Comparison of pathophysiology in subclinical hyperthyroidism with different etiologies.

Subclinical hyperthyroidism (SHyper) is defined as normal levels of free thyroxine (fT4) and free triiodothyronine (fT3) with suppressed levels of TSH. Previous studies have reported the individual pathophysiology of endogenous SHyper patients and athyreotic patients receiving TSH suppression therapy with levothyroxine; however, apparently no studies have compared the two conditions. Five-hundred-forty untreated endogenous SHyper patients and 1,024 patients receiving TSH suppression therapy who underwent total thyroidectomy for papillary thyroid carcinoma were sampled. Thyroid hormone profiles and peripheral indices related to thyrotoxicosis were investigated in endogenous SHyper patients, athyreotic patients receiving TSH suppression therapy, and healthy participants. Endogenous SHyper patients showed significantly higher thyroid hormone levels (fT4 [p < 0.001] and fT3 [p < 0.001]), and peripheral indices showed a significant tendency towards thyrotoxicosis (strong TSH suppression: alkaline phosphatase [ALP, p < 0.001], creatinine [Cre, p < 0.001], pulse rate [p < 0.05]; and mild TSH suppression: Cre [p < 0.05]) than healthy participants. In contrast, athyreotic patients receiving TSH suppression therapy showed a significant tendency towards thyrotoxicosis than healthy participants only when TSH was strongly suppressed (fT3 [p < 0.001] and Cre [p < 0.001]). Endogenous SHyper patients showed significantly higher fT3 levels (p < 0.001) than athyreotic patients receiving TSH suppression therapy; however, there was a significant tendency towards thyrotoxicosis only when TSH was strongly suppressed (ALP [p < 0.05] and pulse rate [p < 0.05]). The effects of endogenous SHyper and TSH suppression therapy on target organ function are different. Although the serum thyroid hormone profile is similar to that of the thyrotoxic state, athyreotic patients receiving TSH suppression therapy with mildly suppressed serum TSH levels are not thyrotoxic.

Outcomes of immediate surgery for low-risk papillary thyroid microcarcinoma in patients with or without risky features at surgery.

Active surveillance (AS) is an accepted management option for patients with low-risk papillary thyroid microcarcinoma (PTMC), although some patients undergo immediate surgery (IS). At surgery, patients may have risky features such as adhesion or invasion to the adjacent organs. The surgical outcomes of this subset of patients are unknown. Here, we investigated the surgical and oncological outcomes of these patients in comparison with others. Between 2005 and 2019, 4,635 patients were diagnosed with low-risk PTMC at our institute. Of these, 1,739 patients underwent IS. In total, 114 patients had risky features at surgery (risky feature group), while the remaining 1,625 did not (no-risky feature group). The median follow-up periods in the risky and no-risky feature groups were 8.5 and 7.6 years, respectively. The risky feature group had higher incidences of tracheal invasion (8.8%), recurrent laryngeal nerve invasion (RLN) (7.9%), and permanent vocal cord paralysis postoperatively (10.0%) and higher frequency of pathological lateral lymph node metastasis (6.1%) than the no-risky feature group (0%, 0%, and 0.2%, and 0%, respectively [p < 0.01]). However, unexpectedly, the former had a lower incidence of high Ki-67 labeling index (1.1%) and lower locoregional recurrence rate (0%) than the latter (8.3% and 0.7, respectively [p < 0.01], not calculable). None of the groups developed distant metastasis or died of the disease. The risky feature group required resection of the trachea and/or the RLN more often than the no-risky feature group. However, unexpectedly, the tumor growth activity in the risky feature group was low, and their oncological outcome was excellent.

Active surveillance is an excellent management technique for identifying patients with progressive low-risk papillary thyroid microcarcinoma requiring surgical treatment.

Although the outcomes of active surveillance (AS) for low-risk papillary thyroid microcarcinoma (PTMC) are generally excellent, some patients undergo conversion surgery for various reasons, including disease progression. We studied the outcomes of PTMC patients who underwent AS, who underwent conversion surgery after AS, and who underwent immediate surgery. Between 2005 and 2019, 4,635 patients were diagnosed with low-risk cT1aN0M0 PTMC at Kuma Hospital: 2,896 opted for AS (AS group) and 1,739 underwent immediate surgery (Surgery group). In the AS group, 242 patients underwent conversion surgery (Conversion group): 72 owing to disease progression (Conversion-prog group) and 170 for other reasons (Conversion-non-prog group). Of the 1,739 patients in the Surgery group, 1,625 had no high-risk features (Surgery-low-risk group). Locoregional recurrence (LRR) occurred in 9, 1, 1, and 0 patient in the Surgery-low-risk group, the Conversion-prog group, the AS group, and the Conversion-non-prog group, respectively. The LRR rate of the AS group was significantly lower than that of the Surgery-low-risk group (0.1% vs. 0.7% at 10 years, p = 0.006). Additionally, the LRR rate of the Conversion group (0.6% at 10 years, p = 0.741) and that of the Conversion-prog group (3.3% at 10 years, p = 0.103) did not significantly differ from the LRR of the Surgery-low-risk group. As the postoperative prognosis of patients with progressive PTMC who underwent conversion surgery did not significantly differ from that of patients who underwent immediate surgery, we think that AS may have resulted in efficient identification of the small proportion of patients with progressive PTMC that require surgical treatment.

Observational management of papillary microcarcinoma appearing in the remnant thyroid after hemithyroidectomy.

Active surveillance for papillary thyroid microcarcinomas (PTMCs) initiated in Japan is becoming adopted worldwide as a management option. However, it remains unclear how to manage newly appearing PTMCs in the remnant thyroid after hemithyroidectomy. We investigated the outcomes of similar observational management (OM) for PTMCs appearing in the remnant thyroid after hemithyroidectomy for papillary thyroid carcinoma (PTC) and benign thyroid nodules. Eighty-three patients were newly diagnosed with PTMC in the remnant thyroid between January 1998 and March 2017. Of these, 42 patients underwent OM with >3 times ultrasound examinations. Their initial diagnoses were PTC (initially malignant group) in 37 patients and benign nodule (initially benign group) in 5 patients. We calculated the tumor volume doubling rate (TV-DR) during OM for each PTMC. The TV-DR (/year) was <-0.1, -0.1-0.1, 0.1-0.5, and >0.5 in 12, 19, 5, and 6 patients, respectively. The TV-DRs in both groups did not statistically differ, but six patients (16%) in the initially malignant group showed moderate growth (TV-DR >0.5/year). They underwent conversion surgery and none of them had further recurrence. The remaining 36 patients retained OM without disease progression. The TV-DR in the initially malignant group was not significantly associated with patients' backgrounds or their initial clinicopathological features. None of the patients in this study showed distant metastases/recurrences or died of thyroid carcinoma. Although a portion of PTMCs appearing after hemithyroidectomy for thyroid malignancy are moderately progressive, OM may be acceptable as a management option for PTMCs appearing in the remnant thyroid after hemithyroidectomy.

The magnitude of increased Levothyroxine dose during pregnancy in patients on thyroid-stimulating hormone (TSH) suppression treatment after total thyroidectomy for papillary carcinoma.

The dose of L-T4 replacement for hypothyroidism often needs to be increased after pregnancy. In our institution, patients are instructed to double the dose 2 days a week after pregnancy. However, there is scarce evidence supporting the need for a dose increase after pregnancy in patients with preconception thyroid-stimulating hormone (TSH) suppression (TSH <0.3 µIU/mL). This study aimed to determine the need for a dose increase in L-T4 among women with a TSH-suppressive dose of L-T4 before pregnancy. In this retrospective observational study, between January 2008 and December 2018, we analyzed 166 pregnancies in 134 patients on TSH suppression treatment after total thyroidectomy for papillary carcinoma. Thyroid function tests were performed before and in the first trimester of pregnancy. The dose was adjusted and maintained during the first trimester of pregnancy in 76 pregnancies (group A) and 90 pregnancies (group B), respectively. The median serum TSH level was significantly lower in group A than that in group B (0.014 µIU/mL (IQR, 0.005-0.071) vs. 0.155 µIU/mL (IQR, 0.021-0.657), p < 0.001). TSH suppression could not be maintained after pregnancy in 15.8% and 38.9% of the pregnancies in groups A and B, respectively. Increasing the post-pregnancy dose by an average of 27.4% resulted in maintenance of TSH suppression after pregnancy in 84.2% of pregnancies. In conclusion, this study suggests that increasing the L-T4 dose after pregnancy may be appropriate in postoperative thyroid cancer patients whose serum TSH levels should be suppressed.

Favorable outcomes of papillary thyroid microcarcinoma concurrent with Graves' disease after radioactive iodine therapy.

Graves' disease (GD) may coexist with papillary thyroid microcarcinoma (PTMC). The main purpose of this study was to evaluate whether treatment with radioactive iodine (RAI) may cause acute exacerbation of PTMC concurrent with GD or not. From the medical records of 10,257 GD patients who underwent RAI therapy between 2000-2017, 12 subjects with concurrent PTMC were retrieved. Further, 49 patients with concurrent GD and PTMC who underwent no RAI administration throughout their clinical course were enrolled as controls. Size of the PTMC nodules was evaluated based on maximal diameter and tumor volume-doubling rate (TV-DR). Among the 12 subjects who underwent RAI therapy (median dose, 13 mCi), 2 showed tumors >10 mm in maximal diameter with slow growth for more than 10 years, while the other 10 showed tumors with maximal diameter ≤10 mm. No subject showed any clinical findings of nodal or distant metastasis during the follow-up periods (0.4-11.5 years) before surgery or during active surveillance. No significant differences were observed in the TV-DR values (median, 0.044/year; range, -0.81-1.40) between the study subjects and controls (median, 0.025/year; range, -0.70-1.29; p = 0.69). When comparing the TV-DR before and after RAI administration in 3 individuals in particular, in whom PTMC were cytologically confirmed before RAI administration and whose prospective follow-up data were available, tumor progression was observed to be stable or decreased after RAI administration. There were no acute exacerbations or unfavorable outcomes of concurrent PTMC and GD after low-dose RAI administration.

Evaluation of the diagnostic utility of the aminotransferase/lactate dehydrogenase ratio for the suspension of tissue specimens during thyroid surgery for the identification of parathyroid tissue.

Identification of the parathyroid glands during surgery is crucial for preventing postoperative hypoparathyroidism. Kikumori et al. reported that the aspartate aminotransferase (AST)/lactate dehydrogenase (LDH) ratio for the saline suspension of a suspicious tissue can differentiate parathyroid tissue from other tissues. The aim of this study was to evaluate the utility of this method and investigate the appropriate time for measurement. We obtained 465 tissue specimens during thyroidectomy of 102 patients with papillary thyroid carcinoma (PTC), and 422 specimens (129 parathyroid, 92 PTC, and 201 other tissues) with measurable AST and LDH were analyzed. Small pieces of the tissues were immersed in saline and sent for measurement of AST and LDH. The assay was performed immediately after thyroidectomy for 245 specimens (the same-day group) and during the next morning for the remaining 177 specimens (the next-day group). The accuracy of diagnosing parathyroid tissue was significantly better in the same-day group than in the next-day group. A cut-off value of 0.18 gave the best diagnostic precision, with an area under the receiver operating characteristic curve of 0.95 and 88.7% sensitivity and specificity in the same-day group. When the cut-off value was set to 0.20, the specificity for excluding carcinomatous tissues was 100%. When measured on the day of the surgery, the AST/LDH ratio for the saline suspension of the surgical specimens is useful for discriminating parathyroid tissues from other tissues. This method can be utilized at most hospitals where intraoperative frozen sections or rapid parathyroid hormone assays are not available.

Association between serum thyroid hormone balance and thyroid volume in patients treated with levothyroxine monotherapy for hypothyroidism.

Many previous studies including ours have reported that athyreotic patients on levothyroxine (LT4) have relatively low serum free triiodothyronine (FT3) levels, whereas patients with large goitrous diseases often have high serum FT3 levels. Here we investigated Hashimoto thyroiditis (HT) patients on LT4 to study the relationship between thyroid volume (TV) and thyroid hormone status in hypothyroid patients on LT4. We retrospectively studied 408 euthyroid HT patients treated with LT4 for hypothyroidism; divided them as per TV and compared serum levels of free thyroxine (FT4) and FT3 and the FT3/FT4 ratio in each patient group with those in euthyroid matched control group. We also evaluated the association between serum FT3 level and FT3/FT4 ratio and TV among HT patients on LT4. In patients with TV <15 mL, serum FT3 levels were significantly lower than those in controls. In patients with TV 15-80 mL, serum FT3 levels were equivalent to those in controls. In patients with TV ≥80 mL, the serum FT3 levels were significantly higher than those in controls. The serum FT3 level (r = 0.35, p < 0.01) and FT3/FT4 ratio (r = 0.42, p < 0.01) showed a positive correlation with TV. TVs in HT patients on LT4 caused differences in serum thyroid hormone balance, as increasing volume increases the serum FT3 level and FT3/FT4 ratio. Serum thyroid hormone balance in HT patients with smaller thyroids was similar to that in athyreotic patients. Mild thyrotropin suppression with LT4 is needed to achieve normal FT3 levels in such patients.

[Clinical Findings of Thalamic and Brainstem Glioma Including Diffuse Midline Glioma, H3K27M Mutant:A Clinical Study].

BACKGROUND: Diffuse midline glioma, H3K27M mutant is a glioma located in the thalamus, brainstem, or spine with the H3K27M mutation, which is a new entity in the 2016 revised WHO classification. The treatment of thalamic glioma(TG)and brainstem glioma(BSG), which includes diffuse midline gliomas, the H3K27M mutant is challenging, and there are no standard therapeutic strategies. It is important to determine the characteristics of these brain tumors. Here, we retrospectively reviewed 31 consecutive patients with TG and BSG who were treated at our institute between January 1994 and May 2018, including methionine-positron emission tomography(MET-PET)data. RESULTS: Fourteen patients had TG, while 17 patients had BSG. Six patients were children, and 25 were adults. Nine patients with TGs and seven with BSG were enhanced by gadolinium. Twenty-seven patients were treated with radiotherapy, and 20 patients were treated with chemotherapy. All 21 tumors that underwent surgery showed wild-type IDH. The H3K27M mutation was present in four TG and two BSG. There was no statistically significant association between methionine uptake and gadolinium contrast enhancement and tumor grade. The median overall survival period(OS)of all cases was 16.9 months, whereas those of TG and BSG were 22.8 and 10.0 months, respectively. CONCLUSION: Because TG and BSG still have poor prognoses, it is necessary to elucidate the pathology of the disease and establish its standard therapy.

Needle Tract Implantation Following Fine-Needle Aspiration of Thyroid Cancer.

BACKGROUND: Needle tract implantation (NTI) can occur after thyroid fine-needle aspiration cytology (FNAC). To date, no studies enrolling a large number of patients and studying the cumulative incidence (CI) of NTI have been published. This study analyzed the clinicopathological features of NTI and calculated the CI. METHODS: A total of 11,745 patients who underwent first FNAC, resection for thyroid carcinomas and related lymph node metastases, and postoperative ultrasonography in Kuma Hospital between 2006 and 2017 were evaluated. NTI was defined as macroscopically visible and/or sonographically detected recurrent tumors at the sites of the previous aspiration. Lymphovascular invasion and/or nodal metastasis were excluded. RESULTS: We found 22 NTI-THY (originated from aspiration of thyroid tumors) and 8 NTI-LN (originating from lymph nodes) cases with CI of 0.15% and 0.37%, and 0.37% and 0.58% at 5 and 10 years after FNAC, respectively. A large percentage (53%) of cases are presented as more aggressive histologic subtypes than their original tumors. Of these NTI patients, 4 (12.1%) died of disease and 10 (33.3%) developed distant metastases but remained alive with stable disease, three (9.1%) developed local recurrences, and the remaining 15 (10%) were free of recurrence. CONCLUSIONS: We demonstrated for the first time the CI and detailed clinicopathological features of thyroid NTI associated with possible histological transformation. Despite the low CI, the risk of death and distant metastases increase manifold in NTI patients than that in patients without recurrence. Therefore, NTI could be an important prognostic variable and impact patient survival.

Quality of Life in Patients with Low-Risk Papillary Thyroid Microcarcinoma: Active Surveillance Versus Immediate Surgery.

OBJECTIVE: This study aimed to compare the quality of life (QoL) and psychological issues of patients with papillary thyroid microcarcinoma (PMC) who were under active surveillance (AS) and those who underwent immediate surgery (OP). METHODS: This was a cross-sectional study conducted on 347 patients with low-risk PMC who were under AS (n = 298) or who underwent OP (n = 49). They were asked to complete two questionnaires (thyroid cancer-specific health-related QoL [THYCA-QoL] and the Hospital Anxiety and Depression Scale [HADS]). The results between the AS and OP groups were compared. RESULTS: The mean ages of patients in the AS and OP groups were 58.6±12.5 and 58.4±13.1 years (P =.94), respectively, and the male ratios were 34/298 (11%) and 2/49 (4.1%) (P =.14), respectively. The median follow-up periods from diagnosis in the AS and OP groups were 56.5 months (interquartile range [IQR], 32 to 88 months) and 84 months (IQR, 64 to 130 months) (P<.001), respectively. In the THYCA-QoL questionnaire, the OP group had more complaints about "voice" (P<.001), "psychological" (P =.025), "problems with scar" (P<.001), and "gained weight" (P =.047) than the AS group. Other scales of the THYCA-QoL were comparable in the two groups. In the HADS questionnaire, the AS group had significantly better anxiety (P =.020), depression (P =.027), and total scores (P =.014) than the OP group. CONCLUSION: PMC patients in the OP group had more complaints and were more anxious and depressed than the AS group. These findings suggest that AS is a reasonable alternative to surgery for patients with low-risk PMC from the point of view of QoL and psychology. ABBREVIATIONS: AS = active surveillance; CI = confidence interval; HADS = Hospital Anxiety and Depression Scale; LT4 = levothyroxine; OP = immediate surgery; PMC = papillary microcarcinoma; PTC = papillary thyroid carcinoma; QoL = quality of life; STAI = State-Trait Anxiety Inventory; THYCA-QoL = thyroid cancer-specific health-related quality of life; TSH = thyrotropin.

Papillary thyroid carcinomas are highly obscured by inflammatory hypoechoic regions caused by subacute thyroiditis: a longitudinal evaluation of 710 patients using ultrasonography.

Subacute thyroiditis is a self-limited inflammatory disease and very few patients undergo ultrasonographic re-examination if no nodules are found at the initial examination. The objective of the study was to assess the diagnostic accuracy of ultrasonography in detecting nodular lesions in patients with subacute thyroiditis. We conducted a longitudinal study involving 710 patients with subacute thyroiditis who underwent ultrasonographic examinations in a single center between 2008 and 2018. These examinations were performed at initial diagnosis and during follow-up, with subsequent evaluation of nodules using fine needle aspiration cytology. Ultrasonographic examination used for the initial screening of thyroid nodules in patients with subacute thyroiditis showed a sensitivity of 72.4%, specificity of 89.0%, positive predictive value of 80.4%, and negative predictive value of 83.8%. Twenty-two patients (3.1%) had concomitant papillary thyroid carcinoma, 10 of whom underwent thyroidectomy while the remaining 12 opted for active surveillance owing to having low-risk microcarcinomas. Approximately 30% of papillary carcinomas (7/22) were identified during follow-up ultrasonography, but not during the initial scan. All tumors in this false-negative group were latently localized in the bilateral hypoechoic regions of the thyroid and showed no calcified components. Of the 15 tumors that were detected during both initial and follow-up examinations, 7 exhibited calcified components and 5 were located in unaffected areas apart from the inflammatory hypoechoic region. Subacute thyroiditis highly obscures any coexisting papillary carcinoma when inflammatory hypoechoic regions are present. Ultrasonographic re-examination after a sufficient interval is indispensable for patients with subacute thyroiditis.

[A Case Report of Clivus Chordoma Presenting with Cerebrospinal Fluid Rhinorrhea].

Chordomas are uncommon tumors occurring from remnants of the notochord. They are mainly localized in the sacrococcygium, the spine and the central skull base. Here we report a rare case of clivus chordoma presenting with cerebrospinal fluid(CSF)rhinorrhea. A 41-year-old man with a 11-year history of recurrent CSF rhinorrhea was found to have a clival lesion. Bone image CT revealed lytic bone destruction at the clivus. MRI showed a cystic mass with a membrane enhanced by gadolinium protruding into the sphenoid sinus thorough the bone defect. However, there was no solid component observed. The membrane was partially resected and the CSF fistula was repaired via endoscopic endonasal approach. The pathological diagnosis was chordoma, and there has been no recurrence for three years after the surgery. It is necessary for chordoma to be considered as a differential diagnosis for cystic lesions of the clivus when the cyst membrane is enhanced by gadolinium.

Cribriform-Morular Variant of Papillary Thyroid Carcinoma Shows High Ki-67 Labeling Indices, despite Its Excellent Prognosis.

OBJECTIVE: This study aimed to demonstrate that the cribriform-morular variant (CMV) of papillary thyroid carcinoma (PTC) has high Ki-67 labeling indices, despite its excellent prognosis. METHODS: We examined 21 CMV-PTCs and 5 conventional PTCs (C-PTCs) resected at Kuma Hospital between 2008 and 2018. All of the patients with CMV-PTC were women. Their ages ranged from 17 to 35 years, with a mean of 25.2 years. An immunohistochemical study using ß-catenin, estrogen receptor (ER), and Ki-67 was performed. For apoptotic analysis, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining was performed. RESULTS: All CMV-PTCs were encapsulated with thick fibrous connective tissue. Eleven and one CMV-PTCs exhibited capsular invasion and extrathyroidal invasion, respectively. Two patients showed regional nodal metastasis. The Ki-67 labeling index ranged from 4.8 to 36.4% (mean 15.2%). Apoptotic cells were counted, which showed 2-52 positive cells (mean 12.6) per 10 high-power fields. The Ki-67 labeling index was positively correlated with the apoptotic cell count (r = 0.48, p = 0.030). Ki-67 labeling indices of CMV-PTCs were significantly higher than those of C-PTCs (p = 0.0027). Ages and tumor sizes did not have significant correlations with Ki-67 labeling indices or apoptotic cell counts. CONCLUSION: This study is the first to demonstrate disproportionally high Ki-67 labeling indexes in a large number of CMV-PTC cases, despite the fact that these cases had favorable prognoses. The favorable prognosis of CMV-PTC may be attributable to encapsulation and nuclear ER expression.

Spontaneous Deceleration and Acceleration of Growth Rate in Medullary Thyroid Carcinomas Suggested by Changes in Calcitonin Doubling Times Over Long-Term Surveillance.

BACKGROUND: Based on our long-term observation of medullary thyroid carcinoma (MTC) patients, we hypothesized that some MTCs have spontaneous deceleration or regression of tumor growth over a long term and that a minority may acquire growth acceleration. We thus compared the calcitonin doubling time (Ct-DT) in the earlier and later half-periods of MTC patients' postoperative course. METHODS: We followed 26 MTC patients (14 hereditary and 12 sporadic MTCs) with postoperative hypercalcitoninemia with periodic measurements of serum calcitonin (Ct) for >10 years without major interventions. The median period of Ct measurements was 18.3 years (range 10.6-30.2 years). We divided the individual patients' study periods into the earlier and later halves and calculated the Ct-DTs for both periods. RESULTS: In the hereditary group, the Ct-DT in the later half-period (Later-Ct-DT) was significantly longer than that in the earlier half-period (Earlier-Ct-DT) (median 20.0 years vs. 7.1 years, p = 0.013). These values in the sporadic group were 20.0 years versus 11.1 years, respectively (p =0.774). Twelve patients (seven hereditary and five sporadic) had Later-Ct-DTs significantly longer than their Earlier-Ct-DTs (median 27.4 years vs. 4.9 years) and good prognoses. Two patients (one hereditary, one sporadic) had Later-Ct-DTs significantly shorter than their Earlier-Ct-DTs, and both developed structural recurrence and died of the disease. CONCLUSION: Many of the hereditary and some of the sporadic MTC patients had elongated Ct-DTs over a long period, suggesting spontaneous deceleration and regression of tumor growth. A minority of the MTC patients showed Ct-DT shortening, suggesting tumor growth acceleration.

Optimal needle size for thyroid fine needle aspiration cytology.

Concerning the needle size for thyroid fine needle aspiration cytology (FNAC), 25-27-gauge needles are generally used in Western countries. However, in Japan, the use of larger needles (21-22-gauge needles) is common. The aim of our study was to determine the optimal needle size for thyroid FNAC. We performed ultrasound-guided FNAC for 200 thyroid nodules in 200 patients using two different-sized needles (22 and 25 gauge). For each nodule, two passes with the different-sized needles were performed. The order of needle sizes was reversed for the second group of 100 nodules. The second aspiration was more painful than the first, regardless of the needle size. An association with more severe blood contamination was more frequently observed with the use of 22-gauge needles (32.0%) than with the use of 25-gauge needles (17.5%) and in the second aspiration (37.5%) than in the initial aspiration (12.0%). The initial aspiration samples were more cellular than the second aspiration samples. Regarding the unsatisfactory and malignancy detection rates, there was no statistical difference between the needles. In three of seven markedly calcified nodules, it was difficult to insert 25-gauge needles into the nodules. In terms of the diagnostic accuracy and pain, either needle size can be used. We recommend using 22-gauge needles for markedly calcified nodules because 25-gauge needles bend more easily in such cases. We demonstrated that the initial aspiration tended to obtain more cellular samples and to be less contaminated. Thus, the initial aspiration is more important and should be closely attended.

Thyroid function related symptoms during levothyroxine monotherapy in athyreotic patients.

Previous reports by us and other investigators showed that among athyreotic patients on levothyroxine (LT4) following total thyroidectomy patients with normal serum thyroid-stimulating hormone (TSH) levels had mildly low serum free triiodothyronine (FT3) levels, whereas patients with mildly suppressed serum TSH levels had normal serum FT3 levels and patients with strongly suppressed serum TSH had elevated serum FT3 levels. The objective of this study was to clarify which of these three patient groups are closer to their preoperative euthyroid condition based on reported subjective symptoms. We prospectively studied 148 consecutive euthyroid patients with papillary thyroid carcinoma who underwent a total thyroidectomy. Symptoms reflecting thyroid function documented preoperatively and following 12 months of LT4 after thyroidectomy were compared. In 65 patients with strongly suppressed TSH levels significant changes in symptoms with tendencies towards thyrotoxicosis were seen with regards to heat and cold tolerance (p < 0.01), bowel movements (p < 0.05), and hand tremors (p < 0.05). In 33 patients with normal TSH levels, significant changes in symptoms with tendencies towards hypothyroidism were seen with regards to heat and cold tolerance (p < 0.05) and activity (p < 0.05). Lastly, in 50 patients with mildly suppressed TSH levels and FT3 levels equivalent to preoperative levels, all symptom items remained equivalent to their preoperative levels. Symptoms reflecting thyroid function in patients on LT4 following total thyroidectomy suggested that patients with mildly suppressed TSH levels were closest to a euthyroid status. These data provide useful findings regarding the management of patients following total thyroidectomy.

The association between thyroid hormone balance and thyroid volume in patients with Hashimoto thyroiditis.

While patients with large goitrous thyroid diseases often have a relatively high serum free triiodothyronine (FT3)/free thyroxine (FT4) ratio, athyreotic patients have a relatively low FT3/FT4 ratio. Here we investigated the relationship between thyroid hormone status and thyroid volume (TV) among a large number of euthyroid Hashimoto thyroiditis (HT) patients. We retrospectively enrolled 2,603 untreated HT patients who visited the Kuma hospital from 2012 to 2016, and divided them into four groups as per the TV: normal TV (<20 mL), slight goiter (20 ≤ TV < 50 mL), moderate goiter (50 ≤ TV < 80 mL), and the large goiter group (≥80 mL). Baseline characteristics and laboratory data of each group were compared to those of 1,554 control subjects. The association between FT3/FT4 ratio and TV among HT patients was then analyzed. We observed a change in laboratory parameters among 13 patients in the large goiter group who were prescribed levothyroxine (LT4) for reducing TV. Compared to normal subjects, the moderate and large goiter groups exhibited significantly higher serum FT3 levels, while all HT groups exhibited lower serum FT4 levels. Serum FT3/FT4 ratios showed a positive correlation with TV (r = 0.35, p < 0.01), which was independent of age, sex, body mass index, and TgAb and TSH levels. LT4 treatment lowered serum FT3 levels and FT3/FT4 ratios significantly. Our results indicated that HT patients with increased TV tended to present with high serum FT3, low FT4, and high FT3/FT4 ratios. The elevation of deiodinase activity may be an important factor affecting thyroid hormonal balance in such patients.

[Effectiveness of Color-Coded Doppler Ultrasonography for Detecting the Trajectory in the Surgical Management of Distal ACA Aneurysms].

Distal anterior cerebral artery(DACA)aneurysms are relatively rare. The detection of the surgical trajectory of DACA aneurysmal clipping is difficult because DACA aneurysms are located at various sites in the ACA. The purpose of this study was to evaluate the effectiveness of intraoperative use of color Doppler ultrasonography for the surgery of DACA aneurysms. DACA aneurysms of ten patients(three men, seven women;64.5 years old on median)were examined using intraoperative color Doppler imaging(CDI), which was performed before microscopic procedures, to detect the location of the aneurysms. Among them, six patients had ruptured aneurysms with diameters ranging from 2.5 to 10.8mm, and four of them had intracerebral hematomas. All the aneurysms and surrounding arteries were clearly detected using CDI. Moreover, in larger aneurysms, blood flow dynamics inside the aneurysm were also observed using CDI. As a result, we concluded that the intraoperative use of color Doppler ultrasonography was effective of detecting the trajectory for the DACA aneurysms without causing any damage to the brain by redundant dissections.

Serum calcitonin reference values for calcium stimulation tests by electrochemiluminescence immunoassay in Japanese men with non-medullary thyroid carcinoma.

PURPOSE: Calcitonin is the most sensitive tumor marker of medullary thyroid carcinoma (MTC) and a calcium stimulation test is used to improve this sensitivity. In Japan, the electrochemiluminescence immunoassay (ECLIA) is currently the only test performed to measure serum calcitonin. There is a gender difference in the reference value of serum calcitonin; however, a reference upper limit for use with ECLIA has been reported only for women, but not for men. METHODS: We conducted the calcium stimulation test using ECLIA in 21 men with non-medullary thyroid carcinoma (non-MTC), before and after total thyroidectomy. RESULTS: Preoperatively, the basal calcitonin values were within normal limits in all patients. They increased to a mean value of 37.6 pg/mL after calcium stimulation, and we calculated that the reference upper limit was 83.7 pg/mL. The stimulation test results after total thyroidectomy showed undetectable basal and stimulated calcitonin values in every patient (<0.5 pg/mL). CONCLUSIONS: To our knowledge, this is the first study to calculate reference values for this stimulation test using an ECLIA in men with non-MTC. We propose that men can be regarded as biochemically cured or as having normal serum calcitonin values when the stimulated calcitonin values obtained by ECLIA are <83.7 pg/mL before and <0.5 pg/mL after total thyroidectomy.