[Endocrine disorders in gastrointestinal diseases].
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Biomedical subjects
Publications and source records attributed to R Hehrmann.
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In a series of 6 patients out of 47 cases with extrarenal hyperparathyroidism we investigated the clinical, laboratory and ultrastructural peculiarities of acute hyperparathyroidism. It was found that there are characteristic differences between both entities which, however, are fluid. Clinically more severe were neuromuscular psychiatric and mental signs. In the laboratory parameters PTH determined by radioimmunoassay and calcium were higher whereas hemoglobin was lower. The weights of the adenomas did not differ in both groups and this was also true for light microscopy findings. Electron microscopy revealed accelerated hormone extrusion and autodigestion of retrived membrane material in the cases of acute hyperparathyroidism similar to characteristics of parathyroid cells stimulated by hypocalcemia in tissue culture.
Patients after kidney transplantation were investigated for parameters for kidney function and calcium metabolism including a definitively characterized parathyroid hormone (PTH) radioimmunoassay, of which quality criteria have been documented. In 72 transplanted patients 3 months to 7 years after operation a close correlation between graft function and plasma PTH concentrations was found. Patients with clearly elevated PTH revealed definitively decreased graft function. Three patients with normal GFR and clearly elevated PTH showed - at least transiently - all criteria of an autonomous hyperparathyroidism including hypercalcaemia and hypophosphataemia. Borderline PTH elevations associated with normal GFR can be explained by corticosteroid treatment. In 100 patients, which were investigated before and during the first 10 days after transplantation, again a close correlation was documented between the development of PTH concentrations and the function of the transplanted kidney. PTH concentrations are not only a very sensitive parameter of graft function; in various situations plasma PTH concentrations additionally allow an estimate of graft prognosis. This is particularly true in primary graft failure and in early rejection episodes.
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The changes of thyroid hormones and TSH in plasma of males in the early stage of myocardial infarction are described. Already on admission T3 was diminished and went on falling. On admission rT3 was elevated and reached its maximum after 19 hours. T4 and TSH did not show essential alterations. The results suggest that in the early stage of myocardial infarction a rapid shift of the monodeiodination of T4 to rT3 occurs instead of T3 with a quick decrease of T3 and increase of rT3 in the blood.
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PTH antibodies were raised in two sheep (S 469 and S 478) by immunizing with porcine and bovine parathyroid extracts. Both antisera were characterized with various PTH preparations and fragments. Both antisera cross react with human, bovine and porcine PTH, one antiserum also binds rat PTH. Region specificity could be attributed to the mid region of the PTH molecule with particularly high affinities of both antisera for the fragment 44-68 hPTH. S 478 has similarly high affinity for intact hormone (affinity constants 0.6 x 10(13) l/mol), while S 469 has much higher affinity for the 44-68 fragment (affinity constant 0.84 x 10(13) l/mol) than for intact hormone. The antibodies are useful not only for clinical radioimmunoassay, but also for experimental work. They have been distributed to many laboratories.
A new antiserum (Ab Giselle) raised in sheep against extracted human parathyrin was evaluated and compared with an established antiserum (Ab S-478 VI) under several test conditions. The assay system contained an extracted 1--84 human parathyrin standard and a 1--84 bovine parathyrin tracer. The total assay time was 24 h and the main assay characteristics as follows: B0/T 0.28 +/- 0.02 and 50% intercept 553 +/- 47 U . 1(-1). The corresponding data for Ab S-478 VI were: B0/T 0.23 +/- 0.02 and 50% intercept 890 +/- 142 U . 1(-1). The normal range in 152 normocalcaemic volunteers (age range 16--67 years) was 10.6--423 U . 1(-1) (where 1 vial MRC reference preparation 75/549 for human parathyrin = 25 U), compared with 0--300 U . 1(-1) for Ab S-478 VI. With the new antiserum, differentiation between hypoparathyroid patients and those with normal function was often possible, and differentiation between normal and elevated levels, as in hyperparathyrinaemia, was very good. Correlation between Ab Giselle and Ab S-478 VI in 80 normal volunteers was positive (r = 0.450, p = 0.01) although the regression line showed that the antisera had different specificities (data for the regression line y = a + bx, a = 0.13, b = 0.55). Under the assay conditions, the association constant for Ab Giselle was 0.41 +/- 10(14) l . mol-1 in contrast to Ab S-478 VI which had a Ka for 0.53 x 10(10) l . mol-1 under identical conditions. Assays using Ab Giselle could be performed at room temperature, whereas those using Ab S-478 VI performed best at 0 degrees C. Preliminary results suggest that Ab Giselle is better for the routine assay of human parathyrin in serum than Ab S-478 VI, especially in the case of hypoparathyroid patients.
The skeletal X-rays (magnification radiography of hand, pelvis, knee and shoulder joint) of 20 children before and after successful kidney transplantation were compared with the parathormone concentrations measured in the interval closest to the roentgenological examination. In 19 children, renal osteodystrophy existed before kidney transplantation, which was diagnosed based on the following radiographic findings of varying frequency: rarefaction and fuzziness of the spongiosa, fraying of metaphysical ends, widening of the growth plates, subperiosteal resorption and acroosteolysis. The parathormone concentrations were definitely increased before kidney transplantation. After kidney transplantation the abnormal radiographic findings receded corresponding to normalisation of the parathormone concentrations. Nevertheless, in 14 out of 19 children a rarefaction of the spongiosa remained, the cause of which is presumed to be steroid therapy.
In 21 males (age 50-78 yrs) without endocrine diseases, plasma thyroxine, triiodothyronine, reverse-triiodothyronine and TSH were determined by specific RIAs in the early stage of an acute myocardial infarction. Blood was taken every 4 hours up to 43 hours after admission. The patients were separated in 2 groups, depending on the severity of the infarction (group A with 11 patients = severe infarction; group B with 10 patients = not severe infarction). 25 healthy men served as an aged-matched control group (age 56-83 yrs). Thyroxine in all patients (group A and B together) did not show essential fluctuations during the 43 hours of observation. The mean values were elevated, the individual values were predominantly in the normal range. There were no significant differences between the groups A and B. As well in the total-patients group as in the groups A and B already on admission, T3 was diminished and went on falling during the 43 hours. From 35 hours after admission, T3 was significantly decreased in group A compared to group B. On admission, rT3 was elevated in both the total-patients group and group A and B; it reached its maximum after 19 hours. Group A showed from 7 hours after admission a tendency more increased levels compared to group B. In all cases (total-patients group, group A and B) TSH levels were constant within the normal range during the whole time. The results suggest that in the early stage of myocardial infarction an important alteration in the thyroxine metabolism with enhancement of the inactive reverse-triiodothyronine production occurs very quickly. Moreover, the results show that this alteration may depend on the severity of myocardial infarction. Hypothyreoidism can be excluded because of the normal or elevated thyroxine values and the normal TSH levels.
A radioimmunoassay for porcine parathyroid hormone has been developed and applied to measure immunoreactive parathyroid hormone (PTH) in plasma of pigs with hereditary vitamin D dependency rickets (VDDR) (pseudovitamin D deficiency rickets). Levels of 25-hydroxycholecalciferol (25-(OH)-D3) in plasma were measured by a protein binding assay. Both plasma concentrations of PTH and 25-(OH)-D3 showed an approximately 4-fold increase compared to normal pigs. PTH levels increased with duration of the disease. Daily dosing of the animals with 1--4 micrograms of 1,25-dihydroxycholecalciferol (1,25-(OH)2-D3) reduced PTH concentrations and resulted in clinical healing. Iv administration of 10 micrograms of 25-(OH)-D3/day did not alter PTH concentrations nor the clinical symptoms. The results suggest that these animals suffer from regulatory hyperparathyroidism. The metabolic defect could be due to a failure of the kidney to convert 25-(OH)-D3 to 1,25-(OH)2-D3.
The kinetics of extracellular water (82Br) and total body water (THO) in controls and patients with liver cirrhosis are studied. Analysis of the plasma activity of the radionuclides as a function of time shows that distribution volumes and kinetics can be described by a linear open three-compartment model and that the volumes are of about equal size. Measuring is carried out in the central compartment in which the radionuclides are injected as a bolus. In cirrhotic patients equilibration into a third compartment is attained about four times slower than in controls. Elimination is reduced by about the same factor. Reduced diffusion and effective blood flow in the cirrhotic patients are discussed as possible reasons for the differences.
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Various methods for the measurement of intact PTH, PTH fragments and PTH binding to receptors were applied to clarify the role of renal receptors for the bioexpression of PTH. Glomerular receptors may contribute approximately 20% of the renal PTH catabolism. PTH also binds to tubular receptors at the luminal side (brush border membranes) as well as at the antiluminal site (basal-lateral membrane). Scatchard plot analysis of PTH binding to these receptors allows the calculation of an equilibrium dissociation constant and binding capacity, if correction is made for inactivation of bioactive PTH (measured by LAMA). Binding to receptors is--in our systems--invariably associated with degradation of the intact hormone to N-terminal and C-terminal fragments of different molecular weight. Antibodies against basal lateral membranes and against brush border membranes are able to inhibit PTH binding to tubular membranes. Sera of uremic patients with inappropriately high PTH contain a globulin which interferes with PTH binding to the receptor, suggesting that uremia may be another example for a "hormone receptor antibody disease".
Distribution and metabolic degradation of bPTH was studied in man after infusion of 400 U bPTH and blood sampling up to 2h. Disappearance rates of intact 1-84 bPTH, carboxyl- and amino-regional peptides were calculated for healthy subjects (n = 12); patients suffering from moderate (GFR 15--30 ml/min, n = 4) and advanced (GFR less than or equal to 10 ml/min, n = 36) chronic renal failure; and bilateral nephrectomized patients (n = 3). Two components with a rapid and a slow disappearance rate can be separated ("distribution", "metabolism"). Half-lives are found to be in the range known from animal experiments with marked differences between intact 1-84 PTH and peptide fragments. Influence of impaired renal function on metabolic turnover rates of PTH is given.
We studied six different antisera to bovine or porcine parathyrin (parathyroid hormone, PTH), produced in rabbit, guinea pigs, sheep or goat, two of which are commercially available. The antisera were characterized with regard to species specificity, affinity and their ability to identify patients with primary hyperparathyroidism. In this heterologous radioimmunoassay system in which [125I]parathyrin is used as a tracer, some cross-reactivity of the antisera to the hormone or hormone fragments present in human serum was demonstrated. However, there is some overlap of serum immunoreactive parathyrin in patients with or without primary hyperparathyroidism. The results of this and other studies illustrate the necessity for a homologous radioimmunoassay for human parathyrin.
The case of a 45-year old female patient with primary hyperparathyroidism is described to show that this disease can occur under the principal sign of a destruction of the cervical vertebral column. The roentgenological changes associated with primary hyperparathyroidism are discussed and their differential diagnostic significance is emphasised. The radially located subperiostal absorptions are the first roentgenological changes seen in PHPT and represent signs which make it highly probably that this disease is present.