how can u reach accurate diagnosis of laboratory diseases

1. Interpretation of laboratory thyroid function tests The “Hidden” Health Problem Dr. Hussam El-Mouzi Clinical Pathologist Al Borg Laboratory

2. Who do you know with thyroid disease?

3. 5 % of world population suffers from thyroid diseases Khan A, Muzaffar M, Khan A et al. Thyroid Disorders, Etiology and Prevalence. J Med Sci. 2002;2:89-94

4. Hypothalamic-Pituitary-Thyroid Axis

5. Thyroid Hormones AffectsMany Organs and General Health Eyes Lungs Brain Heart Skin GI Tract Liver Kidney Uterus

6. Thyroid Disease – Who Is At Risk ? All newborns (neonatal screening) personal history of thyroid disease strong family history of thyroid disease Have an autoimmune disease, such as Type 1 Diabetes Some genetic conditions (e.g. Down, Turner syndromes) past history of neck irradiation drug therapies such as lithium and amiodarone women over age 35 elderly patients Pregnant women during the first trimester women 6 weeks to 6 months post-partum Have elevated lipid levels Investigation and Management of Primary Thyroid Dysfunction. Toward Optimized Practice Program, Edmonton: AB, 2008 Update.

7. American Association of Clinical Endocrinologist (AACE), American Academy of Family Physicians (AAFP), The American College of Physician (ACP) and the American Thyroid Association (ATA) vary greatly in their recommendations. ATA recommending routine screening at age 35 then every five years To screen or not to screen for thyroid dysfunction

8. When the Thyroid Doesn’t Work Hyperthyroidism Hypothyroidism

10. Anti TPO antibodies (90%)

11. Anti Thyroglobulin antibodies (20-50%)

12. Postpartum (silent):

13. Silent/painless

14. Occurs within 6 weeks6 months postpartum

15. Subacutethyroiditis:

16. Most common cause of painful thyroiditis2001; Intenzo CM, et al. Scintigraphic features of autoimmune thyroiditis. 21: 957-964

17. Common Signs and Symptomsof Hypothyroidism Dry skin Brittle and lustreless hair Weight gain Tiredness Constipation Muscle aches Bradycardia Cold intolerance Depression Memory Loss Heavy periods

19. Low FT4

20. TPO Ab(+)

21. Macrocyticanemia due to VIT B12 deficiency

22. ↑CPK-MB

23. ↑LDL,↑Chol (↓ lipid clearance)

26. Most common cause of hyperthyroidism

28. Occurs mostly in older age than gravesT3 Thyrotoxicosis: Approximately 5% of clinically hyperthyroid patients with normal FT4

29. Common Signs and Symptomsof Hypothyroidism Worm moist skin Hair loss Weight loss Nervousness Increased bowel movements Muscle weakness Tachycardia Heat intolerance Insomnia Difficulty in concentrating Light or Absent periods

31. Elevated FT4 or FT3

32. Mild leukopenia

33. N/N anemia

34. ESR elevated

35. ↑LFT’s and alkphosph

36. Mild ↑ Ca++

37. ↓Albumin

39. Spectrum of Thyroid Disease Sever mild Subclinical

40. Subclinical Thyroid Disease Asymptomatic Among the group with subclinical thyroid disease, 73.8% are hypothyroid and 26.2% are hyperthyroid. TSH outside the reference interval but normal serum levels of T3 and T4 The prevalence of SCH is about 4% to 10%in the general population and may be as high as 20 percent in women older than 60 years Antithyroid antibodies can be detected in 80% of patients with SCH. 80% of patients with SCH have a serum TSH of less than 10 mIU/L. To treat or not to treat

42. Also she developed fatigue and a weight gain of 9.1 kg in the past 6 months in spite of her tight trials for diet control.

43. She say she become to much depressed , asked psychiatric advices and started antidepressant therapy which claimed as a cause for her weight gain. She was planning for pregnancy before but she also loss her desire for sex.

44. She has a sister who is receiving levothyroxine therapy for hypothyroidism.

45. On examination, she looked slightly pale, pulse 72/min regular,bl pr 110/80,chest ,heart and abdomen :clinically free, thyroid is not palpable.

47. TSH is above the upper reference interval limit, but ≤10 mU/L and any of the following are present:

48. elevated thyroid peroxidase (TPO) antibodies

49. goitre

50. strong family history of autoimmune disease

51. Pregnancy

52. DyslipidemiaThyroid function test: a clinical lab perspective. Medical Laboratory Observer, February, 2007:10-19.

54. Subclinical hyperthyroidism is much less common than Subclinical hypothyroidism

55. Treatment for subclinical hyperthyroidism is recommended when:

56. Any cardiac disease

57. Age > 60

58. OsteoporosisSubclinical Hyperthyroidism: to treat or not to treat? Postgrad Med J. 2004;80:394-398.

59. Case Study 67 year old man admitted to the hospital with severe decompensated CHF. Responds to initial therapy in terms of oxygenation, but does not regain normal mental status as quickly. Lab work was done to rule out reversible causes of altered mental status. TSH is elevated at 13. On further testing, free T4 is normal, but T3 is low. Is this patient hypothyroid?

60. Sick Euthyroid Syndrome Thyroid related changes that occur during systemic illness in the absence of intrinsic thyroid disease The syndrome is acute, reversible, and occurs commonly after surgery, starvation and in many acute febrile illnesses, These changes may be observed in up to 75% of hospitalized patients Any abnormality in hormone level is possible, usually low fT3 and tT3 Thyroid Disorders in Elderly Patients, S Med J 2005;98(5):543-549

61. Drugs that can lead to alterations inthyroid function Lithium:decreased TH release Amiodarone:iodine-rich drug widely used for the management of arrhythmiaswhich may cause hypo or hyperthyrodism SSRI anti-depressants (example Prozac): increased TSH Estrogens: Increase TBG, decrease FT4 level Androgens/corticosteroids : Decrease TBG, increase FT4 level

62. Misleading TSH Results TSH in normally released in a pulsatile fashion, peaking during the night it generally takes 4-6 weeks for TSH levels to reflect the status of thyroid hormone in the blood Acutely ill patients: “sick euthyroid syndrome” Following thyroid hormone replacement: “pituitary reset”, wait 6-8 weeks before measuring TSH During treatment phase of hyperthyroid patients: “pituitary reset”, wait 3 months before measuring TSH Patients with severe hypo- or hyperthyroidism may display an abnormal TSH for several months after clinical euthyroidism is achieved.

63. TSH Reference range ? What the American Association of Clinical Endocrinologists Said... AACE believes the new range will result in proper diagnosis for millions of Americans who suffer from a mild thyroid disorder, but have gone untreated until now."

64. Thyroid Disease in Pregnancy Three factors alter thyroid function in pregnancy 1) Transient ↑ in hCG, during the 1st trimester can stimulate the TSH-R - Gestational Transient Thyrotoxicosis (GTT) - Hyperemesisgravidarum 2) E2-induced ↑ in TBG during the 1st trimester, which is sustained during pregnancy affecting TT4 and TT3 3) Alterations in immune function leading to onset, exacerbation, or improvement of an underlying autoimmune thyroid disease.

67. Congenital Hypothyroidism Because newborns are asymptomatic at birth, screening programs developed worldwide Incidence 1 in 3,000 One of the commonest treatable causes of mental retardation

69. Asymptomatic and TPO Ab (+): TSH > 5

70. Symptomatic: TSH > 5

71. Pregnant female: TSH > 5

72. Goitrous: TSH > 5Annual Monitoring only with TSH every 6 to 8 weeks until the TSH level reaches 0.5mIU/L to 2.0 mIU/L After the TSH level has normalized, maintenance dosage is continued and the TSH test repeated annually or whenever the patient becomes symptomatic Hypothyroidism

74. Possible explanations for various result combinations

76. Used to monitor the recurrence of the common thyroid cancers (follicular cell–derived tumors)

77. Tg measurements should always be interpreted in the context of simultaneous measurement of Tg autoantibodies (TgAB). TgAB occur in about 20% of thyroid cancer patients and can lead to falsely low Tg measurementsCalcitonin Assay: Used to detect and monitor the recurrence of medullary thyroid cancer

79. Conclusion TSH is a good screening test to assess thyroid function in an outpatient setting. If TSH is abnormal, the diagnosis is confirmed with thyroid hormone levels. Screening for thyroid diseases especially those at high risk is cost effective as up to 20% of those with subclinical thyroid disease may turn to clinical thyroid disease Timing and choosing the right thyroid test is the best approach in understanding the meaning of the results.

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