Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0221002 (primary hyperparathyroidism)
 4,921 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have measured classic markers of bone turnover, serum alkaline phosphatase (sAP), urinary hydroxyproline/creatinine ratio (uOH-Prol/creatinine) and osteocalcin (sBGP), in two bone disorders characterized by an increase in bone remodelling, namely Paget's disease of bone and primary hyperparathyroidism (PHPT) and in two other bone diseases characterized by an increase in bone resorption without the concomitant increase in bone formation, hypercalcaemia of malignancy (HM) and involutional osteoporosis (IO). Serum BGP was increased in patients with Paget's disease of bone (6.7 +/- 3.1; n = 25; p less than 0.01) and in PHPT patients (8.3 +/- 5.3; n = 20; p less than 0.005) with respect to control patients (4.2 +/- 1.2 ng/ml; n = 12). Two subgroups of patients with high and normal levels of sBGP were found in both pathologies. Serum BGP was decreased in HM patients (2.1 +/- 1.7; n = 9; p less than 0.01) and in IO patients (1.9 +/- 1.4; n = 31; p less than 0.001). Two subgroups of patients with normal and low sBGP values were found in these two last disorders. A positive linear correlation was found between sBGP and sAP (y = 14.6x + 73.7; r = 0.44; p less than 0.05) and between sBGP and uOH-Prol/creatinine (y = 0.008x + 0.007; r = 0.67; p less than 0.001) in Paget's disease of bone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Osteocalcin and bone remodelling in Paget's disease of bone, primary hyperparathyroidism, hypercalcaemia of malignancy and involutional osteoporosis. 278 49

Pharmacokinetic properties of pharmacological doses of 24,25-dihydroxyvitamin-D3 [24,25(OH)2D3] were determined in healthy volunteers. Four male subjects received 25 micrograms of 24,25(OH)2D3 as an intravenous bolus injection. Plasma concentrations of 24,25(OH)2D3, 25-hydroxyvitamin D and 1,25-dihydroxy-vitamin D were monitored during 14 days. In addition, serum ionized calcium, total calcium, inorganic phosphate, albumin, creatinine and intact hPTH(1-84) were measured during 14 days. The concentration-time curve of 24,25(OH)2D3 could be described by a two-exponential curve with half-lives of 3.0 +/- 0.9 hrs and 8.2 +/- 2.9 days (mean +/- SD). The volume of distribution was 0.19 +/- 0.02 liters/kg. None of the mentioned biochemical parameters, except serum 24,25(OH)2D3, changed markedly. In 18 subjects suffering from primary hyperparathyroidism, taking 25 micrograms of 24,25(OH)2D3 daily during three months, an average plateau level of 39 +/- 12 nmol/l of serum was observed. Bioavailability as estimated from this plateau level was approximately 70%.
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PMID:Pharmacokinetics of 24,25-dihydroxyvitamin D3 in humans. 280 47

The increase of nephrogenic cyclic AMP is an excellent index of parathyroid hypersecretion. A successful treatment of primary hyperparathyroidism results in a rapid fall in nephrogenic cAMP. In a series of 24 patients with proven primary hyperparathyroidism (hyperplasia 3, adenoma 21) and 2 patients with suspected hyperparathyroidism, the success of surgical excision was evaluated by measuring the urinary cAMP/urinary creatinine ratio (R), which in the absence of renal impairment, is proportional to the level of nephrogenic cAMP. Sequential assays of urinary cAMP and creatinine were performed during surgery; laboratory results were available within less than one hour. Among 22 patients with elevated baseline value or R, R became normal in 18 and decreased by more than 50% in 3; these findings suggested that the operation would be successful. In 1 case, R was not measured as the patient had impaired renal function. In another patient with normal baseline value of R, R did not significantly decrease after excision. Surgery failed in 1 patient, although the high value of R at the end of the operation should have prompted us to continue. Finally, in 2 patients the diagnosis was erroneous since R was lower than 0.5 as in controls. Surgeons, therefore, now have a reliable biochemical method at their disposal, but its use will be limited by its cost and complexity.
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PMID:[Surgery of primary hyperparathyroidism. Contribution of the peroperative assay of urinary cyclic AMP]. 282 56

1. Twenty-four patients with primary hyperparathyroidism were studied before and 18 restudied 6.5 months (mean) after parathyroidectomy, to investigate the pathogenesis of the hypertension which may accompany this condition. Comparison was made with age-matched patients with essential hypertension and with normotensive control subjects. 2. There was a significant inverse relationship between mean arterial pressure and 51Cr-labelled ethylene-diaminetetra-acetate (51Cr-EDTA) clearance in patients with hyperparathyroidism both before and after parathyroidectomy, but not in patients with essential hypertension. 3. Creatinine clearance appeared to overestimate glomerular filtration rate in some patients with hyperparathyroidism, falling significantly after surgery while 51Cr-EDTA clearance was unchanged. This observation may explain the failure of some previous studies to relate hypertension to impairment of renal function. 4. Plasma renin activity, plasma aldosterone and whole-body exchangeable sodium did not differ between normotensive and hypertensive patients with primary hyperparathyroidism and were unchanged after surgery. 5. Parathyroidectomy did not result in any change in blood pressure or in glomerular filtration rate measured by 51Cr-EDTA clearance.
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PMID:Hypertension and renal dysfunction in primary hyperparathyroidism: effect of parathyroidectomy. 292 21

Increased bone resorption (BR) and increased renal tubular reabsorption of calcium (TRCa) may both be involved in the pathogenesis of hypercalcemia of malignancy (HM). We have evaluated the relative importance of these two mechanisms in 33 patients with HM after extracellular volume expansion and after single infusion of clodronate (C12MDP: 500 mg iv over 8 h). The fasting urine Ca/creatinine ratio was taken as an index of BR (BRI). An index of TRCa was calculated (TRCaI) from a nomogram based on the relationship between urine Ca excretion per unit of glomerular filtration rate and plasma Ca (PCa). Mean (+/- SEM) PCa fell from 3.29 +/- 0.07 to 2.69 +/- 0.05 mmol/l three days after C12MDP (n = 33, p less than 0.001), a response similar to that obtained with repeated daily iv injections of 500 to 1000 mg C12MDP. The pathogenesis of hypercalcemia varied according to the type of neoplasm. BRI was the highest in multiple myeloma and breast tumors. TRCaI was markedly increased in squamous-cells lung, bladder, kidney and liver carcinomas, reaching levels observed in primary hyperparathyroidism. TRCaI was normal in most cases of multiple myeloma. Breast tumors appeared to be heterogeneous with respect to TRCaI. The fall in PCa in response to a single infusion of C12MDP was usually most marked in cancer patients with elevated BRI and normal TRCaI. It was very modest in patients with high TRCaI and slightly elevated BRI. In conclusion, this study confirms that stimulation of bone resorption is not the only mechanism of the maintenance of hypercalcemia of malignancy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bone and renal components in hypercalcemia of malignancy and responses to a single infusion of clodronate. 297 82

The effect of renal function on the cyclic AMP (cAMP) response to exogenous parathyroid hormone (PTH) was examined in patients with chronic renal failure (n = 22) and primary hyperparathyroidism (n = 19). In the patients with chronic renal failure there was marked resistance to the effect of exogenous PTH. In primary hyperparathyroidism the cAMP responses were variable; most of the patients with an abnormally small response having impaired renal function. After parathyroidectomy, responsiveness improved to varying degrees. In three patients repeatedly tested up to several months after parathyroidectomy, the recovery of responsiveness was a gradual process which began within days but did not, however, return to normal. Thus, there was an irreversible component to the resistance to PTH in these patients. A strong negative correlation between plasma creatinine and the cAMP response to PTH (P less than 0.001) was found in a group of patients, some with treated primary hyperparathyroidism and some with chronic renal failure. Thus, renal impairment is an important, but probably not the sole, contributory factor involved in the irreversible resistance to the action of PTH in hyperparathyroidism.
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PMID:Effect of renal function on renal responsiveness to parathyroid hormone in primary hyperparathyroidism and chronic renal failure. 298

The clinical utility of the urinary cyclic AMP:creatinine ratio in assessing parathyroid function was evaluated in 33 hypercalcemic patients and compared this with the determination of the renal component of urinary cyclic AMP. We found the discriminatory value of urinary cyclic AMP:creatinine ratio to be slightly superior and to have additional advantages. Not only did the urinary cyclic AMP:creatinine ratio show empirically somewhat better discrimination between normals and patients with primary hyperparathyroidism, but it is technically simpler than the determination of the nephrogenous cyclic AMP. Our urinary cyclic AMP excretion data show 90% discrimination of primary hyperparathyroid subjects from normals. Among all hypercalcemic patients studied who had both elevated urinary cyclic AMP and elevated parathyroid hormone (PTH) levels by radioimmunoassay (RIA), 77% had primary hyperparathyroidism, and 23% had malignancy-associated hypercalcemia. Of those patients with malignant tumors and hypercalcemia, half had elevated urinary cyclic AMP and two thirds had elevated PTH by RIA. These data suggest that these tests have little discriminatory value in differentiating primary hyperparathyroidism from malignancy-associated hypercalcemia. No hypercalcemic patient who had both serum PTH and urine cyclic AMP in the normal range was found to have primary hyperparathyroidism. This suggests that further observation and evaluation is indicated in such patients before exploratory surgery is undertaken.
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PMID:Urinary cyclic AMP:creatinine ratio and nephrogenous cyclic AMP as indicators parathyroid functional status. 300 73

109 patients with calcium-containing nephrolithiasis and 10 normal controls underwent oral calcium load test. After thorough examination, 6 of the 109 patients were diagnosed as having primary hyperparathyroidism (PHPT) and the remainder as having normocalcemic nephrolithiasis without PHPT. Following the oral calcium load test, the latter were operationally divided into 3 groups - normocalciuric nephrolithiasis (NN), n = 78; absorptive hypercalciuria (AH), n = 10, and renal hypercalciuria (RH), n = 15 - according to the criteria reported by Pak et al. Before the oral calcium load test, nephrogenous adenosine 3',5'-monophosphate (NcAMP), urinary adenosine 3'-5'-monophosphate (urinary cAMP), and plasma immunoreactive parathyroid hormone (iPTH) were determined to evaluate parathyroid function. This function, as assessed by mean basal NcAMP in the NN, AH and RH groups as well as the PHPT group, was significantly increased as compared with that in the normal controls. Within the NcAMP-elevated 4 groups, the mean basal NcAMP was highest in the PHPT group followed by the RH, AH and NN groups. In view of the mean basal NcAMP, disregarding the PHPT group, the NN and AH groups seemed to be intermediate types between the normal controls and the RH groups. Similar, but less distinctive results were obtained in the determination of urinary cAMP and plasma iPTH. On the other hand, when leaving the PHPT group out, the mean basal urinary calcium creatinine ratio (Ca/Cr) was highest in the RH group followed by the AH and NN groups, and lowest in normal controls, suggesting that the NN and AH groups were intermediate between normal controls and the RH group. The mean basal urinary Ca/Cr ratio in the PHPT group was moderately elevated but not remarkable. Almost similar tendencies were observed in 24-hour urinary calcium excretions on a calcium-restricted diet. A weakly positive correlation (r = 0.232, p less than 0.05) between basal NcAMP and basal urinary Ca/Cr ratio was observed in accumulated cases of the NN, AH and RH groups, whereas a negative correlation (r = -0.664, p less than 0.05) was obtained in normal controls. It is concluded that a possible abnormal calcium metabolism is suggested in stone formers without PHPT. Additionally, it is speculated that 'relative hypercalciuria' in NN and hypercalciuria in AH and RH might be accounted for in a single line of a primary renal leak of calcium.
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PMID:Possibility of elevated parathyroid function in patients with calcium-containing nephrolithiasis as compared with normal controls. 303 19

We studied the natural history of primary hyperparathyroidism in patients in whom the disease was discovered fortuitously by multichannel biochemical screening and who were selected for conservative management because they were asymptomatic, had no renal stone disease or radiographic osteitis fibrosa, and had serum calcium values below 3.00 mmol/L, serum creatinine levels below 133 mumol/L, and forearm bone density not more than 2.5 SD below the mean expected for age, sex, and race. One hundred and seventy-four patients meeting these criteria were encountered during a 10-yr period, of whom 80 (mean age, 61 yr) had adequate follow-up; they did not differ significantly in any initial characteristic from the remaining 94 patients. These 80 patients were followed for 1-11 yr (mean, 46 months; median, 38 months), during which there was no change, mean or individual, in any index of PTH secretion or any of its biochemical effects and no decline in forearm bone density apart from that expected from increased age. There were 4 deaths from causes unrelated to hyperparathyroidism, and the overall death rate was not increased. The data suggest that no change occurred in either the number of parathyroid cells or secretory set-point, the 2 principal determinants of basal PTH secretion. This implies a biphasic course, with a short period of disease progression followed by a long period of disease stability. Our data support the decision to withhold surgical intervention in such patients, but to establish this as the correct policy for all asymptomatic patients will require a controlled clinical trial.
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PMID:Lack of biochemical progression or continuation of accelerated bone loss in mild asymptomatic primary hyperparathyroidism: evidence for biphasic disease course. 319 82

The results are presented of an oral calcium tolerance test with 1,000 mg calcium in 20 patients with recurrent renal calcium calculosis, a woman with primary hyperparathyroidism and incipient renal failure (serum creatinine 1.8 mg%), creatinine clearance 55 ml/min) and 9 healthy persons as controls. The serum osteocalcin level was determined before and after the oral test. The results show that the serum osteocalcin level alone is of no differential diagnostic value for differentiation of the various types of hypercalciuria in patients with recurrent renal calcium calculosis. As a marker of osteoblasts functional state however the determination of serum osteocalcin level is of great importance for the early diagnosis of osteoporosis. In 3 patients with renal hypercalciuria, often leading to general osteoporosis, an acute rise of serum osteocalcin level was found after the oral calcium tolerance test. High osteocalcin level was also found in the patient with primary hyperparathyroidism and incipient renal failure.
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PMID:[Serum osteocalcin level as a marker of the functional state of osteoblasts after oral calcium tolerance test]. 326 44


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