The pituitary gland plays a central role in maintaining physiological homeostasis by secreting multiple hormones that regulate diverse body functions. Dysregulation of pituitary hormones can arise from various conditions, such as pituitary tumors and autoimmune diseases, leading to a broad spectrum of symptoms. During embryonic organogenesis, the pituitary gland originates from the oral ectoderm in close contact with the adjacent hypothalamus. This tissue interaction is essential for proper development. Although the molecular mechanisms underlying pituitary development and related disorders have been extensively studied using animal models, such as rodents and zebrafish, species-specific differences limit the translatability of these findings to humans. Moreover, the scarcity of established human pituitary cell lines has hindered the investigation of human-specific mechanisms. Recent biotechnological advances have addressed these limitations by enabling the long-term culture of human pituitary tumor tissues and in vitro generation of pituitary hormone-producing cells from human pluripotent stem cells. These emerging platforms provide powerful tools for deepening our understanding of pituitary biology and diseases. In this review, we summarize current in vitro experimental models derived from pituitary tissues and pluripotent stem cells and discussed their applications in the study of pituitary development, physiology, and related disorders.

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.

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.

This study aimed to clarify the expression levels of autophagy-related molecules, such as β-catenin, LC3B, and p62, in thyroid carcinoma (TC) cases of different histological types and clinicopathological characteristics. A total of 70 surgically resected thyroid nodules, including 43 papillary thyroid carcinoma (PTC), and other control groups such as five follicular adenoma (FA), five hyalinizing trabecular tumor (HTT), five follicular TC (FTC), six poorly differentiated TC (PDTC), and six anaplastic follicular cell-derived thyroid carcinoma (ATC), were analyzed by dual-color immunofluorescence for β-catenin, LC3B, and p62. Statistical analyses were used to determine the association of autophagy-related molecules with BRAF^V600E/TERT promoter mutations, Ki-67 labeling index, and clinicopathological characteristics. p62 immunoreactivity was most frequently observed in PTC, particularly in classical and tall cell subtypes. This protein appeared to co-localize with LC3B and β-catenin in intranuclear cytoplasmic inclusions (INIs) of PTC. Conversely, p62 expression was rarely observed in either FTC or PDTC. The expression levels of p62 and its co-localization with β-catenin and LC3B correlated significantly with the presence of the BRAF^V600E mutation. Frequent co-localization of dot-shaped perinuclear β-catenin signals with a component of the trans-Golgi apparatus in tall cell PTC subtype was also observed. This study revealed differences in the expression patterns of β-catenin, LC3B, and p62 among different TC types. Abnormal β-catenin expression may be linked to autophagy dysfunction, which triggers genomic instability and promotes tumor aggressiveness. These autophagy-related molecules may be cooperatively associated with INI formation during PTC carcinogenesis.

Hepatic carbohydrate and lipid metabolism is strictly regulated by hormones such as insulin, glucagon, cortisol, and adrenaline, dynamically adapting to diet and stress. Metabolic zonation, a key feature of liver function, has been studied for decades. It refers to the spatial arrangement of hepatocytes with distinct metabolic roles along the portal-to-central vein axis, shaped by nutrient and oxygen gradients, as well as signaling molecules. However, traditional methods have struggled to reveal the spatial regulation of gene expression and signaling within these zones. Recent advances in single-cell and spatial omics technologies now allow detailed analysis of gene expression, signaling pathways, and cell-cell interactions with spatial resolution, providing new insights beyond classical models. Metabolic zonation research is rapidly advancing, and the concept of immune zonation, describing the spatial distribution of immune cells, has gained attention for its role in liver metabolism. These findings have improved our understanding of metabolic changes in conditions like fatty liver disease and diabetes. However, many questions remain, including the dynamic effects of diet and hormones and disease-related alterations. This review summarizes past and recent findings on metabolic zonation, explores the role of immune zonation and hormonal regulation, and discusses the latest technologies and future challenges.

Hypercalcemia, a common electrolyte imbalance, requires accurate differential diagnosis to guide appropriate management. PTH-dependent hypercalcemia, predominantly caused by primary hyperparathyroidism (PHPT) and rarely by familial hypocalciuric hypercalcemia (FHH)—mainly due to heterozygous loss-of-function mutations in the CASR gene encoding the calcium-sensing receptor (CaSR)—now includes acquired hypocalciuric hypercalcemia (AHH) as an emerging disease entity. Initially identified as analogous to FHH, AHH was characterized by blocking antibodies targeting the CaSR. However, our research has identified unique autoantibodies, termed biased antibodies, that paradoxically regulate signaling by enhancing Gq activity while suppressing Gi activity. Investigating their mechanisms has not only provided insights into specific treatments for AHH but also suggested novel activation mechanisms and binding sites of the CaSR, offering a fresh perspective on the regulation of PTH secretion. In clinical practice, recognizing AHH is crucial. A key diagnostic feature is fluctuating serum calcium levels, making a wait-and-see approach viable for mild hypercalcemia. Conversely, hypercalcemic crises necessitate immediate diagnostic and therapeutic interventions. The most important diagnostic clue to differentiate AHH from PHPT is hypermagnesemia. Additionally, AHH is less likely to involve AVP resistance (i.e., nephrogenic diabetes insipidus) and acute kidney injury (AKI), owing to preserved medullary hyperosmolarity and minimal interference with AVP signaling. Finally, a relatively low PTH level serves as another distinguishing feature. Based on these observations, we propose a novel diagnostic guide for PTH-dependent hypercalcemia. We anticipate that this guide will help identify previously undiagnosed AHH cases in routine practice, enabling timely and effective management of this rare condition.

The parathyroid glands (PTGs) regulate calcium metabolism by secreting parathyroid hormone (PTH). Patients with hypoparathyroidism require lifelong replacement therapy, which is associated with risks of chronic kidney disease, bone fractures, and a reduced quality of life. Generating PTGs from pluripotent stem cells (PSCs) offers a potential regenerative therapy for this condition. This review first explains PTG organogenesis, followed by an overview of both in vitro and in vivo approaches to PTG generation. In vitro studies have successfully induced PTH-expressing parathyroid cells from human PSCs. However, challenges remain, particularly in achieving sufficient PTH secretion and functional efficacy in vivo. Meanwhile, an in vivo organ generation technique known as blastocyst complementation has successfully produced functional PTGs in rodents. However, whether this technology can be applied using human PSCs and animal embryos remains unclear. Pluripotent stem cell-derived PTGs hold promise for both clinical applications and basic research, but further advancements will be necessary to overcome existing challenges in this field.

Glucose-dependent insulinotropic polypeptide (GIP) is secreted by enteroendocrine K cells, primarily located in the upper small intestine, in response to food intake and plays a significant role in the postprandial regulation of nutrient metabolism. Although the importance of GIP in metabolic regulation has long been recognized, progress in developing GIP as a therapeutic target has been limited. However, the GIP/GIP receptor (GIPR) axis has garnered increasing attention in recent years. Emerging evidence suggests that dual GIP/GLP-1 receptor agonists and triple GIP/GLP-1/glucagon receptor agonists provide beneficial metabolic effects in individuals with type 2 diabetes and obesity. In this review, we outline the physiological roles of GIP, detailing the mechanisms of GIP secretion from K cells in response to macronutrients, its actions on key target organs involved in metabolic regulation, and ongoing developments in its therapeutic applications.

Hypopituitarism, characterized by reduced secretion of pituitary hormones, profoundly impacts systemic metabolic homeostasis and quality of life. Its etiology ranges from congenital anomalies in pituitary development to acquired conditions involving inflammation and autoimmune processes. Despite advances in understanding its pathogenesis, diagnostic challenges persist, particularly in cases with complex extra-pituitary manifestations or novel genetic variations. Congenital hypopituitarism often stems from disruptions in transcription factors and signaling pathways critical for pituitary organogenesis. Emerging studies employing next-generation sequencing and developmental biology techniques have revealed new genetic loci and mechanisms implicated in combined pituitary hormone deficiency. However, the pathogenesis of most congenital cases remains elusive, underscoring the need for functional and phenotypic analyses of novel variants. Acquired hypopituitarism, frequently associated with pituitary tumors or systemic diseases, has also been increasingly linked to autoimmune mechanisms. Notably, the concept of paraneoplastic autoimmune hypophysitis has emerged, highlighting malignancy-driven immune responses as a novel etiological framework. Investigations into immune checkpoint inhibitor-related hypophysitis and anti-PIT-1 hypophysitis exemplify the intricate interplay between tumor immunity and endocrine dysfunction, suggesting shared mechanisms involving ectopic antigen expression and autoimmunity. This review synthesizes recent insights into the genetic, developmental, and immunological underpinnings of hypopituitarism. By exploring both congenital and acquired etiologies, we aim to bridge gaps in the current understanding of this complex disorder and provide a foundation for improved diagnostic and therapeutic strategies. Future perspectives emphasize the integration of advanced genetic tools, deeper exploration of tumor-immunity interactions, and a heightened focus on extra-pituitary phenotypes to refine clinical practice and enhance patient outcomes.

Cushing’s disease is a rare endocrine disorder that presents many systemic complications, and its initial phase management can be difficult in atypical and severe cases or at institutes with limited experience. It is a disease in which several complications may have already progressed at the time of diagnosis, and complications may become more severe during the initial management phase, potentially becoming life-threatening. In addition, many patients are young, and depending on this phase management, their quality of life will significantly decline later on. Therefore, this review summarizes the evidence accumulated to date and outlines strategies for disease management, focusing on the initial stages from detection, diagnosis, and referral of patients to surgery.

Ghrelin produced in the stomach promotes food intake and GH secretion, and acts as an anabolic peptide during starvation. Ghrelin binds to the growth hormone secretagogue receptor, a G protein-coupled receptor (GPCR), whose high-resolution complex structures have been determined in the apo state and when bound to an antagonist. Anamorelin, a low-molecular-weight ghrelin agonist, has been launched in Japan for the treatment of cancer cachexia, and its therapeutic potential has attracted attention due to the various biological activities of ghrelin. In 2019, liver-expressed antimicrobial peptide (LEAP2), initially discovered as an antimicrobial peptide produced in the liver, was identified to be upregulated in the stomach of diet-induced obese mice after vertical sleeve gastrectomy. LEAP2 binds to the GHSR and antagonizes ghrelin’s activities. The serum concentrations of human LEAP2 are positively correlated with body mass index, body fat accumulation, and fasting serum concentrations of glucose and triglyceride. Serum LEAP2 elevated and ghrelin reduced in obesity. Ghrelin and LEAP2 regulate body weight, food intake, and GH and blood glucose concentrations, and other physiological phenomena through their interactions with the same receptor, GHSR.

Androgen is widely acknowledged to regulate skeletal muscle mass. However, the specific mechanism driving muscle atrophy resulting from androgen deficiency remains elusive. Systemic androgen receptor knockout (ARKO) mice exhibit reduction in both muscle strength and muscle mass while skeletal muscle fiber specific ARKO mice have decreased muscle strength without affecting skeletal muscle mass in the limbs. Therefore, androgens may indirectly regulate skeletal muscle mass through effects on non-myofibers. Considering this, our investigation focused on blood fluid factors that might play a role in the regulation of skeletal muscle mass under the influence of androgens. Using a male mouse model of sham, orchidectomy and DHT replacement, mass spectrometry for serum samples of each group identified epidermal growth factor receptor (EGFR) as a candidate protein involving the regulation of skeletal muscle mass affected by androgens. Egfr expression in both liver and epididymal white adipose tissue correlated with androgen levels. Furthermore, Egfr expression in these tissues was predominantly elevated in male compared to female mice. Interestingly, male mice exhibited significantly elevated serum EGFR concentrations compared to their female counterparts, suggesting a connection with androgen levels. Treatment of EGFR to C2C12 cells promoted phosphorylation of AKT and its downstream S6K, and enhanced the protein synthesis in vitro. Furthermore, the administration of EGFR to female mice revealed a potential role in promoting an increase in skeletal muscle mass. These findings collectively enhance our understanding of the complex interplay among androgens, EGFR, and the regulation of skeletal muscle mass.

This study aimed to focus on the role of radiologists in the diagnosis and management of adrenal lesions, particularly primary aldosteronism (PA) and secondary hypertension. As hypertension affects more than one-third of the population in Japan, identifying secondary causes such as PA and adrenal lesions is crucial. Establishing a radiological differential diagnosis of adrenal lesions using advanced imaging techniques, such as computed tomography and magnetic resonance imaging, is crucial. Knowledge of the imaging findings of various benign and malignant adrenal lesions, such as adrenocortical adenomas, cortisol-producing lesions, pheochromocytomas, adrenocortical carcinoma, malignant lymphoma, and metastatic tumors, is necessary. Adrenal venous sampling (AVS) plays a crucial role in accurately localizing aldosterone hypersecretion in PA, especially when imaging fails to provide a clear diagnosis. This paper details the technical aspects of AVS, emphasizing catheterization techniques, anatomical considerations, and the importance of preprocedural imaging for successful sampling. Furthermore, we explore segmental adrenal venous sampling (SAVS), a more refined technique that samples specific adrenal tributary veins, offering enhanced diagnostic accuracy, particularly for microadenomas or challenging cases that may be missed with conventional AVS. The methodology for performing SAVS, along with the interpretation criteria for successful sampling and lateralization, is also outlined. Furthermore, radiologists have initiated treatments for unilateral PA, such as radiofrequency ablation, and play an integral role in the management of adrenal lesions. Collaborative approaches across clinical departments are required to enhance patient management in medical care involving the adrenal gland.

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.

Cushing’s disease is associated with increased morbidity and mortality. Osilodrostat, a potent oral 11β-hydroxylase inhibitor, provided rapid, sustained mean urinary free cortisol (mUFC) normalization in Cushing’s disease patients in two Phase III studies (LINC 3, NCT02180217; LINC 4, NCT02697734). Here, we evaluate the efficacy and safety of osilodrostat in Cushing’s disease in patients of Asian origin compared with patients of non-Asian origin. Pooled data from LINC 3 and LINC 4 were analyzed. Outcomes were evaluated separately for Asian and non-Asian patients. For the analysis, 210 patients were included; 56 (27%) were of Asian origin. Median (minimum–maximum) osilodrostat dose was 3.8 (1–25) and 7.3 (1–47) mg/day in Asian and non-Asian patients, respectively. mUFC control was achieved at weeks 48 and 72 in 64.3% and 68.1% of Asian and 68.2% and 75.8% of non-Asian patients. Improvements in cardiovascular and metabolic-related parameters, physical manifestations of hypercortisolism, and quality of life were similar in both groups. Most common adverse events (AEs) were adrenal insufficiency (44.6%) in Asian and nausea (45.5%) in non-Asian patients. AEs related to hypocortisolism and pituitary tumor enlargement occurred in more Asian (58.9% and 21.4%) than non-Asian patients (40.3% and 9.1%). Of Asian and non-Asian patients, 23.2% and 13.6%, respectively, discontinued because of AEs. Asian patients with Cushing’s disease generally required numerically lower osilodrostat doses than non-Asian patients to achieve beneficial effects. Hypocortisolism-related AEs were reported in more Asian than non-Asian patients. Together, these findings suggest that Asian patients are more sensitive to osilodrostat than non-Asian patients.