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Biomedical subjects

U Kracht

Publications and source records attributed to U Kracht.

18 recordsLinked to original sources

Biochemical markers of bone turnover, intact serum parathyroid horn and renal calcium excretion in patients with pseudohypoparathyroidism and hypoparathyroidism before and during vitamin D treatment.

In addition to the well-documented hyporesponsiveness of the kidney, resistance to parathyroid hormone (PTH) has been postulated for bone in pseudohypoparathyroidism type I (PHP). In some of these patients reduced bone density and even frank osteitis fibrosa suggest osteoclastic overactivity. To address the possibility that the skeletal system of patients with PHP may be affected by their increased PTH secretion we measured intact serum PTH and three biochemical markers of bone turnover in a large number of patients with PHP (n = 20). The results were compared with subjects with low (hypoparathyroidism, HP n = 29), normal (controls, n = 31) and high (primary hyperparathyroidism, 1 degree HPT, n = 13) PTH secretion. Both markers of osteoblastic bone formation, alkaline phosphatase activity and osteocalcin concentration in serum, and one index of osteoclastic bone degradation, the urinary hydroxyproline/creatinine ratio (OH-P/Cr), were decreased in HP and increased in 1 degree HPT, whereas only OH-P/Cr was elevated in patients with PHP. Although intact serum PTH was significantly more increased in PHP than in 1 degree HPT, the markers of bone turnover were not significantly different in these two groups, suggesting some bone resistance in the patients with PHP. In these subjects intact serum PTH was elevated even at normocalcaemia during vitamin D treatment with a negative correlation with the respective serum calcium concentration (r = -0.69, P less than 0.001), indicating an elevated set-point for the suppression of their parathyroid glands. OH-P/Cr was negatively related to serum calcium in PHP, it normalized in most patients during normocalcaemia induced by vitamin D treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Intact serum parathormone (PTH 1-84). A suitable parameter for the diagnosis of calcium metabolism disorders].

Intact parathormone (PTH 1-84) was measured with a new immunoradiometric method in serum from 83 children and adults with various abnormalities of calcium metabolism. The results were compared with those of an assay of midregional PTH fraction (44-68). Both measurements discriminated well between normal controls and patients with primary or secondary hyperparathyroidism. In patients in chronic renal failure intact PTH measurement was best for demonstrating parathyroid secretion. An important advantage of the new method is in the diagnosis of PTH hyposecretion in hypoparathyroidism and of tumour hypercalcaemia, which is not possible by mid-regional PTH determination. Intravenous injection of calcium (2 mg/kg over 5 min) and of synthetic PTH fragment (6 U/kg 1-38 hPTH over 2 min) caused a reduction in intact serum-PTH to about half the initial value after five minutes. Measuring intact PTH is thus a suitable method for determining both raised and decreased parathyroid secretion in disease and in the course of function tests. It is simple to perform, subject to only minor interference, and thus suitable also as a routine laboratory test.

Adolescent↗

[Disorders of calcium and bone metabolism in glucocorticoid treatment].

The effects of glucocorticoids on calcium and bone metabolism were investigated in 11 children (aged 6 months to 13 years) who were treated with dexamethasone, prednisolone and depot-ACTH because of different disorders. Alkaline phosphatase activity and osteocalcin in serum, representing indices of osteoblastic bone synthesis, and urinary hydroxyproline in relation to creatinine in morning fasting urine specimens, an index of osteoclastic bone degradation, decreased by 53-61% from baseline (P less than 0.01), with a highly significant relationship of all 3 indices to each other. Additional influences of glucocorticoids were hyperphosphaturia due to decreased renal phosphate reabsorption not mediated by secondary hyperparathyroidism, as well as marked hypercalciuria. As the consequence of the present study the following prophylactic or therapeutic recommendations are given during steroid-treatment: 1. Approvement of the negative balance of calcium and phosphate by correcting the hypercalciuria with hydrochlorothiazide, and the hypophosphatemia with oral phosphate and 2. in elder children with osteoporosis, stimulation of the decreased osteoblastic bone formation by sodium fluoride.

Adolescent↗

A simplified diagnostic test in hypoparathyroidism and pseudohypoparathyroidism type I with synthetic 1-38 fragment of human parathyroid hormone.

Bovine parathyroid extract of E. Lilly (Indianapolis), which has been used to differentiate pseudohypoparathyroidism (PHP) and hypoparathyroidism (HP) is no longer available. We therefore evaluated the usefulness of the synthetic 1-38 fragment of human parathyroid hormone (1-38 hPTH), the biologically active part of the intact hormone, in a simplified modification of the traditional Ellsworth-Howard test. 1-38 hPTH was slowly injected over 2 min at a dose of 0.5 micrograms/kg body weight in healthy children and adults (n = 7), as well as in children with HP (n = 4) and PHP (n = 4). In the controls PTH administration induced a significant rise of plasma cAMP (at least 146 nmol/l), urine cAMP and serum prolactin, as well as a decrease of the tubular phosphate reabsorption. The respective responses were similar in the children with HP but markedly impaired in the patients with PHP. In four healthy adults a second PTH administration at an interval of 3 h induced a comparable response of cAMP and prolactin, indicating that these PTH effects are reproducible and not impaired by the first injection. The two PTH administrations caused a significant but variable rise of serum 1,25-dihydroxy-vitamin D in all four adults. In conclusion 1-38 hPTH has effects on the kidney and anterior pituitary similar to purified parathyroid extracts but has the advantage of being chemically and biologically defined and well tolerated. Since timed urine collections may be unreliable in young children, the plasma cAMP measurement at 5 and 10 min after the PTH injection is a good substitute for the traditional Ellsworth-Howard test, peak values over 100 nmol/l being regarded as a normal response.

Adolescent↗

Evaluation of serum osteocalcin as an index of altered bone metabolism.

Recent evidence suggests that the protein osteocalcin is like the bone alkaline phosphatase produced by osteoblasts and circulates in human blood. With the introduction of a radioimmunoassay for serum osteocalcin it was hoped that this test would provide a useful index of altered bone metabolism. Therefore serum osteocalcin was measured in 88 controls and 112 patients with disorders of calcium and phosphate metabolism, isolated elevation of alkaline serum phosphatase in the absence of disease (isolated hyperphosphatasaemia) and children prone to osteopenia. In the controls serum osteocalcin was higher in children less than 15 years (median and range: 11.9, 7.7-15.3 ng/ml) than in adults (3.7, 2.6-5.2 ng/ml) and was highly correlated to alkaline serum phosphatase activity (r = 0.87, n = 88, P less than 0.01). Osteocalcin was elevated in primary hypoparathyroidism, low in untreated hypoparathyroidism but normal in hypoparathyroidism (including pseudohypoparathyroidism) during vitamin D treatment. The bone protein was low-normal and increased to high-normal levels during vitamin D therapy in vitamin D deficiency rickets and familial hypophosphataemic rickets, but remained low in patients with end organ resistance to 1,25-dihydroxyvitamin D. Osteocalcin (and urinary hydroxyproline) were not elevated in isolated hyperphosphatasaemia, indicating that mechanisms other than increased bone turnover may account for the markedly elevated serum alkaline phosphatase activity in these subjects. Osteocalcin was decreased in children with diabetes mellitus type I and in patients on glucocorticoid treatment, indicating decreased bone formation. It is concluded that the measurement of serum osteocalcin seems to be a reliable index of bone formation provided that the vitamin D status and renal function are normal.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Carboxyglutamic Acid↗

[Isolated elevation of serum alkaline phosphatase].

The isoenzymes of serum alkaline phosphatase (AP) were determined in 17 children and 3 adults who had transiently or persistently raised serum AP levels without clinical, laboratory or radiographic evidence of hepatobiliary or bone disease. Liver and bone AP were both raised in 8 of 11 children having transient hyperphosphatasia whereas a rise in only one of the two enzymes (liver- or bone-AP) was detected in the serum of children and adults having persistent hyperphosphatasia. Isolated hyperphosphatasaemia is an anomaly having no pathological significance which, when found, has importance since expensive and invasive investigation methods that come into question can be avoided.

Adult↗

Reference values for urinary calcium excretion and screening for hypercalciuria in children and adolescents.

Hypercalciuria is of continuing interest as one of the risk factors for stone disease in children, but the definition, incidence and pathogenesis are controversial. Therefore reference values for the urinary calcium/creatinine (Ca/Cr) ratios were established in 564 healthy children aged 6-17.9 years during the fasting state (09.00 h) and in 236 of them also in the post-absorptive state about 2 h after lunch (14.00-16.00 h). The Ca/Cr ratios in both urine specimens were independent of age and sex, rendering it possible to determine a common normal range and to calculate centiles for Ca excretion in a large sample of healthy children and adolescents. To provide information about the incidence of hypercalciuria the Ca/Cr ratios of 1013 other apparently healthy children aged 6-17.9 years were measured during the post-absorptive state on two consecutive days. In 39 (3.8%) of them, 21 girls, and 18 boys, the Ca excretion was elevated in both urine specimens. Thirty-six of these children, all presenting without renal complaints, underwent further investigations to elucidate the possible mechanisms of the hypercalciuria. On the basis of the Ca/Cr concentration during the fasting state and the calciuric response to a standardised oral Ca tolerance test the children were subclassified into three groups: (1) Absorptive hypercalciuria (AH, n = 12): Increased calciuric response to the Ca load, but normal fasting Ca/Cr; (2) Renal hypercalciuria (RH, n = 8): Increased Ca/Cr after Ca load and during the fasting state; (3) Normal Ca excretion during the fasting state and after the Ca tolerance test, but increased sodium excretion (dietary hypercalciuria, DH, n = 16).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Parathyroid function in different stages of vitamin D deficiency rickets.

Direct measurements of parathyroid activity are available in only small numbers of children with vitamin D deficiency rickets (VDR). Therefore serum immunoreactive parathyroid hormone (iPTH) and the urinary cyclic adenosine-3',5'-monophosphate excretion (UcAMP) were measured together with other important indices of calcium metabolism in 24 patients (aged 2-42 months) with VDR before vitamin D treatment. iPTH and UcAMP were significantly elevated in comparison to age-matched controls. In patients there was a highly significant positive correlation between iPTH and UcAMP and a negative relationship between both indices of parathyroid activity to serum phosphate and urine calcium, respectively, indicating that the simple measurement of serum phosphate and/or urine cAMP and Ca provides a reliable tool for the assessment of secondary hyperparathyroidism in VDR. In two patients classified as being in the early stage of VDR the parathyroid activity was not elevated despite hypocalcemia indicating relative hypoparathyroidism. Twelve patients with VDR were followed during vitamin D therapy: Within the first 2 weeks of treatment UcAMP slightly increased and thereafter decreased in most patients, but was still elevated in three patients even after 7 weeks, whereas iPTH became normal within 3 weeks of treatment. This favors the concept that vitamin D deficiency diminishes the activation of renal adenylate cyclase by PTH which is overcome by the highly increased PTH secretion in the advanced stages of rickets. The basal and calcium-stimulated serum calcitonin (CT) levels, determined in some of the patients, were normal, ruling out a significant disturbance of CT secretion in VDR.

Calcitonin↗

[Hydroxyproline in morning urine. A reliable parameter for bone turnover in childhood].

OH-P/Cr was measured in morning fasting urine specimens of 300 healthy subjects and of children with disorders of calcium metabolism receiving no diet. In healthy children the values were sex and age dependent reflecting the different height velocities. The OH-P excretion was not different in schoolchildren receiving a OH-P-poor diet for at least two days in comparison to subjects of the same age group with unrestricted diet. OH-P/Cr correlated well with serum alkaline phosphatase (AP) activity and decreased rapidly after a calcium load. OH-P/Cr and AP were elevated in patients with increased bone turnover (hyperparathyroidism and hypophosphatemic rickets). In contrast, the OH-P excretion was normal in children with permanent or transient isolated hyperphosphatasemia. In children with vitamin D deficiency rickets there was a further increase of OH-P/Cr in response to vitamin therapy, while the AP activity, which reflects osteoblastic activity, tended to fall. This indicates that the observed increment of the OH-P excretion in these children is due to a temporary resorption of osteoid caused by the increasing levels of vitamin D metabolites. It is concluded that the measurement of OH-P/Cr provides a useful tool of bone turnover in children, in that it makes complete 24 h-urine collections and a OH-P free diet unnecessary. In combination with other indices of calcium metabolism the determination of the OH-P ratio is considered to be a valuable measure for the diagnosis and follow-up of bone disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Response of kidney and bone to parathyroid hormone in children receiving anticonvulsant drugs.

The response of kidney and bone to parathyroid extract (PTE) was investigated in 8 epileptic children on long-term treatment with primidone in combination with phenytoin or other anticonvulsant drugs. The results indicate a dissociation between normal and cyclic AMP excretion and disturbed renal handling of phosphate which resembles type II pseudohypoparathyroidism suggesting an anticonvulsant drug related inhibition of cyclic AMP-induced phosphaturia. It is speculated that antiepileptic drugs may provoke renal conservation of phosphate which may explain the relative low incidence of manifest rickets or osteomalacia in site of low 25-hydroxy-vitamin D levels in epileptic patients. A normal bone response of PTE indicates that antiepileptic treatment with phenobarbital and phenytoin does not affect PTH-stimulated bone resorption in the investigated patients.

Adolescent↗

Renal threshold phosphate concentration (TmPO4/GFR).

The ratio of maximum rate of renal tubular reabsorption of phosphate to glomerular filtration rate (TmPO4/GFR) was determined in 546 schoolchildren, aged between 6 and 17.9 years, using the nomogram of Walton and Bijvoet.1 TmPO4/GFR correlated with chronological age in girls and boys and in each remained significantly higher than in adults. TmPO4/GFR in the children correlated neither with fasting serum immunoreactive calcitonin and parathyroid hormone levels nor with the urinary cyclic AMP excretion. The study showed a parallel decrease in TmPO4/GFR, excretion of total hydroxyproline and serum alkaline phosphatase activities after puberty, with a significant relationship of both these indices of bone turnover to TmPO4/GFR values. This indicates that the high renal phosphate threshold of children may be an important factor for bone mineralisation by providing high extracellular inorganic phosphate concentrations during normal growth.

Adolescent↗

Deficient prolactin response to parathyroid hormone in hypocalcemic and normocalcemic pseudohypoparathyroidism.

The PRL response to the infusion of 8 U/kg BW parathyroid extract (PTE) was studied in three children with pseudohypoparathyroidism type I (PHP), three patients with idiopathic hypoparathyroidism, and eight epileptic children. PTE produced a clear-but increase of serum PRL in the epileptics and patients with idiopathic hypoparathyroidism, but not in the children with PHP. Prolonged PTE administration (six doses of 4 U/kg BW over 48 h) was also without effect on the low serum PRL levels in the three patients with PHP. These patients exhibited an isolated diminished PRL reserve to other potent PRL stimuli in the presence of intact function of the remainder of the anterior pituitary. The data suggest a pituitary receptor defect in patients with PHP in addition to disturbed renal and bone responses. One patient with normocalcemic PHP, seeming to be in the early stage of the disease, demonstrated the same distinct PRL deficiency as the other two patients with manifest PHP. This suggests that the pituitary receptor defect may be an early sign and marker of PHP.

Adolescent↗

Inhibitory effect of calcium on serum prolactin.

The effect of calcium (Ca) infusions on serum prolactin (Prl) was studied in normal controls and children with disorders of Ca metabolism: Three patients with secondary hyperparathyroidism (vitamin D deficiency rickets), 2 children with idiopathic hypoparathyroidism, 13 epileptic patients with anticonvulsant drug induced inhibition of calcitonin (CT) secretion and 1 patient with vitamin D resistant rickets with normal CP and low PTH secretion. Ca induced a significant decline of serum Prl in most subjects which could not be explained by the associated increase of CT or decrease of iPTH. The important role of Ca for the in vitro secretion of dopamine has been established for a long time. It is speculated that the inhibitory effect of Ca infusion or serum Prl may be due to dopamine release from nerve tracts in the hypothalamus.

Adolescent↗

Parathyroid function and serum calcitonin in children receiving anticonvulsant drugs.

Serum calcitonin (CT) levels and other aspects of calcium metabolism were investigated in 40 epileptic children receiving long-term treatment with phenytoin and/or other anticonvulsant drugs, and in 38 age-matched controls. In the patients CT levels were significantly lower. Immunoreactive parathyroid hormone (iPTH) was significantly elevated exceeding the upper limit of controls in 11 patients. We also observed a highly significant correlation between iPTH and urinary cyclic AMP (cAMP) excretion but a lack of such a correlation with the renal handling of phosphate; this indicates to us a dissociation between cAMP production and phosphaturia. A significant correlation between iPTH levels and urinary hydroxyproline excretion points to a normal action of PTH on bone in the patients. The low CT levels are not due to hypocalcemia and may be directly attributed to the effects of anticonvulsant drugs. As the primary effect of CT is a direct inhibition of PTH induced calcium loss from bone, the drug-related low CT levels in association with secondary hyperparathyroidism possibly is an additional factor in anticonvulsant bone disease.

Adolescent↗