Almost a century has passed since Plummer reported the efficacy of short-term preoperative inorganic iodine therapy for Graves’ disease in the 1920s. Since there were concerns about the escape phenomenon and exacerbation with inorganic iodine, antithyroid drugs became the mainstay of pharmacotherapy for Graves’ disease following their development in the 1940s. With regard to long-term inorganic iodine monotherapy, Trousseau reported a case in the 1860s, and several subsequent reports suggested its efficacy. Around 1930, Thompson et al. published a number of papers and concluded that long-term inorganic iodine monotherapy was useful if limited to mild cases under careful follow-up. From Japan, in 1970, Nagataki et al. reported that, of 12 patients treated with inorganic iodine, three remained eumetabolic for more than two years. Since 2014, some reports have also been published from Japan. A summary of these recent reports is given below. The starting dose of potassium iodide is around 50 mg/day, and candidate responders have mild disease, with FT4 <2.76 ng/dL (35.5 pmol/L), a small goiter, and are female and elderly. Response rates are relatively high, at 60–80%, and the remission rate is about 40%. In cases of insufficient response, changing therapy should be considered. Inorganic iodine can be used as a possible alternative if the patient experiences adverse events with antithyroid drugs and/or prefers conservative treatments, with an understanding of their efficacy and limitations. These recent reports have been published from Japan, where iodine is sufficient, and the dose of inorganic iodine is empirical and requires further study.

The mean height is taller in males than in females, except for early teens. In this regard, previous studies have revealed that (1) distribution of the mean adult heights in subjects with disorders accompanied by discordance between sex chromosome complement and bioactive sex steroids and in control subjects (the British height standards) indicates that, of the ~12.5 cm of sex difference in the mean adult height, ~9 cm is accounted for by the difference in the sex chromosome complement and the remaining ~3.5 cm is explained by the dimorphism in sex steroids (primarily due to the growth-promoting effect of gonadal androgens); (2) according to the infancy-childhood-puberty growth model, the sex difference in the childhood growth function produces height differences of ~1 cm in childhood and 8–10 cm at 18–20 years of age, whereas the sex difference in the pubertal growth function yields height difference of ~4.5 cm at 18–20 years of age; and (3) SHOX expression and methylation analyses using knee cartilage tissues and cultured chondrocytes have shown lower SHOX expression levels in female samples than in male samples and methylation patterns consistent with partial spreading of X-inactivation affecting SHOX in female samples. These findings suggest that small but persistent sex difference in SHOX expression dosage leads to the variation in the sex steroid independent childhood growth function, thereby yielding the sex difference in height which remains small in childhood but becomes obvious in adulthood.

Non-high-density lipoprotein cholesterol (non-HDL), a more readily available and reliable lipid parameter, is unclear in its association with type 2 diabetes (T2D). Previous studies assessing the relationship between non-HDL and T2D risk remains inconsistent results. We performed a meta-analysis to systematically evaluate this association. The PubMed, EMBASE, Medline, Web of Science, and Cochrane Library databases were systematically searched to find articles on “non-HDL” and “T2D” from inception to December 6, 2023. A random-effects model was used to calculate the effect estimates and 95% confidence intervals. Subgroup analyses and univariate Meta-regression were performed to explore sources of heterogeneity. The main exposure and outcome were non-HDL and T2D, respectively, in the general population. A total of 8 studies included 251,672 participants who met the inclusion criteria for this study. Meta-analysis showed that higher non-HDL increased the risk of T2D compared with the lower non-HDL group (total effect size: 1.16; 95% CI 1.079–1.251, p < 0.001). Subgroup analyses and Meta-regression of the association between non-HDL and T2D were not affected by region, proportion of men, sample size, or adjustment for confounders (including BMI, hypertension, waist circumference, and family history of diabetes). Higher non-HDL may be associated with an increased risk of T2D. Large prospective cohort studies are needed to validate these findings, and further studies are required in order to elucidate the underlying pathophysiologic mechanisms underlying the association between non-HDL and T2D.

Significant overlap in the epidemiology and coinfection of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) has been identified, which accelerates the development of severe liver cirrhosis and hepatocellular carcinoma worldwide. Interferon-α (IFN-α), a cytokine with antiviral properties, exerts profound physiological effects on innate immunity by regulating interferon-stimulated genes (ISGs) within cells. However, the underlying mechanism of IFN-α in hepatic inflammation remains to be fully elucidated. Here, we utilized LO2 cells treated with the recombinant IFN-α protein and conducted microRNA (miR) sequencing. MiR-122-3p and miR-122-5p_R+1 were the most enriched miRNAs involved in the pathogenesis of IFN-α-induced inflammatory responses and were significantly downregulated by IFN-α treatment. Furthermore, we identified interferon induced protein with tetratricopeptide repeats 1 (IFIT1) as a potential target gene of miR-122. IFN-α markedly increased the expression of proinflammatory cytokines and fibrogenic genes but decreased the mRNA expression of ISGs. Additionally, IFN-α significantly activated the NF-κB p-p65, MAPK p-p38, and Jak/STAT pathways to trigger inflammation. Importantly, supplementation with a miR-122 mimic significantly alleviated IFN-α-induced inflammation and induced IFIT1 expression in LO2 cells. Conversely, the suppression of miR-122 markedly exacerbated the inflammatory response triggered by IFN-α. Furthermore, silencing IFIT1 via an siRNA elicited an inflammatory response, whereas IFIT1 overexpression ameliorated hepatic inflammation and fibrosis in a manner comparable to that induced by IFN-α treatment. Taken together, our findings suggest that miR-122 and its target, IFIT1, reciprocally regulate the inflammatory response associated with IFN through the Jak/STAT pathway.

We and other investigators reported that mild TSH suppression with levothyroxine (LT₄) was needed to achieve normal free triiodothyronine (FT₃) levels and metabolic euthyroid state in athyreotic patients. Consequently, management methods based on thyroid tissue volume have been implemented for patients receiving LT₄ at the Kuma Hospital. This retrospective study examined the composition of the thyroid hormone measurement items (serum-free thyroxine [FT₄], FT₃, and FT₄ + FT₃) in patients receiving LT₄ monotherapy. According to the etiology of hypothyroidism, 36% of the 25,523 patients included in this study underwent total thyroidectomy (TT). Thirteen percent and 14% had undergone ¹³¹I treatment for hyperthyroidism (RIT) and partial thyroidectomy (PT), respectively. Moreover, 37% of patients had received non-invasive treatment (NIT). The proportion of patients who underwent only FT₃ measurements was higher (TT, 93%; RIT, 61%) in the first two groups, whereas the proportion of patients who underwent only FT₄ measurements was higher (PT, 50%; NIT, 65%) in the remaining two groups. Only FT₃ measurements were performed in 58% of patients. Only FT₄ measurements were performed in 34% of patients. The serum TSH levels were suppressed in nearly half of the patients (46%). Thus, FT₃ was the major thyroid hormone measured in patients receiving LT₄ treatment, and the serum TSH levels were suppressed in nearly half of the patients. This may be attributed to the management guidelines at our hospital, a specialized facility for thyroid disease, wherein half of the patients present are athyreotic or have atrophic thyroid glands after TT or RIT.

Circular RNAs (circRNAs) play an important role in regulating inflammation and oxidative stress during the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD); however, the underlying mechanism is unclear. This study aimed to determine the role of mmu_circ_0009303 in MASLD. We used a bioinformatics approach to identify potential targets and established an in vitro model of MASLD. Oil red O staining, cell transfection and dual-luciferase reporter assay were used to determine the role of mmu_circ_0009303. The results indicated that the mmu_circ_0009303 expression was significantly increased in the MASLD model both in vitro and in vivo and was associated with oxidative stress levels and inflammation. Moreover, bioinformatics analyses revealed that miRNA-182-5p and Foxo3 are targets of mmu_circ_0009303 and miRNA-182-5p, respectively. In the in vitro MASLD model, mmu_circ_0009303 promoted fat deposition in NCTC1469 cells, which was induced by free fatty acid (FFA) through the regulation of miRNA-182-5p/Foxo3. The expression of miRNA-182-5p and Forkhead box O3 (Foxo3) was associated with mmu_circ_0009303 expression in the liver of mice with MASLD, which was induced by a high-fat diet. Furthermore, mmu_circ_0009303 may be involved in regulating the expression of lipid metabolism-related regulatory proteins, such as CPT1A, SLC27A4, ACBD3, SREBP1, FAS, PPARα, and PPARγ. Taken together, mmu_circ_0009303 promotes oxidative stress, inflammation, and excessive fat accumulation in NCTC1469 cells induced by FFA through the regulation of miRNA-182-5p/Foxo3 and lipid metabolism-related regulatory proteins. These findings provide a potential target for the treatment of MASLD.

There are differences in the responsiveness to differential diagnostic tests for Cushing’s disease (CD), corticotroph tumor size, and the somatostatin receptor (SSTR) 5 expression in corticotroph tumors between CD patients. The differences in SSTR5 expression are particularly significant for identifying therapeutic targets for CD. However, prospective predictors of SSTR5 expression remain unclear. Thus, our objective was to elucidate the relationships among these clinical characteristics of CD, including SSTR5 expression. In 27 hospitalized patients with CD at Osaka University Hospital, Osaka, Japan, associations between corticotroph tumor diameter, the response of ACTH and cortisol to differential diagnostic tests for CD (CRH, desmopressin [DDAVP], and high-dose dexamethasone suppression test [HDDST]), the ACTH/cortisol index, and the SSTR5 immunoreactive score were retrospectively investigated. The response to differential diagnostic tests, ACTH/cortisol index, tumor diameter, and SSTR5 expression were significantly related (vs. tumor diameter [CRH: r = –0.54; DDAVP: r = –0.54; HDDST r = –0.67; ACTH/cortisol index: r = 0.76; SSTR5: r = –0.61], vs. CRH [DDAVP: r = 0.63, HDDST: r = 0.72, ACTH/cortisol index: r = –0.45; SSTR5: r = 0.56], vs. DDAVP [HDDST: r = 0.66; ACTH/cortisol index: r = –0.46; SSTR5: r = 0.76], vs. HDDST [ACTH/cortisol index: r = –0.62; SSTR5: r = 0.77], ACTH/cortisol index vs. SSTR5: r = –0.67). The areas under the receiver operating characteristic curve for the prediction of high SSTR5 expression via the CRH test, DDAVP test, HDDST, ACTH/cortisol index, and tumor diameter were 0.79, 0.87, 0.80, 0.71, and 0.71, respectively. Tests for differential diagnosis of CD, the ACTH/cortisol index, and the corticotroph tumor diameter have the potential for identifying SSTR5 expression in corticotroph tumors. These parameters may reflect the biological characteristics of corticotroph tumors.

It has been reported that Graves’ disease (GD) sometimes improves spontaneously during pregnancy, although exacerbation of GD during postpartum period or relapse of hyperthyroidism caused by GD might occur. This study aimed to investigate the incidence of postpartum diagnosis of thyroid eye disease (TED) in relation to thyroid dysfunction. This retrospective cross-sectional study enrolled 11,104 deliveries from the patients with GD between January 2004 and August 2022. Within the 12-month postpartum period, 72 patients (0.65%) were diagnosed with TED. The thyroid function of the 72 patients comprised 9 remission, 13 continued antithyroid medicine, and 50 thyroid dysfunction; 30 newly diagnosed GD, 1 hypothyroidism, and 19 relapse/recurrence of GD. In the 49 patients with thyroid dysfunction, no difference was observed in the median values of thyroid-stimulating hormone (TSH) receptor antibody (TRAb) and TSH receptor stimulating antibody between the TED diagnosis and the development of hyperthyroidism. However, when the patients were classified into the newly developed GD and relapse/recurrence of GD groups, the difference became significant and the TRAb level was high in the newly developed GD (16.1 vs. 5.0 IU/L, p < 0.0001, and 15.0 vs. 6.0 IU/L, p = 0.0003). Thyroid dysfunction preceded TED diagnosis in more than half of the patients and the median time for each event was 6.5 vs. 8.1 months. The active phase TED was observed in 8 of the 72 patients. Of the 72 patients newly diagnosed with TED in postpartum, two-thirds were accompanied by thyroid dysfunction and 8 of them were in active phase.

A 55-year-old woman transitioned from hypothyroidism to Graves’ disease (GD) and then developed thyroid eye disease (TED) with proptosis and diplopia. After three cycles of daily methylprednisolone pulse therapy, her condition progressed to dysthyroid optic neuropathy with decreased visual acuity in both eyes. Her clinical activity score (CAS) was 7 points. Orbital magnetic resonance imaging (MRI) showed that the enlarged extraocular muscles were compressing the optic nerve in the area of the cones. Although her visual acuity recovered during two further cycles of daily pulse therapy, disease activity persisted for 4 years. TED exacerbated five times. Each time, the patient received weekly pulse therapy with no adverse reactions until her ophthalmopathy was relieved. The total cumulative dose of methylprednisolone was 59.5 g. Thyroid-stimulating antibody (TSAb) was positive from the time of hypothyroidism onset and became strongly positive with the onset of GD and the progress of TED. In addition, MRI was useful for the evaluation of the pathophysiology of ophthalmopathy. This case report suggests that careful monitoring by both endocrinologists and ophthalmologists using CAS, ophthalmological assessments, TSAb measurement, and orbital MRI are useful for making treatment decisions for TED.