Complement activation in postpartum thyroiditis.

BACKGROUND: Postpartum thyroid dysfunction (PPTD) develops in 50% of pregnant women who have raised levels of circulating thyroid peroxidase autoantibodies (TPOAb) at booking. Although these antibodies are able to activate the complement cascade in vitro, it is not known whether complement activation plays any role in the pathogenesis of this disease. AIM: To investigate potential and actual activation of the complement system in women with postpartum thyroiditis. DESIGN: Complement activation was monitored on a weekly basis in 24 postpartum women who had raised TPOAb at 16 weeks gestation, attending an antenatal clinic in Mid-Glamorgan, Wales. METHODS: ELISA procedures were used to measure both in-vitro complement C3 activation by TPOAb and circulating terminal complement complexes (TCC) in serum. RESULTS: Higher levels of bioactive TPOAb activity were seen in women who developed PPTD when compared to those who did not. However, TCC remained undetectable in serum throughout the period of study. CONCLUSIONS: In PPTD, despite the presence of circulating bioactive TPOAbs, the extent of complement activation is inadequate to cause detectable increases in peripheral blood TCC, suggesting that the complement system may not play a major role in PPTD pathogenesis.

Age-related changes in bone density among healthy Greek males.

Osteoporosis in men is increasingly recognized as a problem in clinical medicine, but it has received much less attention than its counterpart in women. It is termed idiopathic if no known cause of bone disease can be identified clinically or in the laboratory. The true incidence of idiopathic osteoporosis (IO) in males is difficult to estimate because population characteristics and referral patterns differ so widely. The aim of this study was to investigate the incidence of IO in healthy Greek male volunteers by measuring bone mineral density (BMD) at four skeletal sites and examining the relations among age, BMI, and bone status. This type of information has not yet been published. We considered osteoporosis to be present when the BMD was less than or equal to -2.5 SD from the average value for healthy young men. Three hundred and sixty-three normal male volunteers were investigated. The mean age was 51.3+/-8.7 yr, and BMI was 27.5+/-3.7 kg/m2. In all subjects BMD at four skeletal sites - lumbar spine (LS), femoral neck (FN), Ward's triangle (WT), and finally trochanter (T) - was measured using dual-energy X-ray absorptiometry (DEXA). T-score, Z-score and g/cm2 values were estimated. Forty-four subjects (11%) had BMD< or =-2.5 SD (T-score). The mean age and BMI for the men with decreased BMD was 54.8+/-6.4 yr and 26.3+/-3.3 kg/m2, whereas mean age and BMI for those with normal BMD was 51.0+/-8.9 yr and 27.6+/-3.6 kg/m2, respectively. These differences were statistically significant (p<0.001 and p<0.05, respectively). A positive correlation was found between BMI and bone density (g/cm2) at three skeletal sites: LS (r=0.235, p<0.001), WT (r=0.126, p<0.001) and FN (r=0.260, p<0.001). A positive correlation was also found between BMI and T-score at all skeletal sites studied: LS (r=0.276, p<0.001), WT (r=0.133, p<0.05), FN (r=0.233, p<0.001), and T (r=0.305, p<0.001). Finally, a positive correlation was also found between BMI and Z-score: LS (r=0.256, p<0.001), WT (r=0.117, p<0.005), FN (r=0.240, p<0.001), and T (r=0.187, p<0.001). A negative correlation was found between age and bone density (g/cm2) at FN (r=-0.157, p<0.01) and WT (r=-0.183, p<0.001). The same was true between age and T-score at FN only (r=0.137, p<0.05). Furthermore, a similar correlation was found between age and Z-score at LS (r=0.174, p<0.001). When ANOVA one-way analysis was used, a significant difference was found between the different age groups and BMD (g/cm2) at FN, T, and WT (p<0.001 for all sites). For T-score, a significant difference between age groups was found only at FN (p<0.005). Finally, a significant difference in Z-score was found at FN (p<0.001) and LS (p<0.005). When multiple regression analysis was applied, it was found that BMD (g/cm2) at two sites, FN and WT, independently correlated with age and BMI (FN: p<0.001 for both, WT: p<0.01 and p<0.05, respectively). Finally, we found an accelerated trend toward decreased BMD (g/cm2), when the odds ratio was applied. In conclusion, this study demonstrated that 11% of otherwise healthy Greek men had BMD less than or equal to -2.5 SD. A strong association was found between BMD (g/cm2) and age at three skeletal sites when ANOVA one-way analysis was applied. Moreover, BMD was positively correlated with BMI and negatively correlated with age. Currently available data are sparse and much more research is needed to increase our understanding concerning the etiology of this condition as well as illuminating the relationship between bone density and fracture.

Serum levels of tumor necrosis factor-alpha, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and soluble interleukin-1 receptor antagonist in patients with thyroid eye disease undergoing treatment with somatostatin analogues.

The aim of this prospective, randomized study was to investigate the serum levels of tumor necrosis factor-alpha (TNF-alpha), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble interleukin-1 receptor antagonist (sIL-1RA) in patients with thyroid eye disease (TED) before and 1 and 3 months after treatment with somatostatin analogues (SM-a). Thirty patients, all with signs and symptoms of TED, were studied. Twenty-two patients (13 females) had active eye disease with a clinical activity score (CAS) > or = 4 (patients with active disease [PA]) and 8 patients (5 females) had inactive TED with CAS < or = 3 (patients with inactive disease [PI]). All PA patients had a positive orbital octreoscan, whereas PI patients had a negative one. Fifteen patients from the PA group were selected randomly and received SM-a (PA-S subgroup), while the remaining 7 patients were used as control subgroup (PA-C), received neither therapy, nor placebo. From the 15 patients who received SM-a (PA-S), 6 received octreotide (OCT) and 9 lanreotide (LRT). TED was reevaluated using the CAS 1 and 3 months after the initiation of SM-a treatment. Ten healthy individuals (6 females) were used as controls (group C). We found an increase in the basal levels of TNF-alpha (14.2 +/- 7.1 pg/mL), sICAM-1 (809.1 +/- 167.0 ng/mL), and sIL-1RA (542.1 +/- 259.0 pg/mL) in PA patients as a total group compared with the PI (1.6 +/- 1.9, 676.8 +/- 73.4, 267.6 +/- 152.8, respectively) group and C (1.9 +/- 1.4, 598.0 +/- 126.2, 258.6 +/- 155.1, respectively). The basal levels of TNF-alpha (13.3 +/- 8.3 pg/mL) and sIL-1RA (533.7 +/- 308.9 pg/mL) in PA-S as well as in PA-C (16.0 +/- 2.9, 560.2 +/- 107.3, respectively) subgroups were also increased compared with PI patients and C (1.9 +/- 1.4 and 258.6 +/- 155.1, respectively). The same was true for sICAM-1 when baseline levels compared with C (817.1 +/- 187.3 and 791.9 +/- 123.5, respectively vs. 598.0 +/- 126.2 ng/mL). After SM-a, serum levels of sICAM-1 and sVCAM-1 were decreased significantly 1 (781.2 +/- 205.9, 1,193.5 +/- 511.8 ng/mL) and 3 months (786.8 +/- 199.6, 1,122.1 +/- 225.3 ng/mL) after the initiation of treatment. In conclusion, serum levels of TNF-a, sICAM-1, and sIL-1RA were elevated in patients with active TED compared to controls. Furthermore, sICAM-1 and sVICAM-1 levels declined during the treatment with SM-a in patients with active TED.