Anthropometric indicators of insulin resistance.

During recent years, there have been numerous published reports associating increased circumferences of certain regions of the human body with insulin resistance or increased risk of cardiovascular disease. In the present review, we summarize the findings and conclusions of some of these publications.

The interrelationship of serum 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D in pregnancy at term: a meta-analysis.

OBJECTIVE: To assess the relationship between circulating 25(OH)D, 1,25(OH)2D, and 24,25(OH)2D in pregnancy at term, and to test the hypothesis that serum 25(OH)D and 24,25(OH)2D are repressed by high serum 1,25(OH)2D levels. DESIGN: Twenty studies in pregnant women at term and 14 studies in young non-pregnant women were selected from the electronic literature. From these studies the mean serum concentrations of 25(OH)D, 1,25(OH)2D, and 24,25(OH)2D from 26 groups of pregnant and 14 groups of non-pregnant young women were analyzed. The grand mean (mean of the means) of serum 25(OH)D, serum 1,25(OH)2D, and of the ratio 1,25(OH)2D/25(OH)D were compared between pregnant and non-pregnant women. Also, the means of serum 1,25(OH)2D were regressed on the means of serum 25(OH)D. The relationship between 25(OH)D and 24,25(OH)2D was also evaluated using similar methods. RESULTS: The grand mean of 1,25(OH)2D was two-fold higher, and the grand mean of the ratio 1,25(OH)2D/25(OH)D was 2.5-fold higher in pregnant than in non-pregnant women with comparable serum 25(OH)D. Regression showed no significant relationship between 1,25(OH)2D and 25(OH)D in pregnant and non-pregnant women. The ratio 24,25(OH)2D/25(OH)D was not different in pregnant and non-pregnanat women. Regression showed significant relationship between 24,25(OH)2D and 25(OH)D in both pregnant and nonpregnant women. CONCLUSIONS: Serum 1,25(OH)2D is not, whereas serum 24,25(OH)2D is significantly related to serum 25(OH)D in pregnant women. Serum 24,25(OH)2D seems not to be repressed by the high 1,25(OH)2D levels during pregnancy, whereas a similar conclusion for 25(OH)D is less clear.

Bisphosphonate-associated adverse events.

The adverse events of the nitrogen-containing bisphosphonates are reviewed. Oral bisphosphonates (alendronate, risedronate and ibandronate), mainly used for the treatment of osteoporosis, have been associated with adverse events from the upper gastrointestinal tract, acute phase response, hypocalcaemia and secondary hyperparathyroidism, musculoskeletal pain, osteonecrosis of the jaw and ocular events. Intravenous bisphosphonates (pamidronate, ibandronate and zoledronic acid), used in oncology and for the treatment of osteoporosis, have been associated with all the above adverse events, except those from the upper gastrointestinal tract. Moreover, pamidronate and zoledronic acid have been associated with renal toxicity. Association of bisphosphonates with atrial fibrillation and atypical fractures of the femoral diaphysis remains uncertain. There are a few case reports relating bisphosphonates to cutaneous reactions, oral ulcerations, hepatitis and esophageal cancer. Generally, intravenous are more potent than oral bisphosphonates and the frequency and severity of some of the bisphosphonate- associated adverse events are dose and potency dependent.

Corpus callosum aplasia in a young patient with a parathyroid adenoma.

A young man with primary hyperparathyroidism due to a parathyroid adenoma and aplasia of the corpus callosum is presented. We hypothesize a possible genetic association of the two pathologies: a proportion of the sporadic parathyroid adenomas are associated with genetic abnormalities of chromosome 11 and in some cases of corpus callosum aplasia, aneuploidy or polyploidy of this chromosome has been described.

The philosopher Socrates had exophthalmos (a term coined by Plato) and probably Graves' disease.

According to a previously published theory, Socrates was afflicted with temporal lobe epilepsy since his childhood. Plato, Xenophon, and Aristoxenus described Socrates as having exophthalmos, probably diplopia, and some symptoms compatible with hyperthyroidism. Using these data, we theorize that Socrates had Graves' disease. In order to determine a cause of his temporal lobe epilepsy, we speculate that the philosopher also had autoimmune thyroiditis and Hashimoto encephalopathy during his childhood and his epilepsy may have been a sequel to this hypothesized encephalopathy.

Hypercalcemia due to sun exposure in a patient with multiple myeloma and elevated parathyroid hormone-related protein.

A patient with multiple myeloma who developed hypercalcemia during three different stages of his disease, with a different hypercalcemic agent elevated in his serum on each occasion, is described. The initial episode of hypercalcemia was associated with high serum interleukin-6 (IL-6). After treatment for myeloma normocalcemia was achieved. Subsequently, a relapse of hypercalcemia occurred, this time characterized by frankly elevated plasma parathyroid hormone-related protein (PTHrP) but normal IL-6. Monotherapy with pamidronate infusions resulted in remission of the hypercalcemia and a significant fall in PTHrP levels. A third spell of hypercalcemia characterized by an acute rise in serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D to abnormally high levels occurred during the summer season after prolonged and intense exposure to the sun.

L-thyroxine therapy attenuates the decline in serum triiodothyronine in nonthyroidal illness induced by hysterectomy.

It is controversial whether the administration of thyroid hormone to patients with nonthyroidal illness has any beneficial effect. Two groups of patients undergoing abdominal hysterectomy under the same general anesthesia were studied. Group A consisted of 15 women taking chronically l-thyroxine therapy (1.8 mug/kg daily), and group B (control) consisted of 16 apparently healthy euthyroid women taking placebo. Thyroid hormones, cortisol, and interleukin (IL)-6 were measured 1 day before and 1, 2, 3, and 6 days after surgery. Total triiodothyronine (TT(3)) decreased to a significantly greater degree (P <.05) and for a longer period of time in group B than in group A. The significant increase of reverse T(3) (rT(3)) noted early in group B failed to reach the baseline levels until the end of the study, whereas in group A, rT(3) returned to the preoperative values by day 2. Both groups had similar free thyroxine (FT(4)) at baseline. FT(4) increased significantly at day 1 and remained significantly elevated throughout the postoperative period in group B only. Serum TT(4), thyroid-stimulating hormone (TSH), and cortisol did not change significantly in either group. In all patients, IL-6 increased significantly to a peak value at day 1, showing a slow decrease thereafter. A stronger negative correlation was found between T(3) and IL-6 in group B than in group A (r = -.66, P <.0001 v r = -.38, P <.001, respectively) and a strong positive correlation was observed between rT(3) and IL-6 in group B only (r =.57, P <.001). The long-term treatment with T(4) seems to attenuate the decrease of serum T(3), which occurs during the development of nonthyroidal illness postoperatively. The elevation of IL-6 accounted for a greater proportion of the variations of the T(3) and rT(3) in the control group B than in the T(4)-treated group A.

An Average Body Circumference Can Be a Substitute for Body Mass Index in Women.

Introduction. Significant correlations between BMI and some body circumferences have been previously reported. In this study we investigated if the average of the sum of eight body circumferences can be a substitute for BMI. Patients and Methods. BMI and eight body circumferences (neck, waist, hip, arm, forearm, wrist, thigh, and ankle) were measured in 193 apparently healthy women aged 20-83, and within a wide range of BMI. Women with BMI ≤ 24.9 were designated as normal, with BMI 25-29.9 as overweight and with BMI ≥ 30 as obese. The relationship of the average body circumference (ABC) of the sum of the eight circumferences, and of each individual circumference with BMI, was evaluated. Results. ABC had the strongest correlation with BMI (r = 0.95, P < 0.001) among all the circumferences tested. Hip circumference had the strongest correlation with BMI (r = 0.89, P < 0.001) among the circumferences of individual body sites. Receiver-Operator Characteristic analysis showed that women with ABC > 44.0 cm could be recognized as having BMI ≥ 25 with sensitivity 90.2% and specificity 88.5%, while women with ABC > 47.1 cm could be diagnosed as having BMI ≥ 30 with sensitivity 92.2% and specificity 91.5%. Conclusion. An average body circumference strongly correlated with BMI in women and can serve as a surrogate of BMI.

Maximinus Daia, a Roman emperor who may have had Graves' disease and died of a thyrotoxic crisis.

Evidence is presented that the Roman emperor Maximinus Daia had Graves' disease and died of severe thyrotoxicosis. The information about this emperor's terminal illness is drawn from the writings of the 4th century writers Eusebius and Lactantius. An existing statue indicates that the emperor had bilateral Graves' ophthalmopathy.

Hyperinsulinemia during oral glucose tolerance test and high normal serum cortisol are associated with increased secretion of calcitonin in normal subjects.

OBJECTIVE: Previous studies showed that insulin stimulated directly calcitonin (Ct) secretion in the pig thyroid, while dexamethasone stimulated the production of Ct and Ct mRNA in medullary thyroid carcinoma (MTC) cell lines. The objective of this study was to investigate if hyperinsulinemia during the oral glucose tolerance test (GTT) stimulates Ct secretion in normal subjects as well as to examine the relationship between serum cortisol and Ct. DESIGN: In 26 normal subjects (9 men and 17 women) with detectable basal serum Ct, aged 22-70 yr [51.5±14.6 (mean±SD), median 55.5], we measured serum or plasma Ct, cortisol, ACTH, insulin, and blood glucose before (0 min) and at 30, 60, 90, and 120 min after ingestion of 75 g glucose. RESULTS: During GTT mean serum cortisol increased slightly by 9.3% at 30 min, whereas mean serum insulin increased 9.4-fold, reaching a peak value at 60 min. Median serum Ct increased by 51% (p<0.001) in normal subjects (by 27% in men, p=0.004, and by 44% in women, p<0.001) at 30 min and remained significantly higher thereafter (up to 120 min) when compared to median baseline level. Regression analysis showed that basal serum cortisol, but not basal serum insulin, was correlated with basal serum Ct (p=0.01). Peak concentrations of Ct were also correlated with peak concentrations of cortisol at 30 min (p<0.001) but not at later time points. Serum insulin was correlated with serum Ct at the serum insulin peak level (60 min), and at later time points (90 and 120 min) (p=0.001). Multiple and simple regression analysis showed that calcitonin-AUC (Area Under Curve) values correlated with insulin-AUC (p=0.003), and also with cortisol-AUC (p=0.02) values, the standardized effect of insulin-AUC on Calcitonin-AUC being greater than that of cortisol-AUC. CONCLUSIONS: These findings suggest that acute hyperinsulinemia during GTT is very likely associated with increased Ct secretion in normal subjects. Serum cortisol within the physiological range was also correlated with serum Ct under basal conditions, as well as during GTT.

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.

Virilization caused by an ectopic adrenal tumor located behind the iliopsoas muscle.

OBJECTIVE: Virilization due to androgen-secreting neoplasms in women is a result of androgen overproduction from benign or malignant tumors that are found in the ovaries or rarely in the adrenal glands. Virilizing tumors that arise from ectopic adrenal tissue are extremely rare. We describe a very rare case of an ectopic androgen-producing adrenal tumor. DESIGN: Case report study. SETTING: Endocrinology outpatient department of university-affiliated teaching hospital. PATIENT(S): A 45-year-old woman with symptoms of virilization of abrupt onset and rapid progression, with high serum androgen hormone levels and normal glucocorticoid secretion. INTERVENTION(S): Basal hormonal levels, stimulation and suppression tests, imaging techniques, and selective venous sampling. MAIN OUTCOME MEASURE(S): Localization and surgical removal of the source of androgen production. RESULT(S): An ectopic mass was detected behind the left iliopsoas muscle. The patient was operated on and an oblong-shaped lesion, weighing 6 g, was removed. Histologically, the tissue was identified to be of adrenal origin. Postoperatively the androgen levels decreased to normal levels. CONCLUSION(S): This case illustrates difficulties in detecting and localizing the rare contingence of an ectopic adrenocortical androgen-secreting tumor.

Bone mineral density in hyperthyroidism.

OBJECTIVE: To investigate whether previous hyperthyroidism is a cause of permanent secondary osteoporosis. DESIGN AND PATIENTS: In this cross-sectional study, 164 women with untreated or previously treated overt and symptomatic hyperthyroidism were examined 0-31 years after the initial episode of hyperthyroidism and its treatment, and were compared with a control group of 79 age-matched women without previous history of hyperthyroidism. Subjects with current or previous metabolic bone disease, any antiresorptive treatment for osteoporosis or treatments and habits known to affect bone metabolism were excluded. MEASUREMENTS: The age of the first manifestation of the disease, the age at the measurement of bone mineral density (BMD) at the spine and femoral neck and the interval between diagnosis and treatment of hyperthyroidism and BMD measurement were recorded and the Z-scores and T-scores of BMD were analysed. RESULTS: Untreated hyperthyroidism and hyperthyroidism up to 3 years after its diagnosis and treatment were associated with decreased BMD. Three or more years after the first episode of the disease the mean Z-score at both skeletal sites was near zero and not different from the controls. The age at which hyperthyroidism was manifested for the first time had no effect on the final outcome. Women affected at a young age (13-30 years) had a more pronounced loss of BMD when examined untreated or early (< 3 years) after diagnosis, but a BMD significantly above zero if examined later (> 3 years). Older women (aged 51-70 years) showed a similar pattern, although the differences were not significant. Middle-aged subjects (31-50 years) had the smallest loss of BMD during the first 3 years. Analysis of T-scores of former hyperthyroid women aged > or = 51 years showed no significantly different relative risk (RR) for osteoporosis in comparison with the controls. However, the study was not powered enough to give meaningful RR results. CONCLUSIONS: Overt symptomatic hyperthyroidism is associated with decreased BMD during the first 3 years after diagnosis and treatment of the disease. After this interval, former hyperthyroid women have a Z-score near zero and not different from women without a history of the disease, apparently because of recovery of the bone density lost early during the course of the disease. Symptomatic hyperthyroidism does not seem to be a cause of long-lasting osteoporosis, and the age of the patient during the first episode is irrelevant.