Parathyroid exploration for primary hyperparathyroidism

Parathyroidectomy was studied retrospectively in 107 patients with primary hyperparathyroidism. This condition was diagnosed by measuring both the total serum calcium and ultrafilterable calcium (non-protein-bound) levels. The identification of ultrafilterable calcium is an important adjunct to parathyroid surgery as it allows the diagnosis of hyperparathyroidism when the total serum calcium level is normal. The surgical technique for selective parathyroidectomy and multiple biopsies was uniform. Parathyroid adenoma was discovered in 73 patients, diffuse hyperplasia in 26 and combined disease in 8. Postoperatively, two patients suffered from permanent hypocalcemia and three had hypercalcemia.     

Critical appraisal of oral calcium load test for indirect assessment of intestinal calcium absorption.

Two methods of oral calcium load or tolerance test for the indirect assessment of calcium absorption were compared. In 16 patients in whom the diagnosis of absorptive hypercalciuria was made independently, an exaggerated urinary total calcium excretion during four hours following calcium load, indicative of increased calcium absorption according to the method of Pak et al., was found in 15 patients. An abnormally high increment in urinary calcium during third and fourth hours post-calcium load, suggestive of enhanced calcium absorption by the criteria of Broadus et al., was encountered in 14 patients. However, an exaggerated urinary total calcium following calcium load was found in all 7 patients with renal hypercalciuria, whereas only 4 were shown to have an enhanced increment in calcium excretion. It is concluded that both methods are equally reliable in the detection of increased calcium absorption in absorptive hypercalciuria. However, the technique of Broadus et al. is probably superior to that of Pak et al. in the disclosure of increased calcium absorption in renal hypercalciuria.     

Parathyroidectomy: new criteria for evaluating outcome

Following successful parathyroidectomy, subjective improvement in recognized symptoms and in the overall "well being" of asymptomatic primary hyperparathyroid patients has been well documented. Because quantitative methods for measuring parathyroid hormone (PTH) and normal reference ranges of serum calcium have changed in recent years, a revised biochemical criteria for evaluating postoperative outcome has become necessary. Two hundred seventy-one selected patients were followed for an average of 6.3 years after parathyroidectomy. Although 257 patients had serum calcium levels <10.6 mg/dL during the entire follow-up period, 15 per cent of them had elevated intact PTH (iPTH) levels. Fourteen patients had calcium levels > or =10.6 mg/dL at some point during follow-up, with nine patients (64%) showing high iPTH levels and eight (57%) of them developing recurrent hyperparathyroidism (calcium > or =11 mg/dL and iPTH > or =68 pg/mL). Of the 14 remaining patients, 5 had hypercalcemia with normal iPTH levels. In patients with successfully treated primary hyperparathyroidism, the recommended annual follow-up is: 1) monitor total serum calcium only if serum calcium level is <10.6 mg/dL, or if serum calcium level is > or =10.6 mg/dL; and 2) monitor serum calcium and PTH levels, because these patients have an increased incidence of hyperfunctioning parathyroid glands, which may point to late recurrence.     

Total parathyroidectomy for posttransplantation hyperparathyroidism

The acute and short-term clinical course of 19 subjects who underwent total parathyroidectomy and forearm implantation for persistent hyperparathyroidism following successful kidney transplantation (mean [+/- SD] time after transplant 43.7 +/- 29.5 months) is described. Their mean preoperative serum calcium level of 10.8 +/- 0.5 mg% decreased to a nadir of 7.9 +/- 0.9 mg%, 62.5 +/- 27.7 hr after the operation. The lowest serum ionized calcium (1.80 +/- 0.2 mEq/L) was recorded 57 +/- 49 hr postoperatively. After an average of five hospital days, the patients were discharged with a mean serum total calcium concentration of 8.3 +/- 1.0 mg%. Three months following the operation, the mean serum total calcium concentration was 9.5 +/- 0.6 mg%. With an average follow-up of 19 months (range 3-36 months) serum total calcium was 9.6 +/- 0.6 mg%, with only one subject requiring calcium supplementation. Total parathyroidectomy with forearm implantation was associated with normalization of serum-immunoreactive parathyroid hormone concentrations and maintenance of stable allograft function. Our experience suggest that this procedure is an effective modality with a predictable postoperative recovery of parathyroid function when used to treat persistent hyperparathyroidism in the long-term survivor of renal transplantation.     

Validation of a short questionnaire for estimating dietary calcium intakes

Summary

Concern about calcium supplements, and mainly minor side effects (e.g. constipation) impacting on compliance, means that assessing dietary calcium intake is important. There is no suitable biomarker. Compared to food diaries, a short questionnaire was an efficient way of confirming that patients had adequate calcium intakes (>700 or >1,000 mg)

Introduction

Calcium is usually given alongside treatments for osteoporosis, but recent concerns about potential side effects have led to questioning whether supplements are always necessary. It is difficult to assess calcium intake in a clinical setting and be certain that the patient is getting enough calcium. The aim of this study was to determine whether a short questionnaire for estimating dietary calcium intakes in a clinical setting was fit for purpose.

Methods

We assessed dietary calcium intakes using a short questionnaire (CaQ) in patients attending an osteoporosis clinic (n?=?117) and compared them with calcium intakes obtained from a 7-day food diary (n?=?72) and a food frequency questionnaire (FFQ) (n?=?33).

Results

Mean (SD) daily calcium intakes from the CaQ were 836 (348)?mg; from the diaries, 949 (384)?mg; and from the FFQ, 1,141 (387)?mg. The positive predictive value (PPV) was >80 % for calcium cut-offs?>?700 mg and 70 % for cut-offs?>?1,000 mg. The calcium intakes for the false positives results were not far below the cut-off. For 1,200 mg, the PPV was 67 % or less.

Conclusion

The CaQ is an adequate tool for assessing whether a patient has daily calcium intakes above 700 or 1,000 mg; if below these cut-offs, it is possible that the patient still has enough calcium in the diet, which could be clarified by questioning the patient further. As there were few patients with calcium intakes above 1,200 mg a day, the CaQ cannot be recommended as a tool for confirming higher dietary calcium intakes.     

Risk factors for urinary calcium oxalate crystals as revealed by their specific enzymatic assay

Calcium oxalate crystal concentrations were assayed by a new highly specific enzymatic method in 1200 urine samples from normal subjects and stone formers. Examination of the crystals was also carried out by light microscopy and urines were analysed for oxalate, calcium, magnesium, citrate, urate, pH and osmolality. A striking positive correlation was established between urinary oxalate concentration and calcium oxalate crystal concentration as well as incidence of calcium oxalate crystals and aggregates seen by microscopy. A less striking relationship, also supported by light microscopy, was found between calcium oxalate crystal concentration and urinary calcium concentration. A small rise in calcium oxalate crystalluria was seen with increasing osmolality, but no relationship found between concentration or urinary urate, citrate or magnesium and that of calcium oxalate crystals. Higher levels of calcium oxalate crystal concentration appeared in alkaline urines in association with calcium phosphates. The dominance of urinary oxalate as a risk factor for calcium oxalate crystalluria is confirmed.     

Effects of oral furosemide and salt loading on parathyroid function in normal subjects. Physiological basis for renal hypercalciuria

With oral furosemide administration and salt loading, urinary calcium was significantly increased in 8 normal subjects, accompanied by parallel natriuresis. In spite of the excessive calcium loss in the urine, total and ionized serum calcium remained unchanged. All subjects had significant increases in nephrogenous cyclic AMP, suggesting that parathyroid activity is elevated in subjects with furosemide-induced hypercalciuria. With furosemide, fecal calcium was significantly decreased, and resultantly, there was no significant change in the cumulative calcium balance. It is suggested that urinary calcium loss with furosemide is compensated for by secondary hyperparathyroidism via increased intestinal calcium absorption in order to maintain serum calcium at a normal level. The experimental model thus mimics the condition of the renal type of idiopathic hypercalciuria.     

Evidence for a new mammalian organ. II. Calcium kinetics

The calcium content and calcium kinetics of the fatty tissue complex comprising the renal sinus organ of the rat kidney are reported. A comparison is made to control brown and white fat in the same animal. The calcium content of the renal sinus tissue is significantly greater than controls. Calcium localization in the mitochondria of the sinus tissue complex is demonstrated. Radioactive isotope studies (45Ca, 85Sr and 99mTc) indicate a dynamic exchange of calcium between the systemic pool and the sinus organ. Active accumulation appears to be operative. Supporting evidence for the existence of a portal vascular system joining the renal sinus complex and the renal parenchyma is presented. The significance of a calcium sink in the renal sinus tissue of the rat kidney is discussed.     

A urinary calcium-citrate index for the evaluation of nephrolithiasis

We have performed a multivariate analysis of urine abnormalities in patients with calcium oxalate nephrolithiasis, in which effects of gender were also considered. The characteristic of patients that most clearly sets them apart from normal people is a high level of urine calcium for any given level of urine citrate. Other urine measurements cannot improve upon the separation between patients and normals provided by urine calcium and citrate, and their abnormal relationship to each other. Normal women have higher urine citrate and lower urine calcium than normal men or patients of either sex; normal men differ from stone forming men only moderately. Direct measurements of supersaturation are not helpful in distinguishing between patients and normals, once calcium and citrate have been considered. From our analysis, we have derived a new index for evaluating the significance of urine calcium and citrate levels that seems to offer a better basis for clinical diagnosis than criteria presently in use.     

Models for protein binding to calcium oxalate surfaces

It is widely believed that proteins rich in Asp, Glu or Gla (gamma carboxyglutamic acid) interact strongly with calcium oxalate surfaces and inhibit calcium oxalate crystal growth. An alternative hypothesis would be that the interaction of Asp, Glu and Gla residues with surfaces could facilitate nucleation and crystal aggregation. Prothrombin fragment 1 and bikunin have been studied extensively as inhibitors, beta-microglobulin, transferrin and antitrypsin have been found in stone matrix and tubulin has been observed in the attachment of crystals to cell surfaces. The aim of this study is to examine how well carboxylate groups in proteins found either in stone matrix, or proposed as inhibitors, could fit with the calcium ion sub-lattice of both calcium oxalate monohydrate and dihydrate surfaces. The carboxylate groups in the acidic Asp, Glu and Gla residues were marked in the Protein Data Bank structures and matched to calcium oxalate surfaces using the Cerius 3D molecular modeling program. A contact was defined if a carboxylate oxygen atom approached a surface calcium atom in such a way that the separation was less than 6 Angstrom but greater than 2.4 Angstrom, the sum of the ionic radii. If the proteins maintain their 3D structure, the number of contacts was no more than 3 or 4 for all the proteins studied, irrespective of the calcium oxalate surface.     

Evaluation of markers for calcium homeostasis in a population of obese adults undergoing gastric bypass operations

BACKGROUND: Gastric bypass operation has become a very common procedure for treatment of obesity. Changes in calcium absorption can result in changes in total body calcium, parathyroid hormone (PTH), and vitamin D levels. There is little known about the longterm effects of Roux-en-Y gastric bypass on calcium metabolism and bone homeostasis. STUDY DESIGN: Between January 2000 and January 2006, 535 morbidly obese patients underwent standard Roux-en-Y gastric bypass. All patients were given a standard multivitamin, vitamin D, and calcium supplement starting on day 12 after the operation. Metabolic parameters, such as serum calcium levels, vitamin D, and PTH, both pre- and postoperatively, were measured and compared at several intervals. RESULTS: Four-hundred and forty-four patients were followed for a minimum of 2 years. No statistical significance was found between the pre- and postoperative serum levels of calcium and vitamin D, although vitamin D levels generally increased during the first year after operation. Serum levels of PTH were substantially higher at 18 and 44 weeks after the operation. CONCLUSIONS: Hypocalcemia did not develop in any patients during the postoperative period. Increased PTH levels were observed after gastric bypass operation. This can result in calcium mobilization of calcium from the skeleton and increased renal calcium reabsorption. Total body calcium depletion could occur from bone mobilization, if longterm calcium supplementation is not maintained. Vitamin D supplementation can assist in prevention of bone calcium depletion.     

Improved liver preservation for transplantation due to calcium channel blockade.

Intracellular calcium is an important determinant for cell death in organ hypothermic preservation for transplantation. In this study, we show that prevention of calcium entry improves the result of liver cold storage in UW solution. The isolated perfused rabbit liver was used. After 48 hr of cold storage in UW solution, bile production was reduced by 70% (P less than 0.005). However, by adding the calcium channel blockers verapamil or nifedipine (40 microM) to the UW solution, this reduction was abolished, and the livers produced the same amount of bile as unpreserved livers. Furthermore, addition of the calcium channel activator, BAY K8644 (40 microM), to the UW solution, reduced bile production by 50% (P less than 0.01) already after preservation for 24 hr. We conclude that calcium entry is of importance for liver function after preservation and cold storage, and that including a calcium channel blocker to the preservation solution makes long-term liver preservation safer.     

Calcium levels as a risk factor for delayed graft function

BACKGROUND: Delayed graft function (DGF) occurs in up to 50% of renal transplants. Hypercalcemia and hyperparathyroidism are associated with impaired renal function. Little is known on the effects of serum calcium levels on DGF. This issue was addressed in the current study. METHODS: Patients receiving a cadaveric renal transplant between 1986 and 1996 were studied. Data on calcium metabolism and histologic characteristics of nephrocalcinosis, acute tubular necrosis (ATN), and acute rejection in biopsies taken within the first week were related to the occurrence of DGF. RESULTS: The incidence of DGF in a cohort of 585 cadaveric transplants was 31%. DGF correlated independently with serum calcium levels (odds ratio [OR] 1.14 [95% confidence interval (CI) 1.04-1.26] per 0.1 mmol/L). The use of calcium channel blockers before transplantation protected against DGF (OR 0.5 [95% CI 0.29- 0.87]). In this selected group, we found an association with histologic signs of ATN and DGF. However, most of the biopsies also had features of acute rejection or nephrocalcinosis. Nephrocalcinosis was found in 12 of 71 biopsies and was not associated with serum calcium levels or the occurrence of DGF. CONCLUSIONS: In this study, serum calcium levels were independently associated with DGF. This could not be explained by the presence of microscopic nephrocalcinosis. Therefore, DGF is attributed to high intracellular calcium levels. Because calcium supplementation and vitamin D analogues are commonly used in dialysis practice, hypercalcemia influences long-term graft outcome by its effect on DGF. The pretransplant use of calcium channel blockers has a protective effect on the occurrence of DGF.     

Evidence for adaptation of the entire PTH-calcium curve to sustained changes in the serum calcium in haemodialysis patients

BACKGROUND: Based on in vitro studies, the set point of calcium has often been considered to represent an intrinsic property of parathyroid gland function. However, in the dialysis patient, the serum calcium does not consistently reflect the magnitude of hyperparathyroidism; in addition, little information is available on whether the PTH-calcium curve is modified by sustained changes in the serum calcium. The present study in haemodialysis patients was designed to evaluate whether the set point of calcium and the dynamics of PTH secretion were modified by sustained changes in the serum calcium. METHODS: To accomplish the goal of the study and obtain a wide range of changes in the serum calcium, haemodialysis patients were dialysed with either a 1.75 mM (group I) or a 1.25 mM (group II) calcium dialysate for 2 weeks, and were then changed to a 1.25 mM (group I) or a 1.75 mM (group II) calcium dialysate for an additional 2 weeks. At the end of the first and second 2-week periods, low and high calcium studies were performed to obtain PTH-calcium curves. RESULTS: In group I, the serum ionized calcium decreased with the lower calcium dialysate (P < 0.02) and the set point of calcium was reduced (P < 0.02); in group II, the serum calcium did not change and the set point of calcium was not modified. When both groups were evaluated together, the delta serum calcium correlated directly with the delta set point of calcium (r = 0.87, P < 0.001) and inversely with the delta PTH (r = -0.73, P < 0.005); at the same time, an inverse correlation was observed between the delta PTH and the delta set point of calcium (r = -0.67, P < 0.01). Moreover, the delta serum calcium correlated with both the delta ratio of basal/maximal PTH (r = -0.71, P < 0.005) and the change in predialysis serum calcium necessary to maximally stimulate PTH (r = 0.84, P < 0.001); these latter two are indicators of the position of PTH along the PTH-calcium curve. Finally, in group I the entire PTH- calcium curve shifted to the left on the 1.25 mM calcium dialysate as compared with the 1.75 mM calcium dialysate. CONCLUSION: The findings of the present study indicate that: (1) the set point of calcium followed sustained changes in the serum calcium independently of PTH secretion, and (2) the parathyroid gland was able both to adjust the position of PTH secretion on the PTH-calcium curve and to adapt PTH secretion to the existing serum calcium concentration.      

A special rongeur for removal of extensively calcified mitral valves

A rare complication of advanced mitral valve disease occurs when calcium extends from the valve downward along the wall of the left ventricle into the ventricular cavity. This unusual condition can be recognized on fluoroscopy because the calcium is visible at right angles to the calcium in the valve. The surgeon faces a very difficult technical problem because it is hard to obtain adequate exposure and to remove the calcium without injury to adjacent tissues or loss of calcific fragments, with resulting embolization. Such difficulties were encountered a year ago in a patient undergoing mitral and aortic valve replacement and ultimately resulted in the patient's death. After this event, the special rongeurs described here were designed.     

A model system for assessing physicochemical factors affecting calcium absorbability from the intestinal tract

An in vitro model system was utilized to critically examine physicochemical factors that could play a role in determining the amount of potentially absorbable ionic calcium as well as soluble complexes in the proximal jejunum following ingestion of tricalcium dicitrate, calcium carbonate, or tricalcium diphosphate. The solubility of calcium salts (500 mg calcium each) was tested in 300 ml water containing varying amounts of hydrochloric acid (0, 0.72, 2.4, 7.26, and 24.2 mEq) intended to mimic achlorhydric to peak acid secretory states. Whereas 20% of calcium citrate dissolved in the absence of hydrochloric acid, a negligible amount of calcium carbonate and calcium phosphate underwent dissolution. In solutions containing 0.72-7.26 mEq hydrochloric acid, calcium citrate was more than twofold soluble than calcium carbonate, and calcium phosphate had intermediate solubility. At simulated peak acid secretion, all three salts were completely soluble, or nearly so. To simulate pancreatic bicarbonate secretion, the filtrates obtained from solubility studies were titrated to pH 5, 6, and 7 with sodium hydroxide. Reprecipitation of calcium citrate and calcium carbonate did not occur. However, substantial calcium phosphate reprecipitation took place especially at high pH and in filtrates derived from high hydrochloric acid content. In filtrates derived from reprecipitation experiments (at pH 6 and 7), anionic complexation of calcium was calculated in order to estimate the amount of ionic and complexed calcium. Considerable amount of calcium from dissolved calcium citrate was complexed (60-65%), principally as soluble CaCit-, whereas calcium complexation was negligible in the calcium carbonate and calcium phosphate systems.     

Does calcium contribute to the effectiveness of a coagulum for pyelolithotomy?

Adding calcium to a mixture of thrombin and fibrinogen increased the breaking strain of the resultant coagulum by 10-fold, but did not significantly reduce the length to which it could be stretched. There was no detectable change in the time taken for the coagulum to dissolve in urine. Simulation pyelolithotomies were performed on pig kidneys containing ball-bearings which represented calculi. Coagula formed with calcium were significantly more effective at retrieving the ball-bearings than coagula without calcium. It is concluded that the ideal coagulum formula should include 1 mmol of calcium.     

Oxalate loading test for outpatients with calcium oxalate stones

A spinach loading experiment was performed on 9 normal subjects, 25 outpatients who were single calcium oxalate stone formers and 25 recurrent calcium oxalate stone formers. The experimental diet contained 445 mg of total oxalate, 163 mg of soluble oxalate and 115 mg of calcium. Urinary oxalate excretion was observed 2 hrs before and 6 hrs after the experimental diet was consumed. There was no significant difference in urinary oxalate excretion in preloading urine of normal subjects and stone formers. However, urinary oxalate excretion in postloading urine was significantly elevated in stone formers. This loading test is recommended as a simple and valuable screening method of hyperabsorption of oxalate on outpatients with calcium oxalate stones.     

Calcium Mobilization is Required for Spreading in Human Osteoblasts

Adhesion-induced changes in intracellular calcium concentration ([Ca²⁺]_i) were measured in populations of human osteoblasts spreading on bone matrix proteins. In cells spreading on collagen type I, fibronectin, or laminin, average values for [Ca²⁺]_i were found to increase approximately 2× over baseline and then decline. The speed with which [Ca²⁺]_i increased and declined was dependent upon the matrix protein on which the cells were plated but was generally complete within 1 hour from the time of plating. Calcium mobilization was found to be due to influx of calcium across the osteoblast plasma membrane and was integrin dependent. Carboxyamido triazole (CAI), a specific inhibitor of nonvoltage-dependent calcium channels, or BAPTA-AM, a chelator of intracellular calcium, inhibited osteoblast adhesion and spreading on collagen type I, fibronectin and laminin in a dose-dependent manner. In conclusion, these results demonstrate that calcium mobilization is induced upon integrin-ligand contact and that calcium influx is required for cell adhesion and spreading. Received: 10 September 1999 / Accepted: 18 January 2000     

Early biochemical response to parathyroidectomy for primary hyperparathyroidism and its predictive value for recurrent hypercalcemia and recurrent primary hyperparathyroidism

BackgroundThe traditional definition of cure after parathyroidectomy (PTX) for primary hyperparathyroidism is normocalcemia. Our hypothesis was that early postoperative levels of serum calcium and parathyroid hormone after PTX would have predictive value for later recurrence.MethodsWe performed a retrospective study of 1,146 patients with primary hyperparathyroidism who underwent PTX and had long-term biochemical follow-up. The first postoperative serum level of calcium and parathyroid hormone values were used to categorize patients into the following four early biochemical response groups: (1) complete response (normal calcium and normal parathyroid hormone), (2) partial response with hyperparathormonemia (normal calcium and increased parathyroid hormone), (3) partial response with hypercalcemia (increased calcium and normal parathyroid hormone), and (4) non-response (increases in both calcium and parathyroid hormone). Incidences of recurrent hypercalcemia and recurrent primary hyperparathyroidism >6 months after operation were then analyzed.ResultsThe overall rate of any elevated serum levels of calcium and any increase in serum levels of parathyroid hormone during >6-month follow-up was 9.8% (112 of 1146), with 6.6% (57 of 861) for group 1, 27% (35 of 129) for group 2, and 16% (20 of 127) for group 3 (P < .02). Partial biochemical responses with either increased serum calcium or increased parathyroid hormone levels were the strongest predictors of any episode of increased serum levels of calcium after 6 months and was associated with 2.7× to 4.3× the risk of recurrent primary hyperparathyroidism, respectively.ConclusionThis study demonstrates the importance of measuring parathyroid hormone in the early postoperative period to better predict later recurrent primary hyperparathyroidism.