Elaine M. Kaptein

RELATIONSHIP OF ALTERED THYROID HORMONE INDICES TO SURVIVAL IN NONTHYROIDAL ILLNESSES

Although alterations of serum thyroid hormone indices are frequent in nonthyroidal illnesses, their relationship to survival is poorly defined. Consequently, the prevalence and prognostic relevance of alterations in thyroidal indices were evaluated prospectively in 195 patients requiring intensive medical therapy and in 75 critically ill patients with serum total T4 (TT4) levels below 3 μg/dl. In the 195 patients, serum total T3 (TT3) and TT4 levels were reduced in 69% and 43% respectively. Decreased TT4 levels had the highest correlation with mortality (P < 0·001) and correctly predicted outcome in 70% of patients. Other thyroidal indices, which were significantly different between survivors and nonsurvivors, correlated with TT4 and did not contribute independently to prediction accuracy when assessed by discriminant function analysis.

Prolactin modulation of dehydroepiandrosterone sulfate secretion

To clarify the controversy about the effect of prolactin (PRL) on dehydroepiandrosterone sulfate (DHEA-S), this study was undertaken to investigate the effects of alterations in plasma PRL on plasma DHEA-S concentrations in hyperprolactinemic women, as well as in normal male subjects. DHEA-S was measured in a group of 21 women with hyperprolactinemia, galactorrhea, and amenorrhea (PRL:257 +/- 89 ng/ml; mean +/- SEM). In these women, mean plasma concentrations of DHEA-S (2.54 +/- 0.2 microgram/ml) were significantly higher (p < 0.005) than those in 41 normal control women (1.78 z microgram/ml) and those in a group of 11 amenorrheic patients (1.77 +/- 0.2 microgram/ml). Eight women with hyperprolactinemia were given 5 mg of bromocriptine each day for 4 consecutive weeks. Within 1 week of medication, PRL levels fell by 60% (p < 0.05). To test whether lowering normal plasma levels of PRL would affect plasma concentrations of DHEA-S, five normal male subjects received a 48-hour infusion of dopamine at an average rate of 6 microgram/kg/min. Plasma levels of PRL fell by 60% (p < 0.01) after 8 hours of infusion, and DHEA-S decreased by 27% by 16 hours (p < 0.05). These data suggest that PRL modulates the secretion of DHEA-S: an increase in plasma levels of PRL is correlated with elevated concentrations of DHEA-S, whereas a decrease in PRL is followed by a fall in DHEA-S.

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.

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.

Peripheral tissue mechanism for maintenance of serum triiodothyronine values in a thyroxine-deficient state in man.

The present study was undertaken to define the source of endogenous triiodothyronine (T3) production responsible for maintaining serum T3 levels in euthyroid subjects with depressed serum thyroxine (T4) values. After withdrawal from 4 wk of exogenous T3 administration, a 22% decline in serum T3 values (from 129 +/- 6 to 99 +/- 4 ng/dl) was observed in six euthyroid subjects, despite a twofold reduction in serum T4 concentrations (from 7.5 +/- 0.5 to 3.2 +/- 0.5 micrograms/dl). This was accompanied by a nearly twofold increase in serum T3/T4 ratio values (17 +/- 1 to 29 +/- 6) but no significant alteration in reverse T3/T4 ratio values. This phenomenon did not appear to be thyroid stimulating hormone (TSH) dependent, since base-line serum TSH values were subnormal. Nor was it dependent on changes in thyroid gland function, since a blunted T3 response to exogenous bovine TSH occurred and pharmacologic doses of iodide did not influence the phenomenon. The finding in three athyreotic subjects that serum T3/T4 ratio values increased from 14 +/- 1 on T4 therapy (mean serum T4, 9.6 +/- 0.8 micrograms/dl and T3, 132 +/- 8 ng/dl) to 40 +/- 2 after withdrawal from 2 wk of T3 administration (serum T4 1.2 +/- 0.1 micrograms/dl and T3 46 +/- 3 ng/dl) provided direct evidence that an alteration in peripheral thyroid hormone metabolism was probably responsible for these findings previously observed in euthyroid subjects. The results of this study support the possible existence in euthyroid man of a peripheral tissue autoregulatory mechanism for maintaining serum T3 values in states of T4 deficiency. Whether this process involves an alteration in the efficiency of T4 to T3 conversion or the rate of T3 clearance is presently unknown.

Thyroid Hormone Therapy for Obesity and Nonthyroidal Illnesses: A Systematic Review

CONTEXT Thyroid hormone therapy to enhance weight loss in obesity during caloric deprivation and to improve morbidity and mortality in adults with nonthyroidal illnesses remains controversial. OBJECTIVE The aim of this study was to conduct a systematic review evaluating effectiveness and risks of T(3) and/or T(4) therapy in these populations. DATA SOURCES Electronic databases and reference lists were searched. STUDY SELECTION Studies with comparable control groups comparing T(3) and/or T(4) therapy to placebo in randomized controlled trials (RCTs) or prospective observational studies were selected. DATA EXTRACTION Three reviewers performed serial abstraction. DATA SYNTHESIS During caloric deprivation of obese subjects, T(3) therapy decreased serum TSH and T(4) concentrations. Consistent effects of T(3) or T(4) on weight loss, protein breakdown, metabolic rate, and heart rate could not be established. In euthyroid cardiac patients, T(3) decreased TSH and free T(4) levels, without consistent effects of T(3) or T(4) on heart rate, cardiac output, or systemic vascular resistance. Mortality increased 3.3-fold with T(4) therapy in acute renal failure patients, whereas an effect in cardiac, critically ill, and burn patients could not be established. Equivalence testing indicated that larger RCTs are required to determine whether thyroid hormone therapy alters end-points in obesity or nonthyroidal illnesses. LIMITATIONS Numbers of usable unique studies were small, numbers of patients in each study were inadequate, end-points were variable, few RCTs were performed, and study quality of non-RCTs was poor. CONCLUSIONS Available data are inconclusive regarding effectiveness of thyroid hormone therapy in treating obesity or nonthyroidal illnesses, whereas data support that such therapy induces subclinical hyperthyroidism.

Thyroid Function in Patients with Nephrotic Syndrome and Normal Renal Function

Alterations of thyroid hormone indices have been described in patients with nephrotic syndrome. However, the majority of these patients also had either diabetes mellitus or significant renal failure,

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.

Thyroid Hormone Therapy for Postoperative Nonthyroidal Illnesses: A Systematic Review and Synthesis

CONTEXT Effects of thyroid hormone therapy on postoperative morbidity and mortality in adults remain controversial. OBJECTIVE The aim was to conduct a systematic review evaluating effects and risks of postoperative T(3) therapy in adults. DATA SOURCES Electronic databases and reference lists through March 2010 were searched. STUDY SELECTION Studies with comparable control groups comparing T(3) to placebo therapy in randomized controlled trials were selected. DATA EXTRACTION Two reviewers independently screened and reviewed titles, abstracts, and articles. Data were abstracted from 14 randomized controlled trials (13 cardiac surgery and one renal transplantation). In seven studies, iv T(3) was given in high doses (0.175-0.333 μg/kg · h) for 6 to 9 h, in four studies iv T(3) was given in low doses (0.0275-0.0333 μg/kg · h for 14 to 24 h), and in three studies T(3) was given orally in variable doses and durations. DATA SYNTHESIS Both high- and low-dose iv T(3) therapy increased cardiac index after coronary artery bypass surgery. Mortality was not significantly altered by high-dose iv T(3) therapy and could not be assessed for low-dose iv or oral T(3). Effects on systemic vascular resistance, heart rate, pulmonary capillary wedge pressure, new onset atrial fibrillation, inotrope use, serum TSH and T(4) were inconclusive. LIMITATIONS Numbers of usable unique studies and group sizes were small. Duration of T(3) therapy was short, and dosages and routes of administration varied. CONCLUSIONS Short duration postoperative iv T(3) therapy increases cardiac index and does not alter mortality. Effects on other parameters are inconclusive.