Endocrine journal最新文献

We investigated the association between a 500 MBq dose of radioactive iodine treatment (RAIT) and both thyroid nodule volume and thyroid function in patients with a single autonomous functioning thyroid nodule (AFTN). We retrospectively studied 201 patients with an AFTN who received RAIT at a dose of 500 MBq and were followed up for more than 2 years. Thyroid function at diagnosis, thyroid antibody positivity, treatment with antithyroid drugs before RAIT, cystic components of the nodule, and ¹³¹I uptake outside the nodule were assessed. Nodule enlargement was observed in 18 patients (9%), persistent hyperthyroidism in 13 patients (6.5%), and hypothyroidism in 45 patients (22.3%). Nodule volume before RAIT was significantly larger in the nodule enlargement group compared to the non-enlargement group. The risk factors for persistent hyperthyroidism were larger nodule volume and absence of a cystic component in multivariate analysis. The cutoff nodule volume before RAIT for predicting nodule enlargement was 15.5 mL, and for predicting persistent hyperthyroidism was 16.6 mL. Nodule volume decreased to 47% in the first year and continued to gradually decrease thereafter. This study provided long-term outcome data regarding nodule volume change and thyroid function in AFTN patients following single fixed-dose RAIT, and it identified risk factors for nodule enlargement and persistent hyperthyroidism after RAIT. Nodule volume before treatment was a good predictor of treatment response.

Pasireotide (PAS), a multireceptor somatostatin analog, has been demonstrated to effectively control hormone levels, including those of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), in patients with acromegaly. However, it induces hyperglycemia by inhibiting insulin secretion via somatostatin receptor 5 (SSTR5). Despite the extensive literature on the occurrence of PAS-induced hyperglycemia, there is still no consensus on the optimal first-line treatment for this complication. Herein, we present two cases of acromegaly treated with PAS and highlight its short- and long-term effects on glucose metabolism. In the first case, postprandial hyperglycemia manifested rapidly following the commencement of PAS treatment and was effectively managed with dulaglutide under continuous glucose monitoring (CGM). In the second case, long-term PAS therapy resulted in a dose-dependent glycemic response that was controlled by different GLP-1 receptor agonists (GLP-1RAs), including semaglutide. CGM facilitated the early detection of significant glycemic fluctuations, underscoring the necessity for close monitoring in patients receiving PAS therapy. These cases demonstrate the efficacy of GLP-1RAs in managing PAS-induced hyperglycemia and highlights the value of CGM in early detection and intervention. Our findings suggest that GLP-1RAs, particularly semaglutide, are a valuable treatment option for this condition. Further research is needed to determine the optimal treatment strategy, particularly in East Asian populations, and to establish a clear consensus on the first-line therapy for PAS-induced hyperglycemia.

Adult growth hormone deficiency (AGHD) is often accompanied with metabolic dysfunction-associated steatotic liver disease (MASLD). Although some studies reported that MASLD is ameliorated by growth hormone replacement therapy (GHRT), the characteristics of AGHD that are associated with an improvement of hepatic steatosis by GHRT remain unknown. We aimed to investigate whether GHRT affects hepatic lipid accumulation as well as biochemical parameters, and investigated the association between these parameters (UMIN000044989). Thirty people with AGHD were recruited, and assigned to either the GHRT group or the non-GHRT group. Serum laboratory data were analyzed before and after GHRT. Hepatic lipid content was evaluated using magnetic resonance imaging-proton density fat fraction (MRI-PDFF). Correlations between MRI-PDFF and other clinical parameters were investigated. Twenty-nine people completed this study (19 in the GHRT group and 10 in the non-GHRT group). In the GHRT group, significant decreases in MRI-PDFF and serum levels of aspartate aminotransferase, alanine aminotransferase, and γ-glutamyl transpeptidase were observed after the treatment. The decrease in MRI-PDFF levels after GHRT significantly correlated with initial MRI-PDFF, triglyceride (TG), lactate dehydrogenase, and ALT levels, and age. Multiple regression analysis demonstrated that younger age and high serum TG levels were independent predictors of a decrease in MRI-PDFF levels. GHRT in people with AGHD significantly reduced lipid accumulation in the liver on MRI, and improved serum liver parameters. Age and serum TG levels were found to be associated with the effectiveness of GHRT.

Nerve aberrations and vascular lesions in the distal lower limbs are the etiological factors for diabetic foot ulcers (DFUs). This study aimed to understand the regulatory mechanism of angiogenesis in patients with DFU by examining lncRNA, as well as to explore effective targets for diagnosing and treating DFU. The serum levels of A1BG-AS1 and miR-214-3p and the predictive power of A1BG-AS1 for DFU were determined by quantitative PCR and ROC analysis. The correlation of A1BG-AS1 with clinical characteristics was examined using chi-square tests. The risk factors for DFU in patients with type 2 diabetes mellitus (T2DM) were identified using the logistic regression model. Furthermore, the binding sites of A1BG-AS1 and miR-214-3p were determined. Next, A1BG-AS1 interference plasmid and miR-214-3p inhibitor were co-transfected into high glucose-induced cells to investigate their effects on the expression of angiogenesis-related genes and cell proliferation. The A1BG-AS1 levels were upregulated, whereas the miR-214-3p levels were downregulated in patients with DFU. The upregulation of A1BG-AS1 was significantly associated with both blood glucose levels and ulcer grades. A1BG-AS1 served as a crucial biomarker for diagnosing DFU and evaluating the risk of DFU occurrence in patients with T2DM. Co-transfection experiments revealed that the inhibition of miR-214-3p effectively recovered the suppressive effects of A1BG-AS1 on angiogenesis-related gene expression, endothelial cell differentiation, and proliferation. The sponging effect of A1BG-AS1 on miR-214-3p impaired angiogenesis in patients with DFU. Thus, A1BG-AS1 is a potential therapeutic target for DFU.

Nerve conduction studies (NCS) are the standard method for diagnosing diabetic polyneuropathy. Because a clear association between handgrip strength and diabetic neuropathy can serve as a screening tool, the present study evaluated the association between handgrip strength and NCS and diabetes-related complications. A total of 436 patients with type 2 diabetes (T2D) who were admitted to our hospital between April 1, 2018 and March 31, 2023, and evaluated using Baba's diabetic neuropathy classification (BDC) were included. The participants were grouped by sex using the grip strength tertile method to assess correlations with the prevalence of diabetic microvascular complications in the high-handgrip group (HG), middle-handgrip group (MG), and low-handgrip group (LG). The percentage of BDC-0 was 65% in the HG, 54% in the MG, and 36% in the LG. Furthermore, none of the participants in the HG had BDC-3/4, whereas 4% in the MG and 15% in the LG had BDC-3/4. The morbidity progression of diabetic neuropathy was seen in the order of LG, MG, and HG (p < 0.001). Patients with T2D and advanced diabetic neuropathy had decreased handgrip strength. Early evaluation of BDC and other NCS should be considered if decreased handgrip strength is evident.

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.

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.

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.

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.

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.