Paul D. Woolf

Hormonal responses to trauma

ObjectivesTo review the hormonal changes that have been reported after trauma, to define their etiologies, and to describe their consequences. Data SourcesLiterature review using MEDLINE and original data. Data SynthesisHormonal responses to trauma are bidirectional. Functional derangements include increases in adrenocorticotropin hormone and cortisol, growth hormone, and prolactin levels. In contrast, gonadotropin and gonadal steroid, and thyroid hormone concentrations decrease. The response is immediate but not necessarily sustained for those hormones that respond with increased secretion, whereas the effect may not become apparent for several hours, may be maximal after 1 to 4 days, and may persist for the duration of illness for those hormones that decrease. The reduction in hormone concentrations generally reflect diminished secretion, with the exception of the thyroid hormones where altered metabolic pathways and enhanced metabolic clearance play a major role. ConclusionsThe changes in circulating levels do not appear to be injury specific, but tend to reflect the severity of the traumatic insult, and there are some data for cortisol and thyroxine that show their concentrations may be of predictive value. In head-injured patients, structural as well as functional pituitary changes may be present. Patients may show varying degrees of pituitary insufficiency. However, the presence of hyperprolactinemia strongly suggests involvement of the hypothalamus. With the exception of bonafide hypopituitarism, the relevance of the hormonal changes after trauma awaits clarification.

Thyrotoxicosis with painless thyroiditis.

Four women and one man with painless subacute thyroiditis presented with hypermetabolic signs and symptoms. Thyroxine (T4) and triiodothyronine (T3) resin uptakes (T3R) were increased but the 24 hour radioactive iodine (RAI) uptakes were less than 1 per cent. Surreptitious use of thyroid hormone was excluded. The thyroid was enlarged in one patient and nontender in all. Exophthalmos was absent. The protein-bound iodine level was 1.1 to 9.5 mug/dl greater than the T4 level. The sedimentation rate was normal or minimally increased, and antithyroglobulin and antimicrosomal antibodies were undetectable. In one hospitalized patient 84 per cent of the administered dose of 131I was recovered in the urine within 48 hours (normal 64 per cent) excluding extrathyroidal uptake. In all subjects the T4 and T3R levels fell to normal or slightly below normal within one to four months. An increase in the 2 and 24 hour RAI uptake to minimally increased or high normal values and return of the T4 and T3R levels to normal occurred in four of five patients within six months. In one of these, the administration of thyroid-stimulating hormone (TSH) resulted in an appropriate increase in 24 hour RAI uptake from 14.9 to 37.1 per cent. One woman remained clinically hypothyroid for six months with a low T4 concentration (3.2 mug/dl), an elevated TSH level (48 muU/ml) and evidence of a persistent organification defect -- two hour RAI uptake decreasing from 33 to 23 per cent after the administration of perchlorate and the 24 hour RAI uptake increasing from 32 to 76 per cent following the administration of TSH. At 21 months after the initial onset of her illness, she is euthyroid but increased RAI uptake persists. The clinical course in four of the five patients is similar to that in an additional eight patients treated during the same time period who presented with typical subacute thyroiditis. Thus, these patients have a form of painless subacute thyroiditis which presents as thyrotoxicosis but is differentiated from it by a low RAI uptake and in whom recovery of thyroidal iodine trapping is the first indicator of recovery. The hyperthyroidism is self-limiting and should be treated conservatively.

Autonomic control of heart rate after brain injury in children

OBJECTIVES To study sequential changes in heart rate, respiratory rate, blood pressure, heart rate power spectra, and plasma catecholamine concentrations in patients with acute brain injury and correlate these variables with the severity of neurologic dysfunction and patient outcome. DESIGN Prospective, clinical study. SETTING Pediatric intensive care unit. PATIENTS Thirty-seven pediatric patients with acute brain injury caused by trauma, anoxia/ischemia, hemorrhage, or infection. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS We found significant associations between low-frequency (0.01 to 0.15 Hz) heart rate power and severity of neurologic dysfunction (as assessed by the admission Glasgow Coma Scale) (p < .001) and patient outcome (as assessed by the Glasgow Outcome Scale) (p = .05). The admission (p = .05) and maximum (p < .001) values for low-frequency heart rate power and the minimum value for high-frequency (0.15 to 0.50 Hz) heart rate power obtained during hospitalization (p = .001) predicted an increased likelihood of survival. Ten brain-dead patients had significantly decreased low-frequency heart rate power (p = .008) and plasma norepinephrine (p = .015), epinephrine (p = .03), and dopamine (p = .04) concentrations when compared with six non-brain-dead patients with a Glasgow Coma Scale score of 3. CONCLUSIONS Our results imply that autonomic nervous system control of heart rate is disrupted in proportion to the degree of neurologic insult in children after acute brain injury. Thus, heart rate power spectral analysis and plasma catecholamine concentrations may prove to be useful adjuncts in determining severity of neurologic injury and prognosis for recovery in children suffering from brain injury. In addition, these techniques may aid in the determination of brain death.

Autonomic modulation of heart rate variability during endotoxin shock in rabbits

OBJECTIVE Gram-negative septic shock is associated with severe hypotension and autonomic cardiovascular dysfunction. We hypothesized that in an anesthetized rabbit model of endotoxin shock, autonomic modulation of cardiac activity, as measured by power spectral analysis of heart rate (HR) variability, would be decreased compared with the anesthetized control rabbits. DESIGN Experimental, comparative study. SETTING Laboratory of a university hospital. SUBJECTS Fourteen adult male New Zealand white rabbits (2.7 to 3.1 kg body weight) were studied under anesthesia. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS We studied the absolute and temporal changes in HR power spectra and plasma catecholamine concentrations in eight experimental and six control New Zealand white rabbits during Escherichia coli endotoxin-induced shock. HR, respirations, arterial blood pressure (BP), HR power spectra, and plasma catecholamine concentrations were measured at 5- to 10-min intervals for 60 mins in control rabbits or until the mean arterial pressure (MAP) decreased by > or = 20 mm Hg in experimental rabbits. There were no differences in basal HR, respiratory rate, BP, HR power spectra, or catecholamine concentrations between groups. After endotoxin administration, MAP decreased (82 +/- 7 vs. 62 +/- 5 mm Hg; p < .05) as did log low-frequency HR power (-2.14 +/- 2.46 vs. -2.20 +/- 2.48 beats/min2; p < .05). Low-frequency HR power and MAP remained unchanged in control animals. Log high-frequency HR power decreased in control and experimental rabbits (-1.02 +/- 1.34 vs. -1.69 +/- 2.12 [control], p < .05; -1.53 +/- 2.19 vs. -2.19 +/- 2.85 beats/min2 [experimental], p < .05). While there was an inverse relationship between low- and high-frequency HR power and MAP, the direction of change was opposite in six of six rabbits in the control group and in six of eight rabbits in the experimental group. Plasma catecholamine concentrations did not change during the experiment in either group. CONCLUSIONS Sympathetic modulation of cardiac activity decreased, while the sympathomedullary response remained unchanged during endotoxin shock. We speculate that a concomitant decrease in low-frequency HR power as MAP decreases may prove to be an early marker for impending shock.

Thyroid test abnormalities in traumatic brain Injury: Correlation with neurologic impairment and sympathetic nervous system activation

Acute illness is well known to affect thyroid function, but there are few studies correlating the severity of the underlying medical problem with indexes of thyroid function and little is known about its cause. Traumatically brain-injured patients were selected because they were a relatively homogeneous, previously healthy group with a condition whose severity was readily quantifiable. In 66 such patients, the relationships between changes in thyroid function tests (thyroxine, free thyroxine, triiodothyronine, reverse triiodothyronine, and thyrotropin levels), catecholamine and cortisol concentrations measured on admission and again four days after the accident, and neurologic function assessed by the Glasgow Coma Score (GCS) were studied. Triiodothyronine and thyroxine levels fell significantly within 24 hours of injury. Four days after the accident, patients with the greatest neurologic dysfunction had the lowest triiodothyronine and thyroxine levels; significant correlations were present between the Day 4 GCS and concomitant thyroxine (r = 0.47, p less than 0.0001), free thyroxine (r = 0.32, p less than 0.02), and triiodothyronine (r = 0.50, p less than 0.0001) levels. Reverse triiodothyronine values remained unchanged throughout the study even in the most severely affected patients; the rise in thyrotropin levels was not significant (1.2 +/- 0.2 to 1.7 +/- 0.3 microU/ml, p = NS). Patients who died or remained vegetative had thyroxine and triiodothyronine levels 30 percent to 50 percent lower than those who had a good recovery (p less than 0.05). Highly significant correlations were present between Day 4 thyroxine and triiodothyronine levels and admission and Day 4 norepinephrine and epinephrine concentrations. There was no association between admission or concomitant cortisol levels and thyroid function on Day 4; treatment with high-dose dexamethasone did not influence these indexes. Thus, patients with traumatic brain injury exhibit a gradient of thyroid dysfunction that occurs promptly, is dependent upon the degree of neurologic impairment, and reflects ultimate outcome. The significant association with catecholamine levels suggests a role for sympathetic nervous system activation in its causation, independent of a generalized stress response, since there is no correlation of thyroid test abnormality with the degree of adrenocortical secretion.

Autonomic cardiovascular state after severe brain injury and brain death in children

ObjectiveTo study and compare the autonomic cardiovascular state of children after severe brain injury and brain death. DesignProspective clinical study. SettingPediatric ICU. PatientsPediatric patients suffering severe brain injury caused by trauma, anoxia, or hemorrhage. InterventionNone. Measurements and Main ResultsWe analyzed cardiorespiratory parameters, heart rate power spectra, plasma catecholamine concentrations, and the response to the cold pressor test in nine brain-dead patients and compared the results with the test findings of 11 patients with severe brain injury.Low-frequency total heart rate power (p < .03), peak amplitude (p < .02), and plasma catecholamine concentrations (p < .001) were different with no overlap of values between groups. Cold pressor testing in patients with severe brain injury showed changes in respiratory rate and low-frequency heart rate power that were ±20% to 100% from baseline values; however, there were no measurable changes in brain-dead patients. ConclusionsOur results support the concept of a damaged sympathetic cardiovascular system in severe brain injury and complete interruption of the autonomic cardiovascular pathways in brain death. Since determination of brain death may be difficult, our findings have implications for corroborating brain death using autonomic cardiovascular testing. (CritCare Med 1993; 21:228–233)

Plasma ACTH levels in primary depression: Relationship to the 24-hour dexamethasone suppression test

The failure of adequate cortisol suppression after 1 mg dexamethasone in 50% of patients with endogenous depression has been attributed to abnormal hypothalamic-pituitary-adrenal axis regulation, resulting in high levels of adrenocorticotropic hormone (ACTH). Because studies of plasma ACTH have been conflicting, we studied plasma ACTH levels during the 24-hour dexamethasone suppression test in a homogeneous group of 29 hospitalized patients with primary endogenous depression and 19 normal volunteers. No differences were found in ACTH levels among normal volunteers, depressed cortisol suppressors, and depressed cortisol nonsuppressors at either 4 p.m. or 11 p.m.

Plasma ACTH levels in depression before and after recovery: Relationship to the dexamethasone suppresion test

Sixteen patients with major depressive disorder who were nonsuppressors on the dexamethasone suppression test (DST) on hospital admission were studied for plasma levels of adrenocorticotropic hormone (ACTH). Eight patients reverted to normal suppression with clinical recovery, while eight remained nonsuppressors. There was a significant reduction of ACTH levels in those who normalized on their DST, while ACTH levels remained high in the group that continued to be nonsuppressors. The results favored the hypothesis that dexamethasone nonsuppression in depression is mediated by high ACTH levels.

Abnormal prolactin responsivity to dopaminergic suppression in hyperprolactinemic patients

Abstract Previous in vivo studies have shown that the constant infusion of dopamine suppresses prolactin (PRL) levels to within the normal range in a variety of hyperprolactinemic states, but there are no data on the relative suppressibility of the lactotroph in patients with hyperprolactinemia or on their metabolism of dopamine. Consequently, six patients with elevated PRL levels received a dopamine infusion of 4 μg/kg/min to study PRL clearance while another eight patients underwent a graded infusion at rates of 0, 1, 2 and 4 μg/kg/min to test PRL suppressibility. In four patients of the latter group an 8 μg/kg/min infusion rate was added. Healthy volunteer control subjects underwent comparable studies. PRL was measured by radioimmunoassay and dopamine by radioenzymatic techniques. The absolute PRL levels at each infusion rate were greater in the patients than in the control subjects. During the 4 μg/kg/min infusion rate, the respective PRL concentrations were 8.2 ± 1.8 and 2.0 ±0.1 ng/ml, (p

Parathyroid hyperplasia and carcinoma within one gland

A 47-year-old Scottish woman vacationing in the United States presented with a serum calcium level greater than 20 mg/dl and a parathyroid hormone level 16 times greater than normal after a one-week history of severe vomiting and unrelenting abdominal pain. Surgical exploration of the thymus revealed the very rare association of a large (7 by 4 by 0.8 cm) parathyroid carcinoma adjacent to apparently normal parathyroid tissue, separated by a thin fibrous band. Two other hyperplastic and one normal parathyroid glands were also identified. Postoperatively, the patient became hypocalcemic and, for the past nine months, has received maintenance 1-alpha-hydroxycholecalciferol therapy (1 microgram per day) with normal calcium and barely detectable parathyroid hormone levels.