Thyroid Treatment and Vitamin D Update
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Transcript of Thyroid Treatment and Vitamin D Update
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THYROID TREATMENT AND VITAMIN D UPDATEA CPMC Regional CME Event
- An Integrated Approach
Saturday October 27, 2012
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HYPOTHYROIDISM
Diana M. Antoniucci, MD, MASSutter Pacific Medical Foundation
Division of Endocrinology, Diabetes and OsteoporosisAssistant Clinical Professor Medicine
University of California, San Francisco
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IN YOUR OFFICE…
• 56 yo man presents complaining of fatigue and constipation
• His PMHx is significant for coronary artery disease
• What is the best screening test for thyroid disease?
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HYPOTHYROIDISM
• 2% of adult women • 0.1-0.2% of adult men
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Fatigue
Forgetfulness/Slower ThinkingMoodiness/ Irritability
DepressionInability to ConcentrateThinning Hair/Hair Loss
Loss of Body Hair
Dry, Patchy Skin
Weight GainCold Intolerance
Elevated CholesterolFamily History of Thyroid Disease
or Diabetes 1
Muscle Weakness/Cramps
Constipation
Infertility
Menstrual Irregularities/Heavy Period
Slower HR and low voltage ECGDifficulty Swallowing
Persistent Dry or Sore Throat
Hoarseness/Deepening of Voice
Small or Enlarged Thyroid (Goiter)
Peri-orbital Edema
CLINICAL FEATURES
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DIFFERENTIAL DIAGNOSIS
• Hashimoto’s, or autoimmune thyroiditis – most common
• Drugs: amiodarone, lithium, interferon, iodide
• Iatrogenic: post surgical, post RAI rx or post XRT for neck cancer
• Rare causes: iodine deficiency, central hypothyroidism, peripheral resistance to thyroid hormone.
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THYROID TESTS• Thyroid Function Tests (TFTs):
- TSH – good to screen initially- Free T4 – needed to follow patients and to rule out
central thyroid disease- Total or Free T3 – to r/o or r/i T3 thyrotoxicosis only- Thyroglobulin – thyroid cancer or presumed
subacute thyroiditis• Thyroid antibodies
- TPO and Tg Ab’s: sensitive for autoimmune thyroid dz, esp. Hashimoto’s
- TSH rcptr stimulating immunoglobulins (TSI): specific for Graves’ disease
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BACK TO OUR CASE…
• His TSH is elevated at 63 uIU/ml (0.4-4.5)
• What other laboratories/studies should you order?
• How could you make a diagnosis of Hashimoto’s?
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RESULTS
• His TPO antibodies and TG antibodies are positive
• No need to check ultrasound in this setting
• Thyroglobulin level also not necessary
• Should you treat?• If so with what?
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HYPOTHYROIDISM THERAPY
• Standard: synthetic thyroxine (T4)- Little intrinsic activity- Converted to T3 in peripheral tissues- Most physiologic replacement
• Controversy of generics vs brand bioequivalence- 1997 study Synthroid, Levoxyl and 2 generics1
- Used FDA recommended methodology to determine bioequivalence• All 4 preparations were bioequivalent
1Dong BJ et al. JAMA 1997; 277:1205
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HYPOTHYROIDISM THERAPY
• Preferable to stay with one formulation when possible (generics – request same manufacturer)
• Levoxyl reportedly easier to absorb than Synthroid
• Tirosint – supposed to be unaffected by concomitant food intake
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HYPOTHYROIDISM THERAPY
• Estimated weight based replacement dose:- 1.6 mcg/kg/d
• Dose depends on cause of hypothyroidism and stage of disease- Athyroid patients tend to need higher
doses• Starting dose depends on age, co-
morbidities and TSH
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HYPOTHYROIDISM THERAPY
• In young healthy patients, can start full expected dose (1.6 mcg/kg/d)
• Older patients start at 25-50 mcg/d• Goal of therapy
- Symptom amelioration- TSH 1-2 uIU/ml
• Adjust no more often than every 6-8 weeks
• Small adjustments are best: - 12 mcg to at most 25 mcg increments in dose
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BACK TO YOUR OFFICE
• 56 yo hypothyroid man with hx of CAD• START LOW AND GO SLOW: Start low doses of
LT4 and slowly increase dose, be particularly careful in patients with heart disease
• Start LT4 12.5-25 mcg po qd. Recheck TFTs in 4-6 weeks and increase dose as needed
• Given his CAD, would start very low, increase every 4 weeks until approaching final expected dose
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ANOTHER DAY IN YOUR OFFICE…
• 28 yo woman with long standing hypothyroidism
• On stable replacement dose levothyroxine 112 mcg/d for years
• She reports fatigue, constipation and more irregular cycles
• TSH: 9.5 uIU/ml (0.4-4.5)• Talking to her you discover she added
prenatal vitamins to her regimen…
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HOW TO TAKE LEVOTHYROXINE
• Ideally:- 1st thing in AM- Empty stomach- No food for 30 min- Delay any calcium containing foods at
least 1 hr.• Move any iron or calcium containing
supplements to dinner time.
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IN THE OFFICE
• She moves prenatal vitamin to dinner time
• 6 weeks later, TSH is back down to 1.2 uIU/ml
• 4 months later, repeat TSH is 3.5 uIU/ml
• What happened?• Pregnancy test is now positive!
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HYPOTHYROIDISM IN PREGNANCY
• Requirement of levothyroxine increase 25-50% in pregnancy
• It is common for TSH to rise early on• Recommendations are to maintain TSH <2.5
uIU/ml throughout pregnancy• Check TSH, FT4 and TT4 every 4 weeks in
first 16 weeks and adjust as needed• Management of hypothyroidism in pregnancy
is a very appropriate referral to endocrinology
Journal of Clinical Endocrinology & Metabolism, 97: 2543–2565, 2012).
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AND ANOTHER PATIENT…
• 34 yo woman with 5 year history hypothyroidism
• TSH has been between 1-2 uIU/ml (0.4-4.5) for a few yrs
• Reports continued fatigue and not feeling same as before hypothyroidism
• Should you treat her with combination T4 and T3?
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HYPOTHYROID PT WITH PERSISTENT SYX
• Symptoms reported:- Fatigue- Diminished concentration and working memory- Poorer psychological well being
• Start with evaluation by PCP:- H&P- Labs: CMP, CBC, ESR, celiac dz testing, sleep apnea
screening or testing• Then Endo evaluation:
- 25OHD- Adrenal evaluation
• Consider possibility of depression
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TREATMENT WITH COMBINATION THERAPY
• Multiple randomized trials• Systematic review of 11 randomized trials
- One trial (n=35): beneficial effects on mood, quality of life and psychometric performance of T4-T3 combo vs T4 alone
- Remainder failed to show benefit• Subanalysis in one study1 homozygous
polymorphisms in a deiodinase (in 16% people)- Worse baseline neuro-cognitive scores- Significant improvement with combo T4/T3 rx
1Panicker V et al J Clin Endocrinol Metab 2009; 94: 1623
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TREATMENT WITH COMBINATION THERAPY
• Not necessary• Up to 16% hypothyroid patients may
benefit• No genetic test available now• Trial in still symptomatic patients is
reasonable- T4:T3 ratio of 10:1 to 14:1- Typically 2.5-5 mcg liothyronine qd to bid
added to T4- Goals of therapy same
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T3 CONTAINING PREPARATIONS
• Include desiccated thyroid (Armour), T4-T3 preparations (Thyrolar, Naturethroid)
• Wide fluctuations in serum T3 concentrations• Often unavailable due to manufacturing issues• T4/T3 Ratio is not physiological• No clear benefit and more difficult to dose and
adjust • Consider referral for convertion to T4 or T4+T3• Avoid in pregnancy
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PEARLS
• TSH best screening test• No need to order Tg or ultrasound in patients with
hypothyroidism• Always review how patients are taking LT4 pills• Aim for TSH 1-2• If still symptomatic, consider T3 addition• Sensitivity to TSH changes and how much TSH changes in
response to dose changes are somewhat variable• Refer if:
- Pregnancy- Worried about co-morbidities- TSH is not responding as expected- Patients still fatigued even at goal TSH and other causes of fatigue ruled
out