The surgical treatment of acromegaly reduces mortality, however its impact on cardiovascular risk factors is unclear. This study was carried out to determine the changes in cardiovascular risk factors in patients with acromegaly who received trans-sphenoidal surgery. We recruited 127 patients with acromegaly who received trans-sphenoidal adenomectomy between August 2003 and May 2014 and follow-up for 12 months. Fasting GH and IGF-1 levels were evaluated every 3 months, and cardiovascular risk factors were assessed before and 12 months after surgery. The main outcomes were changes in cardiovascular risk factors after surgery. One year after trans-sphenoidal adenomectomy, 68 patients (53.5%) had a fasting GH level <2.0 ng/mL, IGF-1 was normalized in 74 patients (58.3%), and both fasting GH and IGF-1 were under control in 51 patients (40.2%). Levels of glycated hemoglobin (HbA1c) (8.57 ± 3.19 vs. 6.66 ± 0.90%, p = 0.001) and triglycerides (130.6 ± 61.5 vs. 108.0 ± 47.5 mg/dL, p = 0.027) were significantly decreased and serum creatinine was significantly increased (0.665 ± 0.222 vs. 0.754 ± 0.223 mg/dL, p = 0.001) after trans-sphenoidal adenomectomy. However, there were no significant changes in body weight, systolic blood pressure, diastolic blood pressure, total cholesterol, high-density lipoprotein cholesterol and cardiovascular risk score after trans-sphenoidal adenomectomy. In the patient with high cardiovascular risk before surgery, systolic blood pressure, total cholesterol, fasting glucose, triglycerides and high-density lipoprotein cholesterol improved after trans-sphenoidal adenomectomy. In this study, HbA1c and triglycerides were significantly decreased after trans-sphenoidal adenomectomy in the patients with acromegaly irrespective of endocrinological outcomes. The other traditional cardiovascular factors might be improved after trans-sphenoidal adenomectomy in the patients with a high cardiovascular risk.

Primary macronodular adrenal hyperplasia (PMAH) is a rare cause of Cushing syndrome (CS). In many cases of the PMAH family, variant in ARMC5, a putative tumor suppressor gene, are thought to induce the disease. The purpose of this study was to report a large Chinese family, in which a new germline heterozygous variant of ARMC5 (c.52C>T (p.Gln18X)) was found. A 64-year-old female patient (proband) was admitted to the hospital due to bilateral adrenal masses. In order to clarify the nature and function of adrenal masses, the proband completed several relevant screening tests of the adrenal function. After an ectopic receptor screening test and genetic testing, a new ARMC5 gene variant was found that might had led to the occurrence of PMAH. Because of its characteristic of autosomal dominant inheritance, the proband’s relatives were recommended to conduct the genetic test. We collected the family members’ genetic information, in which have 27 individuals, the proband tested the whole exon sequence, and 12 participants tested the Sanger sequence. Finally, 7 individuals were found have the same germline variant of ARMC5 as the proband. Subsequent computer analysis predicted that the variant significantly impaired protein function and resulted in inactivation of ARMC5. We found a new germline ARMC5 variant (c.52C>T (p.Gln18X)), which may induced PMAH. ARMC5 sequencing can improve the identification of clinical forms of PMAH and allow early diagnosis of the disease.

The adoptive transfer of ex vivo-expanded natural killer (NK) cells has recently been employed as an alternative cancer treatment in certain institutions. However, the safety profiles of this strategy remain uncharacterized. We evaluated three patients who exhibited elevated serum parathyroid hormone (PTH) levels without the relevant clinical manifestations and had a history of autologous NK cell therapy. The serum PTH concentration was measured using a second-generation PTH assay, and the serum thyroglobulin concentration was measured using a second-generation thyroglobulin assay. Subsequently, the PTH or thyroglobulin concentration obtained using heterophile-blocking tube (HBT) for a secondary confirmation assay was measured and compared with the result of the initial assay. The three patients had falsely elevated serum PTH and thyroglobulin levels owing to heterophile antibody interference associated with NK cell therapy that persisted for at least up to 12 months after the treatment and was confirmed by normalization of hormone levels after HBT treatment. We propose that certain types of mouse monoclonal antibodies used to stimulate NK cells can induce heterophile antibodies. Abnormal laboratory test results in individuals administered NK cell therapy without the relevant clinical manifestations must be examined in the context of heterophile antibody interference to avoid misdiagnosis and unnecessary testing.

After thyroidectomy in differentiated thyroid cancer (DTC), radioactive iodine (RAI) treatment is often used for remnant ablation. However, RAI treatment has been associated with bone marrow suppression, and leukopenia, anemia, and thrombocytopenia may occur after a single RAI administration. In this study, we examined the change in complete blood counts at 1 week after RAI administration; this is less well studied. A group of 189 DTC patients who received RAI treatment and underwent blood tests before and after treatment, were included. Peripheral blood counts at baseline were compared to those obtained at 1 week, 1–6 months, and 6–12 months after RAI treatment in order to test for bone marrow suppression. At 1 week after RAI treatment, there was a significant decrease in the white blood cell count (WBC, 5.8 ± 1.6 × 10⁹/L vs. 5.4 ± 1.5 × 10⁹/L, p < 0.001) and hemoglobin level (Hb, 13.5 ± 1.7 g/dL vs. 13.3 ± 1.4 g/dL, p = 0.001). The WBC decrease was mostly due to lymphocyte counts (2.2 ± 0.6 × 10⁹/L vs. 1.6 ± 0.5 × 10⁹/L, p < 0.001), with no decrease in the neutrophil count. Although not significantly changed at 1 week, platelets counts were altered within 6 months (265 ± 69 × 10⁹/L vs. 239 ± 53 × 10⁹/L, p < 0.001). The decline in the WBC count recovered within 6 months; lymphocyte and platelet counts recovered within 12 months. In conclusion, RAI treatment after a thyroidectomy was associated with a statistically significant but temporary decline in WBC counts and Hb levels at 1 week. Physicians treating DTC patients should not decrease usage of moderate dose RAI treatments.

An increase in arterial stiffness with advance aging is a risk for cardiovascular disease. Cardiovascular dysfunction is associated with the imbalance of adrenal cortex hormones, especially with the cortisol/dehydroepiandrosterone sulfate (DHEAs) ratio. However, the impact of aerobic fitness on arterial stiffness and cortisol/DHEAs ratio is unclear. The aim of this study was to investigate the relationship between aerobic fitness, arterial stiffness, and cortisol/DHEAs ratio. A total of 198 middle-aged and older adults (aged 50–79 years old) participated in this study. The aerobic fitness evaluated by peak oxygen consumption (VO_2peak), carotid-femoral pulse wave velocity (cfPWV) as an indicator of arterial stiffness, and serum cortisol and DHEAs and their ratio were measured. The subjects were divided into the lower (n = 100) and the higher (n = 98) aerobic fitness groups based on the median value of VO_2peak. There were no significant differences in serum cortisol and DHEAs concentration alone between the lower and higher fitness groups. However, the cortisol/DEHAs ratio and cfPWV in the higher fitness group was smaller than in the lower fitness group (p < 0.05). The cortisol/DHEAs ratio was significantly correlated with cfPWV (r = 0.159, p < 0.05). These findings suggest that the cortisol/DHEAs ratio is associated with aerobic fitness and arterial stiffness in middle-aged and older adults.

Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and invasive encapsulated follicular variant of papillary thyroid carcinoma (EFV-PTC) are indistinguishable preoperatively. CD26 expression in follicular tumor-uncertain malignant potential (FT-UMP) is reported to be clearly higher than in that without capsular invasion. To verify the diagnostic significance of CD26 immunostaining in EFV-PTC, we examined the expression pattern of CD26 in non-invasive EFV-PTC (NIFTP) and invasive EFV-PTC. We performed immunohistochemical analysis using CD26 antibody for 37 NIFTPs and 54 EFV-PTCs (34 minimally invasive EFV-PTCs and 20 widely invasive EFV-PTCs). Most NIFTP samples showed an apical membranous pattern or a cytoplasmic diffuse pattern of expression. Invasive EFV-PTCs more frequently showed a cytoplasmic dot-like pattern, and the labeling indices of tumor cells with cytoplasmic dot-like patterns were significantly higher than those in NIFTPs. The sizes of dots seen in NIFTPs (mean: 1.12 μm) were significantly smaller than in invasive EFV-PTCs (1.33 μm), minimally invasive EFV-PTC (1.27 μm), and widely invasive EFV-PTC (1.38 μm). We, therefore, conclude that cytoplasmic diffuse and/or cytoplasmic dot-like CD26 expression, particularly the larger CD26-positive dots, could be useful markers for capsular invasion in EFV-PTC. CD26 immunostaining, using cell blocks or cytological specimens, may preoperatively distinguish between NIFTP and invasive EFV-PTC.

The tyrosine kinase inhibitors (TKIs) sorafenib, lenvatinib, vandetanib, and cabozantinib are currently used for thyroid cancer treatment; however, the differences in their clinical efficacy and toxicity remain unclear. This meta-analysis assessed the efficacy and toxicity of these four TKIs based on 34 studies. The pooled incidence of partial response (PR), stable disease (SD), TKI-related adverse events (AEs), and pooled median progression-free survival (PFS) were calculated with 95% confidence intervals (CI). Complete response to TKIs was extremely rare (0.3%). The highest PR rate and longest PFS were observed for lenvatinib in differentiated thyroid cancer (69%, 95% CI: 57–81 and 19 months, 95% CI: 9–29, respectively) and vandetanib in medullary thyroid cancer (40%, 95% CI: 25–56 and 31 months, 95% CI: 19–43, respectively). Although the discontinuation rate due to AEs was similar for each TKI, there was a difference in the most frequently observed AE for each TKI (hand-foot syndrome for sorafenib, hypertension and proteinuria for lenvatinib, and QTc prolongation for vandetanib). The identified differences in the TKI efficacy and AE profiles may provide a better understanding of thyroid cancer treatment. Although TKIs are promising agents for thyroid cancer treatment, they are unlikely to lead to a cure. Thus, even in the TKI era, a multimodal treatment including surgery, radioiodine therapy, external beam radiotherapy, and TKIs is required to optimize patient chances of improved survival.

Hypophosphatasia (HPP; OMIM 241510, 241500, and 146300) is an inherited metabolic disease characterized by defects of bone and tooth mineralization, which is caused by loss-of-function mutations in the ALPL gene encoding tissue non-specific alkaline phosphatase (TNSALP). In the last three decades, several studies have focused on the genotype-phenotype correlation in hypophosphatasia (HPP). In particular, functional tests based on in vitro analysis for the residual enzymatic activities of mutations have revealed a clear but imperfect genotype-phenotype correlation, suggesting that multiple potential factors modulate the phenotype. One of the missense variants identified in the tissue non-specific alkaline phosphatase (ALPL) gene, c.787T>C, has been considered as a benign polymorphism in HPP; however, its pathogenicity and role in disease manifestation remain controversial. We here report our recent experience of three unrelated families harboring the c.787T>C variant, suggesting clinical implications regarding the controversial pathogenicity of c.787T>C. First, despite the lack of obvious clinical phenotypes, homozygous c.787T>C would decrease the serum level of ALP activity. Second, c.787T>C might deteriorate phenotypes of a patient harboring another ALPL variant, especially one that has thus far presumed to be benign, e.g., the c.1144G>A variant. These cases contribute to the recent advances in understanding HPP to facilitate clinical recognition of more subtle phenotypes, further providing insights into the pathogenesis of HPP.

The Fukushima Daiichi Nuclear Power Plant accident occurred on March 11 2011, following the Great East Japan Earthquake and tsunami. Radioactive materials, including I-131, were released into the environment after the accident. Shortly after, the prefectural government initiated the Fukushima Health Management Survey for monitoring the long-term health conditions of the residents of Fukushima Prefecture. In the survey, thyroid ultrasonography was scheduled for all people aged 18 years or younger who were living in Fukushima Prefecture at the time of disaster. The total number of examinees was approximately 370,000 in the Preliminary Baseline Survey (PBLS), and 380,000 in the first Full-scale Survey (FSS). First, thyroid ultrasonography was performed as the Primary Examination. When a thyroid nodule that meets the fine needle aspiration cytology (FNAC) guideline is detected, thyroid FNAC is performed. By the end of June 2017, the cytological specimens of 187 examinees had been interpreted as Malignant or Suspicious for Malignancy (SFM). In this article, the cytological results of whole categories are presented using the criteria of The Bethesda System for Reporting Thyroid Cytopathology. The total numbers of examinees with SFM or Malignant in PBLS and at the first FSS were 106 (62.0%) and 71 (38.0%), respectively. The data of the cytological results of SFM and Malignant were already reported. However, this is the first report of cytological data from categories other than SFM and Malignant. The results of the current study will contribute to future research into the thyroid conditions of children and adolescents.

Werner syndrome (WS), a type of progeria, is a hereditary condition caused by a mutation in the WRN gene. A 62-year-old Japanese woman was diagnosed with WS at the age of 32 and has been visiting the hospital for follow-up since the last 30 years. The patient developed diabetes at the age of 46, and at the age of 60, her body mass index increased from 20.1 to 22.7 kg/m² owing to her unhealthy eating habits; her visceral fat area at the age of 61 was 233 cm². With dietary control, her body weight, including the visceral fat and subcutaneous fat, decreased at the age of 62, and her insulin secretion, obesity, and fatty liver improved. We conducted the oral glucose challenge test four times, including at the prediabetic stage, to evaluate the insulin-secretion ability. The patient’s insulin resistance gradually increased for more than 14 years, and her insulin secretion ability began to decrease 14 years after her diabetes diagnosis. Despite a remarkable decrease in body weight and fat mass with dietary management, the psoas muscle index did not decrease significantly in proportion to the body weight or fat mass. However, muscle mass monitoring is important for preventing the progression of sarcopenia. Hence, gradual reduction of visceral fat and weight by dietary management may be useful in treating diabetes in patients with WS, particularly in those whose visceral fat is significantly increased.

Amiodarone is an effective antiarrhythmic drug. However, it is associated with changes in thyroid function in euthyroid patients due to its high iodine content and intrinsic drug effects. Studies have been conducted in iodine-deficient and iodine-sufficient countries; however, data from countries with excessive iodine intake are lacking. Thus, this study aimed to evaluate the effect of long-term amiodarone treatment on thyroid function in euthyroid Japanese patients. Japanese adults aged ≥18 years who were treated with amiodarone for at least 90 consecutive days were included in this retrospective chart review. Patients with abnormal thyroid function test results at baseline were excluded. Serial changes in thyroid function tests at baseline and at days 30, 90, 180, 270, and 360 were analyzed using a mixed-effects model for repeated measures. In total, 46 patients with a mean age of 63.7 years were evaluated. The mean TSH level significantly increased from 1.62 μIU/mL at baseline to 3.43, 2.75, 2.84, 2.78, and 2.65 μIU/mL at days 30, 90, 180, 270, and 360, respectively. The mean free T₄ level significantly increased from 1.3 ng/dL at baseline to 1.4, 1.5, 1.5, 1.5, and 1.5 ng/dL at days 30, 90, 180, 270, and 360, respectively. The mean free T₃ level significantly decreased from 2.8 pg/mL at baseline to 2.4, 2.3, 2.3, 2.4, and 2.4 pg/mL at days 30, 90, 180, 270, and 360, respectively. In conclusion, significant changes in thyroid function persisted not only in the acute phase but also in the chronic phase of long-term amiodarone treatment.