Indication for radioactive iodine in patients with papillary thyroid carcinoma without apparent disease after total thyroidectomy but with elevated antithyroglobulin antibodies.

OBJECTIVE: To evaluate a criterion for the selective indication of radioactive iodine (RAI) based on the short-term behaviour of antithyroglobulin antibodies (TgAb) in patients with papillary thyroid carcinoma (PTC) who have negative thyroglobulin (Tg) and neck ultrasonography (US) without abnormalities after total thyroidectomy but elevated TgAb. DESIGN: This was a prospective study that evaluated 216 patients with low- or intermediate-risk PTC who had nonstimulated Tg ≤ 0.2 ng/ml and no US abnormalities but elevated TgAb 3 months after thyroidectomy. RAI was not indicated in patients with negative TgAb or a >50% reduction in TgAb concentrations 6 months after initial assessment followed by a negative test or an additional reduction (also >50%) after 12 months. RESULTS: Only two of the 114 patients who did not receive RAI developed recurrences; another 108 patients met the criterion of an excellent response to therapy in the last assessment and TgAb persisted in four patients but there was an additional reduction in their concentration during follow-up. Among the 102 patients who received RAI, post-therapy whole-body scanning (RxWBS) detected persistent disease in 8 (8%). Two of the 94 patients without persistent disease on RxWBS developed recurrences. In the last assessment, in the absence of additional treatment, 54/92 patients (58.7%) without structural recurrence had negative TgAb. CONCLUSIONS: The indication for RAI can be based on the short-term behaviour of TgAb in patients with PTC and elevated TgAb after thyroidectomy who are not high risk and who do not have apparent disease (nonstimulated Tg ≤ 0.2 ng/ml and no US abnormalities).

Ultrasonography screening in children and adolescents who have one parent with familial non-medullary thyroid carcinoma.

AIM: To evaluate ultrasonography (US) screening for thyroid cancer in children and adolescents who have one parent with familial non-medullary thyroid carcinoma (FNMTC) unrelated to known genetic syndromes. METHODS: In this prospective study, we selected 72 children and adolescents (age ≤18 years) without a palpable thyroid nodule or history of radiation exposure, but who have one parent diagnosed with FNMTC (i.e. at least one other affected first-degree relative). The children and adolescents were evaluated by US during initial assessment and after 5 years. RESULTS: Initial US revealed pure cysts in five participants and nodules in seven, which were ≥5 mm in five. These patients were submitted to fine needle aspiration, which revealed benign cytology in four and a follicular lesion of undetermined significance in one. Fine needle aspiration was repeated in the last case and in one case with benign cytology but suspicious US. The second cytology was benign in both cases. After 5 years, another two participants with initially normal US had nodules <5 mm in the absence of suspicious findings. The frequency of lesions detected by US was not associated with participant sex or age, number of relatives with thyroid cancer (2 or 3), maternal or paternal origin of tumour, or age of the relatives at diagnosis. CONCLUSION: The present results suggest that US screening is not necessary in children or adolescents when one parent has a diagnosis of FNMTC (≥2 affected relatives).

Report of one case of malignancy among 17 autonomous thyroid nodules in children and adolescents.

AIM: This study aimed to report a case of malignancy in a series of 17 autonomous thyroid nodules in children/adolescents. METHODS: We performed a retrospective analysis of patients with thyroid nodules between 2003 and 2018 who had the following characteristics: (i) low serum thyroid stimulating hormone (TSH); (ii) nodule(s) > 1 cm on ultrasonography; (iii) homogenous uptake on scintigraphy with radioiodine in the area corresponding to the nodule(s); (iv) suppression of the remaining parenchyma; and (v) age ≤ 18 years. The approach of the institution was to perform fine-needle aspiration in all children/adolescents with autonomous thyroid nodules, as well as surgery in all patients of this age group with toxic nodular disease. RESULTS: Thirteen patients, 11 girls and 2 boys aged 9-18 years, had 17 autonomous nodules ranging in size from 1.4 to 5.5 cm. Cytology was benign in 11 nodules (64.7%) and histology confirmed the benign nature in all of them. Two nodules (11.7%) had non-diagnostic cytology and were also benign. Cytology was indeterminate in three other nodules (17.6%), with two adenomas and one follicular tumour of uncertain malignant potential. Finally, cytology was suspicious for malignancy in only one nodule (5.9%) for which the infiltrative follicular variant of papillary thyroid carcinoma was confirmed. The patient was a 13-year-old girl whose nodule exhibited highly suspicious ultrasonography features. CONCLUSION: The incidence of malignancy in this series of 17 autonomous thyroid nodules in children/adolescents was 5.9%.

Natural history of subclinical hypothyroidism with TSH ≤10 mIU/l: a prospective study.

OBJECTIVE: The risk of progression of subclinical hypothyroidism (SCH) to clinical dysfunction is one of the factors considered in the decision to treat this condition. This study evaluated the natural history of SCH in women with TSH ≤10 mIU/l. DESIGN: This is a prospective study. PATIENTS: Two hundred and fifty-two women with SCH and TSH levels ranging from 4·5 to 10 mIU/l were followed up for a period of 5 years. RESULTS: Among the 241 patients followed up until the completion of the study, 46 (19%) required levothyroxine (L-T4) therapy, 55 (22·8%) had spontaneous normalization of serum TSH, and 140 (58·1%) continued to meet the criteria for mild SCH. In multivariate analysis, only initial TSH >8 mIU/l was a predictor of the need for L-T4. In contrast, initial TSH ≤8 mIU/l and the absence of thyroiditis [negative antithyroid peroxidase antibodies (TPOAb) and ultrasonography (US)] were predictors of TSH normalization. Of note, the natural history was similar in TPOAb-positive patients and patients with negative TPOAb but with positive US. CONCLUSIONS: Most women with mild elevation of serum TSH, ranging from 4·5 to 10 mIU/l, do not progress to overt hypothyroidism and even normalize their TSH. However, initial TSH seems to be a more important predictor of progression than the presence of antibodies or ultrasonographic appearance.

A low postoperative nonstimulated serum thyroglobulin level excludes the presence of persistent disease in low-risk papillary thyroid cancer patients: implication for radioiodine indication.

OBJECTIVE: To evaluate the presence of persistent disease, including on post-therapy whole-body scan (RxWBS), in low-risk patients with papillary thyroid carcinoma (PTC) >1 cm who have low nonstimulated thyroglobulin (Tg) (measured with a sensitive assay), negative anti-Tg antibodies (TgAb) and neck ultrasound (US) showing no metastases after total thyroidectomy. PATIENTS: We studied 154 patients with PTC >1 cm classified as low risk, who had US without metastases, negative TgAb, nonstimulated Tg ≤ 0·25 ng/ml and TSH ≤ 2 mIU/l about 3 months after total thyroidectomy. RESULTS: Tg measured immediately before (131) I was ≤ 1 ng/ml in 89·5% of the patients and >1 ng/ml in 10·5%. None of the patients showed ectopic uptake on RxWBS. Uptake in the thyroid bed was observed in 146 (94·8%) patients and was ≤ 2% in all of them. In the control assessment 9-12 months after ablation, stimulated Tg (sTg) ≤ 1 ng/ml was achieved in 150 patients (97·4%). Only one patient had sTg >2 ng/ml (2·5 ng/ml) and none of the patients had apparent disease detected by imaging methods. During further short-term follow-up after control assessment (median of 24 months), none of the patients had tumour recurrence. CONCLUSIONS: The combination of nonstimulated Tg ≤0·25 ng/ml, negative TgAb and US without metastases after thyroidectomy rules out the presence of persistent disease (including on RxWBS) in low-risk patients with PTC >1 cm. This demonstration weakens the indication of ablation with (131) I in these cases.

Ultrasonographic differentiation of cervical lymph nodes in patients with papillary thyroid carcinoma after thyroidectomy and radioiodine ablation: a prospective study.

OBJECTIVE: The objective of the present study was to validate an ultrasound (US) classification of cervical lymph nodes (LNs) in patients with papillary thyroid cancer (PTC) after thyroidectomy and radioactive iodine (131I) ablation. METHODS: We performed a prospective study in which the patients were submitted to thyroidectomy and 131I ablation and then followed until neck US revealed LN(s) ≥5 mm. A total of 288 LNs from 112 patients with PTC were evaluated. Patient management was based on LN characteristics grouped according to the classification system studied here. RESULTS: The presence of microcalcifications and/or cystic degeneration of cervical LNs were highly suggestive of a metastatic etiology (specificity of 99.4%). In contrast, the most sensitive finding for LNs affected by PTC was the absence of an echogenic hilum (sensitivity of 100%). In the absence of these findings (microcalcifications, cystic degeneration, echogenic hilum), a metastatic etiology was the most likely in the case of a round LN (specificity of 89%). The differentiation of a spindle-shaped LN without a visible hilum by Doppler analysis permitted us to dichotomize an initial probability of metastases of 13% in 25% (with peripheral vascularization) versus 3.3% (without peripheral vascularization). CONCLUSIONS: Our results confirm that the classification proposed for cervical LNs in patients with PTC is valid for determining patient management following initial therapy.

Thyroid dysfunction in pregnancy: definition of TSH cut-off should precede the decision of screening in low-risk pregnant women.

OBJECTIVE: To evaluate the frequency of elevated TSH in pregnant women of low risk for thyroid dysfunction. SUBJECTS AND METHODS: TSH was measured in 838 pregnant women during the first trimester of gestation (from 6 to 14 weeks, median 9 weeks) and who were considered to be of low risk for thyroid dysfunction because they did not meet any of the following criteria: known or clinically suspected thyroid disease; history of head and neck radiotherapy; personal history of autoimmune diseases; family history of thyroid disease; history of abortion or prematurity. RESULTS: The frequency of elevated TSH was 0.25%, 1.2% and 5.5% at cut-off values of 4, 3 and 2.5?mIU/l, respectively. These rates increase to 1.43%, 2.4% and 6.2% if cases of TSH> 2 mIU/l with TPOAb are included. TSH was undetectable in 18 women (2.1%), but only six (0.71%) had elevated T4. CONCLUSIONS: The definition of a TSH cut-off that defines subclinical hypothyroidism (SCH) should precede the decision of screening pregnant women without any risk factors for thyroid dysfunction.

Fluorine-18-fluorodeoxyglucose positron emission tomography in thyroid nodules with indeterminate cytology: a prospective study.

BACKGROUND: Up to 20% of thyroid nodules subjected to fine-needle aspiration exhibit indeterminate cytology. The rate of malignancy in these nodules ranges from 10 to 40%. The objective of this prospective study was to evaluate the utility of fluorine-18-fluorodeoxyglucose (F-FDG) PET in nonautonomous thyroid nodules of more than 1 cm whose cytology is indeterminate (Bethesda categories III or IV) and that are not highly suspicious on ultrasonography. PATIENTS AND METHODS: Fifty-nine patients with 63 nodules were studied. RESULTS: F-FDG PET result was positive in 31 nodules. Of these, 22.6% were malignant, 25.8% were noninvasive follicular thyroid neoplasm with papillary-like nuclear features, 6.5% were tumors of uncertain malignant potential, and 45.1% were benign. F-FDG PET result was negative in 32 nodules. Of these, 3.1% were neoplasm with papillary-like nuclear features, 3.1% were tumors of uncertain malignant potential, and 93.8% were benign. CONCLUSION: This study suggests a high negative predictive value of F-FDG PET in thyroid nodules of more than 1 cm whose cytology is indeterminate and that are not highly suspicious on ultrasonography.

[Contribution of computed tomography in patients with lung metastases of differentiated thyroid carcinoma not apparent on plain radiography who were treated with radioiodine]. / Contribuição da tomografia computadorizada em pacientes com metástases pulmonares de carcinoma diferenciado de tireóide não-aparentes na radiografia e tratados com radioiodo.

Computed tomography (CT or CAT Scan) of the chest is more sensitive than radiography in the detection of lung metastases of differentiated thyroid cancer (DTC), but little information is available regarding the aggregated value of this method. The present study evaluated the response of patients with lung metastases of DTC not apparent on radiography to treatment with 131I and the value of CT in these cases. Twenty-five patients with lung metastases not apparent on radiography, who initially received 100-200 mCi I151, were evaluated and those presenting pulmonary uptake on post-therapy WBS were submitted to a new treatment after 6 to 12 months, and so on. The chance of detection of pulmonary uptake on post-therapy WBS did not differ between patients with negative and positive CT (100% versus 91.5%). Mean serum Tg levels were higher in patients with positive CT (108 ng/ml versus 52 ng/ml). Negative post-therapy WBS was achieved in 82% of patients with positive CT and in 92.3% with negative CT and the cumulative I131 activity necessary to achieve this outcome did not differ between the two groups (mean=300 mCi). Stimulated Tg was undetectable in 47% of patients with negative CT at the end of treatment, but in none of the patients whose CT continued to be positive. In patients with elevated Tg, the CT result apparently did not change the indication of therapy or the I131 activity to be administered. In cases with lung metastases, the persistence of micronodules on CT was associated with the persistence of detectable Tg in patients presenting negative post-therapy WBS.

Is adjuvant therapy useful in patients with papillary carcinoma smaller than 2 cm?

To evaluate tumor recurrence after total thyroidectomy in patients with single papillary carcinoma with size 0.5 mIU/L in >or=50% of the measurements in all patients. Complete remission (stimulated thyroglobulin (Tg) 0.05). Six patients who still had stimulated Tg > 1 ng/mL (<5 ng/mL) showed a >50% decrease in comparison with Tg measured 12-24 months earlier. In conclusion, we suggest a more conservative approach with respect to central-compartment neck dissection, postoperative (131)I, and suppressive therapy in patients with small tumors restricted to the thyroid.

[Usefulness of neck ultrasonography in the follow-up of patients with differentiated thyroid cancer]. / Emprego da ultra-sonografia cervical no seguimento de pacientes com carcinoma diferenciado de tireóide.

Neck ultrasonography (US) is recommended for the assessment of all patients with thyroid carcinoma after initial therapy, since even low-risk patients with undetectable stimulated thyroglobulin (Tg) may present cervical metastases. In the case of these metastases, US is the most sensitive method and is superior to whole-body 131I scanning. Cervical lymph nodes with a diameter > 5 mm presenting thin calcifications and/or cystic degeneration have almost always a malignant etiology. In the absence of these characteristics, a round shape and the absence of an echogenic hilum are "suspicious" findings, whereas elongated lymph nodes with a visible echogenic hilum are considered benign. Doppler flow analysis helps with the differential diagnosis, usually revealing peripheral or mixed hypervascularization in malignant cases. In the presence of "suspicious" lymph nodes upon US, fine-needle aspiration cytology and measurement of Tg in the needle lavage fluid are useful and complementary exams for the definition of the etiology, with the combination of the two methods showing elevated sensitivity and 100% specificity. US is also useful before thyroidectomy, even contributing in some cases to modify the surgical planning, and before ablation for the measurement of thyroid remnants and detection of persistent lymph node metastases. Another application of this imaging method is to guide the injection of ethanol (sclerotherapy) or the introduction of electrodes for radiofrequency ablation in selected cases of isolated lymph node metastases as an alternative to traditional therapies.

Management of low-risk patients with thyroid carcinoma and detectable thyroglobulin on T4 after thyroidectomy and ablation with iodine-131.

OBJECTIVE: To evaluate the positive predictive value of detectable Tg during T4 therapy (Tg on T4) in patients with thyroid cancer after total thyroidectomy and remnant ablation, discussing the work-up in this situation and the empirical indication of 131I. PATIENTS AND METHODS: Initially, 234 low-risk patients [tumor < 5cm, completely resected, no extensive extrathyroid invasion (pT4)] submitted to total thyroidectomy and ablation with 131I (3.7-5.5 GBq) who presented no ectopic uptake on RxWBS were studied. Of these, 23 patients with detectable Tg on T4 (> 1ng/ml) during the first year after initial therapy were selected. RESULTS: Metastases were detected by neck US in 7 patients, by chest CT in 2 and by US and CT in 3. Four of five patients with lung metastases upon CT had a positive RxWBS. Eleven patients with negative US and CT received a new 131I dose (without DxWBS), and RxWBS showed ectopic uptake in 3 patients. Among the patients with negative RxWBS, 7 remained free of apparent disease and Tg was declining (5 with undetectable Tg on T4 at the end of the study). One patient presented an increase in Tg and FDG-PET was positive for lymph node and bone metastases. CONCLUSIONS: All patients with Tg on T4 > 5ng/ml presented apparent disease. In these cases, even when US and CT are negative, the administration of a therapeutic dose of 131I (without DxWBS) and FDG-PET are recommended. Among patients with detectable Tg on T4

[Thyroid nodules and differentiated thyroid cancer: Brazilian consensus]. / Nódulos de tireóide e câncer diferenciado de tireóide: consenso brasileiro.

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.