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Previous research suggests that the use of snus, a smokeless tobacco product, is associated with increased all-cause and cardiovascular mortality, but the underlying mechanisms are unknown. We aimed to evaluate the associations of snus use with biomarkers of cardiometabolic importance: high-sensitivity C-reactive protein (hs-CRP), 25-hydroxyvitamin D (25(OH)D) and calculated free testosterone (cfT). We performed cross-sectional analyses within the population-based Northern Sweden MONICA-study. The study sample consisted of 6 158 never-smoking men and women (of whom 21 and 3.3% were current snus users, respectively), examined between 1990 and 2014. Harmonized analyses on biomarkers were conducted 2016 to 2018. We evaluated the relationships between snus use and biomarker concentrations using linear and logistic regression. Snus use, compared to never-use, was associated with lower hs-CRP (exp(β_ln) 0.88, 95% CI 0.81; 0.96) and 25(OH)D-concentrations (β − 1.01, 95% CI −1.70; −0.33) in mixed-sex analyses. Among men, snus use was also associated with higher cfT-concentrations (exp(β_ln) 1.04, 95% CI 1.01; 1.07). Former snus users had no significant differences in biomarker concentrations. Snus users have lower concentrations of 25(OH)D and hs-CRP, irrespective of sex, while male users have higher cfT-concentrations. These findings may in part contribute to the previously observed increased mortality among snus users.

Context: Substantial diagnostic delay in acromegaly contributes to increased morbidity and mortality. Screening attempts in high-risk groups have yielded few positive cases, underscoring the need for simple and precise prescreening methods.

Objective: Machine-learning analysis of facial images shows promise for acromegaly detection but requires validation in larger, well-characterized cohorts using robust machine-learning frameworks as performed in this study.

Methods: Facial images from different angles were collected via smartphone from 155 acromegaly patients (79% biochemically controlled) and 153 matched controls at all Swedish university hospitals. Six machine-learning models were trained to distinguish acromegaly from control images, including 3 deep neural networks pretrained on diverse image datasets (ImageNet models: ResNet50, InceptionV2, and DenseNet121) and 1 network pretrained specifically on facial images (FaRL). Model performance was compared to assessment by 12 experienced endocrinologists.

Results: The diagnostic accuracy of the FaRL-based model was superior to all ImageNet models and matched the accuracy of human experts (area under the receiver operating characteristic curve 0.89 for both) with similar specificity (0.87 vs 0.93) but higher sensitivity (0.82 vs 0.66). Classification agreement between the best machine-learning model (FaRL) and human experts was 86% for true negatives and 60% for true positives. Machine-learning models and human experts both showed greater sensitivity in identifying acromegaly in male patients.

Conclusion: A deep learning model pretrained on facial features (FaRL) can detect acromegaly from standard photographs with accuracy comparable to that of expert endocrinologists. This supports the feasibility of face analysis as a screening tool for acromegaly.

Context: There is a considerable diagnostic delay in acromegaly, contributing to increased morbidity. Voice changes due to orofacial and laryngeal changes are common in acromegaly.

Objective: Our aim was to explore the use of digital voice analysis as a biomarker for acromegaly using broad acoustic analysis and machine learning.

Methods: Voice recordings from patients with acromegaly and matched controls were collected using a mobile phone at Swedish university hospitals. Anthropometric and clinical data and the Voice Handicap Index (VHI) were assessed. Digital voice analysis of a sustained and stable vowel [a] resulted in 3274 parameters, which were used for training of machine learning models classifying the speaker as “acromegaly” or “control.” The machine learning models were trained with 76% of the data and the remaining 24% was used to assess their performance. For comparison, voice recordings of 50 pairs of participants were assessed by 12 experienced endocrinologists.

Results: We included 151 Swedish patients with acromegaly (13% biochemically active and 10% newly diagnosed) and 139 matched controls. The machine learning model identified patients with acromegaly more accurately (area under the receiver operating curve [ROC AUC] 0.84) than experienced endocrinologists (ROC AUC 0.69). Self-reported voice problems were more pronounced in patients with acromegaly than matched controls (median VHI 6 vs 2, P < .01) with higher prevalence of clinically significant voice handicap (VHI ≥20: 22.5% vs 3.6%).

Conclusion: Digital voice analysis can identify patients with acromegaly from short voice recordings with high accuracy. Patients with acromegaly experience more voice disorders than matched controls.

Primary aldosteronism (PA) is a common cause of hypertension. Compared to patients with essential hypertension, untreated PA is associated with a two- to fourfold greater risk of cardiovascular disease, renal failure, and death. PA is caused by increased secretion of aldosterone from one adrenal gland in 30% of the patients and both adrenal glands in 70%. Patients with unilateral PA can be cured by adrenalectomy, whereas patients with bilateral PA should be treated with mineralocorticoid receptor antagonists. With these disease-specific treatments, the long-term prognosis is generally favorable. A major challenge in the management of patients with PA is, however, subtype differentiation, that is, to determine whether the disease is unilateral or bilateral. Adrenal imaging using CT or MRI misclassifies more than one third of patients, and clinical variables—including blood pressure, aldosterone, and renin concentrations—provide limited guidance, underscoring the need for more accurate diagnostic approaches. Adrenal vein sampling is currently considered the gold standard for this purpose, but it is a technically challenging procedure performed only in specialized centers. After adrenalectomy for unilateral PA, histopathological assessment and subtyping are crucial for determining postoperative prognosis. This process is complex and relies on detailed functional analyses that are not always straightforward to interpret. Therefore, new approaches for subtyping PA are required. In this review, we summarize recent advances in the management of patients with PA, with particular focus on the limitations of current approaches to subtype differentiation and the emerging roles of novel techniques, including positron emission tomography, steroidomics, proteomics, and transcriptomics.

Objective: A delayed diagnosis of pituitary adenomas (PAs) can lead to increased morbidity and reduced quality of life. The aim was to estimate diagnostic delay and investigate the concordance between patient-reported symptoms and the medical record documentation in patients with PA.

Design: Cross-sectional study.

Setting: Seven university hospitals.

Participants: 654 patients: non-functioning PA (NFPA, 314), prolactinoma (118), acromegaly (164) and Cushing's Disease (CD, 58).

Data collection: Questionnaires and medical record extraction.

Primary and secondary outcomes: Type of first healthcare contact, delay of PA diagnosis and patient-reported symptoms and symptoms documented in medical records.

Results: First healthcare contact was usually a general practitioner. Estimated time from symptoms to diagnosis varied from <1 year (66%), 1-5 years (12%), 5-9 years (13%) and >10 years (9%). The longest diagnostic delays were observed in acromegaly and CD. A longer delay was observed in women compared with men (p<0.001). The most frequent patient-reported symptoms among NFPA were headache and visual disturbances; for prolactinomas, menstrual irregularities and headache; for acromegaly, change in appearance and snoring; and for CD, weight gain and tiredness. Concordance between patient-reported symptoms at diagnosis and medical records was found for visual disturbances in NFPA and prolactinomas (Cohen's kappa >0.6) and for menstrual irregularities in prolactinomas (Cohen's kappa >0.7).

Conclusion: We report a large variation in symptom duration before diagnosis with a substantial diagnostic delay in patients with CD and acromegaly. An increased awareness about endocrine diseases in the general population and health professionals may contribute to earlier diagnosis of pituitary adenomas.

Glukokortikoidinducerad binjurebarkssvikt är ett underdiagnostiserat tillstånd som troligen bidrar till ökad mortalitet bland patienter med pågående eller nyligen avslutad kortisonbehandling. Konsensus om handläggning av glukokortikoidinducerad binjurebarkssvikt hos patienter med kortisonbehandling har tidigare saknats, men internationella riktlinjer har nyligen publicerats och sammanfattas i stora drag i denna ABC-artikel. Dessutom presenteras ett nytt svenskt kortisonkort som är avsett att delas ut till patienter som sätts in på prednisolon >5 mg dagligen eller motsvarande i >3–4 veckor, för att informera patient och vårdpersonal om risken för potentiellt livshotande binjurebarkssvikt.

Glucocorticoid-induced adrenal insufficiency is an underdiagnosed condition that possibly contributes to increased mortality. Consensus regarding management of glucocorticoid-induced adrenal insufficiency in patients receiving glucocorticoid therapy has previously been lacking, but the European Society of Endocrinology and the Endocrine Society have recently published joint international guidelines on the diagnosis and treatment, summarized in this article. To further support patients and healthcare professionals, and to prevent a potentially fatal adrenal crisis, a national blue corticosteroid treatment card has been introduced. The card is intended to be provided to patients treated with prednisolone >5 mg daily (or equivalent) for >3-4 weeks.

Purpose: The aim of this study was to evaluate if intrasellar pressure (ISP) is associated with the risk of visual impairment in patients with a pituitary tumor, and the prognosis for visual function after tumor surgery.

Method: Retrospective, single-center study including 100 consecutive patients operated for a pituitary tumor, who had their ISP measured. Data on patient and tumor characteristics, pre- and postoperative visual acuity, visual fields, and cranial nerve III, IV, and VI deficits were collected from patient files.

Results: Before surgery, 64% had visual acuity impairment and 65% visual field deficits. Postoperatively, the frequencies were 40% for visual acuity impairment and 41% for visual field deficits. Risk factors for preoperative visual impairment were tumor volume, suprasellar tumor extension (SIPAP grade 3–4), and female sex. ISP was associated with higher risk of visual acuity impairment at postoperative follow up. No other correlations between ISP and pre- or postoperative visual and cranial nerve outcome were found. Age was associated with lower chance of visual acuity improvement and increased risk of visual field deficits postoperatively.

Conclusion: Overall, ISP does not seem to play an important role as a risk factor or prognostic factor for visual and cranial nerve impairment in pituitary tumor disease. However, ISP showed an association with postoperative visual acuity impairment. The clinical relevance of this results is not straight-forward. Tumor size, suprasellar growth pattern, and female sex are confirmed risk factors for preoperative visual symptoms. High age appears to negatively influence visual outcome after surgery.

Objective: Acromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries.

Methods: A Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1−7). Consensus was defined as ≥80% of panelists rating their agreement as ≥5 or ≤3 on the Likert-type scale.

Results: Consensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists.

Conclusion: This consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.

Purpose: The aim of this study was to establish a valid national cohort of patients diagnosed with acromegaly by combining data from the general National Patient Register (NPR) and the disease-specific Swedish Pituitary Register (SPR).

Methods: Patients ≥ 18 years of age at diagnosis of acromegaly reported from 1991 to 2018 who were registered in the NPR and/or SPR were included. The diagnosis of acromegaly was considered correct for patients identified in both registers or confirmed through chart review. Medical records were reviewed in two of Sweden´s six health care regions if the patient was reported only in the NPR. An algorithm for the NPR, with criteria requiring multiple diagnosis registrations and tumour and/or surgery codes, was constructed to reduce the number of patients to review in the remaining four regions.

Results: A total of 1866 patients were identified. Among these, 938 were reported in both registers. After application of the algorithm and chart review, the diagnosis was confirmed for 83 of the 906 patients found only in the NPR. Among 22 patients only registered in the SPR, a review of medical records confirmed acromegaly in 13. This resulted in a total of 1034 cases with acromegaly during the study period. The incidence rate of acromegaly in Sweden 1991–2018 was calculated to 4.0/million/year in the entire population and 5.1/million/year among subjects ≥ 18 years of age.

Conclusion: The combination of the SPR and NPR established a valid cohort of patients diagnosed with acromegaly and increased the estimated incidence in Sweden.

Background: Stress is today a common feature of patients seeking medical care and a growing public health issue in society. A method has been developed to measure biological chronic stress by Hair Cortisol Concentrations (HCC). This biomarker, for chronic stress, captures information about cumulative cortisol levels over the course of several months. Long-term stress might be one of the factors contributing to the onset of cardiovascular conditions and also affecting different risk factors. The aim of this study was to analyse the association between Hair Cortisol Concentrations and previous cardiovascular diseases and cardiovascular risk factors.

Methods: The method of measuring chronic stress by Hair Cortisol Concentration was applied in a large Swedish national observational cross-sectional study. A population-based random sample of N = 4,821 Swedish middle-aged men and women was analysed for hair cortisol levels in relation to diagnosed previous cardiovascular diseases and biologically measured cardiovascular risk factors.

Results: Long-term stress, measured by hair cortisol, was significantly associated with the classical cardiovascular risk factors hypertension and high cholesterol, but not smoking. Those with elevated HCC levels also had a significantly increased pre-history of myocardial infarction, type 2 diabetes, atrial fibrillation and by-pass surgery, but not regarding stroke, angina pectoris or sleep apnoea. Higher HCC was significantly associated (p < 0.001) with Body mass index and waist circumference, but only for females. HCC was also associated with the risk markers leukocytes, and high-sensitivity CRP, indicating a possible linkage between HCC and inflammation and hypothetically also the bodily immune defense. No association was found between perceived stress and HCC.

Conclusions: An overall conclusion of our results is that health care should put more emphasis on patients reporting that they have been exposed to long term stress. Altogether, these analyses of Hair cortisol levels in a large middle-aged population show that chronically elevated cortisol levels represent a relevant and significant factor associated with cardiovascular diseases and classical cardiovascular risk factors.