CIRCULATING TUMOR CELLS IN MINIMALLY INVASIVE FOLLICULAR THYROID CARCINOMA AND BENIGN THYROID TUMORS WITH A FOLLICULAR PATTERN: PILOT EXPERIENCE.

PURPOSE: Minimally invasive follicular thyroid carcinomas (MIFCs) are uncommon; literature offers limited guidance on their natural history and management. Starting January 2015 we measured circulating tumor cells (CTCs) in patients with MIFC (n=22) or benign thyroid tumors with follicular features (n=4). METHODS: In a retrospective analysis, we assessed detectability of and serial changes in CTC, compared demographic/clinical differences between CTC-positive versus CTC-negative subgroups using Student's t-test, and examined correlations between CTC status and serum thyroglobulin using Spearman's test. CTCs were quantitated via immunomagnetic separation/microscopic inspection. RESULTS: Thirteen patients (50%: 12/22 MIFC, 1/4 benign tumor) were initially CTC-positive; 3 remained CTC-positive in ≥1 subsequent measurement. CTC-positive patients had larger tumors and more frequent multifocality and vascular invasion versus CTC-negative patients (n=13). However, no tested variable differed significantly between the subgroups. After 17.2±10.5 months, neither subgroup showed evidence of disease. Significant correlation was absent (p ≥ 0.263) between CTC and Tg negativity (r = 0.243; n=13 evaluable) or initial CTC positivity and Tg positivity (r = -0.418; n=9 evaluable). CONCLUSIONS: In the studied settings, CTC measurement is feasible, has unclear clinical/outcome implications, but may provide different information versus thyroglobulin testing. Lengthier assessment is warranted in larger series.

Highly-sensitive C-reactive protein, a biomarker of cardiovascular disease risk, in radically-treated differentiated thyroid carcinoma patients after repeated thyroid hormone withholding.

AIMS: In patients radically treated for differentiated thyroid carcinoma, we assessed the response of highly-sensitive C-reactive protein, an inflammatory biomarker for cardiovascular risk, after thyroid hormone withholding ("deprivation"), as well as factors potentially influencing this response. MATERIAL AND METHODS: We included 52 adults (mean age 45.6±14.0 years, 35 females) who were disease-free after total thyroidectomy, radioiodine ablation and chronic thyroid hormone therapy. They were lifelong non-smokers without apparent inflammatory comorbidity, cardiovascular history beyond pharmacotherapy-controlled hypertension, anti-dyslipidemic medication, or C-reactive protein >10 mg/L in any study measurement. The index deprivation lasted ≥2 weeks, elevating serum thyrotropin >40 mIU/L or ≥100 × the individual's suppressed level. We examined the relationship of age, number of prior deprivations, and gender with the magnitude of post-deprivation C-reactive protein concentration through multivariable statistical analyses using the F test on linear regression models. RESULTS: Post-deprivation, C-reactive protein reached intermediate cardiovascular risk levels (based on general population studies involving chronic elevation), 1-3 mg/L, in 44.2% of patients and high-risk levels, >3 mg/L, in another 17.3%. Mean C-reactive protein was 1.77±1.50 mg/L, differing significantly in females (2.12±1.66 mg/L) vs. males (1.05±0.69 mg/L, P <0.001). In multivariable analysis, patients ≤45 years old (odds ratio, 95% confidence interval 0.164 [0.049-0.548]) were less likely, and females, more likely (3.571 [1.062-12.009]) to have post-deprivation C-reactive protein ≥1 mg/L. CONCLUSIONS: Thyroid hormone withdrawal frequently elevated C-reactive protein to levels that when present chronically, were associated with increased cardiovascular risk in general population studies.

Acute and chronic hypothyroidism are associated with similar left ventricular diastolic dysfunction relative to the euthyroid state: results of doppler echocardiographic comparisons.

BACKGROUND: How the duration of hypothyroidism affects left ventricular diastolic function is not well-characterized. AIM: We sought to compare left ventricular diastolic function in acutely vs chronically hypothyroid patients vs euthyroid controls, and within individuals while on vs off T4. SUBJECTS AND METHODS: We prospectively performed such comparisons measuring pulsed-wave and color M-mode Doppler echocardiographic variables: early or late mitral peak velocities (E wave or A wave, respectively), E wave/A wave ratio, E wave deceleration time, isovolumic relaxation time (IVRT), mitral flow propagation velocity (Vp), E wave/Vp ratio. Subjects comprised the acute HYPO group, 10 patients undergoing T4 withdrawal ≥ 6 months post-primary treatment for differentiated thyroid cancer (DTC); the chronic HYPO group, 23 treatment-naïve Hashimoto thyroiditis patients; and 21 healthy euthyroid controls. Subjects were adults aged ≤ 60 yr, predominantly female, with sinus rhythm; exclusion criteria were cardiovascular or thyroid disorder besides DTC (Hashimoto thyroiditis) in acute (chronic) HYPO patients or medication (besides thyroid hormone) affecting cardiac or thyroid function. RESULTS: Mean IVRT was significantly delayed and mean Vp, significantly slowed in both HYPO groups vs controls (p<0.0005), but did not differ between HYPO groups. These variables also were significantly impaired (p<0.05) within individuals when off vs on T4 (no.=8 acute, 10 chronic HYPO patients). Both HYPO groups had elevated mean E wave/Vp ratios vs controls, but the elevation reached significance (p<0.05) only in the larger chronic HYPO group. CONCLUSIONS: Left ventricular diastolic dysfunction is largely similar in acutely or chronically hypothyroid patients off T4 vs healthy controls or the same patients on T4.

Thyroid remnant dose: 124I-PET/CT dosimetric comparison of rhTSH versus thyroid hormone withholding before radioiodine remnant ablation in differentiated thyroid cancer.

AIM: Recombinant human thyroid-stimulating hormone (rhTSH) recently was approved as an alternative to thyroid hormone withholding (THW) to elevate TSH for thyroid remnant ablation in differentiated thyroid carcinoma patients. High ablation success rates are reported with diverse rhTSH-aided (131)I activities. Improved renal function causes approximately 50% faster radioiodine clearance under euthyroidism versus hypothyroidism. Knowledge of comparative remnant radioiodine kinetics, particularly the remnant radiation dose in Gy/GBq of administered (131)I activity (RDpA), could assist in choosing rhTSH-aided ablative activities. MATERIAL AND METHODS: To compare the RDpA, determined through (124)I-positron emission tomography/computed tomography (PET/CT), under the two stimulation methods, we retrospectively divided into two groups 55 consecutive totally-thyroidectomized, radioiodine-naïve patients. The rhTSH group (n=16) received (124)I on thyroid hormone, 24 h after two consecutive daily intramuscular injections of rhTSH, 0.9 mg. The THW group (n=39) received (124)I after weeks-long THW, when serum TSH first measured > or = 25 mIU/L. We performed PET investigations 4 h, 24 h, 48 h, 72 h and 96 h and PET/CT 25 h after (124)I administration. RESULTS: Median stimulated serum thyroglobulin was 15 times higher (p=0.023) and M1 disease almost twice as prevalent (p=0.05) in rhTSH versus THW patients. Mean+/-standard deviation RDpA was statistically equivalent between the groups: rhTSH, 461+/-600 Gy/GBq, THW, 302+/-329 Gy/GBq, two-sided p=0.258. CONCLUSIONS: rhTSH or THW deliver statistically equivalent radiation doses to thyroid remnant and may be chosen based on safety, quality-of-life, convenience and pharmacoeconomic factors. Institutional fixed radioiodine activities formulated for use with THW need not be adjusted for rhTSH-aided ablation.

124-iodine positron emission tomography/computed tomography dosimetry in pediatric patients with differentiated thyroid cancer.

AIM: Publications on 124-iodine (124I-)-positron emission tomography/computed tomography (PET/CT) dosimetry contain few if any data on pediatric patients with differentiated thyroid carcinoma (DTC). Aim of our study is to determine safety and informativeness of 124I-PET/CT dosimetry in DTC patients2Gy blood dose portending serious myelotoxicity. RESULTS: Besides hypothyroid fatigue, no symptoms were noted. In 4 dosimetry procedures before the first radioiodine therapy, RDpAs were generally high (median 288 Gy/GBq, range 59-648 Gy/GBq). LDpAs (4 lymph node metastases) were much lower (median 6.5 Gy/GBq, range 1-9 Gy/GBq). CBAs were high (median 26 GBq, range 19-42, n=5). Disease management was modified or disease extent clarified in 2/4 patients. CONCLUSIONS: A standard adult 124I-PET/CT dosimetry protocol appears to be safe and informative in pediatric DTC patients.

124I-PET dosimetry in advanced differentiated thyroid cancer: therapeutic impact.

PURPOSE: This study evaluated the impact of (124)I-positron emission tomography (PET) dosimetry on post-primary surgery therapy in radioiodine-naïve patients with advanced differentiated thyroid cancer (DTC). PATIENTS, MATERIAL, METHODS: In each of 28 thyroidectomized patients with high-risk DTC (one or more of pT4, pN1 or pM1), we gave 23-50 MBq of (124)I as an oral capsule and performed PET dosimetry to calculate the individualized therapeutic (131)I activity that would, insofar as possible, achieve a radioiodine dose >or=100 Gy to all metastases without exceeding 2 Gy to the blood (a surrogate for bone marrow toxicity). We thus determined the absorbed lesion dose per GBq of administered 131I activity (LDpA) based on serial PET (4, 24, 48, 72 and 96 h after oral 124I intake) and PET/computed tomography (25 h after (124)I intake) and the critical blood activity (CBA) based on blood and whole-body radiation counting (2, 4, 24, 48, 72, 96 h after 124I intake). We compared the dosimetry-based interventions with our standard empirical protocol. RESULTS: 25 patients had a total of 126 iodine-positive metastases. 18 (72%) of the 25 had solely iodine-avid metastases, while seven (28%) had both iodine-avid and -non-avid metastases. In two patients (8%), none of the iodine-avid metastases could have been practically treated with a sufficient radiation dose. Relative to the empirical protocol, (124)I-PET dosimetry findings changed management in 7 (25%) patients, e.g. allowing application of activities >11 GBq (131)I. Further changes included implementation of hematological back-up in a patient found to be at risk of life-threatening marrow toxicity, and early multimodal therapy in 9 (32%) patients. CONCLUSION: 124I-PET dosimetry is a useful routine procedure in advanced DTC and may allow safer or more effective radioiodine activities and earlier multimodal interventions than do standard empirical protocols.