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).

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).

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%.

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.

Chronic lymphocytic thyroiditis does not influence the risk of recurrence in patients with papillary thyroid carcinoma and excellent response to initial therapy.

BACKGROUND: This study evaluated the recurrence in patients with papillary thyroid cancer and an excellent response to initial therapy, comparing those with and without chronic lymphocytic thyroiditis. METHODS: This was a prospective study. Patients who met the following criteria were selected: diagnosis of papillary thyroid cancer; submitted to total thyroidectomy followed or not by ablation with 131I; and neck ultrasonography without abnormalities, nonstimulated thyroglobulina (Tg) ≤0.2 ng/ml, and undetectable antithyroglobulin antibodies (TgAb) 12-18 months after initial therapy. The patients were divided into two groups: group A, with chronic lymphocytic thyroiditis on histology; group B, without chronic lymphocytic thyroiditis on histology. RESULTS: Groups A and B were similar in terms of sex and age of the patients, characteristics of the tumor, tumor-node-metastase stage and risk category. The time of follow-up ranged from 24 to 120 months (median 66 months). During follow-up, 5 patients of group A (2.6 %) and 9 patients of group B (2 %) developed recurrence (p = 0.77). Patients with chronic lymphocytic thyroiditis were more likely to progress to persistently borderline TgAb. No patient had positive TgAb (above the reference value) during follow-up. Recurrences occurred in 12/588 patients (2 %) with undetectable TgAb in all measurements, in 1/32 (3.1 %) with detectable TgAb on some occasion but that returned to undetectable spontaneously, and in 1/13 (7.7 %) with persistently borderline TgAb. These rates did not differ significantly (p = 0.25). CONCLUSION: The results of the present study showed the absence of an association between chronic lymphocytic thyroiditis and recurrence risk at least in patients with an excellent response to initial therapy.

Elevated IGF-1 with GH suppression after an oral glucose overload: incipient acromegaly or false-positive IGF-1?

OBJECTIVE: To report the evolution of patients with a suggestive clinical scenario and elevated serum insulin-like growth factor-1 (IGF-1), but growth hormone (GH) suppression in the oral glucose tolerance test (OGTT), in whom acromegaly was not initially excluded. SUBJECTS AND METHODS: Forty six patients with a suggestive clinical scenario, who had elevated IGF-1 (outside puberty and pregnancy) in two measurements, but GH < 0.4 µg/L in the OGTT, were selected. Five years after initial evaluation, the patients were submitted to clinical and laboratory (serum IGF-1) reassessment. Patients with persistently elevated IGF-1 were submitted to a new GH suppression test and magnetic resonance imaging (MRI) of the pituitary. RESULTS: Four patients were lost to follow-up. During reassessment, 42 patients continued to show no "typical phenotype" or changes in physiognomy. Fifteen of the 42 patients had normal IGF-1. Among the 27 patients with persistently elevated IGF-1 and who were submitted to a new OGTT, GH suppression was confirmed in all. Two patients exhibited a lesion suggestive of microadenoma on pituitary MRI. In our interpretation of the results, acromegaly was ruled out in 40 patients and considered "possible" in only 2. CONCLUSION: Our results show that even in patients with a suggestive clinical scenario and elevated IGF-1, confirmed in a second measurement and without apparent cause, acromegaly is very unlikely in the case of GH suppression in the OGTT.

Elevated IGF-1 with GH suppression after an oral glucose overload: incipient acromegaly or false-positive IGF-1?

ABSTRACT Objective To report the evolution of patients with a suggestive clinical scenario and elevated serum insulin-like growth factor-1 (IGF-1), but growth hormone (GH) suppression in the oral glucose tolerance test (OGTT), in whom acromegaly was not initially excluded. Subjects and methods Forty six patients with a suggestive clinical scenario, who had elevated IGF-1 (outside puberty and pregnancy) in two measurements, but GH < 0.4 µg/L in the OGTT, were selected. Five years after initial evaluation, the patients were submitted to clinical and laboratory (serum IGF-1) reassessment. Patients with persistently elevated IGF-1 were submitted to a new GH suppression test and magnetic resonance imaging (MRI) of the pituitary. Results Four patients were lost to follow-up. During reassessment, 42 patients continued to show no “typical phenotype” or changes in physiognomy. Fifteen of the 42 patients had normal IGF-1. Among the 27 patients with persistently elevated IGF-1 and who were submitted to a new OGTT, GH suppression was confirmed in all. Two patients exhibited a lesion suggestive of microadenoma on pituitary MRI. In our interpretation of the results, acromegaly was ruled out in 40 patients and considered “possible” in only 2. Conclusion Our results show that even in patients with a suggestive clinical scenario and elevated IGF-1, confirmed in a second measurement and without apparent cause, acromegaly is very unlikely in the case of GH suppression in the OGTT.

Efficacy of adjuvant therapy with 3.7 GBq radioactive iodine in intermediate-risk patients with 'higher risk features' and predictive value of postoperative nonstimulated thyroglobulin.

AIM: This study evaluated the efficacy of adjuvant therapy with 3.7 GBq radioactive iodine (RAI) in patients with papillary thyroid carcinoma (PTC) of intermediate risk with higher risk features and determined the predictive value of postoperative nonstimulated thyroglobulin (Tg). METHODS: This was a prospective study including 85 patients with PTC of intermediate risk and higher risk features: tumor greater than 1 cm and aggressive histological subtype or vascular invasion; and/or more than three positive lymph node (LN) or LN greater than 1.5 cm or showing macroscopic extracapsular extension; and/or a combination of tumor greater than 4 cm, microscopic extrathyroidal extension, aggressive histology, and LN metastases (cN1). After thyroidectomy, all patients had nonstimulated Tg of at least 0.3 ng/ml and ultrasonography showed no anomalies. RESULTS: When evaluated 12 months after RAI therapy, an excellent response to initial therapy was achieved in 61 patients (71.7%). Structural disease was detected in five patients (5.9%). During follow-up, 6/80 patients (7.5%) without structural disease 1 year after RAI developed relapse. In the last assessment, 80 patients (94.1%) had nonstimulated Tg less than 1 ng/ml and no evidence of structural disease. There was no case of death because of the tumor. Postoperative nonstimulated Tg was a predictive factor of the main outcome (structural disease 1 year after RAI or recurrence) and the best cut-off was 1.8 ng/ml (sensitivity: 72.7%, specificity: 83.4%, negative predictive value: 95.4%). CONCLUSION: In patients with PTC of intermediate risk with higher risk features treated with 3.7 GBq RAI, postoperative nonstimulated Tg up to 1.8 ng/ml was a predictor of low risk of structural disease 1 year after therapy or recurrence.

Long-term results of ablation with low radioiodine activity in patients with papillary thyroid carcinoma and predictive value of postoperative nonstimulated thyroglobulin.

AIM: This study evaluated the long-term results of ablation with low iodine-131 (131I) activity in patients with papillary thyroid carcinoma (PTC) with a lower risk of recurrence and who remained with nonstimulated thyroglobulin (Tg) of at least 0.3 ng/ml after total thyroidectomy. METHODS: This was a prospective study including 119 patients with PTC (except for microcarcinoma restricted to the thyroid and tumor with extensive extrathyroidal extension, aggressive histology, extensive lymph node involvement, or known residual disease). After thyroidectomy, all patients had nonstimulated Tg of at least 0.3 ng/ml (range: 0.3-8.5 ng/ml). The patients were treated with low 131I activity (30 or 50 mCi). RESULTS: Post-therapy whole-body scanning showed ectopic uptake in two patients. When evaluated 12 months after ablation, nonstimulated Tg up to 0.2 ng/ml with negative antithyroglobulin antibodies and neck ultrasonography, defined as excellent response to initial therapy, was achieved in 92 patients (77.3%). Only one patient had persistent structural disease. During follow-up, 3/118 patients (2.5%) developed structural recurrence. In the last assessment, 102/115 patients who were not subjected to any additional therapy had nonstimulated Tg up to 0.2 ng/ml, negative antithyroglobulin antibodies, and ultrasonography with no anomalies. No death occurred because of the tumor. CONCLUSIONS: Postoperative nonstimulated Tg up to 2 ng/ml had a negative predictive value of 98% for recurrent or persistent structural disease. In patients with PTC who have a lower risk of recurrence and who remain with nonstimulated Tg of at least 0.3 ng/ml after total thyroidectomy, Tg up to 2 ng/ml can be used as a criterion for ablation with low 131I activity.

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.