Assessment of maximum weight change and duration of therapeutic effect for non-surgical treatment of obesity using an exponential model.

Efficacy of weight loss and maintenance therapies in obesity is difficult to quantify due to continuous weight changes over time. We assessed a single exponential model of weight changes during selected non-surgical therapies of non-diabetic obese subjects. We analyzed published mean weight data from 6 studies of ≥12 weeks duration, with comparable treatment groups, and ≥4 weight measurements during very low carbohydrate or fat diets, or treatment with Lorcaserin, Sibutramine or Orlistat. We fit data to a single exponential model to estimate maximum predicted weight loss or regain and duration of weight loss or regain for each therapy. A single exponential is the appropriate model as determined by Kolmogorov-Smirnov, constant variance, and Durbin-Watson tests. Validity of parameter estimates was indicated by coefficients of variation <25%. Sensitivity analysis showed that weight regain at the end of the weight loss phase affected parameter estimates in some instances, with variations of weight loss of 0.2-0.7% of basal. Estimated weight loss and regain were similar to observed weight changes in all studies. The model could also be used to assess dose-response relationships. Estimates from the model were used to compare concurrent obesity regimens using 95% confidence intervals, taking into account pre-determined minimal clinically important differences. This exponential model may provide accurate estimates of maximum achievable weight loss or regain and optimal duration of efficacy for a variety of non-surgical weight loss and maintenance regimens from published mean weight data and may be useful to more accurately evaluate weight loss and maintenance regimens.

Radioiodine dosimetry in patients with end-stage renal disease receiving continuous ambulatory peritoneal dialysis therapy.

In patients with end-stage renal disease (ESRD), Na131I dosages for thyroid cancer may have to be reduced to avoid excess radiation doses to red marrow, because radioiodine is primarily excreted by kidneys. In ESRD patients receiving continuous ambulatory peritoneal dialysis (CAPD) therapy (three to five 2-L exchanges daily) creatinine clearance rates are very low (mean, 7 mL/min), and radioiodine clearance rates may be proportionately reduced. Thus, radioiodine kinetic studies were performed in two hypothyroid CAPD patients with thyroid cancer, in eight euthyroid CAPD patients, and in eight thyroid cancer patients with normal renal function. All received Na131I or Na123I orally, with serial blood, urine, and/or dialysate sampling for 24-70 h. Dosimetry calculations were performed using the MIRDOSE3 computer program. In CAPD patients, serum radioiodine half-times were 5 times longer, and radioiodine clearance rates by urine plus dialysate were 20% of those in patients with normal renal function. Na131I dosages for the two CAPD patients with thyroid cancer were reduced from 150 mCi [5.6 gigabecquerels (GBq)] to 26.6 mCi (0.98 GBq) and 29.9 mCi (1.11 GBq), respectively, resulting in radiation doses to red marrow and total body comparable to those in patients with normal renal function who received a mean of 148 mCi (5.5 GBq) Na131I. Thus, in patients receiving continuous ambulatory peritoneal dialysis therapy, 5-fold reductions in radioiodine clearance rates require 5-fold decreases in Na131I dosages to avoid excessive radiation doses to total body and red marrow.

Diagnostic sonography of HIV-associated nephropathy: new observations and clinical correlation.

OBJECTIVE: HIV-associated nephropathy is an important cause of morbidity that is characterized clinically by uremia and proteinuria and histologically by focal segmental glomerulosclerosis. In the largest series yet analyzed to our knowledge, we describe new sonographic findings and record the prevalence of other findings. We review the sonographic findings in a large group of HIV-infected patients. MATERIALS AND METHODS: Seventy-six consecutive HIV-infected patients underwent renal sonography. Abnormalities seen on sonography were recorded. RESULTS: Of 152 kidneys imaged, sonography showed that 30 kidneys (20%) were enlarged. Abnormal echogenicity was present in 136 kidneys (89%). Eighty-one kidneys (53%) were globular; 58 (38%) had decreased corticomedullary definition; 74 (49%) had decreased renal sinus fat; and 66 (43%) had heterogeneous parenchyma, some with echogenic striations. CONCLUSION: Our data reveal several sonographic abnormalities that have not previously been described: decreased corticomedullary definition, decreased renal sinus fat, parenchymal heterogeneity, and globular renal configuration. These new findings were found mainly in patients with advanced HIV infection.

Hormone-specific alterations of T4, T3, and reverse T3 metabolism with recent ethanol abstinence in humans.

Effects of recent alcoholic withdrawal on thyroxine (T4), 3,5,3'-triiodothyronine (T3), and reverse T3 (rT3) metabolism were determined by serum tracer kinetic studies in recently abstinent alcoholics without overt hepatocellular injury or caloric deprivation. Data were compared with those of normal subjects using a three-pool model, with rapidly and slowly equilibrating pools exchanging with serum. Significant differences included 1) reduced serum total rT3 levels (to 69% of normal) and rT3 degradation rates (to 61%); 2) increased rT3 binding in rapidly (to 557%) but reduced binding in slowly (to 13%) equilibrating tissues, with opposite effects on rT3 fractional transfer rates to serum from rapidly (to 7.5%) and slowly equilibrating sites (to 669%); 3) increased T4 fractional transfer rates from serum to rapidly equilibrating tissues (to 122%); and 4) increased T4 binding to both rapidly (to 195%) and slowly (to 190%) equilibrating tissues. T3 kinetics were not significantly altered. Thus recently abstinent alcoholics have hormone-specific alterations of T4, T3, and rT3 transfer, distribution, and metabolism distinct from other nonthyroidal illnesses or caloric deprivation. Furthermore, these data indicate separate transfer processes for T4, T3, and rT3 from serum to tissue sites and hormone-specific tissue binding characteristics in humans in vivo.

Thyroid hormone metabolism and thyroid diseases in chronic renal failure.

Patients with ESRD have multiple alterations of thyroid hormone metabolism in the absence of concurrent thyroid disease. These may include elevated basal TSH values, which may transiently increase to greater than 10 mU/liter, blunted TSH response to TRH, diminished or absent TSH diurnal rhythm, altered TSH glycosylation, and impaired TSH and TRH clearance rates. In addition, serum total and free T3 and T4 values may be reduced, free rT3 levels are elevated while total values are normal, serum binding protein concentrations may be altered, and disease-specific inhibitors reduce serum T4 binding. Changes in T4 and T3 transfer, distribution, and metabolism resemble those of other nonthyroidal illnesses, while changes in rT3 metabolism are disease specific. Dialysis therapy minimally affects thyroid hormone metabolism, while zinc and erythropoietin administration may partially reverse thyroid hormone abnormalities. Thyroid hormone metabolism normalizes with renal transplantation; however, glucocorticoid therapy may induce additional changes. ESRD patients may have an increased frequency of goiter, thyroid nodules, thyroid carcinoma, and hypothyroidism. Goiter and hypothyroidism may be induced by iodide excess, due to reduced renal iodide excretion, and may be reversed with iodide restriction in some patients. The increased frequency of thyroid nodules and malignancies in ESRD may relate to secondary hyperparathyroidism. After renal transplantation, the higher frequency of thyroid malignancies may relate to the immunosuppressed state. Clinical symptoms and signs and biochemical features of hypothyroidism and hyperthyroidism may be altered by concurrent ESRD. ESRD patients with hyperthyroidism or follicular neoplasms require reduced dosages of Na 131-I depending upon type, frequency, and duration of dialysis therapy.

Thyroid hormone metabolism. A comparative evaluation.

Knowledge of thyroid hormone and iodide metabolism is derived from a combination of in vivo and in vitro studies in a variety of mammalian species including cats, dogs, and humans. Each species provides a unique opportunity to investigate various aspects of normal or altered thyroid hormone physiology. Availability of sensitive and specific human TSH assays has allowed detailed studies of the human hypothalamic-pituitary-thyroid axis which have not been possible in cats and dogs to date. Similarities and differences of thyroid hormone metabolism in dogs, cats, and humans provide the basis for a better understanding of normal physiology as well as shedding light on the significance of changes induced by spontaneous or induced thyroidal and nonthyroidal disorders.

Clinical application of free thyroxine determinations.

The clinical diagnosis and management of thyroid hormone excess and deficiency are dependent on accurate laboratory measurements and the interpretation of serum free T4 and TSH values. A variety of free T4 methods are available that perform well in otherwise healthy patients with hypothyroidism or hyperthyroidism and in euthyroid subjects with mild alterations of T4 binding to serum-carrier proteins. In contrast, only free T4 values by direct equilibrium dialysis, a method that is available in larger clinical laboratories, and ultrafiltration of undiluted sera, which is a research method, provide appropriate free T4 values in the majority of patients with significant alterations of serum T4 binding, including severe nonthyroidal illnesses. In patients with a normal pituitary-thyroid hormone axis, an inverse log10-linear relationship exists between serum TSH and free T4 levels; a decreased direct equilibrium dialysis free T4 value with an elevated TSH level confirms the diagnosis of primary hypothyroidism, and an increased free T4 value with a TSH level less than 0.01 mU/L is consistent with nonpituitary hyperthyroidism. When this relationship is altered, as in nonthyroidal illnesses, TSH secreting tumors and thyroid hormone resistant states, a direct equilibrium dialysis free T4 level plus a third-generation TSH assay is the most sensitive and specific approach to diagnose thyroid hormone excess or deficiency. Use of other free T4 methods in patients with significant alterations of serum T4 binding results in a variably increased frequency of false-positive values, which require additional testing to define the thyroid hormone status.

Hyponatremia in hospitalized patients with the acquired immunodeficiency syndrome (AIDS) and the AIDS-related complex.

STUDY OBJECTIVE: To determine the frequency, etiology, and clinical association of hyponatremia in patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC). PATIENTS AND METHODS: A prospective analysis of 167 patients with AIDS and 45 patients with ARC admitted on 259 occasions to a large metropolitan teaching hospital during a 3-month period. RESULTS: Eighty-three patients (39%) with hyponatremia (serum sodium concentration less than 135 mmol/L) were observed during 99 hospitalizations, for a frequency of 38%. The mean (+/- standard error) of the lowest serum sodium concentration was 128 +/- 1 mmol/L in the hyponatremic patients and 138 +/- 1 mmol/L in the normonatremic patients. Hyponatremia was present on admission during 57 hospitalizations and was associated with gastrointestinal losses and hypovolemia in 43%. When hyponatremia developed during hospitalization, 68% of the patients were clinically euvolemic and had a syndrome consistent with inappropriate secretion of antidiuretic hormone (SIADH). Patients with hyponatremia were hospitalized longer than those with normal serum sodium concentrations (17 +/- 1 versus 9 +/- 1 days, p < 0.001). In addition, the mortality rate in the hyponatremic group was higher than that in the normonatremic group (36.5% versus 19.7%, p < 0.01). CONCLUSION: Hyponatremia is a common electrolyte disorder in patients hospitalized with AIDS or ARC and is frequently associated with gastrointestinal losses or SIADH as well as increased morbidity and mortality.

Thyroxine and triiodothyronine distribution and metabolism in thyroxine-replaced athyreotic dogs and normal humans.

Reported parenteral L-thyroxine (T4) replacement doses (10-20 micrograms.kg-1 x day-1) are larger than T4 production rates (2.5 micrograms.kg-1 x day-1) in athyreotic dogs but not humans. Furthermore, initial volumes of 3,5,3'-triiodothyronine (T3) tracer distribution exceed those for T4 in both species. To evaluate these discrepancies, serum T4 and T3 tracer kinetic studies from T4-replaced athyreotic dogs (5 micrograms.kg-1 x day-1 sc) and euthyroid humans were analyzed in a three-pool model (rapidly and slowly equilibrating pools with serum). Dogs had lower total T4 (41%) and T3 (31%) and higher free fractions of T4 (432%) and T3 (456%) than humans. Initial T3 distribution volumes were 454% those for T4 in dogs and 149% in humans, 498% of predicted plasma volumes in dogs and 121-138% in humans. Thus plasma volumes were used as time 0 estimates for T3 data analysis. Dogs had higher fractional T4 and T3 transfer rates from serum to the rapid pools (440-451%), total T4 clearance (353%) and production rates (147%), similar total T3 clearance, but lower free T3 clearance (32%) and production rates (45%) than humans. These findings suggest: 1) higher fractional transfer rates of T4 and T3 from serum to tissues and total serum T4 clearance rates in dogs than humans relate to lower canine serum T4 and T3 binding, and 2) parenteral L-T4 replacement doses required to achieve upper-normal serum total T4 concentrations in athyreotic dogs (5 micrograms.kg-1 x day-1) correspond to T4 production rates (6.8 micrograms.kg-1 x day-1).

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.

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.

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)

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.

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.

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)

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)

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.

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.

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)

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.