An early rise in urine N-telopeptide predicts the growth response of normal prepubertal short children to growth hormone therapy

The effects of growth hormone (GH) therapy on biochemical markers of bone turnover were investigated in 11 short prepubertal children without GH deficiency by measuring serum osteocalcin, a marker for bone formation, and urinary concentrations of pyridinium cross-linked amino acids of collagen (PCL), and the peptide-bound pyridinoline residue N-telopeptide (NT), which are specific markers for bone resorption. GH treatment for three months increased bone turnover in this group of children: urinary PCL concentrations increased from 69 +/- 6.2 to 114 +/- 9.3 nmol/mmol Cr (p < 0.01), and urinary NT levels increased from 512 +/- 65 to 766 +/- 74 pmol BCE/mumol Cr (p = 0.058). Serum osteocalcin concentrations increased from 13.64 +/- 2.57 ng/ml to 26.45 +/- 1.39 ng/ml (p < 0.01). The increment in 12-hour urinary concentrations of PCL was highly correlated with the increment in 12-hour urinary NT levels (r = 0.92, p < 0.01). Stepwise multiple regression analysis revealed that the urinary concentrations of NT after 3 months of GH therapy were the best predictor of growth after 12 months of treatment (r = 0.78, F = 7.9, p = 0.037).     

Average length of spontaneous labor in Chinese primigravidas

The effect of long-term L-thyroxine (LT4) replacement therapy on bone mineral density and on biochemical markers of bone turnover were studied in children with congenital hypothyroidism (CH). Forty-four children and adolescents (mean age 8.5 +/- 3.5 years) with primary CH who began LT4 replacement therapy within the first month of life were studied. Bone mineral density (BMD) of the lumbar vertebrae and the upper femoral bone was measured by dual energy X-ray absorptiometry. Serum osteocalcin (OC) and bone alkaline phosphatase were measured as markers of bone formation and urinary deoxypyridinoline was taken as a marker of bone resorption. Bone mineral densities of CH children were not different from those in age-matched controls. The biochemical markers of bone turnover were normal except for the serum OC levels which were found to be higher than in controls and positively correlated with the free thyroid hormone levels (for FT4 r = 0.42, p = 0.02). Eight CH children demonstrated low BMD values (below -1 SDS) at -2 +/- 0.7 SDS for the lumbar spine and -1.6 +/- 0.5 SDS for the femoral site. These eight children showed lower mean weight (p < 0.05) and their dietary calcium intake tended to be less (p <0.06) than that seen in the normal BMD group. In conclusion, our results show that LT4 replacement therapy for 8 years is not detrimental to the skeletal mineralization of CH children. As in a healthy population, weight and current intake of calcium seem to be major determinants of bone density. Dietary recommendations, especially when calcium intake is below the recommended dietary allowance, may have to be reconsidered.     

Plasma cholesteryl ester transfer protein activity in hyper- and hypothyroidism

Thyroid dysfunction is associated with multiple changes in lipoprotein metabolism, and we have determined the effects of thyroid dysfunction on plasma cholesteryl ester transfer protein (CETP) activity. CETP is a plasma protein that mediates the exchange of cholesteryl ester and triglyceride between plasma lipoproteins and plays an important role in high-density lipoprotein metabolism and in the reverse cholesterol transport pathway. Plasma CETP activity was assayed in 18 hyperthyroid and in 17 hypothyroid patients, before and after treatment, by measuring the transfer of cholesteryl esters from exogenous radiolabeled high-density lipoprotein to apolipoprotein B-containing lipoproteins. Plasma CETP activity was increased in hyperthyroid patients, compared with their matched controls (22.11 +/- 8.92% transferred/5 microL.4 h vs. 16.75 +/- 6.48, P < 0.05), whereas in hypothyroid patients, plasma CETP activity was decreased (11.14 +/- 4.84% transferred/5 microL.4 h vs. 17.26 +/- 7.13, P < 0.01). Plasma CETP activity decreased after treatment of thyrotoxicosis, although a significant change was observed, mainly in the severely thyrotoxic patients with free T4 > 100 pmol/L (n = 11, 25.61 +/- 8.12% transferred/5 microL.4 h vs. 21.71 +/- 7.84, P < 0.05). In the hypothyroid patients, there was a significant increase in plasma CETP activity after thyroxine replacement (11.14 +/- 4.84% transferred/5 microL.4 h vs. 15.46 +/- 6.71, P < 0.01). There was a strong positive correlation between log(free T4) and plasma CETP activity (r = 0.51, P < 0.001). In summary, both hyper- and hypothyroidism are associated with significant changes in plasma CETP activity, and these changes are corrected when the patients have been rendered euthyroid.     

Bone metabolism markers in patients with Basedow-Graves disease

Collagen type I is the main collagen type found in bones. Carboxyterminal propeptide, deriving and cleaved from procollagen type I (PICP) during collagen synthesis, is delivered into the blood, where it might represent an useful marker of bone formation similarly to osteocalcin. PICP, osteocalcin, alkaline phosphatase, serum and urinary calcium excretion were measured in 58 premenopausal females affected by Graves' disease and also 28 of them after attainment of euthyroidism by methimazole treatment to study these biochemical indices of bone remodelling before and after treatment. Before therapy PICP (mean +/- S.D.: 244.2 +/- 112.3 vs. 136.8 +/- 32.4 micrograms/l), osteocalcin (mean +/- S.D.: 17.8 +/- 6.7 vs. 7.5 +/- 2.7 micrograms/l) and other markers were significantly (p < 0.05) higher than sex and age matched controls (n = 24). Treatment induced a significant decrease of PICP, alkaline phosphatase, calcaemia and calciuria compared to pretreatment values, while osteocalcin did not significantly differ (mean +/- S. D.: 17.8 +/- 6.7 vs. 14.7 +/- 8.7 micrograms/l). These data suggest that hyperthyroidism due to Graves' disease causes an increase of serum levels of these markers, but further studies are necessary to asses the differences between PICP and osteocalcin as markers of osteoblast activity in hyperthyroidism.     

Effects of growth hormone (GH) replacement on bone metabolism and mineral density in adult onset of GH deficiency: results of a double-blind placebo-controlled study with open follow-up

It is known that GH stimulates bone turnover and that GH-deficient adults have a lower bone mass than healthy controls. In order to evaluate the influences of GH replacement therapy on markers of bone turnover and on bone mineral density (BMD) in patients with adult onset GH deficiency, a double-blind placebo-controlled study of treatment with recombinant human GH (rhGH; mean dose 2.4 IU daily) in 20 patients for 6 months and an extended open study of 6 to 12 months were conducted. Eighteen patients, fourteen men and four women, with a mean age of 44 years with adult onset GH deficiency were evaluated in the study. Compared with placebo, after 6 months serum calcium (2.39 +/- 0.02 vs 2.32 +/- 0.02 mmol/l, P = 0.037) and phosphate (0.97 +/- 0.06 vs 0.75 +/- 0.05 mmol/l, P = 0.011) increased and the index of phosphate excretion (0.03 +/- 0.03 vs 0.19 +/- 0.02, P < 0.001) decreased significantly, and there was a significant increase in the markers of bone formation (osteocalcin, 64.8 +/- 11.8 vs 17.4 +/- 1.8 ng/ml, P < 0.001; procollagen type I carboxyterminal propeptide (PICP), 195.3 +/- 26.4 vs 124.0 +/- 15.5 ng/ml, P = 0.026) as well as those of bone resorption (type I collagen carboxyterminal telopeptide (ICTP), 8.9 +/- 1.2 vs 3.3 +/- 0.5 ng/ml, P < 0.001; urinary hydroxyproline, 0.035 +/- 0.006 vs 0.018 +/- 0.002 mg/100 ml glomerular filtration rate, P = 0.009). BMD did not change during this period of time. IGF-I was significantly higher in treated patients (306 +/- 45.3 vs 88.7 +/- 22.5 ng/ml, P < 0.001). An analysis of the data compiled from 18 patients treated with rhGH for 12 months revealed similar significant increases in serum calcium and phosphate, and the markers of bone turnover (osteocalcin, PICP, ICTP, urinary hydroxyproline). Dual energy x-ray absorptiometry (DXA)-measured BMD in the lumbar spine (1.194 +/- 0.058 vs 1.133 +/- 0.046 g/cm2, P = 0.015), femoral neck (1.009 +/- 0.051 vs 0.936 +/- 0.034 g/cm2, P = 0.004), Ward's triangle (0.881 +/- 0.055 vs 0.816 +/- 0.04 g/cm2, P = 0.019) and the trochanteric region (0.869 +/- 0.046 vs 0.801 +/- 0.033 g/cm2, P = 0.005) increased significantly linearly (compared with the individual baseline values). At 12 months, BMD in patients with low bone mass (T-score < -1.0 S.D.) increased more than in those with normal bone mass (lumbar spine 11.5 vs 2.1%, P = 0.030, and femoral neck 9.7 vs 4.2%, P = 0.055). IGF-I increased significantly in all treated patients. In conclusion, treatment of GH-deficient adults with rhGH increases bone turnover for at least 12 months. BMD in the lumbar spine and the proximal femur increases continuously in this time (open study) and the benefit is greater in patients with low bone mass. Therefore, GH-deficient patients exhibiting osteopenia or osteoporosis should be considered candidates for GH supplementation. However, long-term studies are needed to establish that the positive effects on BMD are persistent and are associated with a reduction in fracture risk.     

Thyroid hormones modulate serum leptin levels: observations in thyrotoxic and hypothyroid women

Thyroid hormones and leptin are both involved in the regulation of energy metabolism. Serum leptin concentrations were measured in women with thyrotoxicosis (n = 21, mean age 45 years) or hypothyroidism (n = 14, mean age 44 years) before and 3 months after restoration of the euthyroid state. Serum leptin concentration tended to increase in both hypothyroid (14.7+/-3.5 vs 17.8+/-3.9 ng/ml, p = 0.06) and thyrotoxic (11.9+/-1.7 vs 14.4+/-2.0, p = 0.08) women after treatment (values given as mean +/- SE in the untreated and the euthyroid state respectively). Body mass index (BMI) was lower in thyrotoxic women than in hypothyroid women in the untreated state (22.1+/-0.7 vs. 26.2+/-1.9, p < 0.05). BMI was not different between both groups after treatment (24.5+/-0.7 vs. 26.3+/-2.1, p = 0.37), due to an increase of BMI in the thyrotoxic women; BMI did not change in the hypothyroid group. After controlling for BMI in a multivariate regression analysis, serum leptin concentrations were lower in hypothyroid women than in thyrotoxic women (p < 0.05), whereas posttreatment values of leptin did not differ (p = 0.44). When leptin concentrations were expressed as standard deviation scores (Z-scores) from the mean value of female controls matched for BMI and age as reported earlier, Z-scores were lower in the hypothyroid than in the thyrotoxic women (-0.63+/-0.21 vs. 0.53+/-0.18, p = 0.001). After treatment, Z-scores did not deviate from the expected values (0.05+/-0.28 vs. 0.08+/-0.16, p = 0.98). Z-scores differed before and after treatment in both hypothyroid (p = 0.01) and thyrotoxic (p = 0.02) patients. In conclusion, these data obtained in thyrotoxic and hypothyroid women indicate that thyroid states modulates serum leptin concentrations independent of BMI, with a small decrease in hypothyroidism and a small increase in thyrotoxicosis.     

Treatment of portal hypertension

Abnormalities of carbohydrate metabolism in hyperthyroid patients have been long noted. Elevated proinsulin level is considered as an early marker of B-cell impairment. Proinsulin levels in hyperthyroid patients decreased after antithyroid drug therapy. However, proinsulin in hypothyroid patients was only rarely reported, and the difference was only demonstrated after glucose stimulation-there was a greater response of proinsulin secretion after thyroxine therapy-and the basal fasting proinsulin level was not different after therapy. One of the reasons might be that the assay was not sensitive enough to detect the change of basal proinsulin levels in patients with hypothyroidism after therapy. A newly developed immunochemiluminometric assay of proinsulin was used to demonstrate that the suppressed proinsulin level increased after thyroxine therapy in hypothyroid patients (4.2 +/- 2.4 vs. 10.0 +/- 5.6 pmol/L, p < 0.05; n = 7). On the other hand, our study also confirmed that the proinsulin levels decreased in hyperthyroid patients after antithyroid therapy by methimazole (27.8 +/- 26.0 vs. 15.8 +/- 15.7 pmol/L, p < 0.05; n = 12). In conclusion, proinsulin increased in hypothyroid patients after thyroxine therapy and decreased in hyperthyroid patients after methimazole therapy. The results demonstrated there is a high correlation between thyroid function and B-cell function in hypothyroid as well as hyperthyroid patients.     

Residual urine in 75-year-old men and women. A normative population study

To evaluate the therapeutic effects of high dose pulse oral calcitrol, 3.5 micrograms calcitrol three times a week and calcium carbonate were administered to 13 patients with end-stage renal disease on chronic hemodialysis with hyperparathyroidism refractory to conventional calcitrol therapy. Serum parathyroid hormone and osteocalcin were detected by radioimmunoassay. Serum parathyroid hormone level of the patients decreased from 1111 +/- 344 ng/L to 492 +/- 218 ng/L by 57.5 +/- 11.5 percent (P < 0.01) in 6 months after the beginning of treatment. Both serum alkaline phosphatase and osteocalcin levels declined markedly, and correlated positively with that of parathyroid hormone. Plasma calcium concentration was markedly elevated, but no obvious increase of plasma phosphate was found. High dose pulse oral calcitrol was effective on secondary hyperparathyroidism. During the course of treatment timely and individual adjustment of calcitrol dose and dialysate calcium concentration is essential.     

Blunted cortisol response after administration of corticotropin releasing hormone in endotoxemic dogs

To evaluate the effects of a standard inflammatory challenge on the dynamics of the hypothalamic-pituitary-adrenal (HPA) axis, we studied the effects of low-dose endotoxin (1.0 microgram/kg) on plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations in a saline-controlled study in five awake dogs. Four hours after endotoxin or saline challenge human corticotrophin-releasing hormone (hCRH; 1.0 microgram/kg) was administered. Plasma ACTH and cortisol levels increased considerably in response to endotoxin, from 13 +/- 1 ng/l to 360 +/- 85 ng/l (p < 0.01) and from 60 +/- 20 nmol/l to 710 +/- 80 nmol/l (p < 0.01). Despite a considerable difference in ACTH and cortisol levels prior to CRH administration between both studies (p < 0.01), the absolute increase in ACTH levels induced by hCRH was not different (231 +/ 43 ng/l vs 238 +/- 45 ng/l, control vs endotoxin). Plasma cortisol levels increased significantly in the control study (from 40 +/- 10 nmol/l to 330 +/- 40 nmol/l, p < 0.01), whereas they did not change in the endotoxin study after hCRH administration (from 710 +/- 80 nmol/l to 730 +/- 70 nmol/l, ns). We conclude that the HPA-axis reacts initially to endotoxin in such a way that cortisol, but not ACTH, secretion is maximized. Therefore, a blunted cortisol response to CRH testing is part of the initial response to infection.     

Cardiovascular and metabolic responses to adrenaline infusion in patients with short-term hypothyroidism

OBJECTIVE: The relation between the clinical manifestations of thyroid disease (both hypo and hyper-thyroidism) and tissue sensitivity to catecholamines remains uncertain. It has been suggested that tissue adrenergic responsiveness is decreased in hypothyroidism, but the reports have been conflicting and have invariably focused on a single physiological response. Therefore the aim of the present study was to determine in patients with moderate, short-term, symptomatic hypothyroidism the responses of heart rate, systolic and diastolic blood pressure, forearm blood flow and metabolic rate to adrenaline infused at a rate known to achieve plasma concentrations in the middle of the physiological range. PATIENTS: Ten subjects (5M, age 43 +/- 3 years, mean +/- SEM) were studied. All were on thyroxine replacement for hypothyroidism following either thyroidectomy or radioactive iodine and had been biochemically euthyroid for at least 6 months. DESIGN: Studies were performed in random order. One study was undertaken on full replacement therapy and the other after 50 micrograms thyroxine daily for 2 weeks. After basal, supine measurements adrenaline was infused at 25 ng/kg/min for 30 minutes. MEASUREMENTS: Heart rate, blood pressure, blood glucose, metabolic rate and forearm blood flow were measured at rest and at 10-minute intervals throughout the adrenaline infusion. RESULTS: Free T4 (10.6 +/- 1.3 vs 17.6 +/- 2.0 pmol/l, P < 0.001) and free T3 (3.6 +/- 0.2 vs 4.6 +/- 0.3 pmol/l, P < 0.01) concentrations were significantly lower on 50 micrograms thyroxine than full replacement therapy. Fasting blood glucose concentrations (4.7 +/- 0.2 vs 4.7 +/- 0.1 mmol/l) were similar. The resting adrenaline concentrations were comparable, 0.29 +/- 0.18 and 0.24 +/- 0.14 nmol/l on 50 micrograms thyroxine and full replacement therapy respectively, and increased to a similar level (2.36 +/- 0.39 and 2.36 +/- 0.35 nmol/l) throughout the adrenaline infusion. The resting heart rate and metabolic rate were significantly lower on 50 micrograms thyroxine than full replacement therapy (68 +/- 2 vs 72 +/- 3 beats/min, P < 0.01; and 4.48 +/- 0.35 vs 4.88 +/- 0.39 kJ/min, P < 0.01) respectively, but the increase in heart rate (7 +/- 2 vs 8 +/- 2 beats/min) and metabolic rate (0.43 +/- 0.09 vs 0.43 +/- 0.06 kJ/min) did not differ on the two study days. Resting systolic blood pressure, diastolic blood pressure and forearm blood flow were comparable on 50 micrograms thyroxine and full replacement therapy as were the changes in systolic blood pressure (1 +/- 1 vs 1 +/- 1 mmHg), diastolic blood pressure (-7 +/- 2 vs -7 +/- 1 mmHg), forearm blood flow (1.4 +/- 0.1 vs 1.7 +/- 0.2 ml/min/100ml forearm) and blood glucose concentration (0.7 +/- 0.1 vs 0.7 +/- 0.1 mmol/l). CONCLUSIONS: Patients with short-term hypothyroidism appear to have a normal response to adrenaline infusion despite reduced baseline heart rate and metabolic rate. Thus, under physiological and mild pathophysiological conditions there appears to be no evidence of any synergy between thyroid status and sensitivity to catecholamines.     

Low levels of HDL cholesterol in hypothyroid patients with cardiovascular diseases

BACKGROUND: Hypothyroidism is a frequent cause of hyperlipidemia, particularly in women, but its true prevalence, both in the general population and in dyslipidemic subjects, is unknown. It is uncertain if low thyroid function significantly influence HDL metabolism and if sub-clinical disease may cause metabolic abnormalities and increase cardiovascular risk. METHODS: Three-hundred and three consecutive female patients (mean age 59.2 +/- 0.5 yrs), observed in a metabolic ward because of dyslipidemia, were evaluated. RESULTS: Forty-three women (14.1% of the total) showed sub-clinical hypothyroidism, while in 12 cases (4.0%) overt hypothyroidism was diagnosed; 8 further women (2.6%) had been previously diagnosed to be hypothyroid and were under hormone replacement therapy. On the whole, hypothyroid patients showed higher mean triglyceride levels and lower HDL-cholesterol than dyslipidemic euthyroid women, but the difference did not reach statistical significance. Total cholesterol concentration did not change with impaired thyroid function. Hypothyroid patients reported a clinical history of cardiovascular disease, or had severe atherosclerosis demonstrated, more often than euthyroid subjects (25.0% vs 19.7%, p = n.s.). When only women with arterial disease were considered, HDL plasma levels were significantly lower in the hypothyroid than in the euthyroid group (44.3 +/- 3.1 vs 56.2 +/- 1.7 mg/dl, respectively; p < 0.01). Hypertriglyceridemia and obesity often coexisted. CONCLUSIONS: In conclusion, among dyslipidemic women, unrecognised hypothyroidism is highly prevalent (both sub-clinical and manifest). In hypothyroid subjects atherosclerosis seem to associate with particularly low HDL plasma levels. This might precede atherosclerosis development (reinforced by concomitant thyroid failure) and represent a marker of the polymetabolic syndrome.     

Serum beta-2 microglobulin is a marker of high bone remodelling in elderly women

Beta-2 microglobulin (beta2m), the water soluble extrinsic light chain of class I MHC, has been recently isolated from the adult bone culture medium. Serum beta2m plays a role as a bone-derived growth factor regulating both osteoblast and osteoclast cell activity. Serum beta2m has been proposed as a bone remodeling biological marker in high bone turnover conditions. The purpose of our study was to determine the relationship between beta2m and vitamin D status in post-menopausal women. We have studied 44 healthy women from 20 to 80 years with normal hepatic and renal function, without diabetes mellitus and/or inflammatory, tumoral or infectious diseases. We measured the serum levels of calcium, phosphorus, parathyroid hormone (PTH), vitamin D binding protein (DBP), 25-OHD3 (calcidiol), 1,25(OH)2D3 (calcitriol) and beta2m. Serum beta2m levels increased with age (r = 0.54, P < 0.001). Post-menopausal women had higher serum levels than pre-menopausal women of beta2m (1.76 +/- 0.22 mg/l vs. 1.35 +/- 0.2 mg/l, P < 0.01); PTH (61.5 +/- 7.5 ng/ml vs. 39 +/- 6 ng/ml, P < 0.001) and lower serum levels of 25-OHD3 (7.5 +/- 2.3 ng/ml vs. 18.2 +/- 2.5 ng/ml, P < 0.001). Moreover, serum levels of beta2m were negatively correlated with 25-OHD3 (r = -0.34, P < 0.05) and with ionized calcium (r = -0.45, P < 0.01) and positively with PTH (r = 0.48, P < 0.01). These results support the role of beta2m as a regulator of bone metabolism and its potential use as a marker of high bone turnover in post-menopausal women, specially in elderly women with vitamin D deficiency and secondary hyperparathyroidism.     

Magnesium deficiency and bone loss after cardiac transplantation

Magnesium depletion adversely affects many phases of skeletal metabolism and has been implicated as a risk factor in several forms of osteoporosis. Magnesium deficiency has also been reported after cardiac transplantation. To evaluate whether altered magnesium homeostasis could be related to the pathogenesis of early bone loss after cardiac transplantation, we prospectively measured serum and urinary magnesium and evaluated them with respect to biochemical indices of mineral metabolism and rates of bone loss. The study population included 60 patients (45 men, 15 women) aged 53 +/- 11 years (SD) with measurements of biochemistries and bone mineral density by dual-energy X-ray absorptiometry before and 3 months after transplantation. All received prednisone, cyclosporine A, and azathioprine, plus calcium (1000 mg) and vitamin D (400 IU). After transplantation, serum magnesium decreased by 16 +/- 15% (SD) from 2. 0 +/- 0.3 mg/dl to 1.6 +/- 0.2 mg/dl (normal 1.8-2.2 mg/dl; p < 0. 0001), accompanied by an increase in the fractional excretion of magnesium (7.1 +/- 3.9% to 13.3 +/- 5.6%; p < 0.0017). Forty-three patients with low 3-month serum magnesium levels (相似文献   

Bone mass improves in alcoholics after 2 years of abstinence

To evaluate the effect of abstinence on bone mass and bone mineral metabolism in chronic alcoholics, a 2 year longitudinal follow-up study was carried out in a group of 30 chronic alcoholic males who started a rehabilitation program. Lumbar and femoral bone mineral density (BMD) and serum levels of osteocalcin and 25-hydroxyvitamin D were measured at entry and after 1 and 2 years in all patients. Circulating cortisol and parathyroid hormone were measured in 14 and 6 patients, respectively, at entry and every year. Testosterone was measured in 18 patients at entry and after 1 year. At entry, lumbar BMD was significantly lower in alcoholics (1.06 +/- 0.03 g/cm2) than in age-matched healthy men (1.22 +/- 0.03 g/cm2; p < 0.001). Circulating osteocalcin and vitamin D levels were also significantly lower in alcoholics than in controls. Lumbar and femoral neck BMD increased in alcoholics after 2 years of abstinence (lumbar BMD, mean +/- SEM, 1.06 +/- 0.03 to 1.10 +/- 0.04 g/cm2, p < 0.05; femoral BMD, 0.82 +/- 0.02 to 0.84 +/- 0.02 g/cm2; p < 0.02). Moreover, lumbar BMD increased in alcoholics (2.9 +/- 1.4%) and decreased in controls (-1.1 +/- 0.2%; p < 0.02). Femoral BMD also increased in alcoholics (2.8 +/- 1.0%) but the expected mean decrease of -0.92% was found in healthy age-matched males. Baseline low osteocalcin levels (5.1 +/- 0.6 ng/ml) increased after 1 year (8.6 +/- 0.5 ng/ml, p < 0.001) and 2 years of abstinence (9.5 +/- 0.7 ng/ml, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of dihydrotestosterone on bone biochemical markers in sham and oophorectomized rats

Evidence exists to suggest that androgens stimulate bone formation in the estrogen-deficient state, however the mechanism of action is unclear. The following study investigates the effect of dihydrotestosterone (DHT) on biochemical markers of bone turnover and calcium homeostasis in sham and oophorectomized (oophx) rats when either vehicle, 40, 80, or 160 mg/kg body weight (bw) DHT were administered at the time of operation or at 15 weeks postoperation. Serum alkaline phosphatase (ALP) increased following DHT administration in sham and oophx rats in all groups (mean ALP +/- SEM [U/l] week 8; sham vehicle, 40 +/- 7; sham 160 mg DHT/kg bw, 72 +/- 5; oophx vehicle, 60 +/- 6; oophx 160 mg DHT/kg bw, 88 +/- 11) (p < 0.001). In contrast, serum osteocalcin was significantly suppressed in oophx rats administered DHT 15 weeks following operation (mean osteocalcin +/- SEM [micrograms/l] week 8; oophx vehicle, 17.6 +/- 3.5; oophx 160 mg DHT/kg bw, 10.5 +/- 1) (p < 0.01). Urine deoxypyridinoline was significantly decreased when DHT was administered 15 weeks postoophorectomy (p < 0.001); however, urine hydroxyproline was not affected by DHT treatment in any group. Urine calcium was decreased by DHT treatment (mean Ca/Cr +/- SEM week 8; sham vehicle, 0.87 +/- 0.13; sham 160 mg DHT/kg bw, 0.24 +/- 0.08; oophx vehicle, 0.68 +/- 0.16; oophx 160 mg DHT/kg bw; 0.45 +/- 0.1) (p < 0.005) which was associated with an increase in the renal tubular reabsorption of calcium (p < 0.05). This study demonstrates the direct effects of DHT on both bone cell activities and the renal handling of calcium.     

Discharge planning in a community hospital--a multidisciplinary approach

OBJECTIVES: Osteoporosis is common in subjects over 70 years of age. Likewise, the incidence of monogammapathies of undetermined signification (MGUS) increases with age. We conducted this study to determine whether the biological and histomorphometric characteristics of osteoporosis in patients with MGUS are different from those in primary osteoporosis and to ascertain whether any cause and effect relationships could exist between MGUS and osteoporosis, excluding signs of active myeloma. PATIENTS AND METHODS: Serum and urinary phosphorus and calcium, histomorphometric measurements, hormone levels and serum cytokines (IL1, IL6 and TNF alpha) were determined in 7 patients (mean age 71.8 years, 2 men and 5 women) with MGUS associated with osteoporosis with vertebral fractures (OP) and compared with those in 7 osteoporosis patients without MGUS matched for age, sex, and osteoporosis severity and 7 other age and sex matched patients with MGUS without OS. The MGUS + PS patients were followed for 9 years (4.5 to 20) so slowly progressive myeloma could be excluded. RESULTS: Cytokine levels were the same in the three groups of patients but MGUS + OP patients had higher urinary calcium levels (ca/cr = 0.21 +/- 0.08 vs 0.12 +/- 0.1 (OP) and 0.13 (MGUS); p = 0.04), decreased osteocalcin levels (7 +/- 4.6 ng/ml vs. 12 +/- 4 (OP) and 11.5 +/- 5 (MGUS); p = 0.01) and increased surface resorption (8 +/- 1.4 vs. 3.6 +/- 1.2 (OP) and 5.5 +/- 1.7 (MGUS); p = 0.05). DISCUSSION: It has been demonstrated that MGUS in patients with increased resorption and lower osteocalcin levels frequently progresses to active myeloma. The question is raised as to whether, in certain cases of MGUS, in situ stimulation of bone cells by monoclonal plasma cells could exist without ongoing transformation to active myeloma.     

Influence of metabolic acidosis on serum 1,25(OH)2D3 levels in chronic renal failure

Metabolic acidosis has been shown to alter vitamin D metabolism. There is also evidence that calcium may modulate 1,25(OH)2D3 by a parathyroid hormone (PTH)-independent mechanism. To investigate the effect of rapid correction of chronic metabolic acidosis on serum 1,25(OH)2D3 levels by free calcium clamp in chronic renal failure, 20 patients with mild to moderate metabolic acidosis (mean pH 7.31 +/- 0.04) and secondary hyperparathyroidism (mean intact PTH 156.47 +/- 84.20 ng/l) were enrolled in this study. None had yet received any dialysis therapy. Metabolic acidosis was corrected by continuous bicarbonate infusion for 3-4 h until plasma pH was around 7.4, while plasma ionized calcium was held at the preinfusion level by calcium solution infusion during the entire procedure. The plasma pH, bicarbonate, total CO2, sodium, and serum total calcium levels were significantly increased while serum concentrations of alkaline phosphatase and albumin were significantly decreased after bicarbonate infusion. The plasma ionized calcium, potassium, serum magnesium, inorganic phosphorus, and 25(OH)D levels showed no significant change before and after bicarbonate infusion. The serum 1,25(OH)2D3 levels were significantly increased (38.66 +/- 11.77 vs. 47.04 +/- 16.56 pmol/l, p < 0.05) after correction of metabolic acidosis. These results demonstrate that rapid correction of metabolic acidosis raises serum 1,25(OH)2D3 levels in vitamin D-deficient chronic renal failure patients, and may underline the importance of maintaining normal acid-base homeostasis in the presence of secondary hyperparathyroidism in chronic renal failure.     

Thyroid hormones in diabetic ketoacidosis before and after therapy

Fifteen IDDM patients were evaluated for thyroid hormone abnormalities before and after control of diabetes mellitus/ketoacidosis. Blood sugar mean +/- SEM mg/dl on admission was 430 +/- 20.3 and after therapy fasting and post prandial blood sugar values were 120 +/- 14.5 and 150 +/- 20.2 respectively. GHb mean +/- SEM % on admission was 15.2 +/- 0.36. Serum T3 mean +/- SEM ng/dl of 0.36 +/- 0.04 was in hypothyroid range and rT3 mean +/- SEM ng/ml 0.40 +/- 0.6 was significantly raised (P < 0.001) before therapy. After metabolic control both T3 and rT3 became normal. T4 concentration mean +/- SEM meg/dl of 5.5 +/- 0.7 was well within normal range before therapy and rose to mean +/- SEM mcg/dl 8.8 +/- 0.5 after therapy (P < 0.01). TSH response to TRH was blunted in uncontrolled state. It is concluded that peripheral changes in T3, T4 and rT3 (low T3, high rT3 and low or normal T4) occurred in uncontrolled diabetic state during ketoacidosis. TSH response to TRH was blunted due to suppression of hypothalamic pituitary thyroid axis which takes more than a week for complete recovery.     

Ultrastructural morphometric study of the prostate of the rat after microsurgical denervation

In an epidemiological study, markers of bone formation (serum osteocalcin and C-terminal propeptide of type I collagen) and bone resorption [urinary type I collagen peptides (Crosslaps), urinary total pyridinoline (TPYRI), urinary deoxypyridinoline (DPYRI) as well as female sex hormones (serum estradiol)], follicle-stimulating hormone (FSH) and luteinizing hormone were measured in 237 women. This cohort aged 44-66 years, came for their first medical examination since menopause to the outpatient menopause clinic at the Kaiser-Franz-Josef-Hospital, Vienna. The women were all 0.5-5.0 years since cessation of menses and were not taking medications other than hormone replacement therapy [52 cases, 21.9%)] and had no diseases known to affect bone and mineral metabolism. The best correlation was found between urinary DPYRI and urinary TPYRI (r = 0. 63, P = 0.0001), followed by urinary Crosslaps and urinary DPYRI (r = 0.47, p = 0.0001). Only weak but significant correlations between E2 and urinary Crosslaps (r = -0.21, P < 0.0001) as well as serum E2 and serum osteocalcin (r = -0.16, P = 0.0007), were observed. Of the 237 women 53% suffered from a severe E2 deficiency (E2 < 10.0 ng/liter). In these patients, urinary Crosslaps (+48%) and serum osteocalcin (+22%) were significantly higher (P < 0.0001) compared with those patients with E2 levels > 10 ng/liter. Women with E2 levels >10 ng/liter were further subdivided into those with and without sex hormone replacement therapy, whereby no statistical differences in any of the biochemical markers could be observed between these groups. We could clearly demonstrate that in postmenopausal women suffering from severe E2 deficiency (E2 < 10 ng/liter), urinary Crosslaps and serum osteocalcin are significantly increased, indicating in principle a clear correlation between E2 deficiency and these markers of bone turnover.     

Biologic variation in electrolytes and essential microelements in the blood of neonates and their mothers

Serum concentration and biological variability (CVB%) of total calcium (Ca) magnesium (Mg), iron (Fe), zinc (Zn) and copper (Cu) were determined in 22 sera of maternal and umbilical cord blood in normal pregnancies. The concentrations of Ca (2.48 +/- 0.13 vs 2.27 +/- 0.13 mmol/l), Mg (0.84 +/- 0.06 vs 0.80 +/- 0.07 mmol/l), Fe (24.1 +/- 6.62 vs 10.7 +/- 4.94 mumol/l) and Zn (14.1 +/- 1.78 vs 9.1 +/- 2.21 mumol/l) in the cord sera were significantly higher than in maternal sera (p < 0.01), whereas maternal copper concentrations (36.6 +/- 4.82 vs 9.2 +/- 2.21 mumol/l), were significantly higher than in cord sera (p < 0.01). Biological variability of Ca (5.37 vs 4.84%), Mg (8.39 vs 6.69%), Fe (46.1 vs 27.3%) and Zn (24.1 vs 12.3%) values was higher in the maternal sera than the respective values in the cord sera, while the biological variability of copper in the cord sera was significantly higher than the respective value in the maternal sera (26.7 vs 12.8%). These results are in agreement with those previously reported and suggest that fetal homeostasis of Ca, Mg, Fe and Zn is at least partly independent of maternal factors.