Your thyroid and you notes from an iodine laden gland
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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

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

Oliver Z. Graham, MD

UpToDate-Certified Endocrinologist

Department of Internal Medicine


The agenda
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


Screening for thyroid disease
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


Case study 1
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?


Differential hypothyroidism
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


Elevated tsh low ft4 what do i do now
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


Levothyroxine dose in hypothyroidism
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


Initiating treatment in hypothyroidism
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


Case study 2
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?


Case study 2 cont
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?


Case study 2 cont1
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


Indications for ordering a ft4 when you have a normal tsh
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


Case study 3
Case study #3 TSH

  • 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


Her labs
Her labs…. TSH

How would you manage her levothyroxine dose?


Causes of levothyroxine resistance
Causes of TSH“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


  • 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


Another case
Another case… Requirements

  • 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?


Scheme for Investigating Cases of Suspected Hyperthyroidism Requirements

(TSH)

(FT4)

(FT3)

*If you suspect hyperthyroid but FT4 normal, check FT3!


Back to our patient
Back to our patient… Requirements

  • 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?


Common causes of hyperthyroidism 98
Common causes of hyperthyroidism (98%) Requirements

  • Increased hormone synthesis

    • Graves disease

    • Multinodular goiter / Toxic adenoma

  • Decreased hormone synthesis

    • Thyroiditis

    • Iatrogenic (taking too much levothyroxine)

    • Medication (amiodarone)


Hyperthyroidism secondary to increased hormone synthesis
Hyperthyroidism secondary to increased hormone synthesis Requirements

  • 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)


Hyperthyroidism secondary to decreased hormone synthesis
Hyperthyroidism secondary to decreased hormone synthesis Requirements

  • 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)


Back to our patient1
Back to our patient… Requirements

  • 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)?


Common indications for a thyroid uptake scan
Common indications for a thyroid uptake scan Requirements

  • 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


Treatment of hyperthyroidism
Treatment of hyperthyroidism Requirements

  • 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


Beta blockers in hyperthyroidism
Beta blockers in hyperthyroidism Requirements

  • 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


Antithyroid medications
Antithyroid Medications Requirements

  • 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)


Antithyroid medications and side effects
Antithyroid Medications and side effects Requirements

  • 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


Should i order thyroid antibodies
Should I order Thyroid Antibodies?? Requirements

  • 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


Subclinical hypo thyroidism
Subclinical RequirementsHypothyroidism

  • 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)


Subclinical hyper thyroidism
Subclinical RequirementsHyperthyroidism

  • 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


Subclinical hyper thyroidism treatment
Subclinical RequirementsHyperthyroidism –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


Main points
Main Points Requirements

  • 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


Main points continued
Main points, continued Requirements

  • 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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