Sex steroid replacement in post-menopausal women: effects on thyroid hormone status

We have measured serum thyroxine (T4), triidothyronine (T3), thyroid-stimulating hormone (TSH) free thyroxine (FT4) and thyroxine-binding globulin (TBG) levels in a total of 5 post-menopausal women who were receiving oestrogen alone (Premarin, n = 19), progestogen alone (Primolut-N, n = 12), a combination of oestrogen and progestogen (Prempak C, n = 14) or no treatment (control group, n = 12). No differences were observed between the Premarin and Prempak C groups; both exhibited elevated T4 and TBG levels, although free thyroxin (FT4) and T4/TBG concentrations were normal relative to those in the control group. The Primolut-N subjects showed subnormal T3 and FT4 levels relative to the controls. It was concluded that it is not possible to make general statements regarding the effects of sex steroids on FT4 levels.     

Impaired thyrotrophin secretion following the administration of thyrotrophin-releasing hormone in type II diabetes mellitus

Serum thyrotrophin has been measured before and after the intravenous administration of 200 micrograms of thyrotrophin-releasing hormone in 91 white subjects (33 stable diabetic patients and 58 healthy controls), none of whom had any clinical evidence of thyroid or pituitary dysfunction. Seven of the diabetic subjects failed to achieve a rise of serum thyrotrophin of greater than 2 mU/l above basal concentrations, as compared with only one of the control subjects (P = 0.006). The difference in response between diabetics and controls was confined to patients with Type II (non-insulin-dependent) diabetes: thus 5 of 13 Type II patients and 2 of 20 Type I (insulin-dependent) patients failed to show a normal response to thyrotrophin releasing hormone injection. No significant effect of glycaemic control on thyrotrophin responses was noted. These results suggest that Type II diabetes mellitus may be a cause of impaired thyrotrophin secretion in patients with no clinical evidence of pituitary disease. The mechanism for this impaired pituitary hormone release remains to be clarified.     

Organon OD 14 (tibolone) and menopausal dynamic hormone profiles

Hormonal profiles were studied in 15 post-menopausal women, 7 of whom had been treated with Organon OD 14 (Tibolone) and 8 with placebo tablets for 3 yr. In the Tibolone-treated group, the sex hormone binding globulin (SHBG) levels were significantly lower, while the estimated free testosterone levels, the testosterone/SHBG ratio and the thyroid-stimulating hormone (TSH) response to thyrotrophin-releasing hormone (TRH) were significantly higher than in the placebo group. Prolactin and triiodothyronine (T3) concentrations were lower in the actively treated group, although the differences were not statistically significant. No significant differences were observed with respect to thyroxine (T4), TSH, basal cortisol or cortisol response to synacthen.     

Complications of automatic implantable cardioverter defibrillators: radiographic, CT, and echocardiographic evaluation

Automatic implantable cardioverter defibrillators (AICDs) were studied in three groups: (a) Serial radiographs were reviewed in 51 clinic patients. Twenty of 96 (21%) AICD patches distorted with time. (b) Thirty-six postoperative computed tomographic (CT) scans of asymptomatic patients revealed that pericardial fluid collections were frequent during the month after surgery but rare beyond that. Echocardiography was insensitive for these collections. CT also demonstrated dense fibrosis around some distorted patches, months after surgery. (c) Five other patients with pericardial infection had distorted patches, and the four studied with CT had fluid beneath their patches. (d) A case of constrictive pericarditis had distorted patches but was not diagnosed with CT. The authors conclude that distorted patches may indicate postoperative complications and that CT is the imaging modality of choice.     

A comparison of the effects of alfacalcidol treatment and vitamin D2 supplementation on calcium absorption in elderly women with vertebral fractures

Although vitamin D supplementation in the frail elderly improves calcium absorption, suppresses parathyroid hormone, decreases bone loss and reduces the risk of fractures, such treatment may be ineffective in patients with vertebral osteoporosis, because of impaired vitamin D metabolism or resistance to the action of vitamin D metabolites on the bowel. We have therefore performed a randomized, single masked study comparing the effects of alfacalcidol treatment (0.25 µg twice daily) and vitamin D₂ supplementation (500-1000 units daily) on calcium absorption and bone turnover in 46 elderly women (median age 69 years, range 64–79 years) with radiological evidence of vertebral fractures. Serum 25-hydroxyvitamin D increased significantly after 3 and 6 months of treatment with vitamin D₂ (p<0.001), but was unchanged in the group receiving alfacalcidol. Serum 1,25-dihydroxyvitamin D did not change significantly in either group over the study period. Fractional⁴⁵Ca absorption increased after 3 months of treatment with alfacalcidol (p<0.05), but was unchanged with vitamin D₂. There was also a reduction in plasma intact parathyroid hormone and serum alkaline phosphatase after 6 months of treatment with alfacalcidol (p<0.05) which was not seen in the group receiving vitamin D₂. Our study shows that vitamin D₂ supplementation is ineffective in stimulating calcium absorption in elderly women with vertebral osteoporosis. By increasing calcium absorption in such patients, alfacalcidol may prove more effective than vitamin D in the management of vertebral osteoporosis.     

Effect of long term hormone replacement on plasma prolactin concentrations in women after oophorectomy

Plasma prolactin concentrations were studied in 88 oophorectomised women who had been receiving mestranol or placebo for three to 11 years. Thirty one of them were also studied under basal conditions and by tests with thyrotrophin releasing hormone. Under basal conditions the mean prolactin concentration was higher in the oestrogen treated group but under non-rested, clinic conditions the difference was lost because of a rise in prolactin value in the placebo group only. Hence the groups showed a different prolactin response to the mild stress of clinic attendance but the same proportionate responsiveness to thyrotrophin releasing hormone. The data suggest that long term hormone replacement has no significant effect on circulating prolactin concentrations under non-rested, everyday conditions and that the prolactin stimulating effects of minor stress and oestrogen may share a similar mechanism.     

Alteration of the circadian rhythm of intact parathyroid hormone following a 96-hour fast

OBJECTIVE PTH(1-84) secretion in normal male subjects follows a circadian rhythm. The control of this rhythm is multifactorial with both neuroendocrine and chemical influences. The aim of this study was to assess the effect of a 96-hour fast on the circadian rhythm of PTH(1 -84), serum calcium, phosphate and nephrogenous cAMP (NcAMP), an index of PTH(1-84) bioactivity. DESIGN Blood samples for estimation of all analytes were obtained over a 24-hour period at 30-minute intervals. Urine samples were obtained 4 hourly during the daytime and overnight. Each subject was studied on two occasions after being randomized to either (a) normal hospital diet or (b) a 96-hour fast with water freely available. SUBJECTS Six healthy adult males aged between 28 and 40 years, mean 32 years. MEASUREMENTS PTH(1-84) was measured by an in-house immunoradiometric assay. Serum calcium, phosphate, albumin, creatinine and urinary creatinine were measured by standard automated techniques. Calcium was adjusted for albumin. Plasma cAMP was estimated by a commercial method and urine cAMP by in-house radioimmunoassay and NcAMP obtained by calculation. Rhythm parameters were analysed by cosinor techniques. RESULTS There were alterations in the circadian rhythms of serum phosphate, PTH(1–84) and NcAMP following a 96-hour fast. Fasting abolished the nocturnal rise in phosphate, PTH(1-84) and NcAMP but had little effect on the pattern of adjusted calcium over a 24-hour period. The mean concentrations of serum phosphate, adjusted calcium and NcAMP decreased significantly following the fast and mean PTH(1-84) increased during day time. CONCLUSIONS Fasting for 96 hours significantly alters the circadian rhythm of PTH(1-84) secretion by lowering the mean calcium concentration and attenuating the circadian rhythm of serum phosphate.     

Low calcium dialysate and high-dose oral calcitriol in the treatment of secondary hyperparathyroidism in haemodialysis patients

We treated nineteen haemodialysis patients with secondary hyperparathyroidism with increasing oral doses of 1,25 dihydroxycholecalciferol (calcitriol) over a 12-week period and used low calcium dialysate (1.0 mmol/l) to prevent hypercalcaemia. Nine patients received daily calcitriol and ten received calcitriol thrice weekly, and at the end of the study the mean doses were 2.0 micrograms daily and 2.6 micrograms thrice weekly respectively. The regimen was well tolerated with nine episodes of mild hypercalcaemia, none of which were symptomatic. Mean PTH and alkaline phosphatase concentrations decreased from 62.0 pmol/l (15-125) to 22.0 pmol/l(1-70) (P less than 0.01), and 144 IU/l (48-461) to 123 IU/l (61-346) (P less than 0.05) respectively. Mean serum calcium increased from 2.33 mmol/l (2.05-2.55) to 2.52 mmol/l (2.26-2.67) (P less than 0.01). There were no significant changes in serum phosphate, magnesium, or aluminium concentrations and there were no significant differences in outcome between patients receiving daily therapy compared to those receiving it thrice weekly. A combination of high-dose oral calcitriol and low calcium dialysate can reverse secondary hyperparathyroidism without causing hypercalcaemia and these results suggest a benefit over conventional low-dose calcitriol.     

丹酚酸A对小鼠脑缺血再灌注致学习记忆功能障碍的改善作用及作用机制

本实验采用脑缺血再灌注损伤造成小鼠学习记忆功能障碍模型。通过跳台和避暗实验法研究了丹酚酸对记忆获得功能障碍的改善作用。结果表明丹酚酸Ａ３，１０ｍｇ·ｋｇ－１ｉｖ可以减轻脑缺血再灌注导致的小鼠学习记忆功能障碍状态。并使小鼠脑缺血再灌注后脑组织中脂质过氧化产物ＭＤＡ含量明显降低。体外实验表明丹酚酸Ａ１０－８～１０－７’ｍｏｌ·Ｌ－１可以抑制大鼠脑组织匀浆脂质过氧化反应和羟自由基（·ＯＨ）的生成，表现出较强的抗氧化作用，提示丹酚酸改善脑缺血再灌注损伤的主要机制可能与其抗氧化作用有关。