A case of mixed connective tissue disease complicated with thymic carcinoma and Hashimoto's thyroiditis

Abstract

We report the case of a 63-year-old woman who suffered from mixed connective tissue disease (MCTD) complicated with thymic carcinoma and Hashimoto's thyroiditis. Although many systemic syndromes associated with thymoma and thymic carcinoma, i.e., myasthenia gravis, pure red cell aplasia, hypogammaglobulinemia, and Hashimoto's thyroiditis, are known, this is the first report of MCTD complicated with thymic carcinoma. It was suggested that MCTD may be a paraneoplastic syndrome associated with thymic carcinoma.     

Hypothyroidism associated with mixed connective tissue disease and its response to steroid therapy.

The case is reported of a 49-year-old housewife who presented with arthralgia and severe Raynaud's phenomenon. A diagnosis of mixed connective tissue disease (MCTD) was made on the basis of the clinical picture and serological findings. During the course of her disease she developed hypothyroidism. She was started on prednisolone to control the symptoms of the MCTD, and after this her thyroid function returned to normal despite her never having had any thyroid replacement therapy. There is reported evidence that Hashimoto's thyroiditis responds to systemic steroid preparations, but we can find no report of hypothyroidism in MCTD having a similar response.     

Turner's syndrome associated with Hashimoto's thyroiditis and sarcoidosis: a case report.

A 32-yr-old Japanese female who was suffering from Turner's syndrome associated with Hashimoto's thyroiditis and sarcoidosis is reported. It is known that Hashimoto's thyroiditis is not infrequently complicated with Turner's syndrome on the basis of an abnormal X chromosome. In this case, sarcoidosis occurred 4 months after Hashimoto's thyroiditis. This extremely interesting coincidence of Hashimoto's thyroiditis and sarcoidosis in Turner's syndrome has not been reported to date to our knowledge.     

Mixed connective tissue disease associated with autoimmune hepatitis and thyroiditis.

The case is reported of a 27 year old woman who had mixed connective tissue disease (MCTD) associated with chronic active hepatitis and thyroiditis. Although hepatomegaly is sometimes observed in MCTD, only four cases of MCTD and chronic active hepatitis have been described. It is thought that this is the first report of an association between MCTD, chronic active hepatitis and thyroiditis.     

Thymoma and autoimmune thyroiditis. A case report

We report an association between a thymus tumor and autoimmune thyroiditis. This association is probably related to loss of immune control secondary to loss of thymus integrity. A 48-year-old woman was hospitalized for thoracic pain. Her past history included thyroiditis treated by L-thyroxin for two years. The chest x-ray demonstrated a mediastinal opacity which was confirmed by computed tomography. Surgical resection was performed and histological analysis of the surgical specimen confirmed the diagnosis of lympho-epithelial thymoma. Thyroid immunity tests demonstrated the presence of anti-peroxidase antibodies confirming the diagnosis of Hashimoto's thyroiditis. Chest x-ray and CT-scan are indicated in patients with autoimmune thyroiditis to search for a thymic mass. Conversely, search for autoimmune thyroiditis is warranted in patients with an identified thymic mass.     

Four cases of Graves' disease which developed after painful Hashimoto's thyroiditis

We report four cases of Graves' disease that developed after painful Hashimoto's thyroiditis. All were middle-aged women, who had high titers of anti-thyroid antibodies and thyrotoxicosis at the onset of painful Hashimoto's thyroiditis. After 2 to 7 years, they developed Graves' disease with positive antibody against the thyrotropin receptor. Their clinical courses of Graves' disease went favorably due to the treatment with antithyroid drug or radioactive iodine therapy. Painful Hashimoto's thyroiditis is an atypical variant of Hashimoto's thyroiditis and is one form of destructive thyroiditis. Thyroid damage due to painful Hashimoto's thyroiditis may be associated with the development of Graves' disease.     

Gallium-67 uptake by the thyroid associated with progressive systemic sclerosis

Although thyroidal uptake of gallium-67 has been described in several thyroid disorders, gallium-67 scanning is not commonly used in the evaluation of thyroid disease. Thyroidal gallium-67 uptake has been reported to occur frequently with subacute thyroiditis, anaplastic thyroid carcinoma, and thyroid lymphoma, and occasionally with Hashimoto's thyroiditis and follicular thyroid carcinoma. A patient is described with progressive systemic sclerosis who, while being scanned for possible active pulmonary involvement, was found incidentally to have abnormal gallium-67 uptake only in the thyroid gland. Fine needle aspiration cytology of the thyroid revealed Hashimoto's thyroiditis. Although Hashimoto's thyroiditis occurs with increased frequency in patients with progressive systemic sclerosis, thyroidal uptake of gallium-67 associated with progressive systemic sclerosis has not, to our knowledge, been previously described. Since aggressive thyroid malignancies frequently are imaged by gallium-67 scintigraphy, fine needle aspiration cytology of the thyroid often is essential in the evaluation of thyroidal gallium-67 uptake.     

Enhanced cellular proliferative activity and cell death in chronic thyroiditis and thyroid papillary carcinoma

For the analysis of cellular proliferative activity and cell death in thyroid diseases, the Ki-67 labeling index, bcl-2 protein expression and cell death of follicular epithelia by immunohistochemistry and in situ DNA nick-end labeling methods were evaluated in normal thyroid tissues as well as in surgical specimens from cases of Hashimoto's disease (16 cases), focal lymphocytic thyroiditis (13 cases), Graves' disease (15 cases), follicular adenoma (20 cases) and papillary carcinoma (43 cases). Cellular proliferative activity and cell death were both enhanced in cases of thyroiditis, including Hashimoto's disease and focal lymphocytic thyroiditis. Thyroids from patients with follicular adenoma and papillary carcinoma also showed increased cellular proliferative activity and cell death. In addition, predominant high cellularity and partial loss of bcl-2 protein expression in papillary carcinoma suggested that the overgrowth and dedifferentiation were associated with malignancy.     

Hashimoto's Thyroiditis Presenting as Acute Painful Thyroiditis and as a Manifestation of an Immune Reconstitution Inflammatory Syndrome in a Human Immunodeficiency Virus-Seropositive Patient

Background: An immune reconstitution inflammatory syndrome (IRIS) may complicate immune restoration following start of antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected patients. The occurrence of Graves' disease in the setting of an IRIS is well recognized. We hereby report a case of Hashimoto's thyroiditis, presenting as an acute painful thyroiditis, and as a complication of IRIS. Summary: A painful acute thyroiditis with thyrotoxicosis occurred in a 37-year-old HIV-infected woman 10 months after initiation of ART. This thyroiditis was associated with the appearance of a high titer of anti-thyroid peroxidase (anti-TPO) antibodies and was followed by persistent hypothyroidism, requiring thyroxine replacement therapy. Conclusions: Hashimoto's thyroiditis may present as an acute thyroiditis with thyrotoxicosis in HIV-infected patients after initiation of ART. Clinicians caring for HIV-infected patients should be aware of this possible association.     

Mixed connective tissue disease associated with idiopathic portal hypertension and chronic thyroiditis

We report a patient with mixed connective tissue disease (MCTD) associated with idiopathic portal hypertension (IPH) and chronic thyroiditis. The patient was a 68-year-old Japanese woman who was admitted to our hospital for treatment of bleeding esophageal varices. She had previously exhibited Raynaud's phenomenon and had had arthritis for about 30 years. She also had had high titers anti-U1 of ribonucleoprotein (RNP) anti-single strand-DNA autoantibodies for 2 years, and had been diagnosed with MCTD 1 year previously. The bleeding from esophageal varices was successfully stopped by endoscopic injection sclerotherapy. Results of laboratory examinations, imaging examinations, and laparoscopy, including liver biopsy, indicated that the esophageal varices were caused by portal hypertension due to IPH. The patient also had a diffusely firm and enlarged goiter and hypothyroidism, and she exhibited anti-thyroid microsomal antibodies and anti-thyroglobulin antibodies, she was diagnosed as having a complication of chronic thyroiditis. This association of MCTD, IPH, and chronic thyroiditis is quite rare and provides a unique opportunity to observe immunological involvement in the pathogenesis of IPH.     

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.     

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.     

Rifampin-induced hypothyroidism without underlying thyroid disease.

Rifampin (RFP) increases hepatic microsomal enzyme activity, and there are case reports of RFP-induced hypothyroidism, all associated with Hashimoto's thyroiditis. Here, we report a case of RFP-induced hypothyroidism without underlying thyroid disease.     

Increased Risk of Papillary Thyroid Cancer in Celiac Disease

Patients with celiac disease have an increased rate of malignancies that are not limited to lymphomas. Thyroid carcinoma has not previously been associated with celiac disease. However, among a cohort of patients with celiac disease, we identified an increased risk of papillary carcinoma of the thyroid, standard morbidity ratio of 22.52 (95% confidence interval 14.90–34.04; P < .001), compared to United States national surveillance data. These patients were on a gluten-free diet. Only 1 had Hashimoto's thyroiditis, suggesting that mechanisms apart from autoimmune thyroiditis contribute to the increased risk of carcinoma of the thyroid in celiac disease.     

Hodgkin's disease and hyperthyroidism

In recent years we have had the occasion to observe hyperthyroidism in 6 patients with Hodgkin's disease. All patients had received Mantlefield irradiation and were disease-free when hyperthyroidism appeared. Hyperthyroidism allows three different pictures to be distinguished: 1 case report of Graves' disease without ophthalmopathy, 1 case report of Hashimoto's thyroiditis corresponding to a particular form called hashitoxicosis, and 4 case reports of atypical silent thyroiditis. Reports concerning case studies of postirradiation Graves' disease or Hashimoto's thyroiditis during Hodgkin's disease are only to be found exceptionally. Atypical silent thyroiditis was recently individualized, but no postirradiation case studies have been reported. It is suggested that these 6 cases represent a radiation-induced immune thyroid disease: physiopathology and predisposing factors are discussed.     

Sarcoidosis and Hashimoto's thyroiditis--a chance occurrence?

We present a case of pulmonary sarcoidosis associated with Hashimoto's thyroiditis. This association has been reported previously and may be purely coincidental. However, in light of current knowledge about the immunoregulatory defects postulated for sarcoidosis and for Hashimoto's thyroiditis, three other possibilities that may explain this association in our patient, are discussed.     

Coincidence of Sarcoidosis and Hashimoto's thyroiditis.

A 59-year-old, female patient died of pulmonary embolus 16 days after an operation for a Moore prosthesis. At autopsy, previously unsuspected sarcoidosis and Hashimoto's thyroiditis were found. The sarcoidosis was noted in one focus in the lung and in all lymph nodes examined. In the thyroid gland, Hashimoto's thyroiditis was observed. In addition, structures that could not be differentiated morphologically from papillary Hurthle cell carcinoma were seen in the thyroid.     

Increased thyroid blood flow in the hypoechoic lesions in patients with recurrent, painful Hashimoto's thyroiditis at the time of acute exacerbation

We report two cases with painful Hashimoto's thyroiditis, who developed recurrent fever and painful thyroid. Glucocorticoid treatment was transiently successful but tenderness in the thyroid gland and fever developed when glucocorticoid was tapered. One patient underwent total thyroidectomy uneventfully. As is well known, it is frequently difficult to make differential diagnosis between painful Hashimoto's thyroiditis and subacute thyroiditis particularly at the initial phase. Interestingly, color flow doppler sonography of patient 1 revealed an increased thyroid blood flow in the hypoechoic lesions at the time of acute exacerbation although the serum level of TSH was suppressed. In the other patient, thyroid blood flow was also increased mainly in the hypoechoic lesions when the serum level of TSH was moderately increased, and it disappeared completely after supplementation of prednisolone and L-T4. Since thyroid blood flow in subacute thyroiditis is always decreased, such an increased blood flow in the hypoechoic lesion may be one of clinical characteristics of painful Hashimoto's thyroiditis, and useful for differential diagnosis from subacute thyroiditis.     

Hashimoto encephalopathy. Analysis of four case reports

INTRODUCTION: Encephalopathy associated with Hashimoto's thyroiditis has been recognized for more than 30 years and is probably underestimated. EXEGESIS: We report four patients with Hashimoto's thyroiditis who presented neurological or psychiatric features. There were three women and one man, with a mean age of 68 years. Neurological presentations were various: seizures, psychotic episodes, altered consciousness, hallucinations without usual aetiological diseases (infectious, metabolic, neoplasic, vascular, etc.). Neurological investigations (EEG, brain CT, magnetic resonance imaging) were unspecific. In all cases, a moderately high CSF protein level without pleocytosis was found. Patients presented slight hypothyroidism with high titers of antithyroperoxidase antibodies. Despite hormone therapy replacement, neurological features persisted. Outcome was favorable under steroid therapy. CONCLUSION: Hashimoto's encephalopathy must be considered in the face of neuropsychiatric manifestations without obvious etiology. Pathogenic mechanisms are not clear but probably involve autoimmune cerebral vasculitis because of the efficacy of steroids.     

Thyroidectomy for Hashimoto's thyroiditis: complications and associated cancers

BACKGROUND: Hashimoto's thyroiditis is usually treated medically; however, thyroidectomy is sometimes indicated. Thyroiditis can make thyroid dissection more difficult and possibly increase the risk of surgical complications. The aim of this study was to determine the rate of complications and associated cancer in patients with Hashimoto's thyroiditis. METHODS: Retrospective series of 474 patients treated surgically at the University of California, San Francisco, between January 1985 and June 2005 with final pathology demonstrating Hashimoto's thyroiditis, chronic lymphocytic thyroiditis, or chronic thyroiditis. Parameters evaluated included demographics, surgical indications, and postoperative complications. RESULTS: Among the 474 patients, 133 had thyroidectomy because of preoperative diagnosis of thyroid cancers (median age 39 years; 116 females and 17 males), 316 had thyroidectomy because of benign thyroid nodules or goiter (median age 47.5 years; 292 females and 24 males), and 25 had thyroidectomy to relieve local symptoms caused by thyroiditis but did not have thyroid nodules (median age 42 years; 25 females). No death or permanent surgical complications occurred. One hundred and fifty-two patients (32.1%) had transient postoperative hypocalcemia, 2 (0.4%) had transient recurrent nerve palsy, and 4 (0.8%) had a postoperative neck hematoma. Fifty-three percent had thyroid cancer at final histological examination. CONCLUSIONS: Thyroidectomy can be performed in patients with Hashimoto's thyroiditis with a low risk of permanent surgical complications. Cancer is common in patients who have a thyroidectomy for Hashimoto's thyroiditis even when not suspected preoperatively.