Search

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

Objective Resistance to thyroid hormone beta (RTHβ) is an inherited syndrome caused by mutations in the thyroid hormone receptor β (THRB) gene. Patients with RTHβ typically have elevated thyroid hormone levels with non-suppressed serum thyroid-stimulating hormone (TSH). We aimed to elucidate the clinical, laboratory, and imaging findings of RTHβ patients and further to explore their association with THRB gene mutations. Design and methods We retrospectively reviewed the clinical charts and compared the clinical findings of 68 RTHβ patients (45 probands and 23 relatives) and 30 unaffected relatives in Kuma Hospital. Results Genetic testing revealed 35 heterozygous THRB gene mutations. Among all RTHβ patients, autoimmune thyroid disease (AITD) was detected in 42.1% of men and 40.9% of women, showing that the prevalence of AITD in affected males was significantly higher than in unaffected relatives (P = 0.019). During the follow-up of 44 patients, 13 patients (29.5%; 8 (42.1%) with AITD and 5 (20%) without AITD) temporarily showed thyroid function test results inconsistent with RTHβ. Two patients with the R383H mutation, which has little dominant-negative effect, temporarily showed normal thyroid hormone and TSH levels without AITD. Conclusions The frequency of AITD in male RTHβ patients was significantly higher compared to unaffected relatives. More than 20% of RTHβ patients temporarily showed laboratory findings atypical of RTHβ during their follow-up, and patients with AITD and specific THRB mutations were prone to display such findings. Therefore, genetic testing should be performed even for patients with fluctuations in thyroid function test results to avoid misdiagnosis and inappropriate treatment.

Nephrotic syndrome (NS) is characterized by massive urinary protein leakage and associated hypoproteinemia due to increased protein permeability caused by impaired renal glomerular connections. Although there have been several sporadic reports regarding the relationship between NS and thyroid dysfunction, a consensus has yet to be reached. The mechanism of hypothyroidism in NS is attributed to the loss of protein-bound thyroid hormones, such as thyroxine-binding globulin, transthyretin, and albumin, into the urine. Herein, we report four adults with hypothyroidism that developed or worsened due to the onset of NS. The patients' underlying thyroid status was post-total thyroidectomy with supplemental levothyroxine (L-T4) in two patients, hypothyroidism with supplemental L-T4 due to Hashimoto's disease in one patient, and Hashimoto's disease with normal thyroid function in one patient. Our results suggest that the presence of a reduced thyroid reserve may predispose patients to hypothyroidism in NS. We conclude that NS may cause or exacerbate hypothyroidism. In such cases, an NS assessment, including a urine test, is required.

Hyalinizing trabecular tumor (HTT) of the thyroid is a mostly benign disease. Its cytological and pathological diagnosis is often difficult, because HTT cells and papillary thyroid carcinoma (PTC) cells share similar features (e.g., intranuclear cytoplasmic inclusions and nuclear grooves). At our institution, 38 patients were diagnosed as or highly suspected of having HTT without the possibility of PTC, based on cytology: 19 of these patients underwent immediate surgery (surgery group) and the remaining 19 underwent active surveillance without surgery (AS group). The surgery-group patients' tumor sizes were significantly larger (p < 0.0001) than those in the AS group. During AS (median 38 months), only one patient (5%) showed tumor enlargement by ≥3 mm; the AS was continued. Of the 34 patients pathologically diagnosed with HTT, 22 (65%) were cytologically diagnosed or highly suspected as having HTT without the possibility of PTC. Of the nine patients who were suspected to have HTT but PTC was possible and surgery was performed, two (22%) and seven (78%) were pathologically diagnosed as having PTC and HTT, respectively. Five patients were cytologically diagnosed with PTC, but pathologically diagnosed as having HTT. No patients showed HTT recurrence during postoperative follow-up (median 60 months). These findings suggest that (1) active surveillance can be a valid strategy for managing tumors that are cytologically diagnosed as HTT with no possibility of PTC; (2) surgery is recommended for tumors suspected of being HTT but may be PTC, and (3) the prognosis of HTT in both the AS and surgery groups was excellent.

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

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).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.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.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.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.

Introduction: Marine-Lenhart syndrome (MLS) is now understood to be a combination of Graves’ disease and autonomously functioning thyroid nodule(s) (AFTNs). The prevalence of the syndrome and suitable treatments for those living in iodine-sufficient areas are uncertain. Objectives: We aimed to investigate the prevalence, treatment, and prognosis of MLS in Japan, an iodine-sufficient area. Methods: This study involved patients who visited our hospital between February 2005 and August 2019. Among patients with both thyrotoxicosis and thyroid nodule(s) larger than 10 mm, MLS and isolated AFTNs were diagnosed based on serum thyroid-stimulating hormone receptor antibody levels and scintigraphy using radioiodine or technetium-99m and thyroid uptake. Results: Twenty-two patients were found to have MLS, compared to 372 with isolated AFTNs and 8,343 with Graves’ disease, during the period. Therefore, the rate of MLS cases was 0.26% among all patients with Graves’ disease (22/8,343). Treatments and outcomes were assessed for cases of MLS (n = 18) and isolated AFTNs (n = 269). Antithyroid drugs (ATDs) were withdrawn in 27.8% of cases in the MLS group and 10.3% in the isolated AFTN group. There was no significant difference in the clinical outcome after ATD withdrawal between the 2 groups. However, the rate of hypothyroidism after radioactive iodine (RAI) administration was significantly higher in the MLS group than in the isolated AFTN group (42.9 vs. 9.0%, p = 0.005) despite similar doses of RAI. Conclusions: The prevalence of MLS among patients with Graves’ disease was 0.26% in Japan. RAI therapy induces hypothyroidism more frequently than in those with AFTNs probably because RAI is taken up in the surrounding Graves’ tissues.

Skeletal muscle mass (SMM) obtained using bioelectrical impedance analysis (BIA) is often correlated with isometric muscle strength; furthermore, it might also have correlations with one-repetition maximum (1RM). Accurate prediction of 1RM is important because it is useful for determining progress in resistance training. This study examined the relationship between BIA measurements and 1RM and developed prediction models for 1RM using BIA measurements. Thirty-five healthy young Japanese adults were included in this cross-sectional observational study. The SMM of the dominant leg and the skeletal muscle mass index (SMI) were obtained using a BIA device. The 1RM for the dominant leg was measured using a unilateral leg-press (LP) machine. The correlations between BIA measurements and 1RM were calculated, and simple regression analyses were performed to predict 1RM from the BIA variables. The results showed significant correlations between 1RM and dominant-leg SMM (R=0.845, P=0.0001) and SMI (R=0.910, P=0.0001). The prediction models for 1RM for LP derived from SMM of the dominant leg and SMI were Y=8.21x + 8.77 (P=0.0001), R2=0.73, and Y=15.53x − 36.33 (P=0.0001), R2=0.83, respectively. Our results indicate that SMI may be used to accurately predict the 1RM for LP.

Objective This study aimed to elucidate disproportionately low serum thyroglobulin (Tg) values in Tg antibody (TgAb)-positive patients with structural recurrence of papillary thyroid carcinoma (PTC) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Design A retrospective study was performed on 176 patients in whom Tg and TgAb levels were measured between 2016 and 2021. Several comprehensive analyses of Tg-LC-MS/MS with an electrochemiluminescence immunoassay for Tg (Tg-ECLIA) were conducted using serum samples. Methods TgAb-positive patients who underwent total thyroidectomy with multiple lung metastases due to PTC were evaluated using Tg-LC-MS/MS and Tg-ECLIA. Tg expression in lymph node metastases and metastatic lesions was evaluated by immunohistochemistry and Tg levels of aspiration washouts were also evaluated. Two in vitro assays were performed to elucidate TgAb interference. Results Tg concentrations of negative TgAb in both assays were similar (R2= 0.99; n = 52). Patients with structural recurrence showed higher Tg values with Tg-LC-MS/MS than with Tg-ECLIA. The undetectable proportion was significantly lower with Tg-LC-MS/MS (31.6%, 6/19) than with Tg-ECLIA (68.4%, 13/19; P = 0.023). The spike-recovery rate and Tg concentrations determined by the serum mixture text (n = 29) were significantly reduced to 75.0% (118.3–88.7%) and 81.3% (107.0–87.0%), respectively, with TgAb using Tg-ECLIA (both P < 0.001) confirming assay interference but not using Tg-LC-MS/MS (91.8–92.3%, P = 0.77 and 98.4–100.8%, P = 0.18, respectively). Conclusions TgAb had no effect on the Tg-LC-MS/MS assay but yielded 19–25% lower values in Tg-ECLIA. Tg-LC-MS/MS is preferable for monitoring serum Tg levels in TgAb-positive patients, although those with structural recurrence often had disproportionally low Tg values.

Background: Poorly differentiated thyroid carcinoma is rare and patients are typically euthyroid. We report a novel rare case of poorly differentiated thyroid carcinoma with triiodothyronine (T3) t...

Background: Some studies reported that among athyreotic patients on levothyroxine (LT4) after total thyroidectomy, patients with normal serum thyrotropin (TSH) levels had mildly low serum free triiodothyronine (fT3) levels, whereas patients with mildly suppressed serum TSH levels had normal serum fT3 levels. The reduction of the thyroid volume (TV) after radioiodine treatment for Graves' disease is well known; however, a few studies evaluated thyroidal function including serum triiodothyronine (T3) levels of hypothyroid patients on LT4 after radioiodine treatment in detail. Methods: We retrospectively studied 446 patients treated with LT4 for radioiodine-induced hypothyroidism and who had undergone ultrasonography. We compared serum fT4 and fT3 levels in hypothyroid patients on LT4 who presented an atrophic thyroid change after radioiodine treatment, with those in the euthyroid matched control group with intact thyroids. We also stratified patients with normal TSH levels according to TV and evaluated serum thyroid hormone levels. Results: In 356 of 446 (80%) patients, TV was lower than the lower limit of the 95% reference range of controls. Excluding 43 patients with high serum TSH levels, we assessed thyroid function test results in 313 patients with atrophic thyroid glands. Of these cases, eight patients with strongly suppressed TSH levels had serum fT3 levels that were significantly higher than those in controls (p

The serum free triiodothyronine (FT3)/free thyroxine (FT4) ratio in patients with huge goitrous Hashimoto’s thyroiditis (HG-HT) is relatively high. We investigated the cause of high FT3/FT4 ratios. We measured the serum FT3, FT4, and thyrotropin (TSH) levels of seven patients with HG-HT who had undergone a total thyroidectomy. Eleven patients with papillary thyroid carcinoma served as controls. The activities and mRNA levels of type 1 and type 2 iodothyronine deiodinases (D1 and D2, respectively) were measured in the thyroid tissues of HG-HT and perinodular thyroid tissues of papillary thyroid carcinoma. The TSH levels in the HG-HT group were not significantly different from those of the controls. The FT4 levels in the HG-HT group were significantly lower than those of the controls, whereas the FT3 levels and FT3/FT4 ratios were significantly higher in the HG-HT group. The FT3/FT4 ratios in the HG-HT group who had undergone total thyroidectomy and received levothyroxine therapy decreased significantly to normal values. Both the D1 and D2 activities in the thyroid tissues of the HG-HT patients were significantly higher than those of the controls. However, the mRNA levels of both D1 and D2 in the HG-HT patients’ thyroid tissues were comparable to those of the controls. Interestingly, there were significant correlations between the HG-HT patients’ D1 and D2 activities, and their thyroid gland volume or their FT3/FT4 ratios. Our results indicate that increased thyroidal D1 and D2 activities may be responsible for the higher serum FT3/FT4 ratio in patients with HG-HT.

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.

BACKGROUND: Subacute thyroiditis is generally believed to be induced by viral infection, and little attention has been paid to anti-thyroid antibodies. OBJECTIVES: Our study aimed to assess the prevalence of anti-thyroid antibodies in patients with subacute thyroiditis. METHODS: Anti-thyroglobulin (TgAb) and anti-thyroid peroxidase antibodies (TPOAb) were measured with 4 different immunoassay kits currently used in 40 patients in the early phase of subacute thyroiditis. RESULTS: The proportion of samples positive for TgAb was 52.5 ± 13.7% (mean of 4 kits), which was significantly (p < 0.05) higher than that positive for TPOAb (15.6 ± 6.5%). The prevalence of positive TgAb alone (negative TPOAb) was also significantly higher than that of TPOAb alone (negative TgAb). TgAb titers decreased or disappeared within 4 months to 6 years in 6 patients. CONCLUSIONS: Patient samples were moderately positive for TgAb initially, but the titer decreased or disappeared afterwards in subacute thyroiditis.

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.

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.

Objective: Sporadic nonautoimmune hyperthyroidism caused by germline mutations of the thyrotropin receptor (TSHR) gene is a very rare disease that manifests as severe congenital hyperthyroidism. We describe a case presenting with sporadic nonautoimmune hyperthyroidism during adolescence.Methods: Laboratory data, imaging, histopathology, clinical follow-up, and DNA sequencing were evaluated.Results: The patient was born at term with a normal birth weight but showed increased growth velocity at approximately 7 months. He had no medical consultation before tachycardia was detected at a school physical examination at the age of 13 years. Thyroid function tests confirmed hyperthyroidism with negative anti-TSHR antibodies. After maintaining methimazole therapy for 12 years, he underwent total thyroidectomy, and the weight of the resected thyroid tissue was 131 g. The subsequent histopathologic findings showed an encapsulated follicular adenoma, adenomatous goiter, and hyperplastic changes of the follicular epithelium without stromal lymphoid infiltration in normal parenchyma. Sequence analysis of the TSHR gene showed two compound heterozygous germline variants (R310H and D619G) on different alleles. The TSHRR310H was a nonfunctioning variant from the maternal allele. The TSHR-D619G was previously detected as a somatic mutation in patients with toxic adenomas. The TSHR-D619G mutation, which was absent in his parents, was a de novo mutation on the paternal allele.Conclusion: A TSHR germline mutation (D619G) was identified as the cause of sporadic nonautoimmune hyperthyroidism in a Japanese patient. This patient showed no obvious complications until the age of 13 years, but long-term follow-up with methimazole treatment showed further goiter and benign nodular formation.Abbreviations: MMI methimazole; TRAb thyrotropin-receptor antibody; TSHR thyrotropin receptor

Background: Some investigators reported that among athyreotic patients on levothyroxine (LT4) monotherapy following total thyroidectomy, the patients with normal serum thyrotropin (TSH) levels had mildly low serum free triiodothyronine (fT3) levels, whereas the patients with mildly suppressed serum TSH levels had normal serum fT3 levels, and the patients with strongly suppressed serum TSH had elevated serum fT3 levels. The objective of the present study was to clarify which of these three patient groups is closer to their preoperative euthyroid condition. Methods: A total of 133 consecutive euthyroid patients with papillary thyroid carcinoma who underwent a total thyroidectomy were prospectively studied. The patients' serum levels of lipoproteins, sex hormone-binding globulin, and bone metabolic markers measured preoperatively were compared with the levels measured at postoperative LT4 therapy 12 months after the thyroidectomy. Results: The postoperative serum sex hormone-binding globulin (p