Immune checkpoint inhibitor-associated hypophysitis is an uncommon but clinically important endocrine immune-related adverse event. We report a 70-year-old man with a history of non-small cell lung cancer previously treated with approximately two years of pembrolizumab, with his last dose administered approximately 28 months before presentation. He developed progressive fatigue, anorexia, hypotension, functional decline, and confusion and was subsequently hospitalized with multifocal pneumonia and septic shock. Although the infection and hemodynamic instability improved, encephalopathy, weakness, poor oral intake, and dysphagia persisted. Brain magnetic resonance imaging demonstrated new pituitary enlargement compared with imaging obtained approximately three months earlier. Dedicated pituitary imaging showed enlargement measuring approximately 1.5 × 2.0 cm without definite differential enhancement to suggest a pituitary adenoma. Endocrine testing demonstrated a cortisol level of 3.3 µg/dL with an inappropriately low adrenocorticotropic hormone level of 6.5 pg/mL, free thyroxine of 0.36 ng/dL with thyroid-stimulating hormone of 2.0 µIU/mL, suppressed gonadotropins, and testosterone <10 ng/dL, supporting central adrenal insufficiency and central hypothyroidism with marked gonadal-axis suppression. Cerebrospinal fluid cytology and paraneoplastic studies were unrevealing. The patient was treated with hydrocortisone before thyroid hormone replacement and subsequently showed progressive improvement in mental status, oral intake, and participation in rehabilitation. This case highlights that pituitary immune-related adverse events may be recognized long after pembrolizumab discontinuation and emphasizes the importance of considering prior immune checkpoint inhibitor exposure in patients with unexplained endocrine and constitutional decline.

Potent topical corticosteroids can be absorbed systemically and cause both iatrogenic Cushing syndrome and suppression of endogenous cortisol production. Most paediatric reports involve infants, so clinically important toxicity in adolescents may be overlooked. A 15-year-old girl used clobetasol propionate 0.05% ointment for six months, with a reported cumulative exposure of 250 g and no documented interim clinical review. She developed Cushingoid facial changes, extensive lower-limb striae, fatigue, impaired concentration, insomnia, and low mood. Morning cortisol was <30 nmol/L and ACTH was <5 ng/L. An initial short Synacthen test showed cortisol concentrations of <30 nmol/L at baseline and 30 minutes and 38 nmol/L at 60 minutes, confirming severely impaired adrenal reserve. Clobetasol was discontinued. The patient was started on physiological hydrocortisone replacement, educated on sick-day rules, and supplied with emergency intramuscular hydrocortisone. Serial Synacthen testing showed partial recovery at 2.5 months and adequate adrenal reserve by seven months, allowing hydrocortisone to be discontinued. Her mood subsequently improved, while the striae faded gradually. This case demonstrates a compelling association between prolonged exposure to a very potent topical corticosteroid, clobetasol, and the development of simultaneous Cushingoid features and glucocorticoid-induced adrenal insufficiency in an adolescent. Careful diagnostic review, patient counselling, planned clinical monitoring, and recognition of adrenal suppression are important medication-safety measures when potent or very potent topical corticosteroids are prescribed.

Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of Cushing syndrome (CS), characterized by bilateral adrenal nodules larger than 1 cm. Cortisol hypersecretion in PBMAH is driven by intra-adrenal rather than pituitary adrenocorticotropic hormone (ACTH), with its pathogenesis mediated by aberrant hormone receptor expression in the adrenal cortex. This article reports a case of a 60-year-old woman with PBMAH in whom a marked reduction in bilateral adrenal masses was observed following treatment with osilodrostat. The patient presented with typical Cushingoid features, accompanied by hypertension, diabetes mellitus, osteoporosis, and severe restrictive lung disease. Genetic testing identified a pathogenic mutation in the ARMC5 gene, confirming the diagnosis. Because she was intolerant of surgical treatment, left adrenal artery embolization (AAE) was performed but failed to control hypercortisolism. Osilodrostat therapy was subsequently initiated-this potent 11β-hydroxylase inhibitor was recently approved in China for the treatment of Cushing syndrome. Notably, after 23 weeks of treatment, the patient's 24-hour urinary free cortisol (24 hours-UFC, CLIA) level returned to normal. Treatment was then discontinued, and during 11 months of follow-up the patient's 24 hours-UFC remained within the normal range. Moreover, imaging performed during the period of osilodrostat therapy demonstrated significant shrinkage of both adrenal glands. To our knowledge, this is the first reported case of bilateral adrenal mass reduction observed in temporal association with osilodrostat treatment in a PBMAH patient. However, prior AAE confounds the attribution of tumor shrinkage to osilodrostat alone. These findings highlight an observed association between the drug and mass reduction, warranting further investigation to clarify its potential role beyond symptomatic control.

This study evaluated the effects of dietary n-3 polyunsaturated fatty acids (n-3 PUFA) supplementation on endocrine and metabolic profiles of forty-five nulliparous rabbit does during their first reproductive cycle. Animals were randomly assigned to one of three diets: control (CNT), 5% extruded linseed (L), and 5% extruded linseed plus 0.2% Padina pavonica extract (LPP). Blood was sampled at baseline, artificial insemination, parturition, mid-lactation, and weaning, to determine the concentrations of cortisol, insulin, leptin, thyroid hormones (T3, T4), glucose, and non-esterified fatty acids (NEFA). Reproductive stage significantly influenced endocrine and metabolic dynamics, with cortisol and NEFA peaking at parturition (p < 0.001). Supplemented groups, particularly LPP, showed higher T3 concentrations (p < 0.05) and T3/T4 ratios (p < 0.01). The L diet maintained higher insulin during lactation (p < 0.05), while LPP lowered leptin at parturition (p < 0.01) and NEFA at insemination (p < 0.01), indicating an early decrease in lipid mobilization. Multivariate analysis suggested that n-3 PUFA supplementation promoted an endocrine profile characterized by enhanced thyroid activity and reduced lipid mobilization, consistent with a potentially favorable metabolic shift. In conclusion, enriching diets with n-3 PUFA, especially linseed combined with Padina pavonica extract, represents a promising nutritional strategy to support rabbit does during the highly demanding phases of their first reproductive cycle.

Traumatic events engage stress physiology, with the hypothalamic-pituitary-adrenal axis and cortisol central to adaptation. In naturalistic trauma, physical injury and psychological distress often co-occur, complicating interpretation of acute cortisol changes. Stillbirth offers a natural contrast: it is physiologically similar to live birth but constitutes traumatic bereavement. This study tested whether psychological trauma elicited by stillbirth is associated with acute alterations in diurnal cortisol rhythm versus comparable physiological delivery stress. Fifty-seven postpartum women were included (stillbirth, 24; live birth, 33). Saliva samples were collected at seven fixed time points across the day following childbirth. Cosinor curve fitting yielded the midline estimating statistic of rhythm, amplitude, and acrophase. Traditional indices included area under the curve with respect to ground, area under the curve with respect to increase, and the cortisol awakening response. Group differences were tested using analyzes of variance. Both groups showed a coherent diurnal pattern. Compared with live birth, stillbirth was associated with a lower area under the curve with respect to ground, a lower area under the curve with respect to increase, and a lower midline estimating statistic of rhythm. Stillbirth was also exhibited associated with an earlier acrophase. Compared with comparable physiological delivery stress, stillbirth is linked to reduced total cortisol secretion, lower mean levels, and an advanced circadian phase in the acute postpartum period, suggesting that the psychological trauma of stillbirth may involve alterations in hypothalamic-pituitary-adrenal axis regulatory patterns and providing preliminary evidence for future work on early biological markers and supportive interventions.

Corticosteroid therapy in septic shock has evolved from empirical high-dose anti-inflammatory treatment to low-dose adjunctive pharmacotherapy aimed primarily at restoring vascular responsiveness and accelerating shock reversal. Population-level randomized evidence supports a modest average corticosteroid benefit, most consistently reflected in faster shock reversal and earlier vasopressor liberation, whereas mortality effects remain regimen- and population-dependent. This divergence suggests that average treatment effects alone are insufficient to guide individual decisions. We review how pharmacology, randomized evidence, candidate treatment-effect modifiers, and prespecified longitudinal phenotypes may inform the development of individualized corticosteroid strategies, while defining the evidence required before such strategies can guide clinical care. Glucocorticoid and mineralocorticoid receptor biology provides plausible pathways for both benefit and harm, but no single mechanism, cortisol test, transcriptomic endotype, or clinical trajectory is currently validated for routine treatment selection. Candidate enrichment signals must be distinguished as prognostic, predictive, pharmacodynamic, or safety-related and must be available before corticosteroid exposure when used for treatment selection. Observational studies require explicit alignment of eligibility, time zero, treatment strategies, and follow-up; target trial emulation can reduce avoidable temporal bias but cannot substitute for randomization or remove unmeasured confounding. Trajectory-guided enrichment remains investigational: any candidate trajectory used for treatment selection must be assigned or predicted from information available before exposure, and differential treatment effects require explicit evaluation rather than prognostic association alone. Treatment evaluation should extend beyond mortality to shock reversal, organ-support liberation, kidney outcomes, metabolic toxicity, infection, neuromuscular effects, and longer-term function. Clinical decision support should remain a future, clinician-supervised implementation layer that translates validated evidence into time-stamped actions rather than an autonomous prescribing system. Progress toward precision corticosteroid therapy now requires prespecified enrichment hypotheses, direct regimen comparisons, harmonized outcomes, prospective validation, and trials demonstrating clinical utility.

[This retracts the article DOI: 10.3389/fphar.2023.1202325.].