T3 levels in relation to prognostic factors in breast cancer: a population-based prospective cohort study

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

Prospectively measured triiodothyronine levels are positively associated with breast cancer risk in postmenopausal women

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

Stricture and perforation of the esophagus: Overlooked threats in the Zollinger-Ellison syndrome

This study was undertaken to assess the frequency of significant esophageal involvement in the Zollinger-Ellison syndrome (ZES). In a consecutive series of 24 patients with this disease, 9 (37%) showed endoscopic evidence of acid-induced esophageal lesions ranging from erosive inflammation to ulceration with massive bleeding, severe stricture formation, and perforation. In 3 cases, pronounced esophagitis was known 1–5 years before the underlying disease was diagnosed. Severe esophageal complications developed despite treatment with antisecretory drugs. It is emphasized that the best way to limit such complications is by excision of the underlying gastrin-secreting tumor(s) when possible . Nous avons entrepris cette étude pour établir la fréquence de participation oesophagienne dans le syndrome de Zollinger-Ellison. Pour une série de 24 patients présentant cette maladie, 9 (37%) avaient à l'endoscopie des lésions oesophagiennes dues à l'acidité allant de l'érosion inflammatoire à l'ulcération avec saignement important, sténose sévère, et perforation. Dans 3 cas, une oesophagite importante était connue 1–5 ans avant que la maladie sous-jacente soit diagnostiquée. Des complications oesophagiennes sévères se sont produites malgré le traitement antisécrétoire. Nous insistons sur le fait que le meilleur moyen de limiter ces complications est d'exciser chaque fois que possible la ou les tumeurs sous-jacentes sécrétant la gastrine. El presente estudio fue emprendido con el propósito de determinar la frecuencia de afección ácido péptica significativa del esófago en pacientes con síndrome de Zollinger-Ellison. En una serie de 24 pacientes consecutivos con esta enfermedad, 9 (37%) exhibieron evidencia endoscópica de lesiones esofágicas inducidas por ácido, las cuales variaron entre inflamación erosiva y ulceración con sangrado masivo, estrechez severa, y perforación. En 3 pacientes se conocía la existencia de esofagitis severa entre 1 y 5 años antes del diagnóstico de la enfermedad de base. Se desarrollaron graves complicaciones esofágicas a pesar del tratamiento con drogas antisecretorias en 3 pacientes. Se hace enfasis en que la mejor manera de disminuir tales complicaciones es mediante la resección del tumor(es) secretor de gastrina, cuando ello sea posible.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41287/1/268_2005_Article_BF01658528.pd

Serum calcium and breast cancer risk: results from a prospective cohort study of 7,847 women.

Experimental and epidemiological studies suggest that calcium-regulating hormones-parathyroid hormone (PTH) and vitamin D-may be associated with breast cancer risk. No prospective cohort study has investigated the association between pre-diagnostic calcium levels and subsequent risk of breast cancer. We have examined this in a cohort of 7,847 women where serum calcium levels and established risk factors for breast cancer had been assessed at baseline. During a mean follow-up of 17.8 years, 437 incident breast cancer cases were diagnosed. Incidence of breast cancer was calculated in different quartiles of serum calcium levels and a Cox's proportional hazards analysis was used to obtain corresponding relative risks (RR), with a 95% confidence interval (CI), adjusted for potential confounders. In premenopausal women, serum calcium levels were inversely associated with breast cancer risk in a dose-response manner. The adjusted RR (95% CI) of breast cancer was in the 2nd calcium quartile 0.91 (0.65-1.30), in the 3rd quartile 0.89 (0.60-1.31), and in the 4th quartile 0.56 (0.32-0.98), as compared to the 1st calcium quartile. In postmenopausal overweight women (BMI > 25), breast cancer risk was higher in calcium quartiles 2-4 as compared to the 1st quartile. Our findings may have implications for primary prevention of breast cancer and for the management of asymptomatic primary hyperparathyroidism

Increased markers of inflammation and endothelial dysfunction in patients with mild primary hyperparathyroidism

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

Increase of bioavailable testosterone is associated with gain in bone mineral density after cure of primary hyperparathyroidism in postmenopausal women

Objective The recovery of bone mineral density (BMD) after surgical cure of primary hyperparathyroidism (PHPT) seems to be multifactorial and not just dependent on declining PTH. The aim of the present study was to evaluate the role of sex steroids in this context. Design and patients Thirty-six postmenopausal women with PHPT were examined before and 1 year after curative parathyroidectomy. Their mean age at inclusion in the study was 71.7 +/- 1.1 years (range 54-83). BMD was measured in hip and lumbar spine using dual energy X-ray absorptiometry. No patient received any replacement therapy with sex hormones or treatment with corticosteroids, oestrogen receptor modulators or bisphosphonates. Measurements Serum concentrations of oestradiol, testosterone, androstenedione, dehydroepiandrosterone sulphate, SHBG, PTH and calcium. Results Postoperative increase of free (bioavailable) testosterone was positively correlated to the change of BMD in the hip (P < 0.01), whereas the change of PTH in serum correlated to the change of BMD in the lumbar spine (P < 0.05). Multiple regression analysis showed that bioavailable testosterone was the most important determinant of change in BMD in both spine and hip (femoral neck: P < 0.05; Ward's triangle: P < 0.001; trochanter: P < 0.01; lumbar spine: P < 0.05). The increase of bioavailable testosterone after curative parathyroidectomy was related to declining SHBG. Conclusions An increase of bioavailable testosterone following surgical cure of PHPT is related to improvement of hip and lumbar spine BMD in postmenopausal women. This previously unknown hormonal interaction may also be important to other aspects of hyperparathyroidism