Pavo Hedner

Occupational lead exposure and pituitary function

SummaryTwenty-five moderately exposed lead workers (mean blood-lead level 1.9 γmol/l) had lower plasma levels of follicle stimulating hormone than 25 individually matched controls without occupational lead exposure (blood-lead level 0.2 μmol/l). In addition, the ten most heavily exposed individuals had higher levels of thyroid stimulating hormone, and the 14 workers under the age of 40 had decreased plasma levels of luteinizing hormone and serum levels of cortisol, as compared to the controls. All values were within “normal” reference limits. There was no significant change of the plasma testosterone level. These data indicate a complex effect on the endocrine system by moderate lead exposure, possibly mediated by changes at the hypothalamic-pituitary level. Besides the effect on hormone levels, there was also a decrease in plasma selenium level for the lead exposed workers.

Reversal of decreased hepatic lipase and lipoprotein lipase activities after treatment of hypothyroidism

Abstract. Plasma lipoprotein concentrations, activities of hepatic lipase and lipoprotein lipase in post‐heparin plasma, and the removal rate of exogenous triglyceride were measured in fourteen patients with severe primary hypothyroidism before and after 4 months substitution therapy with 1‐thyroxine. Before treatment plasma LDL cholesterol concentrations were markedly increased while HDL cholesterol and plasma triglycerides were in the upper reference range. Thyroxine substitution led to a normalization of LDL cholesterol in all patients. Plasma triglycerides and HDL cholesterol decreased moderately. Hepatic lipase and lipoprotein lipase activities were initially reduced but increased significantly after treatment, by about 170% and 55%, respectively. The increase in hepatic lipase activities was significantly correlated to the increase in serum triiodothyronine levels and also to the reduction in LDL cholesterol concentrations. The decrease in LDL cholesterol was also significantly correlated to the increase in serum triiodothyronine concentration.

Congestive heart failure: involvement of perivascular peptides reflecting activity in sympathetic, parasympathetic and afferent fibres

Abstract. In controls and in patients suffering from congestive heart failure (CHF) the circulating levels of catecholamines, neuropeptide Y‐like immunoreacti‐vity (NPY‐LI), vasoactive intestinal peptide‐LI (VIP‐LI), substance P‐LI (SP‐LI) and calcitonin gene‐related peptide‐LI (CGRP‐LI) markers of sympathetic, parasympathetic and sensory nervous systems, respectively, have been examined. There was a significant rise in the levels of noradrenaline, NPY‐LI and SP‐LI already in moderate CHF (New York Heart Association Stage I and II). In patients with severe CHF (NYHA Stage III and IV) the circulating levels of noradrenaline, adrenaline, NPY‐LI and SP‐LI were significantly increased. CGRP‐LI was not altered, despite the fact that this peptide co‐exists in many tissues with SP. There was no change in VIP‐LI. The pathophysiological significance of this pattern of reaction of circulating catecholamines and neuropeptides is unclear; however, the rise in SP‐LI may be a reaction to counterbalance the vasoconstrictive effects of the activation of the sympatho‐adrenal system.

Hormonal influence on calcitonin gene-related peptide in man: effects of sex difference and contraceptive pills.

Calcitonin gene-related peptide (CGRP) is one of the peptides encoded for by the calcitonin gene. It has been demonstrated in man to be located in the thyroid and in perivascular nerves and to possess potent vasodilatory properties. In the present study we found plasma levels of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) to be significantly higher in females than in males and that women on contraceptive pills had significantly higher CGRP-LI levels than women not taking contraceptives. These data are in accordance with one earlier report on an increased CGRP level during pregnancy and suggest a positive influence of the female sex hormones on the plasma CGRP level in man, which should be considered in the establishment of a reference range for this analysis.

Screening for medullary carcinoma of the thyroid in families with Sipple's syndrome: evaluation of new stimulation tests

Abstract. In search of new practical diagnostic methods for the early diagnosis of hereditary medullary carcinoma of the thyroid (MCT) calcitonin release has been studied following induction by pentagastrin, cholecystokinin‐pancreozymin (the C‐terminal octapeptide, C8‐CCK, and the native swine extract), and ethanol in eighteen cases of MCT (all but one clinically occult), three ‘borderline cases’, seven first degree relatives of patients with hereditary MCT and thirty‐five healthy controls.

Increased plasma level of substance P in patients with severe congestive heart failure treated with ACE inhibitors

Abstract. The effects of angiotensin‐converting‐enzyme (ACE) inhibitors on circulatory regulating mechanisms in congestive heart failure (CHF) were studied by comparison of plasma levels of catecholamines, neuropeptide Y‐like immunoreactivity (NPY‐LI), substance P (SP‐LI), calcitonin gene‐related peptide (CGRP‐LI), vasopressin (ADH‐LI), atrial natriuretic peptide (ANP‐LI) and renin activity (PRA) in patients with severe CHF (NYHA III‐IV) with (n = 15) or without (n = 17) ACE inhibitors in addition to digoxin and diuretic therapy. Data were also compared with those for healthy subjects (n = 31) and patients with moderate CHF (NYHA I‐II). Catecholamines and NPY‐LI were increased to the same extent in both groups with severe CHF. CGRP‐LI showed no changes relative to controls in any of the patient groups, and was not affected by ACE inhibitors. The SP‐LI level was significantly increased in all patient groups. Patients with severe CHF on ACE inhibition had a SP‐LI level of 4.05±0.79 pmol l−1, compared to a concentration of 2.28±0.30 pmol l−1 (P < 0.05) in the patient group with a comparable degree of CHF but without ACE inhibition. In the latter group, an inverse relationship appeared between the SP‐LI and the serum sodium levels (r = —0.68, P < 0.05). The patients with severe CHF who received ACE inhibitors had significantly lower ADH‐LI levels than the patients with a comparable degree of CHF who were not treated with ACE inhibitors, while the ANP‐ LI level was increased to a similar extent in both groups.

Corticosteroid action on choroid plexus: Reduction in Na+—K+-ATPase activity, choline transport capacity, and rate of CSF formation

SummaryGlucocorticoids have a well-known clinical effect on brain edema and intracranial hypertension, but the mechanism of action is still poorly understood. In the present report the effect of betamethasone on choroid plexus transport and CSF formation was studied. Following 5 days of daily treatment with betamethasone the CSF production rate in rabbits was reduced by 43% as measured by ventriculo-cisternal perfusion with radioactive inulin. Accordingly, the transport capacity in the choroid plexus, measured in terms of choline uptake and accumulation in vitro, and the activity of Na+—K+-ATPase decreased in both rabbit (in the lateral ventricles by 31 and 31%, respectively) and rat (by 16 and 24%, respectively). Thus, the demonstrated influence of glucocorticoids on these functions of the choroid plexus seem to be important components in their therapeutic effect on intracranial hypertension.

Effect of cholecystokinin on the level of cyclic AMP and on mechanical activity in the isolated sphincter of Oddi

Abstract IN the isolated sphincter of Oddi of the cat, relaxation was induced by beta receptor stimulators, glucagon, and theophylline, all agents known to produce an increase in the intracellular level of cyclic AMP (cAMP) in several tissues. cAMP added to the bath relaxed the sphincter. Imidazole, which can decrease the tissue level of cAMP by stimulation of phosphodiesterase (PDE), contracted the sphincter of Oddi. The relaxing effect of the C-terminal octapeptide of cholecystokinin (C8-CCK) was found to be preceded by a 88.8 per cent (n = 5; p It is suggested that C8-CCK increases the level of cAMP in the tissue by stimulation of adenyl cyclase, and that this metabolic effect is of importance for the initiation of the mechanical response to the hormone.

Reduced Size of a Hormonally Silent Pituitary Adenoma during Treatment with CV 205-502, a New Dopamine Agonist Mainly Stimulating D2 Receptors

A 39-year-old woman with secondary amenorrhea and visual field defects underwent craniotomy for a large pituitary tumor that was hormonally silent according to measurement of plasma hormone levels and immunohistochemical analysis. During the preoperative investigation, bromocriptine was administered for 1 month, but there was no change in the tumor size as seen on computed tomographic scans. One month after surgery, visual field defects recurred, and a tumor mass comparable to the preoperative state was found on computed tomographic scan. The tumor size gradually diminished during treatment with CV 205-502, a tricyclic benzoquinoline which stimulates mainly D2 receptors and is better tolerated than bromocriptine. The visual fields were completely normalized after 3 months of treatment with the drug, and surgical management of the tumor mass was no longer considered to be necessary. Thus, as in many similar cases, the hormonally silent pituitary tumor in this patient proved unresponsive to bromocriptine treatment. In contrast, the tumor was reduced by therapy with CV 205-502, a drug that is better tolerated and might permit a more intense stimulation of D2 receptors.

Interrelations between cyclic AMP, cyclic GMP and contraction in guinea pig gallbladder stimulated by cholecystokinin

Abstract The changes in isometric tension and in concentrations of cyclic AMP and cyclic GMP in guinea pig gallbladder muscle induced by the C-terminal octapeptide of cholecystokinin (C8-CCK) were studied before and after the addition of indomethacin 3 × 10 −6 g/ml. The contractile response to the hormone was not affected by indomethacin, nor was the associated decrease in cyclic AMP concentration. However, indomethacin completely prevented the increase in cyclic GMP following addition of C8-CCK. The results suggest that in isolated guinea pig gallbladder, cyclic GMP is not essential for the C8-CCK-induced decrease in cyclic AMP concentration, and that the contractile response induced by the hormone is independent of this nucleotide.