Download Management of Hyperthyroidism

MANAGEMENT OF
THYROTOXICOSIS
Michael D. Puricelli, MD
Jeffrey B. Jorgensen, MD
Overview
• Case
• Thyroid physiology
• Etiology and pathophysiology of Thyrotoxicosis
• Work-up of Thyrotoxicosis
• Complications of Thyrotoxicosis
• Management of Thyrotoxicosis
Case
• 31 y/o female patient is referred for “hyperthyroidism”
• What are key historical and examination findings?
History and Physical Exam
• Comprehensive history:
• Diagnostic clues: duration of symptoms, the degree and pattern of
thyroid enlargement, autoimmune disease, ocular symptoms, other
malignancies
• Factors that impact treatment:prior neck surgery, therapeutic
irradiation with I 131, External beam radiation,
• Comprehensive physical examination
• Measurement of pulse rate, blood pressure, respiratory rate, and
body weight
• Thyroid size; presence or absence of thyroid tenderness,
symmetry, and nodularity
• Pulmonary, cardiac, and neuromuscular function
• Presence or absence of peripheral edema, ocular signs, or pretibial
myxedema should be assessed.
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa
JA, Stan MN; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of
thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid.
2011 Jun;21(6):593-646. doi: 10.1089/thy.2010.0417. Epub 2011 Apr 21. Erratum in: Thyroid. 2011 Oct;21(10):1169. Thyroid. 2012
Case
• 6 months,
progressively
worsening
• Rapid heart
•
•
•
•
•
beat/Palpitations
Irritability, anxiety, fatigue
Increased bowel
movements
Weight loss
Heat intolerance
No ocular changes
• Physical Exam:
• Tachycardia
• Moist, warm skin
• Fine tremor
• Enlarged thyroid, nontender and no nodules
palpated
• Normal vision, no
exophthalmos
Case
• Referring doctor obtained a TSH which was undetectable
and Free T4 which is 3x normal.
• What further diagnostic testing is appropriate?
I-123 Uptake Scan
Reference Normal
Patient’s study
Diagnosis?
http://emedicine.medscape.com/article/121865-workup
Case
• Graves’ Disease
• What are treatment options?
• Which option is best for her?
• I-131
• Antithyroid drugs
• Surgery
• If she chooses surgery, how should she be prepared prior to the
procedure?
Overview
• Case
• Thyroid physiology
• Etiology and pathophysiology of Thyrotoxicosis
• Work-up of Thyrotoxicosis
• Complications of Thyrotoxicosis
• Management of Thyrotoxicosis
Thyroid Physiology
• Two hormones are produced by the thyroid gland:
• 3,5,3′-triiodothyronine (T3) .
• 3,5,3′,5′-tetraiodothyronine or thyroxine (T4).
• Created via iodination of tyrosine within tissue specific
thyroglobulin.
• Active hormone and precursors are stored within the
follicular lumen.
Pellitteri, PK. Ing, S. Jameson, B. Chapter 123 Disorders of the Thyroid Gland.
Cummings Otolaryngology Head & Neck Surgery. 5th Ed.
http://www.chiro.org/nutrition/FULL/Peripheral_Metabolism_of_Thyroid.html
Thyroid Physiology
Pellitteri, PK. Ing, S. Jameson, B. Chapter 123 Disorders of the Thyroid Gland.
Cummings Otolaryngology Head & Neck Surgery. 5th Ed.
Thyroid Physiology
• 100 micrograms of exogenous iodine is required daily to
ensure adequate thyroid hormone production.
• Thyroid gland concentrates iodine for use via
sodium/iodide symporter in the basal membrane.
• A sodium potassium antiporter maintains low intracellular sodium
concentration.
• Iodine travels to the apical membrane.
• Pendrin is a protein which aids in release of iodine into
the follicular lumen
• Hypothyroidism, goiter, hearing loss
Pellitteri, PK. Ing, S. Jameson, B. Chapter 123 Disorders of the Thyroid Gland.
Cummings Otolaryngology Head & Neck Surgery. 5th Ed.
Thyroid Physiology
• Hormone synthesis occurs at the apical surface
(thyroperoxidase).
• Iodine is oxidized and transferred to thyrosyl residues on
thyroglobulin
• Making monoiodotyrosine (MIT) and di-iodotyrosine (DIT).
• Iodotyrosine molecules are coupled
• MIT + DIT = T3
• DIT + DIT = T4
Pellitteri, PK. Ing, S. Jameson, B. Chapter 123 Disorders of the Thyroid Gland.
Cummings Otolaryngology Head & Neck Surgery. 5th Ed.
Thyroid Physiology
• Micropinocytosis is used to retrieve thyroglobulin into
small vesicles
• In lysosomes, the hormones and iodotyrosine precursors
are cleaved from the polypeptide backbone
• MIT and DIT are deiodinated and the iodine returns to the free
iodine pool.
• Some T4 is deiodinated to T3 prior to release.
• T4 and T3 are released from the thyroid gland.
Pellitteri, PK. Ing, S. Jameson, B. Chapter 123 Disorders of the Thyroid Gland.
Cummings Otolaryngology Head & Neck Surgery. 5th Ed.
Thyroid Physiology
Pellitteri, PK. Ing, S. Jameson, B. Chapter 123 Disorders of the Thyroid Gland.
Cummings Otolaryngology Head & Neck Surgery. 5th Ed.
Thyroid Physiology
• In the plasma <1% of thyroid hormones are free iodo-
amino acids
• The remainder are bound to proteins: thyroxine binding
globulin (70%), transthyretin (10%), albumin (10-20%).
• Thyroxine binding globulin has a lower affinity for T3 than
T4 so there is a higher percentage of T3 is free (0.3%
versus 0.2%).
Pellitteri, PK. Ing, S. Jameson, B. Chapter 123 Disorders of the Thyroid Gland.
Cummings Otolaryngology Head & Neck Surgery. 5th Ed.
Thyroid Physiology
• T4 must be deiodinated to T3 to exert much of its
biological activity.
• Three iodothyronine deiodinase enzymes
• Type I deiodinase: Liver, kidney and thyroid – activated by TSH.
Produces most circulating T3
• Inhibited by propylthiouracil
• Type II deiodinase: CNS, pituitary, placenta, skin, thyroid.
Produces T3 for local activity
• Negatively regulated by thyroid hormone
• Unaffected by PTU
• Type III deiodinase: inactivates T4 and T3 by forming reverse T3.
Present in brain, skin, placenta, fetal tissues
Pellitteri, PK. Ing, S. Jameson, B. Chapter 123 Disorders of the Thyroid Gland.
Cummings Otolaryngology Head & Neck Surgery. 5th Ed.
Kumar: Robbins and Cotran Pathologic Basis of Disease, Professional Edition, 8th ed.
Thyroid Physiology
• TSH stimulates G protein receptor
• Efflux of iodide into the follicle and uptake of colloid into the
thyrocyte as well as release of T4, T3.
• Increases synthetic enzyme expression
• Increased T3 production relative to T4.
• Increasing doses of iodine
• Increases hormone synthesis initially, but then reverses as
intrathyroid levels of iodide reach a critical level, and further
organification is inhibited.
• With prolonged TSH-stimulation cell proliferation
eventually leads to goiter
Pellitteri, PK. Ing, S. Jameson, B. Chapter 123 Disorders of the Thyroid Gland.
Cummings Otolaryngology Head & Neck Surgery. 5th Ed.
Overview
• Case
• Thyroid physiology
• Etiology and pathophysiology of Thyrotoxicosis
• Work-up of Thyrotoxicosis
• Complications of Thyrotoxicosis
• Management of Thyrotoxicosis
Definitions
• Thyrotoxicosis
• Clinical state from excessive thyroid hormone action in tissues
• Hyperthyroidism
• Type of thyrotoxicosis due to inappropriately high synthesis and
secretion of thyroid hormone from the thyroid gland.
Thyrotoxicosis
• Prevalence estimated 2% in the US based upon cross-
sectional study.
• More common in older individuals and women (10:1)
• Hyperthyroidism
• Overt:
• High T4 and T3 with low TSH
• Subclinical:
• Normal T4 and T3 with low TSH
Pellitteri, PK. Ing, S. Jameson, B. Chapter 123 Disorders of the Thyroid Gland. Cummings Otolaryngology Head & Neck Surgery. 5 th
Ed.
Canaris GJ, et al: The Colorado thyroid disease prevalence study. Arch Intern Med 2000; 160:526.
Helfand M, Redfern CC. Clinical guideline, part 2. Screening for thyroid disease: an update. American College of Physicians. Ann
Etiology of Thyrotoxicosis
• Inappropriate thyroid stimulation by trophic factors
• Constitutive activation of thyroid hormone synthesis and
secretion
• Stores of preformed hormone are passively released in
excessive amounts
• Exposure to extra-thyroidal sources of thyroid hormone
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa
JA, Stan MN; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of
thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid.
2011 Jun;21(6):593-646. doi: 10.1089/thy.2010.0417. Epub 2011 Apr 21. Erratum in: Thyroid. 2011 Oct;21(10):1169. Thyroid. 2012
Etiology of Thyrotoxicosis
• Inappropriate thyroid stimulation by trophic factors (60-
85%)
• Graves Disease
• Thyrotropin receptor antibodies stimulate the TSH receptor causing
increased hormone production
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa
JA, Stan MN; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of
thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid.
2011 Jun;21(6):593-646. doi: 10.1089/thy.2010.0417. Epub 2011 Apr 21. Erratum in: Thyroid. 2011 Oct;21(10):1169. Thyroid. 2012
Etiology of Thyrotoxicosis
• Constitutive activation of thyroid hormone synthesis and
secretion leading to autonomous release of excess
thyroid hormone
• Activating mutations in genes regulating thyroid hormone synthesis
• Activating mutations of the TSH receptor
• Toxic multinodular goiter in 10-30% of patients
• Toxic Adenomas in 2-20% of patients
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa
JA, Stan MN; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of
thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid.
2011 Jun;21(6):593-646. doi: 10.1089/thy.2010.0417. Epub 2011 Apr 21. Erratum in: Thyroid. 2011 Oct;21(10):1169. Thyroid. 2012
Etiology of Thyrotoxicosis
• Stores of preformed hormone are passively released in
excessive amounts
• Inflammation of thyroid tissue due to autoimmune, infectious,
chemical, or mechanical insult
• Painless thyroiditis is the etiology of about 10% of hyperthyroidism in
the post-partum period (post partum thyroiditis)
• Subacute thyroiditis is thought to arise from viral infection
• Drugs: Lithium, interferon-alpha, amiodarone
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa
JA, Stan MN; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of
thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid.
2011 Jun;21(6):593-646. doi: 10.1089/thy.2010.0417. Epub 2011 Apr 21. Erratum in: Thyroid. 2011 Oct;21(10):1169. Thyroid. 2012
Etiology of Thyrotoxicosis
• Exposure to extra-thyroidal sources of thyroid hormone
• Endogenous
• Struma ovarii
• Metastatic differentiated thyroid cancer
• Exogenous
• Factitious thyrotoxicosis
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa
JA, Stan MN; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of
thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid.
2011 Jun;21(6):593-646. doi: 10.1089/thy.2010.0417. Epub 2011 Apr 21. Erratum in: Thyroid. 2011 Oct;21(10):1169. Thyroid. 2012
Franklyn JA, Boelaert K. Thyrotoxicosis.
Lancet. 2012 Mar 24;379(9821):1155-66.
doi: 10.1016/S0140-6736(11)60782-4. Epub
2012 Mar 5. Review. PubMed PMID:
Overview
• Case
• Thyroid physiology
• Etiology and pathophysiology of Thyrotoxicosis
• Work-up of Thyrotoxicosis
• Complications of Thyrotoxicosis
• Management of Thyrotoxicosis
Work-up of Clinically or Incidentally
Discovered Thyrotoxicosis
• TSH concentrations
• Circulating thyroid hormone levels
• Thyroidal I-123 uptake scan
Pellitteri, PK. Ing, S. Jameson, B. Chapter 123 Disorders of the Thyroid Gland.
Cummings Otolaryngology Head & Neck Surgery. 5th Ed.
Biochemical Evaluation
•
•
There is an inverse log-linear
relationship between free T4
and TSH such that small
changes in free T4 result in
large changes in TSH.
Third generation assays
represent the most sensitive
test for TSH offering ability to
detect differences of 0.01
mU/L.
de los Santos ET, Starich GH, Mazzaferri EL. Sensitivity, specificity, and cost-effectiveness of the sensitive thyrotropin assay in the
diagnosis of thyroid disease in ambulatory patients. Arch Intern Med. 1989 Mar;149(3):526-32. PubMed PMID: 2493228.
Biochemical Evaluation
• If hyperthyroidism is strongly suspected, diagnostic
accuracy improves if serum TSH and T4 are measured at
the same time.
• In early stages of hyperthyroidism (usually from
adenomas), T3 may be elevated and free T4 normal.
• Called “T3 toxicosis”
• Free T3 measures are less well validated than free T4 so total T3 is
usually preferred
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa
JA, Stan MN; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of
thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid.
2011 Jun;21(6):593-646. doi: 10.1089/thy.2010.0417. Epub 2011 Apr 21. Erratum in: Thyroid. 2011 Oct;21(10):1169. Thyroid. 2012
Franklyn JA, Boelaert K. Thyrotoxicosis.
Lancet. 2012 Mar 24;379(9821):1155-66.
doi: 10.1016/S0140-6736(11)60782-4. Epub
2012 Mar 5. Review. PubMed PMID:
Radioactive Iodine Uptake Test
• Indicated when the clinical presentation of thyrotoxicosis is not
•
•
•
•
diagnostic of Graves’ disease (symmetric enlarged thyroid,
recent onset of ophthalmopathy, and moderate to severe
hyperthyroidism).
Performed by administering an isotope of iodine (usually I-123)
orally and measuring the percentage of the I-123 trapped by
the thyroid gland.
The test is usually performed 24 hours after administration of
the isotope, although this may be done earlier.
The principal usefulness of this test is in differentiating
hyperthyroidism into high-uptake (focal vs diffuse) or low
uptake states with uncertain diagnosis.
Not to be done in pregnancy.
Pellitteri, PK. Ing, S. Jameson, B. Chapter 123 Disorders of the Thyroid Gland. Cummings Otolaryngology Head & Neck Surgery. 5th Ed.
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa
JA, Stan MN; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of
thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid.
2011 Jun;21(6):593-646. doi: 10.1089/thy.2010.0417. Epub 2011 Apr 21. Erratum in: Thyroid. 2011 Oct;21(10):1169. Thyroid. 2012
Radioactive Iodine Uptake Test
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa
JA, Stan MN; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of
thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid.
2011 Jun;21(6):593-646. doi: 10.1089/thy.2010.0417. Epub 2011 Apr 21. Erratum in: Thyroid. 2011 Oct;21(10):1169. Thyroid. 2012
Pattern of Uptake is Diagnostically Useful
(A) Normal
thyroid
• http://emedicine.medscape.com/article/2094805-overview
Pattern of Uptake is Diagnostically Useful
(A) Normal
thyroid
(B) Graves
disease
(C) Plummer
disease
(toxic
multinodular
goiter)
(D) Toxic
adenoma
(E) Thyroiditis
• http://emedicine.medscape.com/article/2094805-overview
Additional Diagnostic Testing
• Indicated when radioactive iodine uptake test is
contraindicated or not useful (pregnancy, recent iodine
exposure etc.)
• Measurement of thyrotropin receptor antibodies (TRAb)
• TRAb: Sensitive (99%) and specific (95%) for Graves’ Disease
• Ratio of total T3 to total T4
• Elevated >20 (T3/T4) in Graves’ Disease and Toxic nodular goiter,
while <20 in painless or postpartum thyroiditis
• Factitious thyroiditis
• Associated with low thyroglobulin level
• Ultrasonography
• Flow may differentiate between Graves’ Disease and Destructive
thyroiditis
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa
JA, Stan MN; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of
thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid.
2011 Jun;21(6):593-646. doi: 10.1089/thy.2010.0417. Epub 2011 Apr 21. Erratum in: Thyroid. 2011 Oct;21(10):1169. Thyroid. 2012
Thyroid Scan
• A thyroid scan should be done in patients with
thyrotoxicosis and thyroid nodularity.
• Thyroid cancer in Graves’ Disease has a frequency of 2% or less.
• When a palpable, a hypofunctional thyroid nodule is found in a
patient with Graves’ disease, it has about 45% probability of being
a malignancy.
Pellitteri, PK. Ing, S. Jameson, B. Chapter 123 Disorders of the Thyroid Gland. Cummings Otolaryngology Head & Neck Surgery. 5th Ed.
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa
JA, Stan MN; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of
thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid.
2011 Jun;21(6):593-646. doi: 10.1089/thy.2010.0417. Epub 2011 Apr 21. Erratum in: Thyroid. 2011 Oct;21(10):1169. Thyroid. 2012
Overview
• Case
• Thyroid physiology
• Etiology and pathophysiology of Thyrotoxicosis
• Work-up of Thyrotoxicosis
• Complications of Thyrotoxicosis
• Management of Thyrotoxicosis
Complications of Thyrotoxicosis
• Interestingly, there is only moderate correlation between
elevation in thyroid hormone concentration and clinical
signs/symptoms.
• In 25 patients with Graves’ Disease, Hyperthyroid
Symptom Scale scores:
• Correlate inversely with age and thyroid size
• Scores did not correlate with free T4 or T3
Trzepacz PT, Klein I, Roberts M, Greenhouse J, Levey GS. Graves' disease: an analysis of thyroid hormone levels and hyperthyroid signs and
symptoms. Am J Med. 1989 Nov;87(5):558-61. PubMed PMID: 2816972.
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa
JA, Stan MN; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of
thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid.
2011 Jun;21(6):593-646. doi: 10.1089/thy.2010.0417. Epub 2011 Apr 21. Erratum in: Thyroid. 2011 Oct;21(10):1169. Thyroid. 2012
Complications of Thyrotoxicosis
• Weight loss
• Osteoporosis
• There are also increased fracture rates in post menopausal women
with subclinical hypothyroidism
• Bone mineral density is improved after treatment with antithyroid drugs or
radioactive iodine.
• Atrial fibrillation
• Among those with subclinical hypothyroidism, 2.8 fold higher risk of
atrial fibrillation among those >60 years
• Improvement is noted with restoration of euthyroid state or beta blockers.
• Embolic events
• Cardiovascular collapse
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa
JA, Stan MN; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of
thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid.
2011 Jun;21(6):593-646. doi: 10.1089/thy.2010.0417. Epub 2011 Apr 21. Erratum in: Thyroid. 2011 Oct;21(10):1169. Thyroid. 2012
Overview
• Case
• Thyroid physiology
• Etiology and pathophysiology of Thyrotoxicosis
• Work-up of Thyrotoxicosis
• Complications of Thyrotoxicosis
• Management of Thyrotoxicosis
Management of Thyrotoxicosis
• Symptomatic control
• Disease Specific Management
• Graves’ Disease
• Toxic Multinodular Goiter
• Toxic Adenoma
• Special Considerations
Symptomatic Control
• Beta blockers are useful in almost all forms of thyrotoxicosis,
while antithyroid drugs are useful only in some.
• Decrease in heart rate, systolic blood pressure, muscle weakness, and
tremor.
• It improves irritability, emotional variability, and exercise intolerance
• Beta-adrenergic blockade should be given to thyrotoxic
patients with resting heart rates >90 beats per minute or
cardiovascular disease
• Beta-adrenergic blockade should be given to children with
symptoms of hyperthyroidism or HR >100 bpm
• Beta-adrenergic blockade should be considered in all patients
with symptomatic thyrotoxicosis
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa
JA, Stan MN; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of
thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid.
2011 Jun;21(6):593-646. doi: 10.1089/thy.2010.0417. Epub 2011 Apr 21. Erratum in: Thyroid. 2011 Oct;21(10):1169. Thyroid. 2012
Management of Thyrotoxicosis
• Symptomatic control
• Disease Specific Management
• Graves’ Disease
• Toxic Multinodular Goiter
• Toxic Adenoma
• Special Considerations
Graves’ Disease
• In a randomized controlled trial, patients receiving treatment with antithyroid
medication, I-131 or surgery were compared.
•
•
•
•
•
20-34 yr: received antithyroid drugs for 18 months (medical) or subtotal thyroidectomy
35-55 yr of age, received medical, surgical, or radioiodine (iodine-131) treatment
Follow-up time was at least 48 months
All treatments normalized the mean serum hormone levels within 6 weeks
The risk of relapse was highest in the medically treated young and old adults (42% vs. 34%),
followed by that in those treated with iodine-131 (21%) and than in the surgically treated young
and old adults (3% vs 8%), respectively
Torring O, Tallstedt L, Wallin G, et al. Graves’ hyperthyroidism:
treatment with antithyroid drugs, surgery, or radioiodine—a
prospective, randomized study. Thyroid Study Group. J Clin
Endocrinol Metab 1996; 81: 2986–93.
Graves’ Disease
• Torring et al continued:
• Satisfaction (below)
• Conclusion: The increased risk of ophthalmopathy in patients with high serum T3 levels,
especially when treated with iodine-131, and the relatively high frequency of relapse after
treatment with antithyroid drugs are important factors to consider when selecting therapy for
Graves' disease.
• Patients with overt Graves’ hyperthyroidism should be treated with any of the following
modalities: I-131 therapy, antithyroid medication, or thyroidectomy
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa
JA, Stan MN; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of
thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid.
2011 Jun;21(6):593-646. doi: 10.1089/thy.2010.0417. Epub 2011 Apr 21. Erratum in: Thyroid. 2011 Oct;21(10):1169. Thyroid. 2012
Anti-thyroid Drugs for Graves’ Disease
Favorable Considerations:
• High likelihood of remission
•
•
•
•
•
(females, with mild disease, small
goiters, and negative or low-titer
TRAb)
Elderly or others with comorbidities
increasing surgical risk or with
limited life expectancy
Individuals in nursing homes or other
care facilities who may have limited
longevity and are unable to follow
radiation safety regulations
Patients with previously operated or
irradiated necks
Lack of access to a high-volume
thyroid surgeon
Moderate to severe active Graves’
Ophthalmopathy.
Contraindications:
• Previous known major
adverse reactions to
ATDs.
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa
JA, Stan MN; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of
thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid.
Anti-thyroid Drugs
• Goal in Graves’ Disease is to achieve euthyroidism while
awaiting spontaneous remission (~30% in Graves’ Disease,
higher in selected populations).
• Methimazole and propylthiouracil
• Inhibit thyroid hormone biosynthesis by inhibiting the oxidation and
organification of iodine and the coupling of iodotyrosines (thyroid
peroxidase)
• Propylthiouracil also inhibits the thyroidal and extrathyroidal
conversion of T4 to T3
• Neither drug has an effect on the release of thyroid hormones
stored in the thyroid gland.
• Most patients have normalized T4 in 8-12 weeks.
• Methimazole and PTU have immunosuppressive actions that
may contribute to the occurrence of remissions of Graves’
disease.
Pellitteri, PK. Ing, S. Jameson, B. Chapter 123 Disorders of the Thyroid Gland. Cummings Otolaryngology Head & Neck Surgery. 5 th
Ed.
Anti-thyroid Drugs
• Methimazole should be used in virtually all patients choosing
antithyroid drug therapy except during the first trimester of
pregnancy, treatment of thyroid storm, and in patients with
minor reactions to methimazole who refuse I-131 and surgery.
• Methimazole is dosed once daily, while propylthiouracil requires
multiple daily administrations
• Methimazole compliance 83%.
• Propylthiouracil compliance 53%.
• Methimazole use in the first trimester is associated with
choanal and esophageal atresia
• A “block and replace” therapeutic strategy has been executed
in some cases, however, this is not recommended due to
increased adverse effects
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa
JA, Stan MN; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of
thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid.
2011 Jun;21(6):593-646. doi: 10.1089/thy.2010.0417. Epub 2011 Apr 21. Erratum in: Thyroid. 2011 Oct;21(10):1169. Thyroid. 2012
Adverse Effects of Antithyroid Drugs
• A CBC with differential should be obtained during febrile illness and
at the onset of pharyngitis in all patients taking antithyroid
medications.
• Liver function and hepatocellular integrity studies (CMP) should be
checked with evidence of hepatic dysfunction.
Duration of Anti-thyroid Drug Therapy
• If methimazole is chosen as primary therapy for Graves’
Disease, it should be continued for 12-18 months and
then tapered/stopped if the TSH is normal
• Thyrogen receptor antibodies should be measured prior to
cessation, as normal levels predict greater chance for
remission.
• Mild disease, small goiters and negative TRAb have remission rate
>50%
• If remission is not achieved in patients with Graves’
Disease by 12-18 months, consideration should be given
to alternative treatments, though methimazole may be
continued if patients prefer this approach.
• Remission rate does not improve with treatment longer than 18 mo
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa
JA, Stan MN; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of
thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid.
2011 Jun;21(6):593-646. doi: 10.1089/thy.2010.0417. Epub 2011 Apr 21. Erratum in: Thyroid. 2011 Oct;21(10):1169. Thyroid. 2012
I-131 For Graves’ Disease
Favorable Considerations:
• Females planning a pregnancy
•
•
•
•
in the future (more than 4–6
months following radioiodine
therapy, provided thyroid
hormone levels are normal).
Individuals with comorbidities
increasing surgical risk.
Previously operated or
externally irradiated necks.
Lack of access to a highvolume thyroid surgeon.
Contraindications to antithyroid drug use.
Contraindications:
• Pregnancy, lactation,
females planning a
pregnancy within 4–6
months.
• Coexisting thyroid cancer,
or suspicion of thyroid
cancer.
• Individuals unable to
comply with radiation
safety guidelines
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa
JA, Stan MN; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of
thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid.
I-131 Administration
• Sufficient radiation should be administered in a single
dose to make the patient hypothyroid
• 10 mCi leads to hypothyroidism in 69% at 1 year
• 15 mCi leads to hypothyroidism in 75% at 6 mo.
• Hypothyroidism may occur as soon as within 4 weeks, but
most commonly between 2-6 months post treatment
• If hyperthyroidism persists >6 mo or response if minimal after 3 mo,
retreatment with I-131 is recommended.
• Surgery should be considered in patients with refractory
hyperthyroidism to several treatments.
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa
JA, Stan MN; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of
thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid.
2011 Jun;21(6):593-646. doi: 10.1089/thy.2010.0417. Epub 2011 Apr 21. Erratum in: Thyroid. 2011 Oct;21(10):1169. Thyroid. 2012
I-131 Administration
• Once, euthyroid, there is no evidence of reduced fertility
and offspring show no increased rate of congenital
anomalies
• Women should stop breastfeeding at least 6 weeks prior
to treatment to prevent concentration in the breast tissue
• There is a long-term increase in cardiovascular and
cerebrovascular deaths after I-131 therapy
• Thought to be due to hyperthyroidism rather than treatment
• One study showed an increase in cancer deaths following
treatment, however, other studies have failed to
demonstrate this finding.
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa
JA, Stan MN; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of
thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid.
2011 Jun;21(6):593-646. doi: 10.1089/thy.2010.0417. Epub 2011 Apr 21. Erratum in: Thyroid. 2011 Oct;21(10):1169. Thyroid. 2012
Malignancy After I-131 Treatment
• The pediatric study with the longest follow-up reported 36-
year outcomes of 116 patients.
• The patients ranged in age at treatment from 3 to 19 years. No
patient developed thyroid cancer or leukemia.
• A study using phantom modeling, estimated that at 0, 1, 5,
10, and 15 years of age, and adulthood, respective total
body radiation activities are 11.1, 4.6, 2.4, 1.45, 0.90, and
0.85 rem (1 rem = 0.1 Sv)
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa
JA, Stan MN; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of
thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid.
2011 Jun;21(6):593-646. doi: 10.1089/thy.2010.0417. Epub 2011 Apr 21. Erratum in: Thyroid. 2011 Oct;21(10):1169. Thyroid. 2012
Theoretical Projections of Cancer
Incidence for I-131 Therapy
I-131 should be avoided in children <5 yr, though it is acceptable for ages 5-10 yr
if the calculated dose is <10 mCi. I-131 is acceptable for children >10 years if the
activity is >150 mCi/g thyroid tissue.
Toohey RE, Stabin MG, Watson EE. The AAPM/RSNA physics tutorial for residents: internal radiation dosimetry: principles and applications.
Radiographics. 2000 Mar-Apr;20(2):533-46; quiz 531-2. PubMed PMID: 10715348.
Mortality after I-131
• A population-based study of mortality in a cohort of 7209
subjects with hyperthyroidism who were treated with
radioactive iodine. Causes of death were compared with data
on age-specific mortality.
• During 105,028 person-years of follow-up,
• Standardized mortality ratio, 1.1; 95 percent confidence interval, 1.1 to
1.2; P<0.001).
• The risk was increased for deaths related to the following:
• Thyroid disease (standardized mortality ratio, 24.8; 95 percent confidence
interval, 20.4 to 29.9),
• Cardiovascular disease (standardized mortality ratio, 1.2; 95 percent
confidence interval, 1.2 to 1.3)
• Cerebrovascular disease (standardized mortality ratio, 1.4; 95 percent
confidence interval, 1.2 to 1.5)
• Fracture of the femur (26 excess deaths; standardized mortality ratio, 2.9;
95 percent confidence interval, 2.0 to 3.9).
Franklyn JA, Maisonneuve P, Sheppard MC, Betteridge J, Boyle P. Mortality after the treatment of hyperthyroidism
with radioactive iodine. N Engl J Med. 1998 Mar 12;338(11):712-8. PubMed PMID: 9494147.
Antithyroid Drugs vs I-131
• Prospective observational population based study of
1,086 subjective age >40 yr treated with either antithyroid
drugs of I-131
• 12 868 person-years of follow-up
• Standardized mortality ratio 1.15 for the population
• All-cause mortality was increased during thionamide treatment (SMR,
1.30 [95% CI, 1.05-1.61]) and after 131-I not associated with
hypothyroidism (SMR, 1.24 [95% CI, 1.04-1.46]; P = .01)
• After I-131 treatment requiring T4 replacement (SMR, 0.98 [95% CI,
0.82-1.18]; P = .85).
Boelaert K, Maisonneuve P, Torlinska B, Franklyn JA. Comparison of mortality in hyperthyroidism during periods of treatment with
thionamides and after radioiodine. J Clin Endocrinol Metab. 2013 May;98(5):1869-82. doi: 10.1210/jc.2012-3459. Epub 2013 Mar 29.
PubMed PMID: 23543662.
Surgery for Graves’ Disease
Favorable Considerations:
• Symptomatic compression or large
•
•
•
•
•
goiters (≥80 g)
Thyroid malignancy is documented
or suspected (e.g., suspicious or
indeterminate cytology)
Large nonfunctioning, photopenic, or
hypofunctioning nodule
Coexisting hyperparathyroidism
requiring surgery
Females planning a pregnancy in
<4–6 months (i.e., before thyroid
hormone levels would be normal if
radioactive iodine were chosen as
therapy), especially if TRAb levels
are particularly high
Patients with moderate to severe
active Graves’ Ophthalmopathy.
Contraindications:
• Substantial comorbidity such as
cardiopulmonary disease, end-stage
cancer, or other debilitating disorders
• Pregnancy is a relative contraindication
and should only be used in this
circumstance, when rapid control of
hyperthyroidism is required and
antithyroid medications cannot be used.
• Thyroidectomy is best avoided in the first
and third trimesters of pregnancy because of
teratogenic effects associated with
anesthetic agents and increased risk of fetal
loss in the first trimester and increased risk
of preterm labor in the third.
• Optimally, thyroidectomy is performed in the
latter portion of the second trimester.
Although it is the safest time, it is not without
risk (4.5%–5.5% risk of preterm labor)
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa
JA, Stan MN; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of
thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid.
Surgery
• Near total or total thyroidectomy may be performed for treatment of
Graves’ Disease.
• Near total: 8% recurrence at 5 years post-op
• Total: nearly 0% recurrence.
• Surgery should be done by a high volume thyroid surgeon.
• Thyroid procedures in Maryland between 1991 and 1996 reviewed by surgeon
volume.
• <10 Cases
• Length of stay 1.9 days
• Complications 8.6%
• 10-100 Cases length of stay
• Length of stay 1.7 days
• Complications 6.1%
• >100 Cases length of stay
• Length of stay 1.4 days
• Complications 5.1%
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa
JA, Stan MN; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of
thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid.
2011 Jun;21(6):593-646. doi: 10.1089/thy.2010.0417. Epub 2011 Apr 21. Erratum in: Thyroid. 2011 Oct;21(10):1169. Thyroid. 2012
Nov;22(11):1195. PubMed PMID: 21510801.
Sosa JA, Bowman HM, Tielsch JM, Powe NR, Gordon TA, Udelsman R. The importance of surgeon experience for clinical and economic
Graves’ Ophthalmopathy
• Present in approximately 50% of patients with Graves’ Disease,
severe in 5%
• Natural history: rapid deterioration followed by gradual improvement
• Quality of life is impaired by the condition and current
therapeutic approaches fail to significantly improve quality of
life
• Prevention is the focus of treatment
• Several retrospective cohort studies and randomized trials
have compared the risk of Graves’ Ophthalmopathy
development or progression after therapy (15% and 33%)
• One RCT found that risk to be 23/150 (15%) for radioactive iodine,
compared with 4/148 (3%) for antithyroid drugs
• Another RCT 13/39 (33%) for radioactive iodine compared with 4/38
(10%) for antithyroid drugs and 6/37 (16%) for surgery
• In contrast, one prospective but nonrandomized cohort study identified
no difference among antithyroid drugs, surgery, and radioactive iodine
treatment, with an overall 4.9%–7.1% frequency of GO development
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa
JA, Stan MN; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of
thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid.
Graves’ Ophthalmopathy
• All therapies (antithyroid drugs, I-131 and surgery) are
considered appropriate for patients with Graves’
Ophthalmopathy except in certain situations.
• Patients with Graves’ hyperthyroidism and active moderate-tosevere or sight-threatening ophthalmopathy should be treated
with either methimazole or surgery
• Comparison of two different surgical approaches (total thyroidectomy
vs. subtotal thyroidectomy) for patients with moderate-to-severe GO
showed that the eye disease improved over 3 years of follow-up in all
patients.
• In another series of 42 patients with progressive GO treated with total
thyroidectomy, exophthalmos was stable in 60% of cases and
improved in the remainder
• Limited data of other treatments in this population, however, antithyroid
drugs are also felt to be safe.
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa
JA, Stan MN; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of
thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid.
2011 Jun;21(6):593-646. doi: 10.1089/thy.2010.0417. Epub 2011 Apr 21. Erratum in: Thyroid. 2011 Oct;21(10):1169. Thyroid. 2012
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa
JA, Stan MN; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of
thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid.
2011 Jun;21(6):593-646. doi: 10.1089/thy.2010.0417. Epub 2011 Apr 21. Erratum in: Thyroid. 2011 Oct;21(10):1169. Thyroid. 2012
Surgery - Preparation
• Thyroid storm is a risk from the stress of surgery, anesthesia, or thyroid
manipulation.
• Patients undergoing surgery for Graves’ Disease, TMNG, or TA should be
rendered euthyroid with methimazole prior to surgery whenever possible.
• Typically takes 4-6 weeks
• Potassium iodide should be given in the immediate pre-operative period in
Graves’ Disease.
• Iodide administration pre-operatively decreases thyroid blood flow, vascularity, and intraoperative
blood loss during thyroidectomy.
• Mechanism: reduced thyroglobulin proteolysis and inhibited thyroidal iodine transport, oxidation,
and organification.
• When it is not possible to render a patient with Graves’ Disease euthyroid prior to
thyroidectomy, beta blockade should be initiated along with potassium iodide.
• Antithyroid drugs should be stopped at the time of thyroidectomy and betablockers weaned following surgery.
• Following thyroidectomy, levothyroxine should be started at a daily dose
appropriate for the patient’s weight (0.8 microgram/pound or 1.7 microgram/kg)
and TSH measured at 6-8 weeks post-operatively.
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa
JA, Stan MN; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of
thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid.
2011 Jun;21(6):593-646. doi: 10.1089/thy.2010.0417. Epub 2011 Apr 21. Erratum in: Thyroid. 2011 Oct;21(10):1169. Thyroid. 2012
Thyroid Storm
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa
JA, Stan MN; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of
thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid.
2011 Jun;21(6):593-646. doi: 10.1089/thy.2010.0417. Epub 2011 Apr 21. Erratum in: Thyroid. 2011 Oct;21(10):1169. Thyroid. 2012
Thyroid Storm
• Multimodality treatment
approach is indicated
•
•
•
•
•
•
•
•
Beta blockade
Antithyroid drug therapy
Inorganic iodide
Corticosteroids
Antipyretics
Cooling blankets
Volume resuscitation
Respiratory support.
Toxic Multinodular Goiter & Toxic
Adenoma
• Patients with TMNG or TA should be treated with either I-131 or
thyroidectomy. On occasion, low dose treatment with
methimazole may be appropriate.
• TMNG
• <1% risk of needing further treatment following total or near total
thyroidectomy, cessation of thyroid hormone secretion within days, need for
exogenous thyroid replacement in 100%, 100% improvement in
compressive symptoms
• I-131 therapy has a 20% retreatment rate, 50-60% response by 3 months
and 80% by 6 months, and hormone replacement in 3% at one year and
64% at 24 years, 46% improvement in compressive symptoms
• TA
• Surgical treatment failure <1%, following lobectomy 2.3% have
hypothyroidism
• I-131 there is a 6-18% risk of persistent hyperthyroidism and 5.5% risk of
recurrent hyperthyroidism, 75% response rate within 3 months, risk of
hypothyroidism increases with time (8% by 1 year and 60% by 20 years),
reduction in nodule volume noted up to 24 months after treatment
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa
JA, Stan MN; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of
Antithyroid Drugs for TMNG or TA
• No spontaneous/induced remission as in Graves’
Disease, however, this may be the best choice for some
patients.
Alternative Treatments
• Toxic adenoma: Percutaneous ethanol injection under
sonographic guidance demonstrated cure rate (absent
uptake of the nodule) in 93% and major complication rate
of 3%
• Reduced volume of nodules by 66%.
• Limited experience, “PEI or alternative treatments should be
employed only in the very rare situation when standard therapies
have failed, are contraindicated or refused”.
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa
JA, Stan MN; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of
thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid.
2011 Jun;21(6):593-646. doi: 10.1089/thy.2010.0417. Epub 2011 Apr 21. Erratum in: Thyroid. 2011 Oct;21(10):1169. Thyroid. 2012
Summary
Franklyn JA, Boelaert K. Thyrotoxicosis. Lancet. 2012 Mar 24;379(9821):1155-66. doi:
10.1016/S0140-6736(11)60782-4. Epub 2012 Mar 5. Review. PubMed PMID: 22394559.