Plasma Potassium and Phosphate Concentrations—Influence by Adrenaline Infusion, β-blockade and Physical Exercise

ABSTRACT. Ljunghall S, Joborn H, Rastad J, Åkerström G (Departments of Internal Medicine, and Surgery, University Hospital, Uppsala, Sweden). Plasma potassium and phosphate concentrations—influence by adrenaline infusion, β-blockade and physical exercise. Acta Med Scand 1987; 221:83–93. Infusion of adrenaline into healthy male subjects reduced the plasma concentrations of both potassium and phosphate to a similar extent, in a dose-dependent manner, an effect which was prevented by the administration of propranolol. Ergometer bicycling until exhaustion, which caused marked accumulation of lactic acid in the blood and reduction of pH, induced great elevations of both plasma potassium and phosphate with close relationships between the raised plasma concentrations and the reduction in pH, also during β-blockade. However, longer-term aerobic exercise, without acidosis, also caused some rise of the potassium and phosphate concentrations. During recovery from anaerobic, but not from aerobic, exercise there was a rapid decrease of the plasma potassium levels while the phosphate values normalized gradually together with pH. From measurements of the ion concentrations both in the femoral effluent of one leg, which carried out maximal isokinetic work, and in the opposite antecubital vein it could be calculated that there was for potassium, but not for phosphate, a post-exercise uptake both in the exercised muscle and in the entire organism, indicating the participation of systemic factors.     

Clodronate Treatment in Patients with Malignancy-associated Hypercalcemia

ABSTRACT. Rastad J, Benson L, Johansson H, Knuutila M, Pettersson B, Wallfelt C, Åkerström G, Ljunghall S (Departments of Surgery and Internal Medicine, University Hospital, Uppsala, Sweden). Clodronate treatment in patients with malignancy-associated hypercalcemia. Acta Med Scand 1987; 221:489–94. The possibility of reducing symptomatic hypercalcemia and of maintaining total serum calcium concentrations <2.8 mmol/1 with clodronate (dichloromethylene bisphosphonate) was evaluated in 28 patients with various types of malignant tumors. Four episodes of hypercal-cemic crisis with mean serum calcium concentrations of 4.43 mmol/1 were controlled within 4–6 days of intravenous clodronate (4 mg/kg BW/day). This was accompanied by a moderate increase in serum creatinine values which, however, returned to pretreatment levels after therapy withdrawal in all but one case. Oral clodronate successfully reduced a mean serum calcium concentration of 3.16 mmol/1 in 22 out of 25 patients after 3–12 days (800–3 200 mg/ day). After reversal of the hypercalcemias oral clodronate controlled the serum calcium concentration for up to 42 weeks in six out of 15 patients After discontinuation of initial therapy five of seven recurrent hypercalcemias were successfully treated with oral or intravenous clodronate. Hypocalcemia and subjective side-effects were uncommon. It is concluded that clodronate is a valuable clinical tool in the management of patients with malignancy-associated hypercalcemia.     

Low plasma levels of insulin-like growth factor 1 (IGF-1) in male patients with idiopathic osteoporosis.

Experimental studies in vitro indicate that insulin-like growth factor 1 (IGF-1) could be of importance for normal bone growth and remodelling, but the clinical relevance of these observations is unknown. In 12 consecutive young to middle-aged male patients (mean age (+/- SD) 46 +/- 8 years, range 30-57 years) with symptomatic idiopathic osteoporosis, the plasma concentrations of IGF-1 were significantly lower than in healthy subjects (0.51 +/- 0.25 vs. 0.73 +/- 0.23 U ml-1; P less than 0.01). The bone mineral densities in the spine, the femoral neck, and the forearm were significantly different between patients and control subjects. There were positive correlations between the plasma IGF-1 concentrations and the bone densities of the spine and the forearm. Three of the patients received a 5-d course of human recombinant growth hormone (GH). During this short period significant increases in plasma IGF-1 levels and in biochemical indices of bone turnover (serum bone-specific alkaline phosphatase, urinary calcium excretion) were recorded. These observations indicate that circulating IGF-1 could have an important role in maintaining bone mass, and suggest that impairment of IGF-1 production is involved in the pathogenesis of osteoporosis.     

PROLONGED LOW-INTENSITY EXERCISE RAISES THE SERUM PARATHYROID HORMONE LEVELS

Twelve healthy males performed 5 h exercise on a bicycle ergometer at a constant work load of approximately 50% of their maximum capacity. The serum concentrations of parathyroid hormone (PTH) increased after the first hour and were continuously elevated throughout the exercise period. The rise in PTH was 5-7% above pre-exercise levels, corresponding to 20-30% of the maximal increase obtained by the same assay during prolonged hypocalcaemia. The probable cause for the rise in PTH was that the plasma ionized calcium tended to be lowered during exercise. Since the total serum calcium concentrations were raised (by 3-5%) during exercise the reduction of the free, ionized, fraction was presumably largely due to increased complex-binding although an outward transport from plasma was not excluded. The serum concentrations of magnesium were gradually reduced during exercise while those of phosphate and potassium were raised throughout, probably as a result of leakage from the working muscle.     

SCREENING FOR MULTIPLE ENDOCRINE NEOPLASIA SYNDROME (TYPE 1) IN PATIENTS WITH PRIMARY HYPERPARATHYROIDISM

In 63 consecutive patients with primary hyperparathyroidism (HPT) a prospective screening study was undertaken for coexistent multiple endocrine neoplasma-(MEN)-syndrome type 1. The screening consisted of a clinical examination, a radiological examination of the sella turcica with skeletal tomography (and in equivocal cases computed tomography), visual field examination by perimetry and a hormonal evaluation including measurements of the serum levels of prolactin, gastrin, pancreatic polypeptide (PP) and subunits of human chorionic gonadotrophin (HCG-alpha and -beta). Clinical examination did not reveal any signs of endocrine disease suggestive of a MEN-1 syndrome. In only one case there was a radiological abnormality of the sella turcica; this patient had an empty sella syndrome and a raised serum prolactin value. All other prolactin values were within the normal range. In 41% of the patients raised serum gastrin levels were found; these tended to normalize after parathyroidectomy. As a group, patients with raised gastrin values were older than the others and generally they had hypo- or achlorhydria. The serum PP levels were raised in 28% of the patients but there was no clinical evidence of a pancreatic tumour in any of these cases, and the serum HCG-alpha and -beta levels were within the normal range in all patients but two. We conclude that the incidence of MEN-1 syndrome in unselected patients with primary HPT must be low, and that investigations for this syndrome are justified only in HPT patients with specific symptoms or with a positive family history.     

Prevalence of hypercalcaemia in a health survey: a 14-year follow-up study of serum calcium values

Among 16,401 subjects attending two health screenings, in 1969 and 1971, 176 showed hypercalcaemia on both occasions, i.e. serum calcium values above 2.60 mmol l-1. The prevalence of hypercalcaemia increased in women with advancing age and occurred in close to 3% of those above the age of 60, whilst in men it was found in less than 0.7% in all age groups. The mean serum calcium concentration in women above the age of 50 was significantly higher than in men. This observation could at least partly explain why hyperparathyroidism (HPT) is more often diagnosed in females. Only nine persons were initially referred for neck exploration. Most of the others were not even notified of the biochemical disturbance and thus it was possible to study the serum calcium values in an unattended cohort until follow-up after 14 years. In the hypercalcaemic patients there was little or no increase in serum calcium during these years. In no patient did the serum calcium level rise above 3.0 mmol l-1. Altogether, 24 patients from the initial cohort were subsequently operated on for primary HPT but there were only two further cases of verified HPT, which developed during the follow-up period, in those who had been clearly normocalcaemic at the health surveys. In conclusion, hypercalcaemia, presumably caused by primary HPT, is common but apparently develops slowly and with little risk of a progressive rise of serum calcium concentrations.     

EFFECTS OF EXOGENOUS CATECHOLAMINES AND EXERCISE ON PLASMA MAGNESIUM CONCENTRATIONS

Catecholamines and physical exercise are known to influence the metabolism of several minerals in man, but the effects on magnesium (Mg) have been scarcely investigated. In the present study, infusion of adrenaline (5 micrograms/min for 30 min followed by 10 micrograms/min for 30 minutes) significantly reduced the plasma Mg levels in healthy males. This effect was abolished by simultaneous infusion of propranolol. Noradrenaline had no such effect. In order to stimulate endogenous catecholamine release healthy males carried out physical exercise in four different ways: ergometer bicycling at maximum load until exhaustion with and without oral beta-blockade, ergometer bicycling with stepwise increasing load until exhaustion, isokinetic maximal exercise with one leg, with blood sampling both from the venous effluent of the exercising leg and the opposite resting arm and long-term (60 min) steady state ergometer bicycling at approximately 65% of estimated maximum capacity. During short-term (less than 20 min) intense exercise (i.e. experiments 1-3) the plasma Mg concentrations were increased. This was probably due to a reduction of plasma volume and to an influx of Mg to the vascular pool. During long-term steady state exercise (experiment 4) the Mg levels were not significantly affected but decreased during the first hour of recovery. These results suggest that both the beta-adrenergic system and muscular activity by itself affect Mg homeostasis.     

Reduction of Blood Pressure by Treatment with Alphacalcidol

ABSTRACT Disturbances of calcium or vitamin D metabolism have been suggested to be of pathogenetic importance both for hypertension and impaired glucose tolerance, two disorders that are commonly associated. In the present study 65 men, aged 61–65 years, with impaired glucose tolerance were enrolled in a prospective, double-blind, placebo-controlled study over 12 weeks evaluating the effects of 0.75 μg alphacalcidol, a synthetic analog to the active metabolite of vitamin D. In the 26 patients with blood pressure ≥ 150/90 mmHg before treatment a significant reduction (p < 0.01) of both the systolic (SBP) and diastolic (DBP) blood pressure was found after therapy (from 171/95 to 150/88 mmHg). The effect was additive to concomitant antihypertensive treatment and was correlated (p = 0.03) to a reduction of serum levels of parathyroid hormone. Also in the whole group of patients given alphacalcidol blood pressure was moderately lowered from a mean of 152/87 ± 22/10 (SD) to 143/84 ± 17/8 mmHg. There were no relationships between the changes in body weight, blood glucose or insulin parameters and the changes in blood pressure during the trial. The findings are compatible with the concept that calcium metabolism influences blood pressure regulation and suggest that supplementation with a physiologic dose of active vitamin D could be beneficial for patients with high blood pressure.