Anne-Greth Bondeson

Chromosome studies in thyroid neoplasia

Cytogenetic studies in thyroid neoplasia were performed by G‐banding of chromosome preparations obtained from the in vitro cultures of nine adenomas, one follicular carcinoma, five papillary carcinomas, and two medullary carcinomas. Complex structural chromosome aberrations were found in one adenoma. Two more adenomas, both composed of Hürthle cells, showed multiple numerical chromosome deviations with trisomy 4 and tetrasomy 7 in common. Six metastasizing carcinomas were characterized by normal stemlines, which indicates that malignancy in thyroid neoplasia cannot be excluded by cytogenetic techniques used currently. Comparisons between cytogenetic findings and cytophotometric DNA measurements in the material studied illustrate that euploid tumors represent a heterogenous group including cases with various gross structural chromosome aberrations of yet unknown clinical significance. Further studies of additional material with long‐term follow‐up are called for by our findings of structural and numerical chromosome aberrations in follicular neoplasms that are benign according to histologic criteria.

Oxyphil tumors of the thyroid: follow-up of 42 surgical cases.

Histopathologic and clinical follow-up data on 42 patients observed 2-20 years after operations for oxyphil neoplasms of the thyroid are presented. In eight patients histologic signs of malignancy were found but only two patients showed a clinically malignant course with development of distant metastases. The results do not indicate that oxyphil thyroid neoplasms are especially prone to assume a malignant course with the mode of treatment applied. Our policy is to remove any differentiated epithelial thyroid neoplasm with at least lobectomy. Total thyroidectomy is reserved for cases with capsular penetration, blood vessel invasion and/or metastases.

Serum levels of vitamin D, PTH and calcium and breast cancer risk-a prospective nested case-control study.

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 prediagnostic serum levels of vitamin D (25OHD2 and 25OHD3), 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 analyzed 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 25OHD3, PTH and calcium. There was a weak, nonsignificant inverse association between breast cancer risk and 25OHD3, and the OR for the 2nd, 3rd and 4th 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 premenopausal women (OR for the 4th quartile = 3.10:1.33–7.22 and p for quartile trend = 0.04), and in women with BMI > 25 (OR for the 4th 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.

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

IntroductionThe 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.MethodsIn the Malmö 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 Coxs 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.ResultsOverall 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.ConclusionsThis 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.

Fat staining in parathyroid disease—Diagnostic value and impact on surgical strategy: Clinicopathologic analysis of 191 cases

The study comprised 191 cases of surgically treated hyperparathyroidism, with all principal types of parathyroid disease represented. At least two complete glands stained with a modified isopropanol oil red O method for fat, in addition to sections stained with hematoxylin-eosin, were available in each case. On the basis of the morphologic evaluation and the clinical follow-up data, it is concluded that access to two complete glands and the use of fat staining allow highly reliable intraoperative distinction between adenoma and hyperplasia. Of 105 patients followed up for at least one year (mean, 20 months) in whom adenomas were diagnosed, a single possible error was identified. In each of 68 cases classified as hyperplasia on the basis of two abnormal glands, every additional complete gland available (total, 182 glands) was at least partially abnormal, with distinct signs of hyperactivity, irrespective of size. The rate of equivocal findings for cases in which two glands were available (probably adenoma but hyperplasia not excluded) was 8 per cent in 165 cases of primary hyperparathyroidism. These results justify limitation of surgery to one side of the neck in patients in whom adenoma is diagnosed on the basis of a complete, functionally normal (inactive) gland in addition to the presumed adenoma. Thus, the methods described provide a basis for optimal utilization of imaging techniques that allow preoperative localization of parathyroid adenomas.

Surgical strategy in hyperparathyroidism due to solitary adenoma.

Based on the postulate that parathyroid adenoma is practically always a solitary lesion, unilateral parathyroidectomy including the homolateral normal parathyroid was applied as a principle in the treatment of this form of primary hyperparathyroidism. The exploration was confined to the adenoma side if this was the first to be explored. Intraoperative oil-red-O staining of frozen sections was used to exclude the possibility of a multiglandular involvement. This principle was applied in a consecutive series of 102 patients operated for hyperparathyroidism from 1977 to 1981 and diagnosed as parathyroid adenoma. In 43 patients where the abnormal gland was found on the side explored first, unilateral parathyroidectomy was performed on that side, avoiding exploration of the contralateral side. In 45 patients where normal glands were found on the side first explored, unilateral parathyroidectomy was performed on the contralateral side. In 14 patients other types of operations were performed as the above-mentioned principle could not be achieved. At follow-up 1 to 5 years after surgery, no cases of hypocalcemia were recorded. The results of the different operations were compared as to early and late hypocalcemia. Early hypercalcemia was more pronounced after a bilateral exploration. Two of the patients who had an atypical operation had a permanent need for vitamin D in order to maintain an adequate serum calcium level. Surgical principles for various possible exploratory findings are outlined. These are based upon the idea of performing a unilateral parathyroidectomy whenever intraoperative oil-red-O staining excludes multiglandular involvement as a cause for the hyperparathyroidism.

Nuclear DNA content and behavior of oxyphil thyroid tumors

Microspectrophotometric measurement of nuclear DNA content was made on archival smears of fine‐needle aspirates from 23 oxyphil thyroid neoplasms. Fourteen tumors were considered benign as judged from the histologic picture as well as follow‐up for 7 to 18 years after the operation. Nine tumors were malignant; five of these showed capsular penetration and/or blood vessel invasion as the only signs of malignancy, whereas the remaining four in addition had histologically verified metastases and were the cause of death. The DNA patterns found—diploid, polyploid or aneuploid—appeared to have a limited diagnostic value, since malignancy could not be excluded on this basis. A practically useful finding was, however, that aneuploidy appeared to be associated with a high probability of invasive growth. As regards prognostic information, it was found that euploid patterns occurred in tumors from patients with long survival after surgical treatment, while tumors with aneuploid patterns showed a variable clinical course. Cancer 58:672‐675, 1986.

Effect of successful parathyroidectomy on 24-hour ambulatory blood pressure in patients with primary hyperparathyroidism

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.

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

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.

Chronic parathyroiditis associated with parathyroid hyperplasia and hyperparathyroidism.

Two cases of chronic parathyroiditis associated with parathyroid hyperplasia and hyperparathyroidism are described. There was no evidence of an underlying infectious disease, a developmental anomaly, or a drug reaction that could explain the inflammatory component. It is suggested that an autoimmune process might have been involved in the pathogenesis of this previously unreported clinicopathologic entity.