A rare cause of hyperthyroidism: functioning thyroid metastases.

Hyperthyroidism is a common medical problem that is readily treated with antithyroid medications. However, attributing the correct aetiology of hyperthyroidism alters management and outcome. We present a case of a 66-year-old woman with a seemingly common problem of hyperthyroidism associated with a goitre, which was initially attributed to a toxic nodule. However, Tc-99m pertechnetate uptake scan and thyroid-stimulating hormone receptor antibody were negative, inconsistent with a toxic nodule or Grave's disease. Her thyroid function tests proved difficult to control over the next few months. She eventually proceeded to a total thyroidectomy and histology revealed follicular variant papillary thyroid carcinoma. She was started on levothyroxine postoperatively but developed severe hyperthyroidism, revealing the cause of hyperthyroidism to be autonomously functioning thyroid metastases. Although functioning thyroid metastases are very rare, they need to be considered among the differential diagnoses of hyperthyroidism, as there are nuances in management that could alter the eventual outcome.

Morphological difference in adult thyroid papillary carcinoma between Japan and Ukraine.

Geographic differences have been reported to affect the morphological and molecular features of papillary thyroid carcinomas (PTCs). The area around Chernobyl is well-known to be iodine-deficient in contrast to Japan, an iodine-rich country. We reviewed histological differences in adult PTC between Ukraine and Japan. In total, 112 PTCs from age- and sex-matched adults (Ukraine 56, Japan 56) were evaluated histologically for several factors including tumor size, capsulation, tumor components (papillary, follicular, solid, trabecular), lymph node metastasis, extrathyroid invasion, lymphocytic infiltration, oxyphilic metaplasia, and MIB-1 index. We demonstrated that tumors were smaller (1.56 vs. 2.13 cm, p<0.05) and more solid and that lymph node metastasis was less frequent (14.3% vs. 48.2%, p<0.001) in Ukrainian cases. PTC subtype distribution was significantly different between the two groups. Solid variant (8.9% vs. 1.8%) and mixed subtypes with solid components were more frequent in Ukrainian patients. In contrast, classical papillary carcinomas were more frequent in Japanese cases (10.7% vs. 50.0%, p<0.001). Marked oxyphilic metaplasia was more common in Ukrainian cases (33.9 % vs. 8.9 %, p<0.001). MIB-1 index was significantly higher in Ukrainian cases (2.9% vs. 1.8%, p<0.001). However, the frequencies of tumor capsule formation and background lymphoid follicle formation around the tumor were similar between groups. Morphological differences in adult PTCs were similar to those in pediatric PTCs as reported previously, suggesting that morphogenesis of PTC is influenced by environmental factors, especially dietary iodine, as well as genetic factors.

Metástasis en cuero cabelludo como primera manifestación de cáncer de tiroides mixto folicular-papilar / Scalp metastasis as the first manifestation of mixed follicularpapillary thyroid cancer

La aparición de metástasis a distancia en los cánceres diferenciados de tiroides es poco frecuente, y cuando se detectan en piel, suelen darse en el contexto de una enfermedad diseminada después de muchos años de evolución desde el diagnóstico. Se presenta el caso de una paciente de 77 años, sin enfermedad tiroidea conocida que debutó con una metástasis en región parietooccipital del cuero cabelludo en la que se identificó tejido tiroideo. En la ecografía tiroidea se identificó un nódulo informado como tumor folicular y el estudio de extensión precirugía fue negativo. Se le hizo tiroidectomía total más vaciamiento ganglionar del compartimento central y el estudio AP fue informado de carcinoma mixto folicular-papilar sin afectación ganglionar. En el RCT post-I131 (dosis de 104,7 mCi) se detectaron micrometástasis pulmonares, y a los 2 meses de una segunda dosis de I131 (125 mCi), la tiroglobulina fue indetectable. El cáncer tiroideo debe incluirse en el diagnóstico diferencial de las metástasis cutáneas, puesto que su diagnóstico y tratamiento temprano, excepto en los casos de enfermedad muy avanzada, el pronóstico de su hallazgo suele ser más favorable que en el resto de tumores sólidos (AU)

Distant metastases are a rare occurrence in differentiated thyroid cancer, and when detected in skin, often arise in the context of disseminated disease after many years of progression since diagnosis. This study presents the case of a 77-year-old female without known thyroid disease, who presented with metastases in the parieto-occipital scalp region, in which thyroid tissue was identified. Thyroid ultrasound identified a nodule reported as a follicular tumour and preoperative investigation of tumour spread was negative. Total thyroidectomy plus central lymph node dissection were performed and histopathology reported mixed papillary-follicular carcinoma without lymph node metastasis. Lung micrometastases were detected in the post-I131 whole-body scan (104.7 mCi dose), and two months after a second dose of 131I (125 mCi), thyroglobulin was undetectable. Thyroid cancer should be included in the differential diagnosis of cutaneous metastases, since with early diagnosis and treatment, prognosis is generally more favourable than in other solid tumours (AU)

Evaluation of thyroid diseases and differentiated thyroid cancer in acromegalic patients.

Thyroid diseases are frequently seen in patients with acromegaly. The aim of this study is to evaluate thyroid diseases and thyroid cancer in acromegalic patients followed in a single institution. The data of 92 acromegalic (43 male, 49 female) patients followed over 12 years were retrieved retrospectively from the hospital recordings. All available data for gender, age, body weight and height, duration of acromegaly, age at diagnosis of acromegaly, treatment methods for acromegaly and history of thyroid disease, serum GH, IGF-1, thyroid function tests, thyroid ultrasonography (US), thyroid scintigraphy and thyroid fine needle aspiration biopsy (FNAB) results were recorded for the patients. The mean age of the patients was 43.9 ± 10.8 years and the mean disease duration was 12 ± 6.9 years. Thyroid US was performed in 64 patients who had nodular or diffuse goiter on palpation during the post-treatment follow-up and nodules were found in 44 (47.8 %) patients. Final diagnosis in 64 patients with thyroid US results and thyroid function tests including 26 patients with FNAB were as follows: 31 (48.4 %) benign multinodular goiter (MNG), 6 (9.4 %) simple nodular goiter, 1 (1.6 %) toxic MNG, 1 (1.6 %) Hurthle cell adenoma, and 5 (7.8 %) differentiated thyroid cancer. In addition, 9 (14.1 %) patients had diffuse goiter. One of the patients with diffuse goiter had amiodarone induced thyrotoxicosis. Eleven (17.1 %) patients had normal thyroid US and no other thyroid disease. Patients with nodules had longer disease duration than patients without nodules (14.2 ± 6.6 vs. 9.4 ± 3.4 years, p = 0.043). Thyroid volume was positively correlated with post-treatment GH and post-treatment IGF-1 levels (r = 0.309, p = 0.041 and r = 0.423, p = 0.004), respectively. We found that 7.8 % of our acromegalic patients with thyroid US results were diagnosed with thyroid cancer. Therefore, acromegalic patients must be considered as a high risk group for the development of thyroid cancer and must be closely followed for thyroid nodules and tumors.

Mixed Medullary-follicular-derived carcinomas of the thyroid gland.

Tumors of the thyroid are subclassified based on the cell of origin and commonly include follicular-derived tumors and C-cell-derived tumors. The most common follicular-derived tumors are papillary carcinoma and follicular carcinoma, whereas the malignant C-cell-derived tumor is medullary thyroid carcinoma. Rare cases in the literature describe patients who have follicular-derived and C-cell-derived tumors in the same thyroid gland. These can be synchronous but anatomically separate carcinomas, or they can show some mixing of the 2 components. The mixture may be at an interface, as in collision tumors, or can be throughout the entire lesion, as in true mixed medullary-follicular-derived carcinomas. The clinical, histologic, and molecular features of these mixed tumors and the classification guidelines are reviewed.

Clinicopathological characteristics of thyroid cancer in patients on dialysis for end-stage renal disease.

BACKGROUND: The prevalence rate of thyroid cancers in patients with renal failure is variable in different studies. Our aim was to determine the prevalence and clinicopathological characteristics of thyroid cancers in the dialysis population and to evaluate the potential risk factors. METHODS: We performed a retrospective analysis on end-stage renal disease (ESRD) patients on dialysis and thyroidectomized patients without ESRD (2000-2006). Then we compared the data of thyroid cancer patients on dialysis (n = 9) with the data of patients who had histopathologically verified benign thyroid disease on dialysis (n = 23) and with the histopathological data of thyroid cancer patients without ESRD. RESULTS: Papillary thyroid cancer (PTC) was the only histotype that was found in 9 of 420 (2.1%) ESRD patients on dialysis. Multifocal PTC was found in eight of nine patients; of them, four had follicular variant of PTC (FVPTC). Two patients had lymphatic metastasis at diagnosis. Eight PTCs were classified as tumor-node-metastasis (TNM) stage I and one as stage II. Among the analyzed factors, age (r = 0.374, p = 0.01) and duration of dialysis (r = 0.436, p = 0.007) showed a significant positive correlation with the occurrence of thyroid cancer. CONCLUSIONS: We conclude that the prevalence of thyroid cancer in patients undergoing dialysis was not higher than that in the background population. Age and duration of dialysis showed a significant positive correlation with the occurrence of thyroid cancer in patients on dialysis. Among the histotypes, there may be higher percentage of PTC, FVPTC, and multifocality in dialysis patients. The effect of these characteristics on prognosis of thyroid cancer in dialysis patients is needed to be further evaluated.

[A case of follicular carcinoma of thyroid gland with concurrent tuberculous lymphadenitises].

We report a case of follicular carcinoma of the thyroid gland with concurrent tuberculous lymphadenitises as neck lymph node metastases of thyroid carcinoma. A 71-year-old woman presented with multiple painless masses in the thyroid gland and painless lymphadenopathies in the right neck. She and her family had no previous history of tuberculosis. A diagnosis of thyroid cancer with lymph node metastases was made, and the patient underwent total thyroidectomy with neck dissection. Lymph nodes were hard and severely adhered to the internal jugular vein. The histopathological diagnosis was follicular carcinoma and multiple nodes of adenomatous goiter of the thyroid gland, and tuberculous lymphadenitises of lymph nodes in the right neck. There was no findings of coexisting pulmonary tuberculosis. The possibility of coexisting tuberculous lymphadenitis must thus be ruled out when we find painless lymph node swelling in aged patients with head and neck cancer including thyroid cancer.

Clinical curiosity: cribriform-morular variant of papillary thyroid carcinoma.

BACKGROUND: There is an increasing awareness of the association of papillary thyroid carcinoma and familial adenomatous polyposis (FAP). Although the incidence is rare, most tend to occur in women. Several authors have described a distinctive histologic variant of papillary thyroid carcinoma, the cribriform-morular variant, which is associated with FAP but also may be encountered in patients with non-FAP. This diagnosis may precede the symptoms of colorectal polyposis. METHODS: A healthy 36-year-old woman was seen with a left thyroid nodule, and a 34-year-old woman with FAP was seen with a right thyroid nodule; both masses were suspicious for papillary thyroid carcinoma. Both patients underwent total thyroidectomy. RESULTS: Pathologic examination of both specimens revealed papillary thyroid carcinoma, cribriform-morular variant. The first patient subsequently underwent colonoscopy, which was negative for polyposis. CONCLUSIONS: Patients diagnosed with the cribriform-morular variant of papillary thyroid cancer should be screened for the presence of FAP.

BRAF mutation is unusual in chronic lymphocytic thyroiditis-associated papillary thyroid carcinomas and absent in non-neoplastic nuclear atypia of thyroiditis.

Chronic lymphocytic thyroiditis (CLT) has an epidemiological relationship to papillary thyroid carcinoma (PTC). The follicular epithelium in CLT can be markedly atypical, with cytologic changes ranging from oncocytic morphology to clearing and overlapping. At the molecular level, the association between CLT and PTC is more controversial. In order to further characterize the molecular changes in CLT, this study examined the BRAF gene in 27 patient samples with CLT and without carcinoma and 28 samples with CLT and carcinoma (12 conventional papillary carcinomas, 13 follicular variants, and 3 tall cell variants). Microdissection, PCR, and sequencing of exon 15 of the BRAF gene were performed. BRAF mutations were uncommon in the cases studied with only two microscopic and two clinically sized PTCs had BRAF mutations (14%). There was no evidence of BRAF mutation in any of the areas with atypical follicular epithelium in CLT. These data suggest that BRAF is a less frequent mechanism of tumorigenesis in a background of CLT and that BRAF mutation is not present in the atypical follicular epithelium of CLT.

Insular carcinoma of the thyroid with jugular vein invasion.

BACKGROUND: Gross angioinvasion with intraluminal tumor thrombus is rarely seen in thyroid cancer, with few cases reported in the literature. METHODS: We report an insular carcinoma of the thyroid displaying this aggressive local invasion and angioinvasion of the internal jugular chain. Complete surgical removal of the intraluminal disease, regional metastasis, and primary tumor was carried out. RESULTS: Adjuvant external beam radiation therapy and iodine-131 were administered, and the patient died with pulmonary metastases 30 months after surgery. No locoregional recurrence was noted at last follow-up. CONCLUSIONS: Treatment of insular carcinoma of the thyroid with invasion of the internal jugular vein is amenable to surgical resection. Postoperative radioactive iodine and external beam radiotherapy can achieve locoregional disease control and prolonged survival.

Follicular thyroid lesions coexisting with Hashimoto's thyroiditis: incidence and possible sources of diagnostic errors.

Our objectives were to study the types and incidence of thyroid follicular lesions coexisting with Hashimoto's thyroiditis (HT), the pitfalls in their cytodiagnosis, and the effect on management. All cases of HT diagnosed by fine-needle aspiration (FNA) and/or histology over a 7-yr period were retrospectively studied. HT coexisted with follicular adenoma (FA) in 6 cases, follicular variant of papillary carcinoma (FVPC) in 1 case, and goitrous nodule (GN) in 2 cases. The overall incidence rates of thyroid neoplasm and goitrous nodules coexistent with HT were 15% and 3.5%, respectively. A preoperative FNA diagnosis was available in 10 histologically proven cases of HT. A false-positive diagnosis of follicular neoplasm (FN) that led to unnecessary thyroidectomies was given in 3 cases. In 2 of these, the cytological diagnosis was HT with the possibility of coexisting FN, and in the third case, the cytological finding of HT was misinterpreted as FN. The main causes of these diagnostic pitfalls were the presence of hyperplastic follicular cells with nuclear pleomorphism, a paucity of lymphoid cells in burned-out HT, and lack of ones exposure. Nuclear pleomorphism was observed in none of the follicular adenomas. FNA diagnosed accurately the coexisting lesions in 6 cases; 3 FA, 1 FVPC, and 2 GN, but it did not sample HT. In one case, FNA diagnosed correctly both HT and the coexisting FA. Therefore, the presence of a coexistent neoplasm or goitrous nodule reduced the chances of sampling HT by 85.7%, with no false-negative results. Indeed, aspiration on and around the thyroid nodule helps in sampling HT. However, HT may dominate the smear and obscure neoplasia. This can be avoided if the procedure is performed by the pathologist and the aspiration is done on the nodule only. The overlapping cytological features of FN and HT were the main causes of false-positive results. This can be reduced by avoiding the diagnosis of FN in the presence of follicular-cell pleomorphism and/or moderate to excessive numbers of lymphoid cells, provided proper aspiration technique is maintained.

Prevalence of RET/PTC rearrangements in Hashimoto's thyroiditis and papillary thyroid carcinomas.

The relationship between Hashimoto's thyroiditis (HT) and follicular cell-derived thyroid cancer remains unclear. Recently, 2 studies reported a 95% prevalence of RET/PTC rearrangements in histologically benign tissue affected by HT, suggesting that multiple occult tumors exist in HT patients with high frequency. We tested the prevalence of RET/PTC rearrangements in 26 HT, in 6 papillary carcinomas arising in the background of HT, and in 27 papillary carcinomas not associated with HT. We detected no RET/PTC rearrangements in HT or papillary carcinomas arising in the background of HT, in contrast to a 33% prevalence among papillary carcinomas not associated with HT. However, the expression of wild-type RET was found in more than half of papillary carcinomas. These results suggest that, if the association between HT and thyroid cancer exists, its molecular basis is different from RET/PTC rearrangement.

Iodine-131 ablation therapy for a patient receiving peritoneal dialysis.

The authors describe a patient with follicular thyroid carcinoma who was receiving continuous ambulatory peritoneal dialysis to manage end-stage renal disease. To deliver radioiodine therapy to ablate thyroid remnants safely and under optimal conditions, the behavior of 37 MBq (1 mCi) I-131 was followed daily for 3 days. Blood activity and total body count decreased with a half-life of 100 hours (4.17 days). The daily iodide removal rate, estimated as a percentage of the total administrated activity, was low: 5.3% to 8.6% in peritoneal dialysate and 1.3% to 2.2% in urine. The thyroid uptake, measured using a probe, was 2.4% to 2.1% from day 1 to day 3 and 1.9% later at day 8. The volume of thyroid remnants was determined by ultrasonography to be 0.6 g. The patient received a reduced ablative I-131 dose of 814 MBq (22 mCi). Radiation emitted from the patient after I-131 therapy, monitored using a radiation monitor probe located at a distance of 1 meter, decreased with an effective half-life of 70 hours (2.9 days). The integration of the curve from t = 0 showed a level always less than 25 microSv/hour as early as 24 hours after treatment. Because the iodine removal rate is continuous but low in a case of peritoneal dialysis, smaller therapeutic doses must be administered to deliver maximal radiation to residual thyroid tissue while minimizing excessive radiation exposure to patients, their families, and medical staff.

Toxic multinodular goitre in a patient with generalized resistance to thyroid hormone who harbours the R429Q mutation in the thyroid hormone receptor beta gene.

The association of resistance to thyroid hormone (RTH) due to a receptor defect with toxic multinodular goitre or with carcinoma of the thyroid has not been previously reported. Previous histopathological studies of the thyroid gland in patients with RTH have revealed changes similar to multinodular goitre, probably due to continuous stimulation by TSH. We report here a case of generalized resistance to thyroid hormone associated with a multinodular goitre, which became toxic. The patient was a 46-year-old Japanese woman who noticed a goitre although she had no symptoms of thyrotoxicosis. Initial examination revealed elevated serum thyroid hormone levels and a normal TSH level. Ultrasonography disclosed a multinodular goitre with cystic lesions. Three years later, the patient complained that the goitre had become larger and that she had developed symptoms of thyrotoxicosis such as palpitation and hyperhydrosis. Progressive hyperthyroxinaemia with relatively suppressed TSH, increased radioiodine uptake and negative anti-TSH receptor antibodies led to the diagnosis of toxic multinodular goitre. Subtotal thyroidectomy was performed, and pathological examination revealed a micropapillary carcinoma within the multinodular goitre. Occurrence of thyroid carcinoma should be considered in RTH because its incidence is high in multinodular goitre. Molecular examination revealed the R429Q mutation in the thyroid hormone receptor beta gene, which is one of the mutations usually manifesting as the pituitary resistance phenotype. That thyrotoxic manifestations appeared only during toxic stage of multinodular goitre in this case suggests that the phenotype of this type of mutation can be dependent on the amount of thyroid hormone.

Unilateral proptosis with thyrotoxicosis resulting from solitary retroorbital soft tissue metastasis from follicular carcinoma thyroid.

Unilateral proptosis can be of neoplastic origin, even if the results of thyroid function tests suggest hyperthyroid disease, and it needs proper investigation with a computed tomographic scan of the orbit. The authors present a case of left-sided proptosis resulting from a metastasis in the retroorbital soft tissue from follicular carcinoma of the thyroid. A nodular goiter involving the left lobe and isthmus was found. The initial thyroid function test values suggested hyperthyroid disease and the patient had clinical signs of toxicity. A computed tomographic scan of the orbit revealed a left-sided retroorbital soft tissue mass, part of which was resected and found be to a metastasis from follicular carcinoma of thyroid. Total thyroidectomy was performed and the patient was treated with I-131 after operation. The proptosis resolved with I-131 treatment.

Radioiodine dosimetry in patients with end-stage renal disease receiving continuous ambulatory peritoneal dialysis therapy.

In patients with end-stage renal disease (ESRD), Na131I dosages for thyroid cancer may have to be reduced to avoid excess radiation doses to red marrow, because radioiodine is primarily excreted by kidneys. In ESRD patients receiving continuous ambulatory peritoneal dialysis (CAPD) therapy (three to five 2-L exchanges daily) creatinine clearance rates are very low (mean, 7 mL/min), and radioiodine clearance rates may be proportionately reduced. Thus, radioiodine kinetic studies were performed in two hypothyroid CAPD patients with thyroid cancer, in eight euthyroid CAPD patients, and in eight thyroid cancer patients with normal renal function. All received Na131I or Na123I orally, with serial blood, urine, and/or dialysate sampling for 24-70 h. Dosimetry calculations were performed using the MIRDOSE3 computer program. In CAPD patients, serum radioiodine half-times were 5 times longer, and radioiodine clearance rates by urine plus dialysate were 20% of those in patients with normal renal function. Na131I dosages for the two CAPD patients with thyroid cancer were reduced from 150 mCi [5.6 gigabecquerels (GBq)] to 26.6 mCi (0.98 GBq) and 29.9 mCi (1.11 GBq), respectively, resulting in radiation doses to red marrow and total body comparable to those in patients with normal renal function who received a mean of 148 mCi (5.5 GBq) Na131I. Thus, in patients receiving continuous ambulatory peritoneal dialysis therapy, 5-fold reductions in radioiodine clearance rates require 5-fold decreases in Na131I dosages to avoid excessive radiation doses to total body and red marrow.

Cáncer tiroideo en el hipertiroidismo: una asociación no tan excepcional / Thyroid cancer in hyperthyroidism: not such an uncommon association

Objetivo. Analizar la tasa de asociación entre hipertiroi dismo y cáncer tiroideo en nuestra experiencia, así como la que existe con los distintos tipos de enfermedades tiroideas que cursan con hipertiroidismo. Pacientes y métodos. Se han estudiado, de forma retrospectiva, las piezas quirúrgicas y los historiales clínicos de aquellos pacientes intervenidos por hipertiroidismo y en los que se detectó un cáncer tiroideo en el estudio anatomopatológico. Los pacientes fueron agrupados según presentaran enfermedad de Graves-Basedow, bocio multinodular o adenoma tóxico. Resultados. En 10 casos de 265 pacientes se detectó un cáncer tiroideo asociado (3,8 por ciento). Fueron mayoría los pacientes con enfermedad de Graves (63 por ciento), aunque sólo el 3,5 por ciento de éstos presentaron asociación con cáncer, frente al 5,5 por ciento de los bocios multinodulares. No se encontró ningún caso en los pacientes con adenoma tóxico. Todos los casos de tumor correspondieron a cáncer papilar. En 3 casos se encontró multicentricidad del tumor en el mismo lóbulo. Conclusiones. Debe realizarse un estudio detallado de las piezas quirúrgicas en los pacientes intervenidos por hipertiroidismo y considerar siempre la posibilidad de esta asociación al planificar el tratamiento de estos pacientes (AU)