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Biomedical subjects

S Ljunghall

Publications and source records attributed to S Ljunghall.

At least 325 records · Page 18Linked to original sources

Parathyroid pathology in hyperparathyroidism secondary to chronic renal failure.

Weights and histopathological changes in parathyroid glands were evaluated in relation to clinical and biochemical parameters in 42 patients who underwent parathyroidectomy for hyperparathyroidism (HPT) secondary to chronic renal failure. There was a positive relation (r = 0.71, p less than 0.01) between duration of renal insufficiency and total parathyroid glandular weight. The glandular weight was also closely related to the serum levels of parathyroid hormone (r = 0.67, p less than 0.01). No correlation was found between total parathyroid glandular weight or histopathological findings and clinical symptoms, serum levels of calcium, phosphate, alkaline phosphatases, calcium X phosphorus product or radiological evidence of bone disease. The enlargement of the glands was mostly uniform in the individual patient and all patients showed multiple gland involvement. This indicates that when parathyroid surgery is performed in patients with uraemia and secondary HPT, a radical approach, i.e. total parathyroidectomy with autotransplantation or subtotal parathyroidectomy, should always be used. In smaller glands only diffuse hyperplasia of parenchymal cells was generally found; fat cells were present in near-normal amounts. With increasing glandular weight, fat cells were more sparse and nodularity was common. In general, the proportion of oxyphil cells increased parallel with the total glandular weight, suggesting that this cell type is sensitive to stimulation. As a group, patients undergoing conservative renal treatment had suffered longer with renal disease, had larger parathyroid glands with more nodularity, and had more oxyphil cells than those undergoing parathyroidectomy while on haemodialysis.

Adolescent↗

Ultrasound scanning for preoperative location of parathyroid tumours.

Ultrasonic examination of the parathyroid glands has been used in 50 consecutive patients with surgically verified hyperparathyroidism. It revealed 21 of 32 parathyroid adenomas located in the neck. In 16 patients with primary or secondary (uraemic) hyperplasia, 11 out of 48 hyperplastic glands in the neck were identified by ultrasound. A parathyroid adenoma was revealed in all (3) patients with hypercalcaemic crisis. Enlarged parathyroid glands were correctly located in all (5) patients with adenomas and previous explorations of the neck, whereas two out of three glands were visualized by ultrasound prior to secondary explorations in 3 patients with hyperplasia associated with the multiple endocrine neoplasia syndrome type 1. Undetected parathyroid glands were generally smaller than those visualized by ultrasonic examination. It was often difficult to unequivocally establish that identified lesions represented parathyroid glands. Irregular noduli and cysts of the thyroid as well as lymph nodes could be misinterpreted as parathyroid lesions. A nodular thyroid goitre was present in almost half of the patients with a negative ultrasonic examination of the parathyroid glands.

Adenoma↗

Ambulatory diagnostic evaluation of 389 recurrent renal stone formers. A proposal for clinical classification and investigation.

389 consecutive renal stone formers (275 males, 114 females) were investigated in an out-patient stone clinic. Renal tubular acidosis (RTA) was found in 83 patients (22%). Proximal RTA was twice as common as the distal tubular type. The acidification defects were exclusively of the incomplete form with normal basal blood acidbase status. Main diagnoses besides RTA were primary hyperparathyroidism (3.5%), medullary sponge kidney (3.5%), infection induced stones (3%), urate stones (2%), intestinal disorder (1.5%) and cystinuria (0.5%). The metabolic evaluation was mainly based on 24 h urine sampling on a free diet. In 248 patients (64%) no distinct abnormality was considered to be primarily responsible for stone formation. Clinical and biochemical analysis of these so-called idiopathic stone formers disclosed a male preponderance (80%) and, compared to a non-stone-forming control group, a higher urinary calcium excretion, yet with a considerable overlap between the two groups. Hyperuricosuria and hyperoxaluria were rare findings. The conclusion of the study is given as a proposal for clinical classification and ambulatory investigation of renal stone formers.

Adolescent↗

Uricemia and urinary acidification in renal calcium stone disease.

Serum urate concentrations were determined in 487 consecutive patients with stone disease and in 89 controls. Male controls had higher concentrations than female controls but men and women with stones had lower concentrations than controls. Renal acidification defects, incomplete and complete forms, were found in 25 per cent of the patients with stones, with the highest frequency in patients with hyperuricemia. Patients with proximal renal acidification defects had a higher serum urate concentration than patients with normal acidification of the urine. The urinary excretion of urate was higher in hyperuricemic than in normouricemic patients but lower in patients with hyperuricemia and renal acidification defects than in those with hyperuricemia and normal acidification of the urine. This finding indicates that underexcretion rather than overproduction contributes to the higher serum urate concentration in patients with renal acidification defects. Stone patients with high serum urate levels, especially in combination with renal acidification defects, had more severe stone disease and underwent more operations than other patients with stones. Thus, hyperuricemia does not appear to be a common feature in patients with calcium stone disease, although it is associated with formation of large stones for unknown reasons.

Adult↗

The influence of a high dietary intake of purine-rich animal protein on urinary urate excretion and supersaturation in renal stone disease.

1. Eight recurrent renal stone-forming patients were housed in a metabolic ward and fed on a low (LPD) and a high (HPD) animal protein diet, which were isoenergetic. Metabolic studies were made after 2 weeks on each diet. 2. There was a 90% increase in urinary urate on HPD compared with LPD, whereas serum urate did not change consistently. 3. The urinary acid excretion increased by 200%, including a 100% increase in ammonium ion excretion. A fall in urine pH by 0.9 unit was also seen. 4. The calculated ion activities of the urines revealed a profound increase in the uric acid supersaturation, from undersaturation to supersaturation, and in some cases even surpassing the formation product ratio. The ammonium urate supersaturation also increased. The sodium urate supersaturation was unchanged, despite an induced natriuresis. 5. The risk of forming uric acid or ammonium urate crystals or stones in the urine was increased on a high protein diet, whereas the risk of forming sodium urate crystals was no greater than on a low protein diet. 6. As uric acid and ammonium urate crystals under certain conditions may adsorb a macromolecular fraction of the human urine, which inhibits calcium oxalate crystal growth, it is proposed that this mechanism, along with a decrease in urine pH, may also interfere with the inhibitory activity of calcium oxalate crystal growth and aggregation.

Adult↗

Diabetes mellitus, glucose tolerance and insulin response to glucose in patients with primary hyperparathyroidism before and after parathyroidectomy.

In a retrospectively analyzed series of 441 patients operated for primary hyperparathyroidism (HPT), the prevalence of diabetes mellitus was 8.2%, which was three times higher than in the unselected age-matched population. Following parathyroid surgery, the need for antidiabetic treatment was unchanged. The insulin response to an intravenous glucose load was enhanced preoperatively [95 mU/1 +/- 41 (SD)] in twenty-six prospectively studied patients compared to postoperative (65 +/- 41 mU/1) investigations (P less than 0.01). This response was inversely correlated (r = 2, P less than 0.01) to the serum phosphate concentrations but not related to calcium or parathyroid hormone levels. Postoperatively, most HPT patients experienced a deterioration of their glucose tolerance (t 1/2 for i.v. glucose 54 +/- 12 and 64 +/- 21 min, respectively, P less than 0.05), and one-third of them had pathological values at follow-up. Despite this, neither the fasting blood glucose levels nor the values for haemoglobin A1c were significantly affected.

Adult↗

Normalization of hypercalcaemia of primary hyperparathyroidism by treatment with methallenestril, a synthetic oestrogen with low oestrogenicity.

The oestrogenic compound methallenestril has a relatively low oestrogenicity but a marked growth-inhibiting property in experimental studies. Methallenestril was administered in a dose of 6 mg daily to 6 postmenopausal women with hypercalcaemia and primary hyperparathyroidism (HPT) for periods between 5 and 24 weeks. In all the patients, serum calcium was normalized during treatment, presumably due to a reduction of bone resorption since fasting urinary calcium and urinary hydroxyproline excretion were lowered as well. This pilot study indicates that certain oestrogenic compounds with high potencies for growth inhibition but with low oestrogenic properties might be worth further investigation in the medical management of primary HPT.

Aged↗

Evaluation of renal concentrating ability with DDAVP and pitressin.

This paper reports an attempt to develop a rapid test of the renal concentrating ability using a newly synthetized vasopressin analogue, DDAVP (1-desamino-8-D-arginine-vasopressin), which was given intravenously in a dose of 2 micrograms. Patients investigated for various endocrinological disorders were evaluated with both DDAVP and pitressin. There was a good correlation between the maximal urine osmolalities with both tests. Since DDAVP has fewer side effects and a more rapid onset of action it appears advantageous for investigations of renal concentrating ability.

Arginine Vasopressin↗

Differential diagnosis of hypercalcaemia and indications for treatment.

Primary HPT is a common medical problem of the middle-aged and elderly. The diagnosis is generally simple and seldom requires elaborate studies. The precise consequences of mild-to-moderate virtually asymptomatic disease are not clarified and provided there is regular follow-up attendance expectancy may be justified. In most patients, however, the experienced surgeon will have a more than 90% chance of success at the first exploration, which for the patient is a fairly safe procedure.

Calcium↗

Parathyroid autotransplantation. An investigation of parathyroid autograft function.

During a four-year period, 27 patients underwent total parathyroidectomy with autotransplantation of parathyroid tissue to the forearm. In order to minimize the risk of persistent or recurrent hyperparathyroidism (HPT), a routine thymic resection and a wide excision of fat tissue around the parathyroids was performed to ensure excision of possible supernumerary glands or rudimentary parathyroid tissue. The indications for operation were HPT secondary to chronic renal failure in 24 patients (22 of whom had hypercalcaemia) and persistent or recurrent primary HPT in 2 cases. One further patient, who had a multiple endocrine neoplasia syndrome type I, underwent this procedure at the primary parathyroid operation. Preoperative hypercalcaemia was reversed in all patients but three during the first postoperative days, concomitantly with a fall in the parathyroid hormone (PTH) level. Fourteen patients showed marked hypocalcaemia postoperatively, necessitating calcium or vitamin D supplementation. This medication could later be discontinued in all of them. Thirteen patients, including two of those with primary HPT, never required any supplemental therapy. Survival of the grafts was documented by several observations. In all patients normal serum calcium values were being maintained without supplemental therapy at follow-up. During induced hypocalcaemia a PTH secretory response was demonstrated in all eight studied patients with a gradient between the grafted and non-grafted arm. In two patients in whom the grafts were examined histologically 19 and 28 months after the transplantation, viable parathyroid tissue was observed. In the initial part of the study excised tissue was cryopreserved. Since persistent hypocalcaemia did not occur in our patients, we have now abandoned this safety precaution. Thus, total parathyroidectomy with autotransplantation of parathyroid tissue is a valuable method for restoring long-term parathyroid function in patients with secondary HPT and uraemia. It also appears of value in selected cases of primary HPT.

Adolescent↗

Dietary animal protein and urinary supersaturation in renal stone disease.

Eight stone-forming patients were given diets that were high (HPD) and low (LPD) in dietary animal protein, each for two weeks. Urines were collected by the end of each diet period. Urinary calcium, phosphate, urate and acids were increased on HPD whereas citrate and urine-pH decreased. The urinary supersaturation and thereby the risk of forming crystals and stones of uric acid and ammonium urate was increased on HPD. The supersaturation of calcium oxalate was unchanged, but the inhibition of calcium oxalate crystallisation may have become unfavourably affected.

Calcium↗

Optimal screening for patients with hyperparathyroidism with use of serum calcium observations. A decision-theoretical analysis.

The conventional upper 95 percentile references limit of serum calcium does not necessarily constitute an optimal decision limit in screening for patients with hyperparathyroidism. The design of optimal screening procedures has to consider (a) the prevalence of disease; (b) the relative importance of making correct classifications of patients; and (c) the influence of analytical imprecision and inaccuracy. Based on serum calcium determinations from three reference sample groups (healthy individuals, patients with hyperparathyroidism, and patients with hypercalcaemia due to malignant disease) optimal decision limits were calculated for different screening situations. Optimum was defined in terms of estimated 'costs' due to misclassification. Different values for disease prevalence were used, as well as different weighting factors reflecting the importance related to correct classification of healthy and pathological patients. For a disease prevalence of 5% the optimal decision limit varies between 2.59 and 2.65 mmol/l for a weighting ratio false positives to false negatives of between 1:5 to 5:1. For a prevalence of 0.1% the corresponding range was 2.67-2.72 mmol/l. Compared to classification on the basis of the conventional upper reference limit, the application of optimal decision limits means significantly lower costs due to misclassification. Analytical bias then has to be kept stable within +/- 0.01 mmol/l. Inter-laboratory analytical variation also has to be reduced to the same level in order to make it possible to transfer reference values, decision limits and single patient values to other laboratories.

Adolescent↗

Urinary excretion of urate in renal calcium stone disease and in renal tubular acidification disturbances.

The 24-hour urinary excretion of urate was investigated in 467 consecutive stone formers - 350 males and 117 females - and 89 apparently healthy controls with no history of stone disease. Males had a higher urinary excretion of urate than females but there was no difference between stone formers and controls. Urinary urate decreased with advancing age. Patients with a proximal tubular acidification defect had a lower urate clearance than patients with a normal acidification of the urine. Patients with hyperuricosuria presented a higher frequency of stone operations but a lower stone episode rate than matched normouricosuric stone formers. Hyperuricosuria in combination with renal acidification defects was associated with the highest frequency of stone operations. Hyperuricosuric patients also had a higher excretion of calcium than normouricosuric patients. Hyperuricosuria is not a common feature of calcium stone disease but when present is associated with a more severe stone disease in terms of stone operations.

Acidosis, Renal Tubular↗

Effects of bendroflumethiazide on urate metabolism during treatment of patients with renal stones.

Treatment with bendroflumethiazide (2.5 mg, twice daily with potassium supplements) in 63 patients with calcium-containing renal stones for a minimum period of 1 year (average duration of treatment 2.6 years) increased the serum urate values in all patients with an average of 90 mumol./l. (conversion factor: 1 mmol. urate = 183 mg.). Despite this the mean urinary urate excretion was unchanged. In the individual patient a systematic effect of therapy was evident since in patients with low pretreatment values the thiazide increased the urate output while in those with the highest levels before therapy it caused a reduction. In most patients there was a reduction of the urate clearance during therapy, which was most evident in those with the highest pretreatment clearance values. In patients with incomplete types of renal acidification defects the same effects were seen on urate metabolism during thiazide treatment as in the other, idiopathic, stone formers. Although the possible role of urate in calcium stone formation has not been definitely settled this study shows that thiazides do not cause hyperuricosuria and hence their beneficial effects on calcium excretion are not counteracted.

Adult↗

Inhibitory activity of human urine on calcium oxalate crystal growth: effects of sodium urate and uric acid.

1. Freshly voided urine from healthy subjects was pooled and ultrafiltered (10,000 daltons). The ultrafiltrable and the macromolecular portions were preincubated with calcium oxalate, uric acid and sodium urate crystals and the effects on the inhibitory activity of calcium oxalate crystal growth assessed by monitoring the disappearance of [14C]oxalate from the solution. 2. The inhibitory activity of the ultrafiltrate was higher than that of the urinary macromolecular fraction. Both uninhibited and inhibited crystal growth processes followed second-order kinetics. 3. Calcium oxalate crystals adsorbed almost all the urinary macromolecular inhibitors whereas sodium urate or uric acid crystals adsorbed only 10-20%. 4. In the presence of a metastable solution of calcium oxalate, the incubation of the urinary macromolecular fraction with sodium urate crystals caused a pronounced reduction in the inhibitory activity. A similar effect was seen with uric acid crystals, but to a lesser degree. 5. We conclude that the effect of sodium urate or uric acid crystals alone on naturally occurring urinary macromolecular inhibitors of calcium oxalate crystal growth is weak, but that in the presence of metastable calcium oxalate this is greatly enhanced. A substantial adsorption of the inhibitors on to the crystals is suggested, possibly secondary to epitaxial growth of calcium oxalate on the surface of the urate crystals.

Calcium Oxalate↗

Effects of magnesium hydroxide in renal stone disease.

Magnesium is a known inhibitor of the formation of calcium oxalate crystals in the urine and was proposed for prophylactic treatment in renal stone disease as early as the 17th and 18th centuries. We have treated 55 patients with recurrent renal calcium stone disease without signs of magnesium deficiency (normal serum magnesium, urinary magnesium, intracellular magnesium in muscle biopsies, gastrointestinal absorption of 28Mg, and magnesium loading test) from our outpatient stone clinic for up to four years with 500 mg Mg2+, in the form of Mg(OH)2, daily. The mean stone episode rate before therapy was 0.8 stones/year/patient. Forty-three recurrent renal calcium stone-formers without medical therapy served as controls. Serum magnesium increased initially but after one year returned to the pretreatment level. Urinary magnesium excretion increased promptly and remained elevated during the follow-up period. The urinary calcium excretion remained unchanged. The magnesium/calcium ratio in the urine increased and approached a value earlier found in healthy subjects without stone disease. Urinary citrate increased on therapy when analysed after three years of treatment. The mean stone episode rate decreased from 0.8 to 0.08 stones/year on treatment and 85% of the patients remained free of recurrence during follow-up, whereas 59% of the patients in the control group continued their stone formation. Side effects were few. Magnesium treatment in renal calcium stone disease is effective with few side effects. No clinical signs of magnesium excess were observed.

Adult↗

Effects of beta-adrenergic blockade on serum parathyroid hormone in normal subjects and patients with primary hyperparathyroidism.

Recent experimental studies suggest that the autonomous nervous system can effect the secretion of parathyroid hormone (PTH) and that these effects could be of physiological importance. The short-term effects of propranolol were investigated in 13 patients with primary hyperparathyroidism (HPT) and 6 normal subjects. During a 2-hour infusion there were no changes in serum PTH or calcium concentrations in any of the individuals studied. During long-term treatment of HPT patients with beta-blocking agents for 2-6 months no reduction or raised PTH levels was detected and the hypercalcaemia was unaffected. These findings question the importance of the adrenergic system for the normal regulation of serum PTH levels and its role for hormone hypersecretion in primary HPT. Our experience does not support the use of propranolol as an alternative to surgery in patients with primary HPT.

Adrenergic beta-Antagonists↗

Clinical studies on phosphate handling in hypercalcaemia.

Phosphate indices (serum phosphate, tubular reabsorption of phosphate, renal threshold phosphate concentration (TmP/GFR) and index of phosphate excretion) were studied in 88 hypercalcaemic subjects: 64 with primary hyperparathyroidism (HPT) and 24 with hypercalcaemia from other causes, predominantly malignant disease. HPT patients as a group could easily be separated from normal subjects (n = 16) and patients with functional hypoparathyroidism (n = 7) by use of the phosphate variables but these indices were of little discriminating value for the differential diagnosis between HPT and hypercalcaemia from other causes. There was no difference in the urinary cyclic adenosine monophosphate (cAMP) excretion between the two hypercalcaemic patient groups, but HPT patients had clearly elevated serum parathyroid hormone (PTH) levels compared with normal PTH concentrations in patients with other causes of hypercalcaemia. A positive correlation between cAMP and serum calcium and an inverse relationship between cAMP and TmP/GFR were found in patients with hypercalcaemic malignant disease. These findings suggest the existence of a humoral factor with PTH-like effects in malignant disease. Since PTH levels were low, the physiological actions were apparently not mediated by circulating PTH. No difference in the values for phosphate variables, PTH, cAMP or serum calcium was found between renal stone-forming and stone-free patients with HPT.

Adolescent↗