Helen Karga

Bone mineral density in hyperthyroidism

objective  To investigate whether previous hyperthyroidism is a cause of permanent secondary osteoporosis.

Vitamin D deficiency in the elderly in Athens, Greece

Vitamin D deficiency characterized by low 25-hydroxyvitamin D [25(OH)D] levels has been found to be prevalent among the elderly in many regions of the world. To investigate the vitamin status in elderly community-living persons in Athens, we measured 25(OH)D and parathyroid hormone (PTH) in elderly persons and young blood donors during the winter and summer. The changes in these parameters in a subgroup of the elderly were studied longitudinally. The blood donors had mean 25(OH)D levels similar in winter and summer and twice as high in winter compared to the elderly. At the end of the winter, about 20% of the elderly had severe vitamin D deficiency, with 25(OH)D below 25 nmol/l, and only 6.5% could be judged as vitamin D sufficient with values above 80 nmol/l. The situation improved during summer, although 64.8% of the elderly continued to have levels below 80 nmol/l. Mean plasma PTH in the elderly in summer was not different from that of blood donors; however, it was doubled during the winter. Regression of PTH on 25(OH)D demonstrated that PTH starts to rise when 25(OH)D falls below approximately 80 nmol/l. We conclude that severe vitamin deficiency associated with secondary hyperparathyroidism is not uncommon in the elderly in Athens during the winter; it subsides during summer, although only one-third of the elderly population attain vitamin D sufficiency during summer. We found that a threshold value of 25(OH)D exists at approximately 80 nmol/l, below which secondary hyperparathyroidism ensues, as described previously.

Heterophilic antibodies causing falsely high serum calcitonin values

Heterophilic antibodies (HA) may interfere in some immunoassays, causing falsely high hormone values, of wich practitioners should be aware when measuring calcitonin (CT) used as tumor marker for medullary thyroid carcinoma (MTC). We studied four patients with thyroid nodules, three of whom underwent surgical neck exploration, after an erroneous diagnosis of MTC because of falsely high serum CT eventually proved to be due to HA. One patient had a lingual thyroid, two autoimmune thyroiditis and the fourth a colloid goiter. The minimal incremental CT response to calcium infusion raised our suspicion of possible false high CT values due to HA. There was no linearity of the CT values obtained by testing serial dilutions of the sera in the CT assay, which employs two monoclonal mouse anti-CT antibodies. Addition of normal mouse gamma globulin eliminated the interference by HA in the sera of two patients. Serum assayed in a polyclonal radioimmunoassay using goat anti-CT antibodies gave normal CT values. Finally, incubation of the sera in Heterophilic Blocking Tubes® (HBT) eliminated the false CT immunoreactivity. A spontaneous change of the CT serum concentrations was noticed in three patients over several months, apparently due to changing titles of HA. We suggest that, in patients a) whose CT response to calcium or pentagastrin infusion is minimal despite high basal CT values, b) with autoimmune thyroiditis and c) in whom an unexpected change in serum CT concentrations occurs, the possibility of spuriously high CT values because of circulating HA should be considered.

Effect of an Oral Glucose Load on PTH, 250HD3, Calcium, and Phosphorus Homeostasis in Postmenopausal Women

Introduction. Previous studies particularly in children and neonates have shown that serum calcium declines and parathyroid hormone (PTH) rises during an oral glucose load. However, there is not a general agreement in this regard. This study was carried out to evaluate the effects of an oral glucose load on calcium and phosphorus homeostasis in postmenopausal women along with serum insulin, PTH, and 250HD3 changes. Patients and methods. After an overnight fasting, an oral glucose tolerance test was performed in 50 postmenopausal women; and glucose, insulin, PTH, and D3 were measured at baseline and every 30 min during the 2 hours of the test. Results. Serum glucose and insulin increased as expected and reached their peak values at 60 and 90 min, respectively. PTH and phosphorus decreased significantly and the maximum decline was observed at 30 and 120 min after glucose load (p < 0.0001), respectively. Serum calcium, magnesium, and D3 levels showed no significant changes at any time measured. Serum PTH values had a significant negative correlation with glucose and insulin values (p = 0.026 and p = 0.031, respectively). Serum D3 also correlated negatively with glucose (p = 0.002). Conclusion. Our study shows that an oral glucose load induced hyperglycemia/hyperinsulinemia promotes a significant decline in serum PTH and phosphorus levels without changes in calcium or 250HD3 in postmenopausal women.

Ras oncogenes and p53 tumor suppressor gene analysis in cardiac myxomas

Although ras oncogenes and p53 tumor suppressor gene mutations are implicated in the development of several human tumors, little is known about their role in the pathogenesis of primary cardiac tumors. Paraffin-embedded tissue from 19 cardiac myxomas were investigated for the presence of ras oncogenes and p53 tumor suppressor gene abnormalities. Immunohistochemical analysis was used to identify the accumulation of p21-ras and p53 proteins. A polymerase chain reaction was used to amplify exons 1 and 2 of the ras genes and exons 5 to 8 of the p53 gene. The PCR products were analyzed by single strand conformation polymorphism analysis and by direct DNA sequencing. Three of 19 myxomas showed strong positive staining for the ras p21 protein. In contrast, nuclear p53 was not detectable in any of the myxomas. Among the ras p21 immunopositive myxomas, 2 were heterozygous for a missense point mutation of the K-ras, Gly 12Asp. Further screening of the remaining myxomas showed no mutation or even silent polymorphism in any exon of the ras and p53. The results suggest that although genetic alterations of ras oncogenes and p53 are uncommon events in cardiac myxomas, ras mutations may be involved in the pathogenesis of a subgroup of this type of tumor.

Cytokines and Insulin Resistance after Zoledronic Acid-Induced Acute Phase Response

Zoledronic acid is known to induce a transient acute phase response (APR). The aim of the study was to investigate whether an APR caused by zoledronic acid administration can induce insulin resistance in post-menopausal osteoporotic women and the potential involvement of different inflammatory markers, cytokines and adipokines to this response. Insulin resistance was calculated by the homeostasis model assessment (HOMA-IR). APR symptoms appeared in 30 post-menopausal osteoporotic women within 24 h and attenuated on day 3 after zoledronic acid infusion. Twenty-eight age- and body mass index-matched, patients without an APR following zoledronic acid administration, served as a control group. In patients with APR, concurrently with a significant increase in serum high sensitive C-reactive protein (hsCRP), interleukin-6 (hsIL-6), tumour necrosis factor-alpha (hsTNF-α) and cortisol levels on days one and two, serum insulin was also significantly elevated, resulting in an increased HOMA-IR. Leptin and resistin significantly increased on day two in contrast to adiponectin which declined, though not statistically significant. The alterations in HOMA-IR were mainly associated to the increase of hsCRP and leptin. In conclusion, zoledronic acid induces an acute, short term insulin resistance, due to an APR, by altering the levels of various adipokines and cytokines.

Changes in risk factors and Tumor Node Metastasis stage of sporadic medullary thyroid carcinoma over 41 years, before and after the routine measurements of serum calcitonin

The measurement of serum calcitonin (CT) in all thyroid nodules for the detection of medullary thyroid carcinoma (MTC) is controversial. We compare several prognostic factors, Tumor Node Metastasis (TNM) stage, and survival in sporadic MTC patients operated on before and after the use of routine measurements of serum CT in combination with thyroid ultrasonography (US). Thirty-seven patients had been operated on between 1969 and 1989 (group I), before the use of routine measurements of serum CT and the routine use of thyroid US, and 39 (group II) had been operated on between 1990 and 2009, after the introduction of routine use of serum CT and thyroid US. There were no between-group differences concerning age and sex. Group I had larger tumors at the time of operation (P < .001) and higher postoperative serum CT levels (P < .001). Cervical lymph node and distant metastases were found more frequently in group I in comparison with group II. The cases with TNM stage I were significantly higher in group II than in group I, in contrast with the cases with TNM stage IV that were significantly higher in group I. Univariate analysis revealed a significantly higher 15-year survival rate in group II than in group I (P = .002). The postoperative CT levels were positively correlated with tumor size (P < .001). During the last 2 decades, the diagnosis of sporadic MTC at an earlier stage has been made possible by the routine use of serum CT in combination with thyroid US. The significant increase of the 15-year survival rate shows better outcome in these patients.

Metabolic and hormonal effects of antenatal betamethasone after 35 weeks of gestation.

BACKGROUND Antenatal corticosteroid therapy recently has been considered for term and near-term infants, in addition to preterm infants, delivered by elective cesarean section, with the aim of preventing an adverse respiratory outcome. OBJECTIVES The objective of this study was to investigate hormonal and metabolic effects of antenatal betamethasone when administered to term fetuses. METHODS Cord blood levels of cortisol, C-peptide, insulin-like growth factor I and its binding protein 3, and 5 more analytes including glucose were measured in singleton newborns of over 35 weeks of gestational age. In anticipation of a cesarean delivery, the mother was either treated or not treated with 12 mg of intramuscularly administered antenatal betamethasone approximately 24 hours prior to birth. Babies of comparable gestational age, sex, and nutritional status who were not treated antenatally served as controls. RESULTS Cord serum cortisol levels of the betamethasone-treated fetuses were suppressed to <10% of that of untreated controls (median levels of 11.6 nmol/L vs. 138.2 nmol/L, respectively), and their C-peptide and glucose levels were significantly higher (2.85 mcg/L vs. 1.19 mcg/L, respectively, p < 0.0001; and 62.5 mg/dL vs. 56.0 mg/dL, respectively, p = 0.01). CONCLUSIONS Prophylactic betamethasone therapy causes immediate hormonal alterations, which might interfere with the metabolic adaptation of the newborn. This issue deserves thorough investigation.

Autoimmune thyroiditis in benign and malignant thyroid nodules: 16-year results.

It is controversial whether autoimmune thyroiditis is associated with higher frequency of papillary thyroid carcinoma (PTC).

Changes in TNM stage, reoperation and 131‐I ablation rate during the use of newer methods for the preoperative diagnosis of differentiated thyroid carcinoma

Objective  To define and discuss the changes of important risk factors and TNM staging over the last 40 years in patients operated on for differentiated thyroid carcinoma (DTC), resulting from the introduction of newer sensitive diagnostic procedures in the preoperative evaluation of thyroid nodules.