The possible role of the vasopressin system in hematopoiesis.

Vasopressin is a pleiotropic hormone that controls body fluid homeostasis. Vasopressin has also been proposed to be involved in erythropoiesis, thrombocyte activity and inflammation. However, whether increasing vasopressin is associated with changes in hematopoietic markers is not known. To evaluate this gap of knowledge we measured the vasopressin marker copeptin and markers of erythropoiesis (erythrocyte count, hemoglobin (Hb), red blood cell distribution width (RDW), mean corpuscular volume (MCV), erythrocyte volume fraction (EVF)), leukocyte count (total count, lymphocytes, neutrophils) and thrombocyte count in 5312 participants from the Swedish CArdioPulmonary bioImage Study (SCAPIS). The associations between increasing copeptin tertile and the hematopoietic markers were analyzed in multivariate linear regression analyses. We found that increasing copeptin tertile was significantly (p < 0.001) associated with increasing erythrocytes, RDW, EVF, Hb, leukocytes and neutrophils after adjustment for age, sex, current smoking, prevalent diabetes, hypertension, creatinine, body mass index and physical activity. Increasing copeptin tertile was, however, not associated with change in MCV, lymphocyte or thrombocyte count. In conclusion, we found that increasing copeptin levels are positively associated with markers of erythropoiesis and leukocyte count in the general population. These results warrant further research on possible mechanistic effects of vasopressin on hematopoiesis.

Copeptin as a marker of atherosclerosis and arteriosclerosis.

BACKGROUND AND AIMS: The precursor peptide of vasopressin, copeptin, has previously been linked to increased risk of developing diabetes mellitus, coronary artery disease and cardiovascular mortality. Whether elevated copeptin is associated with markers of atherosclerosis and arteriosclerosis in the general population is not known. METHODS: In this population-based, cross-sectional study, coronary artery calcium score (CACS), carotid-femoral pulse wave velocity (c-f PWV) and fasting plasma copeptin were measured in 5303 individuals in the Swedish cardiopulmonary bioimage study (SCAPIS). Multivariable logistic regression models were used to analyze the associations between copeptin and high CACS (>100) and high c-f PWV (>10 m/s), respectively. RESULTS: The number of individuals with high CACS and c-f PWV increased across increasing tertile of copeptin (11.7%, 13.3% and 16.3% for CACS and 6.9%, 8.5% and 10.6% for c-f PWV). The top tertile of copeptin was, compared with reference tertile 1, significantly associated with both high CACS and high c-f PWV after adjustment for age, sex, hypertension, diabetes mellitus, HDL, triglycerides, BMI, smoking status, creatinine and high sensitive CRP with an odds ratio (OR) of 1.260 (95% confidence interval (CI): 1.022-1.555) for CACS and OR 1.389 (95% CI: 1.069-1.807) for PWV. CONCLUSIONS: Copeptin is associated with both coronary atherosclerosis and increased arterial stiffness in the general population. Our data indicates that copeptin may be a useful marker in the assessment of cardiovascular risk.

Copeptin as a predictive marker of incident heart failure.

AIMS: Heart failure (HF) is a common disease with increasing prevalence and poor prognosis. The vasopressin (VP) marker copeptin predicts development of diabetes mellitus, diabetic heart disease, coronary artery disease, and premature mortality. Copeptin is elevated in HF patients and predicts a worse outcome. This study aims to investigate whether copeptin can predict HF development. METHODS: Copeptin was analysed in 5297 individuals (69.6% men) without prevalent HF from the Malmö Preventive Project, a population-based prospective cohort. Cox proportional hazards models were used to analyse risk of incident HF by copeptin levels after adjusting for conventional cardiovascular risk factors. RESULTS: During a median follow-up time of 11.1 years, 350 subjects (6.6%) were diagnosed with HF. Of these events, 99 were classified as myocardial infarction (MI) related HF and 251 as non-MI-related HF. Individuals in the top quartile of copeptin had, after multivariate adjustment for conventional risk factors (age, sex, systolic blood pressure, diabetes mellitus, body mass index, antihypertensive therapy, smoking, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol), a significantly increased risk of developing HF by 1.63 [confidence interval (CI) 1.20-2.21] for HF compared with the reference quartile 1. After adjustment for conventional risk factors, the hazard ratio (HR) per standard deviation increase of log-transformed copeptin for any HF was 1.30 (95% CI 1.17-1.46), whereas it was 1.39 (CI 1.13-1.71) for MI-related HF and 1.26 (CI 1.11-1.44) for non-MI-related HF. The associations remained after additional adjustment for estimated glomerular filtration rate [HR 1.24 (95% CI: 1.10-1.40)] and for pro atrial natriuretic peptide on top of conventional risk factors [HR 1.14 (95% CI: 1.02-1.28)]. CONCLUSIONS: Elevated copeptin predicts development of HF in older adults. Copeptin is a risk marker of VP-driven HF susceptibility and a candidate to guide prevention efforts of HF targeting the VP system.

Pituitary Metastases: A Nationwide Study on Current Characteristics With Special Reference to Breast Cancer.

OBJECTIVE: To investigate the contemporary presentation of pituitary metastases. PATIENTS: Thirty-eight patients diagnosed with pituitary metastases from 1996 to 2018 in Sweden. METHODS: Pituitary metastases were confirmed by histopathology (n = 27) or considered highly likely according to radiological findings, including rapid tumor progression (n = 11). Medical records were reviewed and sellar images reexamined centrally. RESULTS: Breast and lung cancers were the most common primary tumors, in 45% and 21% of patients, respectively. Sixty-seven percent of breast cancers overexpressed human epidermal growth factor receptor 2 (HER2); 53% of pituitary metastases from breast cancers appeared ≥10 years after diagnosis of the primary tumor. At presentation, 71% appeared to have ACTH deficiency, 65% had TSH deficiency, and 26% had diabetes insipidus. Fatigue, nausea/vomiting, loss of appetite, weight loss, myalgia, and/or arthralgia were reported in 47% of patients with morning cortisol <100 nmol/L vs 23% with cortisol ≥200 nmol/L. Sixteen patients had visual field defects, and eight had diplopia. Intrasellar and suprasellar tumor growth was the most frequent finding. Initially, a pituitary adenoma was considered the etiology in 18% of patients.Radiotherapy, pituitary surgery, and chemotherapy were used in 68%, 68%, and 11% of patients, respectively. One and 2 years after diagnosis of pituitary metastases, 50% and 26% of patients were alive. CONCLUSION: Pituitary metastases may be mistaken for pituitary adenomas and can appear late, especially in breast cancer. Breast cancers overexpressing HER2 seem prone to metastasize to the pituitary. Hypocortisolism may be misdiagnosed as cancer-related malaise. An increased awareness of pituitary metastases and undiagnosed pituitary failure can improve management in these patients.