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Differential Diagnosis I Week 4

Differential Diagnosis I Week 4. Fatigue. Divided into organic and psychogenic; each represents about half of all cases 10%-30% have no identifiable cause 75% of all patients with fatigue improve in a 1-3 year period 50%-80% of all chronic fatigue patients have a psychiatric problem.

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Differential Diagnosis I Week 4

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  1. Differential Diagnosis I Week 4

  2. Fatigue Divided into organic and psychogenic; each represents about half of all cases 10%-30% have no identifiable cause 75% of all patients with fatigue improve in a 1-3 year period 50%-80% of all chronic fatigue patients have a psychiatric problem

  3. Fatigue Metabolic/Hormonal Depression Infection Chronic Fatigue Syndrome Sleep Disorders

  4. Anemia • Anemia is a decrease in RBCs, hematocrit, or hemoglobin • Anemia represents either: • decreased production • increased loss • increased breakdown • Divide into three categories based on size: • Macrocytic (increase in MCV) - B12/Folic Acid, hypothyroid/liver • Microcytic - Thalessemia minor, iron deficiency • Normal - Chronic disease

  5. Important Hx with Anemia Pregnancy - B12, Folic Acid, Iron Def. Alcohol abuse - B12, Folic Acid, Iron Def. Ethnic background/Family Hx - Thalessemia, Sickle Cell Blood loss - iron deficiency Chronic disease - RA, Diabetes, Cancer Drugs - chemotherapy, corticosteroids

  6. Thyroid Lab Evaluation • Supra-sensitive or ultrasensitiveTSH best test is most sensitive initial test. • Increase in FT4 or FT3 with a decrease in TSH indicates hyperthyroidism; opposite for hypothyroidism • Most common cause of hyperthyroidism is Graves • Test also for antithyroid antibody titer • Hypothyroid may occur with goiter (Hashimoto's) or without (atrophic thyroiditis)

  7. Diabetes Questioning • Ask about associated signs/symptoms such as blurred vision, tingling in feet or hands, poly- uria, dypsia, phagia, and in women frequent yeast infections • Ask about signs/symptoms of other disorders that may mimic diabetes • For known diabetics, determine control through questioning and test for glycosolated hemoglobin • Screen patients at high risk; blood glucose above 125 mg d/L is diagnostic; new category of pre-diabetes begins at levels above 100 mg d/L • Adult-onset managed with diet/exercise initially; if not controlled, medically managed with hypoglycemic agents first, if not controlled, then insulin

  8. Diabetes and Immunity In two recent studies researchers examined a possible relationship between gluten and IA (Norris and Ziegler refs). This investigation was prompted by the observation that there is an increased association between type I DM and celiac disease (Cronin ref). It was found that exposing an infant before the age of 3 months and after 7 months or older increased IA frequency especially in those with the HLA genotype HLA-DRB1*03/04, DQB8. This implies a possible relationship to cereal feeding (gluten specifically) and the timing of exposure in genetically predisposed individuals. It must be clear though that these studies focused on the construct of islet cell autoantibodies and not diagnoses of type I DM. These studies also involved a small group of individuals. It is likely that the combination of genetics and exposure to a multitude of environmental factors will be identified in the future versus a single stimulator of autoimmunity.

  9. References Norris JM, Beaty B, Klingensmith G et al. Lack of association between early exposure to cow’s milk protein and beta cell autoimmunity. JAMA 1996;276:609-614. Hummel M, Fuchtenbusch M, Schenker M, Ziegler A-G. No major association of breast feeding, vaccinations, and childhood with diseases with early islet autoimmunity in the German BABYDIAB study. Diabetes Care 200023:969-974. Couper JL, Steele C, Beresford S, et al. Lack of association between duration of breast-feeding or introduction of cow’s milk and development of islet autoimmunity. Diabetes 1999;48:2145-2149. Norris JM, Barriga K, Klingensmith G, et al. Timing of initial cereal exposure in infancy and risk of islet autoimmunity. JAMA 2003290:1730-1720. Ziegler AC, Schmid S, Huber D, et al. Early infant feeding and risk of developing type1 diabetes-associated autoantibodies. JAMA 2003;290:1721-1728. Conin CC, Shanahan F. Insulin-dependent diabetes mellitus and celiac disease. Lancet 1997;349:1096-1097.

  10. Life-Style and Diabetes (Type II) Results from a monumental study by the Diabetes Prevention Program Research Group comparing the effect of lifestyle versus metformin versus placebo in the reduction of incidence of type 2 diabetes were recently reported (DPPR ref). The results instigated the recommendation from the American Diabetes Association among other groups to change. The surprise to many was that the reduction of the incidence of diabetes was 58% for those on the lifestyle intervention compared to 31% for those using metformin.

  11. Although this is similar to other reports such as the Finland (Tuomeielehto ref) and China (Pan ref) reports, the effects were more dramatic. The researchers suggest that the primary reason may be the individualized approach used in their study. In addition to a low carbohydrate, low-fat diet, participants engaged in physical activity of moderate intensity (such as brisk walking) for at least 150 minutes per week. They also participated in a 16-hour curriculum designed to support the changes in diet, exercise, and behavior modification. The goal was to maintain a weight reduction of at least 7% of the initial body weight.

  12. A 12-year follow-up study of over 42,000 males involved a comparison between two dietary regimens and the relative risk of type 2 diabetes. The researchers concluded that a western dietary pattern (i.e. high in red meat, fat, refined, grains, and sweet/deserts) combined with low physical activity or obesity substantially increased the risk of type 2 diabetes compared to a “prudent” dietary pattern (i.e. high consumption of vegetables, fruit, fish, poultry, and whole grains) (van Dam ref). Another, more recent study, estimated the lifetime risk for type 2 diabetes in the U.S.. The researchers estimated that for individuals born in the U.S. in 2000, the lifetime probability of being diagnosed with diabetes for males was 33% and for females 39% ( Venkat ref ).

  13. Among many studies emphasizing the need for exercise in reducing the morbidity of diabetes, some indicate minor life-style changes may affect mortality. One such study indicated that if diabetic patients were convinced to walk 2 hours per week, the rate of death would decrease by one per year for every 61 people (ref). A similar outcome was found with women who performed an 8-week walking program of 10,000 steps/day with benefits of improved glucose tolerance and a reduction in blood pressure (Swartz ref).

  14. Life-Style References • Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with liefestyle intervention or metformin. N Engl J Med 2002;346:393-401. • Tuomilehto J, Lindsrohm J, Erikson JG, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001;344:143-150. • Pan XR, Li GW, Hu YH, et al. Effect of diet and exercise in preventing NIDDM in people with impaired glucose tolerance: the DaQing IGT and Diabetes Stud. Diabetes Care 1997;20:537-544. • Van Dam RM, Rimm EB, Willett WC, et al. Dietary patterns and risk for type 2 diabetes mellitus in U.S. men. Ann Intern Med 2002;136:201-209. • VenkatNarayan KM, Boyle JP, Thompson TJ, Sorensen SW, Williamson DF. Lifetime risk for diabetes mellitus in the United States. JAMA 2003;290:1884-1890. • Cregg EW, Gerzoff RB, Caspersen CJ, et al. Relationship of walking to mortality among US adults with diabetes. Arch Internal Med 2003;163:1440-1447. • Swartz AM, Strath SJ, Bassett DR, et al. Increasing daily walking improves glucose tolerance in overweight women. Prev Med 2003;37:356-362.

  15. Depression • Following hypertension, depression is the next most common chronic condition seen in an average primary care medical office (ref Wells). • Of these patients, approximately 10% suffer from major depression. Wells KB, Sturm R, Sherbourne CD, Meredith LS. Caring for Depression Cambridge, Mass; Harvard University Press, 1996

  16. Depression • Exogenous depression (reactive) has a known cause and is usually self-limiting. Examples include loss of relationship, job, etc. • Prolonged grief reactions (longer than 6 months) often require medication • Endogenous depression is thought to be due to an imbalance of neurotransmitters (primarily serotonin); there is no identifiable outside cause • Two types: unipolor, bipolar (manic depressive)

  17. Depression Hx Clues • Feeling “blue” • Anhedonia - loss of joy in life • Fatigue • Sleep disturbance (early morning awakening) • Eating disturbance (no eating; loss of weight) • Memory dysfunction or inability to make decisions • Motor dysfunction • Feelings of guilt and worthlessness • Suicidal thoughts

  18. Depression • Asking two history questions regarding depressed mood and anhedonia (loss of life’s pleasures) has a sensitivity of 96 percent but a specificity of 57 percent which means additional questions are needed if the patient indicates a depressed mood or anhedonia (ref Whooley). • Absence of these positives virtually rules out depression (assuming the patient is being honest). Whooley MA, Avins AL, Miranda J, Browner WC. Case-finding instruments for depression: two questions are as good as many. J Gen Intern Med 1997;12(4)439-445.

  19. Placebo With Depression Tx • Particularly important because of large psychological overlay • One example: a study found that hypericum (St. John’s Wort), sertraline (SSRI), and placebo had somewhat equal positive response rates when compared with two outcome measuring tools (Hamilton Depression Scale and Clinical Global Impression Scale) (38% for hypericum, 43% for placebo, and 49% for sertraline) De Smet P. Herbal remedies.N Engl J Med 2002;347(25):2046-2056.

  20. Drug Treatment of Depression • Tricyclic antidepressants • Selective serotonin re-uptake inhibitors (SSRI) • MAO (monoamine oxidase) inhibitors • Lithium • anti-anxiety drugs Tricyclics and SSRI drugs are used first, then MAO inhibitors for unipolar; lithium for bipolar

  21. Chronic Fatigue Syndrome • Clinically evaluated, unexplained persistent or relapsing chronic fatigue that is new; not life-long, not the result of exertion, and not substantially relieved by rest • Significant reduction in occupational, social and personal activities • Evidence suggests a chronic immunologically mediated inflammatory process involving the CNS • No strong evidence that it is due to EBV or chronic yeast infection

  22. Fibromyalgia 11 tender points out of possible 18 are used as the primary diagnostic test for fibromyalgia Similar to depression and chronic fatigue syndrome in that depression and fatigue are associated Management is difficult and may involve a medical approach that includes tricyclics to normalize sleep; conservative approach includes adrenal support, liver detox program, melatonin, among others

  23. Fibromyalgia • In one study, fibromyalgia patients were randomized to either an exercise group (exercise bicycle and treadmill) or a relaxation group (stretches and relaxation exercises) for one hour, twice a week, for 12 weeks. At the end of the trial treatment 35% of patients in the exercise group rated feeling “much better” or “very much better” versus 18% for patients in the relaxation group. The effect seemed to be maintained at nine months follow-up for the exercise group (38%) with a small increase in the relaxation group to 22%. Richards SCM, Scott DL. Prescribed exercise in people with fibromyalgia: Parallel group randomized controlled trial. Br Med J 2002;325:185-188.

  24. Sleep Disorders Difficulty falling asleep? Early morning awakening? Frequent awakening? Excessive daytime sleepiness?

  25. Sleep Disorders Insomnia • Depression (reactive) • Medications • Sleep environment Sleep Apnea Narcolepsy/Cataplexy Enuresis Somnabulism

  26. Polysomnogram of a Patient with Severe Obstructive Sleep Apnea, Using CPAP Basner R. N Engl J Med 2007;356:1751-1758

  27. Patient Receiving CPAP Treatment with Nasal Interface Basner R. N Engl J Med 2007;356:1751-1758

  28. Hyperlipidemia • Prognosis and management based on risk factors and lab findings • Risk factors include older age, male gender, obesity, diabetes, smoking, hypertension, and familial predisposition • An HDL level above 50 mg/dL is somewhat protective • Key high-risk lab values are cholesterol above 240 and LDL cholesterol above 130 mg/dL (caution levels are >200 for cholesterol and >100 for LDL)

  29. Hyperlipidemia • Management based on NCEP recommendations through step diet program and exercise • Medical management includes: • bile-acid-binding resins (Questran) • nicotinic acid (niacin) • HMG CoA reductase inhibitors (statins) • fibric acid derivatives (Lopid) • probocol (Lorelco)

  30. Hypertension • Confirmed by readings taken twice for three days at same time of day if possible • Rule out transient causes such as anxiety, drugs/alcohol, smoking, examiner error (i.e. improper positioning or wrong-size cuff) • Follow guidelines based on categorization into normal, prehyertension, stage 1 and stage 2

  31. Hypertension Classifications The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. NIH Publication 03-5233, May 2003. National Institutes of Health. • Normal - <120 mmHg systolic and <80 mmHg diastolic: medication not needed, lifestyle recommendations are encouraged • Prehypertensive – 120-139 mmHg systolic OR 80-89 mmHg: medication not needed, lifestyle modification given • Stage 1 hypertension – 140-159 mmHg systolic OR 90-99 mmHg diastolic: lifestyle modifications given, medications recommended starting with thiazide-type diuretics (consider others if ineffective) • Stage 2 hypertension - > 160 mmHg systolic OR >100 mmHg diastolic; lifestyle modifications given; two-drug combination therapy recommended

  32. Why Do Patients Have Primary Hypertension? Keller G, et al. NEJM, 348(2), 101-108, 2003 The vast majority of patients have what is called essential or primary hypertension No single cause has been identified although subtypes involving sensitivity to sodium, for example, have been found This study evaluated the number of glomeruli per kidney and matched to normotensive controls Patients with hypertension had significantly fewer glomeruli and it was determined this was not a result of having hypertension

  33. Hypertensive Medications Diuretics Beta-Blockers Calcium Channel Blockers ACE Inhibitors General vasodilators

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