing thyroid tumors by analyzing ribonucleic acids (RNAs) extracted from the needles used for fine needle aspiration biopsy (aspiration biopsy-RT-PCR). By applying the aspiration biopsy-RT-PCR method to detection of the monoclonality of IgH messenger RNA (mRNA), an accurate molecular-based diagnosis of malignant lymphoma can be established as an adjunct to cytological diagnosis. We first studied RNAs from fresh tissues samples of 8 cases of Hashimoto's thyroiditis and 18 malignant lymphomas to detect the monoclonality of IgH mRNA by seminested RT-PCR. Monoclonality was detected in 8 of 18 (44.4%) malignant lymphomas, but in none of the 8 cases of Hashimoto's thyroiditis. We then studied aspirates from 10 cases of thyroid malignant lymphoma, 4 cases of Hashimoto's thyroiditis, and 1 case each of adenomatous goiter and papillary carcinoma. Monoclonality was detected in the aspirates from 4 of 10 malignant lymphomas (40%), but not from other tissues. Thus, RT-PCR detection of monoclonality of IgH mRNA in addition to cytological examination may be useful in diagnosing thyroid malignant lymphoma.     

Thyroidal prelymphoma

We treated a 32-year-old man with "thyroidal prelymphoma", morphologically resembling Hashimoto's thyroiditis and associated with monoclonal gammopathy (IgG, lambda). Immunohistochemistry revealed intracytoplasmatic monoclonal immunoglobulin (IgG, lambda) containing lymphoid cells in the interstitium of the thyroid tissue. After total thyroidectomy had been performed, the monoclonal immunoglobulin disappeared. Three years have passed since the surgery and this writing, there has been no recurrence. The existence of thyroidal prelymphoma suggests that chronic antigenic stimulation might produce lymphocytes which are more susceptible to neoplastic change (Hashimoto's thyroiditis----thyroidal prelymphoma----malignant lymphoma of the thyroid).     

Hashimoto's thyroiditis. An uncommon cause of painful thyroid unresponsive to corticosteroid therapy

The records of eight patients with thyroid tenderness secondary to Hashimoto's thyroiditis were reviewed. The pathologic characteristics of thyroid tissue sections from these patients were compared with those from patients with nontender Hashimoto's thyroiditis, and no difference was identified. Laboratory features helpful in distinguishing tender Hashimoto's thyroiditis from subacute (de Quervain's) thyroiditis include normal erythrocyte sedimentation rate, significant 131I uptake, and significant antithyroid antibody titer. Diagnosis should be confirmed by fine-needle aspiration biopsy. Corticosteroid therapy was unsuccessful in treating these patients; L-thyroxine and aspirin were successful more often. Two patients required thyroidectomy to control pain.     

A variant of thyrotoxicosis associated with chronic thyroiditis characterized by prolonged fever, absence of anti-thyroidal antibodies, and favorable response to naproxen

An unusual form of thyrotoxicosis due to chronic thyroiditis is described. A 78-year-old debilitated woman was admitted because of fever to 38 degrees C persisting for the previous 16 months, for which the antipyretic effect of diclofenac sodium and pranoprofen had been insufficient or transient. Intense accumulation of gallium-67 citrate in the thyroid gland provided an initial clue to the diagnosis of masked thyrotoxicosis as a cause of the fever, and naproxen (300 mg/d) eliminated the fever and flaring of thyrotoxicosis. Despite the absence of autoantibodies related to chronic thyroiditis, needle biopsy revealed destructive thyroiditis due to chronic lymphocytic thyroiditis. This case suggests a previously unrecognized variant of thyrotoxicosis due to chronic thyroiditis, that is, neither painless thyroiditis nor acute exacerbation of Hashimoto thyroiditis, and instead characterized by prolonged fever, nontender thyroid, absence of antibodies associated with autoimmune thyroiditis, and excellent response to naproxen.     

Subacute thyroiditis associated with positive antibodies to the Epstein-Barr virus

Subacute thyroiditis is an inflammatory disorder of the thyroid caused probably by viruses. It is clinically characterized by the presence of anterior cervical pain and/or painful goiter, and rarely as fever of unknown origin or as prolonged fever syndrome. We report a case of a 49-year-old female admitted to the hospital because of fever during last month, leukocytosis and accelerated erythrocyte sedimentation rate. Following observation, slight tenderness over the thyroid gland and signs of hyperthyroidism occurred. After the laboratory studies, low thyroidal radioactive iodine uptake and fine-needle aspiration cytology (FNAC) of thyroid, she was diagnosed of subacute thyroiditis with hyperthyroidism. We believe that the etiologic agent was the Epstein-Barr virus because heterophile and Epstein-Barr virus-specific antibodies were positive. The patient was treated with acetaminophen (1.500 mg/day) with prompt and complete resolution of the clinical and laboratory abnormalities. There has been no recurrence of the disease during a 1 year follow-up.     

A case of Hashimoto's thyroiditis with thyroid immunological abnormality manifested after habitual ingestion of seaweed

An interesting case of iodide induced goitre with immunological abnormalities is described. The patient who was sensitive to synthetic penicillin had previously been treated for exudative pleuritis, congestive heart failure and acute renal failure. Following recovery, he began to ingest large amounts of seaweed after which he developed goitrous hypothyroidism. It was of interest that the serum level of gamma-globulin increased, and subsequently the antithyroid microsomal antibody became strongly positive, suggesting that thyroidal autoimmune processes had been precipitated. Biopsy of the thyroid gland revealed chronic thyroiditis, with evidence suggesting extreme stimulation by TSH. Hight thyroidal uptake of 131I, positive perchlorate discharge test and biochemical analysis of the thyroidal soluble protein showed severe impairment of hormone synthesis following continuous accumulation of excess iodide. While there is evidence suggesting that increased iodide may be an important factor in the initiation of Hashimoto's thyroiditis, this may result from the marked increased sensitivity of Hashimoto's gland to the effects of iodine. Thus an occult lesion could be unmasked in this manner. The mechanism by which iodide mediates this effect is not clear.     

Thyroid amyloidosis with recurrent subacute thyroiditis-like syndrome

We studied 2 men with a subacute thyroiditis-like syndrome (STLS) associated with systemic amyloidosis. Both had very tender, diffuse, firm goiters, low thyroidal radioactive iodine uptake values, and increased erythrocyte sedimentation rates. Glucocorticoid therapy resulted in dramatic improvement. Compared to 18 patients with subacute thyroiditis, these 2 men had 1) persistence of goiter even in remission, 2) repeated exacerbation of STLS, 3) pain always localized in the same site, and 4) gastrointestinal, renal, and cardiac abnormalities. Histological examination of the patients' thyroid glands revealed amyloid deposition and no evidence of subacute thyroiditis. In addition, 1 man had low T3 thyrotoxicosis with an elevated rT3/T3 ratio, suggesting impaired peripheral conversion of T4 to T3, and immunological and histological evidence of Hashimoto's thyroiditis. These findings suggest that thyroid amyloidosis may be associated with STLS. When patients with clinical features of subacute thyroiditis have an unusual course, the possibility of thyroid amyloidosis should be considered.     

桥本甲状腺炎甲状腺细针穿刺两种细胞学亚型临床特点比较

回顾性分析397例经甲状腺细针穿刺细胞学(FNAC)确诊桥本甲状腺炎患者的临床特点.发现嗜酸细胞型(n=181)及淋巴细胞型(n=186)桥本甲状腺炎临床表现、抗甲状腺自身抗体(甲状腺球蛋白抗体、甲状腺过氧化物酶抗体)水平无差异.嗜酸细胞型较淋巴细胞型更倾向进展为甲状腺功能减退,可能为疾病进程中晚期阶段.     

NON-TOXIC GOITRE: DIAGNOSTIC ROLE OF ASPIRATION CYTOLOGY, ANTIBODIES AND SERUM THYROTROPHIN

Fifty cases of bilateral non-toxic goitre, largely unselected, have been studied using fine needle aspiration cytology (without local anaesthesia); four techniques of thyroid antibody tests; serum thyroid biochemistry (including radioimmunoassay of TSH) and clinical evaluation. Autoimmune thyroiditis was found cytologically in 64%; simple colloid goitre in 24%; subacute thyroiditis of de Quervain in 10%. Aspiration cytology was the most sensitive means of detecting autoimmune thyroiditis and subacute thyroiditis. Two antibodies directed against the intra-cellular cyto-plasmic antigen-the complement fixation test and an immunofluorescent antibody were of lesser value in detecting autoimmune thyroiditis (80% positivity) though equal to each other. Serum TSH was of some value-being elevated in 63% of cases of autoimmune thyroiditis and in no cases of simple colloid goitre. Two major cytological subtypes of autoimmune thyroiditis have been described-with significant differences in duration of goitre, mode of presentation, frequency of hypo-thyroidism, and response to thyroxine therapy. The high frequency of autoimmune thyroiditis in this series suggests that endemic goitre is unlikely in Western Australia.     

Interpretation of serum calcitonin in patients with chronic autoimmune thyroiditis

Calcitonin (CT) is an important clinical marker for the diagnosis and follow-up of medullary thyroid carcinoma, although it is not absolutely specific. Some authors have reported C-cell hyperplasia in a number of thyroid specimens affected by Hashimoto's thyroiditis. The association between thyroiditis and hypercalcitoninemia is still controversial because some authors have reported low CT levels. The aim of this study is to evaluate the basal CT values in patients with and without thyroid autoimmunity. From May 2005 to February 2010, 1073 patients underwent ultrasonography-guided fine-needle aspiration cytology at the Thyroid Center of Sapienza University of Rome, with evaluation of basal serum FT4, FT3, TSH, and antithyroid peroxidase (anti-TPO) antibodies as well as CT levels. Forty-one patients presented a basal CT level above the reference upper limit. The mean serum CT was significantly lower in women than in men (4.28 ± 6.63 vs 7.50 ± 25.50 pg/ml; P<0.01). Basal serum CT was not significantly higher in patients showing anti-TPO Ab positivity (4.71 ± 6.46 vs 4.84 ± 13.11 pg/ml; P>0.05). Importantly, the rate of 'suspicious' CT values (above the 10 pg/ml cutoff) was not significantly different between patients with or without thyroid autoimmunity (3.9 vs 3.0%). Patients with hypercalcitoninemia suffering from chronic autoimmune thyroiditis should undergo the same clinical evaluation procedure as patients do without thyroid autoimmunity.     

Detection and properties of TSH-binding inhibitor immunoglobulins in patients with Graves' disease and Hashimoto's thyroiditis.

TSH-binding inhibitor immunoglobulins (TBII) have been detected in patients with Graves' disease and Hashimoto's thyroiditis by using the radioreceptor assay of TSH. In untreated Graves' patients, TBII levels correlated well with thyroidal 99mTc uptake at 30 min and the grade of epithelial hyperplasia of thyroid follicles. There were many Graves' patients whose sera contained high TBII levels but no detectable bioassayable thyroid-stimulating activity (LATS), and in these patients, close correlation was observed between serum levels of TBII and bioassayable LATS-protector activity. TBII were detectable in 2 (10%) of 20 patients with Hashimoto's thyroiditis, both of whom were clinically hypothyroid. The serum or IgG fraction from one of them, however, did not contain any significant LATS, LATS-protector, or human thyroid adenylate cyclase-stimulating activity and caused inhibition of adenylate cyclase stimulation by TSH. In that patient, TBII may be acting to block TSH binding to TSH receptors, thus causing TSH unresponsiveness and hypothyroidism.     

Subacute cutaneous lupus associated with Hashimoto's thyroiditis

Subacute cutaneous lupus erythematosus is a widespread, non-scarring, photosensitive form of histologically specific cutaneous LE. These patients frequently have mild systemic illness marked by musculoskeletal complaints and characteristic serologic abnormalities. Hashimoto's thyroiditis coexists with other diseases of presumed autoimmune nature, including systemic lupus erythematosus. The association between subacute lupus and Hashimoto's disease has not been described. We describe here a patient with Hashimoto's thyroiditis and Sj?gren's syndrome who developed subacute cutaneous lupus two years later.     

Maltoma of the thyroid in a man with Hashimoto's thyroiditis

We report the case of a 42-yr-old man with primary thyroid lymphoma arising from mucosa-associated lymphoid tissue (MALT-lymphoma, maltoma). The patient underwent a hemithyroidectomy for a growing mass in the right lobe of the thyroid while being treated with 1-thyroxine for Hashimoto's thyroiditis. The clinical diagnosis of Hashimoto's disease was confirmed by aspiration biopsy of the mass during the course of L-thyroxine treatment. Postoperatively, histology showed atypical lymphoproliferative infiltrates suspicious of low-grade non-Hodgkin's lymphoma of mucosa-associated lymphoid tissue-type, coexisting with a reactive process typical of chronic lymphocytic thyroiditis. Immunophenotyping showed a mixed B- and T-lymphocyte population, which was nondiagnostic. However, Southern blot analysis revealed a clonal rearrangement of the Ig heavy chain gene. This case demonstrates that cytology or histology may not distinguish between reactive or low-grade lymphomatous thyroid processes. The use of molecular technique was essential to prove clonality and the presence of lymphoma.