Objective Data on sex differences in acromegaly at the time of diagnosis vary considerably between studies. Design A nationwide cohort study including all incident cases of acromegaly (1978–2010, n = 596) and a meta‐analysis on sex differences in active acromegaly (40 studies) were performed. Method Sex‐dependent differences in prevalence, age at diagnosis, diagnostic delay, pituitary adenoma size, insulin‐like growth factor 1 (IGF‐I) and growth hormone (GH) concentrations were estimated. Results The cohort study identified a balanced gender distribution (49.6% females) and a comparable age (years) at diagnosis (48.2 CI95% 46.5–49.8 (males) vs. 47.2 CI95% 45.5–48.9 (females), p = 0.4). The incidence rate significantly increased during the study period (R2 = 0.42, p < 0.01) and the gender ratio (F/M) changed from female predominance to an even ratio (SR: 1.4 vs. 0.9, p = 0.03). IGF‐ISDS was significantly lower in females compared to males, whereas neither nadir GH nor pituitary adenoma size differed between males and females. In the meta‐analysis, the weighted percentage female was 53.3% (CI95% 51.5–55.2) with considerable heterogeneity (I2 = 85%) among the studies. The mean age difference at diagnosis between genders was 3.1 years (CI95% 1.9–4.4), and the diagnostic delay was longer in females by 0.9 years (CI95% −0.4 to 2.1). Serum IGF‐I levels were significantly lower in female patients, whereas nadir GH, and pituitary adenoma size were comparable. Conclusion There are only a minor sex differences in the epidemiology of acromegaly at the time of diagnosis except that female patients are slightly older and exhibit lower IGF‐I concentrations and a longer diagnostic delay.

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Objective To study the socioeconomic status in acromegaly in a population-based follow-up study. Methods All incident cases of acromegaly (n=576) during the period 1977-2010 were included. For every patient, 100 persons were sampled from the general population matched for date of birth and gender (comparison cohort). Cox regression and hazard ratios (HR), conditional logistic regression and linear regression with 95% confidence intervals (CI) were used. Outcome measures Retirement, social security benefit, annual income, cohabitation, separation, parenthood and educational level. Results The proportion of retired individuals was significantly higher in patients with acromegaly after the time of diagnosis (HR:1.43, CI95%:1.26-1.62) and also during the 5-year pre-diagnostic period (HR:1.15, CI95%:1.03-1.28). More individuals with acromegaly received social security benefit compared to the comparison cohort during the initial period after the time of diagnosis. Among patients who maintained a job, the annual income was similar to the comparison cohort. Compared with the background population, cohabitation was lower (HR:0.69, CI95%:0.50-0.95) as was parenthood (HR:0.56, CI95%:0.39-0.80), whereas neither educational level (HR:0.61, CI95%:0.35-1.06) nor separation (HR:1.13, CI95%:0.86-1.47) were different. Female gender and insufficient disease control were associated with a significantly worse socioeconomic status. Conclusion 1) Socioeconomic status is impaired in patients with acromegaly even before a diagnosis of acromegaly. 2) Females and patients without disease remission have worse outcomes. 3) Early diagnosis and effective treatment of acromegaly could be important factors in mitigating the negative impact on socioeconomic factors.

Objective Primary aldosteronism (PA) is the most common cause of endocrine hypertension and adrenalectomy is the firstline treatment for unilateral PA. Suppression of aldosterone secretion of the nondominant adrenal gland at adrenal venous sampling (AVS), that is, contralateral suppression (CLS) has been suggested as a marker of disease severity. However, whether factors such as CLS, age, gender or comorbidities are associated with remission after surgery is controversial. The objective of this study is to investigate the prognostic value of CLS, age, gender, aldosterone‐to‐renin ratio, antihypertensives and comorbidities for clinical and biochemical remission following unilateral adrenalectomy in patients with PA. Design and patients A retrospective study of patients with PA referred for AVS at Rigshospitalet from May 2011 to September 2020, who subsequently underwent adrenalectomy. Clinical remission was defined according to the PA surgical outcome criteria, whereas complete biochemical remission was defined as normalization of hypokalaemia without potassium substitution. Results Eighty‐four patients were available for analysis of primary outcome. Among patients with CLS, 28/58 (48.3%) obtained complete clinical remission after surgery compared with 10/26 (38.5%) without CLS (p = .40). Complete biochemical remission was obtained in 55/58 (94.8%) of patients with CLS compared with 25/28 (89.3%) without CLS (p = .44). Female gender and lower number of antihypertensives at baseline were associated with higher odds for complete clinical remission, whereas none of the investigated variables were associated with biochemical remission. Conclusion CLS was not significantly associated with complete clinical or biochemical remission in this cohort. Our results confirmed that female gender and lower number of antihypertensives were predictors of clinical remission.

Background and methods Inflammation is a hallmark of cancer and its progression. Plasma levels of C‐reactive protein (CRP), interleukin‐6 (IL‐6) and YKL‐40 reflect inflammation, and are elevated in patients with cancer. This study investigated whether plasma CRP, IL‐6 and YKL‐40 had diagnostic value in 753 patients referred with nonspecific signs and symptoms of cancer to a diagnostic outpatient clinic. Results In total, 111 patients were diagnosed with cancer within 3 months and 30 after 3 months. CRP, IL‐6 and YKL‐40 were elevated in 44%, 60% and 45% of the cancer patients, and in 15%, 33% and 25% of the patients without cancer. Elevated levels of all three markers were associated with risk of cancer within 3 months: CRP (odds ratio (OR) 4.41, 95% confidence interval (CI) 2.86–6.81), IL‐6 (OR = 2.89, 1.91–4.37) and YKL‐40 (OR = 2.42, 1.59–3.66). Multivariate explorative analyses showed that increasing values were associated with the risk of getting a cancer diagnosis (continuous scale: CRP (OR = 1.28, 1.12–1.47), carcinoembryonic antigen (CEA) (OR = 1.61, 1.41–1.98), CA19‐9 (OR = 1.15, 1.03–1.29), age (OR = 1.29, 1.02–1.63); dichotomized values: CRP (OR = 2.54, 1.39–4.66), CEA (OR = 4.22, 2.13–8.34), age (OR = 1.42, 1.13–1.80)). CRP had the highest diagnostic value (area under the curve = 0.69). Combined high CRP, IL‐6 and YKL‐40 was associated with short overall survival (HR = 3.8, 95% CI 2.5–5.9, p < 0.001). Conclusion In conclusion, plasma CRP, IL‐6 and YKL‐40 alone or combined cannot be used to identify patients with cancer, but high levels were associated with poor prognosis. CRP may be useful to indicate whether further diagnostic evaluation is needed when patients present with nonspecific signs and symptoms of cancer.

Background and objective: Adrenalectomy for primary aldosteronism (PA) has been associated with decreased kidney function after surgery. It has been proposed that elimination of excess aldosterone unmasks an underlying failure of the kidney function. Contralateral suppression (CLS) is considered a marker of aldosterone excess and disease severity, and the purpose of this study was to assess the hypothesis that CLS would predict change in kidney function after adrenalectomy in patients with PA. Design and patients: Patients with PA referred for adrenal venous sampling (AVS) between May 2011 and August 2021 and who were subsequently offered surgical or medical treatment were eligible for the current study. Results: A total of 138 patients were included and after AVS 85/138 (61.6%) underwent adrenalectomy while 53/138 (38.4%) were treated with MR‐antagonists. In surgically treated patients the estimated glomerular filtration rate (eGFR) was reduced by 11.5 (SD: 18.5) compared to a reduction of 5.9 (SD: 11.5) in medically treated patients (p = .04). Among surgically treated patients, 59/85 (69.4%) were classified as having CLS. After adrenalectomy, patients with CLS had a mean reduction in eGFR of 17.5 (SD: 17.6) compared to an increase of 1.8 (SD: 12.8) in patients without CLS (p < .001). The association between CLS and change in kidney function remained unchanged in multivariate analysis. Post‐surgery, 16/59 (27.1%) patients with CLS developed hyperkalemia compared to 2/26 (7.7%) in patients without CLS (p = .04).Conclusion: This retrospective study found that CLS was a strong and independent predictor of a marked reduction of eGFR and an increased risk of hyperkalemia after adrenalectomy in patients with PA.

Background. Alpha-receptor blockade is the mainstay in preoperative treatment of patients with pheochromocytoma and paraganglioma (PPGL). However, evidence regarding optimal dosage regimen is lacking. This study compares the per- and postoperative hemodynamics in patients pre-treated with a high or low dose of phenoxybenzamine. Methods. 30 consecutive patients with PPGL undergoing laparoscopic adrenalectomy were identified retrospectively. All were pretreated with phenoxybenzamine but at two separate endocrine departments aiming at different blood pressure target. End-dosage of phenoxybenzamine differed significantly between departments with 14 patients receiving a high dose regimen and 16 a low dose regimen. As a control group, we included 42 patients undergoing laparoscopic adrenalectomy for other reasons. Primary purpose was to compare per- and postoperative hemodynamics in the high and low dose groups. Secondly, to compare these endpoints to the control group. Results. Baseline characteristics did not differ between the phenoxybenzamine treated groups. The high dose group had less intra-operative systolic and diastolic blood pressure fluctuation (p = 0.03) and less periods with heart rate above 100 bpm (p = 0.04) as compared to the low dose group. Use of intravenous fluids were similar between the two groups. However, postoperatively, more intravenous fluids were administered in the high dose group. Overall, the control group was more hemodynamic stable as compared to either group treated for PPGL. Conclusions. High dose phenoxybenzamine improves per-operative hemodynamic stability but causes a higher postoperative requirement for intravenous fluids. Overall, PPGL surgery is related to greater hemodynamic instability compared to adrenalectomy for other reasons.

Genome-wide cfDNA fragmentation patterns have previously been demonstrated to distinguish with high sensitivity and specificity between plasma samples from individuals with and without cancer. To further evaluate cfDNA fragmentation as a blood-based screening test for cancer, we have used low coverage whole genome sequencing to analyze plasma samples from 280 patients referred to an advanced diagnostic center due to non-organ specific signs and symptoms of cancer. Within three months of inclusion, 74 of these patients were diagnosed with one of 16 different solid cancers while 206 patients did not have cancer. Using an improved version of our genome-wide cfDNA fragmentation analyses, we observed high performance in distinguishing cancer and non-cancer samples (AUC=0.92, 95% CI 0.88-0.96), including lung cancer (n=12, AUC=0.91, 95% CI 0.80-1.00) and colorectal cancer (n=12, AUC=0.94, 95% CI 0.89-0.99). Although many of the patients in this cohort had other common illnesses including cardiovascular, autoimmune, and inflammatory diseases, the machine learning models of cfDNA fragmentation were able to detect cancer with high sensitivity and specificity. These data support the development of genome-wide cfDNA fragmentation analyses as a non-invasive detection screening approach for both single and multiple cancers. Citation Format: Jacob Carey, Alessandro Leal, Bryan Chesnick, Denise Butler, Michael Rongione, Sian Jones, Rob Scharpf, Mette Villadsen, Stig E. Bojesen, Julia S. Johansen, Claus L. Feltoft, Victor E. Velculescu, Nicholas C. Dracopoli. Detecting cancer using genome-wide cfDNA nucleosomal fragmentation in a prospective multi cancer cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 570.