Thyroid Disorders
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Thyroid Disorders Thyroid Disorders Presentation Transcript

  • Thyroid Disorders William Harper, MD, FRCPC Endocrinology & Metabolism Assistant Professor of Medicine, McMaster University
  • Case 1
    • 31 year old female
    • Somalia  Canada 3 years ago
    • G2P1A0, 11 weeks pregnant
    • Well except fatigue
    • Hb 108 , ferritin 7 (Fe and LT4 interaction?)
    • TSH 0.2 mU/L, FT4 7 pM
    • Started on LT4 0.05  TSH < 0.01 mU/L
    • FT4 12 pM, FT3 2.1 pM
  • Case 1
    • How would you characterize her hypothyroidism?
    • What are the ramifications of pregnancy to thyroid function/dysfunction?
  • TSH Low High FT4 FT4 & FT3 Low 1 ° Hypothyroid Low Central Hypothyroid TRH Stim. If equivocal MRI, etc. High 1 ° Thyrotoxicosis High 2 ° thyrotoxicosis
    • Endo consult
    • FT3, rT3
    • MRI, α -SU
    RAIU
  • TRH Stimulation test A) 1 ° Hypothyroidism B) Central Hypothyroidism C) Euthyroid D) 1 ° Thyrotoxicosis
  • Case 1
    • GH, IGF-1 normal
    • LH, FSH, E2, progesterone, PRL normal for pregnancy
    • 8 AM cortisol 345, short ACTH test normal
    • MRI: normal pituitary
    • TGAB, TPOAB negative
    • LT4 increased until FT4 in hi-normal range
    • Normal pregnancy, delivery, baby, lactation
    • Considering TRH stim once done breast-feeding
  • Thyroid Tests
    • Thyroid Function
    • Iodine Kinetics
    • Thyroid Structure
    • FNA
    • Thyroid Antibodies
    • Thyroglobulin
  • T4 T3 80% (peripheral) 20% Protein* binding + 0.03% free T4 Protein* binding + 0.3% free T3 (10-20x less than T4) Total T4 60-155 nM Total T3 0.7-2.1 nM T 3 RU/THBI 0.77-1.23 TBG 75% TBPA 15% Albumin 10% *
  • Thyroid Function Tests
    • TSH 0.4 –5.0 mU/L
    • Free T4 (thyroxine) 9.1 – 23.8 pM
    • Free T3 (triiodothyronine) 2.23-5.3 pM
  • TSH Assay (0.4-5 mU/L)
    • Early RIA < 1.0 mU/L
        • Thyrotoxicosis / 2 º hypothyroidism
          • Unable to detect lower range of normal
    • Monoclonal SEN < 0.1 mU/L
    • Super SEN < 0.01 mU/L
  • Case 1
    • How would you characterize her hypothyroidism?
    • What are the ramifications of pregnancy to thyroid function/dysfunction?
  • Thyroid & Pregnancy: Normal Physiology
    • Increased estrogen  increased TBG
    • Higher total T4, T3 (normal FT4, FT3 if thyroid gland working properly)
    • hCG peak end of 1 st trimester, weak TSH agonist so may cause slight goitre
    • Fetal thyroid starts working at 11 wks
    • T4 & T3 do NOT cross placenta (or do so minimally)
    • Do cross placenta: PTU, MTZ, TSH-R Ab (stim or block)
    • MTZ  aplasia cutis scalp defects
  •  
  • Thyroid & Pregnancy: Hypothyroidism
    • Will need ~ 25% increase in LT4 during pregnancy due to increased TBG levels
    • Risks: increased spont abort, HTN, preterm pregnancy, 7 IQ points for fetus (NEJM, 341(8):549-555, Aug 31, 2001)
  • LT4 dose adjustment in Pregnancy: Need TSH at baseline & q2mos while pregnant Starting LT4: 2 ug/kg/d and check TSH q4wk until euthythyroid Increase dose by 100 ug/d TSH > 20 Increase dose by 50-75 ug/d TSH 10-20 Increase dose by 50 ug/d TSH increased but < 10 Dose Adjustment TSH
  • Thyrotoxicosis & Pregnancy
    • Risks: fetal anomalies, spont abort, preterm labor, fetal hyperthyoridism, thyroid storm in labor
    • No RAI ever
    • Rx options: ATD or 2 nd trimester thyroidectomy
    • PTU drug of choice (avoid MTZ due to scalp defects)
    • Aim to keep FT4 levels in hi normal range
    • OK to breast feed on PTU as does not go into breast milk
  • Neonatal Grave’s
    • Rare < 2% infants born to Graves” moms
    • 2 types:
    • Transplacental trnsfr of TSH-R ab (IgG)
        • Present at birth, self-limited
        • Rx PTU, Lugol’s, propanolol, prednisone
        • Prevention: TSI in mom 2 nd trimester, if 5X normal then Rx mom with PTU (crosses placenta to protect fetus) even if mom is euthyroid (can give mom LT4 which won’t cross placenta)
    • Child develops own TSH-R ab
        • Strong family hx of Grave’s
        • Present @ 3-6 mos
        • 20% mortality, persistant brain dysfunction
  • Postpartum & Thyroid
    • 5% (3-16%) postpartum women (25% T1DM)
    • Up to 1 year postpartum (most 1-4 months)
    • Lymphocytic infiltration (Hashimoto’s)
    • Postpartum  Exacerbation of all autoimmune dx
    • 25-50% persistant hypothyroidism
    • Small, diffuse, nontender goitre
    • Transiently thyrotoxic  Hypothyroid
  •  
  • Postpartum & Thyroid
    • Distinguish Thyrotoxic phase from Grave’s:
        • No Eye disease
        • Less severe thyrotoxic, transient (repeat thyroid fn 2-3 mos)
        • RAI (if not breast-feeding)
    • Rx:
        • Hyperthyroid symptoms: atenolol 25-50 mg od
        • Hypothyroid symptoms: LT4 50-100 ug/d to start
            • Adjust LT4 dose for symtoms and normalization TSH
            • Consider withdrawal at 6-9 months
            • (25-50% persistent hypothyroid, hi-risk recur future preg)
  • Postpartum & Thyroid
    • Postpartum depression
        • When studied, no association between postpartum depression/thyroiditis
        • Overlapping symtoms, R/O thyroid before start antidepressents
    • Screening for Postpartum Thyroiditis
        • HOW: TSH q3mos from 1 mos to 1 year postpartum?
        • WHO:
          • Symptoms of thyroid dysfn.
          • Goitre
          • T1DM
          • Postpartum thyroiditis with prior pregnancy
  • Case 2
    • 47 year old female
    • Concerned about weight gain over past 15 years (15 lbs). Otherwise asymptomatic
    • BMI 25, Thyroid: 40 gm, rubbery firm.
    • TSH 6.7 mU/L, FT4 13 pM, FT3 2.5 pM
    • FHx: mother, sister – both on LT4
    • Medications: “Thyrosol” (health store)
    • Wondering about hypothyroidism causing her weight gain
    • Read on internet about “Wilson’s Disease”
  • Case 2
    • When to treat “Subclinical” thyroid dysfunction?
    • Naturopathic thyroid remedies
    • Hypothryoidism Rx other than Levothyroxine
    • What is Wilson’s Thyroid Disease?
  • Subclincal Hypothyroidism
    •  TSH, normal FT4
    • Most asymptomatic & don’t need Rx (monitor TSH q2-5y)
    • Rx Indications:
      • Increased risk of progression
        • TSH > 10, Female > 50 y.o.
        • Anti-TPO Ab titre > 1:100,000 ?
        • Goitre present ?
      • Dyslipidemia?
        • Total cholesterol (TC)  6-8% if TSH > 10 and TC > 6.2 nM
      • Symptoms?
      • Pregnancy, Infertility, Ovulatory Dysfn.
  • Case 2
    • When to treat “Subclinical” thyroid dysfunction?
    • Naturopathic thyroid remedies (Thyrosol)
    • Hypothryoidism Rx other than Levothyroxine
    • What is Wilson’s Thyroid Disease?
  •  
  • Hashimoto’s Disease
    • Most common cause of hypothyroidism in North America (not idodine defeciency!)
    • Autoimmune
    • lymphocytic thyroiditis
    • Females > Males, Runs in Families
    • Antithyroid antibodies:
        • Thyroglobulin Ab
        • Microsomal Ab
        • TSH-R Ab (block)
  • Hashimoto’s Disease
    • Treatment:
        • Thyroid Hormone Replacement
        • Levothyroxine (T4)
        • T3?, T4/T3 combo?, dessicated thyroid?
    • No benefit to giving iodine!
        • In fact, iodine may decrease hormone production
        • Wolff-Chaikoff effect (lack of escape)
  • Case 2
    • When to treat “Subclinical” thyroid dysfunction?
    • Naturopathic thyroid remedies
    • Hypothryoidism Rx other than Levothyroxine
    • What is Wilson’s Thyroid Disease?
  • Treatment of Hypothyroidism
    • Iodine only if iodine deficiency is the cause
        • Rare in North America!
    • Replacement thyroid hormone medication:
        • T4?
        • T3?
        • T4 + T3 Mixture?
        • Thyroid Hormone from “natural sources” ?
  • T4 T3 85% (peripheral conversion) 15% Protein* binding + 0.03% free T4 Protein* binding + 0.3% free T3 (10-20x less than T4) Normal Daily Thyroid Secretion Rate: T4 = 100 ug/day T3 = 6 ug/day ( ratio T4:T3 = 14:1 )
  • < 24h 5-7d Half-Life 6 ug/d 100 ug/d Secreted by thyroid 1 10-20 Protein Bound 10 1 Potency T3 T4
  • Levothyroxine (T4)
    • Synthroid (Abbott), Eltroxin (GSK)
    • Synthetically made
    • 50 ug white pill  no dye (hypoallergenic)
    • Most commonly prescribed treatment for hypothyroidism
    • No T3 (but 85% of T3 comes from T4 conversion)
    • All patients made euthyroid biochemically
    • Most (but not all) patients feel normal
  • Levothyroxine (T4)
    • Average dose 1.6 ug/kg
    • Age > 50-60 or cardiac disease: must start at a low dose (25 ug/d)
    • Recheck thyroid hormone levels every 4-6 weeks after a dose change
    • Aim for a normal TSH level
  • Levothyroxine (T4)
    • Medical situations where T4 medication may be affected.
    • Estrogen: Pregnancy, OCP, HRT
        • Need to increase T4 dose!
    • Drugs that interfere with T4 absorption
        • Iron, Calcium
        • Cholestyramine (cholesterol resin Rx)
        • At least 4h between T4 and these drugs!
  • “ I still don’t feel normal on Synthroid even though my blood tests are normal.”
    • Free T4, Free T3
        • wide range of normal
    • TSH ( 0.4 –5.0 mU/L)
        • Narrow range of normal, but still a range!
        • Adjust dose for a lower TSH still in the normal range?
    • Tissue levels versus circulating levels?
        • No human studies
        • Rodents: High T4 and normal T3 tissue levels
  • Liothyronine (T3)
    • Cytomel (Theramed)
    • Shorter half-life
        • Fluctuating levels (i.e. need a slow-release pill)
        • Twice daily dosing often needed
    • 10x more potent: palpitations & other cardiac side effects
    • High T3 levels, low T4 levels (not physiologic either!)
  • T3/T4 Liotrix
    • Thyrolar
    • Combo pill of T3 and T4
    • Ratio of T4:T3 = 4:1 (not 14:1)
    • T3 still not slow release
    • Few small studies showing benefit
        • 1999 NEJM study 33 patients
        • Benefit: mood & cognitive function
    • Not available in Canada
  • Desiccated Thyroid (Armour)
    • Desiccated powder derived from thyroids of slaughtered pigs or cows
        • Vegetarian?
        • Mad Cow Disease?
    • Contains T4 and T3
    • Still no slow-release of T3
    • Ratio of T4:T3
        • Variable
        • Still not physiologic, often too high in T3 (T4:T3 = 3:1)
  • “ In an ideal world…”
    • Mixed compound with T4:T3 = 14:1
    • T3 component slow release formulation
    • Resultant:
        • Normal circulating TSH, FT4, FT3
        • Normal tissue levels of T4 and T3
    • Good, large studies (RCTs) demonstrating clear benefit over T4 alone
  • Case 2
    • When to treat “Subclinical” thyroid dysfunction?
    • Naturopathic thyroid remedies
    • Hypothryoidism Rx other than Levothyroxine
    • What is Wilson’s Thyroid Disease?
  • “Wilson’s Syndrome”
    • Wilson’s disease: copper toxicity  liver failure
    • “ Wilson’s Syndrome”
        • Dr. E. D. Wilson “discovered” this condition and named it after himself in late 1980’s
        • Decreased body temperature (low normal range)
        • Hypothyroid symptoms (nonspecific)
        • Normal thyroid function tests
        • “ Impaired T4  T3 conversion”
        • “ Build up of reverse T3”
        • Treat with “Wilson’s T3-therapy” (presumably T3)
  • Sick Euthyroid Syndrome, not Wilson’s syndrome!
  • “Wilson’s Syndrome”
    • No scientific evidence that this condition exists
    • No randomized trials proving safety or any benefit of giving people T3 when their thyroid hormone levels are normal
    • This condition not endorsed by:
        • Canadain Society of Endocrinology and Metabolism (CSEM)
        • American Thyroid Association (ATA)
        • Endocrine Society
  • Case 3
    • 62 y male
    • Afib: amiodarone, warfarin x 11 months
    • 2 months: fatigue, muscle weakness, increasing dyspnea/edema, weight gain
    • O/E: HR 110 irreg-irreg, appears malnourished,  JVP, SOA, lung crackles
  • Case 3
    • TSH < 0.05 mU/L, FT4 60 pM, FT3 24 pM
    • INR 4.2, Echo: LVH, normal LV syst fn.
    • RAIU 2%, Thyroid scan: no gland seen
    • Rx: Methimazole 40 mg/d, lasix, aldactone, ramipril, reduced warfarin
    • Cardiolgist: d/c amiodarone  bisoprolol
  • Case 3
    • F/up @ 2 mos:
    • weight loss (more muscle, less fluid)
    • Resolved: Fatigue, SOB, SOA
    • HR 76 irreg-irreg
    • TSH < 0.05, FT4 8 pM, FT3 2.1 pM
    • INR 1.5
  • Case 3
    • What is difference between thyrotoxicosis and hyperthyroidism?
    • What is “apathetic” hyperthyroidism?
    • Amiodarone induced thyrotoxicosis?
    • Thyroid & drug-interactions (warfarin)?
    • Subclinical Thyrotoxicosis?
  • RAIU
    • Oral dose of I 131 5 uCi (or I 123 200 uCi but more $)
    • Measure neck counts @ 24h (+/- 4h if suspect high turnover)
    • RAIU = neck counts – bkgd (thigh counts) x 100
    • pill counts - bkgd
  • RAIU
    • Normal 4h RAIU = 5-15 %
    • 24h RAIU :
        • >25% Hyperthyroid
        • 20-25% Equivocal (check TSH)
        • 9-20% Normal
        • 5-9% Equivocal (check TSH)
        • <5% Hypothyroid
    • Dependent on dietary iodine intake!
    • Must be: not pregnant! ( ß-hCG), no ATD x 7d, no LT4 x 4d, no large doses of iodine or radiocontrast for 2 wk (prefer 4-6 wk)
  •  
  • Thyrotoxicosis Treatment
    • Beta-blockers (hyperadrenergic symptoms)
    • Hyperthyroidism:
        • Anti-thyroid Drugs
          • Propylthiouracil (PTU), Methimazole
        • Radioiodine Ablation
        • Surgical Thyroidectomy
    • Thyroiditis:
        • ASA, NSAIDS, +/- corticosteroids
    • Iodine (high doses  Wolff Chaikoff effect)
  • “ Apathetic Hyperthyroidism”
    • Elderly population
    • Lack of tremor, diaphoresis, heat-intolerance, hyperdefecation and other classic symptoms from sympathetic over-activity
    • TMNG more likely than in young (but Grave’s still most common)
    • Less likely to have a goitre
    • Common symptoms:
        • Weight loss, anorexia
        • Constipation despite thyrotoxic
        • Tachycardia, Afib, CHF, angina
        • Cognitive Dysfunction
  • Amiodarone and Thyroid
    • PHYSIOLOGIC EFFECTS
    • 1) Increase iodine pool in body and therefore decrease RAIU.
    • 2) Decrease peripheral deiodination of T4 to T3.
    • 3) Decrease pituitary deiodination and therefore transient rise in TSH for 1st 3 mos of Rx.
    • Amiodarone Induced Thyroid Dysfunction:
    • 3 months to 4 years after starting amiodarone
    • Hypothyroidism 8% (subclinical hypothyroidism 20%)
    • Thyrotoxicosis 3% (10% iodine deficiency areas)
  • Amiodarone induced Hypothyroidism
    • 1) Increased TSH (not useful 1st 3 mos).
    • 2) Decreased FT4
    • 3) Decreased FT3 (not neccesary to measure)
    • 4) More common in areas of hi iodine intake (North America) d/t Wolff Chaikoff effect.
    • 5) Rx:
        • Stop amiodarone if possible.
        • LT4 aim dose to keep FT4 level at high normal to slightly above normal.
        • Unlike other types of hypothyroidism do NOT try to normalize TSH as this requires dose ~ 250 ug/d and clearly causes hyperthyroidism.
  • Amiodarone induced Thyrotoxicosis (AIT)
    • 1) Decreased TSH
    • 2) Increased FT4
    • 3) Increased FT3 in some patients (inhibition of deiodinase)
    • 4) More common in areas of low iodine intake (Europe) d/t Jodbasedow effect or iodine/amiodarone induced thyroid damage.
    • 5) Two types of AIT:
        • Hyperthyroidism (RAIU low but measurable) – Jodbasedow, often goitre/nodule(s)
        • Thyroiditis (RAIU 0%)
    • 6) May present without hyperthyroid symptoms and simply worsening of cardiac disorder (arrythmia, angina, CHF, etc).
  • Amiodarone induced Thyrotoxicosis (AIT)
    • Rx:
    • Stopping amiodarone may not help as amiodarone still present in body tissue stores for months
    • May need amiodarone to still treat arrythmias made worse by thyrotoxicosis
    • Radioactive I-131 useless d/t decreased RAIU.
    • Thionamide ATDs (PTU, methimazole): Rx of choice
    • Glucocorticoids if RAIU indicates thyroiditis & no response to ATD
        • Prednisone 40 mg/d
    • Surgery? Somewhat risky d/t unknown safety wrt thyroid storm & underlying heart condition that required amiodarone in the first place!
    • KClO4 (potassium perchlorate)?
  •  
  • Thyroid & Drug Interactions
    • 1) Warfarin
    • T4 increases catabolism of vitamin K dependent clotting factors.
    • Increase LT4/hyperthyroidism will increase sensitivity to warfarin (decrease dose).
    • Decrease LT4/hypothyroidism will decrease sensitivity to warfarin (increase dose).
    • 2) Cholestyramine
    • Binds T4 & T3
    • 4-5h between resin & LT4 or T3.
    • 3) Iron or Calcium
    • Also binds T4 & T3
  • Thyroid & Drug Interactions
    • 4) Estrogens
    • Increase TBG, decrease FT4 level
    • Need to increase LT4 in some patients
    • 5) Androgens/corticosteroids
    • Decrease TBG, increase FT4 level
    • Need to decrease LT4 in some patients
    • 5) Diabetes
    • Increase LT4/hyperthyroidism will increase insulin/OHA requirements.
    • Decrease LT4/hypothyroidism will decrease insulin/OHA requirements.
  • Subclinical Hyperthyroidism
    •  TSH, Normal FT4 and FT3
    • Progression to overt hyperthyroidism low:
        • Men 0% per year
        • Women 1.5% per year
        • TMNG or toxic adenoma present 5% per year
    • Indications to Rx:
        • Any cardiac disease (CAD, AFIB, etc.)
        • Age > 60 (10 year risk AFIB 32%, 10% if normal TSH)
        • TMNG or toxic adenoma
        • Osteoporosis
  • Case 4
    • 29 year old female, engaged to be married
    • T1DM
    • Thyroid U/S:
        • 2.9 cm R lower pole
        • 2.0 cm L lower pole,
        • Many others ranging from 0.5-1.5 cm
    • TSH < 0.05 mU/L, FT4 19 pM, FT3 6.9 pM
    • RAIU/Scan: 45% RAIU, hot nodule on Left
  • Case 4
    • FNA of 3cm nodule on Right: benign
    • Rx’s offered:
        • RAI ablation versus thyroidectomy
    • Patient chose Thyroidectomy
  • Thyroid Structure
    • Physical Exam
    • Thyroid Ultrasound
    • Thyroid Scan
  • Thyroid nodules
    • U/S more sensitive than P.E., particularly for nodules that are < 1 cm or located posteriorly in the gland.
    • U/S also more SEN than thyroid scan
    • U/S too Sensitive?
        • Thyroid Incidentaloma (Carotid duplex, etc.)
  • Thyroid U/S Microcalcification Egg shell calcification Intranodular vascular spots (color doppler) N/A Hypoechoic (more vascular) Hyperechoic Irregular border No Halo Regular border Halo (sonolucent rim) Malignant Characteristics Benign Characteristics
  • Thyroid Scan Thyroid nodule: risk of malignancy 6.5% Cold nodule 16-20% malignant “Warm” Nodule (indeterminant) 5% malignant Hot Nodule Tc-99m < 5% malignant I 123 < 1% malignant only 5-10% of nodules
  • Fine Needle Aspiration (FNA)
    • 25G Needle, 10cc syringe
    • Done in Office
    • +/- Local
    • 3-5 passes
    • SEN 95-99% (False Negative rate 1-5%)
    • SPEC > 95%
  • FNA Results
    • Nondiagnostic: repeat FNA
    • Benign: macrofollicular or &quot;colloid&quot; adenomas, chronic autoimmune (Hashimoto's) thyroiditis
    • Suspicious or Indeterminant: microfollicular or cellular adenomas (follicular neoplasm)
    • Malignant
  • Benign Lesions
  • Papillary Carcinoma FNA Surgical Specimen
  • Follicular Lesions on FNA: Can’t Distinguish!
  • Thyroid Nodule Palpable >15mm TSH Low Normal or High Scan Hot Not Hot FNA Malignant Suspicious (Follicular) Benign Insufficient Sample Repeat FNA +/- U/S guide Clin suspicion Low Clin suspicion High Total Thyroidectomy RAI Hemithyroidectomy with quick section + - Close
    • Rx Plummer’s
    • Surgery
    • RAI
    Follow U/S q1y
  • Thyroid Nodule Palpable >15mm Incidentaloma (Size < 15mm) Hx of XRT exposure? FHx of thyroid cancer? Malign features on U/S? Age < 20 or > 60? Grave’s Disease? Familial Adenomatosis Polyposis No Follow U/S q1y ? Yes TSH Low Normal or High Scan Hot Not Hot FNA Malignant Suspicious (Follicular) Benign Insufficient Sample Repeat FNA +/- U/S guide Clin suspicion Low Clin suspicion High Total Thyroidectomy RAI Hemithyroidectomy with quick section + - Close
    • Rx Plummer’s
    • Surgery
    • RAI
    Follow U/S q1y
  • Case 5
    • 19 year old female
    • PMHx: Eating Disorder, Bulimia
    • Weight loss despite witnessed food intake
    • Tachycardia, palpitations
    • FHx: Hypothyroidism (mother)
    • No palpable goitre
    • TSH < 0.05 mU/L, FT4 23 pM, FT3 5.0 pM
    • 24h RAIU 2%, Thyroid Scan: no gland seen
  • Case 5
    • TSH-R antibody negative
    • Thyroglobulin < 2 ng/mL (undetectable)
  • Autoimmune Thyroid Disease TSH-R ab stim Graves’ Dx (hyperthyroid) TSH-R ab block Thyroglobulin ab Microsomal ab Hashimoto’s (hypothyroid)
  • Thyroid Antibodies
    • Hashimoto’s
        • Thyroglobulin AB (<40 KIU/L)
        • Thyroid peroxidase AB (< 35 KIU/L)
    • Grave’s
        • TSI or TSH Receptor Ab (Stim): IgG antibody
        • SEN 60% SPEC 90%
        • 2-3 month turn-around time
        • Indications:
            • Pregnant & present or past hx Grave’s: check 2 nd trimester
            • (if hi-titre > 5X normal needs PTU as TSI crosses placenta)
            • ? Euthyroid Grave’s ophthalmopathy
            • Alternating hyper/hypo function due to alternating Stim/Block TSI
  • Thyroglobulin (Tg)
    • Normal < 40 ng/mL
    • Increased in all thyroid disease
    • Thyrotoxicosis factitia : low or undetectable Tg
    • Useful for thyroid cancer surveillance post surgery & radioiodine ablation
    • Not useful for thyroid cancer diagnosis
    • Thyroglobulin antibodies in Hashimoto’s patients may falsely elevate or decrease thyroglobulin levels