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Background and aims: Glucagon-like peptide-1 receptor agonists (GLP-1ra) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have each shown kidney protective effects in large clinical outcome-studies. The mechanisms behind these effects are sparsely elucidated and the effects of combination therapy remains obscure. In this randomized clinical trial, we compared kidney function in persons with type 2 diabetes receiving either the GLP1-ra semaglutide (SEMA), the SGLT2-i empagliflozin (EMPA) or the combination (COMBI). EMPA treatment was double blinded. Kidney oxygenation was primary outcome and regional (cortex and medulla) assessments were included.Materials and methods: 80 participants with type 2 diabetes (age 68.1 ± 6.5 years, male 76.25 %, diabetes duration 8[4;12] years), were randomized to either placebo, EMPA, SEMA or COMBI for 32 weeks. Kidney excretory function was assessed by urinary albumine/creatinine ratio (UACR) and glomerular filtration rate (GFR). Magnetic resonance imaging was used to assess kidney oxygenation with R2*(Hz) (higher values indicating lower oxygenation) by a blood oxygen level depedent sequence (BOLD) and renal perfusion (arterial spin labelling (ASL)).Results: UACR was reduced significantly for the COMBI group (-35% 95% CI [-46;-92]%, p=0.01), with the same tendency for each of the separate treatment arms. GFR decreased significantly from baseline and compared to placebo in all three treatment groups (SEMA -19 mL/min 95% CI [-7;-31]mL/min, p=0.001; EMPA -18 mL/min 95% CI [-6;-30]mL/min, pConclusion: Our data demonstrate joined effects of EMPA and SEMA on UACR and GFR and reveal important differential effects of EMPA and SEMA on renal physiology. As hypoxia is considered a main driver in kidney disease, we hypothesized that EMPA and/or SEMA would exert their beneficial effects through improved kidney oxygenation. Contrary to our hypothesis, EMPA treatment for 32 weeks was not associated with improved medullary oxygenation but even slightly reduced it. This is in line with recent rodent studies. SEMA treatment is associated with a substantial reduction in kidney perfusion, probably leading to reduced hyperfiltration. To our knowledge, these effects have not previously been demonstrated in humans.

With wider application and technical improvement of imaging the discovery of adrenal incidentalomas (AI) has been skyrocketing. AI need to be investigated for evidence of hormonal hypersecretion and malignancy, and this causes a considerable use of health resources and potential medicalisation. In the "no-need-to-see" process, the clinical assessment of the citizen will only take place, if the diagnostic tests are abnormal. In this review, we examine the predictive values of imaging and paraclinical testing and argue, that normal test results in people without extra-adrenal cancer exclude disease.

Background Pheochromocytomas and catecholamine-secreting paragangliomas (PPGL) are rare catecholamine-producing tumors. Due to the rarity, limited data on prognosis exists. Here, we present national data on mortality for radically operated patients compared to the background population over a period of 40 years. Materials and methods We have previously identified a national cohort of 588 PPGL patients diagnosed in Denmark 1977-2016. After excluding 80 patients diagnosed post-mortem, we found that out of 508 patients diagnosed alive, 479 (94%) underwent radical surgery. Each operated patient was matched on birth year, age and sex with 100 random controls from the general population. PPGL patients and comparison cohort members were then followed from date of surgery (or matched index date) to date of death, emigration or 31st of December 2016. Mortality rate-ratios (MRR) were calculated in patient-comparisons strata using Cox regression and adjusted for Charlson Comorbidity Index (CCI). CCI was determined using diagnosis codes registered before time of PPGL diagnosis (or matched index date). To identify prognostic factors, we obtained health records and analyzed clinical data in a geographic subgroup of patients (N=162). Results Operated PPGL patients had a median age of 55 years (Q1-Q3 42-65) and 56% were female. 26% of PPGL patients had a Charlson Comorbidity Index of 2 or more, compared to only 9% in the comparison cohort, with a higher proportion of patients registered with cardiovascular disease (19% vs 7%), cancer (16% vs 5%) and with diabetes (12% vs 3%). Median follow-up time for patients was 7.2 years (Q1-Q3 3.4-15.6), with 10- and 20-year survival after surgery of 78% (95% CI 73-82) and 64% (95% CI 57-69), respectively. MRR for PPGL patients was 1.8 (95% CI 1.5-2.2) compared to the comparison cohort and 1.4 (95% CI 1.2-1.7) when adjusted for CCI. In the subcohort of PPGL patients with available clinical data (N=162), we found, that patients diagnosed with PPGL due to diagnostic work-up for secondary hypertension (N=27) had the highest mortality after surgery with an adjusted MRR of 3.1 (95% CI 1.7-5.8) compared to these patients’ matched comparison cohorts. Adjusted MRR was 0.9 (95% CI 0.4-1.8, N=49) for patients evaluated for paroxysmal symptoms, 1.0 (95% CI 0.2-4.6, N=16) for patients diagnosed due to hereditary PPGL in family or after syndromic presentation, 1.3 (95% CI 0.7-2.2, N=58) for adrenal incidentalomas, and 2.2 (95% CI 0.9-4.9, N=10) in patients diagnosed due to other causes. Conclusion PPGL patients undergoing radical curative surgery have a higher mortality compared to the background population even when considering their higher comorbidity index at time of diagnosis. Especially patients diagnosed due to work-up for secondary hypertension have an increased mortality. These results indicate that radical surgery might not completely reverse the harmful effects of PPGL.

Background: The completeness of REarranged during Transfection (RET) testing in patients with medullary thyroid carcinoma (MTC) was recently reported as 60%. However, the completeness on a population level is unknown. Similarly, it is unknown if the first Danish guidelines from 2002, recommending RET testing in all MTC patients, improved completeness in Denmark. We conducted a nationwide retrospective cohort study aiming to evaluate the completeness of RET testing in the Danish MTC cohort. Additionally, we aimed to access the completeness before and after publication of the first Danish guidelines and characterize MTC patients who had not been tested.Methods: The study included 200 patients identified from the nationwide Danish MTC cohort 1997-2013. To identify RET tested MTC patients before December 31, 2014, the MTC cohort was cross-checked with the nationwide Danish RET cohort 1994-2014. To characterize MTC patients who had not been RET tested, we reviewed their medical records and compared them with MTC patients who had been tested.Results: Completeness of RET testing in the overall MTC cohort was 87% (95% CI: 0.81-0.91; 173/200). In the adjusted MTC cohort, after excluding patients diagnosed with hereditary MTC by screening, completeness was 83% (95% CI: 0.76.-0.88; 131/158). Completeness was 88% (95% CI: 0.75-0.95; 42/48) and 81% (95% CI: 0.72-0.88) (89/110) before and after publication of the first Danish guidelines, respectively. Patients not RET tested had a higher median age at diagnosis compared to those RET tested. Median time to death was shorter in those not tested relative to those tested.Conclusion: The completeness of RET testing in MTC patients in Denmark seems to be higher than reported in other cohorts. No improvement in completeness was detected after publication of the first Danish guidelines. In addition, data indicate that advanced age and low life expectancy at MTC diagnosis may serve as prognostic indicators to identify patients having a higher likelihood of missing the compulsory RET test.