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your thyroid and you: notes from an iodine-laden gland

your thyroid and you: notes from an iodine-laden gland. Oliver Z. Graham, MD UpToDate-Certified Endocrinologist Department of Internal Medicine. The Agenda. Differential Diagnosis of hypo and hyperthyroidism Dosing Levothyroxine Management of Hyperthyroidism

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your thyroid and you: notes from an iodine-laden gland

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  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

  4. 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?

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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?

  10. 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?

  11. 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

  12. 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

  13. 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

  14. Her labs…. How would you manage her levothyroxine dose?

  15. 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

  16. 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

  17. 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?

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

  19. 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?

  20. 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)

  21. 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)

  22. 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)

  23. 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)?

  24. 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

  25. 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

  26. 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

  27. 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)

  28. 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

  29. 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

  30. 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)

  31. 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

  32. 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

  33. 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

  34. 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

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