Patients with active acromegaly (ACRO) exhibit low hepatocellular lipids (HCL), despite pronounced insulin resistance (IR). This contrasts the strong association of IR with nonalcoholic fatty liver disease in the general population. Since low HCL levels in ACRO might be caused by changes in oxidative substrate metabolism, we investigated mitochondrial activity and plasma metabolomics/lipidomics in active ACRO. Fifteen subjects with ACRO and seventeen healthy controls, matched for age, BMI, sex, and body composition, underwent ³¹ P/ ¹ H-7-T MR spectroscopy of the liver and skeletal muscle as well as plasma metabolomic profiling and an oral glucose tolerance test. Subjects with ACRO showed significantly lower HCL levels, but the ATP synthesis rate was significantly increased compared with that in controls. Furthermore, a decreased ratio of unsaturated-to-saturated intrahepatocellular fatty acids was found in subjects with ACRO. Within assessed plasma lipids, lipidomics, and metabolomics, decreased carnitine species also indicated increased mitochondrial activity. We therefore concluded that excess of growth hormone (GH) in humans counteracts HCL accumulation by increased hepatic ATP synthesis. This was accompanied by a decreased ratio of unsaturated-to-saturated lipids in hepatocytes and by a metabolomic profile, reflecting the increase in mitochondrial activity. Thus, these findings help to better understanding of GH-regulated antisteatotic pathways and provide a better insight into potentially novel therapeutic targets for treating NAFLD.

Purpose: The natural history in unselected cohorts of patients with pheochromocytoma/ paraganglioma (PPGL) followed for a period >10 years remains limited. We aimed to describe baseline characteristics and outcome of a large cohort and to identify predictors of shorter survival.Methods: This retrospective single-center study included 303 patients with newly diagnosed PPGL from 1968 to December 31, 2023, in 199 prospectively supplemented since July 2020. Mean follow-up was 11.4 (range 0.3-50) years, germline genetic analyses were available in 92.1%. The main outcome measures were overall (OAS), disease-specific (DSS), recurrence-free (RFS) survival and predictors of shorter survival evaluated in patients with metastases at first diagnosis (n=12), metastatic (n=24) and nonmetastatic (n=33) recurrences and without evidence of PPGL after first surgery (n=234).Results: Age at study begin was 49.4 ± 16.3 years. There were 72 (23.8%) deaths, 15 (5.0%), 29 (9.6%) and 28 (9.2%) due to PPGL, cardiovascular disease (CVD) and malignant or other diseases, respectively. Median OAS, DSS1 (tumor-related) and DSS2 (DSS1 and death caused by CVD) were 4.8, 5.9 and 5.2 years (patients with metastases at first diagnosis), 21.2, 21.2 and 19.9 years, and 38.0, undefined and 38.0 years (patients with metastatic and with nonmetastatic recurrences, respectively). Major adverse cardiovascular events (MACE) preceded the first diagnosis in 15% (n=44). Shorter DSS2 correlated with older age (P ≤ 0.001), male sex (P ≤ 0.02), MACE (P ≤ 0.01) and primary metastases (P<0.0001, also for DSS1).Conclusion: The clinical course of unselected patients with PPGL is rather benign. Survival rates remain high for decades, unless there are MACE before diagnosis or metastatic disease.

Studies conflict concerning the use of enzyme immunoassays (EIA) for plasma free metanephrines (P-MNs) vs. other methods for pheochromocytoma/paraganglioma (PPGL) diagnosis. We compared commercially available EIAs for P-MNs with high-pressure liquid chromatography (HPLC) for 24 h-urinary MNs (U-MNs) and -catecholamines (U-CATs). 943 (565 female, 378 male) patients (54 PPGL, 889 Non-PPGL) were studied. Simultaneous measurements of all parameters analyzed at the central lab of our university hospital was mandatory for inclusion. Sensitivity of P-MNs (94.4%) was similar to that of U-MNs (100%), and both were higher than of U-CATs (77.8%), specificity of P-MNs (100%) higher than of U-MNs (73.6%), and similar to U-CATs (99.8%). With the recently proposed downward adjusted ULN of P-MNs to correct for the reported negative bias of the EIAs sensitivity (98.1%) raised non-significantly, but specificity decreased significantly (94.8%). Areas under receiver-operating characteristic curves indicated comparable diagnostic performance of P-MNs (0.989) vs. U-MNs (0.995), both better than U-CATs (0.956). In summary, the EIAs to measure P-MNs performed similarly to U-MNs by HPLC, and both better than U-CATs by HPLC. The post-test probability of PPGL given a positive test result was best for P-MNs, and higher than for the other pairs of analytes. Downward corrections of ULN of P-MNs did not improve test performances.

Background: Large-scale data on the diagnostic performance of functional imaging in metastatic pheochromocytoma/paraganglioma (PPGL) are scarce. Objective: To analyze the diagnostic accuracy of functional imaging for the assessment of metastases during long-term follow-up (FU). Design: Retrospective cohort study, 1991–2025. Setting: Referral center. Outcomes: Sensitivity and specificity of ¹²³MIBG-, ¹⁸F-DOPA-, ⁶⁸GaDOTA-based and ¹⁸FDG PET/CT. Patients: Patients with metastatic PPGL and without PPGL, ≥1 functional imaging prior to first diagnosis and/or during FU and FU ≥ 3 months. Results: 59 ¹²³MIBG-, 101 ¹⁸F-DOPA-, 11 ¹⁸FDG- and 74 ⁶⁸GaDOTA-based PET/CT were performed in 57 patients with metastatic PPGL and 37 ¹²³MIBG-, 323 ¹⁸F-DOPA-, 259 ¹⁸FDG- and 641 ⁶⁸GaDOTA-based imaging in 527 patients without PPGL. FU was 11.6 ± 11.4 and 5.1 ± 4.7 years, respectively. Sensitivity for the detection of all metastases (total cohort) by patient-based analysis was comparable between ¹⁸F-DOPA (77%), both ⁶⁸GaDOTA-based tracers combined (67%) and ¹²³MIBG (72%); lesion-based analysis was better for ¹⁸F-DOPA (94%) than for ⁶⁸GaDOTA (85%) and ¹²³MIBG (67%). Specificity (patient- and lesion-based) of ¹⁸F-DOPA vs. ⁶⁸GaDOTA (96–99%) was comparable and better than ¹²³MIBG (73%) and ¹⁸FDG (75%). Conclusions: Sensitivity of ¹⁸F-DOPA was superior to ⁶⁸GaDOTA for the detection of all and bone metastases in the total cohort and in patients with PCC, that of ⁶⁸GaDOTA was better for bone metastases with PGL, specificity was comparable and for both was better than for ¹⁸FDG and ¹²³MIBG. Given the beneficial pharmaceutical properties and favorable diagnostic performance, ¹⁸F-DOPA may be a good alternative to ⁶⁸GaDOTA-based tracers for the functional imaging of metastatic PPGL.

Background: Hemodynamic instability is common during adrenalectomy for pheochromocytoma and paraganglioma (PPGL). Most analyses focus on the risk factors for intraoperative hypertension, but hypotension is a frequent and undesirable phenomenon during PPGL surgery. This study aimed to analyze the risk factors for hypotensive episodes during the removal of PPGL, and whether these episodes are always associated with concomitant intraoperative hypertensive events. Methods: A consecutive series of 121 patients (91.7% receiving preoperative alpha-blockade) treated with transperitoneal endoscopic adrenalectomy at a university hospital were analyzed, and pre- and intraoperative risk factors for intraoperative hypotension with or without intraoperative hypertension were analyzed using univariable and multivariable logistic regression analyses. Results: In total, 58 (56.2%) patients presented with intraoperative hypotension. Of these, 25 (20.7%) patients showed only hypotensive episodes but no hypertensive episodes (group 1), and 43 (35.5%) patients had both intraoperative hypotension and hypertension (group 2). The remaining 53 patients did not present with hypotension at all (group 3). When comparing group 1 (hypotension only) to all other patients with incidental diagnosis, higher age and lower preoperative diastolic arterial blood pressure (ABP) were significant risk factors for intraoperative hypotension; only the latter two were still significant in multivariate analysis. The significant risk factors for hypotension independent of hypertension (group 1 + 2 vs. group 3) were age and incidental diagnosis, pre-existing diabetes mellitus, and intraoperative use of remifentanil. Incidental diagnosis and use of remifentanil reached the level of significance in multivariate analysis. Conclusions: Since older age, incidental diagnosis of PPGL, lower preoperative ABP, and diabetes mellitus are risk factors for intraoperative hypotension, preoperative alpha-blocker treatment should be individualized for those at risk for hypotension. In addition, remifentanil should be used cautiously in the risk group.