Increased lymphocyte thermogenesis in hyperthyroid patients. Role of Na/K pump function. Evaluation of aerobic/anaerobic metabolism.

The role of the Na/K pump for the increased cell energy expenditure in hyperthyroidism was studied by measuring total lymphocyte heat production rate in samples with and without ouabain inhibition of Na/K ATP-ase. In addition, the relative contribution of aerobic processes to lymphocyte thermogenesis was calculated from oxygen consumption measurements. In 12 patients with clinical and laboratory hyperthyroidism total lymphocyte heat production rate was 3.19 +/- 0.21 pW/cell, significantly higher than in 7 patients with subclinical hyperthyroidism (2.14 +/- 0.11 pW/cell) and in 15 euthyroid subjects (2.26 +/- 0.11 pW/cell) (p less than 0.001). The relative decrease in lymphocyte heat production rate after ouabain, giving a quantitative measure of the activity of the Na/K ATP-ase and reflecting the importance of Na/K pump function for the overall rate of lymphocyte metabolism, was not significantly different between the groups: 19.5 +/- 3.6% in hyperthyroid patients, 14.2 +/- 2.3% in subclinical hyperthyroid patients and 17.8 +/- 3.1% in euthyroid subjects. According to the rate of lymphocyte oxygen consumption, aerobic processes represented 58.4 +/- 6.7% of total lymphocyte energy expenditure in hyperthyroid patients, not significantly different from subclinical hyperthyroidism (62.6 +/- 8.4%) or from euthyroidism (66.6 +/- 2.7%). These data do not support the hypothesis of a specific role of the Na/K pump function for the increased cell thermogenesis in hyperthyroidism and indicate a parallel stimulation of aerobic and anaerobic processes by thyroid hormone excess.     

Enhanced endothelin-1-induced contractions in mesenteric arteries from rats with congestive heart failure: role of ET(B) receptors

Studies of congestive heart failure (CHF) in man and in experimental CHF have demonstrated elevated circulating levels of endothelin (ET). In order to examine whether there are concomitant ET receptor alterations, the vasomotor effects of endothelin-1 (ET-1) and sarafotoxin 6c (S6c) were examined in endothelium-intact and -denuded isolated mesenteric arteries from rats with CHF. CHF was induced by ligation of the left anterior descending coronary artery. Vasomotor responses were studied using small mesenteric arteries (approx. 250 microm in diameter, determined after normalisation). The antagonists IRL2500 and FR139317 were used in order to characterise the ET-1-induced response. In mesenteric arteries with intact endothelium, ET-1-induced contractions were more potent in CHF as compared to sham (pEC(50) 9.6+/-0.2 and 9.1+/-0.1, respectively, P<0.01). In endothelium-denuded arteries, there was no difference in potency of ET-1 between CHF and sham arteries, or in maximum contraction. In the presence of IRL2500, a selective ET(B)-receptor antagonist, ET-1 was more potent in endothelium-denuded arteries of CHF rats, while this difference was not seen in sham arteries. S6c had no consistent contractile or dilatory effect in CHF and sham rats. The results indicate that the enhanced contractile effects of ET-1 noted in CHF might be due to an attenuated endothelial function and that inhibition of smooth muscle cell ET(B) receptors increase the effects of contractile ET(A) receptors in CHF rats.     

HLA antigens in two siblings with autoimmune Addison's disease

The diagnosis of autoimmune Addison's disease was established in two siblings by demonstration of serum antibodies against adrenal cortex antigen, elevated P-ACTH combined with a low P-cortisol, and the absence of P-cortisol response to exogenous ACTH. HLA typing in the two siblings and their parents revealed the same HLA phenotype in the two patients. This is compatible with an autosomal recessive mode of inheritance and indicates that a supposed trait for autoimmune Addison's disease may segregate with the HLA complex in the familial form of autoimmune Addison's disease.     

Platelet and adipocyte thermogenesis in hypothyroid patients: a microcalorimetric study

Direct microcalorimetry was used for measurements of heat production in cell suspensions of platelets and adipocytes, obtained from hypothyroid patients before and after 3 months on full L-thyroxine substitution. Platelet heat production was significantly lower than normal before treatment and increased in all 10 patients studied; the mean value increased from 51.3 +/- 1.6 fW/cell before to 57.1 +/- 1.8 fW/cell after therapy (P less than 0.001). Similarily, adipocyte heat production was initially significantly lower than normal and increased during treatment in all 6 patients investigated. The mean value for heat production per adipocyte was 18.8 +/- 1.7 pW/cell before and 32.4 +/- 2.5 pW/cell after therapy (P less than 0.025), which is still below the level recorded in lean healthy subjects. The adipocyte size did not change significantly. The increase in adipocyte heat production was correlated to the increase in S-triiodothyronine levels (r = 0.84, P less than 0.05). In hypothyroidism, the total metabolic activity seems to be comparatively more reduced in adipocytes than in platelets. A difference may exist between these cells with regard to recovery of normal metabolic activity during treatment for hypothyroidism. Direct microcalorimetry appears to be an adequate method for monitoring net metabolic effects of thyroid hormones in these cells.     

Increased biochemical markers of bone formation and resorption in primary hyperparathyroidism with special reference to patients with mild disease

Valdemarsson S, Lindergård B, Tibblin S, Bergenfelz A (Lund University Hospital, Sweden). Increased biochemical markers of bone formation and resorption in primary hyperparathyroidism with special reference to patients with mild disease. J Intern Med 1998; 243 : 115–22.

Objectives

.To evaluate the impact on bone turnover of primary hyperparathyroidism (pHPT) with special reference to patients with mild pHPT, using biochemical markers of bone formation and resorption.

Design

.A longitudinal study of patients with pHPT before and one year after surgical treatment.

Setting

.The Departments of Internal Medicine and Surgery, Lund University Hospital.

Subjects

.Forty consecutive patients with pHPT. Thirty of these patients had mild pHPT and are reported separately. Data on bone mineral was also compared to a reference population.

Intervention

All patients were operated upon and restudied one year later.

Main outcome measures

.Bone resorption and formation was studied by means of the serum concentrations of the telopeptide of the carboxyterminal region of type 1 collagen (ICTP) and of alkaline phosphatase (ALP), osteocalcin and the carboxyterminal propeptide of type 1 procollagen (PICP), respectively. Bone density was measured at the distal radius by single photon absorptiometry (SPA).

Results

.Bone formation markers consistenly decreased after parathyroid surgery: ALP from 3.51 ± 0.23 to 2.94 ± 0.21 µkat L^?1 (P < 0.05), osteocalcin from 6.15 ± 0.53 to 2.89 ± 0.23 µg L^?1 (P < 0.001) and PICP from 126.4 ± 10.9 to 96.0 ± 6.5 µg L^?1 (P < 0.001). In parallel, the ICTP concentration, reflecting bone resorption, decreased from 5.10 ± 0.54 to 3.94 ± 0.34 µg L^?1 (P < 0.001). There was not any significant change in distal radius bone mineral 1 one year after surgery. In the subgroup of patients classified as mild pHPT, a significant decrease was noted for osteocalcin, PICP and for ICTP but not for ALP, without significant changes in variables reflecting distal radius bone mineral content. Glomerular filtration rate was inversely correlated to serum levels of intact PTH, ionized calcium, alkaline phosphatase, osteocalcin and ICTP and directly correlated to the 1.25-dihydroxy-vitamin D concentrations.

Conclusions

.pHPT is associated with substantial changes in circulating levels of biochemical markers of bone formation and resorption. These findings are also present in patients with mild pHPT. Renal function should be considered in the evaluation of the impact of pHPT on bone turnover.

     

Risk factors for postoperative hypocalcemia after surgery for primary hyperparathyroidism

HYPOTHESIS: A variety of clinical and biochemical variables may be associated with hypocalcemia after surgery for parathyroid adenoma. DESIGN: A prospective study of patients who underwent surgery for solitary parathyroid adenoma. SETTING: A university hospital department of surgery. PATIENTS: Eighty-six consecutive patients who underwent surgery for solitary parathyroid adenoma. INTERVENTION: Parathyroidectomy according to the principles of unilateral neck exploration. MAIN OUTCOME MEASURES: Clinical and biochemical risk factors for early (< or =4 days after surgery) and late (1 year after surgery) postoperative symptomatic and biochemical hypocalcemia. RESULTS: Twenty-two patients developed early symptomatic hypocalcemia. The difference in total serum calcium levels between patients, with and without early symptomatic hypocalcemia, was evident on the third and fourth postoperative days. Serum level of osteocalcin greater than 6.0 microg/L, bilateral neck exploration, and history of cardiovascular disease were risk factors for symptomatic hypocalcemia (odds ratios [95% confidence intervals]: 4.4 [1.4-14.1], 3.8 [1.3-11.6], and 0.1 [0.02-0.60], respectively). Patients with up to 1 risk factor had a possibility of only 7% to develop early symptomatic hypocalcemia. One year after surgery, 16 patients had low levels of total serum calcium (late biochemical hypocalcemia) and were asymptomatic. Preoperative intermittent hypercalcemia was associated with an increased risk for late biochemical hypocalcemia (odds ratio, 3.9; 95% confidence interval, 1.0-16.3). CONCLUSIONS: Clinical and biochemical risk factors for early and late postoperative hypocalcemia in patients who underwent surgery for solitary parathyroid adenoma were found. A clinically useful prognostic index for early symptomatic hypocalcemia was constructed using these risk factors.     

Dilatory responses to acetylcholine, calcitonin gene-related peptide and substance P in the congestive heart failure rat

It was examined to what extent congestive heart failure (CHF) in rats, induced by ligation of the left coronary artery, affects the vascular responses to the vasodilatory substances acetylcholine (ACh), calcitonin gene-related peptide (CGRP), and substance P (SP). After induction of CHF status, the basilar, mesenteric and renal arteries and the iliac vein were studied in vitro. Dilatory responses were determined in relation to pre-contraction by the thromboxane mimetic U46619. Sham-operated animals (Sham) served as controls. U46619 induced stronger contraction in CHF basilar and renal arteries compared with the corresponding segments in Sham. ACh induced concentration-dependent dilations in all vessels examined with no difference of maximum relaxation or potency between CHF and Sham. SP induced weak dilations in all arteries examined while the response was markedly attenuated in CHF iliac veins compared with Sham (Emax% 12.2 +/- 3.4 vs. 32.3 +/- 4.8, P = 0.01). The CGRP induced dilation in the CHF basilar artery was weaker (Emax% 18.6 +/- 6.5 vs. 66.9 +/- 5.0, P < 0.001) and less potent (pEC50: 8.2 +/- 0.2 vs. 9.0 +/- 0.2, P = 0.01) compared with Sham. Further, CGRP was less potent in the renal artery of CHF rats compared with Sham (pEC50: 8.1 +/- 0.2 vs. 9.5 +/- 0.3, P < 0.01). In the CHF iliac vein, CGRP was more potent compared with Sham (pEC50: 9.7 +/- 0.4 vs. 8.3 +/- 0.4, P < 0.05). It can be concluded CHF is accompanied by alterations in the vascular response to the dilatory substances studied. The changes differ between vascular beds and between the different substances.     

Preferences and frequencies of visits to public facilities in old age--a pilot study in a Swedish town center

In societies with an increasing proportion of elderly active people it is valuable to gain knowledge about what elderly people actually do and want to do in relation to activity arenas in the public environment. The main aim of this study was to investigate elderly people's preferences and frequencies of visits to public facilities in a Swedish town center. A further aim was to gather information on elderly people's subjective perception of problematic and favorable environmental conditions in public environments. The study was conducted using a previously developed questionnaire, "My visit preferences to the public environment". The sample comprised 39 persons aged 75-84 years, living in a defined geographic area. The results of this study provide an overview of the public facilities elderly people rate as important to visit. There are public facilities preferred by most elderly people but with varying frequencies of visits. The study also generated information about elderly people's subjective perceptions of problematic and favorable environmental conditions in public environments, demonstrating that more problems were perceived along walking routes in the public outdoor environment than in the public facilities per se. The results are indicative for community planning supporting elderly people's activities in the public environment, but the questionnaire used should be further validated.     

Preoperative Normal Level of Parathyroid Hormone Signifies an Early and Mild Form of Primary Hyperparathyroidism

Abstract Contemporary patients are often diagnosed with mild or intermittent hypercalcemia. In addition, most studies demonstrate patients with parathyroid (PTH) levels in the upper normal range. The aim of the present investigation was to define subgroups of patients with mild primary hyperparathyroidism (pHPT), which could be of importance in the decision for or against surgical treatment. Two-hundred and eleven patients, operated for pHPT were investigated with biochemical variables known to reflect PTH activity, renal function, and bone mineral content. The preoperative diagnosis of pHPT was based on the presence of hypercalcemia combined with an inappropriate serum concentration of PTH. The mean age of the patients was 64 ± 14 years and the mean serum level of calcium was 2.78 ± 0.19 mmol/L. One hundred and sixty-two patients (77%) had raised levels of calcium and PTH the day before surgery (overt pHPT), 25 patients (12%) had a normal level of calcium and a raised PTH level (normal calcium group), and 20 patients (9%) had a raised level of calcium and a normal level of PTH (normal PTH group). In four patients the level of calcium and PTH was normal. Between-group analysis demonstrated no major difference in symptom and signs of pHPT. Except for lower adenoma weight, patients in the normal calcium group did not essentially differ from the patients in the overt pHPT group. However, patients in the normal PTH group were a decade younger, and had better renal function, lower bone turnover, and a preserved bone density compared with patients in the overt pHPT group. In conclusion, the data from the present investigation show that pHPT patients with a preoperative normal PTH level have an early and mild form of the disease. Furthermore, the serum calcium concentration does not reflect disease severity in pHPT.     

Evaluation of surgery for acromegaly: role of intraoperative growth hormone measurement?

OBJECTIVE: Intraoperative growth hormone (GH ) measurement has earlier been tried to improve surgery for acromegaly. We calculated GH half-life after adenomectomy and evaluated the possible role of this variable in predicting the final outcome of pituitary surgery in 28 consecutive patients with acromegaly. The sensitivity, specificity and predictive values were determined in relation to the results from GH suppression during an oral glucose load and IGF-1 3 months postoperatively. The GH half-life data were also compared to the corresponding results obtained from GH measurements between 60 min and 180 min after adenomectomy, and early, within 1 week, postoperatively. RESULTS: GH half-life < or =31 min was recorded in 8/13 cured patients but also in 2/15 unsuccessful cases. A mean GH concentration < or =4.4 mU/L between 60 min and 120 min after adenomectomy was found in 11/13 cured subjects but also in 3/15 not cured patients. A mean GH < or =4.0 mU/L between 90 min and 180 min was found in 11/13 cured and in 4/15 not cured patients. A mean early postoperative GH concentration < or =2.6 mU/L was noted in all 13 cured patients, but also in 2/13 unsuccessful cases. The specificity of early postoperative GH < or = 2.6 mU/L was 100% compared to 62% for a GH half-life < or =31 min (p<0.05) and 85% for the GH mean values between 60 min and 120 min and 90 min and 180 min, respectively. The sensitivity for persistent disease of values above the four cut-off limits used was between 73% and 87%. The positive predictive value for a mean early postoperative GH value >2.6 mU/L was 100%, and 72% for a GH half-life >31 min (n.s.). CONCLUSION: Although intraoperative GH half-life might be useful in some cases, it was not a reliable tool for predicting outcome of pituitary surgery in acromegaly. In cases with a 51% decrease of a basal GH concentration >5.5 mU/L, mean GH values < or =4 to < or =4.4 mU/L late intraoperatively were more informative but not as good as those obtained from the mean of a series of GH values drawn on one occasion within 1 week postoperatively, offering a 100% specificity for cure if < or =2.6 mU/L. Intraoperative GH half-life measurements should therefore be used with caution. The predictive values of the cut-off limits used in this study should be further evaluated before general application.