1. your thyroid and you: notes from an iodine-laden gland Oliver Z. Graham, MD UpToDate-Certified Endocrinologist Department of Internal Medicine

2. The Agenda  Differential Diagnosis of hypo and hyperthyroidism  Dosing Levothyroxine  Management of Hyperthyroidism  Subclinical Hypo and Hyperthyroid  Ordering Thyroid Antibodies  When to get FT4, FT3

3. Screening for thyroid disease  Very controversial subject  American Thyroid Association  Check TSH at age 35 and every 5 years afterwards  USPTS  Do not perform routine screening  Clinical consensus group  Reasonable to check TSH in women after 60 years old, also in those with risk for thyroid dysfunction (DM 1 or other autoimmune disease, +FH)  Also reasonable to screen all pregnant women

5. Case study #1  A 54 YO woman presents with fatigue, constipation and cold intolerance.  TSH 66 (0.34-5.6)  Does she need any further workup?  How would you start thyroid replacement therapy?

6. Differential Hypothyroidism  Primary Hypothyroidism (95%)  Idiopathic/Hashimoto’s (most common)  Post radiation/thyroidectomy  Late stage fibrous thyroiditis  Drugs (lithium/interferon/amiodarone)  Infiltrative diseases  Secondary Hypothyroidism (5%)  Pituitary or hypothalamic tumor  Pituitary necrosis

7. Elevated TSH, Low FT4 – What do I do now?  Is patient on amiodarone/lithium/interferon?  Examine thyroid  In Hashimoto’s, exam usually unremarkable  Start treatment

8. Levothyroxine dose in hypothyroidism  Usual dose in healthy adult 1.6 mcg/kg  typical dose 100-150 mcg/day  Usual dose in elderly 1 mcg/kg  Pregnancy – thyroxine requirements may be > 50% higher

9. Initiating Treatment in Hypothyroidism  If healthy patient with high TSH, can start at higher dose (50-100 mcg/daily)  If healthy patient with mild elevation TSH, start 25-50 mcg/day  In elderly, cardiovascular disease   Levothyroxine 25-50 mcg/day  Check TSH q6 weeks, increase by 25-50 mcg until TSH normal

10. Case study #2  A 32 YO woman presents with fatigue, constipation, cold intolerance, dry skin and difficulty with concentration.  TSH 0.37 (0.34-5.6)  Does she need any further workup?

11. Case study #2, cont  A 32 YO woman presents with fatigue, constipation, cold intolerance, dry skin and difficulty with concentration.  TSH 0.37 (0.34-5.6)  FT4 0.23 (0.58-1.65)  Does she need any further workup?

12. Case study #2, cont  She also reports galactorrhea, amennorhea and hot flashes.  TSH 0.37 (0.34-5.6)  FT4 0.23 (0.58-1.65)  Prolactin level 1056 (5-20)  MRI – 2 cm pituitary mass  Dx: Secondary (pituitary) hypothyroidism from prolactinoma

13. Indications for ordering a FT4 when you have a “normal” TSH  Clinical manifestations of hypothyroidism but a low normal TSH and suspected pituitary disease (secondary hypothyroidism)  Known secondary hypothyroidism, to follow response to levothyroxine treatment  Eg – In panhypopitutarism TSH often low regardless of treatment, FT4 needs to be checked to eval levothyroxine dose  On a drug that known to affect TSH secretion  Dopamine agonist/antagonists, amiodarone, glucocorticoids

14. Case study #3  A 43 YO woman with PMH significant for hyperthyroidism s/p radioactive iodine ablation 6 years ago (now hypothyroid), anxiety, hypertension, polysubstance abuse comes in for followup.  Over the past few years her levothyroxine has been increased because of TFT abnormalities, and is now 250 mcg/day. She states she is taking her medications religiously

15. Her labs…. FT4TSH 1/070.61 (0.58-1.65)14 (0.34-5.6) 4/070.1577 8/070.4285 11/070.6822 3/080.2>100  How would you manage her levothyroxine dose?

16. Causes of “levothyroxine resistance”  **Nonadherance**  Clues   Normal FT4 but elevated TSH (playing “catch up” by taking T4 1 week prior to lab test)  Widely fluctuating TSH levels  Conditions that induce hypochlorohydria  Thyroxine requirement 22-33% higher in those with H Pylori, atrophic gastritits, celiac sprue  Medications that affect absorption  Iron, Calcium, PPI, H2 blocker, aluminum containing anacids

17. Drugs Potentially Altering Thyroid Hormone Replacement Requirements Increase replacement requirements Drugs that reduce thyroid hormone production Lithium Iodine-containing medications Amiodarone (Cordarone) Drugs that reduce thyroid hormone absorption Sucralfate (Carafate) Ferrous sulfate (Slow Fe) Cholestyramine (Questran) PPI, H2 blockers Aluminum-containing antacids Calcium products Drugs that increase metabolism of thyroxine Rifampin (Rifadin) Phenobarbital Carbamazepine (Tegretol) Warfarin (Coumadin) Oral hypoglycemic agents Increase thyroxine availability and may decrease replacement requirements (displace thyroid hormone from protein binding) Furosemide (Lasix) Salicylates

18. Another case…  A 34 YO woman comes into clinic with anxiety, palpitations and heat intolerance for 5 months.  PE HR 120, Reg. Mild tremor, mild exopthalmos, mild enlarged thyroid, no nodules  TSH < 0.01  FT4 1.60 (0.58-1.65)  What do you do next?

19. *If you suspect hyperthyroid but FT4 normal, check FT3! Scheme for Investigating Cases of Suspected Hyperthyroidism (TSH) (FT4) (FT3)

20. Back to our patient…  A 34 YO woman comes into clinic with anxiety, palpitations and heat intolerance for 5 months.  PE HR 120, Reg. Mild tremor, mild exopthalmos, mild enlarged thyroid, no nodules  TSH < 0.01  FT4 1.60 (0.58-1.65) FT3 5.8 (2.3-4.2)  (“T3 thyrotoxicosis”)  What is the cause of her hyperthyroidism?

21. Common causes of hyperthyroidism (98%)  Increased hormone synthesis  Graves disease  Multinodular goiter / Toxic adenoma  Decreased hormone synthesis  Thyroiditis  Iatrogenic (taking too much levothyroxine)  Medication (amiodarone)

22. Hyperthyroidism secondary to increased hormone synthesis  Graves disease  Caused by thyroid-stimulating antibodies  Most common cause of hyperthyroidism  Manifested by exopthalmos, pretibial myxedema, smooth enlarged thyroid  Toxic Multinodular Goiter / Toxic adenoma  Caused by nodule(s) functioning independent of feedback mechanism  Approx 10% of hyperthyroidism  (Rare stuff – Iodine load, TSH producing adenomas, trophoblastic disease)

23. Hyperthyroidism secondary to decreased hormone synthesis  Thyroiditis (inflammation of thyroid gland with subsequent release T3/T4)  Subacute (DeQuevain’s) – URI sx with fever, malaise and tender goiter  Silent – No real sx  Postpartum – Often self-limiited  Med induced (amiodarone)  Exogenous administration  (Rare stuff – Struma ovarii, metastatic follicular thyroid CA)

24. Back to our patient…  A 34 YO woman comes into clinic with anxiety, palpitations and heat intolerance for 5 months.  PE HR 120, Reg. Mild tremor, mild exopthalmos, mild enlarged thyroid, no nodules  TSH < 0.01  FT4 1.60 (0.58-1.65) FT3 5.8 (2.3-4.2)  (“T3 thyrotoxicosis”)  Does she need a thyroid scan (Iodine 123 thyroid uptake scan)?

25. Common indications for a thyroid uptake scan  To differentiate between hyperthyroidism from increased vs decreased hormone synthesis  “URI sx, tender thyroid  is this thyroiditis?”  Pre radioactive ablation to determine dose  Results can suggest etiology:  Graves: Diffuse increased uptake  Toxic goiter/adenoma: Focal area(s) increased uptake  Thyroiditis/Iatrogenic: Reduced uptake

26. Treatment of hyperthyroidism  Graves disease:  Spontaneous remission in 30-50%, antithyroid drugs or iodine ablation acceptable (+ beta blocker)  Toxic multinodular goiter:  Remission rare, usually treat with iodine ablation (+ beta blocker)  Thyroiditis:  Treat symptoms with beta blocker +/- NSAIDS, watch closely for hypothyroidism

28. Beta blockers in hyperthyroidism  Used to reduce tachycardia, tremor, other sx  Selective vs nonselective?  Probably doesn’t matter  Reasonable to start  Atenolol 50-100 daily  Toprol XL 100 daily

29. Antithyroid Medications  Methimazole (tapazole) – Preferred agent  Long half life – once daily dosing  Reduced incidence side effects  Usually start 20 daily, increased for severe thyrotoxicosis  PTU  Preferred agent in pregancy (theoretically dosen’t cross placenta)  Used in thyrotoxic storm (prevents conversion T4  T3)

30. Antithyroid Medications and side effects  Agranulocytosis  Usually occurs in first 3 months of therapy  Councel every patient: “If you have sore throat & fever, stop med and go to ER”  Hepatitis (rare)  Rash

31. Should I order Thyroid Antibodies??  Antithyroid Peroxidase (Anti-TPO)  Present in 13% general population  Consider ordering in subclinical hypothyroidism when deciding whether to tx (high levels correlate with progression to overt hypothyroidism)  Antithyroglobulin (Anti-Tg)  Measure in all patients with differentiated thyroid cancer (guides therapy)  Anti-TSH receptor Ab  Usually elevated (with anti-TPO) in setting of Graves disease  Only order if Graves dx is in question

32. Subclinical Hypothyroidism  Defined by elevated TSH with nl FT4  No clear guidelines for how to tx  Suggested approaches:  Treat all with hypothyroid symptoms  Treat all with TSH > 10  Check anti-TPO ab, if +  consider tx (high chance pt will develop overt hypothyroid)

33. Subclinical Hyperthyroidism  Defined by supressed TSH with normal FT3/FT4  Again, no clear guidelines how to tx  Risk of not treating most risky in elderly patients and/or those with cardiac or bone comorbidities  Osteoporosis  Atrial Fibrillation  Cardiovascular disease

34. Subclinical Hyperthyroidism – Treatment  A Suggested approach:  If TSH < 0.1, consider tx (esp in elderly)  If TSH 0.1-0.5, may follow patient, but consider treatment if:  Unexplained weight loss  Osteoporosis  Atrial Fibrillation  Cardiovascular disease  Thyroid scan shows area of high uptake

35. Main Points  Starting dose of levothyroxine depends on patient’s age and elevation of TSH  If hypothyroid sx but low/normal TSH, get FT4 (evaluate 2ndary hypothyroid)  If supressed TSH but normal FT4, get FT3 (evaluate T3 thyrotoxicosis)  “Levothyroixine resistance” usually from noncompliance, but consider hypochlorhydria and medications as etiology

36. Main points, continued  Graves disease can be treated with medications or iodine ablation  Methimazole is the antithyroid medication of choice, but watch for agranulocytosis  There are few indications for ordering thyroid antibodies  Treatment of subclinical hyper and hypothyroidism controversial