Unilateral primary aldosteronism (UPA) is characterized by a severe clinical phenotype and can be cured by adrenalectomy. Establishing accurate cutoff values that indicate the need for adrenal venous sampling (AVS) is crucial. Therefore, we aimed to identify appropriate cutoff values for screening and confirmatory testing to predict UPA by LC–MS/MS-equivalent plasma aldosterone concentration (PAC) using chemiluminescent enzyme immunoassay (CLEIA). A retrospective cohort analysis was conducted as part of the JPAS-II study of 443 patients diagnosed with PA using CLEIA-measured PAC, of whom 179 were confirmed by AVS as having UPA. The screening aldosterone-to-renin ratio (sARR), screening PAC, post-captopril challenge test (CCT) aldosterone-to-renin ratio (ARR), post-CCT PAC, and post-saline infusion test (SIT) PAC were significantly higher in patients with UPA than in those with bilateral PA (p < 0.05). Receiver operator characteristic curve analysis yielded an sARR cutoff value of >183 pg/mL/ng/mL/h (sensitivity of 0.95). The post-CCT ARR (AUC: 0.824 ± 0.022) and post-CCT PAC (AUC: 0.845 ± 0.021) were superior predictors of UPA to post-SIT PAC (AUC: 0.782 ± 0.037). When the cutoff values were designed to maximize sensitivity without a significant reduction in specificity, cutoff values for post-CCT ARR of >153 pg/mL/ng/mL/h (sensitivity: 0.85, specificity: 0.55) and for post-SIT PAC of >48 pg/mL (sensitivity: 0.80, specificity: 0.61) were obtained. Importantly, these cutoff values contributed to a diagnosis of UPA when the presence of hypokalemia or adrenal tumor was also considered. In conclusion, LC–MS/MS-equivalent CLEIA-measured cutoff values for post-CCT ARR of >153 pg/mL/ng/mL/h and for post-SIT PAC of >48 pg/mL are considered to indicate AVS. Study registration number: UMIN ID: 000046631.

Congenital nephrogenic diabetes insipidus (CNDI) is characterized by resistance of the distal nephrons and collecting ducts to arginine vasopressin (AVP). High doses of 1-deamino-8-D-arginine vasopressin (DDAVP), a V2-receptor-selective agonist, are effective in some cases. The present study aimed to demonstrate the use, efficacy, and safety of DDAVP and the characteristics of patients who responded to this treatment. The present, retrospective, multicentric, observational survey of patients with CNDI receiving DDAVP was based on a previous, nationwide survey conducted by the Japanese Society for Pediatric Endocrinology (JSPE) and collected data on the use (formulation, dosage, and treatment duration), efficacy (change in urine output and height SDS), and safety of DDAVP. In the initial survey, 43 of 123 JSPE council members (35.0%) observed the patients. The secondary survey of 13 patients found DDAVP to be effective in five patients (38.5%), as evidenced by a 12.6–31.6% decrease in urine output. The maximum urine osmolality on a water deprivation test and urine osmolality after vasopressin injection were lower in patients who were unresponsive to DDAVP than in those who were responsive to the drug (106 vs. 206 mOsm/H₂O/kg, 140 vs. 525 mOsm/H₂O/kg). The AVPR2 variants identified in the DDAVP-responsive group were p.Ala37Pro, p.Leu44Phe, p.Arg104Cys, and p.Tyr128Ser. DDAVP was effective against CNDI with residual V2R function. The water deprivation test with vasopressin injection and genetic testing may be useful for predicting responsiveness to DDAVP.

The Fukushima prefectural government is implementing the Thyroid Ultrasound Examination (TUE) program for residents aged 18 years or younger living in Fukushima Prefecture at the time of the nuclear accident. The results of the first-round survey showed that the prevalence of thyroid cysts was approximately half the total number of participants. Therefore, we analyzed the detection rate and maximum diameter of thyroid cysts in more detail, based on the results of second- and third-round surveys, to determine their characteristics. We analyzed 284,074 participants who completed Full-scale Surveys (FSSs). The second and third-round surveys were considered the 1st and 2nd FSSs, respectively. The detection rate of thyroid cysts was 57.4% in males and 61.0% in females, with the highest prevalence observed at 11 and 13 years of age, respectively. The median maximum diameter of thyroid cysts was 2.7 mm (interquartile range [IQR]: 2.1–3.3) in males and 2.8 mm (IQR: 2.2–3.6) in females, with a tendency to increase with age. Both the detection rate and maximum diameter were associated with BSA. Among participants who underwent both the 1st and 2nd FSSs, cysts appeared in 10.9% and disappeared in 6.1% at the 2nd FSS. The appearance of cysts was associated with younger age, female sex, and the presence of nodules. Disappearance of cysts was associated with older age, female sex, larger BSA, and smaller maximum cyst diameter. This study is expected to help advance the TUE program and elucidate the mechanisms underlying the formation and disappearance of thyroid cysts.

The biological clock enables organisms to align their intrinsic rhythms with daily environmental cycles thereby maintaining homeostasis and imparting resilience against metabolic derangements. Endocrine hormones and neural networks are key mediators of temporal coordination across remote tissues. The potential impact of maternal-fetal synchronization during pregnancy has been extensively studied, as alterations in maternal circadian rhythms because of mistimed food intake, sleep disturbances, and jet-lagged conditions appear to influence organ development, maturation, and behavior, leading to enduring metabolic consequences in offspring. In support, the in utero environment and maternal nutritional state influence long-term health outcomes, as proposed in the developmental origins of health and disease. While the molecular mechanisms connecting maternal circadian disruption to sustained alterations in progeny are still under investigation, endocrine hormones and metabolites may engage in temporal communication between the mother and fetus and induce epigenetic changes. This review outlines recent discoveries on maternal circadian rhythms as an external input for the fetus and discusses future strategies to strengthen metabolic fitness in subsequent generations.

PaTHway Japan is an ongoing, phase 3, multicenter, single-arm, open-label trial comprised of a 26-week efficacy period with an extension period through week 182 designed to demonstrate the efficacy, safety, and tolerability of palopegteriparatide in Japanese individuals with hypoparathyroidism. Japanese men and women (≥18 years of age) with hypoparathyroidism of any etiology (≥26 weeks) taking stable doses of active vitamin D were enrolled across five sites in Japan. Once-daily palopegteriparatide was self-administered subcutaneously via a pre-filled pen injector. Titration of palopegteriparatide and conventional therapy was performed according to a protocol-specified algorithm. The main outcomes measures included the proportion of participants at week 26 who achieved albumin-adjusted serum calcium in the normal reference range, independence from active vitamin D, and independence from therapeutic doses of elemental calcium. Thirteen participants were enrolled. Hypoparathyroidism etiology was most commonly idiopathic, followed by postsurgical and genetic causes. After 26 weeks of treatment with palopegteriparatide, 92% (12/13) of participants achieved the primary multi-component endpoint. Of the participants who entered the extension period, 92% (11/12) met the multi-component endpoint at week 52. Adverse events were mild to moderate in severity; none led to discontinuation of palopegteriparatide treatment. These findings in Japanese adults are consistent with results of the pivotal phase 3 and phase 2 North American/European trials and demonstrate the reproducibility of the palopegteriparatide treatment benefit in diverse populations and geographies. Japan Registry of Clinical Trials ID: jRCT2051210058.