Immune checkpoint inhibitors, particularly programmed cell death protein 1 (PD-1) inhibitors, can cause endocrine immune-related adverse events, including hypophysitis and secondary adrenal insufficiency. Isolated adrenocorticotropic hormone (ACTH) deficiency is uncommon but may present as a life-threatening adrenal crisis. We report the case of a 65-year-old man with stage IV BRAF wild-type metastatic melanoma receiving pembrolizumab who presented with profound fatigue, nausea, vomiting, weight loss, orthostatic dizziness, and hypotension. Laboratory evaluation revealed severe hyponatremia, mild hyperkalemia, hypoglycemia, and acute kidney injury. Serum cortisol was 2.1 µg/dL with an inappropriately low ACTH concentration of <5 pg/mL. A conventional 250 µg cosyntropin (Synacthen) stimulation test demonstrated an inadequate cortisol response, while other pituitary axes remained preserved. Pituitary magnetic resonance imaging showed mild enlargement and stalk thickening, consistent with hypophysitis. Intravenous hydrocortisone and fluid resuscitation rapidly restored hemodynamic and metabolic stability. At 6 months, ACTH remained <5 pg/mL, with persistent isolated corticotroph deficiency. Pembrolizumab-associated isolated ACTH deficiency should be considered when patients develop unexplained constitutional symptoms, hypotension, hyponatremia, or hypoglycemia. Prompt cortisol and ACTH assessment and glucocorticoid treatment are essential to prevent morbidity and mortality.
A man in his 30s presented with progressive weight loss, fatigue, anorexia, and low mood that developed over several weeks following international migration and transition to night shift work, the changes that disrupted his sleep-wake cycle and circadian rhythm. A low 8 am cortisol level (2.9 mcg/dL) with a borderline low ACTH concentration (7.4 pg/mL), negative anti-adrenal antibodies, normal electrolytes, and unremarkable adrenal imaging, suggestive of secondary adrenal insufficiency. Given his hemodynamic stability, empirical glucocorticoid therapy was deliberately deferred in favor of cessation of night shift work, sleep restoration, and nutritional rehabilitation, which resulted in complete clinical and biochemical resolution within weeks. At six months follow-up, a rising thyroid-stimulating hormone (TSH) level, strongly positive thyroid peroxidase antibodies, and a heterogeneous thyroid on ultrasound revealed previously unrecognized Hashimoto’s thyroiditis, a finding consistent with cortisol inhibitory effect on TSH secretion during adrenal suppression. This case illustrates that circadian rhythm disruption from night shift work and migration can produce a reversible functional form of secondary adrenal insufficiency that may resolve without glucocorticoid replacement. It underscores the value of detailed occupational and sleep history in patients presenting with unexplained constitutional symptoms and highlights how cortisol-TSH interactions can transiently mask the co-existing autoimmune thyroid disease. Clinicians should consider a period of clinical reassessment before treating hemodynamically stable patients with long-term glucocorticoid therapy and should reassess thyroid function once adrenal function normalizes.
Objective A significant proportion of patients with Graves’ orbitopathy do not respond adequately to treatment with glucocorticoids. Early identification of clinical factors associated with therapeutic response may help optimize management. The aim of this study is to characterize the population with active Graves’ orbitopathy and to compare the clinical features of patients who responded and those who did not respond to systemic glucocorticoid treatment. Methods A nested case-control study was conducted within a retrospective cohort of patients with moderate-to-severe or sight-threatening active Graves’ orbitopathy at a tertiary referral center. Adults with a Clinical Activity Score ≥ 3 and sufficient follow-up to assess response to therapy were included. Sociodemographic, clinical, ophthalmological, biochemical, and imaging variables were compared between responders and non-responders. Results Thirty-nine patients were analyzed, of whom 22 (56.4%) responded to first-line glucocorticoid treatment. Responders had a lower baseline Clinical Activity Score (mean 4.0 vs. 4.88; p=0.013), lower weight-adjusted cumulative steroid dose (median 58 vs. 74 mg/kg; p=0.030), and a lower frequency of keratopathy (57.1% vs. 88.2%; p=0.036). No significant differences were observed in thyroid profile, TSH receptor antibody levels, lipids, or tomographic findings. A trend toward higher smoking prevalence was observed among non-responders. Conclusions A lower baseline Clinical Activity Score , the absence of keratopathy, and lower cumulative steroid doses were associated with a better response to treatment. These findings suggest that ophthalmological and inflammatory markers may have greater clinical utility than conventional biochemical parameters.
Ketosis-prone diabetes (KPD) is a heterogeneous diabetes phenotype in which some patients with preserved β-cell function can achieve insulin independence after diabetic ketoacidosis (DKA). The role of sodium-glucose cotransporter 2 (SGLT2) inhibitors in maintaining remission in A−β+ KPD remains uncertain because of concerns regarding ketoacidosis risk. We report the case of a 45-year-old man who presented with severe DKA and was classified as A−β+ KPD based on negative islet autoantibodies and preserved C-peptide secretion. Following acute management, structured insulin withdrawal was performed, and dapagliflozin was initiated at week 4 with intensive metabolic monitoring. Over 12 months, the patient achieved sustained insulin-free remission, with significant improvements in HbA1c (12.1% to 6.4%), robust recovery of stimulated C-peptide (peak 4.8 ng/mL), and a continuous glucose monitoring (CGM) time-in-range of 82%, without recurrence of ketosis. This case suggests that in carefully selected A−β+ KPD patients with preserved β-cell reserve, SGLT2 inhibition may be safely integrated into the remission phase under close surveillance. However, these findings are hypothesis-generating, and the contribution of dapagliflozin to remission cannot be determined from a single uncontrolled observation. Prospective studies are required before this strategy can be recommended for routine use.
Background Insulin patch pumps offer advantages over multiple daily injections (MDI) for pediatric diabetes, but randomized trial evidence in Chinese children remains limited. Objectives To evaluate the efficacy and safety of a tubeless insulin patch pump (Equil™) compared with MDI in children and adolescents with diabetes. Methods This multicenter, open-label, randomized, crossover, non-inferiority trial was conducted at seven pediatric endocrinology centers in China (September 2021 – October 2022). Patients aged 3–17 years with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) were randomized 1:1 to receive continuous subcutaneous insulin infusion (CSII) via Equil™ or MDI via insulin pen for 5 days, followed by crossover. The primary outcome was mean blood glucose (MBG). Non-inferiority margin was pre-specified as 0.386 mmol/L. Secondary outcomes included glycemic variability (standard deviation of blood glucose, SDBG), glycated albumin (GA), total daily insulin dose (TDD), hypoglycemia frequency, and adverse events. Patient satisfaction was assessed using a study-specific 11-item questionnaire. Results Of 74 enrolled patients, 72 (97.3%) completed the study. CSII demonstrated non-inferiority to MDI for MBG (8.43±1.88 mmol/L, n=74, vs 9.00±2.04 mmol/L, n=72); mean difference -0.606 mmol/L; 95% CI -0.988 to -0.223; upper CI limit -0.223 < non-inferiority margin 0.386. No significant differences were observed for secondary outcomes (SDBG: 3.019 vs 3.357; GA change: 2.52±3.03% vs 2.02±3.25%, p=0.184; TDD: 132.17±78.43 vs 147.52±91.59 IU, p=0.159; hypoglycemia events: 114 vs 106). Adverse event rates were similar (75.7% vs 69.4%, p=0.399); no serious adverse events occurred. Patient satisfaction was significantly higher with CSII (total score 21.03±4.47 vs 22.00±3.99; mean difference -0.97, 95% CI -1.75 to -0.19; p=0.015), with 68.1% of patients preferring the patch pump. Conclusion The Equil™ patch pump is non-inferior to MDI in terms of glycemic control and safety for pediatric diabetes patients, with higher patient satisfaction. These findings support the patch pump as an effective alternative for children and adolescents requiring exogenous insulin therapy.
