8/16/2016. What is screening? What makes a good test? Can we screen for endocrine disorders? Screening test Diagnos c test.

Transcription

1 Can we screen for endocrine disorders? What is screening? Principles: Testing performed on asymptomatic individuals Intention is to identify undetected diseases or conditions Objectives: Detection of disease at a stage when treatment can be more effective than it would after the patient develops signs or symptoms. Thomas Schermerhorn, VMD, DACVIM(SAIM) Kansas State University Manhattan, Kansas, USA Identification of risk factors that increase the likelihood of developing disease and use the knowledge to prevent or lessen the disease by modifying risk factors. Herman C, What Makes a Screening Exam Good? Ethics J Am Med Assoc. 8(1):34 37, 2006 What makes a good test? Perceived survival time Screening test Diagnos c test Disorder detected through screening Disease onset Lead time Disease outcome Should be common Should be associated with significant morbidity and mortality Should have treatment available Early detection should be advantageous for the patient Disorder detected from signs Perceived survival time Should detect nearly 100% of diseased individuals in preclinical state. Should be safe. Should be available at a reasonable cost Should lead to improved outcomes Should be available to clinicians Does Early diagnosis improve survival? Lead time implement monitoring, preventative or therapeutic measures. Benefits for early intervention? Herman C, What Makes a Screening Exam Good? Ethics J Am Med Assoc. 8(1):34 37,

2 Test Characteristics Testing and Prediction Sensitivity = a / (a+c) = true positive Specificity = d / (b+d) = true negative Test + Test Dz+ 100% Sensitivity All affected have (+) test. 90% Sensitivity 90% affected have (+) test; 10% affected will be misclassified. a c Dz b d PPV = a/(a+b) NPV = c/(c+d) 100% Specificity All unaffected have ( ) test. 90% Specificity 90% unaffected have ( ) test; 10% unaffected will be misclassified. Test Performance Predictive value (+) = proportion of dogs with (+) tests that have disease increases with increasing prevalence; decreases with decreasing prevalence Predictive value ( ) = proportion of dogs with ( ) tests that do not have disease decreases with increasing prevalence; increases with decreasing prevalence Disorders for which screening might be useful: Canine and Feline thyroid disorders Canine adrenocortical disorders Canine and Feline diabetes Screening for Thyroid Disorders Disorders for whichscreening willnot be useful: Pituitary disorders Pheochromocytoma Parathyroid disorders Rare endocrine disorders 2

3 Target disorder Canine Hypothyroidism Basal serum total T4 (TT4) NORMAL RANGE Can effectively rule out HypoT Interpretation TT4 within the reference range not likely to have HypoT Anti T4 antibodies can interfere with assay (misdiagnosis) Basal serum total T4 (TT4) BELOW NORMAL RANGE Cannot effectively rule in HypoT Interpretation Decreased TT4 is supportive, not diagnostic, for HypoT4 Non thyroidal illness and drugs can suppress TT4 (misdiagnosis) Anti T4 antibodies can interfere with assay (misdiagnosis) Daminet S, Ferguson DC. JVIM 17: , 2003 Basal serum free T4 (ft4) Equilibrium dialysis is preferred method. More specific than TT4 for HypoT Interpretation Decreased ft4 is strongly suggestive for HypoT4 (not 100% sensitive) Non thyroidal illness can suppress ft4 but effect is less than on TT4 Anti T4 antibodies do not interfere with assay. Canine Thyroid Screening Is hypothyroidism common? Sensitivity of various thyroid tests in dogs is generally low. Sensitivity is reported as low as 89% (the % hypothyroid dogs with low T4). Specificity is reported as 75 82% (% euthyroid dogs with normal T4) Abnormal screening test (T4) requires additional testing with a specific test. 3

4 Target disorder Feline Hyperthyroidism Feline Thyroid Screening Basal serum total T4 Extremely reliable screening test Exceeds ref range in 90% of HT cats Free T4 (unbound hormone available to cells) Most reliable if determined by equilibrium dialysis method Other hormone levels (TT3, FT3) are generally not useful Is hyperthyroidism common? Sensitivity better with Total T4 than with Free T4. Specificity Total T4 is high. Screening for Adrenal Disorders Regulation of Cortisol Secretion ACTH secretion is pulsatile ACTH secretion influenced by: Feeding Physiologic/environmental stress Pain Trauma hypoxia Pyrogens Cold exposure Surgery 4

5 Screening Tests UCCR LDDS ACTH stimulation URINE CORTISOL:CREATININE RATIO Sensitivity: % Specificity: LOW (20 25%); two studies reported >75% UCC ( ) ( ) Effective screening test (high sensitivity). Detect most affected (true +) dogs Normal result rules out HAC but low specificity means that normal dogs will frequently classified as affected (+) high low Abnormal result requires a second screening test with greater specificity. LOW DOSE DE SUPPRESSION TEST Sensitivity: %. 95% when data from all studies combined. Specificity: ~ 70% (44% in one study) Effective screening test (high sensitivity). Normal result rules out HAC. Specificity is principal problem of the LDDS test. Specificity with the LDDS test is higher than UCCR Tests responsiveness of the pituitary adrenal axis. Pituitary responsiveness remains in illness. Chronic, non adrenal illness can affect result. Practical aspects limit usefulness as a screening test. ACTH STIMULATION TEST Sensitivity: 73 95% in dogs with PDH and AT. Sensitivity is about 80%, combined patients. Specificity More specific than LDDS Expense is a concern Practical considerations Not an ideal first line test 5

6 Canine Adrenal Screening Screening for Diabetes Is hyperadrenocorticism common? Sensitivity High sensitivity for several screening tests Specificity is the problem for tests used for adrenal screening Follow up limited by lack of available specific tests. UCCR followed by ACTH stimulation Cost:benefit ratio does not favor aggressive adrenal screening. Diabetes Screening Normal < 150 mg/dl Pre-Diabetes mg/dl Diabetes >220 mg/dl Diabetes screening in dogs versus cats. Risk factor identification and correction. Outcome assessment? Single random glucose determination Fasting glucose or mean glucose determination Persistent hyperglycemia Serum fructosamine Urine glucose 6

7 Diabetes Screening Summary Is diabetes common? Available tests are best used in the diagnostic setting. Screening for most endocrinopathies is difficult using currently available resources. The negative effects of ineffective screening may outweigh the positive effects. Screening is useful in select circumstances (feline hyperthyroidism, for example). QUESTIONS? 7