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.

This review summarizes recent basic and clinical advances in cortisol-producing adrenal tumors, including Cushing’s syndrome (CS) and mild autonomous cortisol secretion (MACS). Recent clinical reports on the epidemiology and diagnostic challenges of CS and MACS are presented. The review highlights recent progress in understanding the molecular pathogenesis of adrenal cortisol-producing tumors. A major recent finding is the discovery of loss-of-function mutation in KDM1A as the underlying cause of the long-standing mystery of diet-dependent CS in primary bilateral macronodular adrenal hyperplasia (PBMAH). Furthermore, the recent clarification of the molecular basis of cortisol-producing adenomas (CPAs) has deepened our understanding of the functional differences in the autonomicity of CPAs between overt CS and MACS. These findings made us reconsider the categorization of adrenal tumors, including non-functioning adrenal tumors (NFATs). Finally, we reviewed the rarely discussed but critical condition of immune reconstitution inflammatory syndrome (IRIS) following CS treatment, including a case from our own experience. IRIS should be kept in mind when initiating treatment for CS patients with extremely high serum cortisol levels.

GPR75 has emerged as a therapeutic target for obesity following the discovery of a causal relationship between GPR75 variants and reduced body mass index in humans. Herein, we examined whether GPR75 is dispensable for normal feeding, body growth, and reproduction using newly generated Gpr75 knockout (KO) rats fed normal chow. Gpr75 was highly expressed in the brain, including several hypothalamic nuclei, in rats of both sexes. Gpr75 KO male and female rats exhibited significantly lower food intake, reduced feeding duration during the dark phase, and lower body weight (BW) than wild-type rats. Importantly, Gpr75 KO did not affect reproduction in either sex, including puberty onset, pulsatile luteinizing hormone secretion, or litter size. We also examined the effects of Gpr75 KO on hyperphagia, obesity, hyperglycemia, and hyperinsulinemia in male rats on a high-fat diet (HFD). HFD-fed Gpr75 KO male rats exhibited significantly lower food intake, BW, and fat accumulation than wild-type rats and were normoglycemic and normoinsulinemic. Notably, hypothalamic Ccl5 (encoding C-C motif chemokine ligand 5 [CCL5]) expression was significantly higher in Gpr75 KO male rats than in wild-type rats, suggesting that Gpr75 KO may prevent HFD-induced hyperphagia via central CCL5 signaling in rats. Thus, GPR75 signaling, although dispensable for reproduction, contributes to feeding and body growth in rats on normal chow and is involved in HFD-induced hyperphagia, obesity, hyperglycemia, and hyperinsulinemia development. Therefore, GPR75 antagonism may offer a potential therapeutic approach to control feeding and BW and prevent obesity and insulin resistance without affecting reproduction in humans.