Interpretation of laboratory thyroid function tests

1. Interpretation of laboratory thyroid function tests

2. 5 % of world population suffers from thyroid diseases

3. Hypothalamic-Pituitary-Thyroid Axis

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

5. 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

6. To screen or not to screen for thyroid dysfunction • 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

7. Hyperthyroidism Hypothyroidism When the Thyroid Doesn’t Work

8. Hypothyroidism • More common than hyperthyroidism • 99% is primary (< 1% due to TSH deficiency) • Hashimoto’s: • Most common cause of hypothyroidism • Goiter • Anti TPO antibodies (90%) • Anti Thyroglobulin antibodies (20-50%) • Postpartum (silent): • Silent/painless • Occurs within 6 weeks6 months postpartum • Subacutethyroiditis: • Most common cause of painful thyroiditis 2001; Intenzo CM, et al. Scintigraphic features of autoimmune thyroiditis. 21: 957-964

9. 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

10. Laboratory findings in Hypothyroidism • Elevated TSH • Low FT4 • TPO Ab (+) • Macrocytic anemia due to VIT B12 deficiency • ↑ CPK-MB • ↑ LDL,↑Chol (↓ lipid clearance) • Hyponatremia

12. Hyperthyroidism • less common than hypothyroidism • 99% is primary (< 1% due to TSH deficiency) • Graves’ Disease • Goiter • Most common cause of hyperthyroidism • Anti-TSH antibodies (80%) • Toxic Nodular Disease • Single or multiple nodules • Occurs mostly in older age than graves • T3 Thyrotoxicosis: Approximately 5% of clinically hyperthyroid patients with normal FT4

13. 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

14. Laboratory findings in Hyperthyroidism • TSH nearly undetectable • Elevated FT4 or FT3 • Mild leukopenia • N/N anemia • ESR elevated • ↑ LFT’s and alkphosph • Mild ↑ Ca++ • ↓ Albumin • ↓ Cholesterol

15. Hyperthyroid Algorithm Sensitive TSH 0.1- 0-3 mIU/L Borderline Low TSH 0.3- 4.8 mIU/L Within normal Limits no further testing indicated < 0.1 mIU/L Low TSH Order FT4 FT4 If normal FT4 Hyperthyroid Order FT3

16. Spectrum of Thyroid Disease Sever mild Subclinical

17. 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

18. Case Study • A 30-year-old woman presents to gastroenterology clinic with constipation in last 3 months • 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. • 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. • She has a sister who is receiving levothyroxine therapy for hypothyroidism. • On examination, she looked slightly pale, pulse 72/min regular,bl pr 110/80,chest ,heart and abdomen :clinically free, thyroid is not palpable. • All Laboratory tests are unremarkable except a serum TSH level of 7 mIU/L. Thyroperoxidase (TPO) antibodies are detected.

19. Subclinical hypothyroidism • The TSH level may be borderline elevated in the presence of normal levels of fT4. • Treatment for subclinical hypothyroidism is recommended when: • TSH greater than 10mU/L; • TSH is above the upper reference interval limit, but ≤10 mU/L and any of the following are present: • elevated thyroid peroxidase (TPO) antibodies • goitre • strong family history of autoimmune disease • Pregnancy • Dyslipidemia

20. Subclinical hyperthyroidism • TSH level may be borderline suppressed in the presence of normal levels of fT4 • Subclinical hyperthyroidism is much less common than Subclinical hypothyroidism • Treatment for subclinical hyperthyroidism is recommended when: • Any cardiac disease • Age > 60 • Osteoporosis

21. 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?

22. 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

23. 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 • Estrogens: Increase TBG, decrease FT4 level • Androgens/corticosteroids : Decrease TBG, increase FT4 level

24. 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.

25. TSH Reference range ? What the American Association of Clinical Endocrinologists Said...

26. 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.

27. Thyroid Disease in Pregnancy • Pre-pregnancy and early pregnancy: • TSH screening for hypothyroidism is indicated in women who are planning pregnancy or are in early pregnancy if they have a goiter or strong family history of thyroid disease. • Pregnancy: • TSH may be suppressed as a normal finding within the first trimester of pregnancy. A normal fT4 generally excludes hyperthyroidism. • US Endocrine Society recommends thyroid function screening for all pregnant women • Post pregnancy: • Post-partum thyroiditis (PPT) may occur in 5-10% of women

28. Subclinical hypothyroidism with pregnancy • Undetected SCH during pregnancy may adversely affect the neuropsychological development ,survival of the fetus • Associated with hypertension and toxaemia • Subclinical hypothyroidism is associated with ovulatory dysfunction and infertility..

29. 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

30. Treating Thyroid Disorders Hypothyroidism Indications for LT4 replacement • Asymptomatic: TSH > 10 • Asymptomatic and TPO Ab (+): TSH > 5 • Symptomatic: TSH > 5 • Pregnant female: TSH > 5 • Goitrous: TSH > 5 • Annual 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

31. Treating Thyroid Disorders Hyperthyroidism • Radioiodine Therapy • Stop Thyroid Hormone Production • Anti-thyroid Drugs Often Helpful • Surgery Maybe Necessary • Once treatment begins, FT4 is recommended to monitor therapy during early transition phase ( usually not more than 3 months ) • TSH is not recommended for following treatment of hyperthyroidism unless FT4 drops to low-normal levels, the thyroid gland enlarges and symptoms of hypothyroidism present

32. Possible explanations for various result combinations

33. Thyroid Scale Diagram • Optimal zone is an approximation and that it is meant to be used as a rough guide.

34. Cancer thyroid • Thyroid carcinoma occurs relatively infrequently compared to the common occurrence of benign thyroid disease • Thyroglobulin Assays: • Determines the amount of thyroid tissue after a thyroidectomy ie there should be no thyroglobulin after complete thyroid gland removal. • Used to monitor the recurrence of the common thyroid cancers (follicular cell–derived tumors) • 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 measurements • Calcitonin Assay: Used to detect and monitor the recurrence of medullary thyroid cancer

35. Patients Responsibilities • Tell Your Doctor if You Have Symptoms • Ask Your Doctor for a TSH Test and Free T4 -- Make These Tests as Part of Your Medical Routine if You Are a Woman Over 35 or a man over 60 years • Take Your Medication as Directed • Take Your Thyroid Medication Separately from Iron, Calcium and Multivitamins • Do Not Change Brand or Dose of Your Thyroid Medication Without Consulting Your Doctor • If Symptoms Persist or Return, Tell Your Doctor

36. 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.