Roberto Bernardo Santos

Genetic polymorphisms associated with cigarette smoking and the risk of Graves’ disease

Objective  Cigarette smoking is a well‐recognized risk factor of Graves’ disease and, particularly, Graves’ ophthalmopathy. Hence, germline polymorphisms of detoxification genes and genes belonging to the major DNA repair–apoptosis pathways might have an important role in disease susceptibility. In addition, as some of these genes are regulated by thyroid hormones, they may affect the patients’ outcomes. We aimed to assess the influence of the GST, CYP and TP53 gene polymorphisms in the risk of Graves’ disease and its outcome.

A randomized controlled trial to evaluate the effectiveness of 2 regimens of fixed iodine (¹³¹I) doses for Graves disease treatment.

Aim: To investigate the effectiveness of 2 fixed iodine (131I) doses for the treatment for Graves hyperthyroidism and their impact on eye disease. Methods: We prospectively examined 76 patients who received a fixed dose of 370 MBq (group 1) and 52 patients who received 555 MBq 131I (group 2). Patients were followed up for 12 months and considered in remission when they were in a stable euthyroid or hypothyroid state in the absence of antithyroid drugs 12 months after 131I administration. Eight patients with active eye disease received a daily dose of 0.5 mg/kg prednisone per kilogram of body weight at the time of radioiodine therapy for 1 month. Results: The remission rate obtained was similar in groups 1 (73.7%) and 2 (80.8%; P = 0.35). Hypothyroidism was diagnosed in 56.5% of the 370-MBq group and 71.1% of the 555-MBq group patients (P = 0.13). There was no correlation among clinical features, thyroid uptake, antibody levels, serum hormones levels, and outcome. However, logistic regression analysis demonstrated that patients with large thyroid glands had 2.4 times less chance to go into remission (odds ratio; 95% confidence interval = 1.18–4.96). None of the patients developed eye disease during any fixed-dose treatment regimen or worsened their previously diagnosed ophthalmopathy. Conclusions: Fixed doses of 370 MBq and 555 MBq 131I provided similar remission rates; however, outcome was influenced by the thyroid size. We propose that 370 MBq 131I should be the routine treatment dose for all Graves disease patients, reserving a dose of 555 MBq 131I to palpable large goiters, without any additional concern to eye disease.

Is diffuse and peritumoral lymphocyte infiltration in papillary thyroid cancer a marker of good prognosis

Background: Papillary thyroid carcinoma (PTC) is the most frequently diagnosed endocrine neoplasia, representing 70 to 80% of all diagnosed thyroid cancers. Furthermore, Hashimoto’s thyroiditis is a frequent inflammatory thyroid disease and the main cause of hypothyroidism. The relationship between Hashimoto’s thyroiditis and PTC remains controversial. Methods: Surgery for PTC was performed at our institution on 157 consecutive patients. They were classified by the degree of lymphocyte infiltration (LI). LI was classified as diffuse LI or peritumoral LI (only in or around the tumor), or absent. In addition, age, gender, tumor size, histopathological findings, lymph-node metastasis, extra-thyroidal extension, multifocal tumor, coexistence of LI and clinical outcomes were analyzed. Results: Out of the 141 patients included in the study, 83 (59%) had diffuse LI and 22 (16%) had peritumoral LI. In 36 patients (25%) LI was absent. A comparison of patients in the 3 groups revealed no significant difference in their genders, ages, smoking status, thyroid function, or nodule size at the time of surgery. The characteristics of PTC showed no differences in lymph-node metastasis, tumor invasion into contiguous neck structures, angioinvasion, or PTC subtypes. Tumor-node-metastasis (TNM) classification and classes did not differ among the 3 groups. During the follow-up, 64 out of 141 patients with PTC (55%) had recurrences from 6 to 130 months after the initial treatment. After a mean follow-up period of 8 yr we observed a significantly (p=0.01) high recurrence (66.6%) in the LI absent group with 24 of 36 patients when compared to patients from the diffuse LI group (32 out of 83 patients; 38.5%) and peritumoral LI group (8 out of 22 patients; 25%). Conclusions: Although the role of the inflammatory-immune cells is complex and little understood, we found a more favorable course of PTC in the presence of LI (diffuse or peritumoral); this supports the hypothesis that LI represents a form of immune reaction to control tumor growth and proliferation.

Carcinoma não medular familiar da tiróide

Nonmedullary thyroid carcinoma, originating from thyroid epithelial cells, is the most frequent thyroid malignant neoplasia. Since 1955, there has been increasing evidence that this cancer may have a familial predisposition. It is now established that around 4.2% of all nonmedullary thyroid carcinomas occurs on the background of familial predisposition. These cases are often more aggressive, due to early onset, multifocality and a higher percentual of recurrences. An autossomal dominant inheritance pattern appears likely in most families, although the exact genes responsible for this syndrome have not yet been identified. Patients affected by this cancer should be treated with total thyroidectomy routinely and, in most cases, lymph node dissection, followed by iodine ablation and TSH suppressive therapy with levothyroxine. Some authors also recommend that first-degree relatives of patients with nonmedullary thyroid cancer (especially women) should be submitted to neck ultrasound for thyroid cancer screening, aiming early diagnosis for better treatment results.