Thyroid Diseases: Maia AL

Maia AL, Ward LS, Carvalho GA, Graf H, Maciel RM, Maciel LM, Rosário PW, Vaisman M. · Departamento de Tireóide, Sociedade Brasileira de Endocrinologia e Metabologia, Serviço de Endocrinologia, Hospital de Clínicas de Porto Alegre, Universidad Federal do Rio Grande do Sul, RS, Brazil. · Arq Bras Endocrinol Metabol. · Pubmed #17891253 links to  free full text

Abstract: Thyroid nodules are a common manifestation of thyroid diseases. It is estimated that approximately 10% of adults have palpable thyroid nodules with the frequency increasing throughout life. The major concern on nodule evaluation is the risk of malignancy (5-10%). Differentiated thyroid carcinoma accounts for 90% of all thyroid malignant neoplasias. Although most patients with cancer have a favorable outcome, some individuals present an aggressive form of the disease and poor prognostic despite recent advances in diagnosis and treatment. Here, a set of clinical guidelines for the evaluation and management of patients with thyroid nodules or differentiated thyroid cancer was developed through consensus by 8 member of the Department of Thyroid, Sociedade Brasileira de Endocrinologia e Metabologia. The participants are from different reference medical centers within Brazil, to reflect different practice patterns. Each committee participant was initially assigned to write a section of the document and to submit it to the chairperson, who revised and assembled the sections into a complete draft document, which was then circulated among all committee members for further revision. All committee members further revised and refined the document. The guidelines were developed based on the expert opinion of the committee participants, as well as on previously published information.

Dora JM, Canalli MH, Capp C, Puñales MK, Vieira JG, Maia AL. · Thyroid Section, Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. · Thyroid. · Pubmed #18651801 No free full text.

Abstract: CONTEXT: Medullary thyroid carcinoma (MTC), a tumor of the parafollicular C cells of the gland, comprises 3-5% of all malignant thyroid neoplasms. Calcitonin, a polypeptidic hormone secreted by the neoplastic cells, is considered a very sensitive and specific MTC tumor marker. Patients with MTC usually present elevated serum calcitonin levels, which correlate with tumor burden and prognosis. OBJECTIVES: To describe a case of advanced MTC with normal serum calcitonin and review the literature on this subject. DESIGN: A case study was performed. Intervention: There were no interventions. PATIENTS: A case of advanced MTC with normal serum calcitonin was studied. RESULTS: Serum calcitonin was measured by two distinct assays, a chemiluminescent immunometric and an in-house two-site monoclonal antibody-based immunofluorometric assay. To rule out a "hook effect," or posttranslational modifications of calcitonin molecule, serum dilutions and tumor immunohistochemistry for calcitonin with the same antibodies used for serum calcitonin measurements were performed. Serum calcitonin levels were within the normal range in both assays, whereas the tumor stained strongly positive for calcitonin. These findings suggest that the tumor was able to produce but not to secrete the calcitonin protein. Five other cases of advanced MTC with normal serum calcitonin levels had been previously reported. CONCLUSIONS: We present an unusual case of advanced MTC with normal serum calcitonin levels. Awareness of MTC cases presenting with normal serum calcitonin levels is important in clinical practice and is particularly relevant to centers that use this test for screening.

Zavascki AP, Maia AL, Goldani LZ. · Section of Infectious Diseases and Endocrinology, Hospital das Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul and Hospital São Lucas, Pontifícia Universidade Católica, Porto Alegre, Brazil. · Mycoses. · Pubmed #17944703 No free full text.

Abstract: The authors review the epidemiology, clinical manifestations, diagnosis and treatment of Pneumocystis jiroveci thyroiditis of 15 cases reported in the medical literature. Patients with acquired immunodeficiency disease syndrome were particularly at risk. P. jiroveci thyroiditis was diagnosed at autopsy as a part of disseminated infection in a substantial number of patients without clinical manifestations and laboratory evidence of thyroid dysfunction. Local signs and symptoms of infection were indistinguishable from other infectious thyroiditis and included neck enlargement with or without cervical pain, sometimes associated with dysphagia and dysphonia, and clinical and laboratory features of hypothyroidism. Antemortem diagnosis of fungal thyroiditis was made by direct microscopy and culture of a fine-needle aspirate in most cases. As most patients with P. jiroveci thyroiditis had disseminated Pneumocystis infection with a delay in diagnosis and treatment, the overall mortality was high. Pneumocystis jiroveci thyroiditis is rare but should be suspected in HIV-infected patients with CD4 count lower than 200 cells micro(-1) on prophylatic inhalatory pentamidine who present with neck enlargement with or without pain, and clinical and laboratory evidence of hypothyroidism.

Rocha AP, Magalhães PK, Maia AL, Maciel LM. · Setor de Tireóide, Serviço de Endocrinologia, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. · Arq Bras Endocrinol Metabol. · Pubmed #17891235 links to  free full text

Abstract: Medullary thyroid carcinoma (MTC) is a rare malignant neoplasia, which may occur on sporadic form or on a hereditary basis. Germ line mutations in the RET proto-oncogene is responsible for hereditary MTC. However, most MTC occur in individuals without family history where the pathogenesis is still unclear. Single nucleotide polymorphisms (SNPs) of the RET gene have been described in the general population as well as in patients with MTC. Even though these allelic variants do not seem to confer any transforming activity to the tyrosine kinase domain of the RET protein, cumulative studies suggest that they could modify disease susceptibility and clinical phenotype in patients with sporadic or hereditary MTC. Polymorphisms located in exons 11 (G691S), 13 (L769L), 14 (S836S), and 15 (S904S) seem to be over-represented in sporadic MTC patients from American and European countries. Here, we discuss the results obtained in different studies as well as describe the frequency of RET polymorphisms in Brazilian patients with sporadic MTC.

Meyer EL, Wagner MS, Maia AL. · Setor de Tireóide, Serviço de Endocrinologia, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. · Arq Bras Endocrinol Metabol. · Pubmed #17891232 links to  free full text

Abstract: The iodothyronine deiodinases constitute a family of selenoenzymes that catalyze the removal of iodine from the outer ring or inner ring of the thyroid hormones. The activating enzymes, deiodinases type I (D1) and type II (D2), are highly expressed in normal thyroid gland. Benign or malignant neoplastic transformation of the thyroid cells is associated with changes on the expression of these enzymes, suggesting that D1 or D2 can be markers of cellular differentiation. Abnormalities on the expression of both enzymes and also of the deiodinase type III (D3), that inactivates thyroid hormones, have been found in other human neoplasias. So far, the mechanism or implications of these findings on tumor pathogenesis are not well understood. Nevertheless, its noteworthy that abnormal expression of D2 can cause thyrotoxicosis in patients with metastasis of follicular thyroid carcinoma and that increased D3 expression in large hemangiomas causes severe hypothyroidism.

Goldani LZ, Zavascki AP, Maia AL. · Section of Infectious Diseases, Universidade Federal do Rio Grande do Sul, Brazil. · Mycopathologia. · Pubmed #16482384 No free full text.

Abstract: The authors review the epidemiology, clinical manifestations, diagnosis, and treatment of fungal thyroiditis cases previously reported in the medical literature. Aspergillus was by far the most common cause of fungal thyroiditis. Immunocompromised patients, such as those with leukemia, lymphoma, autoimmune diseases, and organ-transplant patients on pharmacological immunosuppression were particularly at risk. Fungal thyroiditis was diagnosed at autopsy as part of disseminated infection in a substantial number of patients without clinical manifestations and laboratory evidence of thyroid dysfunction. Local signs and symptoms of infection were indistinguishable from other infectious thyroiditis and included fever, anterior cervical pain, thyroid enlargement sometimes associated with dysphagia and dysphonia, and clinical and laboratory features of transient hyperthyroidism due to the release of thyroid hormone from follicular cell damage, followed by residual hypothyroidism. Antemortem diagnosis of fungal thyroiditis was made by direct microscopy and culture of a fine-needle aspirate, or/and biopsy in most cases. Since most patients with fungal thyroiditis had disseminated fungal infection with delay in diagnosis and treatment, the overall mortality was high.

Maia AL, Gross JL, Puñales MK. · Serviço de Endocrinologia, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS. · Arq Bras Endocrinol Metabol. · Pubmed #16444355 links to  free full text

Abstract: The term multiple endocrine neoplasia (MEN) was introduced by Steiner et al. in 1968 to describe disorders that include a combination of endocrine tumors. The Wermer syndrome was designed as MEN 1 and the Sipple syndrome as MEN 2. Sizemore et al. (1974) completed that the MEN 2 category included 2 subgroups: patients with medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid disease and a normal appearance (MEN 2A) and other without parathyroid disease but with mucosal neuromas and mesodermal abnormalities (MEN 2B). MTC is usually the first tumor diagnosed. The diagnosis of MTC has several implications: disease extent should be evaluated, pheochromocytoma and hyperparathyroidism should be screened and whether the MTC is sporadic or hereditary should be determined by a direct analysis of the RET proto-oncogene. Here, the pathological characteristics, genetic abnormalities, and clinical features of MEN 2 are discussed. The diagnostic and therapeutic approaches used to patients with clinical disease and carriers identified through familiar screening are also described. Progresses related especially to genetic screening and earlier intervention have permitted an improvement in the long-term outcome. However, treatment for disseminated disease is still ineffective.

Golbert L, Wajner SM, Rocha AP, Maia AL, Gross JL. · Serviço de Endocrinologia, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS. · Arq Bras Endocrinol Metabol. · Pubmed #16444352 links to  free full text

Abstract: Thyroid carcinoma accounts for roughly 1% of all new malignant diseases. Of these, at least 94% are differentiated thyroid carcinoma (DTC), either papillary thyroid carcinoma or follicular thyroid carcinoma. Patients with DTC are usually considered as having a good prognosis, 80% of patients are cured, 20% will develop loco-regional recurrence and 5-10% distant metastasis. However, the disease may have an aggressive course in some patients. The identification of these patients has a major impact in the clinical management of DTC. Several prognostic factors and classification will be addressed, as well the most useful tests for patients follow-up.

Andrade VA, Gross JL, Maia AL. · Serviço de Endocrinologia, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS. · Arq Bras Endocrinol Metabol. · Pubmed #15611828 links to  free full text

Abstract: Graves' disease is the most frequent cause of hyperthyroidism. Clinical thyrotoxicosis is directly caused by autoantibodies that activate the TSH receptor. The etiology is multifactorial, with genetic and nongenetic factors involved. Current treatment options are antithyroid drugs (ATD), radioiodine (131I) and surgery. Radioactive iodine is increasingly being used as definitive therapy, because it long has proven to be a safe, nonexpensive and effective treatment. Recent publications have discussed the use of 131I associated with ATD as well as the identification of predictors of treatment failure, which are discussed in this review. Antithyroid drugs are still the first choice therapy in patients with mild disease, small goiters, children, adolescents, and in pregnancy. Surgery is now rarely performed. It is indicated only in cases where ATD have not been effective and radioiodine is contraindicated or not acceptable by the patients.

Puñales MK, Rocha AP, Gross JL, Maia AL. · Serviço de Endocrinologia, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS. · Arq Bras Endocrinol Metabol. · Pubmed #15611826 links to  free full text

Abstract: Medullary carcinoma of the thyroid (MTC) may be sporadic or may occur on a hereditary basis. Hereditary MTC can occur either alone -- familial MTC (FMTC) -- or as the thyroid manifestation of multiple endocrine neoplasia type 2 (MEN 2) syndromes (MEN 2A and MEN 2B) or other forms. Germ-line mutations in RET cause MEN 2. Genetic testing, now available, forms the basis for MTC screening procedures. In the past few years, several genotype-phenotype correlations have focused on the relationship between specific mutations and different MEN 2 syndrome variants. Differences in dimerization induction intensities are a reasonable explanation for the phenotypes resulting from mutations of the different cysteines. Here we described the molecular mechanisms, diagnose and treatment as well as our experience on the management of this rare form of thyroid cancer.

Dora JM, Leie MA, Netto B, Fogliatto LM, Silla L, Torres F, Maia AL. · No affiliation provided · Eur J Endocrinol. · Pubmed #18426838 links to  free full text

This publication has no abstract.

Andrade VA, Gross JL, Maia AL. · Endocrine Division, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2350, 90035-003 Porto Alegre, RS, Brazil. · Eur J Endocrinol. · Pubmed #15476447 links to  free full text

Abstract: OBJECTIVE: Radioiodine therapy (131I) in hyperthyroid Graves' disease is generally followed by a transitory increase in levels of thyrotropin receptors antibodies (TRAb). Immunosuppressive effects of antithyroid drugs are still a matter of debate. In this study we evaluated the effect of methimazole pretreatment on the TRAb boost induced by 131I. DESIGN: A randomized, prospective clinical trial. METHODS: 61 patients were randomly assigned to receive 131I alone (32 patients) or 131I plus pretreatment with methimazole (30 mg/day; 29 patients). Serum TRAb levels were measured on the day of 131I dosing (D0), and at 1, 3, 6 and 12 months after 131I administration. RESULTS: The mean serum TRAb levels decreased significantly from baseline to D0 in patients treated with methimazole (80.8 vs 48.8 U/l; P<0.05). After 131I treatment, TRAb levels increased at 3 months (48.8 to 60 U/l; 19%) and they were still elevated at 6 months compared with D0 values (99.9 U/l; 105%). Thereafter, TRAb levels decreased to baseline values (47.8 U/l) at 12 months. In hyperthyroid patients, TRAb levels increased significantly from D0 to 1 month (45.0 to 78 U/l; 73%) reaching their highest levels at 3 months (225 U/l; 400%). After this, we observed a progressive decrease to the baseline levels at 12 months (40.0 U/l). The course of TRAb levels after 131I treatment was significantly different between the two groups (P<0.05). Multiple regression analysis identified serum TRAb levels on D0 as independent predictors of TRAb increment after 131I therapy (r2=0.34; P=0.001). A higher increment in serum TRAb levels was associated with hypothyroidism after 1 year of follow-up. CONCLUSION: Methimazole pretreatment attenuates the 131I-induced rise in serum TRAb levels. The effects of methimazole could be attributed to a direct immunomodulatory action or may be due to its effects on the control of hyperthyroidism, which is a known cause of immune dysregulation.

Andrade VA, Gross JL, Maia AL. · Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, 90035-003 Porto Alegre, Brazil. · J Clin Endocrinol Metab. · Pubmed #11502768 links to  free full text

Abstract: The effect of antithyroid drugs on the efficacy of radioiodine (131I) treatment is still controversial. This study evaluated the effect of methimazole pretreatment on the efficacy of 131I therapy in Graves' hyperthyroidism. Sixty-one untreated patients were randomly assigned to receive 131I alone (32 patients) or 131I plus pretreatment with methimazole (30 mg/d; 29 patients). 131I was administered 4 d after drug discontinuation. The calculated 131I dose was 200 microCi/g thyroid tissue as estimated by ultrasound, corrected by 24-h radioiodine uptake. Serum TSH, T4, and free T4 were measured 4 d before 131I therapy, on the day of treatment, and then monthly for 1 yr. Considering cure as euthyroidism or hypothyroidism, based on free T4 measurement, approximately 80% of patients from both groups were cured 3 months after beginning 131I treatment. After 1 yr the groups were similar in terms of persistent hyperthyroidism (15.6% vs. 13.8%), euthyroidism (28.1% vs. 31.0%), or hypothyroidism (56.3% vs. 55.2%). Relapsed patients presented larger thyroid volume (P = 0.002), higher 24-h radioiodine uptake (P = 0.022), and T3 levels (P = 0.002). Multiple logistic regression analysis identified T3 values as an independent predictor of therapy failure. In conclusion, pretreatment with methimazole had no effect on either the time required for cure or the 1-yr success rate of 131I therapy.

Andrade VA, Gross JL, Maia AL. · Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Brazil. · J Clin Endocrinol Metab. · Pubmed #10566642 links to  free full text

Abstract: Radioiodine (131I) is the preferred definitive treatment for Graves' hyperthyroidism. Pretreatment with antithyroid drugs is often used to avoid thyroid hormone discharge after 131I ablation. However, this may represent an unnecessary increase in risk and costs. Fifty-one patients with Graves' disease were randomly assigned to receive 131I alone (28 patients) or 131I plus pretreatment with methimazole (30 mg/day; 23 patients). Methimazole was interrupted 4 days before 131I therapy. Serum T4, free T4 (FT4), and T3 were measured on days -4 and -1, on the day of treatment, and on days 2, 5, 7, 14, 20, and 30. In patients receiving 131I alone, mean serum T4 levels did not change after therapy. Mean serum FT4 and T3 levels decreased significantly 5 days after 131I administration (15% and 18%, respectively). Serum T3 reached its lowest level on day 30 (38%). With pretreatment, mean serum T4, FT4, and T3 levels increased (38%, 39%, and 70%, respectively) after methimazole discontinuation and before 131I administration. After 131I, serum T4 levels peaked on day 7 (23% vs. treatment day; 70% vs. baseline); FT4 levels peaked on day 14 (53% vs. treatment day; 107% vs. baseline). The serum T3 concentration increased 9% on day 2 (85% vs. baseline) and decreased from day 14 (15%) to day 30 (21%). We conclude that interruption of antithyroid drugs causes a short term increase in serum thyroid hormone levels in patients with Graves' hyperthyroidism receiving 131I. Thyroid hormone levels stabilize or decrease during the first 30 days after 131I therapy.

Silva DR, Gazzana MB, John AB, Siqueira DR, Maia AL, Barreto SS. · Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brasil. · J Bras Pneumol. · Pubmed #19287922 links to  free full text

Abstract: Recent studies have suggested an association between pulmonary arterial hypertension (PAH) and thyroid diseases (hypothyroidism and hyperthyroidism). This combination has a good prognosis, because the increase in the pulmonary artery pressure is usually slight and reverses after the treatment of the thyroid disease. Although the exact mechanism involved in the pathogenesis of this combination has not yet been established, it has been hypothesized that thyroid hormones and autoimmunity have a direct influence. Due to the high prevalence of thyroid disease in patients with PAH, thyroid function tests should be considered in the investigation of every patient with PAH. In this review, we describe the prevalence of PAH in patients with thyroid diseases and the prevalence of thyroid disease in patients with PAH, as well as addressing the principal effects that thyroid diseases have on the respiratory system. In addition, we report the treatment effects in patients with these diseases.

Puñales MK, da Rocha AP, Meotti C, Gross JL, Maia AL. · Endocrine Division, Thyroid Section, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul , Porto Alegre, Brazil. · Thyroid. · Pubmed #18991485 No free full text.

Abstract: BACKGROUND: RET genotype analysis allows identification of asymptomatic carriers at risk of developing medullary thyroid carcinoma (MTC). However, there is still controversy regarding the ideal timing and extent of prophylactic thyroidectomy due to the wide spectrum of clinical presentation. Surveillance of a large number of young patients is crucial to advance our understanding of the natural course of the disease. This study aimed to describe the clinical presentation, oncological features, and treatment outcome of children and young adults harboring RET mutations followed at our institution from 1997 to 2007. METHODS: Forty-one individuals aged < or =25 years from 17 independent multiple endocrine neoplasia type 2A kindred were studied. Twenty-one individuals presented with thyroid nodules at diagnosis, and 20 were disease free at physical examination. RESULTS: Preoperative basal calcitonin levels were elevated in 85.7% of patients with clinical disease and in 54.5% of asymptomatic carriers. Thyroid ultrasonography (US) showed one or more nodules in 69.0% of the patients. A positive correlation between age at surgery and tumor-node-metastasis (TNM) stages was observed (p < 0.001). None of the patients under 15 years of age presented lymph node or distant metastasis. After a follow-up of 4.4 +/- 1.4 years all asymptomatic patients were disease free based on physical examination, cervical US, and undetectable serum calcitonin levels. In the group of patients with clinical disease, 47.6% have persistent disease (follow-up of 12.0 +/- 5.9 years). Indeed, palpable thyroid nodule at diagnosis was significantly associated with persistent disease (p < 0.001, odds ratio [OR] 1.9, 95% confidence interval [CI 95%] 1.27-2.87). Of note, none of the patients who presented lymph node metastasis at diagnosis were cured by surgical intervention (p < 0.001, OR 5.0, CI 95% 1.45-17.0). CONCLUSION: Our data show a time-dependent MTC progression. The presence of a palpable thyroid nodule and lymph node metastasis at diagnosis was associated with persistent or recurrent disease after surgical procedure.

Milos IN, Frank-Raue K, Wohllk N, Maia AL, Pusiol E, Patocs A, Robledo M, Biarnes J, Barontini M, Links TP, de Groot JW, Dvorakova S, Peczkowska M, Rybicki LA, Sullivan M, Raue F, Zosin I, Eng C, Neumann HP. · Section of Preventive Medicine, Department of Nephrology, University of Freiburg Medical Centre, Freiburg im Breisgau, Germany. · Endocr Relat Cancer. · Pubmed #18794325 No free full text.

Abstract: RET testing in multiple endocrine neoplasia type 2 for molecular diagnosis is the paradigm for the practice of clinical cancer genetics. However, precise data for distinct mutation-based risk profiles are not available. Here, we survey the clinical profile for one specific genotype as a model, TGC to TGG in codon 634 (C634W). By international efforts, we ascertained all available carriers of the RET C634W mutation. Age at diagnosis, penetrance, and clinical complications were analyzed for medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism (HPT), as well as overall survival. Our series comprises 92 carriers from 20 unrelated families worldwide. Sixty-eight subjects had MTC diagnosed at age 3-72 years (mean 29). Lymph node metastases were observed in 16 subjects aged 20-72 and distant metastases in 4 subjects aged 28-69. Forty-one subjects had pheochromocytoma detected at age 18-67 (mean 36). Amongst the 28 subjects with MTC and pheochromocytoma, six developed pheochromocytoma before MTC. Six subjects had HPT diagnosed at age 26-52 (mean 39). Eighteen subjects died; of the 16 with known causes of death, 8 died of pheochromocytoma and 4 of MTC. Penetrance for MTC is 52% by age 30 and 83% by age 50, for pheochromocytoma penetrance is 20% by age 30 and 67% by age 50, and for HPT penetrance is 3% by age 30 and 21% by age 50. These data provide, for the first time, RET C634W-specific neoplastic risk and age-related penetrance profiles. The data may facilitate risk assessment and genetic counseling.

Meyer EL, Goemann IM, Dora JM, Wagner MS, Maia AL. · Thyroid Section, Endocrinology Division, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, 90035-003 Porto Alegre, RS, Brazil. · Mol Cell Endocrinol. · Pubmed #18514391 links to  free full text

Abstract: Type II deiodinase (D2) plays a critical role in controlling intracellular T3 concentration and early studies indicated a follicular but not a parafollicular C-cell origin of D2 activity in the thyroid gland. Here, we show that D2 is highly expressed in human medullary thyroid carcinoma (MTC), a tumor that arises from the C-cells. D2 transcripts were detected in all MTC samples obtained from 12 unselected MTC patients and the levels of D2 activity were comparable to those found in surrounding normal follicular tissue (0.41+/-0.10 fmol min mg protein vs. 0.43+/-0.41 fmol min mg protein, P=0.91). Additional analysis in the TT cells, a human MTC cell line, demonstrated that the D2 expression is downregulated by thyroid hormones and enhanced by cAMP analogs and dexamethasone. The thyroid hormone receptor alpha1 and beta isoforms were also detected in all MTC samples and in TT cells, thus suggesting a potential role of T3 locally produced by D2 in this neoplastic tissue.

Wajner SM, dos Santos Wagner M, Melo RC, Parreira GG, Chiarini-Garcia H, Bianco AC, Fekete C, Sanchez E, Lechan RM, Maia AL. · Endocrine Division, Thyroid Section, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. · J Endocrinol. · Pubmed #17592020 links to  free full text

Abstract: The testis has been classically described as a thyroid hormone unresponsive tissue, but recent studies indicate that these hormones might play an important role in developing testes. We have previously demonstrated that type 2 iodothyronine deiodinase (D2), a thyroid hormone-activating enzyme, is expressed in adult rodent testis and that its activity is induced by hypothyroidism. Nevertheless, the precise location of D2 in testis is not known. The aim of the present work was to determine the testicular cell types in which D2 is expressed using real-time PCR analysis, in situ hybridization histochemistry, and determination of D2 activity in cell fractions isolated from adult euthyroid and/or hypothyroid rat testis. The D2 mRNA levels in germ cells were higher than those from somatic cells (6.94 +/- 1.49 vs 2.32 +/- 0.79 arbitrary units (au); P = 0.017). Hypothyroidism increased D2 expression in germ cells (6.94 +/- 1.49 vs 8.78 +/- 5.43 au, P = 0.002) but did not change D2 transcripts in somatic cells significantly (2.12 +/- 0.79 vs 2.88 +/- 1.39 au, P = 0.50). In situ hybridization analysis showed that D2 mRNA is specifically present in elongated spermatids undergoing differentiation, whereas other germ cell types and Sertoli cells of seminiferous epithelium and the interstitial cells were virtually negative for this enzyme. The enzyme activity measured in germ and somatic isolated cell fractions (0.23 +/- 0.003 vs 0.02 +/- 0.013 fmol/min per mg protein respectively; P < 0.001) further confirmed the real-time PCR and in situ hybridization results. Hence, our findings demonstrated that D2 is predominantly expressed in elongated spermatids, suggesting that thyroid hormone might have a direct effect on spermatogenesis in the adult rats.

Golbert L, Kolling JH, Leitão AH, Martins L, Kimura ET, Maia AL. · Endocrine Division, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Brazil. · Histol Histopathol. · Pubmed #17290351 No free full text.

Abstract: The RAS protooncogene has an important, although not yet established role in thyroid neoplasia. In this study, we evaluated the H-RAS mRNA and protein levels in human samples of nontoxic and toxic multinodular goiter samples, according to serum TSH levels. The mean of H-RAS mRNA levels in nodules of nontoxic nodular goiter were significantly increased compared to nonnodular tissue (1.49+/-1.21 vs. 0.94+/-0.81 AU, P=0.016). Nine of the 18 specimens (50%) of nontoxic multinodular goiter exhibited increased levels of H-RAS mRNA. The increased H-RAS mRNA levels were paralleled by inRAcreased H-Ras protein levels in about 90% of the cases. Interestingly, no differences were observed in H-RAS expression between nodules and adjacent nonnodular tissue in toxic nodular goiters (0.58+/-0.27 vs. 0.58+/-0.20 AU, P=0.88). None of the 10 samples from toxic multinodular goiters exhibited overexpression of H-RAS. The H-RAS expression was positively correlated with thyroglobulin expression (r2=0.51; P=0.04). In conclusion, we demonstrated increased levels of H-RAS mRNA and protein in samples of nontoxic multinodular goiter, indicating that it might be involved in goiter pathogenesis. In contrast, H-RAS overexpression was not detected in any of the samples of toxic multinodular goiter, suggesting different mechanisms for cell proliferation in nodular goiter according to thyroid status.

de Souza Meyer EL, Dora JM, Wagner MS, Maia AL. · Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. · Clin Endocrinol (Oxf). · Pubmed #15943828 No free full text.

Abstract: OBJECTIVE: Type I iodothyronine deiodinase (D1) catalyses the 5' monodeiodination of T4 and is highly expressed in normal human thyroid gland. We have investigated D1 expression in a series of benign and malignant differentiated thyroid neoplasias. DESIGN: Surgically isolated thyroid tumour fragments were used. D1 expression was determined by reverse transcription polymerase chain reaction (RT-PCR) and enzymatic assay. PATIENTS: Tumours and adjacent normal tissues were obtained from 28 unselected patients (papillary carcinoma, n = 14; follicular adenoma, n = 7; follicular carcinoma, n = 6; anaplastic carcinoma, n = 1). MEASUREMENTS: D1 mRNA levels were determined using specific primers for the human D1 gene and enzymatic assays were performed using T4 as substrate. RESULTS: In papillary thyroid carcinoma (PTC), D1 mRNA and activity levels were decreased compared with the surrounding tissue (0.25 +/- 0.24 vs. 1.09 +/- 0.54 arbitrary units (AU), P < 0.001 and 0.08 +/- 0.07 vs. 0.24 +/- 0.15 pmol T4/min/mg protein, P = 0.045, respectively). Decreased D1 expression was consistent and was observed in all histological subtypes and clinical stages analysed, including microcarcinomas. By contrast, significantly higher D1 mRNA levels and enzyme activity were present in follicular adenoma (1.9 +/- 1.5 vs. 0.83 +/- 0.58 AU, P = 0.028 and 2.67 +/- 1.42 vs. 0.22 +/- 0.06 pmol T4/min/mg protein, P = 0.044, respectively) and in follicular thyroid carcinoma (FTC) than in surrounding normal tissue (1.2 +/- 0.46 vs. 0.67 +/- 0.18 AU, P = 0.038 and 1.20 +/- 0.58 vs. 0.20 +/- 0.10 pmol T4/min/mg protein, P < 0.001, respectively). Type II iodothyronine deiodinase (D2) activity was also significantly higher in metastatic FTC samples than in normal thyroid tissues (5.20 +/- 0.81 vs. 0.30 +/- 0.27 fmol T4/min/mg protein, P < 0.001). CONCLUSIONS: These findings suggest that thyroid cell dedifferentiation promotes changes in D1 gene expression by pretranscriptional mechanisms and indicate that decreased D1 expression might be an early and discrete event in thyroid cell dedifferentiation towards papillary thyroid carcinoma.

Goldani LZ, Klock C, Diehl A, Monteiro AC, Maia AL. · Infectious Diseases Unit, Hospital das Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. · J Clin Microbiol. · Pubmed #11015430 links to  free full text

Abstract: Fungal infection of the thyroid is rare. Most reported cases have involved Aspergillus, Coccidioides, and Candida species in the setting of disseminated disease. Infection of the thyroid with Histoplasma capsulatum is rarely reported as part of disseminated disease, even in geographic areas where histoplasmosis is endemic. We report a 52-year-old woman with a previous Hashimoto's disease and non-Hodgkin's lymphoma in which a diffuse enlarged thyroid gland with a large nodule was the only apparent locus of histoplasmosis. Fine-needle aspiration of the thyroid was an important diagnostic tool in establishing the diagnosis of histoplasmosis of the thyroid. The patient was initially treated with itraconazole (400 mg/day) for the fungal infection and six cycles of chemotherapy for the lymphoma. At a 6-month follow-up examination, the patient was doing well on suppressive therapy of itraconazole (200 mg/day), with no symptoms and with regression of the thyroid nodule and cervical adenopathy.