Update on Thyroid Disorders Unrestricted Siemens Healthcare Diagnostics Inc All rights reserved.

Transcription

1 Linda Rogers, PhD, DABCC, FACB Update on Thyroid Disorders

2 Objectives 1. Define hypothyroidism and hyperthyroidism and describe the common clinical presentations and the general laboratory diagnosis of each 2. Understand and describe the differences in the reference ranges of key thyroid tests in pediatric patients and pregnant women 3. Describe Grave s Disease and the utilization of the thyroid stimulating antibodies (TSI) assay in its diagnosis and management. Page 2

3 Agenda 1. Overview of the thyroid endocrine system 2. Hypothyroidism: clinical presentation and the general laboratory diagnosis 3. Hyperthyroidism: clinical presentation and the general laboratory diagnosis 4. Grave s Disease and the utilization of the thyroid stimulating antibodies (TSI) assay in its diagnosis and management 5. Thyroid disorders and pregnancy 6. Pediatric reference ranges 7. Clinical case studies Page 3

4 Epidemiology of Thyroid Dysfunction: United States Affects 27 million Americans 80 % are female Most common endocrine disorder More common than diabetes Page 4

5 Thyroid Dysfunction and Diagnosis The right test at the right time facilitates correct diagnosis. Page 5

6 Thyroid Hormone Regulation T 4 T 4 T 4 T 4 TSH Receptor T 3 T 4 T 4 T 3 Hypothalamus Anterior Pituitary Posterior Pituitary Page 6 Scott MG. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, 5th edition (Kindle). St. Louis, MO: Elsevier Saunders; 2011.

7 Thyroid Hormone Regulation T 3 T 3 T 4 T 4 T T 4 4 T 3 T 4 T 4 T 3 TSH receptor TRH Hypothalamus Anterior pituitary Page 7 Scott MG. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, 5th edition (Kindle). St. Louis, MO: Elsevier Saunders; 2011.

8 Thyroid Hormone Regulation I - I - I - I - I - I - TPO I - I - I - I - I - Page 8 Thyroid. The Merck Manual. 18th ed p

9 Thyroid Hormone Regulation Lacuna Thyrocyte Page 9 Thyroid. The Merck Manual. 18th ed p

10 Thyroid Hormones are Essential Alters gene expression, protein production. Regulates metabolism proteins, fats, carbohydrates. Essential for normal development of the fetus and newborn brain, and somatic tissue. Page 10 Thyroid. The Merck Manual. 18th ed p

11 Laboratory Tests Aid Diagnosis Lab Tests TSH Third generation TSH Free T 4 Total T 4 Free T 3 Total T 3 Anti-thyroid peroxidase antibody Anti-thyroglobulin antibody Thyroglobulin Thyroxine-binding globulin TRAb TSI(TSAb) T 3 uptake Page 11 McDermott MT. Ann Intern Med Dec 1;151(11):ITC61. British Thyroid Association.

12 Hypothyroidism Page 12

13 Hypothyroidism: Basics Secondary and Tertiary Disease Disease of the hypothalmus Disease of the pituitary Primary Disease Disease of the thyroid gland Insufficient Thyroid Hormone T 4 and/or T 3 Page 13 McDermott MT. Ann Intern Med Dec 1;151(11):ITC61.

14 Hypothyroidism: Risk Factors Age Female Gender Family History Consistent Symptoms Autoimmune Disease Page 14 Landenson PW. Thyroid. ACP Medicine p McDermott MT. Ann Intern Med Dec 1;151(11):ITC61.

15 Classification of Hypothyroidism by Etiology Etiology Gland Injury Drugs Congenital Other Diseases Subacute/acute thyroiditis (subacute/acute, lymphocytic, autoimmune) Thyroid surgery or irradiation Thyroid cancer related thyrotoxicosis Drugs (amiodarone, stavudine, thalidomide) Iodine-induced hyperthyroidism Thyroid dysgenesis Thyroid dysmorphogenesis hcg-mediated thyrotoxicosis TSH-mediated thyrotoxicosis Hemochromatosis Tumors Sarcoidosis Diseases Page 15 Landenson PW. Thyroid. ACP Medicine p.1-25.

16 Hypothyroidism Nonspecific Symptoms Fatigue Muscle weakness Impaired memory Impaired learning Weight gain Alterations in appetite Cold intolerance Dry skin Sexual disturbances Menstrual disturbance Impaired fertility Mental disturbances (depression) Sleep disturbances (sleepiness) Constipation Hair loss Page 16 McDermott MT. Ann Intern Med Dec 1;151(11):ITC61.

17 Impact of Hypothyroidism Myxedema Coma Life threatening, mortality rates 25% to 75%. Extreme hypothermia (24 C to 32.2 C). Complication of long term hypothyroidism, rare. Cardiovascular Disease/Dysfunction Hypercholesterolemia. Impaired cardiac function (diastolic and systolic). Increased systemic vascular resistance. Decreased cardiac output. Page 17 Thyroid. The Merck Manual. 18th ed p Landenson PW. Thyroid. ACP Medicine p.1-25 Rodriguez I. J Endocrinol Feb;180(2):347-50

18 Evaluating Hypothyroidism Myohan CC-BY-3.0 Comprehensive Physical Exam Serology: TSH, Total and Free T 3 and T 4 Landenson PW. Thyroid. ACP Medicine p Baskin et al., Endo Pract. 2002; 6: Bahn, et al, Thyroid. 2011; 21: Drahreg01 CC-BY-SA-4.0 Imaging Page 18

19 American Association of Clinical Endocrinology (AACE) Recommendations: Hypothyroidism A TSH assay should always be used as the primary test to establish the diagnosis of primary hypothyroidism. The most valuable test is a sensitive measurement of TSH level. Landenson PW. Thyroid. ACP Medicine p American Association of Clinical Endocrinologists. Endocrine Practice Nov/Dec 8;(6): Page 19

20 Primary Hypothyroidism: Overt Disease Test TSH Free T4 Free T3 TgAbs Anti-TPO Result High Low Low/normal May be present May be present Structural abnormalities Thyroid scan Ultrasound McDermott MT. Ann Intern Med Dec 1;151(11):ITC61. American Association of Clinical Endocrinologists. Endocrine Practice Nov/Dec 8;(6): Page 20

21 Primary Hypothyroidism: Subclinical Disease Test TSH Free T4 Free T3 TgAbs Anti-TPO Result High Normal Normal May be present May be present Progresses to overt disease in 3% to 20% of cases McDermott MT. Ann Intern Med Dec 1;151(11):ITC61. American Association of Clinical Endocrinologists. Endocrine Practice Nov/Dec 8;(6): Page 21

22 DS2 General Serology for Hypothyroidism TSH FT4 FT3 Hypothyroid T 3 T 3 T 4 T 4 T T 4 4 T 3 Subclinical hypothyroid Normal Normal T 3 T 4 T 3 Baskin et al., Endo Pract. 2002; 6: Vadiveloo T, et al. J Clin Endocrinol Metab Jan;96(1):E1-8. Page 22

23 Slide 22 DS2 Should FT4 & FT3 have the #s as subscripts? Same question throughout. Dina Salzer, 3/7/2016

24 Hypothyroidism: Monitoring Treatment TSH and Free T 4 Every 6-8 weeks until normalized Every 3 6 months Annually McDermott MT. Ann Intern Med Dec 1;151(11):ITC61. American Association of Clinical Endocrinologists. Endocrine Practice Nov/Dec 8;(6): British Thyroid Association. Page 23

25 Hyperthyroidism Page 24

26 American Association of Clinical Endocrinology (AACE) Recommendations: Hyperthyroidism The sensitive TSH assay is the single best screening test for hyperthyroidism and in most outpatient clinical situations, the serum TSH is the most sensitive test for detecting mild (subclinical) thyroid hormone excess or deficiency. Landenson PW. Thyroid. ACP Medicine p American Association of Clinical Endocrinologists. Endocrine Practice Nov/Dec 8;(6): Page 25

27 Hyperthyroidism: Many Nonspecific Symptoms Nervousness and irritability Palpitations and tachycardia Heat intolerance or increased sweating Tremor Weight loss or gain Alterations in appetite Frequent bowel movements or diarrhea Dependent lower-extremity edema Sudden paralysis Hyperthyroidism - Symptoms Exertional intolerance and dyspnea Menstrual disturbance (decreased flow) Impaired fertility Mental disturbances Sleep disturbances (including insomnia) Changes in vision, photophobia, eye irritation, diplopia, or exophthalmos Fatigue and muscle weakness Thyroid enlargement Pretibial myxedema Devereaux, et al. Emerg Med Clin North Am. 2014;32: Page 26

28 Hyperthyroidism: Risk Factors iodine 53 I Intropin CC BY 3.0 Ladenson PW. Thyroid. ACP Medicine. Decker Intellectual Properties; p Page 27

29 Evaluating Hypothyroidism Myohan CC-BY-3.0 Comprehensive Physical Exam Serology: TSH, Total and Free T 3 and T 4 Landenson PW. Thyroid. ACP Medicine p Baskin et al., Endo Pract. 2002; 6: Bahn, et al, Thyroid. 2011; 21: Drahreg01 CC-BY-SA-4.0 Imaging Page 28

30 General Serology for Hyperthyroidism TSH FT4 FT3 Hypothyroid T 3 T 3 T 4 T 4 T T 4 4 T 3 Subclinical hypothyroid Normal Normal T 3 T 4 T 3 Baskin et al., Endo Pract. 2002; 6: Vadiveloo T, et al. J Clin Endocrinol Metab Jan;96(1):E1-8. Page 29

31 A Diagnostic Algorithm: Hyperthyroidism Low TSH Normal No further testing Free T 4 or Total T 4 Normal or Decreased Increased Normal Free T 3 or Total T 3 Increased Test for autoimmune disease Retest in 2 4 mos T 3 thyrotoxicosis TRAb TSI Anti-TPO Ab Mueller AF, et al. Neth J Med Mar;66(3): Page 30

32 Severe Complications of Hyperthyroidism Thyroid storm Confusion, psychosis, spasticity, convulsions coma Hyperthermia Nausea, vomiting, diarrhea Irregular pulse, tachycardia, hypertension followed by hypotension, cardiac collapse, heart failure Fatal without treatment, requires immediate therapy: 20% to 50% mortality even with treatment Cardiovascular disease Decreased systemic vascular resistance Increased cardiac preload and output Systolic hypertension Congestive heart failure Osteoporosis Thyroid. The Merck Manual. 18th ed p Devereaux, et al.. Emerg Med Clin North Am. 2014;32: Page 31

33 Grave s Disease Page 32

34 Graves Disease Diffuse Goiter Symmetrical Firm Drahreg01 CC-BY-SA-3.0 Ophthalmopathy Jonathan Trobe, MD. CC-BY 3.00 Page 33

35 Autoimmunity in Graves Disease Anti-TSH Ab TSH Page 34

36 The TSH receptor Stimulating epitope B A Blocking 74 aa epitope Thyrocyte Membrane (lipid bilayer) Page 35

37 TSH Autoantibodies T 4 T 3 Thyroid stimulating antibody (TSAb) / Thyroid stimulating immunoglobulin (TSI) T 4 T 4 TSH T 4 T 3 T 4 Thyroid blocking antibody (TBAb) / Thyrotropin blocking inhibiting immunoglobulin (TBII) T 4 Neutral antibody Page 36

38 Effect of Thyroid Stimulating Antibody T 3 T 4 T 3 T 4 T 4 T 4 T 4 TRH T 4 T 4 T 4 T 3 T 4 T 3 T 4 TSH T 3 T 4 T 4 T 4 TSH Page 37

39 Effect of Thyroid Blocking Antibody T 3 TRH T 4 T 4 T 4 TSH TSH T 3 T 4 Page 38

40 TRAb Nomenclature Review Antibody type Action Effect TRAb Binds to TSH receptor antibodies to either inhibit or stimulate TbAb Blocks TSH binding, depresses T 3 /T 4 production Hypothyroidism Hypothyroidism or Hyperthyroidism (depending on antibody type and possibly ratio) TSAb Blocks TSH binding, stimulates T3/T4 production Hyperthyroidism DS1 Assay type TRAb Anti-TSHR TBII TSI Antibody type(s) detected TBAb (blocking) and TSAb (stimulating) TBAb (blocking) and TSAb (stimulating) TBAb (blocking) and TSAb (stimulating) TSAb only stimulating Page 39

41 Slide 39 DS1 the text is in the tables and appears on a click - you'll see it in show mode - for the sake of animation, there is a white box over the text which fades to reveal text on a click. Dina Salzer, 3/7/2016

42 Overview of TSI Utility in Graves Disease Indication Diagnosis of Graves Disease Ophthalmopathy Pregnancy Neonatal hyperthyroidism ATD treatment Comments Differential diagnosis (vs. other hyperthyroid disease) Differential diagnosis in unilateral orbitopathy orbitopathy with euthyroid status orbitopathy with hypothyroid status Treatment guidance Useful in pregnant women with current or past treatment previous children with neonatal thyrotoxicosis Fetal hyperthyroidism diagnosis Prediction and diagnosis Helps predicts remission Gupta M. Siemens webinar Laurberg, et al. Eur J Endocrinol Dec;139(6): Gupta Bahn, et al. Thyroid. 2011;21(6): Eckstein, et al. Med Klin (Munich) May 15;104(5): Page 40

43 Graves Disease Diagnosis TSH FT3 FT4 TSI Clinical signs and TSH, free T 4, and/or free T 3 results Nonautoimmune hyperthyroidism Neg T 3 toxicosis Neg / TSI(+) Graves Disease Graves Disease TSI detected in 77.8% 100% of GD patients Bahn, et al. Thyroid. 2011;21: Macchia E, et al. Autoimmunity. 1989;3(2): Takasu N, et al. J Endocrinol Invest Sep;20(8): Page 41

44 Better Diagnostic Accuracy of TSI vs. TRAb 182 sera: 79 GD, 103 non-gd 100 TSI assay demonstrated 100% sensitivity 100% specificity 100% diagnostic accuracy TRAb assay: 96.9% diagnostic accuracy Sensitivity TSI assay TRAb assay 20 Franz, et al. Poster presented at ÖGLMKC Congress, 2007, Vienna Specificity Page 42

45 DS4 Is it Graves Disease? Non-Autoimmune Hyperthyroidism? (e.g. toxic multi-nodular goiter, toxic thyroid adenoma) Autoimmune Hyperthyroidism? (Graves Disease) Graves Disease Non-Autoimmune Hyperthyroidism Is it Graves Disease? Further investigation necessary Page 43

46 Slide 43 DS4 Do you want me to recreate this chart? It looks okay but it is placed as an image so the font is wrong. Dina Salzer, 3/7/2016

47 TSI : Time and Cost Advantages Based on a study by McKee and Peyerl, the use of algorithms that incorporate TSI testing early in the primary care setting resulted in: 46% less time to diagnosis (5.3 weeks earlier) 47% annual payer cost savings ($698,892 or $760/person) Fewer misdiagnoses Faster referral from primary care physicians to endocrinologists Fewer specialist visits Increased patient productivity McKee, et al.. Am J Manag Care. 2012;18:e1-14. Page 44

48 Total Payer Costs of GD Diagnosis $1,480,328 47% decrease = $698,892 $780,918 McKee, et al.. Am J Manag Care. 2012;18:e1-14. Page 45

49 Average Time to Diagnosis 11.7 weeks 46% decrease 6.4 weeks McKee, et al.. Am J Manag Care. 2012;18:e1-14. Page 46

50 DS5 Summary: Utility of TSI Testing in ATD, Radioiodine, and Surgical Treatments Treatment Type Antithyroid drugs Radioiodine Surgery TSI Utility Prognostic during treatment High à relapse Low à remission Prognostic during treatment High à relapse Low à remission Therapy guidance in 3 rd trimester High à continue ATD Treatment guidance for patients at high risk of worsening Graves ophthalmopathy High (pretreatment) à avoid radioiodine therapy Treatment guidance for anticipated pregnancy (with 4 6 months of treatment) High (pretreatment) à surgery preferred over radioablation Bahn, et al. Thyroid 2011;21(6): Page 47

51 Slide 47 DS5 the text is in the tables and appears on a click - you'll see it in show mode - for the sake of animation, there is a white box over the text which fades to reveal text on a click. Dina Salzer, 3/7/2016

52 Pregnancy Page 48

53 Pregnancy and the Thyroid Pregnancy has a profound impact on the thyroid gland and thyroid function tests Serum TBG concentrations rise almost two-fold because estrogen increases TBG production To maintain adequate free thyroid hormone concentrations during this period, T 4 and T 3 production by the thyroid gland increase Total T 4 and T 3 concentrations rise during the first half of pregnancy, plateauing at approximately 20 weeks of gestation, at which time a new steady state is reached and the overall production rate of thyroid hormones returns to prepregnancy rates Considerable homology between the beta-subunits of hcg and TSH. As a result, hcg has weak thyroid-stimulating activity National Endocrine and Metabolic Diseases Information Service. Pregnancy and Thyroid Disease. April NIH Publication No Accessed March 13, 2014 Page 49

54 DS6 Pregnancy: Physiological Changes Physiologic change Thyroid test change é TBG é Total T 3, é Total T 4 First trimester hcg elevation é Free T 4, ê TSH é Plasma volume é Pool size T 3, T 4 é Type III 5-deiodinase é Degradation of T 3, T 4 Thyroid enlargement é Iodine clearance ê Serum thyroglobulin ê Hormone production in deficiency Bahn, et al. Thyroid. 2011;21: De Groot, et al. J Clin Endocrinol Metab. 2012;97: AACE. Endo Pract. 2002;8: update. Lee, et al. Am J Obstet Gynecol. 2009;200:260.e1 Galofre, et al. J Womens Health (Larchmt) : Lazarus JH. Br Med Bull. 2011;97: Abalovich, et al., J Clin Endocrinol Metab. 2007;92(8 Suppl):S1-47. Page 50

55 Slide 50 DS6 the text is in the tables and appears on a click - you'll see it in show mode - for the sake of animation, there is a white box over the text which fades to reveal text on a click. Dina Salzer, 3/7/2016

56 Hypothyroidism in Pregnancy Subclinical hypothyroidism has an estimated prevalence of 2-3% Overt hypothyroidism is seen in about % of pregnancies The most common cause of hypothyroidism is the autoimmune disorder known as Hashimoto s thyroiditis Endemic iodine deficiency accounts for most hypothyroidism in pregnant women worldwide while chronic autoimmune thyroiditis is the most common cause of hypothyroidism in iodine sufficient parts of the world Page 51

57 Complications of Hypothyroidism in Pregnancy Maternal complications: miscarriages anemia pre-eclampsia abruptio placenta postpartum hemorrhage Neonatal complications: premature birth low birth weight increased neonatal respiratory distress Page 52

58 Hyperthyroidism in Pregnancy Hyperthyroidism occurs in about % of all pregnancies The most common cause of maternal hyperthyroidism during pregnancy is the autoimmune disorder Graves disease Must be distinguished from gestational transient thyrotoxicosis, a self-limiting hyperthyroid state due to the thyroid stimulatory effects of beta-hcg Untreated hyperthyroidism is associated with an increased risk of severe pre-eclampsia and up to a four-fold increased risk of low birth weight deliveries Thyroid. The Merck Manual. 18th ed p Devereaux, et al.. Emerg Med Clin North Am. 2014;32: Page 53

59 Pregnancy: Congenital Hyperthyroidism TSAb is Predictive of Graves Disease vs Other Thyrotoxicoses Excess hormone present at birth Rare 0.01% of pregnancies Maternal TSAb levels Higher levels, higher risk for poor outcomes Fetal disease Preterm delivery Death Growth restriction Abalovich, et al. J Clin Endocrinol Metab. 2007;92(8 Suppl):S1-47. Polak, et al. Horm Res. 2006;65: Lazarus JH. British Medical Bulletin. 2010;23:1-12. Endocrine Society s Clinical Guidelines. J Clin Endocr Metab. 2007;92:S1-S47. Page 54

60 DS8 TSI Assay - Clinical Utility Indication Diagnosis of Graves Disease Ophthalmopathy Pregnancy Neonatal Therapy guidance/prognosis Comments Aids in differentiating GD from other forms of thyrotoxicosis Useful for differential diagnosis of GD in patients with unilateral orbitopathy or orbitopathy with euthyroid or hypothyroid status Useful in women who are currently on antithyroid drug therapy, have had either radioactive iodine or surgery for thyrotoxicosis, or have had children with neonatal neonatal thyrotoxicosis Test neonate if mother s TRAb levels are high in third trimester Helps identify patients on ATD who are more likely to remit Gupta M. Siemens webinar Laurberg, et al. Eur J Endocrinol Dec;139(6): Gupta Bahn, et al. Thyroid. 2011;21(6): Eckstein, et al. Med Klin (Munich) May 15;104(5): Page 55

61 Slide 55 DS8 the text is in the tables and appears on a click - you'll see it in show mode - for the sake of animation, there is a white box over the text which fades to reveal text on a click. Dina Salzer, 3/7/2016

62 Summary: TSI Testing Aids Diagnosis Patients diagnosed and treated sooner Can be Automated Ready to use. Improved lab efficiency Specific Detects ONLY stimulating Abs, the cause of GD (differs from TRAB) Your Solution to Graves Disease Testing Page 56

63 Children are not small adults Thyroid function abnormalities are among the most common endocrine problems in children Children s thyroid hormone levels show a clear age dependency. Therefore age-specific reference intervals are critical for proper clinical interpretation of test results One of the most challenging aspects of establishing pediatric reference intervals is the availability of well-characterized healthy pediatric samples and sufficient blood volume to conduct studies across multiple assays Repeated requests from our global customers over the years have been to establish Siemens system specific pediatric thyroid reference intervals We are pleased to announce the launch of Siemens Thyroid Pediatric Reference Intervals Page 57

64 Project Objective Objective To design and run appropriate studies to establish pediatric reference intervals for thyroid hormones across all major Siemens platforms for infant, child and adolescent age groups Scope Assays: 3 rd Gen TSH, FT4, FT3, T 4, T 3 IA Systems: ADVIA Centaur systems, IMMULITE 2000*, Dimension Vista, Dimension EXL (T4 extended to RxL, Xpand) Age Groups: Infants (1 23 mo), children(2 12 yr), adolescents (13 20 yr) IFU updates with claims after FDA 510K clearance * data not yet available Page 58

65 Study Design Study Design: 8 collection sites used across the US to collect samples Samples were aliquoted and shipped frozen to one laboratory for testing Testing was conducted in batch, and run in singleton on the Siemens platforms listed previously Samples were tested with handling conditions recommended for each assay as per the IFU Sample size total per platform: ADVIA Centaur: 391 Dimension Vista: 422 Dimension EXL: 408 Statistical Approach: For the 2-12 yr and yr old age groups, the lower and upper reference limits were established as the 2.5th and 97.5th percentiles of the test result distribution For the infants, the lower and upper reference limits were estimated as the 2.5th and 97.5th percentiles of the distribution produced by the robust method For the child and adolescent subgroups, where >120 subject results were available, a nonparametric approach was used (CLSI guideline) For the infant subgroup where <120 subject results were available, a robust approach by Horn and Pesce were used Page 59

66 Results ADVIA Centaur Systems (Global Release) ADVIA Centaur Pediatric Reference Intervals Age Group Sample Size TSH3-UL* FT4 FT3 T4 T3 µiu/ml (miu/l) ng/dl pmol/l pg/ml pmol/l µg/dl nmol/l ng/ml nmol/l Infants (1-23 mo) Children (2-12 yr) Adolescents (13-20 yr) * The sample size for TSH3UL is the following; infants-94, children-198 and adolescents-150 Page 60

67 Case 1 27-year-old female complaining of fatigue, weight gain, and weakness who is trying to get pregnant. Most recent pregnancy test was negative. Is this individual at risk for thyroid dysfunction? Should thyroid testing be performed? What is the first test that should be run? What other tests should be considered? Page 61

68 Case 1 Is this patient at risk for thyroid dysfunction? Yes, her symptoms are consistent with hypothyroidism Should thyroid testing be performed? Yes What is the first test that should be run? A sensitive TSH test What other tests should be considered? Free T 4, total T 4, anti-tpo Page 62

69 Case 1 What is the likely diagnosis? Hypothyroidism (Hashimoto s disease) Test TSH Free T 4 Free T 3 Anti-TPO Value High Low Normal Present Page 63

70 Case 2 A 45-year-old female complains of nervousness, irritability, and palpitations and difficulty sleeping. She thinks that she might be entering menopause. Her thyroid gland is enlarged but no distinct nodules apparent. Is this individual at risk for thyroid dysfunction? Should thyroid testing be performed? What is the first test that should be run? What other tests should be considered? Page 64

71 Case 2 Is this patient at risk for thyroid dysfunction? Yes, her symptoms are consistent with hyperthyroidism Should thyroid testing be performed? Yes What is the first test that should be run? A sensitive TSH test What other tests should be considered? Free T 4, Total T 4, TRAb, TSI, thyroid scan Page 65

72 Case 2 What is the likely diagnosis? Hyperthyroidism (Graves disease) Test TSH Free T 4 Free T 3 TSI Value Low High Normal Present Page 66

73 Case 3 A 31-year-old female, mother of one, with a history 3 miscarriages and difficulty getting pregnant is planning another pregnancy. She complains of weight gain and decreased heat tolerance. Is this individual at risk for thyroid dysfunction? Should thyroid testing be performed? What is the first test that should be run? What other tests should be considered? Page 67

74 Case 3 Is this patient at risk for thyroid dysfunction? Yes, her symptoms are consistent with thyroid dysfunction Should thyroid testing be performed? Yes What is the first test that should be run? A sensitive TSH test What other tests should be considered? Free T 4, TRAb, TSI, TPO Page 68

75 Case 3 What is the likely diagnosis? Hyperthyroidism, T 3 (Early Graves Disease) Test TSH Free T 4 Free T 3 TSI Value High Normal High Present Page 69

76 Case 4 47-year-old male found a painless lump in his throat while shaving and has also noticed increased fatigue for the past few weeks. He has no other complaints and is a well controlled type 1 diabetic. On physical examination the lump is in the left lobe of the thyroid gland. Is this individual at risk for thyroid dysfunction? Should thyroid testing be performed? What is the first test that should be run? What other tests should be considered? Page 70

77 Case 4 Is this patient at risk for thyroid dysfunction? Yes, he has a nodule and is complaining of fatigue Should thyroid testing be performed? Yes, the nodule will also require investigation What is the first test that should be run? A sensitive TSH test What other tests should be considered? Free T 4, fine needle aspiration and biopsy, radiological studies Page 71

78 Page 72

79 Linda C. Rogers, PhD, DABCC, FACB Senior Clinical Consultant Scientific & Clinical Affairs Siemens Healthcare Mobile: (949) Page 73