Endocrine journal最新文献

Urinary calcium excretion increases in patients with primary aldosteronism (PA) and is associated with higher prevalence of renal stones formations. However, it remains unclear whether the prevalence of urinary stones is higher in patients with PA than in those with nonfunctioning adrenal tumors (NF). We aimed to investigate whether the prevalence of urinary stones is higher in patients with PA than in those without PA. The study was conducted between April 2006 and March 2021. We enrolled 140 PA and 144 NF patients. Urinary stones and renal calcifications were evaluated through patient history or CT findings. Serum and urinary parameters, presence of urinary stones and/or calcifications, were evaluated in both groups. Logistic regression analyses were performed, adjusting for relevant variables. Compared to the NF group, the PA group was younger, and displayed significantly higher blood pressure, aldosterone-rennin ratio, eGFR, serum Na, urinary Ca excretion, and intact PTH levels. In contrast, serum K, Ca and creatinine levels were lower in PA group. PA patients also demonstrated a lower prevalence of diabetes, smaller adrenal tumor size, and a lower percentage of smokers compared to the NF group. Urinary stones and renal calcifications were significantly more frequent in the PA group. Logistic regression confirmed PA as an independent risk factor for urinary stones, regardless of age, sex, BMI, eGFR, serum and urinary calcium, and intact PTH. PA is an independent risk factor for urinary stones and renal calcifications.

Steroidogenesis inhibitors such as metyrapone and osilodrostat, target 11β-hydroxylase to inhibit cortisol synthesis, are used in inoperable or recurrent Cushing disease. While osilodrostat has been reported to be more effective at lower doses than metyrapone, there are only a few reports describing the difference between osilodrostat and metyrapone in clinical practice. In this study, we evaluated the changes in steroid hormone profiles and clinical outcomes in seven Cushing disease patients switched from metyrapone to osilodrostat after incomplete remission post-transsphenoidal sinus surgery. Three of the seven patients were using trilostane, which was discontinued at the same time as metyrapone. Steroid hormone concentrations, including cortisol, progesterone (Prog), pregnenolone (Preg), deoxycorticosterone, corticosterone, 17-hydroxyprogesterone (17Prog), 17-hydroxypregnenolone (17Preg), and 11-deoxycortisol, were measured using high-performance liquid chromatography-mass spectrometry. No adverse events occurred after switching to osilodrostat. Potassium and ACTH levels increased significantly, and dehydroepiandrosterone sulfate and testosterone levels decreased significantly. Cortisol levels did not change significantly, whereas the ratios reflecting CYP17A1 activity (17Preg/Preg and 17Prog/Prog) decreased significantly, suggesting superior inhibition of CYP17A1 with osilodrostat. Clinical improvements included reduced antihypertensive medication requirements, decreased masculinization, and resolved gastric discomfort. Different inhibition patterns of the steroid synthetic enzymes may explain the observed clinical outcomes between these drugs. These data suggest that in patients with Cushing disease receiving metyrapone, switching to osilodrostat may benefit cases with inadequate disease control and complications including hypertension, manifestation of masculinization, and gastric discomfort.

Lenvatinib is approved for the first-line treatment for radioiodine-refractory differentiated thyroid cancer (RR-DTC) at a starting dose of 24 mg/day, but its high toxicity often necessitates dose reductions and interruptions. To clarify the efficacy and safety of the reduced dose-initiation of lenvatinib, especially for smaller-build and/or frail Asians, we retrospectively examined outcomes of 43 Japanese individuals with RR-DTC who were treated with lenvatinib, focusing on the initial dose. Twenty-three patients initiated lenvatinib at a full-dose (24 mg/day) and 20 patients initiated at a reduced-dose (≤14 mg/day). In the full dose-initiation group, 14 of 23 (60.8%) patients required discontinuation of lenvatinib within ~30 days due to adverse effects, which was significantly higher rate compared to that (25.0%) of the reduced dose-initiation group (p = 0.018), and 5 patients of the full dose-initiation group did not resume treatment. Compared to the full dose-initiation group, the reduced dose-initiation group were older (nonsignificant) and had significantly lower body weights, lower overall daily dose exposure, and a lower frequency of adverse events (≥grade 2) but a comparable dose interruption rate and daily dose exposure per kg during overall observation period. In multivariate analyses for progression-free survival and overall survival, malignant pleural effusion and symptomatic metastases but not the starting dose of lenvatinib were significantly associated with worse outcomes. Initiating lenvatinib at a reduced dose based on patients' physical status may be an option, with not only lower adverse events but also efficacy comparable to that of the full dose.

The ectopic intrathyroidal thymus (EIT) is located anywhere in the thyroid gland along the developmental pathway of thymic descent due to thymic migration during embryogenesis. Ultrasonographic findings of papillary thyroid carcinoma (PTC) resemble those of EIT, which is frequently found in children. We comprehensively evaluated the clinical factors associated with EIT to understand its physiological implications and to explore helpful information for clinical discrimination between EIT and PTC. Approximately 320,000 datasets of thyroid ultrasound examinations conducted in the Fukushima Health Management Survey were systematically analyzed. Trend analyses were performed following stratification into groups of the age-sex-adjusted standard deviation score (SDS) for body mass index (BMI-SDS) and body surface area-sex-adjusted SDS for both the width and thickness of the area (BWTAR) as an indicator of thyroid volume (BWTAR-SDS). The prevalence of EIT was 3.2% in the study. Compared with negative EIT, the age- and sex-adjusted odds ratios (95% confidence intervals) for the BMI-SDS, BWTAR-SDS, and presence of diffuse goiter, cysts, and nodules were 0.919 (0.901-0.939), 0.976 (0.957-0.996), 0.821 (0.602-1.121), 0.892 (0.853-0.932), and 1.602 (1.302-1.972), respectively. EIT was not associated with the presence of diffuse goiter but was independently associated with male sex, young age, small thyroid volume, low BMI, absence of cysts, and presence of nodules. The series of clinical factors related to EIT shown in the study might provide complementary information in addition to ultrasonographic findings in cases with asymptomatic thyroid nodules resembling PTC found in young patients.

Proptosis, a key clinical manifestation of thyroid eye disease (TED), serves as an objective indicator of this disease's severity. Although body compositions and the prevalences of myopia and tobacco smoking have changed in Japan, no updated reference exophthalmometry values have been reported since the 1980s. To determine normal values for exophthalmometry in a contemporary Japanese general population and identify factors associated with exophthalmos in people with/without Graves' disease (GD), we conducted a cross-sectional study using a general population cohort and a GD cohort, from October 2023 to October 2024. We used a Hertel exophthalmometer to measure the exophthalmometry values in both cohorts, and we obtained clinical data from medical records and/or questionnaires. Eighty-six patients with GD and 502 general population controls were included. The GD cohort's mean exophthalmometry value (17.0 ± 3.3 mm) was significantly higher than the general population (15.6 ± 2.8 mm), which was larger than the upper limit of the normal references (15.0 mm) defined by the Japan Thyroid Association based on a 1970s' report. Multiple regression analyses revealed that age, BMI, myopia, and dyslipidemia remained independently associated with exophthalmometry values in the general population cohort, whereas height, smoking, and anti-thyroglobulin autoantibody negativity were associated with the GD cohort's exophthalmometry values. Our findings suggest a possible increase in mean exophthalmometry values in the contemporary Japanese general population. They highlight the need to update normative exophthalmometry values, accounting for body-composition including metabolic profiles and myopia, which could lead to accurate assessments of proptosis severity and appropriate therapeutic strategies for patients with TED. Clinical Trials Registry (CTR) registration: UMIN-CTR no. 000051753.

X-linked adrenal hypoplasia congenita (AHC) is a rare, life-threatening disorder caused by pathogenic variants in NR0B1 (DAX1), leading to adrenal insufficiency and hypogonadotropic hypogonadism. AHC is often associated with Xp21 contiguous gene deletion syndrome, which involves the deletion of multiple genes, including NR0B1, GK, DMD, and IL1RAPL1, resulting in a spectrum of phenotypic manifestations, such as glycerol kinase deficiency (GKD), Duchenne muscular dystrophy (DMD), and neurodevelopmental disorders. We report two cases of AHC with neurodevelopmental delays due to contiguous Xp21 deletions involving NR0B1 and IL1RAPL1, each diagnosed through distinct clinical pathways. Case 1 involved a neonate with adrenal insufficiency, persistent hyperCKemia, and excessive urinary glycerol excretion, leading to a diagnosis of Xp21 deletion syndrome with DMD and GKD. The patient's sister, an asymptomatic carrier, exhibited elevated CK levels and mild developmental delays. Array comparative genomic hybridization identified a novel complex structural variation, including duplication-deletion-duplication rearrangement, which may have modified clinical manifestations. Case 2 involved a 10-year-old boy with AHC and developmental delay that was initially considered a consequence of adrenal crises. Genetic analysis confirmed an Xp21 deletion, including IL1RAPL1, implicating it in his intellectual disability. A literature review reveals that Xp21 deletions involving IL1RAPL1 are strongly associated with neurodevelopmental delays, suggesting a distinct phenotype within Xp21 deletion syndromes. Early genetic diagnosis via chromosomal microarray analysis facilitates precise delineation of deletion regions, aiding in clinical management, genetic counseling, and early intervention strategies. Further studies are needed to elucidate genotype-phenotype correlations in Xp21 deletion syndromes and optimize individualized medical care.

The physical and/or electrical properties of the peptide-binding pockets of Human Leukocyte Antigen (HLA) class II molecules vary depending on their amino acid sequence, influencing peptide-binding affinity. Previous studies have reported associations between HLA-DRB1 amino acid polymorphisms and susceptibility to Graves' disease (GD) and Hashimoto's disease (HD). We hypothesized that polymorphisms in the peptide-binding region of HLA-DRB1 contribute to disease development and prognosis. This study investigated associations between HLA-DRB1 amino acid polymorphisms and both the development and prognosis of autoimmune thyroid diseases. We analyzed HLA-DRB1 sequences in 136 GD patients, 132 HD patients, and 109 healthy Japanese controls. HLA-DRB1 typing was performed using polymerase chain reaction (PCR) with sequence-specific primers (PCR-SSP) and PCR with sequence-based typing (PCR-SBT). Glu9, His13, and Leu67 were more frequent in intractable GD than in GD remission or controls. Lys9, Phe13, Tyr26, and Val57 were associated with susceptibility to HD, whereas Trp9, Ser37, Phe47, and Asp57 were associated with resistance to HD. Structural modeling revealed that GD-susceptible pockets showed a positive electrostatic potential in pocket 7, while GD-resistant pockets showed a negative electrostatic potential. In pockets 4, 7, and 9, HD-susceptible pockets showed a positive electrostatic potential, whereas HD-resistant pockets showed neutral or negative electrostatic potential. Therefore, specific amino acids in pockets 4, 7, and 9 of HLA-DRB1 are associated with the development and prognosis of GD and HD in the Japanese population.

Thyroid hormone (TH) prescribing practices, particularly on hypothyroid and euthyroid patients, were compared between Japan Thyroid Association (JTA)-certified thyroid specialists and non-certified members. A nationwide questionnaire survey (Treatment of Hypothyroidism in Europe by Specialists: An International Survey) was conducted among all 2,938 JTA members, including 874 certified specialists and 2,064 non-certified members, to assess self-reported TH prescription choices in various clinical scenarios. Responses from certified specialists and non-certified members were statistically compared. A total of 207 certified specialists (23.7%) and 129 non-certified members (6.3%) responded and completed the questionnaire. Although all certified specialists and non-certified members selected levothyroxine (LT4) as first-line therapy for hypothyroidism, certified specialists more often used liothyronine (LT3) plus LT4 combination therapy than non-certified members (28% vs. 12%, p < 0.001), particularly for LT4-treated patients with persistent hypothyroid-like symptoms (9% vs. 2%, p = 0.02). For euthyroid individuals, 71% of certified specialists and 60% of non-certified members considered TH treatment (p = 0.043). Non-certified members who see >100 hypothyroid patients per year were more inclined to use combination therapy for hypothyroid patients and TH for euthyroid patients than those of ≤100 patients (p < 0.049 and 0.001, respectively). In conclusion, JTA-certified thyroid specialists and non-certified members exhibit distinct TH prescribing patterns. Certified specialists are more open to combination therapy and treating selected euthyroid patients, whereas non-certified members favor guideline-based LT4 monotherapy. These differences underscore the impact of specialization on clinical practice and suggest a need for updated guidelines and targeted education to rationalize thyroid care.

To-and-fro puncture and to-and-fro whirling puncture are two common specimen acquisition methods of thyroid fine-needle capillary (FNC) biopsy. While both techniques are widely used, a direct comparison of their outcomes has been lacking. This prospective study enrolled 110 patients with 138 thyroid nodules. Each nodule underwent four punctures: two using the to-and-fro technique and two using the to-and-fro whirling technique. The primary outcome was specimen adequacy, while secondary outcomes included malignancy diagnosis rate, sensitivity, diagnostic accuracy, and procedure time. No significant difference was found in specimen adequacy between the two techniques (90.58% vs. 89.86%, p = 0.839). However, the to-and-fro technique demonstrated superior performance in terms of malignancy diagnosis rate (31.88% vs. 20.29%, p = 0.028), sensitivity (100.00% vs. 81.82%, p = 0.006), and diagnostic accuracy (97.78% vs. 83.33%, p = 0.041). Additionally, the to-and-fro technique required less procedure time (18.38 ± 8.34 seconds vs. 20.84 ± 10.54 seconds, p < 0.001). In conclusion, both the to-and-fro puncture technique FNC and the to-and-fro whirling puncture technique FNC demonstrated comparable specimen adequacy, and both can achieve good specimen adequacy. The to-and-fro puncture technique shows potential advantages in terms of operation time, reduction of the risk of missed diagnosis of malignant tumors, sensitivity, and diagnostic accuracy. Trial registration: Chinese Clinical Trial Registry, ChiCTR2400080882. Registered 14 February 2024.