Two cases of thyroid sarcoidosis presentation as painful, recurrent goiter in patients with Graves' disease

Sarcoidosis rarely involves the thyroid gland. Pain in the thyroid gland area was only sporadically reported in patients suffering from this disease. The aim of this paper is to report and discuss the cases of two female patients with Graves' disease who presented painful, rapidly growing, recurrent goiters (after strumectomy in their early adult lives). Invasive treatment was applied and sarcoidosis was revealed histologically. The first patient suffered from dysphagia and dyspnoea due to large goiter; skin lesions were present as well. Sarcoidosis was diagnosed in histological examination of the thyroid tissue specimens. Steroid treatment was ineffective; thus, the thyroid was removed. Two years later thyroid sarcoidosis recurred as a painful goiter and surgical treatment was applied once again. In the second case, thyroid ultrasound findings suggesting malignancy, and prompted the decision to perform thyroidectomy despite the fact that FNAB (fine needle aspiration biopsy) revealed cells indicative of a "granulomatous disease in the post-resection scar" and results of the thorax high-resolution computed tomography scan suggested pulmonary sarcoidosis. Pathological examination confirmed sarcoidosis. However, a papillary cancer focus was also found.     

Sarcoidosis of the thyroid and kidneys and calcium metabolism

In sarcoidosis, the thyroid and the kidneys are infrequently affected. Clinically recognizable thyroid involvement occurs in < 1% of sarcoidosis patients. Hyperthyroidism, myxodema, and thyroid occur with an equal frequency. It is important to distinguish sarcoidosis of the thyroid from other infections and disorders of the gland. Renal involvement may present as granulomatous infiltration of the renal parenchyma, glomerulonephritis, renal arteritis, and nephrocalcinosis or renal stones. The latter are due to abnormalities of calcium metabolism. Hypercalcemia occurs in about 10 to 13% of sarcoidosis patients; hypercalciuria is three times more frequent. Calcium abnormalities may precede, follow, or occur at any time during the course of sarcoidosis. An endogenous overproduction of 1,25-dihydroxyvitamin D [1,25-(OH (2))-D (3)] by granulomatous tissue and activated macrophages results in an increase of intestinal absorption of calcium. Corticosteriods, chloroquine, and hydroxychloroquine subdue 1,25-(OH (2))-D (3) production and correct hypercalcemia and hypercalciuria.     

Immune status in a case of thyroid gland sarcoidosis--selected parameters]

On the basis of a case of sarcoidosis and the thyroid gland selected immunological parameters were examined and they were compared with the findings in pulmonary sarcoidosis. While the examination of the immunoglobulins in the present case did not show any characteristic changes, in the examination of the cellular immunity the hyporeactivity of the peripheral lymphocytes typical for the pulmonary sarcoidosis was found. The inclusion of immunological parameters is an enlargement of the possibilities for the differential diagnostic clarification of granulomatous inflammations of the thyroid gland.     

High Incidence of Positive Autoantibodies against Thyroid Peroxidase and Thyroglobulin in Patients with Sarcoidosis

OBJECTIVE  Although abnormalities of the humoral immune system, such as increased immunoglobulin production, are known in sarcoidosis, the relationship between sarcoidosis and autoimmune disorders is uncertain. We studied the incidence of thyroid autoantibodies and the prevalence of Hashimoto's thyroiditis in patients with sarcoidosis.
PATIENTS AND MEASUREMENTS  Sixty-two patients with pulmonary sarcoidosis, diagnosed by a combination of clinical, radiographic and histological findings, were studied. As controls, three groups of subjects aged 40 and over without a known history of thyroid disease (60 patients with pulmonary diseases other than sarcoidosis, 88 hospital employees and 82 company workers), were also analysed. Antibodies against thyroid peroxidase (TPO-Ab) and purified thyroglobulin (Tg-Ab) were measured by radioimmunoassay and antibodies against microsomal antigen (MCHA) and thyroglobulin (TGHA), by haemagglutination.
RESULTS  Seventeen of 62 patients (27.4%) had either positive TPO-Ab or Tg-Ab or both. All the patients with positive thyroid autoantibodies were of middle or advanced age, and the incidence of positive TPO-Ab/Tg-Ab in patients with sarcoidosis aged 40 and over was 54.5% in males, 32.4% in females and 37.8% overall. The prevalence was significantly higher in males compared to age-matched control males (0–7.7% in the controls), and in female patients was twice that found in controls (11.8–16.3%). Seven patients had Hashimoto's thyroiditis, indicating that the prevalence was 11.3%, and much higher than that previously reported.
CONCLUSIONS  The data show a remarkably high incidence of thyroid autoantibodies in patients of middle or advanced age with sarcoidosis, especially in males, and a higher prevalence of Hashimoto's thyroiditis than in previous reports.     

Papillary thyroid carcinoma in a patient with sarcoidosis treated with minocycline

Long-term treatment with minocycline is occasionally associated with the development of black thyroid syndrome in which thyroid cancer is frequently found. Here, we report a patient with cutaneous, pulmonary and thyroid sarcoidosis who developed papillary thyroid carcinoma in the presence of a black thyroid syndrome after being treated with minocycline for 2.5 years.     

Thyroid involvement of sarcoidosis

A 54-year-old woman was found to have abnormal shadows on her chest radiograph taken on an annual medical examination. The chest radiograph showed multiple nodules in the bilateral middle and lower lung fields accompanied with bilateral hilar lymphadenopathy. A computed tomography of the neck and chest revealed nodules in her right middle lobe and bilateral lower lobes with an enlarged thyroid. A metastatic malignant disease involving both thyroid and lungs was suspected, therefore thyroid and lung biopsies were performed. The histological examination of the thyroid and the lung specimens revealed non-caseating epithelioid cell granulomas which were compatible with sarcoidosis. Although the thyroid involvement of sarcoidosis is rare, it should be included in the differential diagnosis with patients with thyroid swelling.     

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.     

Malignancies in patients with sarcoidosis]

We evaluated the occurrence and type of malignant tumors in 148 patients with sarcoidosis followed at the Okayama University Hospital. Nine patients had malignancies; in 2 of 9 patients the development of malignancy preceded that of sarcoidosis, and one patient presented with sarcoidosis and malignancy at the same time. Six patients developed six types of malignancy following the development sarcoidosis; one case each of stomach cancer, lung cancer, breast cancer, thyroid cancer, testicular tumor, laryngeal cancer, and chronic lymphocytic leukemia. There was no significant difference between sexes (3 males and 3 females). The mean age of the cancer group at the onset of sarcoidosis was 56 years, which was significantly higher (p less than 0.05) than that of the control group. In these 6 patients, the mean interval from onset of sarcoidosis to detection of cancer was 11.7 years (range 1.5 to 30.2 years). The relative risk of malignancy was calculated based on the data for 148 patients with sarcoidosis with a total of 1371 person-years. The expected incidences of cancer for all sites and specific sites were estimated by applying age- and sex-adjusted person-years. The observed incidence of cancer was significantly (p less than 0.05) greater than the expected incidence for thyroid cancer, laryngeal cancer, and leukemia. No significant difference in incidence was found for all sites or for the other sites of cancer. The increased cancer incidence in sarcoidosis may be secondary to immunological abnormalities associated with this disease.     

Sarcoidosis of the thyroid gland associated with hyperthyroidism: review of the literature and report of two peculiar cases

Sarcoidosis is a systemic disease characterized by non-caseating granulomas that rarely involve the thyroid gland. Thyroid sarcoidosis has seldom been documented, and few cases have so far been described in association with hyperthyroidism. Here, we review the literature on this association, report two patients presenting with hyperthyroidism and histologically-proven sarcoidosis, and discuss related clinical, biochemical, pathological and genetic findings.     

Amyloid goiter in a case of systemic amyloidosis secondary to ankylosing spondylitis

Infiltrative diseases of the thyroid include systemic sclerosis, hemochromatosis, sarcoidosis, chondrocalcinosis and amyloidosis. Only rarely does thyroid amyloidosis result in clinically palpable goiter. Classically, amyloidosis is associated with tuberculosis, rheumatoid arthritis, multiple myeloma or inflammatory bowel disease. Only rarely does clinical amyloidosis develop in the setting of ankylosing spondylitis. We describe a case of amyloid goiter in a patient with ankylosing spondylitis-associated amyloidosis.     

Concomitant association of thyroid sarcoidosis and Hashimoto's thyroiditis

A female patient had sarcoidosis of the thyroid and Hashimoto's thyroiditis. This seems to be the first report in which these two histological conditions were concomitantly present.     

Thyroid manifestations of sarcoidosis: a case report

Sarcoidosis is a systemic disease with many localizations. Thyroid involvement has been often described but rarely confirmed histologically. A common immune mechanism appears to be the cause. Thyroid sarcoidosis should be envisaged in patients with a thyroid nodule and mediastino-pulmonary involvement. We report the case of a 63-year-old woman with no past history who was hospitalized for dyspnea. Explorations evidenced a cold thyroid nodule associated with diffuse interstitial lung disease and mediastinal node enlargement. Pathology examination disclosed the sarcoid nature of the thyroid nodule and the lung lesions.     

The occurrence of polyglandular autoimmune syndrome type III associated with coeliac disease in patients with sarcoidosis

Abstract. Objectives. To study whether an association between polyglandular autoimmune (PGA) syndrome type III [including autoimmune thyroid disease (ATD) and insulin-dependent diabetes mellitus (IDDM)], coeliac disease and sarcoidosis, exists. Design. In patients with documented sarcoidosis, the presence of the disease constellation of ATD, IDDM and coeliac disease was examined. Setting. The patients were recruited at the Department of Pulmonary Medicine, and the study was conducted at the Department of Endocrinology, Lund University Clinics, General Hospital, Malmö, Sweden. Subjects. Of all patients (n = 89) with documented sarcoidosis attending the Department of Pulmonary Medicine between January 1980 and December 1991, 78 patients (44 males, 34 females; median age at the time of the study 48 years, range 22–81 years; median observation time since the diagnosis of sarcoidosis 120 months, range 1–468 months) were examined in the present study. Results. Amongst the 78 patients with documented sarcoidosis, one female patient was found with PGA syndrome type III, coeliac disease and sarcoidosis. Conclusions. This present patient further indicates the existence of an association between polyglandular autoimmune (PGA) syndrome type III, coeliac disease and sarcoidosis. To determine whether this disease constellation might constitute a new syndrome, further studies on larger groups of patients with sarcoidosis are demanded.     

Thyroid sarcoidosis as a unique localization.

Sarcoidosis is a systemic disorder characterized by granulomatous lesions, principally affecting the lungs. There are numerous reports in the literature of an associated involvement of the thyroid, much more frequently in hypothyroid than in hyperthyroid subjects. The present case report refers to a woman presenting with thyroid nodules and normal biochemical levels and thyroid function parameters, while histology revealed sarcoid-type lesions. Subsequent investigations and a long follow-up showed no evidence of involvement of other sites, including the lungs. Consequently, after a long period of normal health associated with the negative results of the examinations, a diagnosis of sarcoidosis limited to the thyroid was proposed, which was cured by thyroidectomy.     

Cardiac sarcoidosis complicated by multivessel coronary spasm: a case report]

A 63-year-old woman with abnormal Q waves in leads II, III, aVF developed ventricular tachycardia after an operation for thyroid carcinoma. Coronary arteriography revealed no organic stenosis, but acetylcholine induced total occlusion of the right coronary artery and severe narrowing of the left coronary artery. Left ventriculography showed inferoposterior and septal akinesis, and echocardiography revealed slight thinning of these affected walls. She had old myocardial infarction due to spasm. One year later, she developed bilateral uveitis and recurrence of tachycardia. Cardiac sarcoidosis was diagnosed by endomyocardial biopsy. In our patient with cardiac sarcoidosis, the presence of multivessel coronary spasm made the diagnosis difficult and may have contributed to cardiac dysfunction. Coronary arteries are rarely involved, but the development of coronary spasm may be linked to sarcoidosis.     

Coexisting primary hyperparathyroidism and sarcoidosis in a patient with severe hypercalcemia

A 75-year-old woman was admitted to our hospital because of general fatigue. She had suffered from sarcoidosis during her 40s with remission, but subsequently she experienced progression of hypercalcemia and renal dysfunction for 7 years. On admission, she showed marked hypercalcemia (up to 15.5 mg/dl) and renal failure (serum creatinine 2.5 mg/dl). Plasma intact PTH level was elevated (up to 190 pg/ml), and thyroid ultrasonography and (99m) Tc-MIBI scintigraphy detected a parathyroid mass, which was surgically removed and histologically confirmed to be a parathyroid adenoma. However, even after surgery her serum calcium remained elevated, but subsequent administration of glucocorticoid for sarcoidosis completely normalized her hypercalcemia. The simultaneous occurrence of primary hyperparathyroidism and sarcoidosis is rare, and our data suggest that high plasma PTH and 1,25(OH)D exerted an additive effect on the occurrence of severe hypercalcemia.     

Malignant struma ovarii: false positive PET image for suspected metastasis due to sarcoidosis

Struma ovarii is an ovarian teratoma mainly composed of thyroid tissue, which can become malignant with possible peritoneal dissemination or even distant metastases. Therapeutic management follows protocols used for thyroid cancer. We report the first use of (18)F-fluorodeoxyglucose positron emission tomography (PET) in the follow-up of malignant struma ovarii with persistently elevated serum thyroglobulin level and negative diagnostic iodine 131 whole body scan after thyroidectomy and four courses of 131 iodine. Hilar and mediastinal lymph node uptake was detected but histological verification concluded that there was a false-positive localization corresponding to sarcoidosis lesions without malignant aspect.     

A case of sarcoidosis and sarcoid granuloma, papillary carcinoma, and Graves' disease in the thyroid gland.

Sarcoidosis is a systemic chronic granulomatous disease of unknown etiology most commonly affecting young females. The disease was first described in the thyroid gland in 1938. Our patient, a 27-year-old male with known sarcoidosis, was referred to the National University Hospital for acute symptoms of thyrotoxicosis (weight loss of 6 kg, tremor, thyroid enlargement, and tachycardia). Laboratory findings showed suppressed serum thyrotropin (TSH, <0.03 mU/L [0.5-4.20]), increased total thyroxine (T4) (223 nmol/L, [60-140]), and triiodothyronine (T3) (8.5 nmol/L, [1.5-2.7]). Furthermore, Tc-99m pertechnetate scintigraphy disclosed diffuse accumulation of the isotope confirming the diagnosis of Graves' disease. During the next 18 months of antithyroid treatment (thiamazole, Thycapzol) hyperthyroidism was difficult to control, the thyroid gland gradually enlarged, and surgery was recommended. Initially, the patient declined surgery but after an additional 18 months, he accepted surgery. During the 36-month period of antithyroid drug treatment TSH was suppressed (<0.01 mU/L) and T3 often elevated despite high doses of thiamazole. Total thyroidectomy was performed, and histologic examination of the removed thyroid tissue confirmed the diagnosis of Graves' disease and also the presence of sarcoid granuloma and metastatic papillary adenocarcinoma with spread to neck lymph nodes. Four months later, a modified radical neck dissection was performed with removal of neck lymph nodes followed by external radiation therapy (2 Gy x 32 fractions to the neck). The concomitant presence of sarcoidosis, papillary carcinoma, and Graves' disease in a thyroid gland, to our knowledge, has not previously been described in the literature.     

Multi-System Immunologically Mediated Disease: T Lymphocyte Deficiency and Thyroid Immunologic Disease—A Report of Four Cases

Summary: Multi-system immunologically mediated disease: T lymphocyte deficiency and thyroid immunologic disease–A report of four cases.
Four cases are described of multisystem immunologically -mediated disease (systemic lupus erythematosus (two cases), polymyositis, and sarcoidosis) in association with thyroid autoimmunity. In all patients there was evidence of T lymphocyte deficiency, namely poor response of peripheral blood lymphocytes (PBL) to T cell mitogens (four cases) and failure or decreased ability to become sensitized to dinitrochlorobenzene (three cases), a/though two patients were ill and two were being treated with steroids. There was also evidence of B lymphocyte deficiency since PBL of no patient responded normally to pokeweed mitogen, a B and T lymphocyte mitogen. In two patients there was evidence of cell-mediated immunity to human thyroid antigens. Although thyroid stimulating antibody was not detected in the one patient with Graves' disease tested, significant titres of thyroid antibodies were detected in all cases. Possible relationships between T lymphocyte deficiency, organ-specific autoimmune disease and immunologically-mediated multi-system disorders are discussed.     

Angiotensin converting enzyme (ACE) gene polymorphism in sarcoidosis in relation to associated autoimmune diseases

Abstract. Papadopoulos KI, Melander O, Orho‐Melander M, Groop LC, Carlsson M, Hallengren B (University of Lund, Malmö University Hospital, Malmö, Sweden). Angiotensin converting enzyme (ACE) gene polymorphism in sarcoidosis in relation to associated autoimmune diseases. J Intern Med 2000; 247: 71–77. Objectives. To investigate the significance of ACE gene insertion/deletion (I/D) polymorphism in the frequency of autoimmune manifestations in sarcoidosis. Design. In patients with sarcoidosis the ACE gene I/D polymorphism was detected with PCR on genomic DNA. The patients with sarcoidosis were divided according to the presence (n = 30) or absence (n = 32) of autoimmune manifestations. The former group was subdivided into thyroid autoimmunity (n = 10), gluten immune reactivity (n = 10) and gastric autoimmunity (n = 17). Settings. The patients were recruited at the Department of Pulmonary Medicine, and the study was conducted at the Department of Endocrinology, University of Lund, Malmö University Hospital, Malmö, Sweden. Subjects. Sixty‐two patients with documented sarcoidosis (30 females, 32 males, median age/range at diagnosis of sarcoidosis 31.5/19–75 years, median age/range at study 47.5/22–81 years) were examined. A total of 107 healthy unrelated subjects without sarcoidosis (60 females, 47 males, median age/range at study 58/40–82 years) served as controls. Results. S‐ACE values were significantly increased in patients compared to controls (P = 0.00001). The same was true in the subgroup of sarcoidosis patients with associated autoimmunity compared with those with isolated sarcoidosis (P = 0.0328). A significant association was seen between ACE gene polymorphism (II, ID, DD genotypes) and S‐ACE levels in both patients and controls according to the order II < ID < DD. The observed genotype frequency distributions in the different study groups agreed the Hardy–Weinberg equilibrium without significant differences between the patients and the controls. Within the group with autoimmune manifestations the DD genotype was significantly over‐represented in X‐ray stage III compared to the other X‐ray stages (P = 0.0181) and a significant increase in the DD genotype in X‐ray stage III (P = 0.035) in the group with autoimmune manifestations compared to isolated sarcoidosis was detected. Conclusion. We confirmed that the S‐ACE levels corresponded to the order II < ID < DD in patients with sarcoidosis as well as in healthy controls. S‐ACE levels were significantly higher in sarcoidosis patients with autoimmune manifestations. The frequency of the DD genotype was significantly increased in patients with autoimmune manifestations and major granuloma mass (X‐ray stage III). The ACE D allele in its homozygous form may confer susceptibility for autoimmune manifestations in sarcoidosis, possibly via the high levels of S‐ACE it encodes.