TRH INJECTION DURING LABOUR: EFFECT ON MATERNAL AND FETAL PROLACTIN SECRETION

The effect of TRH injection on PRL levels in maternal serum and in serum of umbilical vein (UV) and artery (UA) was investigated in forty-six women. Twenty-two of them, with normal singleton term pregnancy, were given i.v. either saline solution (nine women, control group 1) or 200 μg of synthetic TRH (thirteen women, group 2) 30–45 min before normal delivery. Group 1 PRL values (mean ± SE) (ng/ml) in UV (428 ± 41) and UA serum (434 ± 45) were significantly higher than in maternal serum either before (285 ± 39) or after saline injection (331 ± 14) (P < 0·05). In group 2, TRH induced a marked increase in maternal serum PRL (544 ± 33 v. 285 ± 39, P < 0·001) (difference from corresponding maternal serum PRL of group 1 significant, P < 0·001) but not in UV (409 ± 41) and UA (406 ± 48) PRL values (difference from the corresponding PRL values in UV and UA serum of group 1 non-significant, P > 0·1). Group 2 maternal serum PRL values after TRH were significantly higher than in UV and UA serum (P < 0·05). A significant positive correlation was found between UV and UA serum PRL values in both group 1 (r=0·858, P < 0·01) and group 2 (r=0·870, P < 0·001). Twelve of the remaining twentyfour women were given TRH either 10–20 min (four women), 60–75 min (four women), or 90–110 min (four women) before delivery. UA serum PRL values did not differ significantly from corresponding controls (twelve women). It is suggested, from these findings in women, that TRH injected into the mother in a single dose of 200 μg stimulates maternal but not fetal pituitary in late pregnancy during labour. This is possibly due to inability of TRH to cross the human placenta.     

INSULIN-LIKE GROWTH FACTOR AND ITS CARRIER PROTEIN IN HYPOPITUITARY AND HYPOTHYROID CHILDREN AND ADULTS

Utilizing radioligand assays for the somatomedin, insulin-like growth factor (IGF), and its carrier protein (CP), we have compared their serum levels in normal subjects with those in patients with hypopituitarism and hypothyroidism. The mean (±SEM) serum IGF concentration in children (n= 32, 2–13 yr, 929 ± 46 μU/ml) was virtually identical to that in adults (n= 20, 18–50 yr, 916·29 μU/ml), while CP levels in the former (1·8 ± 0·1 mg/ml) were significantly lower (P < 0·01) than in the latter (2·9 ± 0·1 mg/ml). Both serum IGF and CP were significantly decreased (P < 0·001) in hypopituitary children (n= 5, 6–8 yr, 377 ± 52 μU/ml and 0·9 ± 0·1 mg/ml respectively). Likewise, serum IGF and CP were significantly reduced (P < 0·05) in hypothyroid children (n= 10, 1–15 yr, 497 ± 24 μU/ml and 0·8 ± 0·1 mg/ml respectively) and adults (n= 12, 25–55 yr, 723 ± 40 μU/ml and 1·8 ± 0·2 mg/ml respectively). Growth hormone therapy (4 days) significantly increased (P < 0·05) serum IGF in hypopituitary children (336 ± 80 to 559 ± 59 μU/ml) but did not change the CP level (0·7 ± 0·2 to 0·7 ± 0·1 mg/ml). Thyroxine therapy (4–8 months) significantly increased (P < 0·05) both serum IGF and CP levels in hypothyroid children (497 ± 24 to 666 ± 38 μU/ml, and 0·8 ± 0·1 to 1·0 ± 0·1 mg/ml respectively) but had no effect in adults (723 ± 40 to 937 ± 132 μU/ml, and 1·8 ± 0·2 to 2·1 ± 0·2 mg/ml respectively). These studies indicate that growth retardation in children with hypopituitarism and hypothyroidism is associated with significant reductions in serum IGF and CP levels that are corrected, at least in part, by adequate hormone replacement therapy.     

Plasma visfatin concentrations increase in both hyper and hypothyroid subjects after normalization of thyroid function and are not related to insulin resistance, anthropometric or inflammatory parameters

Objective The objective of this study was to evaluate plasma visfatin levels in thyroid dysfunction and its relationship with inflammatory, anthropometric and insulin resistance parameters. Design and patients Twenty‐four hyperthyroid and 27 hypothyroid patients were studied before and after treatment. Forty‐five euthyroid subjects were used as control group. Measurements Fasting plasma visfatin, IL‐6, C reactive protein, adiponectin, thyroid hormones, waist‐to‐hip ratio, BMI, percentage of body fat and homeostasis model insulin resistance index (HOMA‐IR) were measured. Results Hyperthyroid patients showed increased insulin resistance, IL‐6 and visfatin levels compared with controls (3·21 ± 3·0 vs. 1·67 ± 0·75, P = 0·022; 3·35 ± 0·41 vs. 2·10 ± 0·25 pg/ml, P = 0·016; and 37·4 ± 5·81 vs. 23·79 ± 4·2 ng/ml, P = 0·061 respectively). After normalization of thyroid function, IL‐6 levels and HOMA‐IR decreased (2·35 ± 0·37 vs. 2·10 ± 0·25 pg/ml, P = 0·045 and 3·21 ± 0·60 vs. 2·28 ± 0·38, P = 0·032 respectively), while body weight, adiposity and visfatin levels increased (26·1 ± 1·2 vs. 26·7 ± 1·2 kg/m², P = 0·049; 30·9 ± 1·6 vs. 32·2 ± 1·6%, P = 0·007; and 37·4 ± 5·81 vs. 63·13 ± 8·72 ng/ml, P = 0·047 respectively). C reactive protein and adiponectin levels were similar to those of the control group. Hypothyroid patients showed high visfatin levels (40·59 ± 3·07 vs. 29·34 ± 4·9 ng/ml, P = 0·049) that increased after treatment (81·4 ± 9·2 ng/ml, P = 0·001) without changes in anthropometric or insulin resistance parameters. C reactive protein, IL‐6 and adiponectin levels were similar to those of the control group. No correlations between visfatin and any analysed parameter were found in either hyper‐ or hypothyroidism. Conclusion Visfatin exhibits a marked increase after normalization of thyroid function in both hyper and hypothyroid patients. We suggest that visfatin may play a role in the hormone stabilization process independent of anthropometric, inflammatory or insulin resistance variables.     

Activated protein C levels in Behçet's disease and risk of venous thrombosis

Behçet's disease is a multi‐systemic inflammatory disorder of unknown cause. Most abnormalities have been associated with endothelial injury caused by vasculitis. Thrombosis occurs in about 25% of patients, although the mechanism is unknown. The objective of this study was to evaluate the protein C activation system in Behçet's disease and its correlation with venous thromboembolism (VTE). Thirty‐nine patients (12 with VTE) and 78 age‐ and sex‐matched controls were included in the study, and levels of protein C, protein S, activated protein C (APC), protein C inhibitor (PCI), soluble thrombomodulin (TM), antithrombin (AT), α₁‐antitrypsin, fibrinogen, factor VIII, von Willebrand factor (VWF) and C‐reactive protein (CRP) were measured. APC and TM levels were significantly lower in patients than in controls, whereas protein S, AT, α₁‐antitrypsin, fibrinogen, factor VIII, VWF and CRP levels were significantly higher in patients than in controls. APC, PCI and TM levels were lower in patients with VTE (0·65 ± 0·19 ng/ml, 86% ± 22% and 15·5 ± 7·1 ng/ml respectively) than in those without VTE (0·78 ± 0·17 ng/ml, 100% ± 15% and 22·1 ± 15·3 ng/ml) (P < 0·05). In patients, APC levels below 0·75 ng/ml (10th percentile of the control group) increased the risk of VTE about fivefold (odds ratio = 5·1; 95% confidence interval = 1·1–23·4). These results show that reduced APC levels are associated with the high incidence of VTE in Behçet's disease.     

Left ventricular dysfunction in Klinefelter syndrome is associated to insulin resistance, abdominal adiposity and hypogonadism

Objective Epidemiological data suggest there is an increased risk of dying from heart disease among patients with Klinefelter syndrome (KS). Due to high prevalence of hypogonadism and metabolic syndrome, we speculated that patients with KS may have subclinical changes in the left ventricular function. Therefore, the aim was to assess left ventricular long axis function by tissue Doppler echocardiography in patients with KS and relate these findings to the metabolic status and testosterone levels. Design Cross-sectional study. Out-patient clinic. Patients We investigated 25 unselected patients with KS, recruited from endocrine and fertility clinics. Twenty-five age-matched males served as controls. Measurements Left ventricular systolic long axis function (velocities and strain rate) assessed by tissue Doppler echocardiography related to free testosterone, fasting values of plasma glucose, insulin, homeostasis model assessment (HOMA)-index, cholesterol and triglycerides in addition to dual energy X-ray absorptiometry (DEXA) scan derived assessment of truncal body fat. Results The long axis function was significantly reduced in patients with KS (peak systolic velocities 4·4 ± 1·3 vs. 5·3 ± 1·0 cm/s, P < 0·01 and strain rate –1·3 ± 0·3 vs.–1·6 ± 0·3 s⁻¹, P < 0·01). However, the ventricular dysfunction was mainly attributed KS patients with metabolic syndrome. The peak systolic velocities were significantly correlated to truncal body fat (r = –0·72, P < 0·01) and free testosterone (r = 0·63, P < 0·01), but uncorrelated to plasma glucose, insulin and HOMA-index. Conclusion Systolic long axis function is decreased in patients with KS and metabolic syndrome. The decrease in myocardial systolic function was significantly related to truncal body fat and hypogonadism, but not correlated to insulin sensitivity.     

Biological determinants of bleeding in patients with heterozygous factor XI deficiency

Bleeding risk is not predictable in patients with factor XI (FXI; F11) deficiency. In this prospective study, our objectives were to determine the biological determinants for bleeding risk in patients with heterozygous FXI deficiency. Patients were classified as either bleeding patients or non‐bleeding patients by calculating the bleeding score (BS) described for von Willebrand disease. Primary haemostasis, thrombin generation, thromboelastometry, procoagulant proteins, inhibitors, fibrinolysis, and F11 gene mutations were compared between bleeding and non‐bleeding patients. Thirty‐nine patients were included. BS significantly correlated with clinical assessment (P = 0·001), and a score over 3 discriminated between bleeding (n = 15) and non‐bleeding (n = 24) patients (P = 0·034). Despite normal values, von Willebrand factor (VWF) and thrombomodulin (TM) plasma levels were significantly lower in bleeding patients than non‐bleeding patients [ristocetin cofactor activity (VWF:RCo) = 80·6 ± 29·7 iu/dl and 101·8 ± 29·5 iu/dl respectively, P = 0·043; and VWF antigen (VWF:Ag) = 84·0 ± 28·0 iu/dl and 106·3 ± 36·1 iu/dl respectively, P = 0·035; and TM = 17·7 ± 11·7 ng/ml and 23·6 ± 9·7 ng/ml respectively, P = 0·043]. When considering BS as a continuous variable, only VWF:RCo remained significant (P = 0·042), which accounted for 11% of the variability in BS.     

The pharmacodynamic equivalence of levothyroxine and liothyronine: a randomized,double blind,cross‐over study in thyroidectomized patients

Context The substitution of liothyronine (L‐T3) for levothyroxine (L‐T4) is commonly employed during thyroid hormone (TH) withdrawal in preparation for diagnostic and therapeutic interventions on thyroid cancer patients. Presently, only limited data are available on the L‐T3 for L‐T4 therapeutic substitution. Objective To characterize the pharmcodynamic equivalence of L‐T3 and L‐T4. Design Randomized, double‐blind, cross‐over intervention study. Setting NIH clinical center. Patients Ten thyroidectomized patients. Interventions Study participants were treated with L‐T3 or L‐T4 with a target TSH ≥ 0·5 ≤ 1·5 mU/l for at least 30 days before undergoing inpatient testing. Following testing, subjects crossed‐over according to the same scheme. Main outcome measures Area under the serum concentration–time curve of TSH from 0 to 60 min (AUC_0–60) and peak TSH serum concentration (C_max) following thyrotropin‐releasing hormone (TRH) stimulation test, total L‐T4 and L‐T3 dose (mcg/kg), and L‐T4/L‐T3 ratio. Results No difference was observed for time 0 TSH values between L‐T3 and L‐T4 replacement phases (1·48 ± 0·77 vs. 1·21 ± 0·62 mU/l, P = 0·293) at average daily doses of 40·3 ± 11·3 mcg L‐T3 and 115·2 ± 38·5 mcg L‐T4, L‐T3: L‐T4 ratio 0·36 ± 0·06. TRH stimulation test resulted in similar L‐T3 vs. L‐T4 TSH responses with AUC_0–60 of 326·1 (95% CI 232·6–457·1) and 247·1 (95% CI 153·8–397·1) mU* min/l (P = 0·285); and C_max of 6·83 (95% CI 4·88–9·55) and 5·23 (95% CI 3·31–8·3) mU/l (P = 0·383). Conclusions This is the first study addressing the equivalency between L‐T3 and L‐T4 therapy measured by baseline and TRH‐stimulated TSH. The therapeutic substitution of L‐T3 for L‐T4 was achieved at approximately 1:3 ratio.     

Enhanced proatherogenic inflammation after recombinant human TSH administration in patients monitored for thyroid cancer remnant

Objective To evaluate the effect of recombinant human TSH (rhTSH) on biomarkers of vascular endothelial cell and platelet activation in patients monitored for thyroid carcinoma remnant. Methods Circulating levels of soluble(s) intercellular adhesion molecule (sICAM)‐1 and sE‐selectin, as indices of vascular endothelial cell activation, of sP‐selectin and sCD40 ligand (sCD40L), as indices of platelet activation, and of 8‐iso‐prostaglandin F_2α (8‐iso‐PGF_2α), as an index of lipid peroxidation, were evaluated in 20 patients (16 females, 48·0 ± 13·6 years) at baseline and after intramuscular rhTSH injection (0·9 mg/day on two consecutive days). Results At baseline, serum TSH values were below normal whereas free T3 and free T4 were within the normal range. After rhTSH injection, serum TSH increased significantly but free T3 and free T4 remained unchanged. Concomitantly, plasma sICAM‐1 concentrations increased significantly (from 155·9 ± 39·1 to 183·6 ± 38·1 ng/ml, P < 0·03), as did those of sE‐selectin (from 74·8 ± 15·4 to 91·4 ± 12·2 ng/ml, P < 0·0006), sP‐selectin (from 56·4 ± 13·7 to 72·2 ± 14·9 ng/ml, P < 0·002), sCD40L (from 2·1 ± 0·9 to 2·8 ± 1·1 ng/ml, P < 0·03) and total 8‐iso‐PGF_2α(from 238·5 ± 47·0 to 307·8 ± 41·2 pg/l, P < 0·0001). Changes in circulating levels of sCD40L were directly correlated with changes in levels of plasma total 8‐iso‐PGF_2α (r = 0·523, P < 0·02) and sP‐selectin (r = 0·480, P < 0·03). Conclusions Supraphysiological concentrations of rhTSH might exert proatherogenic effects by promoting activation of vascular endothelial cells and platelets probably through enhanced oxidative stress.     

Nature of suppressed TSH secretion during undernutrition: Effect of fasting and refeeding on TSH responses to prolonged TRH infusions

TSH responses to 4-hr continuous TRH infusions of approximately 0.8 μg/min were assessed during feeding (1500 Kcal), fasting, and refeeding (1500 Kcal) intervals in 9 euthyroid obese subjects. The total area under the TSH response curve was 1854 ± 322 μU/ml · 4-hr during feeding, decreased to 1359 ± 199 μU/ml · 4-hr (p < 0.01) on the 10th day of fasting, and remained low, being 1405 ± 185 μU/ml · 4-hr, despite refeeding a 1500 Kcal diet (40% carbohydrate, 40% fat, 20% protein) for 5 days. Baseline serum T3 concentrations were 167 ± 11 ng/dl during feeding, 86 ± 8 ng/dl during fasting, and 119 ± 12 ng/dl during refeeding. The observed decreases in TSH release appeared to correlate with decreased biologic action on the thyroid gland since the net rise in T3 during the infusion was less in fasting and refeeding than in the control (fed) period. Basal serum rT3 levels were 42 ± 5 ng/dl during feeding, rose as expected to 56 ± 5 ng/dl during fasting (p < 0.005), and were completely restored to normal during refeeding (36 ± 5 ng/dl). These data suggest that: (1) TSH responsiveness to prolonged TRH infusion is diminished during fasting and does not return to control (fed) values despite 5 days of refeeding a 1500 Kcal diet; (2) net T3 increases observed during the TRH infusion are greater in the fed period than in the fasting or refeeding periods; and (3) 5 days of refeeding a 1500 Kcal diet (40% carbohydrate, 40% fat, 20% protein) did not return the T3 to its original fed value whereas rT3 was completely restored to control values. Lastly, since the TSH response was lower both during the early and late phases of the infusion, the decrease in ΔTSH to a bolus of TRH during fasting appears to represent one manifestation of a more general suppression of TSH neogenesis associated with caloric deprivation.     

TRANSIENT THYROTOXICOSIS IN ENDEMIC GOITRE PATIENTS FOLLOWING EXPOSURE TO A NORMAL IODINE INTAKE

Twenty-three endemic goitrous subjects (goitre grade: III and IV) that were living in a chronic iodine-deficient area (iodine intake: less than 40 μg I/d) were submitted to clinical and laboratory evaluation within 3–8 weeks of arrival at the metropolitan area of São Paulo, where daily iodine intake is estimated to be 150–200 μg I/d. Eight patients developed a mild thyrotoxic state (T4 = 14.7 ± 2.3 μg/dl, T3 = 279 ± 55 ng/dl, no TSH response to TRH). Five additional subjects, although euthyroid, had a blunted TSH-response to TRH, and the remaining ten patients were euthyroid and had a normal TSH response to TRH. Thyrotoxicosis was associated with larger goitres (mean thyroid weight: 133 ± 46 g), with high thyroid uptake of RAI (mean 24 h ¹³¹ I uptake: 40 ± 15%) but not with increased urinary iodine excretion. Serum Tg levels were more elevated in the first two groups of patients (respectively, geometric means 68 and 72 ng/ml), than in the euthyroid, TRH-responsive group (52 ng/ml). Thyrotoxicosis resolved spontaneously after three to six months without the need for any specific medication. It was concluded that a relatively small and normal iodide intake due to regular consumption of iodized salt and industrialized foods may induce a transient form of thyrotoxicosis in endemic goitre patients arriving into urban areas.     

THE EFFECT OF OESTROGENS ON HUMAN CALCITONIN SECRETION AFTER CALCIUM INFUSION IN ELDERLY FEMALE SUBJECTS

The effect of oestrogen administration (4–6 weeks) on the response of human calcitonin (hCT) secretion to 5 min calcium infusions was studied in ten elderly women. There was no significant difference in mean basal plasma hCT levels before and after oestrogen administration. However, the mean increment in plasma hCT in response to calcium infusion (ΔhCT) increased significantly (P < 0·001) from 21·9±6·6 (mean ±SE) before treatment, to 79·6±15·5 ng/l after oestrogen administration. Mean serum calcium levels decreased significantly (P < 0·001) from 2·42 ±0·06 before to 2·19·0±07 mmol/l after oestrogen treatment. Mean plasma immunoreactive PTH (iPTH) levels increased significantly (P < 0·05) from 521·41 before to 696·96 ng/l after oestrogen treatment. To exclude out the possibility that the decreased serum calcium level itself might have influenced ΔhCT, 1α-hydroxycholecalciferol (1α-OH-D₃) was administered with oestrogens. While this resulted in a slight increase in serum calcium level, there was no significant difference in ΔhCT in response to calcium infusion following oestrogen treatment alone, and after combination therapy of oestrogen and 1 α-OH-D₃. The primary action of administered oestrogen may be in stimulating hCT secretion which results in a decrease in plasma calcium concentration and an increase in plasma iPTH level.     

SUPPRESSION OF RESIDUAL OESTROGEN PRODUCTION WITH AMINOGLUTETHIMIDE IN WOMEN FOLLOWING SURGICAL HYPOPHYSECTOMY OR ADRENALECTOMY

In postmenopausal women with breast carcinoma, plasma and urinary oestrogens remain detectable following surgical adrenalectomy or hypophysectomy. These residual oestrogens could result from absorption of exogenous steroids, from endogenous production, or from a combination of these two sources. To determine whether endogenous production contributes to this oestrogen pool, we administered a potent steroidogenesis inhibitor, aminoglutethimide (AG), to women with breast carcinoma following hypophysectomy or adrenalectomy. Plasma and urinary oestrogens were measured with radioimmunoassays developed to provide appropriate sensitivity. In five women treated after initial hypophysectomy (hypox), plasma oestrone fell from 66·28 pg/ml (hypox) to 9·1 ± 2·4 pg/ml (hypox and AG) and oestradiol decreased from 8·3 ± 1·8 pg/ml to 2·5 ± 0·69 pg/ml. Similar decrements in urine oestrone (U-E₁) and ostradiol (U-E₂) were observed (U-E₁ hypox: 2·25 ± 0·71 μg/24 h and 0·071·0±015 μg/24 h hypox and AG; U-E₂ 0·47 ± 0·12 μg/24 h hypox to 0·124 ± 0·015 hypox and AG, P<0·05 for all). Similar significant reductions in plasma oestrone and oestradiol were observed in four women treated with aminoglutethimide following surgical adrenalectomy. While the levels of urinary oestrogens also fell in these patients, the differences were not statistically significant. In response to the decrements in oestrogen levels induced by AG, 2/5 women in the post-hypophysectomy group and 2/4 in the post-adrenalectomy group experienced partial objective tumour regression. These observations indicated that the residual oestrogens produced after surgical adrenalectomy or hypophysectomy, even though made in small quantities, were nonetheless biologically active. We conclude that endogenous production of oestrogens in extragonadal and extra-adrenal sites occurs after major surgical endocrine     

A COMPARISON OF NEPHROGENOUS CYCLIC AMP, TOTAL URINARY CYCLIC AMP AND THE RENAL TUBULAR MAXIMUM REABSORPTIVE CAPACITY FOR PHOSPHATE IN THE DIAGNOSIS OF PRIMARY HYPERPARATHYROIDISM

A determination was made of total urinary adenosine 3′-5′cyclic monophosphate (UcAMP), nephrogenous cyclic AMP (NcAMP) excretion and also of the renal tubular maximum reabsorptive capacity for phosphate T_mPO₄/GFR (all expressed as a function of the glomerular filtrate) in fourteen patients with primary hypercalcaemic hyperparathyroidism and twelve control normal subjects. The hyperparathyroid patients gave a mean excretion of UcAMP (7·0 ± 45·68 nmol/100 ml GF; mean ± SEM), NcAMP (6·19 ± 0·64 nmol/100 ml GF) which were significantly greater (P < 0·001) than those of normal controls, (2′45 ± 0·15nmol/100 ml GF and 1·25 ± 0·12nmol/100 ml GF) respectively. The difference between the patients and controls for the maximum renal tubular reabsorptive capacity for phosphate (T_mPO₄/GFR) (patients 0·55 ± 0·04, controls 1·05 ± 0·05 mmol/l GFR) was also highly significant (P<0·001). Statistical evaluation of the results obtained from the patients with primary hyperparathyroidism revealed that there was a positive correlation between the level of plasma calcium and immunoreactive parathyroid hormone (PTH) (r=+0·46), NcAMP(r=+0·337), UcAMP (r=+0·36), and an inverse correlation with the T_mPO₄/GFR (r=?0·62). There was also a positive correlation between plasma immunoreactive PTH and NcAMP(r=+0·31), and UcAMP(r=+0·35), and an inverse correlation with the T_mPO₄/GFR (r=?0–39). Successful removal of a single parathyroid adenoma in six patients was associated with a highly significant fall in the excretion of UcAMP, NcAMP, and a rise in the T_mPO₄/GFR (P<0·005). The combination of a low T_mPO₄/GFR and a high excretion of UcAMP or NcAMP in the presence of hypercalcaemia is highly suggestive of primary hyperparathyroidism in the absence of clinical evidence of malignant disease.     

Increased serum visfatin in patients with metabolic syndrome and carotid atherosclerosis

Objective Visfatin is a newly identified adipocytokine and recent studies indicated that visfatin may have potential proinflammatory effect. However, its pathophysiological role in the metabolic syndrome (MetS) is not fully understood. In this study we investigated whether serum visfatin levels is altered in patients with the MetS, and compared the levels of visfatin between patients with and without carotid plaques. Design and method A total of 139 patients with MetS and 105 controls were included. The patients were further divided into two groups: 40 with carotid plaques and 99 without carotid plaques. Serum visfatin was measured by using enzyme immunoassay method and carotid intimal‐media thickness (IMT) was measured by ultrasound in all subjects. Results Serum visfatin was elevated in both MetS patients with and without carotid plaques compared to controls (log visfatin: 1·14 ± 0·14 vs. 0·99 ± 0·17 ng/ml vs. 0·93 ± 0·23 ng/ml, P < 0·001 and P < 0·05 vs. control group, respectively), and in patients with carotid plaques more than in patients without carotid plaques (P < 0·001). Multiple stepwise regression analysis revealed that only LDL‐cholesterol correlated with visfatin, and visfatin independently correlated with max IMT in the patients with MetS. A log visfatin > 1·08 ng/ml had 70% sensitivity and 67% specificity for detecting patients with carotid plaques. Conclusions/interpretation Our results showed that serum visfatin was increased in patients with MetS, especially in those with carotid plaques. Visfatin may be an inflammatory marker of MetS.     

Elevated Basal and Abnormal Thyrotropin-Releasing Hormone-Induced Thyroid-Stimulating Hormone Secretion in Chronic Alcoholic Men with Liver Disease

Basal levels of serum thyroid-stimulating hormone (TSH). T₃, T₄, free T₃ and free T₄ were measured in 40 chronic alcoholic men and in 31 normal volunteers. Their serum TSH responses to provocative thyrotropin-releasing hormone (TRH) stimulation were then examined serially: in chronic alcoholics, every 5 days for a total of 3 studies; in 25 of the normal volunteers, before and 72 hr after daily ingestion of ethanol (2 cc/kg/day). Basal serum TSH levels were increased in the alcoholic men (3.5 ± 0.2 μU/ml) (mean ± SEM) compared to those of the normal controls (1.7 ± 0.1) (p < 0.01). Both basal serum T₃ and T₄ levels (T₃, 0.89 ± 0.10 ng/ml; T₄, 7.0 ± 0.4 μg/dl) were reduced in the alcoholic men when compared to those of the normal controls (T₃,1.20 ± 0.03 ng/ml; T₄, 8.6 ± 0.3 μg/dl) (p < 0.01 and p < 0.05, respectively). Basal serum free T₃ levels were reduced in the alcoholic men (169 ± 22 pg/dl) compared to the normal controls (380 ± 18) (p < 0.01). In contrast, basal serum free T₄ levels were increased in the alcoholics (4.0 ± 0.2 ng/dl) compared to those of the normal controls (2.9 ± 0.1) (p < 0.01). In response to TRH, the serum TSH levels of the alcoholic men achieved a peak of 13.5 ± 0.9 μU/ml compared to 14.9 ± 0.9 for the normal controls (no significant difference). Despite better nutrition and alcohol abstinence associated with hospitalization for 10 days, no improvement in either the basal levels of TSH, T₃, and T₄ or the TSH responses to provocative TRH was observed in the alcoholic men studied. In normal volunteers, ethanol had no effect on the basal or TRH-stimulated levels of serum TSH and thyroid hormones.     

Coronary artery disease is associated with higher epicardial retinol-binding protein 4 (RBP4) and lower glucose transporter (GLUT) 4 levels in epicardial and subcutaneous adipose tissue

Objective Retinol‐binding protein 4 (RBP4), produced by adipocytes and hepatocytes, contributes to an unfavourable lipid profile and insulin resistance, which can contribute to the development of coronary artery disease (CAD). Recently, several studies have shown that epicardial adipose tissue (EAT) differs from subcutaneous adipose tissue (SAT) and plays a role on the physiopathology of CAD because of its proximity to the coronary arteries. We aimed to study the expression and secretion levels of RBP4 in both fat tissues and explore its possible association with CAD. Research Design and Methods Fifty‐eight patients undergoing heart surgery were included in the study. We analysed RBP4 mRNA expression by real‐time PCR, protein expression by Western blot and immunohistochemistry, and secretion of EAT and SAT explants from CAD and non‐CAD patients by Enzyme Immunoassay. Results Retinol‐binding protein 4 is expressed at similar levels in EAT and SAT, mainly from adipocytes. Protein levels were higher in EAT from CAD than non‐CAD patients (0·63 ± 0·09 arbitrary units (a.u).; n = 10) vs (0·41 ± 0·04 a.u.; n = 13, P = 0·039). In contrast, GLUT4 mRNA levels were lower in EAT from CAD than non‐CAD patients (6·55 ± 0·16 a.u.; n = 13) vs (7·21 ± 0·18 a.u.; n = 14, P = 0·012). We also found differential expression in SAT between samples from CAD and non‐CAD patients [(6·63 ± 0·16 a.u.; n = 14) vs (7·21 ± 0·14 a.u.; n = 14, P = 0·009)]. Besides, EAT releases higher RBP4 levels than SAT after 3, 6, 24 and 48 h of culture. These levels were independent of CAD but significantly higher in diabetic than nondiabetic patients. Conclusion Retinol‐binding protein 4 levels behave differently in EAT and SAT with respect to CAD. However, both adipose tissues have lower GLUT4 levels in patients with CAD. These findings suggest a differential regulation of RBP4 production in EAT and SAT that may be influenced by local factors.     

Postural stimulation test in patients with aldosterone producing adenomas

OBJECTIVE The purpose of this study was to evaluate the postural stimulation test before and after surgical treatment in patients with aldosterone-producing adenomas. DESIGN The retrospective study was made on patients with aldosterone producing adenomas. PATIENTS The postural stimulation test was analysed in 60 patients with surgically proven aldosterone producing adenoma and In 15 healthy volunteers. MEASUREMENTS The postural stimulation test was based on measurements of plasma aldosterone, cortisol and renin activity (PRA) at 0800 h and at noon after 4 hours ambulation. RESULTS The patients were divided into two groups according to the individual pattern of plasma aldosterone concentration following the postural test. Plasma aldosterone concentration decreased or did not change after 4 hours of standing in 42 patients (group 1,70% of total) and increased in 18 patients (group 2, 30% of total). Mean plasma aldosterone was significantly higher in group 1 than in group 2 (1325 ± 164 pmol/l (mean ± SE) and 538 ± 53 pmol/l, respectively). Mean plasma cortisol concentration after 4 hours of upright posture in both groups remained low (242 ± 35 vs 401 ± 63 nmol/l (group 1) and 317 ± 46 vs 367 ± 43 nmol/l (group 2). Mean PRA In both groups was suppressed after 4 hours of upright posture (0·2 ± 0·04 vs 0·2 ± 0·04 pmol/l/s and 0·3 ± 0·06 vs 0·1 ± 0·02 pmol/l/s, respectively). CONCLUSION Diverse changes In plasma aldosterone and cortisol found in response to the postural test may indicate pathogenetic heterogeneity amongst patients with aldosterone producing adenomas and should be considered during diagnosis of primary aldosteronlsm.     

Bone mineral density and bone turnover in Romanian children and young adults with classical 21-hydroxylase deficiency are influenced by glucocorticoid replacement therapy

Objective It remains controversial if glucocorticoid replacement therapy impairs bone mineral density (BMD) in young patients with 21‐hydroxylase deficiency. We aimed to analyze the impact of treatment variables, phenotype and genotype on BMD and bone metabolism in these patients. Design Cross‐sectional study. Measurements Twenty‐eight Caucasian patients with classical 21‐hydroxylase deficiency (5–39 years). Clinical parameters, hormonal status, osteocalcin (OC), C‐terminal telopeptide of type I collagen (CTX), genotype and lumbar BMD (Z‐scores) were assessed. Cumulative and mean hydrocortisone equivalent doses were calculated for the entire treatment period. Results Patients with severely reduced BMD Z‐scores (≤–2·5 SD) had significantly higher mean/cumulative glucocorticoid doses compared to patients with moderately reduced (P = 0·003/P = 0·026) and normal Z‐scores (> –1 SD) (P = 0·005/P = 0·011). Mean hydrocortisone equivalent doses > 20 mg/m²/day led to significantly lower lumbar BMD Z‐scores (–2·16 ± 1·4 SD) vs. doses ≤ 20 mg/m²/day (–0·59 ± 1·25 SD) (P = 0·008). BMD correlated negatively with mean/cumulative glucocorticoid doses and treatment duration. OC (86·45 ± 37·45 ng/ml) and CTX (1·45 ± 0·43 ng/ml) were significantly increased compared to an age‐ and sex‐matched control group in patients with active growth; only CTX was slightly increased in patients who completed growth. Conclusions High cumulative and mean glucocorticoid doses negatively impact on BMD in children and young adults with classical 21‐hydroxylase deficiency. Substitution therapy should be adapted particularly at this life period to prevent bone loss.