The meibomian glands play a central role in maintaining ocular surface homeostasis by producing meibum, which is the lipid layer of the tear film that suppresses tear evaporation. Dysregulation of the secretion of this lipid leads to meibomian gland dysfunction (MGD), the most common cause of evaporative dry eye disease. Accumulating evidence indicates that androgen signaling is a critical regulator of meibomian gland structure and function. In contrast to classical endocrine mechanisms, androgen action in this tissue is largely mediated by intracrine steroid metabolism, whereby circulating adrenal precursors are locally converted to active androgens within the gland. Key steroidogenic enzymes, including 3β-hydroxysteroid dehydrogenase (3β-HSD), are expressed in the meibomian acinar cells, thereby enabling local testosterone production. Simultaneously, the gland exhibits robust metabolic pathways that convert testosterone to downstream androstane derivatives, providing a mechanism for the spatially restricted control of androgen signaling. Recent study has revealed that the intracrine steroidogenic system is affected by circadian rhythms. In particular, 3β-HSD activity exhibits daily rhythmicity that parallels fluctuations in nicotinamide adenine dinucleotide (NAD⁺), suggesting that NAD⁺-dependent metabolic processes contribute to temporal control of local androgen production. Importantly, administration of NAD⁺ precursors improves meibomian gland morphology in experimental models of aging-associated MGD. This review summarizes the current knowledge on intracrine androgen metabolism in the meibomian gland and highlights emerging metabolic and circadian mechanisms that may provide novel therapeutic targets for dry eye disease.

Hypertonic saline infusion and water deprivation tests are commonly used to stimulate arginine vasopressin (AVP) for the diagnosis of AVP deficiency (AVP-D); however, these procedures impose a considerable burden on patients. We aimed to develop machine learning models to predict impaired AVP secretion and thereby reduce the need for AVP stimulation testing. This retrospective cohort study included 64 patients who underwent the hypertonic saline test (HST) at Nagoya University Hospital, Japan, between 2018 and 2024. Impaired AVP secretion was defined as a predicted plasma AVP level <1.0 pg/mL at a serum sodium level of 149 mEq/L during the HST. Feature selection was performed using univariate screening and systematic selection procedures. Logistic regression and support vector machine models were developed using baseline clinical and laboratory parameters obtained before the HST and validated using nested cross-validation. The primary outcome was the area under the receiver operating characteristic curve (AUC); secondary outcomes included the sensitivity, specificity, and positive and negative predictive values. Four variables (urinary osmolality, serum sodium, plasma AVP, and blood urea nitrogen) were selected. The logistic regression model achieved an AUC of 0.862 for predicting impaired AVP secretion. Among 35 patients who underwent the HST for suspected AVP-D, at the optimized threshold, the positive and negative predictive values were 100% (14/14 patients) and 33.3% (7/21 patients), respectively. The developed machine learning model can identify a subset of patients with impaired AVP secretion without requiring the HST, potentially reducing the number of patients who need AVP stimulation testing for AVP-D diagnosis.

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.