Dynamic prediction of the risk of recurrence in patients over 60 years of age with differentiated thyroid carcinoma

ABSTRACT Objective The reclassification of the risk according to the response to the initial treatment makes the treatment of differentiated thyroid cancer (DTC) vary in each individual. As the influence of age on this diagnostic strategy is unknown, we have decided to assess it in adults who are over 60 years of age. Subjects and methods Ninety patients with DTC above 60 years old were enrolled, with total thyroidectomy plus radioiodine ablation, negative anti-thyroglobulin antibodies, follow-up ≥ 2 years and with clinical and pathological information to classify the risk of recurrence according to ATA (American Thyroid Association) and reclassify based on the response to initial therapy according to MSKCC (Memorial Sloan Kettering Cancer Center). The structural persistence at the end of the follow-up was the gold standard of our analysis. Results The structural persistence in ATA low, intermediate and high risk categories was 0, 38, and 100%, respectively. In the intermediate group, none of those with an excellent response to the initial treatment showed structural persistence, whereas 39% of those with an incomplete/indeterminate response showed structural persistence (p < 0.01). Conclusions The re-stratification according to the response to the initial treatment in patients over 60 years of age with an ATA intermediate risk of recurrence allowed for the distinction of disease-free patients at the end of the follow-up from those with structural persistence and a worse clinical progression.

Dynamic prediction of the risk of recurrence in patients over 60 years of age with differentiated thyroid carcinoma.

OBJECTIVE: The reclassification of the risk according to the response to the initial treatment makes the treatment of differentiated thyroid cancer (DTC) vary in each individual. As the influence of age on this diagnostic strategy is unknown, we have decided to assess it in adults who are over 60 years of age. SUBJECTS AND METHODS: Ninety patients with DTC above 60 years old were enrolled, with total thyroidectomy plus radioiodine ablation, negative anti-thyroglobulin antibodies, follow-up ≥ 2 years and with clinical and pathological information to classify the risk of recurrence according to ATA (American Thyroid Association) and reclassify based on the response to initial therapy according to MSKCC (Memorial Sloan Kettering Cancer Center). The structural persistence at the end of the follow-up was the gold standard of our analysis. RESULTS: The structural persistence in ATA low, intermediate and high risk categories was 0, 38, and 100%, respectively. In the intermediate group, none of those with an excellent response to the initial treatment showed structural persistence, whereas 39% of those with an incomplete/indeterminate response showed structural persistence (p < 0.01). CONCLUSIONS: The re-stratification according to the response to the initial treatment in patients over 60 years of age with an ATA intermediate risk of recurrence allowed for the distinction of disease-free patients at the end of the follow-up from those with structural persistence and a worse clinical progression.

Association between worse metabolic control and increased thyroid volume and nodular disease in elderly adults with metabolic syndrome.

BACKGROUND: Metabolic syndrome has been associated with nodular goiter. Our aim was to evaluate which metabolic parameters in elderly patients with metabolic syndrome are associated with thyroid enlargement or increased prevalence of thyroid nodules. METHODS: In this cross-sectional study, 77 patients >65 years of age with metabolic syndrome were included. We evaluated the presence of thyroid nodules and thyroid volume by ultrasonography and several biochemical, metabolic and anthropometric parameters. Only patients with thyrotropin (thyroid-stimulating hormone, TSH) levels between 0.3 and 6 mU/L were included. We further divided subjects into two groups-type 2 diabetes mellitus (T2DM) and non-T2DM and established comparisons between them. RESULTS: Among all parameters analyzed we found a significant correlation between glycated hemoglobin (HbA1c) and volume (r=0.261, P=0.027) or number of nodules (r=0.266, P=0.023). Neither sex, age, body mass index (BMI), metformin, nor levothyroxine use were associated with thyroid volume or nodularity. Within the whole cohort, those patients with T2DM had larger thyroid volumes compared to non-T2DM [median (confidence interval, CI) 6.976 (5.220-10.789) vs. 5.034 (3.796-6.034) mL, P<0.008). Furthermore, a larger proportion of T2DM patients presented thyroid volumes >5.8 mL [69 vs. 23%, P<0.001; odds ratio=7.25 (CI 2.04-25.56)]. CONCLUSIONS: In elderly patients with metabolic syndrome, worse metabolic control, represented by higher HbA1c levels, was found associated to increased prevalence of thyroid nodules and larger thyroid volume. Moreover, within the whole metabolic syndrome group, patients with T2DM had the largest thyroid volumes.

Differential profile of ultrasound findings associated with malignancy in mixed and solid thyroid nodules in an elderly female population.

Objective. Ultrasonographic characteristics are associated with thyroid malignancy. Our aim was to compare the diagnostic value of ultrasound features in the detection of thyroid malignancy in both solid and mixed nodules. Methods. We prospectively studied female patients (≥50 years) referred to ultrasound-guided fine needle aspiration biopsy. Ultrasound features considered suspicious were hypoechogenicity, microcalcifications, irregular margins, high anteroposterior (AP)/axial-ratio, and absent halo. Associations were separately assessed in mixed and solid nodules. Results. In a group of 504 elderly female patients (age = 69 ± 8 years), the frequency of malignant cytology was 6%. Thirty-one percent of nodules were mixed and 60% were solid. The rate of malignant cytology was similar for mixed and solid nodules (7.4 versus 5.8%, P: 0.56). While in mixed nodules none of the ultrasound characteristics were associated with malignant cytology, in solid nodules irregular margins and microcalcifications were significant (all P < 0.05). The combination of irregular margins and/or microcalcifications significantly increased the association with malignant cytology only in solid nodules (OR: 2.76 (95% CI: 1.25-6.10), P: 0.012). Conclusions. Ultrasound features were of poor diagnostic value in mixed nodules, which harbored malignant lesions as often as solid nodules. Our findings challenge the recommended minimal size for ultrasound-guided fine needle aspiration biopsy in mixed nodules.

High TSH and low T4 as prognostic markers in older patients.

OBJECTIVE: To examine the association between thyroid profile and morbidity/mortality (MM) in hospitalized older patients. DESIGN: This is a retrospective study of patients over the age of 60 yr admitted to the Dr. Cesar Milstein Hospital between 2009 and 2010 and who had thyroid function tests (TFT). The patients were grouped as per their thyroid tests and their clinical characteristics and MM was associated with their TFT. High MM was defined as mortality, intensive care unit (ICU) requirement or prolonged hospital stay (>18 days, 75th percentile), and mortality assessed during an 18-month follow-up period after their hospital discharge. RESULTS: Out of 2599 older patients admitted to our hospital, 7% had TFT performed for various reasons. The patients who had TFT were mostly women and presented in a more serious clinical condition compared to the rest of the patients. The patients were grouped as per their thyroid values as follows: 61% of them had a non-thyroidal illness, 25% were euthyroid,7% had overt hyperthyroidism, 5% overt hypothyroidism and 1% had subclinical hyper- or hypothyroidism. The hypothyroid patients had a worse clinical outcome compared to the others. Patients with increased MM exhibited higher TSH and lower TT4 (p<0.005). Short-term MM (OR=2.0,95%CI=1.1-3.6, p<0.01) was associated with the decrease of TT4 adjusted by age, sex, T3 and TSH, while for long-term MM the increase in TSH (OR=1.6,95%CI 1.1-2.3, p<0.05) was also significant. CONCLUSION: Among hospitalized older patients who had TFT tests, low TT4 and high TSH were associated with a worse prognosis. We propose that TFT be used as an additional tool in assessing MM in elderly hospitalized patients.

Lipoprotein alterations, hepatic lipase activity, and insulin sensitivity in subclinical hypothyroidism: response to L-T(4) treatment.

UNLABELLED: Subclinical hypothyroidism (sH) has been associated with atherosclerotic cardiovascular disease even in the absence of hypercholesterolemia. OBJECTIVE: Our study was designed to assess the hypothesis that other pro-atherogenic parameters, such as qualitative lipoprotein changes and insulin resistance, might be present in sH. DESIGN AND METHODS: Twenty-one sH women were compared to 11 female controls matched for body mass index, menopausal status, and age. Before and after 6 months of levothyroxine (L-T(4)) treatment, we determined total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides (TG), apoB levels, hepatic lipase (HL) activity in postheparin plasma samples, the chemical composition and copper-induced oxidation in isolated LDL and homeostasis model assessment (HOMA), quantitative insulin sensitivity check index, and insulinogenic index. MAIN OUTCOME: Lipid profiles were similar between the two groups. No differences in LDL oxidability or the insulin sensitivity assessment parameters were found. HL activity was significantly lower in the sH patients: median (range), 13.1 (2.5-26.7) vs. 18.7 (7.9-28.1) micromol free fatty acids/mL, p < 0.04. The LDL-cholesterol/LDL-TG ratio was decreased in sH: 3.9 (1.8-5.5) vs. 4.7 (3.5-6.8), p < 0.02. HL negatively correlated with thyroid-stimulating hormone (TSH) levels (r = - 0.504, p < 0.01) and positively with LDL-cholesterol/LDL-TG (r = 0.46, p < 0.02). Posttreatment results for all these parameters did not differ significantly compared to baseline. CONCLUSIONS: Increased levels of TSH are associated to a decrease in HL activity, explaining our findings of an LDL particle rich in TG. This qualitative lipoprotein alteration suggests a pro-atherogenic pattern in sH. Treatment with L-T(4), however, did not correct the basal lipid derangement.

[Triiodothyroacetic acid in euthyroid goiter. New data on its mechanisms of action. Comparison with L-thyroxin]. / Intérêt de l'acide triiodothyroacétique pour le traitement du goître euthyroïdien. Nouvelles données sur son mode d'action. Comparaison avec la L-thyroxine.

Euthyroid goiter is usually treated with THS-inhibiting doses of L-thyroxin (L-T4), which can have troublesome adverse effects. It has been suggested that triiodothyroacetic acid (Triac), a TSH suppressor, might have fewer peripheral effects and better tolerability than T4. We therefore compared the risk-benefit ratios of the two drugs. Thirty-six women with euthyroid goiter (no thyroid cancer) were randomized to receive either Triac (19.6 ug/kg) (n=19) or L-T4 (1.7 ug/kg) (n=17) for 11 months. Goiter volume, lumar and femoral bone mineral density, and serum osteocalcin, deoxypyridinoline, TSH, free T4, and total cholesterol, high-density cholesterol (HDL), low-density cholesterol (LDL), and triglycerides were determined before and after treatment. Student's test and X2 analysis were used. TSH values (microunits/ml) in the Triac and T4 groups were respectively 1.91 +/- 0.6 (basal) and 0.18 +/- 01 (after) and 2.1 +/- 2.5 (basal) and 0.18 +/- 0.3 (after). Thyroid volume fell by 37.9 +/- 35.4% in the Triac group and by 14.5 +/- 39.5% in the L-T4 group (p=0.069). Goiter volume fell by at least 50% in 42% of patients treated with Triac and in 17.7% of patients treated with L-T4 (p=0.15). Triac was associated with fewer adverse events. Changes in bone mineral density, serum deoxypyridinoline, serum osteocalcin and the lipid profile did not differ between the treatment arms. However, the Apo B level fell more strongly on Triac than on T4. These results show that Triac is more effective than L-T4 on goiter size, while having similar peripheral effects.

Assessment of left ventricular diastolic function by radionuclide ventriculography at rest and exercise in subclinical hypothyroidism, and its response to L-thyroxine therapy.

Hypothyroidism is associated with intrinsic myocardial changes reflected by alterations in contractility and relaxation. Diastolic function, however, rather than systolic cardiac function, seems to be mostly impaired by thyroid hormone deprivation. Our aim was to evaluate diastolic function at rest and during maximal exercise by means of radionuclide ventriculography in subclinical hypothyroidism before and after restoration of euthyroidism. Ten subclinical hypothyroid patients (50 +/- 8.7 years) (thyroid-stimulating hormone 11 +/- 4.2 microUI/ml) without cardiac disease were studied before and 6 months after levothyroxine (L-T(4)) replacement (thyroid-stimulating hormone 1.9 +/- 1.1 microUI/ml). We compared the basal and post-therapy cardiac parameters with a control group of 14 euthyroid patients (52.5 +/- 10 years) (thyroid-stimulating hormone 2.5 +/- 1.2 microUI/ml). Multigated equilibrium radionuclide ventriculography was performed to assess systolic and diastolic ventricular function. Student's t and paired Student's t tests were applied for statistical analysis. We found a significant difference between the time to peak filling rate (TPFR) at rest before (0.241 +/- 0.002 ms) and after (0.190 +/- 0.012 ms) treatment with L-T(4). A significant difference that disappeared after restoration of euthyroidism was also observed between the basal TPFR values of the subclinical hypothyroid patients and the control group (0.189 +/- 0.01 ms). The same pattern was observed at maximal exercise. Thus, TPFR, a parameter of left ventricular (LV) diastolic function measured by radionuclide ventriculography, is impaired in subclinical hypothyroid patients both at rest and during exercise and returns to normal values after L-T(4) therapy.

Evaluation of innovative skin-marking technique performed before thyroid ultrasound-guided fine-needle aspiration biopsies.

OBJECTIVE: To introduce an innovative skin-marking technique performed before ultrasound-guided fine-needle aspiration biopsy (US-FNAB) of the thyroid. METHODS: We studied 248 patients with thyroid nodules, who were classified on the basis of physical examination into two groups-those with palpable nodules (N = 127) and those with nonpalpable or difficult-to-palpate nodules (N = 121). Each group was further subdivided according to the size of the thyroid nodule (< or = 15 mm versus >15 mm). Before US-FNAB, we performed the skin-marking technique with the aid of a catheter, a permanent marker, and ultrasound guidance. An established point for needle entry was indicated on the skin. The chi-square test was used to compare results between the groups of patients. RESULTS: The proportions of adequate and insufficient biopsy material in the overall group of patients were 88.7% and 11.3%, respectively. When the patients were stratified by palpable and nonpalpable thyroid nodules, biopsy specimens were adequate in 89.8% and insufficient in 10.2% of those with palpable nodules, whereas the corresponding proportions for those with nonpalpable nodules were 87.6% and 12.4%, respectively. No statistically significant differences were noted between the two groups. Comparisons between patients with thyroid nodules >15 mm in their largest diameter versus those with nodules < or =15 mm also showed no statistically significant differences in terms of insufficient biopsy material. CONCLUSION: Our technique creates a marking on the skin that leads directly to the thyroid nodule and facilitates the acquisition of adequate cytologic material. This is particularly relevant when small transducers are not available or when the physician needs reassurance about the accuracy of the thyroid biopsy site.