Purpose: To evaluate the diagnostic accuracy of the 131I-6β-iodomethyl-19-norcholesterol (NP-59) adrenal scintigraphy for the subtyping diagnosis of primary aldosteronism (PA), considering as gold standard for the diagnosis of unilateral PA (UPA), either the results of the adrenal venous sampling (AVS) or the outcome after adrenalectomy. Methods: A retrospective multicenter study was performed on PA patients from 14 Spanish tertiary hospitals who underwent NP-59 scintigraphy with an available subtyping diagnosis. Patients were classified as UPA if biochemical cure was achieved after adrenalectomy or/and if an AVS lateralization index > 4 with ACTH stimulation or >2 without ACTH stimulation was observed. Patients were classified as having bilateral PA (BPA) if the AVS lateralization index was ≤4 with ACTH or ≤2 without ACTH stimulation or if there was evidence of bilateral adrenal nodules >1 cm in each adrenal gland detected by CT/MRI. Results: A total of 86 patients with PA were included (70.9% (n = 61) with UPA and 29.1% (n = 25) with BPA). Based on the NP-59 scintigraphy results, 16 patients showed normal suppressed adrenal gland uptake, and in the other 70 cases, PA was considered unilateral in 49 patients (70%) and bilateral in 21 (30%). Based on 59-scintigraphy results, 10.4% of the patients with unilateral uptake had BPA, and 27.3% of the cases with bilateral uptake had UPA. The AUC of the ROC curve of the NP-59 scintigraphy for PA subtyping was 0.812 [0.707–0.916]. Based on the results of the CT/MRI and NP-59 scintigraphy, only 6.7% of the patients with unilateral uptake had BPA, and 24% of the cases with bilateral uptake had UPA. The AUC of the ROC curve of the model combining CT/MRI and 59-scintigraphy results for subtyping PA was 0.869 [0.782–0.957]. Conclusion: The results of NP-59 scintigraphy in association with the information provided by the CT/MRI may be useful for PA subtyping. However, their diagnostic accuracy is only moderate. Therefore, it should be considered a second-line diagnostic tool when AVS is not an option.

Purpose To evaluate whether the clinical, biochemical and radiological features of patients with primary aldosteronism (PA) can predict both main subtypes of PA. Methods A retrospective multicenter study of PA patients followed in 27 Spanish tertiary hospitals (SPAIN-ALDO Register). Only patients with confirmed unilateral or bilateral PA based on adrenal venous sampling (AVS) and/or postsurgical biochemical cure after adrenalectomy were included. Supervised regression techniques were used for model development. Results 328 patients [270 unilateral PA (UPA), 58 bilateral PA (BPA)] were included. The area under the curve (AUC) for aldosterone/potassium ratio and aldosterone responses following saline infusion test were 0.602 [95%CI 0.520 to 0.684] and 0.574 [95% CI 0.446–0.701], respectively, to differentiate UPA from BPA. The AUC was 0.825 [95% 0.764–0.886] when the prediction model with seven parameters – comorbidities (dyslipidemia, cerebrovascular disease, sleep apnea syndrome [SAS]), systolic blood pressure (SBP), plasma aldosterone levels (PAC), hypokalemia and unilateral adrenal nodule >1 cm and normal contralateral adrenal gland on CT/MRI – was used. In patients without comorbidities, hypokalemia, SBP > 160 mmHg, PAC > 40 ng/dL, and unilateral adrenal lesions were associated with a likelihood of having a UPA of 98.5%. The chance of BPA was higher in individuals with comorbidities, SBP < 140 mmHg, normokalemia, low PAC levels, and no adrenal tumors on the CT/MRI (91.5%). Conclusion A combination of high PAC, SBP > 160 mmHg, low serum potassium, a unilateral adrenal nodule>1 cm and no comorbidities could predict a UPA with a 98.5% accuracy.

Objective: To evaluate the efficacy and safety of osilodrostat in patients with Cushing’s disease (CD). Methods: A retrospective, multicenter, real-world study of patients with CD. The main efficacy endpoint was the proportion of patients who were complete responders (urinary free cortisol [UFC] < the upper limit of normal and/or with adrenal insufficiency development). Results: Thirty-seven CD patients were enrolled. There were 33 patients who initially received osilodrostat in monotherapy and 4 in combination. However, 3 patients of the monotherapy group were switched to combination therapy. The median duration of osilodrostat treatment was 5 months (range 1–93). All the patients were classified as responders: 33 (89.2%) had complete response and 4 partial response. A positive correlation was detected between the percentage of UFC decrease and the maximum (r = 0.481, p = 0.006) and the maintenance doses (r = 0.440, p = 0.011). The initial doses of osilodrostat were a predictor of complete response (vs. partial) (Odds ratio [OR] 2.82, p = 0.030). The median time to UFC normalization in the group of complete responders was 4 weeks (range 1–20) and UFC normalized before or at month 1 in 67% (n = 20/30) of the patients. Osilodrostat led to a significant decrease in systolic and diastolic blood pressure in parallel with a reduction of antihypertensive medications. Conclusions: Osilodrostat leads to a complete UFC normalization in up to 90% of the patients with CD, in parallel with an improvement in the cardiometabolic profile. A proper titration of osilodrostat is important to achieve a complete response since a positive correlation between the doses and the UFC reduction was observed.

Background: The outcomes of transsphenoidal surgery (TSS) for pituitary adenoma (PA) depend on many factors, including the availability of an expert team and the volume of surgeries performed. Data on the outcomes of TSS for PA are scarce in our country. TESSPAIN evaluates TSS outcomes in Spanish centers to assess the influence of surgical volume and specialized neurosurgical teams on success and complication rates.Methods: A retrospective, nationwide, study of Spanish centers performing TSS between January 2018 and December 2022. Centers were classified as high volume (HV) [n=11, defined as centers with recognized expertise in Spain or those performing more than 25 TSS/year] or non-HV. Data collection included surgical success rates, complications, and pituitary adenoma resectability (R-PA). Additional analyses evaluated the impact of dedicated neurosurgical teams (DNT) within HV centers.Results: A total of 2815 TSS from 29 Spanish centers were included (1421 NSPA, 436 GH-secreting, 323 Cushing’s disease, 127 PRL-secreting and 25 TSH-secreting PA). The overall success rate was 50.5%, 76.8% for R-PA. HV centers had a higher overall success rate (53.1 vs. 47.7%; p=0.03). Better TSS outcomes for NSPA accounted for this difference. The overall TSS complication rate was 22.1%, which was higher for NSPA than for SPA (25.0 vs. 17.7%). The overall complication rate of TSS for PA was significantly higher in non-HV centers than in HV centers (24 vs 20.4.0; p <0.01). Centers with a DNT showed a trend to higher success rate in R-PA, while having a lower overall incidence of complications in TSS for PA than HV centers without a DNT (18.5 vs. 23.0; p=0.058), mainly reducing the rate of permanent ADH deficiency in all TSS for PA (2.7 vs. 8.4%; p<0.001).Conclusion: Higher surgical volume and DNT are associated with improved TSS outcomes for PA in Spain. Our results support the recommendation of concentration of pituitary surgery in a reduced number of centers of expertise in our country in order to improve the success rate and reduce complications, mainly postoperative ADH deficiency.

Background: Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy with variable outcomes post-adrenalectomy. The S-GRAS score integrates 5 clinical and pathological factors to predict prognosis but requires external validation in diverse settings. Methods: We validated the S-GRAS score in 138 ACC patients from the Spanish ICARO-GETTHI/SEEN registry (1998-2023). Model performance was assessed using discrimination, calibration, and accuracy. Exploratory refinements included non-linear modeling of age and Ki-67% and an expanded model incorporating venous invasion and tumor size. Cox models examined the interaction between S-GRAS and adjuvant mitotane. Results: A total of 76 recurrence events were recorded. The S-GRAS score demonstrated good discrimination for overall survival (C-index 0.706, 95% CI, 0.628-0.785) and recurrence-free survival (C-index 0.673, 95% CI, 0.601-0.745) with well-calibrated predictions. Five-year survival rates differed significantly across score groups: 100% for scores 0-1, 81.6% for 2-3, 55% for 4-5, and 33.8% for 6-7. Non-linear modeling of Ki-67% improved performance (C-index 0.738 for RFS, 0.761 for OS), but adding clinical variables offered minimal benefit, leaving 75% of recurrence variability unexplained. Higher S-GRAS scores correlated with increased mitotane benefit (HR 0.57, 95% CI, 0.34-0.97 for score 4; HR 0.46, 95% CI, 0.23-0.94 for score 5), indicating a potential incremental benefit pattern. Conclusions: Our findings validate the S-GRAS score in a multicenter cohort and support its use in identifying candidates for adjuvant mitotane. Non-linear modeling of Ki-67% enhances predictive precision without increasing complexity, but the performance plateau of clinical variables suggests that integrating molecular biomarkers may be necessary to improve prognostic accuracy.