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

Since Sherwood's report in 1979, contradictory findings have been published with regards to the treatment of primary hyperparathyroidism with cimetidine. We studied 16 patients with primary hyperparathyroidism treated with 1,200 mg of Cimetidine and followed-up clinically and biochemically. A decrease in serum calcium and urinary CAMP was observed after the fourth week of cimetidine therapy with no significant change in parathormone levels. In none of the cases did Cimetidine seem to provide a treatment of hyperparathyroidism, a condition which remains curable with surgery.
 ...
PMID:[Cimetidine treatment of primary hyperparathyroidism]. 632 36

In vitro parathyroid hormone secretion of normal (n = 10) and adenomatous (n = 20) human parathyroid glands was compared in response to different calcium (Ca++) concentrations. The glands, prepared for tissue culture immediately after surgical removal, were incubated under identical conditions for 6 h. The medium was changed hourly and analyzed for PTH and cAMP using radioimmunoassay. During the first 2 h of the experiment, the Ca++ concentrations of all preparations was kept constant at 1.2 mM equivalent to the normal Ca++ level of the intercellular space. The PTH level of the 2nd h was defined as reference value corresponding to 100%. After the 2nd h of incubation the Ca++ concentration in the medium was shifted either to low (0.9 or 0.6 mM) or to high (1.9 or 2.6 mM) values. In low Ca++ concentrations (0.6 mM) the normal parathyroid glands responded by stimulation of the PTH release up to 310% in relation to the reference value, whereas the adenomas enhanced the PTH release to 160% only. The incubations in 0.9 mM Ca++ resulted in a slightly lower degree of stimulation. During the incubation in high Ca++ the PTH secretion was reduced to 28% by normal glands and to 52% by adenomatous parathyroid glands. Movements of cAMP measurements paralleled PTH values. The study provides evidence for an abnormally low responsiveness of parathyroid adenomas to Ca++ when compared with normal glands. The reduction in Ca++ responsiveness of adenomatous cells appears to have a fundamental role in primary hyperparathyroidism since the tumour cells may obviously recognize normal Ca++ levels as 'hypocalcaemic' and react by a stimulated PTH secretion.
 ...
PMID:Differential calcium response of normal and adenomatous parathyroid glands. 650 6

PTH causes dose dependent transient vasodilatation in various vascular beds, specifically renal, coeliac, coronary, but not osseous. It has an acute dose-dependent hypotensive effect in the intact animal which is not mediated by alpha- or beta-adrenergic, cholinergic or histaminergic mechanisms. Aortic medial smooth muscle cells respond to PTH with an increase of cAMP, cGMP and, presumably via protein kinase, with activation of phosphorylase B kinase. The acute vasodilatory effect of PTH is antagonised by indomethacin and diclofenac as well as by ouabain, suggesting that the membrane Na-K pump and prostaglandins are involved in PTH-induced vasodilatation. Parathyroidectomy and a high calcium diet attenuate the rise of arterial pressure in experimental hypertension, pointing to some permissive effect of PTH for development hypertension. This is most likely due to long term effects of PTH on vessel wall calcium content and exchange. This chronic effect of PTH may explain the high prevalence of hypertension in patients with primary hyperparathyroidism.
 ...
PMID:Vascular effects of parathyroid hormone (PTH). 675 27

The basal values of plasma vitamin D metabolites were evaluated in patients with primary hyperparathyroidism (1 degree HPT, n = 31), hypoparathyroidism (HP, n = 7), pseudohypoparathyroidism (PHP, n = 4) and normal controls (n = 21). Plasma 25-hydroxyvitamin D (25-OH-D) in 1 degree HPT (9.0 +/0 7.3 ng/ml, mean SD) was significantly lower than that of normal controls (17.9 +/- 5.5ng/ml)(p less than 0.001), and in particular 1 degree HPT classified as the skeletal type showed extremely low value (4.7 +/- 4.6 ng/ml). Plasma 1, 25-dihydroxyvitamin D [1, 25-(OH)2D] was significantly higher in 1 degree HPT (69.1 +/- 31.4pg/ml)(p less than 0.001) and significantly lower in Hp (15.2 +/- 11.0 pg/ml) (p less than 0.001) compared to normal controls (37.2 +/- 13.8pg/ml), although there was no significant difference in PHP (22.3 +/- 17.5 pg/ml). Plasma 24, 25-dihydroxyvitamin D [24,, 25-(OH)2D] in 1 degree HPT (1.06 +/- 0.55 ng/ml) was significantly lower than that of normal controls (1.73 +/- 0.62 ng/ml) (p less than 0.05), and particularly 1 degree HPT classified as the skeletal type showed a marked low value (0.85 +/- 0.27 ng/ml), whereas no significant differences were seen in HP (1.84 +/- 0.46 ng/ml) or PHP (1.34 +/- 0.22 ng/ml). There were slight but significant correlations between either plasma 25-OH-D and 1, 25-(OH)2D (r = -0.350, p less than 0.05), or plasma 25-OH-D and 24, 25-(OH)2D (r = 0.356, p less than 0.05), or plasma 1, 25-(OH)2D and 24, 25-(OH)2D (r = -0.444, p less than 0.01) in all subjects. In addition, relationships between plasma vitamin D metabolites and other indicators of parathyroid function in all subjects were analyzed. There were positive correlations between plasma 1, 25-(OH)2D and serum Ca (r = -0.621, p less than 0.001) or urinary cAMP (r = -0.671, p less than 0.001) or nephrogenous cAMP (r = -0.689, p less than 0.001), while negative correlations were seen between plasma 1, 25-(OH)2D and serum P (r = -0.680, p less than 0.001) or %TRP (r = -0.663, p less than 0.001). On the other hand, there were negative correlations between plasma 24, 25-(OH)2D and serum Ca (r = -0.457, p less than 0.01) or urinary cAMP (r = -0.562, p less than 0.005) or nephrogenous cAMp (r = -0.561, p less than 0.005), and a positive correlation was seen between plasma 24, 25-(OH)2D and %TRP (r = 0.519, p less than 0.005). After parathyroidectomy, a distinct depression of plasma 1, 25-(OH)2D and reciprocal elevation of plasma 24, 25-(OH)2D were observed in 1 degree HPT. Furthermore, there was a clear elevation of plasma 24, 25-(OH)2D as well as plasma 1, 25-(OH)2D after treatment with maintenance doses of 1 alpha-OH-D3 or 1 alpha, 25-(OH)2D3 in HP and PHP. It is concluded that plasma vitamin D metabolites are very useful as the indicators of parathyroid function.
 ...
PMID:[Plasma vitamin D metabolites in parathyroid diseases (author's transl)]. 698 Jan 45

Humoral hypercalcemia of malignancy (HHM) results from elaboration by tumors of a circulating bone-resorbing factor(s). THe specific mechanism responsible for this bone resorption is poorly understood, and no comprehensive study employing quantitative histomorphometric analyses of bone biopsies obtained from living patients with HHM has been reported. We describe bone histology and quantitative bone histomorphometry in bone biopsies obtained from seven patients defined biochemically (elevated nephrogenous cAMP excretion) and histologically (no tumor in biopsy sample) as having HHM. These biopsies are compared to biopsies from nine patients with primary hyperparathyroidism (HPT). Compared to patients with HPT, those with HHM displayed (mean +/- SD) greater osteoclastic activity (osteoclast surface, 8.6 +/- 6.1% vs. 2.7 +/- 1.5%; P less than 0.001) and more frequent empty lacunae (9.2 +/- 4.0% vs. 5.8 +/- 3.0%; P less than 0.01), but markedly reduced osteoblastic surface (2.5 +/- 3.1% vs. 13.8 +/- 7.0%; P less than 0.001), osteoid surface (12.9 +/- 11.9% vs. 42.0 +/- 15.0%; P less than 0.001), and osteoid volume (0.3 +/- 0.3% vs. 1.3 +/- 1.0%; P less than 0.01). These findings directly confirm the presence of humorally mediated bone resorption and indicate a striking uncoupling of osteoclast and osteoblast activities in bone from patients with HHM. These findings are in sharp contrast to those in HPT patients, where osteoclast and osteoblast activities are tightly coupled, and net skeletal calcium loss is minimal. This uncoupling provides a mechanism for the marked skeletal calcium losses observed in patients with HHM.
 ...
PMID:Quantitative bone histomorphometry in humoral hypercalcemia of malignancy: uncoupling of bone cell activity. 708 51

Urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) transiently increases after PTH(1-34) infusion in idiopathic hypoparathyroidism (IHP) but this response is impaired in pseudohypoparathyroidism (PHP) type I. We investigated the effects of endogenous PTH, exogenous calcitonin (CT), and dibutyryl cAMP (DBcAMP) on urinary excretion of NAG. Urinary NAG excretion in 14 patients with primary hyperparathyroidism (1 degree HPT) was more than in normal subjects (P < 0.001) and decreased after parathyroidectomy (P < 0.01). Urinary NAG excretion increased after the infusion of 1.5 MRC/kg of eel CT in eight normal subjects (P < 0.001), two patients with IHP, and a patient with PHP type Ib but not in a patient with PHP type Ia. The increases of urinary NAG excretion by CT and by PTH(1-34) were positively correlated with the increases of urinary cAMP excretion (r = 0.752; P < 0.001 and r = 0.534; P < 0.002, respectively). Urinary NAG excretion increased after DB-cAMP infusion in five normal subjects (P < 0.01), two patients with IHP, and two with PHP type I. The increase of urinary NAG by 6.0 mg/kg of DBcAMP was more than by 2.5 mg/kg of DBcAMP in normal subjects (P < 0.01). The increase of urinary NAG by 2.5 mg/kg of DBcAMP in PHP type I was comparable with that by 6.0 mg/kg in normal subjects, suggesting a hyperresponsiveness to DBcAMP in PHP type I. Urinary excretion of NAG is a useful indicator of renal tubular responsiveness to PTH and CT. Cyclic AMP-dependent mechanism is probably involved in PTH and CT-induced increase in urinary excretion of NAG.
 ...
PMID:The effect of endogenous parathyroid hormone, exogenous calcitonin, and dibutyryl cyclic AMP on urinary excretion of N-acetyl-beta-D-glucosaminidase. 805 64

We compared the effect of orally administered 100 mg of hydrochlorothiazide (HCTZ) among eight patients with pseudohypoparathyroidism (PHP) type I, 11 patients with idiopathic hypoparathyroidism (IHP), and 12 patients with primary hyperparathyroidism (1'HPT). Patients with PHP type I or with IHP were studied during the treatment with 1 alpha-hydroxylated metabolites of vitamin D3. HCTZ raised serum levels of calcium (Ca) in 1'HPT (P < 0.001) and PHP type I (P < 0.01) but did not increase urinary excretion of Ca. Serum parathyroid hormone (PTH) in PHP type I decreased (P < 0.02) after HCTZ administration in response to the increase in serum Ca. HCTZ did not raise serum levels of Ca in IHP but increased urinary excretion of Ca in this group (P < 0.01). HCTZ suppressed tubular reabsorption of phosphate (P) in IHP (P < 0.01) and 1'HPT (P < 0.05) but not in PHP type I. Urinary excretion of cAMP did not change after HCTZ administration in PHP type I, IHP, or 1'HPT. Endogenous PTH modulated the effects of HCTZ on Ca mobilization from bone and renal reabsorption of Ca in PHP type I with normal or high serum levels of PTH and in 1'HPT with high serum levels of PTH. The inhibitory effect of HCTZ on renal tubular reabsorption of P (probably from proximal tubules) was independent of PTH. The resistance to this inhibitory effect of HCTZ on P reabsorption in PHP type I suggested a proximal tubular dysfunction in this disorder.
 ...
PMID:The modulatory effect of endogenous parathyroid hormone on the action of hydrochlorothiazide in pseudohypoparathyroidism type I. 808 49

Iliac crest biopsies of normals, uremic patients and subjects with primary hyperparathyroidism (pHPT) were investigated. It appeared that serum 1,25- and 24,25-(OH)2-D3 correlated inversely with basal adenylate cyclase (AC) activity and relative PTH-stimulated AC, respectively. Net PTH-elicited AC (dPTH-AC) activation hence reflected individual vitamin D status. The combination variable serum PTH (s-PTH) x dPTH-AC x [H+] correlated well with resorption surface (RS) in both normals, patients with pHPT or subjects with uremia, while s-PTH, dPTH-AC activity or pH as single variables were only marginally related to RS. For all subjects analyzed, osteoid volume (OV) correlated positively with serum alkaline phosphatase but negatively with serum 1,25-(OH)2-D3. OV showed no correlation with dPTH-AC, while the relationship between OV and s-PTH was strong, suggesting that PTH stimulates osteoid deposition via some signalling pathway other than cAMP. In normals, OV was inversely proportional to s-PTH, due to homologous desensitization of this signalling system. Furthermore, s-PTH was negatively correlated with urine cAMP due to homologous desensitization of the effect of PTH on the kidney 25-(OH)-D3 1 alpha-hydroxylase. This phenomenon was absent in uremic patients. Evaluation of variables by artificial intelligence showed that the prototype uremic patient exhibited serum creatinine > 900 microM, RS > 0.12, pH between 7.15 and 7.34 and s-PTH x dPTH-AC x [H+] between 0.5 and 3.7 units with the distinguishability index 'very good' (< 5% overlap) towards normals. Average similarity of uremic patients with the prototype for normal subjects was only 22%. Cluster analysis of all the variables was conducted for comparison and yielded less clinically relevant information. Hence, emulation done by the expert system was superior and clearly indicates that present treatment modalities restore normal bone turnover only to a minor degree or not at all.
 ...
PMID:PTH-stimulated adenylate cyclase activity and bone histomorphometry in iliac crest biopsies in the evaluation of uremic patients: a pilot study with the use of artificial intelligence. 816 16

Primary hyperparathyroidism (PHP) is rare during pregnancy and has been claimed to be associated with significant increase of neonatal morbidity and mortality. Whether the well recognized changes in calcium (Ca) and phosphate (Pi) homeostasis occurring in pregnancy might influence the biochemical expression of PHP is unclear. We evaluated biochemical parameters of calcium and phosphate metabolism in two cases of PHP in pregnancy diagnosed in the third trimester (patient 1) and in the second trimester (patient 2). Both patients displayed increase in protein-adjusted plasma Ca, bone resorption evaluated by the fasting urinary Ca-to-creatinine ratio, renal tubular reabsorption of Ca, urinary cAMP excretion and decrease in renal tubular reabsorption of Pi. These alterations were identical to those found in 12 non-pregnant women with PHP. The biochemical expression of PHP did not change after delivery in patient 1. This patient underwent the excision of a 1 g parathyroid adenoma on the 13th day after delivery, which led to normalization of all biochemical parameters. The lowest plasma Ca of the newborn of patient 1 was 2.02 mM 72 hours after birth. Thus, the results indicate that these two pregnant women with PHP displayed biochemical alterations of calcium and phosphate metabolism similar to those observed in non-pregnant women with primary hyperparathyroidism.
 ...
PMID:Alterations of calcium and phosphate metabolism in primary hyperparathyroidism during pregnancy. 839 30

The hypercalciuria that eventually remains after the successful removal of a solitary parathyroid adenoma may originate from excessive intestinal calcium absorption, bone resorption or deficient renal reabsorption. In order to clarify this question, ten patients surgically cured from primary hyperparathyroidism (PHPx), ten age-matched normal subjects and five nephrolithiasic patients with renal hypercalciuria (RH) were studied after five days on a low calcium diet, either during fasting or after oral calcium load. Fasting serum calcium, amino-terminal and intact PTH levels and also urinary cAMP excretion were normal in every individual patient. Serum ionized calcium and inulin clearance (GFR) were used for calculations of the filtered load (FL Ca) and the fractional excretion of calcium (FE Ca). Six PHPx patients displayed fasting calciuria above the upper limit calculated for control subjects, despite having the lowest GFR and FL Ca (p < 0.05 vs control). These patients (h-PHPx) had a small calciuric response to oral calcium load. Serum 1,25-(OH)2D3 and 25OHD3 did not correlate with calciuria. Our findings exclude intestinal hyperabsorption and excessive bone resorption in h-PHPx patients, and strongly suggest a renal tubular defect in calcium reabsorption as the cause of their hypercalciuria. This defect could be primary, as in RH, but only three hPHPx patients had recurrent kidney stones before surgery. On the other hand, as a negative correlation between GFR and FE Ca was only found in PHPx patients, it seems probable that the disturbances in glomerular and tubular functions were secondary to the long standing hypercalcemic hyperparathyroidism.
 ...
PMID:The cause of maintained hypercalciuria after the surgical cure of primary hyperparathyroidism is a defect in renal calcium reabsorption. 885 86


<< Previous 1 2 3 4 5 6 7 8 Next >>