Risk of recurrence in patients with papillary thyroid carcinoma and minimal extrathyroidal extension not treated with radioiodine.

PURPOSE: This study evaluated the recurrence rate in patients with papillary thyroid carcinoma (PTC) and minimal extrathyroidal extension (mETE) who had low thyroglobulin (Tg) after total thyroidectomy, and therefore, did not receive radioactive iodine (RAI). METHODS: This was a prospective study including 182 patients with tumors ≤ 4 cm and mETE without aggressive histology or clinically apparent lymph node involvement (cN0pNx). After thyroidectomy, all patients had nonstimulated Tg ≤ 0.3 ng/ml, negative antithyroglobulin antibodies (TgAb), and neck ultrasonography (US) showing no anomalies. Because of these results, the patients were not submitted to RAI. RESULTS: The time of follow-up ranged from 24 to 132 months (median 72 months). One hundred and seventy-eight patients (97.8%) continued to have nonstimulated Tg ≤ 0.3 ng/ml and negative US. Four patients (2.2%) exhibited an increase in Tg and lymph node metastases (structural recurrence). After surgery, these patients obtained nonstimulated Tg < 1 ng/ml and no apparent tumor was detected by the imaging methods. CONCLUSION: The results suggest that patients with mETE and without other adverse features, who have low nonstimulated Tg and negative neck US after thyroidectomy, do not require ablation with RAI.

Basal Serum Calcitonin, After Calcium Stimulation, and in the Needle Washout of Patients with Thyroid Nodules and Mild or Moderate Basal Hypercalcitoninemia.

This prospective study evaluated the concentrations of basal serum calcitonin (Ctn), Ctn after stimulation with calcium, and Ctn in the needle washout (FNA-Ctn) as predictors of sporadic medullary thyroid carcinoma (MTC) in patients with thyroid nodules and basal Ctn between 10 and 100 pg/ml. Forty-one patients were included in the study. MTC was diagnosed in only 6 patients (14.6%). None of the patients with basal Ctn≤24.6 pg/ml (n=26) or stimulated Ctn≤186.5 pg/ml (n=21) had MTC. All patients without MTC had basal Ctn<47 pg/ml and stimulated Ctn<655.2 pg/ml. Among patients with basal Ctn between 24.6 and 47 pg/ml (n=12), 3 (25%) had MTC. Among patients with stimulated Ctn between 186.5 and 655.2 pg/ml (n=18), 4 (22.2%) had MTC. FNA-Ctn distinguished nodules that were MTC (n=6) from those that were not (n=60), without overlapping results. In the calcium stimulation test, 19 patients (46.3%) reported some adverse effect, but none of them was severe or required specific treatment. Our results highlight that in patients without a history suspicious for MTC, mild or moderate basal hypercalcitoninemia should not establish the diagnosis of this tumor. Depending on the concentration found, basal Ctn should be sufficient to define patient management. In doubtful cases, FNA-Ctn seems to be the best diagnostic test. Calcium stimulation testing was safe, but more studies are needed to determine the Ctn cutoff after stimulation with calcium.

Screening for Hyperparathyroidism by Measurement of Calcium in Patients Undergoing Thyroid Surgery: A Prospective Study.

This study screened for asymptomatic primary hyperparathyroidism (PHPT) by measuring calcium (Ca) before thyroid surgery. The study was prospective. A total of 676 patients without a suspicion of PHPT were studied. PHPT was defined as elevated Ca (in 2 measurements) in the presence of PTH>25 pg/ml and in the absence of hypocalciuria. PHPT was diagnosed in 5 patients (0.74%), all of them women. One of the 5 patients with PHPT had no indication for parathyroidectomy (PTx) according to current guidelines. Parathyroid adenoma was easily identified during perioperative assessment of thyroid surgery in 3 patients. In the other 2 patients (0.3%), localization of the adenoma required specific exploration, which was only performed because of the preoperative diagnosis of PHPT. Normalization of Ca and PTH was achieved in all 5 patients. In conclusion, in patients without a clinical or ultrasonographic suspicion of PHPT, approximately 300 individuals should be screened before thyroid surgery to avoid one reoperation (PTx) due to PHPT, which does not seem to be cost-effective.

Usefulness of Serum Calcitonin in Patients Without a Suspicious History of Medullary Thyroid Carcinoma and with Thyroid Nodules Without an Indication for Fine-Needle Aspiration or with Benign Cytology.

This study evaluated the usefulness of serum calcitonin (Ctn) in subjects without a suspicious history of medullary thyroid carcinoma (MTC) and with nodular thyroid disease without an indication for fine-needle aspiration (FNA) or with benign cytology. This was a prospective study that evaluated 421 patients with nodular disease without an indication for FNA and 602 patients with benign cytology. Patients with basal Ctn>10 pg/ml were submitted to calcium stimulation testing. Patients with stimulated Ctn>100 pg/ml were submitted to total thyroidectomy. Basal Ctn was<10 pg/ml in 1001 patients (97.8%). Among patients with basal Ctn>10 pg/ml, 16/22 exhibited stimulated Ctn>100 pg/ml. Two of these 16 patients had MTC. The 2 patients with MTC had undetectable basal Ctn 6 months after surgery. Using a cut-off of 30 pg/ml in women and 60 pg/ml in men for basal Ctn, the 2 cases of MTC of our series would have been identified and there would have been no false-positive case. It should be noted that 14/16 patients with stimulated Ctn>100 pg/ml were false-positive cases. Although uncommon, even subjects without a suspicious history and with nodular thyroid disease without an indication for FNA or with benign cytology can have MTC. The measurement of Ctn permits the diagnosis of these cases. Our results favor the hypothesis that basal Ctn could be superior to stimulated Ctn.

Predictive factors of malignancy in thyroid nodules with repeatedly nondiagnostic cytology (Bethesda category I): value of ultrasonography.

One possible result of fine-needle aspiration (FNA) of thyroid nodules is "nondiagnostic" cytology. Consensus exists in these cases to repeat FNA guided by ultrasonography (US), but the result obtained may continue to be nondiagnostic. The objective of this study was to evaluate predictive factors of malignancy (including US) in nodules with indication for FNA whose cytology result was classified as "nondiagnostic" on 2 occasions. The sample consisted of 158 patients with thyroid nodules >5 mm with indication for FNA whose material obtained by US-guided FNA was classified as nondiagnostic on 2 occasions according to the criteria of the Bethesda classification. Papillary thyroid carcinoma (PTC) was confirmed by histology in 23/158 cases (14.5%). Sex, age, family history of PTC, palpation, number of nodules, serum TSH, or circulating antithyroperoxidase antibodies were not predictors of malignancy. Only US predicted risk of malignancy. US showed a sensitivity of 65.2% and a specificity of 90.4%. When US indicated the nodule to be "suspicious for malignancy", histology confirmed PTC in 15/28 cases (positive predictive value 53.4%). When the nodule showed no suspicious US features, histology detected malignancy in only 8/130 cases (negative predictive value 94%). The diagnostic accuracy of the US was 89.5%. The present results suggest that, in cases of patients with thyroid nodules and repeatedly nondiagnostic cytology, ultrasonographic findings represent an excellent parameter for the selection of those who could be followed up by periodic US and those who should be referred for thyroidectomy because of the risk of malignancy.

Color flow Doppler sonography for the etiologic diagnosis of thyrotoxicosis.

The objective of this prospective study was to compare the results of color flow Doppler sonography (CFDS) and radioiodine scintigraphy in patients with thyrotoxicosis. A total of 176 patients, 102 with clinical thyrotoxicosis and 74 with subclinical dysfunction, were included. Pregnant and breast-feeding women, patients using amiodarone or recently exposed to iodinated contrast, and patients treated with antithyroid drugs were excluded. Total T3, free T4, TSH, and anti-TSH receptor antibodies were measured before scintigraphy and CFDS. Excluding one patient whose etiology of thyrotoxicosis remained undefined, CFDS showed 100% specificity. In fact, in all 10 cases in which scintigraphy and CFDS provided discordant results, the diagnosis suggested by the latter was correct. In patients with clinical thyrotoxicosis, the sensitivity of CFDS was 96% for diffuse toxic goiter, 95% for the absence of hyperfunction, and 100% for toxic nodular disease. In patients with subclinical dysfunction, the sensitivity of CFDS was 72.7% for diffuse toxic goiter, 90% for toxic adenoma, and 86.6% for toxic multinodular disease. CFDS was inconclusive in patients with parenchymal blood flow with patchy uneven distribution or with macronodules in which nodule vascularity compared to the remaining parenchyma did not permit to establish the diagnosis with certainty. CFDS can be used instead of scintigraphy not only in situations in which the latter is contraindicated or of limited value to define the etiology of thyrotoxicosis.

Follow-up of patients with low-risk papillary thyroid carcinoma and undetectable basal serum thyroglobulin after ablation measured with a sensitive assay: a prospective study.

The importance of thyroglobulin (Tg) stimulation after ablation in patients with papillary thyroid carcinoma (PTC) and undetectable basal Tg measured with sensitive assays has been questioned. However, there is a need for prospective studies that evaluate the evolution of these patients when stimulated Tg is omitted and this was the objective of the present investigation. One hundred twenty-two consecutive patients with PTC with the following characteristics were evaluated: submitted to total thyroidectomy and remnant ablation; low risk for recurrence; undetectable basal Tg (functional sensitivity of 0.1 ng/ml) 6 months after initial therapy; anti-Tg antibodies (TgAb) negative, and neck ultrasound (US) showing no abnormalities. These patients were not submitted to Tg stimulation. After follow-up for 24-78 months, only one patient (0.8%) presented apparent disease (lymph node metastases). TgAb were detected at low titers and without progression in 1 patient (0.8%). Tg became detectable and continued to be detectable in 3 patients (2.4%), but at concentrations ≤0.3 ng/ml in the absence of further increases, with stimulated Tg < 1.4 ng/ml. A total of 117 patients (96%) coursed with no apparent disease throughout follow-up and had undetectable Tg at the end of the study. Of these, 111 showed undetectable Tg in all measurements and 6 showed detectable Tg in some of them, although Tg later returned spontaneously to an undetectable range. After ablation, the risk of recurrence is very low in patients with low-risk PTC who show undetectable basal Tg measured with a sensitive assay, negative TgAb and negative US.

Does a highly sensitive thyroglobulin (Tg) assay change the clinical management of low-risk patients with thyroid cancer with Tg on T4 < 1 ng/ml determined by traditional assays?

OBJECTIVE: To evaluate a highly sensitive thyroglobulin (Tg) assay [functional sensitivity (FS): 0.1 ng/ml] (Tg-ICMA) in low-risk patients with known Tg on T4 < or = 1 ng/ml measured by a traditional assay (FS: 1 ng/ml) (Tg-IRMA). METHODS: Tg-ICMA was measured in serum samples stored at -70 degrees C. Samples were obtained 6 months or more after total thyroidectomy and remnant ablation with (131)I, during L-T4 therapy (TSH < 0.4 mIU/l). All patients had well-differentiated and completely resected tumours, no ectopic uptake on post-therapy whole-body scans and were considered to be at low risk for recurrence. On the occasion of collection and retesting for this study, Tg-IRMA was < or = 1 ng/ml in all samples and no antibody interference was observed. RESULTS: Tg-ICMA < or = 0.1 ng/ml was observed in 130/178 (73%) patients and recurrence was diagnosed in only 1/130 (0.8%). Tg-IRMA measured after L-T4 withdrawal was > 1 ng/ml in 5/130 (3.8%) patients. Forty-eight (27%) patients had Tg-ICMA > 0.1 ng/ml (0.12-1.6 ng/ml) and recurrence was diagnosed in 5/48 (10.5%). Tg-IRMA measured after L-T4 withdrawal was > 1 ng/ml in 20/48 (41.6%) patients. A negative predictive value of 100% was achieved with Tg-ICMA on T4 < or = 0.1 ng/ml combined with neck ultrasonography (US) or with stimulated Tg-IRMA < or = 1 ng/ml. CONCLUSIONS: Patients at low risk for recurrence with undetectable Tg on T4 measured by a highly sensitive assay (FS: 0.1 ng/ml) in the absence of antibody interference and with a negative sensitive neck US do not need to be submitted to Tg stimulation. Recurrence is rare in these cases and only a minority of patients convert to stimulated Tg > 1-2 ng/ml.

Ovarian function after radioiodine therapy in patients with thyroid cancer.

OBJECTIVE: To assess ovarian function in young women treated with radioiodine. METHODS: The study was conducted on 50 women with thyroid carcinoma aged less than 40 years (mean, 29.8 years), with regular menstrual cycles and normal FSH levels prior to radioiodine therapy. FSH determination was repeated 6 and 12 months after radioiodine therapy (mean, 4.24 GBq iodine-131) and menstrual cycles were monitored during this period. RESULTS: Twenty percent of the patients reported amenorrhea during the first year. FSH levels increased after 6 months (from 5.1 +/- 1.8 to 10.6 +/- 2.2 IU/l, p < 0.00 001) and 28 % of the patients showed elevated values, which had returned to normal by the end of the first year. CONCLUSION: Radioiodine causes transitory alterations in ovarian function even in younger women and after a mean activity of 4.2 GBq (115 mCi).