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Acute hypothyroidism induced by thyroid hormone withdrawal (THW) in patients with thyroid cancer after total thyroidectomy can affect mood and quality of life (QoL). While loss or dysregulation of thyroid hormone (TH) has these well-known behavioral consequences, the effects of TH alterations on brain function are not well understood. Resting state functional connectivity (FC) measured by functional magnetic resonance imaging (fMRI) allows non-invasive evaluation of human brain function. This study therefore examined whether THW affects resting state FC and whether changes in FC correlate with the mood or QoL of the patients with THW status.Twenty-one patients who had undergone total thyroidectomy for thyroid cancer were recruited. Resting state fMRI scanning of the brain, thyroid function tests, and administration of the 12-Item Short Form Health Survey (SF-12) and the Patient Health Questionnaire-9 (PHQ-9) were performed before and after two weeks of THW. Regional homogeneity (ReHo), one of the measures of resting state FC, was calculated, and each voxel was compared between before and after THW in 19 patients. The ReHo values were extracted from the regions of interest showing within-group differences in ReHo values after THW, and correlations of ReHo values with thyrotropin (TSH) levels, total score of the PHQ-9, and composite scores of the SF-12 were statistically evaluated.Higher ReHo was observed after THW in the brain cortical regions across primary motor and sensory, visual, and association cortices. Among the regions, the ReHo values in the bilateral pre- and postcentral gyri, bilateral middle occipito-temporal cortices, the left precuneus, and the left lingual gyrus showed positive correlations with serum TSH levels after THW. Higher ReHo values in the bilateral pre- and postcentral gyri, the left middle temporo-occipital cortices, and the left ligual gyrus correlated with the lower mental component summary score from the SF-12, while higher ReHo values in the bilateral pre- and postcentral gyri correlated with higher total scores in the PHQ-9.Local brain FC is increased in the acute hypothyroid state. Higher FC correlates with a poorer mental QoL and increased depression in the hypothyroid state.

The BRAF(V600E) mutation is a promising prognostic biomarker for patients with papillary thyroid carcinoma (PTC), but its prevalence differs widely among different geographic regions. A recent study reported that loss of the Cleavage and Polyadenylation Specificity Factor Subunit 2 (CPSF2) gene was associated with increased cellular invasion, cancer stem cells, and aggressiveness of PTC. This study aimed at evaluating CPSF2 protein expression as a prognostic marker for PTC in a region with a high prevalence of the BRAF(V600E) mutation, Korea.This study included 159 patients with classical PTC who underwent a total thyroidectomy and received ablative doses of (131)I. The expression of CPSF2 protein was evaluated by immunohistochemistry and graded semi-quantitatively. The presence of the BRAF(V600E) mutation was evaluated by direct sequencing.Negative protein expression of CPSF2 was observed in 34 (21.3%) of the 159 PTCs. In multivariate analysis, negative CPSF2 expression was significantly associated with cervical lymph node metastasis (odds ratio [OR]=2.56, p=0.28), and distant metastasis (OR=3.48, p=0.02). After adjusting for age, sex, tumor size, extrathyroidal invasion, lymphovascular invasion, and the BRAF(V600E) mutation, the CPSF2-negative group had a significantly lower recurrence-free survival compared to the CPSF2-positive group (hazard ratio=2.14, p=0.03).Negative protein expression of CPSF2 is independently associated with a poor clinical outcome in PTC. CPSF2 could be a useful prognostic marker for PTC in regions with a high prevalence of the BRAF(V600E) mutation.

Measurement of thyroglobulin (Tg) in the washout fluid of fine-needle aspirates (FNA-Tg) is useful for diagnosis of lymph node (LN) metastasis in papillary thyroid carcinoma (PTC). However, the cutoff value of FNA-Tg in the preoperative state is not defined clearly. This study aimed to evaluate the optimal cutoff value of preoperative FNA-Tg according to serum Tg level.FNA-Tg was measured in 135 PTC patients (160 LNs) for preoperative diagnosis of cervical LN metastasis.Of the 160 LNs, 119 (74%) were surgically removed and 110 (69%) were diagnosed as malignant. When we adopted a FNA-Tg of 1.0 μg/L as the cutoff value, the sensitivity and specificity were 99% and 76%, respectively. FNA-Tg levels were correlated with serum Tg levels (Pearson's coefficient 0.42, p=0.002) and the FNA-Tg levels of 12 of the 50 benign LNs were above 1.0 μg/L. We classified the LNs into two groups according to serum Tg level regardless of anti-Tg antibody status: a low Tg group (≤1.0 μg/L, n=22, 14%) and a high Tg group (1.0 μg/L, n=138, 86%). In the low Tg group, the sensitivity and specificity of the FNA-Tg cutoff value of 1.0 μg/L were 93% and 100%, respectively. In the high Tg group, the sensitivity and specificity of the FNA-Tg cutoff value of 19.0 μg/L were 93% and 100%, respectively. A Tg ratio (FNA-Tg level divided by serum Tg level) of 0.5 gave an improved diagnostic performance (sensitivity, 98%; specificity, 98%) in the high Tg group.FNA-Tg levels in the preoperative state are affected by serum Tg levels when they exceeded 1.0 μg/L. For the preoperative diagnosis of metastatic cervical LNs, it seems reasonable to employ different cutoff values of FNA-Tg depending on serum Tg levels. We propose the use of an optimal cutoff value of FNA-Tg of 1.0 μg/L in patients with low serum Tg levels and a Tg ratio of 0.5 in those with high serum Tg levels irrespective of thyroglobulin antibody status.

Low serum vitamin D levels have been associated with several autoimmune diseases, but their association with thyroid autoimmunity is unclear. We evaluated the association of serum vitamin D levels with the prevalence of autoimmune thyroid disease (AITD).Our cross-sectional study included subjects who underwent routine health checkups, which included assays of serum 25-hydroxy vitamin D3 [25(OH)D3] and anti-thyroid peroxidase antibody (TPO-Ab), as well as thyroid ultrasonography (US) between 2008 and 2012 at the Asan Medical Center. We defined AITD according to the levels of TPO-Ab and US findings.A total of 6685 subjects (58% male; 42% female) were enrolled for this study. Overall prevalence of TPO-Ab positivity and both TPO-Ab/US positivity were 10.1% (6.3% male; 15.3% female) and 5.4% (2.3% male; 9.7% female) respectively. In female subjects, mean serum 25(OH)D3 levels were significantly lower in the TPO-Ab(+) (22.0 vs. 23.5 ng/mL, p=0.030) and TPO-Ab(+)/US(+) groups (21.6 vs. 23.4 ng/mL, p=0.027) compared with the control group, respectively. According to the levels of serum 25(OH)D3, the prevalence of TPO-Ab positivity (21.2%, 15.5%, and 12.6% in deficient, insufficient, and sufficient group, respectively; p=0.001) and both TPO-Ab and US positivity (14.7%, 9.9%, and 7.1% in deficient, insufficient, and sufficient group, respectively; p0.001) decreased in female subjects. Interestingly, this pattern was significant only in pre-menopausal women (p=0.003 and p0.001; respectively), but not in postmenopausal women. Multivariate analysis indicated that the adjusted odds ratios (OR) for AITD among those in the 25(OH)D3-deficient [TPO-Ab(+): OR 1.95, p=0.001; TPO-Ab(+)/US(+): OR 2.36, p0.001] and -insufficient groups [TPO-Ab(+): OR 1.31, p=0.043; TPO-Ab(+)/US(+): OR 1.50, p=0.017] were significantly increased when compared with the sufficient group.The levels of serum vitamin D were significantly lower in pre-menopausal women with AITD. Vitamin D deficiency and insufficiency were significantly associated with AITD in pre-menopausal women.