Richard A. Becker

Hypermetabolic Low Triiodothyronine Syndrome of Burn Injury

The free tetraiodothyronine index (FT4I) and free triiodothyronine index (FT3I) in burn patients represented the serum levels of free (dialyzable) T4 and free T3, respectively. FT4I and FT3I were lower with greater burn size and were lower in nonsurvivors than expected for the burn size. There was no compensatory elevation of basal or releasing hormone-stimulated thyrotrophin (TSH) concentrations. Reverse T3 was higher with greater burn size. T3 treatment restored FT3I but did not affect mortality or resting metabolic rate (MR) measured in survivors, compared with placebo therapy. Whereas the hypermetabolic response to burn injury appeared to be independent of thyroid hormones, MR was correlated positively with burn size and with elevated plasma nor-epinephrine and epinephrine concentrations for several weeks after injury. Lack of augmented TSH concentrations, absence of low plasma reverse T3, and presence of hypermetabolism suggest that the reduced plasma free T3 does not indicate functional hypothyroidism, but may represent an adaptation to the assumption of metabolic control by the sympathetic nervous system.

Cortisol and Corticotrophin in Burned Patients

In a study of 36 men burned in a fire, based on sequential early morning samples, plasma cortisol concentration was elevated in proportion to burn size. Plasma corticotrophin (ACTH) was not correlated with burn size, suggesting that factors other than ACTH contribute to the elevated cortisol. Cortisol levels did not fall on the days preceding death in nonsurvivors. During 24-hr sampling, burned patients exhibited a fitted cortisol curve mean that was elevated in proportion to burn size, a rhythm amplitude that was significantly less than that in uninjured controls, and a normal peak time. Metabolic rate, rectal temperature, and urinary catecholamine excretion were also elevated in proportion to burn size. Although plasma cortisol was positively correlated with metabolic rate and with temperature, this appeared to result from a common relationship of these variables with burn size. On the other hand, urinary catecholamine values significantly reduced the residual variance of metabolic rate and temperature after accounting for variance related to burn size. Cortisol appears to be less prominent than catecholamines as a possible mediator of the elevated thermogenesis.

Nonthyroidal control of metabolism after burn injury: Possible role of glucagon

Abstract The endocrine basis for control of metabolism in nonthyroidal illness is not yet understood. Burn injury is associated with reduced serum concentrations of thyroid hormones and with resting hypermetabolism. One index of severity is total burn size (TBS, % body surface). After overnight fasting and recumbency, resting metabolic rate (MR, O 2 consumption) was measured weekly and plasma was sampled for determination of glucose, total cholesterol, triglycerides, insulin, glucagon, somatostatin, growth hormone, norepinephrine, epinephrine, and cortisol in 28 burned men, 17–23 years old, TBS 2%–85%, including 8 controls with minimal injury (TBS ≤ 7.5%). MR was elevated in proportion to burn size mainly in the first week then declined toward normal. Growth hormone was not changed. Two multiple regression analyses (validated by random partitioning of data) determined which plasma variables independently reflected residual variation in MR: without TBS entered as a variable, high MR was associated with elevated glucose, cortisol, and glucagon, and low cholesterol (cumulative r 2 = 0.79); with TBS entered, high MR was associated with greater TBS, elevated norepinephrine, and again high glucagon and low cholesterol ( r 2 = 0.81). Resting metabolism after burn injury is controlled not by the thyroid but may be controlled by a set of antiinsulin hormones that does not include growth hormone, but possibly includes glucagon.

Opioid and dopamine involvement in prolactin release induced by arginine vasotocin and vasopressin in the male rat

The potential involvement of the endogenous opioid and dopamine (DA) systems in the mechanism(s) mediating arginine vasotocin (AVT)- and arginine vasopressin (AVP)-induced prolactin (PRL) release was investigated in vivo. The injection of AVT (5 micrograms) into unanesthetized male rats resulted in a 2-fold stimulation of PRL release 15 min later, followed by an inhibition of PRL release 30 min thereafter; both the stimulatory and inhibitory PRL responses to AVT were obviated by naloxone (NAL) (200 micrograms). Similarly, the administration of either AVT or AVP (5 micrograms) to urethane-anesthetized rats led to a 3- and 5-fold increase in plasma PRL levels, respectively, 10 min after injection. The PRL stimulatory response to both peptides was completely blocked by pretreating the animals with apomorphine (APO) (5 mg); however, the injection of APO by itself had no effect on PRL secretion in these animals. Both AVT and AVP were also effective in stimulating PRL release 10 min after injection in estrogen (50 micrograms)-progesterone (25 mg) (EP)-treated rats anesthetized with urethane. APO negated the PRL stimulatory response to these compounds in the EP-treated rat as well. Normal, urethane-treated rats experienced a 7- to 8-fold increase in PRL levels 20 min following the injection of methysergide (MET) (250 micrograms). Both AVT and AVP caused approximately a 2.5-fold greater PRL response in MET-treated animals than in AVT and AVP controls, respectively; however, only in the MET + AVT-treated rats was the PRL stimulatory response greater than in the MET controls. MET probably stimulated PRL through its DA antagonistic properties.(ABSTRACT TRUNCATED AT 250 WORDS)

Visceral Blood Flow Following Thermal Injury

To determine if visceral blood flow was altered by thermal injury, effective renal blood flow (ERBF) was measured by para-aminohippurate clearance in five control subjects and 13 nonbacteremic burn patients (mean burn size: 50% total body surface, range: 24.5-83.5) 6-25 days after burn injury. Splanchnic blood flow (SBF) and cardiac output were determined in a matched group of ten patients by indocyanine green clearance and dilution techniques, respectively. Renal and splanchnic oxygen consumptions (VO2) were calculated from regional arteriovenous O2 differences and blood flows. ERBF was not significantly elevated in these patients (780 +/- 68 ml/min x m2, mean +/- SE, versus 552 +/- 37 in controls). SBF, at 1463 +/- 96 ml/min x m2, was twice normal and 19% of the cardiac index (7764 +/- 393 ml/min x m2). Individual variations in ERBF and SBF were unrelated to burn size or the time after injury, but ERBF varied with 24-hour sodium excretion. Renal and splanchnic VO2 were twice normal levels at 33 +/- 6 and 66 +/- 4 ml/min, respectively. These results indicate that an increase in ERBF is not an obligatory response to burn injury, but is dependent on sodium load and/or vascular volume. Conversely, SBF is consistently increased by thermal injury and contributes to the rise in cardiac output after injury. While the increase of SBF is appropriate for the rise in local VO2, the cause of the apparent splanchnic vasodilation is unknown.

A Prospective Study of Circulating Prolactin During Primigravid Pregnancy

A prospective, cross-sectional study of 164 primigravid patients was conducted to determine the role of prolactin in the pathogenesis of pregnancy induced hypertension. Clinically normal patients had peripheral venous blood sampled from the lateral and recumbent positions monthly in the morning during their last two trimesters in labor and six weeks postpartum. One-third of the patients had 24 hour urine collections. Homologous double antibody radioimmunoassays were performed to determine prolactin levels. The data were analyzed according to pregnancy outcome: pregnancy-induced hypertension or normotensive throughout pregnancy. Acute positional change did not influence prolactin level. Prolactin levels were significantly elevated in the hypertensive outcome group only at 37-39 weeks and were not correlated with sodium excretion. We conclude that circulating prolactin does not play a significant role in pathogenesis of pregnancy-induced hypertension, but perhaps the elevated levels may be reflecting pathophysiologic changes.

Nonthyroidal Control of Metabolism After Burn Injury Possible Role of Glucagon

The endocrine basis for control of metabolism in nonthyroidal illness is not yet understood. Burn injury is associated with reduced serum concentrations of thyroid hormones and with resting hypermetabolism. One index of severity is total burn size (TBS, % body surface). After overnight fasting and recumbency, resting metabolic rate (MR, O2 consumption) was measured weekly and plasma was sampled for determination of glucose, total cholesterol, triglycerides, insulin, glucagon, somatostatin, growth hormone, norepinephrine, epinephrine, and cortisol in 28 burned men, 17-23 years old, TBS 2%-85%, including 8 controls with minimal injury (TBS less than or equal to 7.5%). MR was elevated in proportion to burn size mainly in the first week then declined toward normal. Growth hormone was not changed. Two multiple regression analyses (validated by random partitioning of data) determined which plasma variables independently reflected residual variation in MR: without TBS entered as a variable, high MR was associated with elevated glucose, cortisol, and glucagon, and low cholesterol (cumulative r2 = 0.79); with TBS entered, high MR was associated with greater TBS, elevated norepinephrine, and again high glucagon and low cholesterol (r2 = 0.81). Resting metabolism after burn injury is controlled not by the thyroid but may be controlled by a set of antiinsulin hormones that does not include growth hormone, but possibly includes glucagon.