1. D- Interpreting Thyroid Function Tests

2. Pt Info:  CC: palpitations  82 y/o F presents with hyperactivity, sweating, palpitations, wt loss, insomnia, moist skin, fine hair, irregular menses, diarrhea  PE: tachy, elevated SBP, damp skin, lid lag, hyperreflexive DTR  Labs: CBC wnl, BMP wnl, TSH <0.01 (L), T4 4.1 (H), T3 wnl

3. Objectives  Pathophysiology  Thyrotoxicosis  Hypothyroid

4. Hormone Regulation  TRH  TSH  iodine uptake, organification  synthesis & release of thyroid hormone  T4/T3 Regulate:  basal metabolism, thermogenesis, lipogenesis  fetal CNS development

5. Thyroid Hormones  Thyroxine (T4)  Thyroid gland  t1/2: 8 days  Triiodothyronine (T3)  80% in Periphery  Liver/kidney remove iodine from T4  Regulate Thyroid Hormone-dependent genes  t1/2: 1-1.5 days  T4  T3  Decreased:  Meds: propranolol, PTU, corticosteroids, amiodarone  Illness: cytokine mediated

6. Binding Proteins  T4/T3 99% protein bound  Prevents excess tissue uptake  Maintains accessible reserve  Thyroxine-binding globulin (TBG) - 70%  Inc: E2, 5-FU, Methadone, Tamoxifen  Dec: Androgens, Corticosteroids, Niacin  Albumin – 15-20%  Transthyretin – 10-15%

7. TFTs TSH HIGH = Hypo Check free T4 NL = No further Testing LOW = Hyper Check free T3/T4

8. Functional Disorders ThyrotoxicosisHypothyroidism -Grave’s Disease - Toxic Adenoma - Toxic Multinodular Goiter -Thyroiditis -Exogenous -TSH Mediated -Hashimoto’s Disease - Post-op/Post-ablative -I deficiency

9. Thyrotoxicosis  Thyroid excess from any cause:  Increased Synthesis  Damaged Gland  Exogenous Intake  RAIU  High (>30%): Hyperfunction  NL (10-30%): Euthyroid  Low (<10%): Thyroiditis, I excess, Amiodarone

10. Symptoms Increased Metabolism:  Weight loss, Dec appetite  Warm, sweating, thirst, fever  Tachycardia, Arrhythmia, Palpitations  Diarrhea  Fatigue, Exhaustion  Goiter  Difficulty concentrating  Panic and anxiety  Hyperreflexia, Tremors  Insomnia Other:  Pregnancy-related problems  Arthralgias  Skin: hives, itching, vitiligo  Hair loss  Finger/nail changes  Eye: bulging, dry, pain  Depression, irrational anger

11. Thyrotoxicosis  Increased Synthesis  Damaged Gland  Exogenous Intake

12. Increased Synthesis: Hyperthyroidism  High T4 & Low TSH  Increased T4/T3 release:  Grave’s  Toxic MNG  Toxic Adenoma  High RAIU

13. Grave’s Disease  Most common cause in US  AutoAb against TSH receptor  Diffuse Goiter, Thyrotoxicosis, High RAIU  Thyroid Scan: Increased activity  Ophthalmopathy, Dermopathy, Acropathy

14. Grave’s Disease - treatment  Medication: 50% remission @ 1 year  Methimazole  PTU  BB while toxic  Radioactive Iodine Ablation  Not for pts with severe ophthalmopathy  Surgical Removal

15. Toxic Multinodular Goiter  Sporadic Goiter  Multinodular Euthyroid  Subclinical  Overt Thyrotoxicosis  Increased RAIU (autonomous production)  Rest of Gland suppressed  Treatment: Radioactive Iodine

16. Toxic Adenoma  HOT Nodule: Autonomous function  Activating Mutation of TSH Receptor  Size = Hormone production  >3 cm  Treatment:  Hemithyroidectomy  Radioactive Iodine

17. Thyrotoxicosis  Increased Synthesis  Damaged Gland  Exogenous Intake

18. Damaged Gland  Low RAIU  Subacute Thyroiditis: BB & NSAIDs  Firm & painful gland  Post-viral  Drug-Induced  Amiodarone, Lithium, α-IFN, IL-2  Postpartum Thyroiditis

19. Amiodarone-Induced  3% of patients in US  Type 1: high iodine content (JodBasedow)  Pre-existing thyroid autonomy  High RAIU  Treatment: methimazole  Type 2: direct toxic effect  No Pre-existing thyroid autonomy  Low RAIU, Inc Inflammation  Treatment: Prednisone, NSAIDs

20. Thyrotoxicosis  Increased Synthesis  Damaged Gland  Exogenous Intake

21. Surreptitious Intake  Low TSH  Low RAIU  Low TG level

22. Thyroid Storm  Iatrogenic  Radioiodine therapy, Contrast dyes  Abrupt cessation of Antithyroid drugs  Surgery  Acute Nonthyroidal Illness  Stroke, PE, DKA, Trauma, Infection

23. Thyroid Storm - treatment DrugPTU/Methimazole Blocks new hormone synthesis Blocks T4  T3 Propanolol/ Esmolol Infusion Blocks T4  T3 in high doses Iodine Blocks new hormone synthesis Blocks hormone release Hydrocortisone/Dexamethasone Blocks T4  T3

24. Subclinical Thyrotoxicosis  Low TSH & High NL T4  Complications  Arrhythmia, Osteoporosis  esp >65y/o with TSH 65y/o with TSH <0.1 mU/L

25. Functional Disorders ThyrotoxicosisHypothyroidism -Grave’s Disease - Toxic Adenoma - Toxic Multinodular Goiter -Thyroiditis -Exogenous -TSH Mediated -Hashimoto’s Disease - Post-op/Post-ablative -I deficiency

26. Hypothyroidism  Low T4 & High TSH  More common than Thyrotoxicosis  Treatment: Synthroid - goal TSH 1-2 mU/L

27. Symptoms Slow Metabolism:  Weight Gain  Constipation  Hypothermia/Cold Intolerance  Fatigued, Lethargy  Slow Movements/speech  Delayed DTRs  Bradycardia Accumulation of Matrix Substance:  Skin: coarse/dry, scaly  Hair: coarse/dry, brittle, loss  Hoarseness  Edema of eyes and face Other:  Arthralgias  Irregular menstrual cycles  Depression

28. Monitoring Replacement TSH HIGH = Not Enough INC Dose NL = Continue Dose LOW = Too Much DEC Dose

29. Medication Controversy  ? T3  1999: improved mood & psych testing with combo therapy  Four subsequent studies refuted  ? Generic Synthroid  Not all bioequivalent when FDA approved

30. Hashimoto’s  Most common cause in North America  Positive anti-TPO Ab  Increase Autoimmune Endocrinopathy  Addison’s, DM1, Premature ovarian failure  No further w/u

31. Myxedema Coma  Obtundation, Hypothermia  CV Changes:  Dec HR, Contractility, SBP, CO  Inc SVR, DBP  Pericardial Effusion  Precipitant: Infection, trauma, cold, sedative

32. Myxedema Coma - treatment  IV Levothroxine replacement  Corticosteroids – adrenal insufficiency  MV – CO2 retention, hypoxia  Treat precipitating cause

33. Subclinical Hypothyroidism  High TSH & Low NL T4  Most have Hashimoto’s  Systemic symptoms, elevated LDL, Cardiac changes

34. Objectives  Pathophysiology  Thyrotoxicosis  Hypothyroid