Search PubMed⌕ Search

Biomedical subjects

E M Kaptein

Publications and source records attributed to E M Kaptein.

17 recordsLinked to original sources
PubMed1992

Effects of prednisone on thyroxine and 3,5,3'-triiodothyronine metabolism in normal dogs.

Pharmacological doses of glucocorticoids may reduce serum T4 and T3 levels in normal dogs and humans due to hypothalamic-pituitary suppression and/or altered peripheral hormone metabolism. To evaluate the chronic effects of antiinflammatory doses of glucocorticoids on peripheral thyroid hormone metabolism, serum T4 and T3 kinetic studies were performed in five thyroidectomized L-T4-replaced (5 micrograms/kg, sc, daily) normocalcemic male dogs at baseline and after 35 days of oral prednisone (0.55 mg/kg every 12 h). Data were analyzed in a three-pool model, with rapidly (liver and kidney) and slowly (muscle and skin) equilibrating pools exchanging with serum and rapid pool losses. Prednisone lowered the percent free fraction of T4 (to 70% of baseline) and total T3 (to 60%) and free T3 (to 51%) levels without significantly changing total or free T4 or percent free fraction of T3. This was associated with reduced T4 fractional transfer rates from serum rapid (to 39%) and slow (42%) pools and from rapid (to 25%) and slow pools (to 7%) to serum, and increased serum free T4 clearance rates (to 144%) as well as binding in the rapid (162%) and slow (710%) pools. Total T4 clearance and degradation rates were not significantly altered. Significant correlations included T4 binding in the rapid pool with percent free fractions of T4 (r = -0.86), T4 fractional transfer rates from rapid pool to serum with rapid pool T4 binding (r = -0.75), and fractional T4 transfer rates from slow pool to serum with slow pool T4 binding (r = -0.88). In contrast, prednisone increased fractional T3 transfer rates from serum to the slow pool (to 289%) and reduced serum (to 42%) and maximum total body degradation and production rates (to 41%) without altering total or free T3 clearance rates. Fractional T3 transfer rates from the slow pool to serum correlated with slow pool T3 binding (r = -0.84). Prednisone redistributed T4 and T3 from the serum and rapid pools to the slowly equilibrating pool. Thus, the peripheral effects of chronic antiinflammatory doses of prednisone on thyroid hormone metabolism include 1) increased T4 binding to serum carrier proteins, which may contribute to lower T4 transfer rates from serum to extravascular sites and increased extravascular T4 binding; 2) reduced fractional transfer rates of T4 from extravascular sites to serum, which may relate to increased tissue binding of T4; 3) redistribution of T4 and T3 from the serum and rapid pools to the slow pool; and 4) decreased T3 production from T4, resulting in reduced serum total and free T3 levels.

Administration, Oral↗
PubMed1991

rT3 metabolism in patients with nephrotic syndrome and normal GFR compared with normal subjects.

To evaluate reverse 3,3',5'-triiodothyronine (rT3) metabolism in nephrotic syndrome, serum rT3 kinetic studies from 10 nephrotics (mean urinary protein losses 7.0 g/day) with normal glomerular filtration rates (GFR; creatinine clearance 107 ml/min) were compared with 9 normal healthy subjects. Serum disappearance data were analyzed in a three-pool model, including rapidly (liver and kidney) and slowly (muscle, skin, and brain) equilibrating pools exchanging with serum, with all losses from the rapidly equilibrating pool. Serum free thyroxine (T4), determined by equilibrium dialysis, and parathyroid hormone levels were unaltered; total T4, T3, and rT3, and free rT3, albumin, and transferrin levels were significantly decreased; and free fractions of T4 and rT3 and thyroid-stimulating hormone (TSH) levels were increased. Despite reduced rT3 binding in serum, fractional transfer rates from serum to extravascular sites and serum clearance rates of total rT3 were unaltered. Free hormone clearance, serum appearance, and maximum hormone production rates were decreased. Total hormone transfer rates between serum and tissue pools and rT3 mass in serum and both tissue pools were reduced. Binding in the slowly equilibrating pool was decreased, and binding in both rapidly and slowly equilibrating pools was correlated with the free fraction of rT3 (r = -0.79, P = 0.007, and r = -0.70, P less than 0.025, respectively), with a shift of rT3 from the slow to the rapid pool. These findings suggest that binding of rT3 and T4 to serum carrier proteins is reduced, the transfer process for rT3 from serum to extravascular sites is decreased by factors in addition to reduced serum binding, degradation of rT3 is impaired, and decreased slow-pool binding may reflect reduced rT3 binding to serum-derived proteins in interstitial fluid. Furthermore, rT3 production rates are reduced, despite normal serum free T4 levels, accounting for low serum free rT3 concentrations. Total rT3 levels are decreased because of decrements in both serum binding and production rates.

Adult↗
PubMed1990

Comparison of reverse triiodothyronine distribution and metabolism in normal dogs and humans.

Serum rT3 tracer kinetic studies were performed in 14 normal dogs and 9 normal human subjects. A number of models were used to evaluate the data. Relative rates of hormone degradation by rapidly equilibrating tissues such as liver and kidney and slowly equilibrating tissues such as muscle, skin, and brain could not be determined using serum data alone. Based on known physiology, all hormone losses were confined to rapidly equilibrating sites. Dogs had significantly higher mean serum total rT3 (175% that in man), free fraction of rT3 (437%), and free rT3 levels (765%). Total rT3 values were determined in different assays, due to species differences, which had similar anti-rT3 antiserum characteristics and rT3 standards. Fractional rates of rT3 transfer from serum to both rapidly and slowly equilibrating pools in dogs were not significantly different from those in man, while the fractional transfer rate from the rapid pool to serum was increased (288%). This was associated with significantly smaller rapid and slow pool extravascular binding (rapid, 3.8%; slow, 2.8%), mass (29% and 21%, respectively), and volume (17% and 12%, respectively) in dogs compared to man. In dogs, 31% of the total 0.791 micrograms rT3 was in serum, 29% was in the rapid pool, and 40% was in the slow pool compared to 16% of 2.677 micrograms in serum, 29% in the rapid pool, and 55% in the slow pool in man (P less than 0.01). Further, 89% of the total unidirectional transfer from serum was to the rapid pool, and 11% to the slow pool in dogs compared to 82% and 18%, respectively, in man. Serum clearance (22%) and appearance rates (39%) as well as maximum total body production rates (34%) of rT3 were lower in the dogs. Serum appearance and maximum production rates, and hormone masses in the rapid and slow pools were no longer significantly different between dogs and man when normalized for either body weight or body surface area. Serum volume was no longer significant when normalized for body surface area. Noncompartmental analysis resulted in a significant underestimation of the mean total fraction rate of hormone exit from serum (by 20%), total volume of distribution (10%), extravascular binding (18%), and mean residence time (11%) in dogs and of extravascular binding (22%) in man. The serum appearance rate of rT3 was 78% of the maximum total body production rate in dogs and 69% in man.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1989

Separation of iodothyronines from iodinated metabolites in serum from reverse T3 tracer kinetic studies in man and dog: a comparison of two methods.

Iodothyronine separation from free iodide and iodoalbumin in serial serum samples obtained from 7 human and 5 dog studies following intravenous injection of radiolabeled reverse triiodothyronine (reverse T3) was compared using acidified ammonium acetate/tetrahydrofuran (THF) elution from C-18 SEP-PAK cartridges or ethyl acetate/butanol (EAB) extraction. Both methods excluded greater than 98% free iodide and greater than 99% iodoalbumin from the iodothyronine fraction. Recovery of labeled reverse T3 was higher for the THF/SEP-PAK (79.4 +/- 4.1%) than for the EAB method (43.2 +/- 6.1%, P less than 0.001), and intra-assay coefficients of variation were lower (2.1 +/- 0.6% and 4.4 +/- 2.0%, respectively, P less than 0.001); HPLC analysis of iodothyronine fractions revealed a single peak co-migrating with injected tracer. The THF/SEP-PAK technique allowed use of larger serum samples at later time points. Serum disappearance curves derived from these two methods were highly correlated in all cases (r = 0.998, P less than 0.001), as were fits of data to sums of exponentials and calculated serum kinetic parameters.

Acetates↗
PubMed1989

Thyroid hormone levels in the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex.

Hypothalamic-pituitary dysfunction and thyroid gland cytomegalovirus inclusions have been described in patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC). We evaluated 80 patients with AIDS or ARC for the frequency of hypothalamic-pituitary or thyroid gland failure and altered serum thyroid hormone levels due to nonthyroidal disorders. One patient had subclinical hypothyroidism. Of these patients, 60% had low free triiodothyronine (T3) index values and 4% had low free thyroxine (T4) indexes; none of the latter had hypothalamic-pituitary or thyroid gland failure, since all serum cortisol values were greater than or equal to 552 nmol per liter (greater than or equal to 20 micrograms per dl) and all thyrotropin levels were less than or equal to 3 mU per liter (less than or equal to 3 microU per ml), respectively. Those who died had lower total T4 and T3, free T3 index, and albumin levels than those discharged from hospital. Serum total T4 and T3 levels correlated with albumin levels and total T3 with serum sodium levels. Serum total T3 levels best predicted the outcome of the hospital stay (accuracy = 82%). Thus, abnormal serum thyroid hormone levels in AIDS or ARC patients are most frequently due to nonthyroidal disorders, but hypothalamic-pituitary or thyroid gland failure may occur.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Amiodarone alters thyroxine transfer and distribution in humans.

Previous studies indicate that increased serum total and free T4 levels may be secondary to a proportionally greater decrease in serum T4 clearance rates than in production rates after short-term amiodarone administration, to increased T4 production rates as well as reduced serum clearance rates in selective hyperthyroxinemia without overt hyperthyroidism following chronic amiodarone administration, and to a relatively greater increase in T4 production rates than in clearance rates in classical hyperthyroidism. To further evaluate amiodarone-induced alterations of T4 metabolism, serum T4 transfer and distribution were evaluated by compartmental analysis of T4 kinetic studies from eight normal subjects receiving short-term amiodarone or an equivalent amount of iodide, five patients with selective hyperthyroxinemia induced by chronic amiodarone therapy (n = 4) or ioxithalamic acid (n = 1), and five with classical hyperthyroidism. The model consisted of rapidly and slowly equilibrating pools exchanging with serum, with all losses occurring from the tissue pools. Short-term amiodarone administration reduced the fractional T4 transfer rates between serum and the rapidly equilibrating pool to 82% of baseline. In selective hyperthyroxinemia the fractional rates of T4 transfer between serum and both extravascular pools were increased sixfold, whereas minimal alterations were present in the hyperthyroid group. The serum equivalent volume of T4 distribution in the slow pool was significantly reduced following short-term amiodarone, whereas serum and rapid pool volumes were reduced in selective hyperthyroxinemia and slow pool volume was increased in hyperthyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

The thyroid in end-stage renal disease.

Previous studies of patients with end-stage renal disease (ESRD) indicate that the prevalence of goiter varies from 0 to 58% while that of hypothyroidism ranges from 0 to 9.5%. In addition, altered serum thyroid hormone levels are present in euthyroid patients with ESRD and may be related to nonthyroidal disorders including malnutrition. To examine these issues further, 306 patients with ESRD were compared to 139 hospitalized patients without renal disease (control population). Goiter was present in 43% with ESRD compared to 6.7% of controls (P less than 0.001). Goiter frequency was greater (49.6%, P = 0.047) and serum parathyroid hormone levels higher (mean: 238.6 microlitersEq/ml, P less than 0.001; normal: less than 15 microlitersEq/ml) in 115 patients dialyzed for longer than 1 year than in 191 dialyzed for less than 1 year or not at all (38.7%, and 61.5 microlitersEq/ml, respectively). In addition, goiter was more common in females (50.0%) than in males (35.1%, P = 0.008) with ESRD. No significant relationships were observed between goiter frequency and age, race, diabetes mellitus, or elevated antimicrosomal antibody titers. The prevalence of primary hypothyroidism was higher in ESRD (2.6%) than in 2122 in- and out-patients (1.1%) (P = 0.024). Compared to the total group of ESRD patients, the hypothyroid patients were predominantly female (88% vs. 50%) and had a higher frequency of positive antimicrosomal antibody titers (50% vs. 6.7%, P = 0.029). The frequency of hyperthyroidism was not significantly different, being 1.0% in ESRD compared to 0.3% in the general population (P = 0.057). There was a higher frequency of reduced free T4 index values in the 287 euthyroid patients with ESRD (12.9%) than in controls (3.6%) (P = 0.002). Similarly, free T3 index values were reduced below 100 in 65.5% with ESRD compared to 33.8% of controls (P less than 0.001). In addition, serum albumin levels were lower in euthyroid patients with ESRD (3.5 g/dl, P less than 0.001) than in controls (3.8 g/dl). Serum T3 levels correlated directly with both serum albumin (r = 0.57, P less than 0.001) and transferrin (r = 0.54, P less than 0.001) levels in ESRD as well as in controls (r = 0.74, P less than 0.001, and r = 0.69, P less than 0.001, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

California↗
PubMed1987

Diagnosis of hypothyroidism in patients with end-stage renal disease.

Hypothyroidism may occur more commonly in patients with end-stage renal disease (ESRD) than in the general population. The signs and symptoms of both hypothyroidism and uremia may be similar. To evaluate the usefulness of clinical and routine laboratory findings in the diagnosis of hypothyroidism in patients with ESRD, we compared 6 patients with documented primary hypothyroidism who had serum thyrotrophin (TSH) levels above 20 microU/ml with 12 euthyroid patients. The euthyroid patients were divided into two groups. The first was matched with the hypothyroid patients for age, renal disease and duration of dialysis, while the second group was matched for serum total thyroxine and free T4 index values. Serum TSH levels were normal (less than 10 microU/ml) in both of these latter groups. There were no significant differences in the clinical manifestations among the three groups of patients, except for hoarseness of voice which was significantly more common in the hypothyroid uremic patients (p = 0.03). No significant differences were noted on electrocardiogram, physical examination, chest x-ray or echocardiography. Routine laboratory values were not different. Therapy of the uremic hypothyroid patients with L-thyroxine was associated with improvement or resolution of many of the symptoms and signs of hypothyroidism that otherwise would have been attributed to the uremic state. Our results indicate that the diagnosis of hypothyroidism in uremic patients cannot be made by clinical or routine laboratory values and rests on the presence of an overtly elevated serum TSH concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Thyroxine transfer and distribution in critical nonthyroidal illnesses, chronic renal failure, and chronic ethanol abuse.

Serum T4 kinetic studies were performed in euthyroid patients with acute critical illnesses, chronic renal failure, or ethanol abuse without overt hepatocellular damage and in healthy euthyroid subjects with normal or altered serum T4 binding to determine the relative effects of altered serum T4 binding and extravascular disturbances on T4 transfer and distribution in nonthyroidal illnesses. A three-pool model with rapidly and slowly equilibrating pools exchanging with serum was used to evaluate the potential sites of alterations. Healthy euthyroid subjects with low serum T4-binding globulin levels had increased serum percent free fraction of T4 (%FFT4) and fractional T4 transfer rates (FTR) from serum to both extravascular pools, while those with high serum T4-binding capacity had decreased %FFT4 and FTR from serum to the rapid pool and increased T4 binding in the slow pool. Critically ill patients had significantly reduced serum total T4 (TT4) with increased %FFT4 but decreased FTR from serum to both extravascular pools and reduced T4 binding in the slow pool. Patients with ethanol abuse had normal serum TT4 and %FFT4 but significantly increased FTR from serum to the rapid pool and increased binding in both extravascular pools. Chronic renal failure patients had no alterations in any of these values. The T4 FTR from serum to both extravascular pools were directly related to the serum %FFT4 in healthy subjects and inversely related in the patients. Further, the FTR from the rapid pool to serum were inversely related to rapid pool binding in healthy subjects but not in the patients, while the FTR from the slow pool to serum were unrelated to slow pool binding in both groups. These findings indicate that in patients with nonthyroidal illnesses the transfer of T4 between serum and the extravascular pools is not primarily a reflection of T4 binding to serum binding proteins or extravascular sites. Further, alterations in slow pool binding may be affected by changes in T4 binding to serum binding proteins, which are known to be present in the interstitial fluid of these tissues. Finally, the type and magnitude of the alterations in T4 transfer and distribution in patients with nonthyroidal illnesses appear to differ for rapidly and slowly equilibrating tissues and may be related to the etiology and/or severity of the nonthyroidal disorder.

Acute Disease↗
PubMed1986

Acute renal failure due to bilateral ureteral obstruction by metastases from breast cancer.

Two female patients with metastatic breast carcinoma had acute renal failure secondary to metastatic ureteral obstruction. Retrograde pyelography showed bilateral segmental constriction and dilatation of the ureters with hydronephrosis. Drainage procedures reversed the renal failure in both patients. A review of the literature indicates that ureteral involvement is frequent in patients with malignancies.

Acute Kidney Injury↗
PubMed1986

Thyroxine kinetics in nonthyroidal illnesses.

Free T4 estimates by equilibrium dialysis appear to reflect serum free T4 levels in vivo in patients with nonthyroidal illnesses. However, patients with either elevated or modestly reduced free T4 values appear to be clinically euthyroid and have relatively normal free T4 availability to tissues as judged by the normal production rates of reverse T3 from T4, and by the minimally altered TSH status. Thus, increased or modestly reduced serum free T4 levels by equilibrium dialysis in patients with nonthyroidal illnesses do not appear to indicate the presence of overt T4 excess or deficiency, respectively, and, therefore, the clinician should strive to avoid unnecessary and potentially harmful therapy in these patients. Conversely, concurrent thyroid gland disease may be present which must be accurately diagnosed and treated to alleviate the morbidity induced by hyperthyroidism or hypothyroidism in sick patients.

Disease↗
PubMed1986

Acute hemodynamic effects of levothyroxine loading in critically ill hypothyroid patients.

To evaluate the acute cardiovascular effects of high-dose levothyroxine sodium therapy, the hemodynamic findings in eight critically ill hypothyroid patients treated with high-dose levothyroxine were compared with those in two critically ill hypothyroid and nine critically ill euthyroid patients not receiving this therapy. The initial cardiac index was significantly lower in the hypothyroid group; all other hemodynamic values were similar to those of the euthyroid patients. Following levothyroxine loading, the free thyroxine index increased to normal while the free triiodothyronine index was unchanged; all patients had a significant rise in cardiac index but no consistent changes in the other hemodynamic values. Cardiac index correlated positively with heart rate (three patients) and/or stroke volume index (six patients). Increases in stroke volume index correlated with decreases in systemic vascular resistance (five patients), but not with increases in pulmonary artery wedge pressure. No consistent patterns of hemodynamic changes were observed in the untreated hypothyroid or the euthyroid patients.

Aged↗
PubMed1985

Metabolic and hormonal factors as predictors of nitrogen retention in obese men consuming very low calorie diets.

The ability to conserve body protein during very low calorie diets in ten obese men was observed to correlate with plasma free amino acid concentrations, urinary N tau-methylhistidine: creatinine ratios, resting oxygen consumption, and serum triiodothyronine levels. A diet consisting of only protein, 1.3 g/kg ideal body weight/24 h, was given for 40 days. Cumulative nitrogen deficit ranged from -64 g to -227 g. Nitrogen balance on days 36 to 40 ranged from + 1.37 g/24 h to -3.30 g/24h. Nitrogen balance during this period had a significant direct correlation with pre-diet concentrations of branched-chain amino acids (r = 0.69 to 0.89), methionine (r = 0.85), histidine (r = 0.66), alanine (r = 0.73), arginine (r = 0.70), ornithine (r = 0.66), total essential (r = 0.87, and nonessential (r = 0.68) amino acids, with initial serum levels of triiodothyronine (r = 0.66) and with the fall in triiodothyronine over the 40 days (r = 0.79). Initial resting oxygen consumption was directly correlated (r = 0.78) with final nitrogen balance and inversely with total nitrogen loss (r = -0.81). On day 0, triiodothyronine levels also correlated positively (r ranging from 0.71 to 0.93) with plasma concentrations of several essential and nonessential amino acids. These correlations suggest that individuals who ultimately will or will not achieve nitrogen equilibrium during very low calorie diets can be identified prior to dieting. These data are consistent with the hypothesis that individuals with higher initial protein flux and triiodothyronine levels are better able to adjust the balance between synthesis and degradation to attain nitrogen equilibrium during hypocaloric dieting.

Adult↗
PubMed1985

Relationship between the changes in serum thyroid hormone levels and protein status during prolonged protein supplemented caloric deprivation.

The relationship between the changes in serum thyroid hormone levels and nitrogen economy during caloric deprivation were investigated in ten obese men during a 40 d, 400 kcal protein-supplemented weight-reducing diet. This regimen induced increases in the serum levels of total T4, free T4 and total rT3, and decreases of total T3, while serum TSH remained unchanged. There were progressive decreases in total body weight and urinary losses of total nitrogen and 3-methylhistidine, with the early negative nitrogen balance gradually returning towards basal values during the 40 days. Subjects with the largest weight loss had the most increase in the serum levels of total T4 and free T4 index and the greatest decrease in T3. The magnitude of the increase of the nitrogen balance from its nadir was correlated with the extent of the reduction of T3 and increase of T3 uptake ratio and free T4 levels. The decrease in the urinary excretion of 3-methylhistidine correlated with the increase in free T4 and rT3 levels. Nadir serum transferrin values were directly related to peak rT3 values, and the lowest albumin concentrations occurred in subjects with the highest total T4 and free T4 index values. Further, the maximum changes in the serum thyroid hormone levels preceded those of the nutritional parameters. These relationships suggest that: (1) increases in serum rT3 and free T4 and reductions in T3 concentrations during protein supplemented weight reduction may facilitate conservation of visceral protein and reduce muscle protein turnover; and (2) the variation in the magnitude of these changes may account for the heterogeneity of nitrogen economy.

Adult↗
PubMedDate not supplied

Renal biopsy-related hemorrhage: frequency and comparison of CT and sonography.

To evaluate the frequency of retroperitoneal hemorrhage related to renal biopsy, we prospectively assessed 182 patients (200 biopsies) using state-of-the-art CT and ultrasound. Our study revealed definite CT evidence of hemorrhage after 90.9% of biopsies. In a blinded analysis of images obtained in biopsied patients and in unbiopsied control patients the overall accuracy of CT was 93.8 versus 76.4% for ultrasound. Our data suggest that detectable hemorrhage is virtually always seen after renal biopsy and its frequency is much higher than noted in earlier studies.

Biopsy↗