Margareta Bramnert

Fracture incidence in GH-deficient patients on complete hormone replacement including GH

Fracture risk in GHD patients is not definitely established. Studying fracture incidence in 832 patients on GH therapy and 2581 matched population controls, we recorded a doubled fracture risk in CO GHD women, but a significantly lower fracture risk in AO GHD men.

The effects of GH replacement therapy on cardiac morphology and function, exercise capacity and serum lipids in elderly patients with GH deficiency

objectives  To assess effects of GH replacement therapy on cardiac structure and function, exercise capacity as well as serum lipids in elderly patients with GH deficiency (GHD).

Characterization and application of a radioimmunoassay for β-endorphin using an antiserum with negligible cross-reactivity against β-lipotropin

Abstract High avidity antisera against β-endorphin (β h - EP ) were obtained in two of five rabbits immunized with unconjugated synthetic human β h - EP . One of these antisera (K-7762) cross-reacted 1.5% on a molar basis with β-lipotropin (β h - LPH ) and did not recognize leucine-enkephalin in a concentration as high as 0.2 mmol/l. The cross-reaction with methionine-enkephalin (β h - LPH 61–65) was 9%, while that with α-endorphin ( β h - LPH 61–76) was 69%. This implied that the specific recognition site was in the amino-terminal region of β h - EP . Although this sequence is present in β h - LPH it was poorly recognized by the antiserum, suggesting that the free amino-terminal is essential. This interpretation was supported by the finding that α-N- acetyl -β h - EP was equally poorly recognized by the antiserum. The sensitivity of the radioimmunoassay was 1.9 pmol/l. β h - EP was not detectable ( β h - EP was detectable ( 5 ± 3 pmol/l ; mean ± S.D.) after metyrapone. β h - EP was elevated in Addisons disease (23, 54 and 76 pmol/l), Nelsons syndrome (37, 39 and 109 pmol/l), ectopic ACTH production (27, 59 and 76 pmol/l), but only detectable in one of three samples from patients with Cushings disease (7 pmol/l). Gel chromatography of extracts of porcine pituitary revealed only one immunoreactive peak co-eluting with synthetic human β h - EP . The specificity of the antiserum K-7762 was such that the β h - EP concentration in plasma extracts could be reliably estimated by radioimmunoassay without prior chromatography.

The effect of captopril on catecholamines, renin activity, angiotensin II and aldosterone in plasma during physical exercise in hypertensive patients

Abstract. The studies were designed to explore the effect of the converting enzyme inhibitor captopril on the activity of the sympathetic nervous system during basal conditions and following graded physical exercise in patients with essential hypertension. Seven males and two females, aged 36–59 years, were hospitalized under metabolic ward conditions and treated for 7 days with captopril given orally in increasing dosages, the final dose being 600 mg daily. The patients were subjected to an individual, graded submaximal work test (bicycling) for 20 min before medication and then again in an identical manner during medication with 600 mg captopril. Blood samples were drawn before exercise and then after 10 and 20 min of work for the determination of plasma angiotensin II (PA II), plasma aldosterone (PAC), plasma renin activity (PRA), plasma noradrenaline (PNA) and plasma adrenaline (PA). Before medication blood pressure (mmHg) was 195/133 immediately before exercise, 230/129 after 10 min of moderate exercise and 263/105 following 20 min of nearly maximal work. During treatment with captopril the respective blood pressure values were 154/110, 200/100 and 245/98. Captopril had no significant effect on the changes in heart rate following physical exercise. PA II and PAC were substantially reduced and PRA considerably increased by captopril. PA II, PAC and PRA increased in response to exercise both before and following captopril. The exercise stimulated increase in PNA and PA was almost identical before and during captopril. Thus, captopril had no major effect on the activity of the sympathetic nervous system in patients with essential hypertension, neither during basic conditions nor during heavy physical exercise in spite of a profound decrease in PA II.

Plasma neuropeptide Y (NPY) and galanin before and during exercise in type 1 diabetic patients with autonomic dysfunction

Plasma neuropeptide Y (NPY), plasma galanin and plasma catecholamines were determined before and during an ergometer exercise test in 11 type 1 diabetic patients (age 19-36 years, mean 30; duration of diabetes 2-18 years, mean 9) with autonomic dysfunction and in 13 age-matched healthy controls (age 24-36 years, mean 29). Before exercise, plasma NPY (100 +/- 6 pmol/l vs 144 +/- 7 pmol/l; P less than 0.001) and plasma galanin (54 +/- 3 pmol/l vs 77 +/- 5 pmol/l; P less than 0.005) were significantly lower in patients than in controls. During exercise, plasma NPY, plasma adrenaline, and plasma noradrenaline increased in patients and controls while galanin only increased in patients. Since there was a direct correlation between plasma NPY before exercise and the increment (delta 80%) in noradrenaline during exercise (r = 0.54; P less than 0.01), it is suggested that plasma NPY determined in the basal situation may be a useful marker of sympathetic nerve failure in diabetic patients.

Insulin Sensitivity in Adults with Growth Hormone Deficiency and Effect of Growth Hormone Treatment

Adult growth hormone deficiency (GHD) is a multifactorial disorder in which pituitary dysfunction associated with pituitary adenomas or their treatment plays a major role. The introduction of recombinant growth hormone (GH) for the treatment of GHD has opened up new treatment avenues but has also raised concerns about possible untoward long-term metabolic effects of GH, such as the potential effect of GH on insulin sensitivity and a deterioration in glucose tolerance. Research has shown that GH induces insulin resistance by the stimulation of lipolysis and a concomitant switch from oxidation of glucose to oxidation of lipids, during both acute and chronic treatment. However, although this is a consistent effect of GH therapy, it does not mean per se that it leads to abnormal glucose tolerance and diabetes mellitus. This article discusses this and other potential long-term metabolic effects of GH, and raises a number of questions to be addressed by future research.

Increased arterial and venous plasma noradrenaline levels in patients with primary hypothyroidism during hypothyroid as compared to euthyroid state

The use of venous plasma noradrenaline levels as a marker of general sympathetic tone has been questioned as changes in local sympathetic activity may influence the venous levels. To compare arterial and venous plasma noradrenaline levels in patients with primary hypothyroidism, arterial and venous blood were sampled during strictly standardized conditions during hypothyroid and euthyroid states. The patients were hospitalized for 5 days at a metabolic ward on a standardized sodium and potassium intake. On the fourth day catheters were positioned in the axillary artery and vein. Blood samples were drawn simultaneously for noradrenaline and adrenaline determinations during resting conditions. The arterial and venous plasma noradrenaline levels did not differ significantly, neither during hypothyroidism nor during euthyroidism. The arteriovenous difference in plasma adrenaline was similar during hypothyroidism compared to euthyroidism, indicating similar peripheral extraction rate of catecholamines during hypothyroidism as compared to euthyroidism. During hypothyroidism venous and arterial noradrenaline were significantly higher as compared to euthyroidism. In conclusion, there is no difference between arterial and venous noradrenaline levels either in the hypothyroid or the euthyroid state, and the peripheral extraction rate of plasma noradrenaline seems to be similar in hypothyroidism and euthyroidism. The local contribution of noradrenaline from the arm, reflecting local sympathetic nervous activity, is limited during resting conditions. In hypothyroid patients plasma noradrenaline levels are increased as compared to the euthyroid state, indicating increased general sympathetic activity in hypothyroidism.

Psychosocial health and levels of employment in 851 hypopituitary Swedish patients on long-term GH therapy

CONTEXT The psychosocial health and working capacity in hypopituitary patients receiving long-term growth hormone (GH) therapy are unknown. OBJECTIVE Psychosocial health and levels of employment were compared between GH deficient (GHD) patients on long-term replacement and the general population. DESIGN AND PARTICIPANTS In a Swedish nationwide study, 851 GHD patients [101 childhood onset (CO) and 750 adult onset (AO)] and 2622 population controls answered a questionnaire regarding current living, employment and educational level, alcohol consumption and smoking habits. The median time on GH therapy for both men and women with CO GHD was 9 years and for AO GHD 6 years, respectively. RESULTS As compared to the controls, the GHD patients were less often working full time, more often on sick leave/disability pension, and to a larger extent alcohol abstainers and never smokers (all; P<0.05). Predominantly CO GHD women and men, but to some extent also AO GHD women and men, lived less frequently with a partner and more often with their parents. Particularly AO GHD craniopharyngioma women used more antidepressants, while AO GHD men with a craniopharyngioma used more analgesics. CONCLUSIONS A working capacity to the level of the general population was not achieved among hypopituitary patients, although receiving long-term GH therapy. Patients were less likely to use alcohol and tobacco. The CO GHD population lived a less independent life.

The activity of the renin-angiotensin-aldosterone system before and during submaximal bicycle exercise in relation to circulatory catecholamines in patients with type 1 (insulin-dependent) diabetes mellitus.

SummaryTo evaluate the renin-angiotensin-aldosterone system in relation to circulatory catecholamines, we determined renin activity, angiotensin II, aldosterone, adrenaline, and noradrenaline in plasma before and during a submaximal bicycle exercise test in 23 Type 1 (insulin-dependent) diabetic patients (aged 19–57 years, mean 37; duration of diabetes 2–32 years, mean 16), 17 with signs of cardiac autonomic neuropathy, and in 18 healthy non-diabetic subjects (aged 24–41 years, mean 29). At rest, Type 1 diabetic patients showed significantly lower aldosterone values than control subjects (0.14±0.02 nmol/l and 0.22±0.02 nmol/l; p<0.01) while renin activity (1.0±0.1 nmol·l−1·h−1 and 0.9±0.1 nmol·l−1·h−1) and angiotensin II (14±1 nmol/l and 18±2 nmol/l) did not differ significantly between patients and control subjects. During exercise, increments (increase from the resting value to the value at 80% of maximal working capacity) in renin (1.5±0.4 nmol·l−1·h−1 and 3.7±0.5 nmol·l−1 ·h−1; p<0.001), angiotensin II (28±8 nmol/l and 60±8 nmol/l; p<0.01), aldosterone (0.16±0.04 nmol/l and 0.25±0.05 nmol/l; p<0.05), adrenaline (1.96±0.49 nmol/l and 2.92±0.51 nmol/l; ps<0.05), and noradrenaline (12.01±1.25 nmol/l and 18.74±1.45 nmol/l; p<0.01) were significantly lower in the patients than in control subjects. There was no difference in the renin-angiotensin-aldosterone response to exercise between patients with and without cardiac autonomic neuropathy but the impaired catecholamine reaction was confined to patients with cardiac autonomic neuropathy. In conclusion, Type 1 diabetic patients demonstrated low resting plasma aldosterone and reduced increments in renin activity, angiotensin II, aldosterone, and catecholamines during exercise. The low aldosterone values might be related to dysfunction of adrenal zona glomerulosa cells while it is unlikely that the reduced response to exercise of the renin-angiotensin-aldosterone system simply reflects sympathetic nerve failure.

The effect of naloxone on blood pressure, heart rate, plasma catecholamines, renin activity and aldosterone following exercise in healthy males

There is evidence that endogenous opioids are involved in blood pressure regulation. In the present study the effect of naloxone on the cardiovascular, sympathoadrenomedullary and renin-aldosterone response to physical exercise was investigated in 8 healthy males. Each subject performed a submaximal work test twice, i.e. with and without naloxone. The test consisted of ergometer bicycling for 10 minutes on 50% of the maximal working capacity (MWC), immediately followed by 10 min on 80% of MWC. Ten minutes before exercise the subjects received in a single blind randomized order a bolus dose of naloxone (100 micrograms/kg) or a corresponding volume of the preservatives of the naloxone preparation (control) followed by a slow infusion of naloxone (50 micrograms/kg/h) or preservatives, respectively. Naloxone was without effect on the exercise-induced changes in systolic blood pressure, heart rate, plasma noradrenaline, renin activity and aldosterone, but the adrenaline response increased markedly. The present results indicate that opioid receptors are involved in the plasma adrenaline response to submaximal exercise, but not in the regulation of systolic blood pressure, heart rate, plasma noradrenaline, renin activity and plasma aldosterone.