Aleksandra Gamrat

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.

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.

Traditional electrocardiographic (ECG) criteria for left ventricular hypertrophy (LVH), introduced in the pre-echocardiographic era of diagnosis, have a relatively low sensitivity (usually not exceeding 25–40%) in detecting LVH. A novel Peguero-Lo Presti ECG-LVH criterion was recently shown to exhibit a higher sensitivity than the traditional ECG-LVH criteria in hypertension. Our aim was to test the diagnostic ability of the novel Peguero-Lo Presti ECG-LVH criterion in severe aortic stenosis. We retrospectively analyzed 12-lead ECG tracings and echocardiographic records from the index hospitalization of 50 patients with isolated severe aortic stenosis (mean age: 77 ± 10 years; 30 women and 20 men). Exclusion criteria included QRS > 120 ms, bundle branch blocks or left anterior fascicular block, a history of myocardial infarction, more than mild aortic or mitral regurgitation, and significant LV dysfunction by echocardiography. We compared the agreement of the novel Peguero-Lo Presti criterion and traditional ECG-LVH criteria with echocardiographic LVH (LV mass index > 95 g/m² in women and >115 g/m² in men). Echocardiographic LVH was found in 32 out of 50 study patients. The sensitivity of the Peguero-Lo Presti criterion in detecting LVH was improved (55% vs. 9–34%) at lower specificity (72% vs. 78–100%) in comparison to 8 single traditional ECG-LVH criteria. Additionally, the positive predictive value (77% vs. 72%), positive likelihood ratio (2.0 vs. 1.5), and odds ratio (3.2 vs. 2.4) were higher for the Peguero-Lo Presti criterion versus the presence of any of these 8 traditional ECG-LVH criteria. Cohen’s Kappa, a measure of concordance between ECG and echocardiography with regard to LVH, was 0.24 for the Peguero-Lo Presti criterion, −0.01–0.13 for single traditional criteria, and 0.20 for any traditional criterion. However, by the receiver operating characteristics (ROC) curve analysis, the overall ability to discriminate between patients with and without LVH was insignificantly lower for the Peguero-Lo Presti versus Cornell voltage as a continuous variable (area under the ROC curve: 0.65 (95% CI, 0.48–0.81) vs. 0.71 (0.55–0.86), p = 0.5). In conclusion, our preliminary results suggest a slightly better, albeit still low, agreement of the novel Peguero-Lo Presti ECG criterion compared to the traditional ECG-LVH criteria with echocardiographic LVH in severe aortic stenosis.

Although ECG used to be a traditional method to detect left ventricular hypertrophy (LVH), its importance has decreased over the years and echocardiography has emerged as a routine technique to diagnose LVH. Intriguingly, an independent negative prognostic effect of the “electrical” LVH (i.e., by ECG voltage criteria) beyond echocardiographic LVH was demonstrated both in hypertension and aortic stenosis (AS), the most prevalent heart valve disorder. Our aim was to estimate associations of the ECG-LVH voltage criteria with echocardiographic LVH and indices of AS severity. We retrospectively manually analyzed ECG tracings of 50 patients hospitalized in our center for severe isolated aortic stenosis, including 32 subjects with echocardiographic LVH. The sensitivity of single traditional ECG-LVH criteria in detecting echocardiographic LVH was 9–34% and their respective specificity averaged 78–100%. The ability to predict echocardiographic LVH was higher for S-waves than R-waves (mean area under the receiver operating curve (AUC): 0.62–0.70 vs. 0.58–0.65). Among combinations of R- and S-waves, the discriminating ability was highest for the Cornell voltage (AUC: 0.71) compared to the Sokolow–Lyon, Romhilt and Gubner–Ungerleider voltage (AUC: 0.62–0.68). By multiple regression, peak aortic pressure gradient was positively related to the Sokolow–Lyon (β = 1.7 ± 0.5, p = 0.002) and Romhilt voltage (β = 1.3 ± 0.5, p = 0.01), but not Cornell (0.5 ± 0.3, p = 0.2) or Gubner-Ungerleider voltage (β = 0.0 ± 0.5, p > 0.9), regardless of LV mass index. In conclusion, echocardiographic LVH and stenosis severity appear to have distinct associations with traditional ECG-LVH criteria in AS. A moderate diagnostic superiority of the Cornell voltage criterion with regard to anatomic LVH might result from its unique ability to include depolarization vectors in both the frontal and horizontal plane with consequent lesser sensitivity to the confounding effect of obesity.

Endothelial dysfunction, associated with depressed nitric oxide (NO) bioavailability, is a well-recognized contributor to both accelerated atherogenesis and microvascular complications in type 2 diabetes (DM). However, growing evidence points to the comorbidities-driven endothelial dysfunction within coronary microvessels as a key player responsible for left ventricular (LV) diastolic dysfunction, restrictive LV remodeling and heart failure with preserved ejection fraction (HFpEF), the most common form of heart failure in DM. In this review we have described: (1) multiple cellular pathways which may link depressed NO bioavailability to LV diastolic dysfunction and hypertrophy; (2) hemodynamic consequences and prognostic effects of restrictive LV remodeling and combined diastolic and mild systolic LV dysfunction on cardiovascular outcomes in DM and HFpEF, with a focus on the clinical relevance of endothelial dysfunction; (3) novel therapeutic strategies to improve endothelial function in DM. In summary, beyond associations with accelerated atherogenesis and microvascular complications, endothelial dysfunction supplements the multiple interwoven pathways affecting cardiomyocytes, endothelial cells and the extracellular matrix with consequent LV dysfunction in DM patients. The association amongst impaired endothelial function, reduced coronary flow reserve, combined LV diastolic and discrete systolic dysfunction, and low LV stroke volume and preload reserve—all of which are adverse outcome predictors—is a dangerous constellation of inter-related abnormalities, underlying the development of heart failure. Nevertheless, the relevance of endothelial effects of novel drugs in terms of their ability to attenuate cardiovascular remodeling and delay heart failure onset in DM patients remains to be investigated.