The Colorado thyroid disease prevalence study

CONTEXT: The prevalence of abnormal thyroid function in the United States and the significance of thyroid dysfunction remain controversial. Systemic effects of abnormal thyroid function have not been fully delineated, particularly in cases of mild thyroid failure. Also, the relationship between traditional hypothyroid symptoms and biochemical thyroid function is unclear. OBJECTIVE: To determine the prevalence of abnormal thyroid function and the relationship between (1) abnormal thyroid function and lipid levels and (2) abnormal thyroid function and symptoms using modern and sensitive thyroid tests. DESIGN: Cross-sectional study. PARTICIPANTS: Participants in a statewide health fair in Colorado, 1995 (N = 25 862). MAIN OUTCOME MEASURES: Serum thyrotropin (thyroid-stimulating hormone [TSH]) and total thyroxine (T4) concentrations, serum lipid levels, and responses to a hypothyroid symptoms questionnaire. RESULTS: The prevalence of elevated TSH levels (normal range, 0.3-5.1 mIU/L) in this population was 9.5%, and the prevalence of decreased TSH levels was 2.2%. Forty percent of patients taking thyroid medications had abnormal TSH levels. Lipid levels increased in a graded fashion as thyroid function declined. Also, the mean total cholesterol and low-density lipoprotein cholesterol levels of subjects with TSH values between 5.1 and 10 mIU/L were significantly greater than the corresponding mean lipid levels in euthyroid subjects. Symptoms were reported more often in hypothyroid vs euthyroid individuals, but individual symptom sensitivities were low. CONCLUSIONS: The prevalence of abnormal biochemical thyroid function reported here is substantial and confirms previous reports in smaller populations. Among patients taking thyroid medication, only 60% were within the normal range of TSH. Modest elevations of TSH corresponded to changes in lipid levels that may affect cardiovascular health. Individual symptoms were not very sensitive, but patients who report multiple thyroid symptoms warrant serum thyroid testing. These results confirm that thyroid dysfunction is common, may often go undetected, and may be associated with adverse health outcomes that can be avoided by serum TSH measurement.     

Lack of Polarized Type 1 or Type 2 Cytokine Profile in Asymptomatic HIV-1-Infected Patients During a Two-Year Bimonthly Follow-Up

The production of type 1 (interferon or IFN-γ) and type 2 (interleukin or IL-4 and IL-10) cytokines by mitogen-stimulated peripheral blood mononuclear cells (PBMCs) obtained from asymptomatic human immunodeficiency virus-seropositive (HIV⁺) patients untreated with any antiviral, antibacterial or antimycotic drugs, and from healthy individuals, was evaluated by quantitative ELISA. Patients who were HIV⁺ were characterized by the absence of abnormal cytokine production. The level of each cytokine differed among individuals in the same group with intersubject variations greater for HIV⁺ patients than for healthy individuals. The longitudinal evaluation of IFN-γ, IL-4 and IL-10 production showed intrasubject variations which were particularly marked in HIV⁺ patients. Accordingly, HIV⁺ patients and, to a lesser extent, healthy individuals were characterized by a wide spectrum of possible profiles, which were confined to type 0 phenotype. In HIV⁺ patients no correlation was found between each cytokine level and the number of CD4⁺ T cells, not even in those with a falling CD4⁺ T-cell count and clinical symptoms.     

Predictors of urinary tract infection based on artificial neural networks and genetic algorithms

BACKGROUND: Among women who present with urinary complaints, only 50% are found to have urinary tract infection. Individual urinary symptoms and urinalysis are not sufficiently accurate to discriminate those with and without the diagnosis. METHODS: We used artificial neural networks (ANN) coupled with genetic algorithms to evolve combinations of clinical variables optimized for predicting urinary tract infection. The ANN were applied to 212 women ages 19-84 who presented to an ambulatory clinic with urinary complaints. Urinary tract infection was defined in separate models as uropathogen counts of > or =10(5) colony-forming units (CFU) per milliliter, and counts of > or =10(2) CFU per milliliter. RESULTS: Five-variable sets were evolved that classified cases of urinary tract infection and non-infection with receiver-operating characteristic (ROC) curve areas that ranged from 0.853 (for uropathogen counts of > or =10(5) CFU per milliliter) to 0.792 (for uropathogen counts of > or =10(2) CFU per milliliter). Predictor variables (which included urinary frequency, dysuria, foul urine odor, symptom duration, history of diabetes, leukocyte esterase on urine dipstick, and red blood cells, epithelial cells, and bacteria on urinalysis) differed depending on the pathogen count that defined urinary tract infection. Network influence analyses showed that some variables predicted urine infection in unexpected ways, and interacted with other variables in making predictions. CONCLUSIONS: ANN and genetic algorithms can reveal parsimonious variable sets accurate for predicting urinary tract infection, and novel relationships between symptoms, urinalysis findings, and infection.     

Contribution of CD4+, CD8+CD28+, and CD8+CD28- T cells to CD3+ lymphocyte homeostasis during the natural course of HIV-1 infection.

The relationship between the number of circulating CD4+ T cells and the presence of particular CD8+ T cell subsets was analyzed by flow cytometry on PBL from asymptomatic HIV-1-infected patients whose specimens were collected every 2 mo for a total period of 32 mo. Only slight variations were detected in the absolute number of lymphocytes and percentage of CD3+ lymphocytes, whereas both CD4+ and CD8+ T cell subsets showed wide intrapatient variation. Variations in the number of CD8+CD28+ cells paralleled those of the CD4+ T cell subset in each patient tested, while the presence of CD8+CD28- T cells correlated inversely with CD4+ and CD8+CD28+ T cells. These data show that changes in the number of circulating CD4+-and CD8+CD28+ T cells are strongly related to the presence of CD8+CD28- T cells in these patients. Insight into the significance of CD8+CD28- T cell expansion will allow us to understand the mechanisms and significance of the HIV-1- driven change in CD4+CD8+ T cell homeostasis and the basic immunopathology of HIV disease.     

The diagnosis of alcohol-related brain damage: a retrospective study in alcoholics undergoing in-patient rehabilitation

Alcohol-related brain damage (ARBD) is a common and prognostically relevant complication of alcohol dependence. Clinical sensitivity for ARBD by routine mental state examination (MSE) is important, but unlikely given the documented insensitivity of the MSE in detecting less subtle disorders. We sought to determine the predictive capacity of a well-documented MSE in 32 detoxified alcohol-dependent patients who had undergone neuropsychological testing. Seventeen patients were found to have impaired performance on neuropsychological testing. The initial medical diagnoses and short-term memory tests did not correlate with neuropsychological findings. Ratings of the non-memory component of the MSE were a weak predictor of neuropsychological impairment. In the absence of any adequate 'screening' procedure, we conclude that all alcohol-dependent patients should be considered at high risk for ARBD and require full investigation.     

Body mass index percentile more sensitive than acanthosis nigricans for screening Native American children for diabetes risk

BackgroundMany Native American tribes use acanthosis nigricans to screen for type 2 diabetes risk. We hypothesized that acanthosis nigricans misses many children at risk for type 2 diabetes.MethodsWe evaluated 5- to 18-year-old Native American children and youth to assess the sensitivity and specificity of acanthosis nigricans as a marker for insulin resistance.ResultsIn a cohort of 161 youth (72 males/89 females), mean age was 10.7 years + 3.9. Mean body mass index (BMI) percentile was 76.8 ± 23.3, and 54% had a BMI at or above the 85th percentile. Acanthosis nigricans was present in 21.7% of the participants and was more common in 12- to 18-year-olds than in 5- to 11-year-olds (p = .02). Of those with acanthosis nigricans, 82.4% had insulin resistance (homeo-static model assessment of insulin resistance >4), but only 48.3% of those with insulin resistance had acanthosis nigri-cans. In contrast, BMI at or above the 85th percentile had a high sensitivity (74%) for insulin resistance, even though its specificity was lower (58%).ConclusionsThe presence of acanthosis nigricans alone was a specific, but not a sensitive, screening tool for identifying youth with insulin resistance. BMI at or above the 85th percentile was a more sensitive screening tool than acanthosis nigricans alone, or acanthosis nigricans and BMI together for identifying children and youth with IR who are at increased risk for type 2 diabetes.     

The effects of proficiency and bias on residents' interpretation of the microscopic urinalysis.

OBJECTIVE: This study aims to determine whether residents are influenced by clinical information when interpreting microscopic urinalysis (UA) and estimating the probability of a urinary tract infection (UTI), and to determine the accuracy and reliability of UA readings. DESIGN: Residents estimated the UA white blood cell count and the probability of a UTI in vignettes using a fractional factorial design, varying symptoms, gender, and the white blood cell count on preprepared urine slides. RESULTS: Individual-level results indicated a clinical information bias and poor accuracy. Seventeen of 38 residents increased the white blood cell count in response to female gender; 14 increased the white blood cell count in response to UTI symptoms. Forty-nine percent of the readings were inaccurate; agreement ranged from 50% to 67% for white and red blood cells and bacteria. CONCLUSION: Many residents gave inaccurate UA readings, and many readings varied with clinical information. A significant portion of residents needs assistance in objectively and accurately interpreting the UA.     

Do traditional symptoms of hypothyroidism correlate with biochemical disease?

Objective  Hypothyroidism often remains undetected because of the difficulty associating symptoms with disease. To determine the relation between symptoms and biochemical disease, we assessed symptoms and serum thyroid function tests, concurrently, for patients with and without hypothyroidism. Design  Cross-sectional study. Setting/Patients  Seventy-six newly diagnosed case patients with overt hypothyroidism and 147 matched control patients identified through outpatient laboratories in Michigan and Colorado. Measurements and main results  Patient symptoms were assessed by questionnaire. Case patients reported a higher proportion of hypothyroid symptoms than did control patients (30.2% vs 16.5%,p<.0001). Univariate analysis identified three significant predictors of an elevated level of thyroid-stimulating hormone (TSH) (p<.05), and 13 symptoms which, when they had changed in the past year, were reported more often by case patients with hypothyroidism than by control patients (p<.005). Individuals reporting changes in 7 or more symptoms were significantly more likely to have hypothyroidism (likelihood ratio [LR]=8.7, 95% confidence interval [CI] 3.8, 20.2); those reporting changes in 2 or fewer symptoms were less likely to have hypothyroidism (LR=0.5, 95% CI 0.4, 0.7). Conclusions  In this sample, the number of hypothyroid symptoms reported was directly related to the level of TSH. The association was stronger when more symptoms were reported. Symptoms that had changed in the past year were more powerful than symptoms reported present at the time of testing. This suggests that traditional symptoms are valuable when deciding which patients to test for hypothyroidism. The pilot to this study was presented as a poster at the regional meeting of the Society of General Internal Medicine, September 1995. The results of this study were presented as a poster at the annual meeting of the Society for Medical Decision Making, October 1996. Supported by the General Clinical Research Center via U.S. Public Health Service Research Grant RR-00051 from the Division of Research Resources at the University of Colorado Health Sciences Center, and a Butterworth Foundation grant, Butterworth Hospital, Grand Rapids, Mich.