| 1. |
- Almquist, Martin, et al.
(författare)
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Serum levels of vitamin D, PTH, calcium and breast cancer risk - a prospective nested case-control study.
- 2010
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 127:9, s. 2159-2168
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies indicate that calcium and its regulating hormones, i.e. parathyroid hormone (PTH) and vitamin D, might affect breast cancer risk. Evidence also suggests that this relationship could be influenced by menopausal status and BMI. We examined breast cancer risk related to pre-diagnostic serum levels of vitamin D (25OHD(2) and 25OHD(3)), PTH and calcium using a nested case-control design within the Malmö Diet and Cancer Study. There were 764 incident breast cancer cases, and 764 controls were selected by incidence density matching, using age as the underlying time scale, matching on calendar time at inclusion, menopausal status and age at inclusion. Using logistic regression analysis, odds ratios (OR) with 95% confidence intervals were calculated for breast cancer risk in different quartiles of the analysed factors. All analyses were adjusted for risk factors for breast cancer, and for levels of albumin, creatinine and phosphate. Analyses were repeated stratified for BMI and menopausal status, and for low vs. high levels of 25OHD(3), PTH and calcium. There was a weak, non-significant inverse association between breast cancer risk and 25OHD(3), and the OR for the 2(nd), 3(rd) and 4(th) quartiles, as compared to the first, were 0.84(0.60-1.15), 0.84(0.60-1.17), and 0.93(0.66-1.33). Serum calcium was positively associated with breast cancer in pre-menopausal women (OR for the 4(th) quartile = 3.10:1.33-7.22 and p for quartile trend=0.04), and in women with BMI>25 (OR for the 4(th) quartile=1.94:1.12-3.37 and p for trend<0.01). There was no association between baseline serum PTH and breast cancer risk. (c) 2010 UICC.
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| 2. |
- Almqvist, Erik G., et al.
(författare)
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Factors influencing insulin sensitivity in patients with mild primary hyperparathyroidism before and after parathyroidectomy
- 2012
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 72:2, s. 92-99
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. Primary hyperparathyroidism (PHPT) is associated with cardiovascular disease. The aims of this study were to investigate lipid and glucose metabolism in mild PHPT, and to identify whether insulin sensitivity correlates with circulating levels of adiponectin, SHBG, and osteocalcin before and after parathyroidectomy (PTX). Materials and methods. Forty-five patients with PHPT were examined before and 1 year after PTX. Circulating levels of triglycerides, total cholesterol, HDL-cholesterol, insulin, glucose, adiponectin, SHBG, osteocalcin, and erythropoietin were measured. Results. At baseline, the mean serum levels of total cholesterol, LDL-cholesterol and triglycerides were above the upper reference limit or in the upper normal range, and insulin sensitivity was reduced as assessed using the HOMA index. One year after parathyroidectomy, serum lipids as well as HOMA index and erythropoietin were unchanged while adiponectin had increased (p < 0.05), and SHBG and osteocalcin had decreased (p < 0.05 and p < 0.0001, respectively). HOMA index correlated negatively with circulating levels of adiponectin, SHBG and osteocalcin. In multiple regression analysis SHBG was the most important predictor of insulin sensitivity, both pre- and postoperatively. Conclusion. Untreated mild PHPT is associated with a moderate derangement of lipid and glucose metabolism. As previously shown in population-based cohorts, insulin sensitivity is positively associated with circulating concentrations of adiponectin, SHBG and osteocalcin. One year after PTX, the mean level of adiponectin was increased, but the levels of SHBG and osteocalcin had decreased and the levels of serum lipids and the insulin sensitivity remained unchanged as compared with baseline.
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| 3. |
- Almqvist, Erik G., et al.
(författare)
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Increased markers of inflammation and endothelial dysfunction in patients with mild primary hyperparathyroidism
- 2011
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 71:2, s. 139-144
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The association between primary hyperparathyroidism (PHPT) and cardiovascular disease is incompletely understood. The aims of this study were to evaluate how cardiac function and markers of inflammation and endothelial dysfunction correlate in patients with mild PHPT, and how these markers are influenced by surgical cure of the parathyroid disease (PTX). Material and methods: Forty-five patients with PHPT were examined before and 1 year after PTX. Serum/plasma concentrations of calcium, PTH, highly sensitive C-reactive protein (CRP), interleukin-6 (IL-6), vascular adhesion molecule-1 (VCAM1), E-selectin, and NT-proBNP were measured as well as erythrocyte sedimentation rate (ESR) and creatinine clearance. Cardiac function was evaluated by equilibrium radionuclide angiography. Results: The baseline serum level of IL-6 correlated negatively with baseline parameters of cardiac function (exercise capacity, p < 0.001, left ventricular ejection fraction at exercise, p < 0.01). The mean serum concentrations of IL-6 and CRP and the ESR had increased 1 year after PTX (p < 0.001, p < 0.01, and p < 0.001, respectively) in parallel with a decrease in cardiac function and an increase in circulating NT-proBNP. The mean serum level of VCAM1 was above the upper normal range at baseline and had not changed significantly 1 year after PTX. Conclusion: Patients with mild PHPT and normal renal function displayed signs of subclinical inflammation and endothelial dysfunction. One year after PTX, the inflammatory markers were increased in parallel with a subclinical decrease in cardiac function. Further studies are warranted to clarify the natural course and clinical implications of these changes.
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| 4. |
- Birgander, Mats, et al.
(författare)
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Adrenergic and cardiac dysfunction in primary hyperparathyroidism.
- 2012
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Ingår i: Clinical Endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 76, s. 189-195
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Primary hyperparathyroidism (PHPT) is associated with cardiovascular morbidity and premature death but the underlying mechanisms are incompletely understood. The aim of this study was to investigate if adrenergic dysfunction may be a contributing factor. Patients and methods: Forty-nine patients with mild PHPT (serum calcium 2.7 ± 0.1 mmol/L) and 48 control subjects, matched for age and sex, were examined; patients within 1 month before parathyroidectomy (PTX) and 6 months postoperatively; control subjects at inclusion. Heart rate variability (HRV) was analyzed in 24-hour electrocardiograms, and plasma concentrations of epinephrine and norepinephrine were measured at rest and immediately after standardized physical tests. Results: At baseline, the patients showed, compared to the controls, reduced stress-related increase of circulating epinephrine (P < 0.05) and norepinephrine (P < 0.05). No significant change was observed 6 months after PTX. At baseline, there were no significant differences between patients and controls in HRV or heart rate but 6 months after curative PTX, the patients showed significantly reduced HRV in both frequency and time domain, and their maximum and average heart rate had decreased (P = 0.011 and P = 0.018, respectively). The patients with the highest preoperative levels of circulating parathyroid hormone showed the greatest changes in heart rate and HRV postoperatively. Conclusions: This study demonstrates a previously unknown impairment of catecholamine response to physical stress in PHPT along with changes of HRV, also indicating adrenergic dysfunction. These factors should be considered in the ongoing controversy regarding the management of patients with mild "asymptomatic" PHPT.
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| 5. |
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| 6. |
- Rydberg, Erik, et al.
(författare)
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Effect of successful parathyroidectomy on 24-hour ambulatory blood pressure in patients with primary hyperparathyroidism.
- 2010
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 142, s. 15-21
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The pathogenesis of hypertension in patients with primary hyperparathyroidism (PHPT) is unclear, and the prevailing opinion is that parathyroidectomy does not affect the blood pressure (BP). Most previous studies have been based on BP measurements at rest in a clinical setting. The aim of this study was to get additional information by 24-hour ambulatory measurements. DESIGN AND PATIENTS: Forty-nine consecutive patients with PHPT (age 63+/-12 years, 44 women) were examined before and 6 months after curative parathyroid surgery. MEASUREMENTS: Serum concentrations of calcium and PTH, and 24-hour ambulatory mean, minimum, and maximum systolic (S) and diastolic BP, and mean arterial BP. RESULTS: On average, the patients showed no BP change after parathyroidectomy. However, those with a history of hypertension (n=20) showed generally increased BP values after parathyroidectomy, with significantly increased minimum and average SBP (P=0.02 and P=0.04, respectively), whereas patients without a history of hypertension (n=29) showed unchanged or slightly reduced BP values after parathyroidectomy, with significantly decreased maximum SBP (P=0.04). Serum concentrations of PTH and calcium were not significantly related to any of the BP variables measured. CONCLUSIONS: The novel finding that patients with both PHPT and hypertension may show increased BP after parathyroidectomy warrants intensified BP control postoperatively in these patients, and motivates early treatment of PHPT in order to prevent the development of complicating hypertension.
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| 7. |
- Simintiriadis, Dimosthenis, et al.
(författare)
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The association between the IGF-I axis, thyroid hormones and cortical bone in patients with mild primary hyperparathyroidism
- 2013
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 73:1, s. 34-41
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. Primary hyperparathyroidism (PHPT) is associated with low bone mineral density (BMD) and increased risk of osteoporotic fractures. This study investigated whether the IGF-I axis and thyroid hormones are associated with BMD and osteoporotic fractures before and after parathyroidectomy (PTX). Materials and methods. Forty-five patients with mild PHPT were examined before and 1 year after PTX. Circulating concentrations of IGF-1, IGFBP-3, and thyroid hormones were measured and related to BMD in hip and lumbar (L:2-L:4) spine. Results. Serum IGFBP-3 concentration decreased 1 year after PTX (p < 0.01), whereas serum IGF-1 and thyroid hormone concentrations were unchanged. Serum IGF1 concentration correlated positively with IGFBP-3 concentration (p < 0.0001) and BMD in the femoral neck (p < 0.05), both pre- and postoperatively. Serum IGFBP-3 concentration correlated positively with BMD in the femoral neck postoperatively (p < 0.05). Serum TSH correlated positively, and free thyroxine (T4) negatively, with all measures of hip BMD at baseline. Patients suffering from previous osteoporotic fractures before inclusion had lower serum TSH concentration compared to patients without fractures (p < 0.01). Conclusion. Serum IGFBP-3 concentration decreased after successful PTX in patients with mild PHPT, while serum IGF1 and thyroid hormone concentrations were unchanged. Both the IGF-I axis and thyroid hormones associated with cortical bone as serum IGF-1 and IGFBP-3 concentrations correlated positively, and free T4 negatively with hip BMD. Moreover, serum TSH concentration was reduced in patients with previous osteoporotic fractures.
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| 8. |
- Tosovic, Ada, et al.
(författare)
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prospectively measured thyroid hormones and thyroid peroxidase antibodies in relation to breast cancer risk.
- 2012
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 131:9, s. 2126-2133
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Tidskriftsartikel (refereegranskat)abstract
- Thyroid hormones influence both normal breast cell differentiation and breast cancer cell proliferation and stimulate the angiogenesis of certain cancer forms. Several cross-sectional studies have measured thyroid hormones / auto antibodies in breast cancer ceases vs. controls, but it is difficult to determine the cause-effect direction in these studies. Only three prospective studies have reported on the subject so far. The aim of the present study was to investigate pre-diagnostically measured levels of thyroid hormones, thyrotropin, and thyroid autoantibodies in relation to subsequent risk of breast cancer. The Malmoe Diet and Cancer study examined 17,035 women between 1991 and 1996. Blood samples were collected at baseline and free T3, free T4, TSH, and TPO-Ab levels were measured in 676 cases and 680 controls. Relative risks with 95% confidence intervals were assessed using a logistic regression analysis adjusted for potential confounders. Free T4 levels were positively associated with a high risk of breast cancer, and the OR for women with free T4 levels above vs. below the median was 1.40 (1.10-1.77). This association was most pronounced in overweight women (1.51:1.07-2.12). Women with high levels of TPO-Ab had a lower risk of breast cancer, but only the analysis of TPO-Ab as a continuous variable reached statistical significance. Free T4 was in this study positively associated with a high risk of breast cancer. This association was most pronounced in overweight/obese women. Women with a high level of TPO-Ab had a relatively low risk of breast cancer. © 2012 Wiley-Liss, Inc.
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| 9. |
- Tosovic, Ada, et al.
(författare)
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Prospectively measured triiodothyronine levels are positively associated with breast cancer risk in postmenopausal women
- 2010
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The potential association between hypo-and hyperthyroid disorders and breast cancer has been investigated in a large number of studies during the last decades without conclusive results. This prospective cohort study investigated prediagnostic levels of thyrotropin (TSH) and triiodothyronine (T3) in relation to breast cancer incidence in pre- and postmenopausal women. Methods: In the Malmo Preventive Project, 2,696 women had T3 and/or TSH levels measured at baseline. During a mean follow-up of 19.3 years, 173 incident breast cancer cases were retrieved using record linkage with The Swedish Cancer Registry. Quartile cut-points for T3 and TSH were based on the distribution among all women in the study cohort. A Cox's proportional hazards analysis was used to estimate relative risks (RR), with a confidence interval (CI) of 95%. Trends over quartiles of T3 and TSH were calculated considering a P-value < 0.05 as statistically significant. All analyses were repeated for pre-and peri/postmenopausal women separately. Results: Overall there was a statistically significant association between T3 and breast cancer risk, the adjusted RR in the fourth quartile, as compared to the first, was 1.87 (1.12 to 3.14). In postmenopausal women the RRs for the second, third and fourth quartiles, as compared to the first, were 3.26 (0.96 to 11.1), 5.53 (1.65 to 18.6) and 6.87 (2.09 to 22.6), (P-trend: < 0.001). There were no such associations in pre-menopausal women, and no statistically significant interaction between T3 and menopausal status. Also, no statistically significant association was seen between serum TSH and breast cancer. Conclusions: This is the first prospective study on T3 levels in relation to breast cancer risk. T3 levels in postmenopausal women were positively associated with the risk of breast cancer in a dose-response manner.
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| 10. |
- Tosovic, Ada, et al.
(författare)
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T3 levels in relation to prognostic factors in breast cancer: a population-based prospective cohort study
- 2014
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: The issue of a potential association between thyroid conditions/hormones and breast cancer has been studied extensively during the last decades but the results have been inconclusive and almost no studies have investigated breast cancer aggressiveness. We have previously found a positive association between prospectively measured levels of triiodothyronine (T3) and breast cancer incidence as well as breast cancer mortality. We now investigated prediagnostic T3 levels in relation to specific prognostic factors in breast cancer. Methods: The Malmo Preventive Project is a population-based prospective cohort including 2185 women in whom T3 levels were measured at baseline. That is, total T3 levels were measured before a potential diagnosis of breast cancer. Mean follow-up was 23.3 years and 149 women in the study population were diagnosed with invasive breast cancer. Tumours were classified according to selected prognostic factors of breast cancer; i.e. grade, tumour size, lymph node metastasis, and hormonal receptor status. T3 was handled both as tertiles and as a continuous variable. A Cox's proportional hazards analysis yielded hazard ratios with 95% confidence intervals. All analyses were also restricted to postmenopausal women. Results: Overall there was a statistically significant association between T3 and "all" breast cancers. The adjusted Hazard Ratio (HR) in the third tertile, as compared to the first, was (1.61:1.07-2.43). There was a statistically significant positive association between the third T3 tertile and large tumours, i.e. > 20 mm, (3.17:1.20-8.36) and the occurrence of lymph node metastases, (4.53:1.60-12.83). Other prognostic factors positively associated with T3 were negative oestrogen receptor (ER) status, (3.52:1.32-9.41) and negative progesterone receptor (PGR) status, (3.52:1.42-8.75). The analyses of T3 as a continuous variable and analysis restricted to postmenopausal women, confirmed the results but also showed an association with smaller tumours and in postmenopausal women a contemporary association with negative lymph nodes. Conclusions: This prospective study of serum T3 levels in relation to breast cancer aggressiveness is the first of its kind. We found statistically significant positive associations between higher prediagnostic T3 levels and larger tumours, occurrence of lymph node metastases, and negative ER and PGR status.
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