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.
Acromegaly is an insidious disease associated with severe somatic morbidity but data on socioeconomic status are scarce.
To study the socioeconomic status in acromegaly in a population-based ...follow-up study.
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.
Retirement, social security benefit, annual income, cohabitation, separation, parenthood and educational level.
The proportion of retired individuals was significantly higher in patients with acromegaly after the time of diagnosis (HR, 1.43; 95% CI, 1.26-1.62) and also during the 5-year pre-diagnostic period (HR, 1.15; 95% CI, 1.03-1.28). More individuals with acromegaly received social security benefit compared with 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; 95% CI, 0.50-0.95) as was parenthood (HR, 0.56; 95% CI, 0.39-0.80), whereas neither educational level (HR, 0.61; 95% CI, 0.35-1.06) nor separation (HR, 1.13; 95% CI, 0.86-1.47) were different. Female gender and insufficient disease control were associated with a significantly worse socioeconomic status.
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.
We investigated whether CRP, IL‐6 and YKL‐40 had diagnostic and prognostic value in patients referred with nonspecific signs and symptoms of cancer. Patients with elevated CRP, IL‐6 and YKl‐40 alone or in combination had significantly shorter overall survival.
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.
Summary
This study investigated the association between contralateral suppression, i.e., suppression of the nondominant adrenal gland, and the change in kidney function after surgery in patients with primary aldosteronism treated with adrenalectomy. We found that contralateral suppression was a strong and independent predictor of post‐surgical decline in eGFR.
We describe a married couple who both presented with hypertension and hypokalaemia. Both patients were diagnosed with pseudohyperaldosteronism triggered by the widely used antifungal drug ...itraconazole. This effect appears to be dose-dependent, where a daily intake of 100 mg itraconazole is enough to induce pseudohyperaldosteronism. Clinicians should be aware of pseudohyperaldosteronism as a possible adverse effect of itraconazole, and we recommend monitoring potassium levels and blood pressure in all patients receiving this drug over a longer period of time. Voriconazole is probably an alternative antifungal treatment to itraconazole but also with this drug potassium levels should be monitored.
Biliary tract cancer (BTC) is associated with a dismal prognosis, partly because it is typically diagnosed late, highlighting the need for diagnostic biomarkers. The purpose of this project was to ...identify and validate multiprotein signatures that could differentiate patients with BTC from non-cancer controls.
In this study, we included treatment-naïve patients with BTC, healthy controls, and patients with benign conditions including benign biliary tract disease. Participants were divided into three non-overlapping cohorts: a case-control-based discovery cohort (BTC = 186, controls = 249); a case-control-based validation cohort (validation cohort 1: BTC = 113, controls = 241); and a cohort study-based validation cohort including participants (BTC = 8, controls = 132) referred for diagnostic work-up for suspected cancer (validation cohort 2). Immuno-Oncology (I-O)-related proteins were measured in serum and plasma using a proximity extension assay (Olink Proteomics). Lasso and Ridge regressions were used to generate protein signatures of I-O-related proteins and carbohydrate antigen 19-9 (CA19-9) in the discovery cohort.
Sixteen protein signatures, including 2 to 82 proteins, were generated. All signatures included CA19-9 and chemokine C-C motif ligand 20. Signatures discriminated between patients with BTC vs. controls, with AUCs ranging from 0.95 to 0.99 in the discovery cohort and 0.94 to 0.97 in validation cohort 1. In validation cohort 2, AUCs ranged from 0.84 to 0.94. Nine signatures achieved a specificity of 82% to 84% while keeping a sensitivity of 100% in validation cohort 2. All signatures performed better than CA19-9, and signatures including >15 proteins showed the best performance.
The study demonstrated that it is possible to generate protein signatures that can successfully differentiate patients with BTC from non-cancer controls.
We attempted to find blood sample-based protein profiles that could differentiate patients with biliary tract cancer from those without cancer. Several profiles were found and tested in different groups of patients. The profiles were successful at identifying most patients with biliary tract cancer, pointing towards the utility of multiprotein signatures in this context.
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•Several circulating proteins were associated with biliary tract cancer.•Diagnostic multiprotein signatures were generated and tested.•The signatures discriminated between individuals with biliary tract cancer and controls.•Combining several proteins improved diagnostic ability compared to single markers.
To study the time-dependent changes in disease features of Danish patients with acromegaly, including treatment modalities, biochemical outcome, and comorbidities, with a particular focus on cancer ...and mortality.
Pertinent acromegaly-related variables were collected from 739 patients diagnosed since 1990. Data are presented across three decades (1990-1999, 2000-2009, and 2010-2021) based on the year of diagnosis or treatment initiation.
Adenoma size and insulin-like growth factor I (IGF-I) levels at diagnosis did not differ significantly between study periods. The risk of being diagnosed with diabetes, heart disease, sleep apnea, joint disease, and osteoporosis increased from the 1990s to the later decades, while the mortality risk declined to nearly half. The risk of cancer did not significantly change. Treatment changed toward the use of more medical therapy, and fewer patients underwent repeat surgeries or pituitary irradiation. A statistically significant increase in the proportion of patients achieving IGF-I normalization within 3-5 years was observed over time (69%, 83%, and 88%). The proportion of patients with three or more deficient pituitary hormones decreased significantly over time.
Modern medical treatment regimens of acromegaly as well as increased awareness and improved diagnostics for its comorbidities have led to better disease control, fewer patients with severe hypopituitarism, and declining mortality in the Danish cohort of acromegaly patients. The risk of cancer did not increase over the study period.
Patients with pheochromocytoma and paraganglioma (PPGL) are treated with α-adrenoceptor antagonists to improve peroperative hemodynamics. However, preoperative blood pressure targets differ between ...institutions. We retrospectively compared per- and postoperative hemodynamics in 30 patients with PPGL that were pretreated with phenoxybenzamine aiming at different blood pressure targets at two separate endocrine departments. All patients were subsequently undergoing laparoscopic surgery at Department of Urology, Herlev University hospital. Fourteen patients were treated targeting to symptomatic and significant orthostatic hypotension and 16 patients to a seated blood pressure below 130/80 mmHg. As a control group, we included 34 patients undergoing laparoscopic adrenalectomy for other reasons. The group titrated to orthostatic hypotension required a higher dose of phenoxybenzamine to achieve the blood pressure target. This group had less intraoperative systolic and diastolic blood pressure fluctuation (Mann–Whitney U test; P < 0.05) and less periods with heart rate above 100 b.p.m. (Mann–Whitney U test; P = 0.04) as compared to the group with a preoperative blood pressure target below 130/80 mmHg. Peroperative use of intravenous fluids were similar between the two groups, but postoperatively more intravenous fluids were administered in the group with a target of ortostatism. Overall, the control group was more hemodynamic stable as compared to either group treated for PPGL. We conclude that phenoxybenzamine pretreatment targeting ortostatic hypotension may improve peroperative 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.
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