Risk for fracture in women with low serum levels of thyroid-stimulating hormone

BACKGROUND: Biochemical evidence of hyperthyroidism may be associated with low bone mass, particularly in older postmenopausal women, but no prospective studies of thyroid function and subsequent fracture risk have been done. OBJECTIVE: To examine the association between low levels of thyroid-stimulating hormone (TSH) and fracture in older women. DESIGN: Prospective cohort study with case-cohort sampling. SETTING: Four clinical centers in the United States. PATIENTS: 686 women older than 65 years of age from a cohort of 9704 women recruited from population-based listings between 1986 and 1988. MEASUREMENTS: Baseline assessment of calcaneal bone mass, spine radiography, and history of thyroid disease. Spine radiography was repeated after a mean follow-up of 3.7 years; nonspine fractures were centrally adjudicated. Thyroid-stimulating hormone was measured in sera obtained at baseline from 148 women with new hip fractures, 149 women with new vertebral fractures, and a subsample of 398 women randomly selected from the cohort. RESULTS: After adjustment for age, history of previous hyperthyroidism, self-rated health, and use of estrogen and thyroid hormone, women with a low TSH level (0.1 mU/L) had a threefold increased risk for hip fracture (relative hazard, 3.6 [95% CI, 1.0 to 12.9]) and a fourfold increased risk for vertebral fracture (odds ratio, 4.5 [CI, 1.3 to 15.6]) compared with women who had normal TSH levels (0.5 to 5.5 mU/L). After adjustment for TSH level, a history of hyperthyroidism was associated with a twofold increase in hip fracture (relative hazard, 2.2 [CI, 1.0 to 4.4]), but use of thyroid hormone itself was not associated with increased risk for hip fracture (relative hazard, 0.5 [CI, 0.2 to 1.3]). CONCLUSIONS: Women older than 65 years of age who have low serum TSH levels, indicating physiologic hyperthyroidism, are at increased risk for new hip and vertebral fractures. Use of thyroid hormone itself does not increase risk for fracture if TSH levels are normal.     

Cord blood lipoprotein-cholesterol: relationship birth weight and gestational age of newborns

Umbilical plasma levels of lipoproteins-cholesterol were measured in 60 premature (less than 37 weeks), 60 small for gestational age (SGA, greater than 37 weeks), and 60 full term newborns (greater than 37 weeks) to ascertain the relationship between gestational age, infant's weight and concentration of plasma lipoprotein cholesterol. Umbilical levels of total cholesterol (TC), unesterified cholesterol (UC), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) in premature newborns were significantly higher (P less than .001) than in term infants. The levels of TC, UC, HDL-C and very low density lipoprotein cholesterol (VLDL-C) were substantially higher (P less than .05) in umbilical cord plasma of SGA newborns than in cord plasma of full term newborns. Lecithin:cholesterol acyltransferase activity in cord plasma was indirectly assessed by measuring the ratio of esterified cholesterol to unesterified cholesterol (CE/UC). This ratio was significantly lower (P less than .01) in preterm and SGA than in full term newborns. In addition, plasma TC, UC, LDL-C and HDL-C levels were inversely correlated with gestational age of newborns. By contrast, CE/UC ratio had an inverse correlation with gestational age and HDL-C of the newborns. These findings suggest that the levels of TC in newborns are regulated by the uptake of LDL-C by the fetal adrenal and, additionally, by the lecithin:cholesterol acyltransferase (LCAT) activity of newborn plasma. Only by careful follow-up of hyperlipidemic neonates can the true incidence of familial hyperlipoproteinemia and the value of early diagnosis be assessed.     

血清促甲状腺素水平与急性缺血性卒中患者转归的相关性

目的 探讨血清促甲状腺素(thyroid-stimulating hormone,TSH)水平与急性缺血性卒中转归的相关性.方法 前瞻性纳入急性缺血性卒中患者,收集一般临床资料、血管危险因素和甲状腺.激素等生化指标.应用美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale,NIHSS)评估基线神经功能缺损程度.在发病后90 d时采用改良Rankin量表(modified Rankin Scale,mRS)评估神经功能转归,0～2分定义为转归良好.采用多变量logistic回归分析确定急性缺血性卒中患者转归不良的独立影响因素.结果 共纳入140例急性缺血性卒中患者,其中男性95例(67.86％),女性45例(32.14％),年龄35 ～94岁.亚临床甲状腺功能减退13例(9.29％),亚临床甲状腺功能亢进17例(12.14％).98例(70.00％)转归良好,42例(30.00％)转归不良.转归良好组男性(x2=4.717,P=0.047)和小动脉闭塞性卒中(r=5.564,P=0.018)患者构成比以及尿酸(t=2.602,P=0.010)、FT3(归2.406,P=0.017)和TSH(t=2.302,P=0.023)水平显著高于转归不良组,年龄(泞-3.489,P=0.001)、空腹血糖(Z=-2.178,P=0.031)和基线NIHSS评分(归-8.009,P＜0.001)显著低于转归不良组.转归良好组TSH位于第1四分位数(＜0.805 mU/L)的患者构成比显著低于转归不良组(17.35％对42.86％;x2=10.204,P=0.003),而位于第4四分位数(＞2.476 mU/L)的患者构成比显著高于转归不良组(30.61％对11.90％;x2=5.488,P=0.020).多变量logistic回归分析显示,在校正各种混杂因素后,基线NIHSS评分较高是发病后90 d时转归不良的独立危险因素(优势比1.690,95％可信区间1.317 ～2.168;P＜0.001),而基线TSH水平较高与转归良好独立相关(优势比0.520,95％可信区间0.408 ～0.867;P =0.007).结论 血清TSH水平较高与急性缺血性卒中患者发病后90 d时神经功能转归良好独立相关.     

Plasma adiponectin levels in newborns are higher than those in adults and positively correlated with birth weight

OBJECTIVE: The aim of this study was to examine plasma adiponectin concentrations during perinatal the period and their correlations with fetal anthropometric parameters and other hormones. DESIGN: Venous cord blood samples were obtained from 59 full-term healthy newborns (36 males and 23 females, gestational age 37.0-41.4 weeks, birth weight 2,146-4,326 g, birth length 44.0-54.5 cm). The blood samples were also obtained from 15 neonates (postnatal day 3-7) whose cord blood had already been collected and the changes in adiponectin concentrations were examined. MEASUREMENTS: The adiponectin concentration was determined by enzyme-linked immunosorbent assay. The leptin concentration was determined by radioimmunoassay. Insulin, GH and IGF-1 concentrations were determined by immunoradiometric assays. RESULTS: The plasma adiponectin concentrations in cord blood ranged from 6.0 to 55.8 microg/ml (median 22.4 microg/ml), which were much higher than those in normal-weight adults (P < 0.0001). In contrast to the findings in adults, these values were positively correlated with birth weight (r = 0.43, P = 0.0005), body mass index (r = 0.44, P = 0.0005), birth weight/birth length ratio (r = 0.46, P = 0.0002) and the leptin concentrations (r = 0.39, P = 0.004). When the effects of fat mass-related anthropometric parameters such as the birth weight/birth length ratio were controlled, plasma adiponectin concentrations had a significant inverse correlation with insulin concentrations (r = -0.35, P = 0.01). There was no significant gender difference in adiponectin concentrations among newborns. The adiponectin concentrations in neonates (postnatal day 3-7) did not change significantly compared with those in cord blood. CONCLUSIONS: In contrast to the findings in adults, these results suggest that the adiponectin concentration increases with the mass of fetal fat.     

Levels of serum thyroid-stimulating hormone in hyperthyroidism.

A modified thyroid-stimulating hormone (TSH) radioimmunoassay with particular sensitivity at the bottom end of the normal range was developed using dog serum in standard tubes and reduced quantities of TSH labeled with radioactive iodine (125I) and antiserum. The standard deviation of B0 points was 1%, implying an assay sensitivity of less than 0.1 microU/mL. This procedure was used to measure serum TSH levels in 32 normal subjects, 18 patients with hyperthyroidism, and seven patients with elevation of serum triiodothyronine (T3) levels. The range of values obtained from normal subjects was less than 0.1 to 4.1 microU/mL, with 97% of the subjects' values greater than 0.2 microU/mL. All of the hyperthyroid patients had values less than or equal to 0.2 microU/mL. Hence, the modified TSH assay was thought to be of use in distinguishing hyperthyroid from normal subjects. The TSH levels in subjects with elevated T3 levels ranged from less than 0.1 to 1.8 microU/mL. These results were thought to indicate heterogeneity within this group and suggest that only certain of these individuals merit the diagnosis of "T3 toxicosis."     

Serum thyroglobulin levels are elevated in newborns from iodine-deficient areas

Newborn infants have elevated serum thyroglobulin (Tg) levels and reduced iodination of Tg. To determine whether a relationship exists between serum Tg levels and the degree of Tg iodination, 699 newborn infants were studied in 3 areas of Sicily: a normal iodine-sufficient (control) area and 2 iodine-deficient areas. In the iodine-sufficient area, the mean cord serum Tg level was 25.8 ng/ml (median, 18.0; n = 183). In the iodine-deficient areas, the serum Tg levels in newborns were significantly higher, with mean levels of 43.4 ng/ml (median, 29.7; n = 304; P less than 0.01) and 60.1 ng/ml (median, 48.0; n = 212; P less than 0.005), respectively. The higher serum Tg level at birth was not entirely due to increased cord serum TSH levels, since newborns from the iodine-deficient areas with serum TSH levels at birth similar to those in infants from the control area had higher serum Tg levels. Serum Tg levels correlated with the serum T3 to T4 ratio, but not with serum TSH, T4, or T3 levels. These data suggest that iodine availability, which affects the degree of thyroid Tg iodination, partially determines serum Tg levels at birth.     

Cord blood serum in newborns of diabetic mothers

Serum cholesterol, triglycerides and lipoprotein cholesterol were measured in cord bloods from 117 newborns. Group I consisted of 39 infants of diabetic mothers and Group II (control) consisted of 78 newborns of non-diabetic mothers. The most significant difference in serum lipids between the two groups was the higher levels of LDL cholesterol and lower levels of HDL cholesterol in the newborns of diabetic mothers. Cord blood serum cholesterol was slightly, but not significantly, higher in children born of diabetic mothers. Serum triglycerides were also not significantly different between the groups. While it remains to be established whether elevated levels of LDL cholesterol and decreased levels of HDL cholesterol at birth in these infants represent a transient phenomenon, this study suggests that newborns of diabetic mothers may be predisposed early in life to LDL hypercholesterolemia and thus may be at a greater risk of developing coronary heart disease later in life.     

Expression of thyroid-stimulating hormone receptors and thyroglobulin in limbic regions in the adult human brain

Expression of the human thyroid-specific proteins, thyroid-stimulating hormone receptor (TSH-R) and thyroglobulin (TG) in non-thyroid tissue is well-documented. TSH-R has been identified in the heart, kidney, bone, pituitary, adipose tissue, skin and astrocyte cultures. TG has been identified in the skin, thymus and kidney. However, none of those previous studies had identified TSH-R or TG in specific human brain regions. Previously, a pilot study conducted by our group on normal adult human brain demonstrated TSH-R and TG in cortical neurons and cerebral vasculature, respectively, within various brain areas. In the present study, we extend this investigation of thyroid proteins specifically in limbic regions of normal human brain. Forensic human samples of amygdalae, cingulate gyrii, frontal cortices, hippocampii, hypothalamii, and thalamii were obtained from five individuals who had died of causes unrelated to head injury and had no evidence of brain disease or psychological abnormality. Tissues were probed with commercial polyclonal antibodies against human TSH-R and TG which resulted in the significant demonstration of neuronal TSH-R in all limbic regions examined. Other novel results demonstrated TG in vascular smooth muscle of all limbic regions and in some neurons. Finding thyroid proteins in limbic areas of the human brain is unique, and this study demonstrates that cerebro-limbic localisation of thyroid proteins may have potential roles in neuro-psycho-pharmacology.     

Immunoglobulin serum levels in very low birth weight infants treated with different intravenous preparations

Summary Parenteral human immunoglobulin (IVIG) administration is widely used in low birth weight (LBW) infants for prevention and therapy of neonatal infection. In previous studies, IVIG preparations containing IgG and low IgM concentrations were commonly used. In this study we compare immunoglobulin serum levels in two groups of healthy preterm infants receiving prophylactically standard IVIG (Sandoglobulin, 0.1 mg/kg IgM) or IgM-enriched IVIG (Pentaglobin, 30 mg/kg IgM). Immunoglobulin levels were assayed by rate nephelometry at birth and at 3, 5, 7, and 14 days after birth. The two groups of patients were matched for gestational age (31±2.3 weeks), birth weight (1320±340 g), and serum IgG (4.1±1.9 g/l) and IgM (0.22±0.18 g/l) levels at birth. Significantly higher IgM levels were observed at 3 and 5 days after IgM-enriched IVIG administration (p<0.01). Higher IgG levels were attained and persisted for 2 weeks after standard IVIG administration (p<0.01). These data indicate different IgG and IgM target levels in LBW infants treated with different immunoglobulin preparations.     

Growth hormone binding protein levels in children are associated with birth weight, postnatal weight gain, and insulin secretion

Rapid infancy weight gain is associated with subsequent higher circulating insulin-like growth factor (IGF) I levels in normal children. We hypothesized that circulating levels of growth hormone binding protein (GHBP), a putative marker of GH sensitivity, may also be associated with postnatal weight gain and insulin secretion. In 751 normal children aged 7 to 8 years, we measured insulin, glucose, GHBP, IGF-I, IGF binding protein (IGFBP) 1, and IGFBP-3 levels in a fasting venous blood sample. Insulin secretion was assessed by measuring insulin and glucose levels 30 minutes after an oral glucose load. After adjustment for current weight, birth weight was inversely related to IGF-I and GHBP levels. Children with lower birth weight and rapid weight gain between birth and 3 years had higher IGF-I and GHBP levels and also lower IGFBP-1 levels than other children. Allowing for current body mass index, GHBP levels were positively related to insulin secretion. In conclusion, children who showed rapid early postnatal weight gain after low birth weight have higher levels of GHBP than other children. Increased GH sensitivity in such children could contribute to links between rapid infancy weight gain and subsequent faster rates of childhood growth and maturation.     

甲状腺功能正常人群血清促甲状腺激素水平与血脂的相关性

目的探讨甲状腺功能正常人群血清促甲状腺激素(TSH)水平与血脂水平的相关性。方法选取2018年4月至2019年4月在北京朝阳医院体检中心进行健康体检的2754名体检人员为研究对象。检测其血游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、TSH、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)及低密度脂蛋白胆固醇(LDL-C)水平。所有研究对象的血TSH、FT3、FT4均在参考值范围内。比较男性和女性人群的一般临床资料及血脂水平。以TSH水平1.0和1.9为界值,对人群进行分组,低于1.0定义为正常低值组,高于1.9定义为正常高值组,介于两者之间定义为正常中值组。比较不同人群在不同TSH水平下的血脂水平差异。采用多元线性回归分析TSH水平与各血脂水平的相关性。结果男性人群的吸烟史、高血压及糖尿病比例、体质指数、FT3、FT4和TG水平显著高于女性,而年龄、TSH、TC和HDL-C水平显著低于女性(均为P<0.01)。在总体人群中,TSH正常高值组的HDL-C水平显著高于正常中值组,同时TC水平显著高于正常低值组和正常中值组(均为P<0.05)。在女性人群中,TSH正常高值组和正常中值组的TG水平均显著高于正常低值组,而正常高值组又显著高于正常中值组(均为P<0.05)。多元线性回归分析表明,TSH水平与TC和TG呈正相关,且这种相关性独立于甲状腺激素(β=0.056,P=0.010;β=0.075,P=0.004)。结论在甲状腺功能正常的人群中,TSH水平与TC、TG呈显著正相关,TSH水平在正常范围内升高可能是血脂升高的危险因素。     

Secular decline in male testosterone and sex hormone binding globulin serum levels in Danish population surveys

CONTEXT: Adverse secular trends in male reproductive health have been reported to be reflected in increased testicular cancer risk and decreased semen quality in more recently born men. These secular trends may also be reflected by changes in Leydig cell function. OBJECTIVE: The objective of the study was to examine whether an age-independent time trend in male serum testosterone levels exists. DESIGN AND SETTING: Testosterone and SHBG were analyzed in 5350 male serum samples from four large Danish population surveys conducted in 1982-1983, 1986-1987, 1991-1992, and 1999-2001. Free testosterone levels were calculated. The effects of age, year of birth, and time period on hormone levels were estimated in a general linear statistical model. MAIN OUTCOME MEASURES: Testosterone, SHBG, and calculated free testosterone levels in Danish men in relation to age, study period, and year of birth were measured. RESULTS: Serum testosterone levels decreased and SHBG levels increased with increasing age. In addition to this expected age effect, significant secular trends in testosterone and SHBG serum levels were observed in age-matched men with lower levels in the more recently born/studied men. No significant age-independent effect was observed for free testosterone. Adjustment for a concurrent secular increase in body mass index reduced the observed cohort/period-related changes in testosterone, which no longer were significant. The observed cohort/period-related changes in SHBG levels remained significant after adjustment for body mass index. CONCLUSIONS: The observed age-independent changes in SHBG and testosterone may be explained by an initial change in SHBG levels, which subsequently lead to adjustment of testosterone at a lower level to sustain free testosterone levels.     

Variation of serum ferritin in low birth weight infants with maternal ferritin, birth weight and gestational age.

Serum ferritin measured at birth in 69 low birth weight infants proved to vary with gestational age as well as with weight. The increase with gestational age was even more striking when the infants small for gestational age were excluded. The relation between maternal and infant serum ferritin concentration was investigated for 2 groups of infants and their mothers (*preterm and term infants, respectively). Neither in preterm nor in term infants was the serum ferritin found to vary with that in the respective mothers.     

Maternal cocaine use and low birth weight newborns: a meta-analysis

Aim/design. Many epidemiological studies published on the association between maternal cocaine/crack use and birth weight have either lacked precision or failed to control for major confounding, predominantly by tobacco smoking. Meta-analysis enables a single summary measure of effect to be calculated by combining data from any number of individual studies, thus enhancing statistical power. We undertook a number of meta-analyses using only studies that had adjusted for tobacco smoking to estimate more precisely the effect of maternal cocaine use on birth weight. Findings. A meta-analysis of five studies presenting data for ‘any’ prenatal cocaine exposure, adjusted far tobacco smoking but unadjusted for gestational age, produced a pooled relative risk estimate from a fixed effects analysis of 2.15 (95% CI 1.75-2.64). However, there was substantial heterogeneity among studies (p < 0.001), and the relative risk from a random effects analysis was smaller (1.65) with a confidence interval that included unity (95% CI 0.94-2.83). Addition of a further study adjusted for gestational age had minimal effect on the pooled estimate: the fixed effects relative risk was 2.14 (1.77-2.60) and the random effects estimate 1.77 (1.15-2.71). When data on more intense prenatal exposure were analysed, the fixed and random effects analysis produced the lame pooled estimate of the relative risk of 4.42 (2.24-8.71), suggesting that more frequent cocaine exposure was associated with a higher relative risk for low birth weight. Data from studies on mean reduction in birth weight produced a pooled estimate of 112 g (95% CI 62-161 g). Conclusions. The current study suggests that maternal cocaine use causes low birth weight, and that the effect is greater with heavier use. However, despite the adjustment for tobacco and the adjustment by some studies for other confounders such as race, maternal age, gravidity and socio-economic status, it could be argued that other life-style factors not controlled for may account for the observed effects. While this argument is not supported by some other types of study, the issue of residual confounding can only be finally addressed by analytical studies which adequately control for important variables.