Background/Objectives: Ectopic Cushing’s syndrome (ECS) is a rare, life-threatening condition caused by uncontrolled ACTH secretion from tumors, most commonly small-cell lung cancer (SCLC). ECS is traditionally reported in 1–6% of SCLC cases; however, recent data suggest it may be much higher. This study compares the clinical presentation of SCLC-related ECS (ECS-SCLC) with other ECS etiologies and analyzes the diagnosis, treatment, and outcomes of ECS-SCLC. Methods: We retrospectively analyzed the records of 39 ECS patients diagnosed between 2000 and 2024 at a tertiary endocrinology center. Seven cases (18%) were due to SCLC. Diagnosis was based on clinical signs, biochemical testing, imaging, and histopathology. Results: ECS-SCLC patients (five men, two women; median age 61), compared to other ECS etiologies, had a shorter time to diagnosis (median 1 vs. 2 months; p = 0.03), worse general condition (ECOG 4 vs. 3; p = 0.01), greater muscle weakness (Lovett scale median 2[IQR 1–2] vs. 2[IQR 2–3]; p = 0.04), more severe hypokalemia (2.12 vs. 2.7 mmol/L; p = 0.03), and required higher potassium supplementation (200 vs. 120 mEq/day; p = 0.001). All ECS-SCLC patients experienced weight loss (median 5 kg). Cortisol-lowering therapy (metyrapone or osilodrostat) was initiated in six patients (mean initiation time 3.7 days), leading to clinical improvement. Oncological treatment (chemotherapy or radiotherapy) was administered in five patients after stabilization. The median follow-up time was 3 months. Conclusions: Early recognition of ECS-SCLC and a multidisciplinary approach are critical. Severe hypokalemia and muscle weakness should prompt timely evaluation for hypercortisolism. Cortisol-lowering therapy may improve clinical status and facilitate oncological treatment.

There is an increased risk for childhood type 1 diabetes (T1D) when T1D and type 2 diabetes (T2D) are reported in relatives. Our objective was to evaluate current family risk factors for T1D development before implementing a national screening program for T1D. A population of 879 Caucasian children and adolescents with T1D and 286 healthy controls were enrolled in the study. All participants completed the same questionnaire, which collected information about family history of diabetes over 3 generations. In statistical analyses, frequency tables and χ2 tests evaluated possible multicollinearity among risk factors that were significantly associated with the outcomes. Family history of diabetes was more frequent in controls (n = 75, 26.2%) than in patients with T1D (n = 146, 16.6%, odds ratio (OR) = 1.785, 95% confidence interval (95% CI): 1.299-2.452, degrees of freedom (df) = 12.976, p = 0.004), especially with a family history of T2D (n = 62, 21.7% compared to n = 79, 9.0%, respectively, OR = 2.803, 95% CI: 1.948-4.034, df = 32.669, p < 0.001). Also, there was a tendency for the nuclear family of T1D patients to be more frequently affected by T1D (n = 74, 8.4%) than the controls (n = 15, 5.2%, OR = 1.605, 95% CI: 0.937-2.751, df = 3.081, p = 0.079). The risk of T1D was associated with the closest family members being affected and accelerated over generations. Indeed, it was highest in siblings, especially brothers (OR = 12.985, 95% CI: 0.782-215.743, Fisher's test: p < 0.001). A positive family history of T2D burden among second-degree relatives was 2.728 times more frequent in the control group than in the T1D group (OR = 2.728; 95% Cl: 1.880-3.962, p < 0.001). Furthermore, a positive family history of T1D among first-degree relatives was less frequent in the controls than in the T1D group (OR = 0.124; 95% Cl: 0.030-0.516, p = 0.004). A family history of T1D, but not T2D, is a significant risk factor for T1D development. Indeed, the priority in screening for T1D should be given to first-degree relatives of T1D patients, starting from siblings.

Background/Objectives: Dopamine agonists (DAs) are the first-line therapy for prolactinomas; however, a subset of patients exhibits resistance or incomplete response. Methods: This retrospective study included 85 of 125 eligible consecutive patients with prolactinoma who were treated with DA, followed for a median of 52.0 (31.5–86.8) months. Clinical, biochemical, and radiological parameters were analyzed at baseline and at 6 and 12 months. Resistance was defined as failure to normalize serum prolactin concentration (PRL) or achieve ≥ 30% reduction in tumor maximal diameter after standard DA therapy. Logistic regression analyses were performed to identify predictors of DA resistance and treatment response. Results: The cohort comprised 54 males (63.5%) and 31 females (36.1%), with a mean age of 41.5 ± 17.2 years. In total, 22.4% had giant prolactinomas. After 6 months of treatment, 24.7% achieved PRL normalization, and 29.4% demonstrated ≥ 50% reduction in tumor volume. At 12 months, PRL normalized in 40% of patients, and a ≥50% volume reduction was observed in 41.2%. DA-resistant patients, compared to DA-non-resistant, were predominantly men (80.0% vs. 56.7%, p = 0.042), with a higher proportion of giant adenomas (44.0% vs. 13.3%, p = 0.002) and significantly higher baseline PRL (2000.000 ng/mL vs. 478.985 ng/mL, p = 0.012). Early reduction in maximal tumor diameter at 6 months predicted a favorable therapeutic response at 12 months (aOR = 1.156; 95% CI = 1.001–1.335, p = 0.049). Conclusions: Male sex, higher baseline PRL, and larger tumor size can be predictors of DA resistance. On the other hand, early radiological tumor shrinkage may predict favorable treatment outcomes. However, new markers of DA resistance, particularly molecular ones, should be identified.