IS IT WORTH SUPPRESSING TSH IN LOW- AND INTERMEDIATE-RISK PAPILLARY THYROID CANCER PATIENTS BEFORE THE FIRST DISEASE ASSESSMENT?

OBJECTIVE: Guidelines recommend thyroid-stimulating hormone (TSH) suppression before the first response to treatment assessment in papillary thyroid cancer (PTC) patients. The aim of this study was to assess the rate of structural disease (SD) in low- and intermediate-risk PTC patients according to TSH levels measured 1 year after primary treatment. METHODS: A consecutive, prospective series of low- and intermediate-risk PTC patients with 3-years follow-up was collected. TSH, thyroglobulin (Tg), antithyroglobulin antibodies (TgAb), and neck ultrasonography (US) 1 and 3 years after primary treatment were analyzed. Recurrence risk and disease status at 1 year were defined according to the American Thyroid Association (ATA) guidelines and as the presence or absence of SD after 3 years. Patients were grouped according to TSH level at 1 year: group 1, TSH <0.1 µUI/mL; group 2, TSH 0.1 to 0.5 µUI/mL; group 3, 0.5 to 2 µUI/mL; and group 4 >2 µUI/mL. RESULTS: This study included 263 patients (70.9% female, median age 47.2 years) of whom the risk of recurrence was low in 170 (65%), intermediate-low in 63 (24%), and intermediate-high in 30 (11%). The response to initial treatment at 1 year was excellent in 149 (57%), biochemical incomplete in 18 (7%), indeterminate in 84 (32%), and structural incomplete in 12 (4%). Group 1 consisted of 53 (20%) patients, group 2 of 85 (32%), group 3 of 61 (23%), and group 4 of 64 (24%). The rate of SD at 1 and 3 years from primary treatment was not significantly different between TSH groups. CONCLUSION: TSH suppression before the first response to treatment assessment does not appear to influence the rate of SD evaluated 1 and 3 years after primary treatment. ABBREVIATIONS: ATA = American Thyroid Association; DTC = differentiated thyroid cancer; FTC = follicular thyroid cancer; LT4 = levothyroxine; PTC = papillary thyroid cancer; SD = structural disease; Tg = thyroglobulin; TgAb = antithyroglobulin antibodies; TSH = thyroid-stimulating hormone; US = ultrasonography.

BRAF V600E and risk stratification of thyroid microcarcinoma: a multicenter pathological and clinical study.

Studies from single institutions have analyzed BRAF in papillary microcarcinomas, sometimes with contradictory results. Most of them have provided limited integration of histological and clinical data. To obtain a comprehensive picture of BRAF V600E-mutated microcarcinomas and to evaluate the role of BRAF testing in risk stratification we performed a retrospective multicenter analysis integrating microscopical, pathological, and clinical information. Three hundred and sixty-five samples from 300 patients treated at six medical institutions covering different geographical regions of Italy were analyzed with central review of all cases. BRAF V600E statistical analysis was conducted on 298 microcarcinomas from 264 patients after exclusion of those that did not meet the required criteria. BRAF V600E was identified in 145/298 tumors (49%) including the following subtypes: 35/37 (95%, P<0.0001) tall cell and 72/114 (64%, P<0.0001) classic; conversely 94/129 follicular variant papillary microcarcinomas (73%, P<0.0001) were BRAF wild type. BRAF V600E-mutated microcarcinomas were characterized by markedly infiltrative contours (P<0.0001) with elongated strings of neoplastic cells departing from the tumor, and by intraglandular tumor spread (P<0.0001), typically within 5 mm of the tumor border. Multivariate analysis correlated BRAF V600E with specific microscopic features (nuclear grooves, optically clear nuclei, tall cells within the tumor, and tumor fibrosis), aggressive growth pattern (infiltrative tumor border, extension into extrathyroidal tissues, and intraglandular tumor spread), higher American Thyroid Association recurrence risk group, and non-incidental tumor discovery. The following showed the strongest link to BRAF V600E: tall cell subtype, many neoplastic cells with nuclear grooves or with optically clear nuclei, infiltrative growth, intraglandular tumor spread, and a tumor discovery that was non-incidental. BRAF V600E-mutated microcarcinomas represent a distinct biological subtype. The mutation is associated with conventional clinico-pathological features considered to be adverse prognostic factors for papillary microcarcinoma, for which it could be regarded as a surrogate marker. BRAF analysis may be useful to identify tumors (BRAF wild type) that have negligible clinical risk.

The relationship between 24 h/4 h radioiodine-131 uptake ratio and outcome after radioiodine therapy in 1402 patients with solitary autonomously functioning thyroid nodules.

OBJECTIVE: To evaluate the role of 24 h/4 h uptake ratio (UR) in response to radioiodine-131 ((131)I) therapy in patients with autonomously functioning thyroid nodules (AFTN). METHODS: A total of 1402 consecutive hyperthyroid patients were treated with (131)I, between 1958 and 2005. Therapeutic doses (D) were calculated according to the formula: D = weight of nodule x dose per gram of nodular tissue (q)/24 h (131)I uptake. The ratios of the 24 and 4 h uptake were retrospectively calculated and the patients were grouped according to outcome and q into three groups of UR (< or =1.25; 1.26-1.68; > or =1.69) by means of terziles. RESULTS: Of the 1402 patients, 95 did not respond to (131)I treatment while 93/1307 developed hypothyroidism. Most non-responders (55.8%) had UR < or =1.25, while many hypothyroid patients (66.7%) had UR > or =1.69 (chi (2): P < 0.001). As q increased, the proportion of successfully treated patients increased (level of significance) only in the group with UR < or =1.25; while in the other two terziles, with increasing dose per gram of nodular tissue, the number of successfully treated patients did not increase (level of significance). The cumulative incidence of hypothyroidism was 2.2% at the 1st year after (131)I treatment, increasing to 13.9% at 5 years and 26.2% at 10 years. CONCLUSIONS: The (131)I UR can predict the outcome of (131)I treatment in AFTN and may have utility in modifying treatment in some patients to limit post-radioiodine induced hypothyroidism and treatment failures in order to achieve euthyroidism.

Short telomeres, telomerase reverse transcriptase gene amplification, and increased telomerase activity in the blood of familial papillary thyroid cancer patients.

BACKGROUND: Differentiated papillary thyroid cancer is mostly sporadic, but the recurrence of the familial form has been reported. Short or dysfunctional telomeres have been associated with familial benign diseases and familial breast cancer. OBJECTIVE: The aim of our work was to study the telomere-telomerase complex in the peripheral blood of patients with familial papillary thyroid cancer (FPTC), including the measurement of relative telomere length (RTL), telomerase reverse transcriptase (hTERT) gene amplification, hTERT mRNA expression, telomerase protein activity, and search of hTERT or telomerase RNA component gene mutations. PATIENTS: Cumulating a series of patients seen at the University of Siena and a series at the University of Rome, the experiments were conducted in 47 FPTC patients, 75 sporadic papillary thyroid cancer (PTC) patients, 20 patients with nodular goiter, 19 healthy subjects, and 20 unaffected siblings of FPTC patients. RESULTS: RTL, measured by quantitative PCR, was significantly (P < 0.0001) shorter in the blood of FPTC patients, compared with sporadic PTCs, healthy subjects, nodular goiter subjects, and unaffected siblings. Also by fluorescence in situ hybridization analysis, the results confirmed shorter telomere lengths in FPTC patients (P = 0.01). hTERT gene amplification was significantly (P < 0.0001) higher in FPTC patients, compared with the other groups, and in particular, it was significantly (P = 0.03) greater in offspring with respect to parents. hTERT mRNA expression, as well as telomerase activity, was significantly higher (P = 0.0003 and P < 0.0001, respectively) in FPTC patients, compared with sporadic PTCs. RTL, measured in cancer tissues, was shorter (P < 0.0001) in FPTC patients, compared with sporadic PTCs. No mutations of the telomerase RNA component and hTERT genes were found. CONCLUSION: Our study demonstrates that patients with FPTC display an imbalance of the telomere-telomerase complex in the peripheral blood, characterized by short telomeres, hTERT gene amplification, and expression. These features may be implicated in the inherited predisposition to develop FPTC.

Type 2 deiodinase polymorphism (threonine 92 alanine) predicts L-thyroxine dose to achieve target thyrotropin levels in thyroidectomized patients.

CONTEXT: Type 2 deiodinase (D2) converts T4 in T3 in several human tissues, including hypothalamus and pituitary, and, therefore, plays a pivotal role in the negative feedback regulation of TSH secretion. A common variant of the gene, threonine (Thr) 92 alanine (Ala), has been identified and associated with decreased D2 enzymatic activity. OBJECTIVE: Our objective was to investigate whether this polymorphism predicts the T4 dosage needed to obtain target TSH levels in thyroidectomized patients. SETTING: Ambulatory patients were included in the study. PATIENTS: A total of 191 consecutive thyroid cancer patients, previously treated by near total thyroidectomy and radioiodine ablation, were studied. They were on stable T4 dose treatment aimed at obtaining either suppressed (supp) (n=117, <0.1 mU/liter) or near-supp (n=74, >or=0.1<0.5 mU/liter) serum TSH levels. MAIN OUTCOME MEASURES: DNA genotyping for D2 Thr92Ala variant and evaluation of T4 dose (microg/kg) needed to obtain target TSH levels were determined. RESULTS: Ala/Ala homozygous patients needed a higher T4 dose as compared with patients carrying the Thr92 variant (X/Thr patients) according to a recessive genetic model (2.08+/-0.43 vs. 1.90+/-0.35 microg/kg; P<0.05). This difference was observable in the near-supp group (P=0.002), but not in the supp group (P=0.4). CONCLUSIONS: D2 Thr92Ala polymorphism seems to predict the need for higher T4 intake in thyroidectomized patients. If this finding is confirmed in additional studies, it may predict the T4 requirement to suppress TSH on the basis of the individual genetic background.

Radioiodine uptake in non-lactating mammary glands: evidence for a causative role of hyperprolactinemia.

CONTEXT: Radioiodine uptake is rarely observed in normal non-lactating breast tissue. Investigation of the in vivo regulation of iodide uptake in breast tissue may be useful for the induction of radioiodine uptake in breast cancer tissue for diagnostic and therapeutic purposes. CASE REPORTS: We report the cases of two post-menopausal women who underwent radioiodine therapy for papillary thyroid carcinoma and in whom breast uptake of radioiodine on post-therapy whole body scan (WBS) was observed. METHODS AND RESULTS: In both patients, elevated serum prolactin levels (123 ng/mL in patient 1 and 48 ng/mL in patient 2) were documented at the time when radioiodine uptake in the breast was observed. The hyperprolactinemia was due to prolonged treatment with the anti-dopaminergic neuroleptic risperidone in Case 1, and chronic renal failure in Case 2. When prolactin levels were normalized (by withdrawal of risperidone in Case 1 and with cabergoline in Case 2), breast tissue uptake was no longer evident on WBS. CONCLUSION: These cases provide the first documented correlation between serum levels of endogenous prolactin and radioiodine uptake by involuted breast tissue in humans.

Age influences TSH serum levels after withdrawal of l-thyroxine or rhTSH stimulation in patients affected by differentiated thyroid cancer.

Recombinant human TSH (rhTSH) has been recently suggested for radioiodine ablation in patients with differentiated thyroid cancer (DTC). To date, studies are still not available about the effectiveness of rhTSH stimulation depending on the age, since serum TSH clearance may be different in younger and in older patients. The aim of this study was to investigate the influence of age to serum TSH levels after rhTSH stimulation and thyroid hormone withdrawal (THW). We retrospectively evaluated two groups of consecutive DTC patients: group 1 (311 patients, age 49.0+/-13.6 years, ranging 15-86) underwent rhTSH stimulation 6-12 months after thyroid ablation (rhTSH-group); group 2 (84 patients, age 46.9+/-13.5 years, ranging 20-77) was followed by THW (THW-group). The influence of age, gender, body mass index and body surface area to serum TSH levels were evaluated in both groups. RhTSH-group: on day 5 (d5), TSH levels were 32.7+/-21.4 microU/ml (range 0.8-136.6). By univariate analysis, d5-TSH was positively related to age (r=0.27, p=0.0001) and no correlations were found with the other parameters. At multivariate analysis, both age and gender (female) were independently associated with d5-TSH levels. THW-group: after thyroid hormone withdrawal, TSH levels were 71.1+/-36.4 microU/ml (range 8.5-200). At univariate analysis, only age was significantly and negatively related to serum TSH levels (r=-0.31, p=0.004). Our data indicate that age and gender seem to positively influence serum TSH levels after rhTSH stimulation. An opposite effect of age on serum TSH levels has been observed after THW. Therapeutic implications ((131)I-treatment) of these findings have to be better investigated in prospective studies.

Strain rate dobutamine echocardiography for prediction of recovery after revascularization in patients with ischemic left ventricular dysfunction.

BACKGROUND: The purpose of the present study was to assess the accuracy of quantitative segmental analysis by strain rate imaging (SRI) technique during dobutamine test for detecting myocardial recovery after revascularization in patients with chronic ischemic regional left ventricular (LV) dysfunction and compare results with those of 2-dimensional echocardiography (2D) and tissue Doppler imaging (TDI) as well as rest-4 hours-24 hours redistribution thallium SPECT (Tl SPECT). METHODS AND RESULTS: Forty-one patients with chronic ischemic regional LV dysfunction (EF 29 +/- 8%) underwent dobutamine 2D/TDI/SRI and Tl SPECT before and after myocardial revascularization. The sensitivity, specificity, and accuracy for the recovery of regional LV function were 73%, 81%, and 77% for dobutamine 2D; 77%, 82%, and 80% for dobutamine TDI; 86%, 88%, and 85% for dobutamine SRI; and 94%, 76%, and 84% for Tl tomography. The area under the ROC curve (AUC), which reflects the overall performance for the prediction of recovery, was 0.79 for systolic-SR, 0.81 for Tl SPECT, 0.83 for postsystolic strain, and 0.87 for isovolumic-SR. If both systolic and postsystolic SRI indexes were combined with Tl SPECT, the AUC was improved to 0.94. CONCLUSIONS: Dobutamine SRI is more accurate than TDI in identifying hibernating myocardium. Systo-diastolic values obtained using dobutamine SRI echocardiography and values derived from nuclear perfusion techniques may be complementary in assessing myocardial viability.

Papillary thyroid carcinomas with biochemical incomplete or indeterminate responses to initial treatment: repeat stimulated thyroglobulin assay to identify disease-free patients.

Papillary thyroid cancer (PTC) patients treated with thyroidectomy and radioiodine remnant ablation (RRA) often have detectable TSH-stimulated thyroglobulin (Tg) levels without localizable disease after primary treatment. To assess the value of repeat stimulated Tg assays in these patients' follow-up, we retrospectively analyzed 86 cases followed in 5 Italian thyroid-cancer referral centers. We enrolled 86 patients with PTCs treated with total/near-total thyroidectomy plus RRA between January 1,1990 and January 31, 2006. In all cases, the initial postoperative visit revealed stimulated serum Tg ≥1 ng/mL, negative Tg antibodies, and no structural evidence of disease. None received empiric radioiodine therapy. Follow-up (median: 9.6 years) included neck ultrasound and basal Tg assays (yearly) and at least 1 repeat stimulated Tg assay. Of the 86 patients analyzed (initial risk: low 63 %, intermediate 35 %, high 2 %), one (1 %) had ultrasound-detected lymph node disease and persistently elevated stimulated Tg levels at 3 years. In 17 (20 %), imaging findings were consistently negative, but the final stimulated Tg levels was still >1 ng/mL (median 2.07 ng/mL, range 1.02-4.7). The other 68 (80 %) appeared disease-free (persistently negative imaging findings with stimulated Tg levels ≤1 ng/mL). Mean intervals between first and final stimulated Tg assays were similar (5.2 and 4.8 years) in subgroups with versus without Tg normalization. Reclassification as disease-free was significantly more common when initial stimulated Tg levels were indeterminate (<10 ng/mL). In unselected PTC cohorts with incomplete/indeterminate biochemical responses to thyroidectomy and RRA, periodic remeasurement of stimulated Tg allows most patients to be classified as disease-free.

Death from differentiated thyroid carcinoma: retrospective study of a 40-year investigation.

Differentiated thyroid carcinoma (DTC) usually has a good prognosis, but sometimes the course of the disease results in death. The aim of the present study was to assess the effect of some variables in time to death on fatal cases in our series. A total of 83 patients with DTC who died between 1958 and 1998 from differentiated thyroid cancer were retrospectively analyzed with respect to gender, age at diagnosis, histology, percentage of (131)I uptake by postoperative thyroid remnant, site of tumor growth, and its (131)I uptake, metastases and time to death. Univariate analysis revealed a significantly shorter time to death in local recurrence when comparing local lymph node metastases and distant metastases even if neither show (131)I uptake. Multivariate analysis revealed that age at diagnosis was the most important factor in conditioning the time to death. In conclusion, in those patients who died from DTC an older age at diagnosis and presence of local recurrence influenced the time to death independently of (131)I uptake.

99mTc-EDDA/HYNIC-TOC in the management of medullary thyroid carcinoma.

An early diagnosis of distant metastases or local recurrences of medullary thyroid carcinoma (MTC) can be achieved by several conventional radiological modalities (e.g., ultrasonography, computed tomography [CT], and magnetic resonance imaging [MRI] as well as by radioisotopic procedures, such as positron emission tomography (PET), scintigraphy with different types of radiopharmaceuticals, and radiolabeled receptor-ligands in particular. The aim of this study was to evaluate the clinical utility of 99mTc-EDDA/HYNIC-TOC, a new octreotide derivative, to detect recurrences of disease or distant metastases in MTC. Images obtained of 5 patients with high levels of serum calcitonin were compared to findings obtained with other diagnostic procedures: 111In-octreotide, 99mTc-DMSA-V, 18F-flouro-D-deoxyglucose-PET, and CT/MRI. 99mTc-EDDA/HYNIC-TOC was positive in all patients and showed 15 areas of pathological uptake in the cervical and mediastinal regions. 111In-octreotide was positive in 3 of 3 patients and showed 4 areas, compared to 8 of 99mTc-EDDA/HYNIC-TOC. 99mTc-V-DMSA was positive in 3 of 4 patients but showed 6 pathological areas, compared to 13 of 99mTc-EDDA/HYNIC-TOC. 18F-FDG-PET was positive in 5 of 5 patients but showed only 11 areas, compared to 15 of 99mTc-EDDA/HYNIC-TOC. The CT scan was positive in only 2 patients. In conclusion, 99mTc-EDDA/HYNIC-TOC detected more sites of pathological uptake than other modalities, showed better imaging properties than 111In-octreotide, and might be the radiopharmaceutical of choice for providing a rationale for radioisotopic therapy.

Atherosclerotic ischemic renal disease. Diagnosis and prevalence in an hypertensive and/or uremic elderly population.

BACKGROUND: Atherosclerotic ischemic renal disease is a frequent cause of end-stage renal failure leading to dialysis among the elderly; Its prevalence is inferred from autopsy or retrospective arteriographic studies. This study has been conducted on 269 subjects over 50 with hypertension and/or CRF, unrelated to other known causes of renal disease. METHODS: All 269 patients were studied either by color-flow duplex sonography (n = 238) or by renal scintigraphy (n = 224), and 199 of the 269 patients were evaluated using both of these techniques. 40 patients, found to have renal artery stenosis (RAS), were subjected to 3D-contrast enhancement Magnetic Resonance Angiography (MRA) and/or Selective Angiography (SA). An additional 23 cases, negative both to scintigraphy and to ultrasound study, underwent renal angiography (MRA and/or SA). RESULTS: Color-duplex sonography, carried out in 238 patients, revealed 49 cases of RAS. MR or SA was carried out in 35 of these 49 patients, and confirmed the diagnosis in 33. Color-duplex sonography showed a PPV value of 94.3% and NPV of 87.0% while renal scintigraphy, carried out in 224 patients, had a PPV of 72.2% and a NPV of 29.4%. Patients with RAS showed a higher degree of renal insufficiency compared to non stenotic patients while there were no differences in proteinuria. RAS, based on color-duplex sonography studies, was present in 11% of patients in the age group 50-59, 18% in the 60-69 and 23% at age 70 and above. CONCLUSIONS: A relatively large percentage of the elderly population with renal insufficiency and/or hypertension is affected by RAS and is at risk of developing end-stage renal failure. Color-duplex ultrasonography is a valid routine method of investigation of population at risk for renal artery stenosis.

Atherosclerotic renal artery stenosis: one year outcome of total and separate kidney function following stenting.

BACKGROUND: Renal artery stenosis (RAS) is a known cause of hypertension and ischemic nephropathy. Stenting of the artery is a valid approach, in spite of cases of unexpected adverse evolution of renal function. METHODS: In this study, 27 patients with unilateral RAS were subjected to stenting and followed for a period of one year, while 19 patients were observed while on medical treatment only. The group of 27 patients, 67.33 +/- 6.8 years of age, creatinine of 2.15 +/- 0.9 mg/dl, following stenting, were followed at intervals with biochemical tests, renal scintigraphy and doppler ultrasonography. The control group (70.0 +/- 6.1 years, creatinine 1.99 +/- 0.7 mg/dl) was also followed for one year. RESULT: One year after stenting mean creatinine clearance (Ccr) increased from 36.07 +/- 17.2 to 40.4 +/- 21.6 ml/min (NS). Arterial BP, decreased after 1,3,6, and 12 months (p < 0.05). The number of antihypertensive drugs also decreased (p < 0.05). A significant increase in proteinuria was also observed. In the control group both Ccr, BP and proteinuria did not show significant changes. Based on renal scintigraphy and Ccr at subsequent times, it was possible to evaluate the timecourse of renal function in both kidneys of the stented patients. In the stented kidneys Ccr increased significantly. On the controlateral kidney a decrease of renal function (p < 0.05) was observed. Resistance index appeared to be a risk factor of the functional outcome. CONCLUSIONS: Stenting of RAS due to atherosclerosis is followed by stabilization or improvement of Ccr, mainly at the stented kidney, while contralateral renal function showed a decrease.

Clinical aggressiveness and long-term outcome in patients with papillary thyroid cancer and circulating anti-thyroglobulin autoantibodies.

OBJECTIVE: The association between papillary thyroid cancer (PTC) and Hashimoto's thyroiditis is widely recognized, but less is known about the possible link between circulating anti-thyroglobulin antibody (TgAb) titers and PTC aggressiveness. To shed light on this issue, we retrospectively examined a large series of PTC patients with and without positive TgAb. METHODS: Data on 220 TgAb-positive PTC patients (study cohort) were retrospectively collected in 10 hospital-based referral centers. All the patients had undergone near-total thyroidectomy with or without radioiodine remnant ablation. Tumor characteristics and long-term outcomes (follow-up range: 2.5-24.8 years) were compared with those recently reported in 1020 TgAb-negative PTC patients with similar demographic characteristics. We also assessed the impact on clinical outcome of early titer disappearance in the TgAb-positive group. RESULTS: At baseline, the study cohort (mean age 45.9 years, range 12.5-84.1 years; 85% female) had a significantly higher prevalence of high-risk patients (6.9% vs. 3.2%, p<0.05) and extrathyroidal tumor extension (28.2% vs. 24%; p<0.0001) than TgAb-negative controls. Study cohort patients were also more likely than controls to have persistent disease at the 1-year visit (13.6% vs. 7.0%, p=0.001) or recurrence during subsequent follow-up (5.8% vs. 1.4%, p=0.0001). At the final follow-up visit, the percentage of patients with either persistent or recurrent disease in the two cohorts was significantly different (6.4% of TgAb-positive patients vs. 1.7% in the TgAb-negative group, p<0.0001). At the 1-year visit, titer normalization was observed in 85 of the 220 TgAb-positive individuals. These patients had a significantly lower rate of persistent disease than those who were still TgAb positive (8.2% vs. 17.3%. p=0.05), and no relapses were observed among patients with no evidence of disease during subsequent follow-up. CONCLUSIONS: PTC patients with positive serum TgAb titer during the first year after primary treatment were more likely to have persistent/recurrent disease than those who were consistently TgAb-negative. Negative titers at 1 year may be associated with more favorable outcomes.

Autonomous functioning thyroid nodules and 131I in diagnosis and therapy after 50 years of experience: what is still open to debate?

PURPOSE OF THE REPORT: Autonomous functioning thyroid nodules (AFTN), defined as "hot nodules" at thyroid scan, are often cured by radioiodine treatment. The aim of our study was to investigate the long-term outcome in patients treated with an 131I calculated dose, to identify a possible "size-tailored" dose, and to simplify follow-up procedures. PATIENTS AND METHODS: Retrospective analysis was carried out on 1402 cases, covering a period of 50 years, of AFTN treated with an 131I calculated dose. Our study focused on nodular size and mean administered dose. Concordance between thyroid scan and serum TSH levels at 3-6 months from treatment was considered. RESULTS: A single 131I dose was effective for the vast majority of patients (93%). The outcome was influenced by nodular size. On the basis of the Italian dose limit for outpatient treatment, our population was divided into subgroups according to administered doses (more or less than 16 mCi) and nodular dimensions: no differences in outcome were observed for each class of nodule size. A dose ≤10 mCi was effective on the smaller nodules (50.1% of our population). The agreement between TSH and scan after treatment was 90.3% at 3 months and 94.5% at 6 months. CONCLUSIONS: 131I therapy with a calculated dose is an effective treatment of AFTN. If a fixed dose is chosen, 16 mCi is often resolutive and for nodules <3 cm a dose of 10 mCi can suffice. Nodules >5 cm are eligible for surgery. TSH is the only parameter required to evaluate the outcome.

Papillary thyroid cancer: time course of recurrences during postsurgery surveillance.

CONTEXT: The current use of life-long follow-up in patients with papillary thyroid cancer (PTC) is based largely on the study of individuals diagnosed and treated in the latter half of the 20th century when recurrence rates were approximately 20% and relapses detected up to 20-30 years after surgery. Since then, however, diagnosis, treatment, and postoperative monitoring of PTC patients have evolved significantly. OBJECTIVES: The objective of the study was to identify times to PTC recurrence and rates by which these relapses occurred in a more recent patient cohort. PATIENTS AND DESIGN: We retrospectively analyzed follow-up data for 1020 PTC patients consecutively diagnosed in 1990-2008 in 8 Italian hospital centers for thyroid disease. Patients underwent thyroidectomy, with or without radioiodine ablation of residual thyroid tissue and were followed up with periodic serum thyroglobulin assays and neck sonography. RESULTS: At the initial posttreatment (≤ 12 months) examination, 948 patients had no structural/functional evidence of disease. During follow-up (5.1-20.4 years; median 10.4 years), recurrence (cervical lymph nodes, thyroid bed) was diagnosed in 13 (1.4%) of these patients. All relapses occurred 8 or fewer years after treatment (10 within the first 5 years, 6 within the first 3 years). Recurrence was unrelated to the use/omission of postoperative radioiodine ablation. CONCLUSION: In PTC patients whose initial treatment produces disease remission (no structural evidence of disease), recurrent disease is rare, and it usually occurs during the early postoperative period. The picture of recurrence timing during the follow-up provides a foundation for the design of more cost-effective surveillance protocols for PTC patients.

Long-term surveillance of papillary thyroid cancer patients who do not undergo postoperative radioiodine remnant ablation: is there a role for serum thyroglobulin measurement?

CONTEXT: Serum thyroglobulin (Tg) assays are considered fundamental in postoperative surveillance of differentiated thyroid cancer (DTC) patients. However, the postsurgical profile of Tg levels has never been specifically investigated in patients who do not undergo radioiodine remnant ablation (RRA). OBJECTIVES: Our objective was to explore the evolution of Tg levels over time in DTC patients treated with total or near-total thyroidectomy without RRA. DESIGN: We retrospectively analyzed 290 consecutively diagnosed cases of low-risk (American Thyroid Association criteria) DTC treated with thyroidectomy alone and followed yearly with neck ultrasonography and serum Tg assays. We compared final Tg values in this group and a matched group of 495 RRA-positive patients. Temporal trends of serial Tg levels were also analyzed in 78 of the RRA-negative patients monitored with a high-sensitivity immunoradiometric assay. RESULTS: After follow-up of 2.5-22 yr (median 5 yr), final Tg levels were undetectable (<1 ng/ml) in 274 of 290 RRA-negative patients (95%) and 492 of 495 RRA-positive controls (99%). In the subset of 78 RRA-negative patients, undetectable Tg levels (<0.2 ng/ml) were recorded in 60% at the first postoperative evaluation (3-12 months) and in 79% after 5 yr. Tg levels increased in the single patient who experienced disease recurrence during the observation period. CONCLUSION: In most RRA-negative patients, postoperative serum Tg values spontaneously drop to undetectable levels within 5-7 yr after thyroidectomy. Thus, in later phases, Tg assays may be a valuable tool for follow-up even in patients who do not undergo RRA.

Identification and optimal postsurgical follow-up of patients with very low-risk papillary thyroid microcarcinomas.

CONTEXT: Most papillary thyroid microcarcinomas (PTMCs; ≤ 1 cm diameter) are indolent low-risk tumors, but some cases behave more aggressively. Controversies have thus arisen over the optimum postoperative surveillance of PTMC patients. OBJECTIVES: We tested the hypothesis that clinical criteria could be used to identify PTMC patients with very low mortality/recurrence risks and attempted to define the best strategy for their management and long-term surveillance. DESIGN: We retrospectively analyzed data from 312 consecutively diagnosed PTMC patients with T1N0M0 stage disease, no family history of thyroid cancer, no history of head-neck irradiation, unifocal PTMC, no extracapsular involvement, and classic papillary histotypes. Additional inclusion criteria were complete follow-up data from surgery to at least 5 yr after diagnosis. All 312 had undergone (near) total thyroidectomy [with radioactive iodine (RAI) remnant ablation in 137 (44%) - RAI group] and were followed up yearly with cervical ultrasonography and serum thyroglobulin, TSH, and thyroglobulin antibody assays. RESULTS: During follow-up (5-23 yr, median 6.7 yr), there were no deaths due to thyroid cancer or reoperations. The first (6-12 months after surgery) and last postoperative cervical sonograms were negative in all cases. Final serum thyroglobulin levels were undetectable (<1 ng/ml) in all RAI patients and almost all (93%) of non-RAI patients. CONCLUSION: Accurate risk stratification can allow safe follow-up of most PTMC patients with a less intensive, more cost-effective protocol. Cervical ultrasonography is the mainstay of this protocol, and negative findings at the first postoperative examination are highly predictive of positive outcomes.