Megan%20Chan,%20PGY-1

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Thyroid Trivia

• Megan Chan, PGY-1
• UHCMC 2015

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Diagnosis of Thyroid disease includes

• 3 Aspects
• Functional aspect
• Pathological aspect
• Anatomical aspect

Example Euthyroid Graves disease with Goiter
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Hyperthyroidism Definitions

• What is the difference between Thyrotoxicosis
  Hyperthyroidism?
• Thyrotoxicosis Elevated T4/T3 that may be due
  to a variety of reasons (e.g. synthetic
  ingestion, thyroiditis)
• Hyperthyroidism Elevated T4/T4 from the thyroid
  gland
• What are the common causes of hyperthyroidism?
• Graves disease (diffuse toxic goiter)80
• Plummers disease (multinodular toxic goiter)15
• Toxic thyroid adenoma (single nodule)2
• If transient Hashimotos thyroiditis, subacute
  thyroiditis (early stage)

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Non-Thyroid Causes of Thyrotoxicosis

• Thyroid carcinoma
• Exogenous hormone
• Hydatiform mole
• Choriocarcinoma
• Excess TRH
• TSH-oma
• Pituitary T3 resistance
• Struma ovarii
• Thyroid destruction
• Hyperemesis

• TSH-R mutation
• Familial gestational hyperthyroidism
• Amiodarone
• INF-alpha induced
• HIV treatment
• Sunitinib therapy

http//www.thyroidmanager.org/chapter/diagnosis-an
d-treatment-of-graves-disease/
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Thyroid exam in Hyperthyroidism

• Guess the diagnosis based on the following
  thyroid exam

Thyroid Exam Diagnosis
Diffusely enlarged, nontender Graves dz
Diffusely enlarged, tender Subacute thyroiditis
Bumpy, irregular, asymmetric Plummers dz
Single nodule within atrophic gland Toxic adenoma
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Hypothyroidism Definitions

• What is Primary Hypothyroidism? What are some
  examples?
• Failure of the thyroid gland, accounts for 95
  cases
• Hashimotos disease (chronic thyoriditis)most
  common
• Iatrogenic radioiodine tx, thyroidectomy, meds
  (e.g. lithium, amiodarone)
• What is Secondary Hypothyroidism? What is
  deficient?
• 2/2 pituitary disease
• Deficiency of TSH
• What is Tertiary Hypothyroidism? What is
  deficient?
• 2/2 hypothalamic disease
• Deficiency of TRH
• What are other causes of Hypothyroidism?
• Subacute hypothyroidism
• Increased TSH production maintains T4 wnl
• Subacute thyroiditis (late stage)

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Blood Work

• What is the best screening test for thyroid
  disease?
• TSH
• Always repeat TSH before starting Tx
• TSH ? in severe illness, steroids
• Why is obtaining free T4 helpful?
• T4 is helpful to see if TSH is inappropriately
  normal (e.g. pituitary cause)
• When should you obtain T3?
• Concerned for subclinical hyperthyroidism (can
  have T3 thyrotoxicosis)
• Iodine deficient diet (body makes T3 instead of
  T4)

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Conditions associated with transient ? Free T4
Condition Explanation
Estrogen withdrawal Rapid decrease in TBG level
Amphetamine abuse Possibly induced TSH secretion(2)
Acute psychosis Unknown
Hyperemesis gravidarum hCG, can cause thyrotoxicosis
Iodide administration Thyroid autonomy
Beginning of T4 administration Delayed T4 metabolism(3)
Severe illness (rarely) Decreased T4 to T3 conversion (4)
Amiodarone treatment Decreased T4 to T3 conversion, iodine load
Gallbladder contrast agents Decreased T4 to T3 conversion, iodine load
Propranolol (large doses) Inhibition of T4 to T3 conversion
Prednisone (rarely) Inhibition of T4 to T3 conversion
High altitude exposure Possibly hypothalamic activation
Selenium deficiency Decreased T4 to T3 conversion
http//www.thyroidmanager.org/chapter/diagnosis-an
d-treatment-of-graves-disease/
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Blood Work

• What Ab tests are positive in Graves disease?
• Thyroid stimulating Ab (TSI)
• 90
• TSI binds TSH receptors on surface of thyroid
  cells triggers synthesis of excess thyroid
  hormone
• TSI also binds tissues in the eye and skin ?
  exophthalmos pretibial myxedema
• Thyrotrophin receptor Ab (TRAb)
• 90, High specificity
• Anti-peroxidase/microsomal Ab (TPO)low titier
• gt95 of pts
• Anti-thyroglobulin Ab
• 50 of pts
• What Ab tests are positive in Hashimotos
  disease?
• Anti-peroxidase/microsomal Ab (TPO)high titer
• 90 of pts
• Non-specific 5-10 of healthy people test
  positive
• Anti-thyroglobulin Ab
• 50 of pts

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Blood Work

• What does Thyroglobulin do?
• Makes T4/T3
• When do you test for Thyroglobulin
  Anti-thyroglobulin binding Ab?
• Testing for lack of thyroid tissue (e.g. s/p
  resection or ablation of thyroid cancer)
• Test in patient who might be taking exogenous
  hormone, as thyroglobulin in suppressed in this
  case
• What does Thyroid Binding Globulin (TBG) do?
• Binds T4 T3 reversibly, making them inactive
• Free T4 is not influenced by TBG
• Increased in pregnancy, hepatitis, OPCs, ASA
• Decreased in glucocorticoids, nephritic syn,
  cirrhosis, androgens

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Imaging

• What is a Radionucleotide uptake scan most
  helpful for?
• Helps identify the cause of hyperthyroidism
  diffuse uptake (Graves) vs patchy (Plummers
  disease) vs hot nodule.
• No real use in euthyroid or hypothyroid patients.
• Usually need to remove hot nodules (no remission)
• When should you order an ultrasound of the
  thyroid?
• If you see a goiter
• If you feel and enlargement or thyroid nodule
• What are signs of a malignant nodule?
• Benign if nodule lt1mm
• Malignant gt2mm, irregular boarders,
  calcifications (papillary), blood supply via
  dopplers
• If multinodular, can perform radionucleotide
  uptake scan to determine which one to biopsy

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Imaging

• If a benign appearing nodule is found, what is
  your next step in management?
• Monitor with repeat US in 6 months to 1 year for
  2-3 years. If remains stable can increase the
  interval.
• If a malignant appearing nodule is found, what is
  your next step in management?
• FNA or resection
• FNA is incorrect 10 of the time (false or
  false -)

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Pocket Medicine, 4th ed.
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http//intranet.tdmu.edu.ua/data/kafedra/internal/
vnutrmed2/classes_stud/en/med/lik/ptn/Internal20m
edicine/420course/06.20Hyperthyroidism.20Pathol
ogy20of20parathyroid20glands.htm
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http//www.advancedonc.com/wp-content/themes/royal
/images/Ultrasound-Guided-FNA-2.jpg
http//endocrine.surgery.ucsf.edu/media/5095649/th
yroid_radionucleide_scan.jpg
Pocket Medicine, 4th ed.
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Hyperthyroid Treatment Pharmacologic

• What is the preferred treatment for
  Hyperthyroidism?
• Methimazole
• Inhibits thyroid hormone synthesis
• Once a day med, Agranulocytosis in 0.5
• What is the second line agent and when is it
  used?
• PTU (propylthiouracil) used if allergic to
  Methimazole or 1st trimester of pregnancy (? risk
  fetal anomalies)
• Inhibits thyroid hormone synthesis
• Inhibits conversion of T4 to T3
• For both Methimazole PTU, what labs should you
  check?
• LFTs, WBC, TSH

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• What agents do you use for acute treatment of
  hyperthyroidism?
• Beta blockers for sxs control partially
  inhibits T4 ? T3 conversion
• Sodium ipodate or iopanoic acid are
  iodine-radiocontrast media that acutely lower
  serum T4 T3 levels by preventing release and
  peripheral conversion
• Lugols solution (iodine salts) inhibits
  synthesis release of thyroid hormone ? size
  vascularity of hyperplastic thyroid.
• Used for thyroid storm in preparation for
  thyroid surgery due to rapid onset of action (2-7
  days) transient effects (several weeks)

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Thioamides Methimazole PTU Thiocynate (SCN- )
Perchlorate (CLO4- ) block uptake of iodide
into thyroid gland. However, rarely used
clinically due to unpredictable effectiveness
risk for aplastic anemia with perchlorate.
Lange Pharmacology, 10th ed.
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Hyperthyroid Treatment Non-Pharmacologic

• When is Radioiodine 131 used?
• Elderly with Graves disease, solitary toxic
  nodule, Graves disease that fails medications,
  recurrent thyrotoxicosis
• Thyroid cells are the only cells in the body that
  absorbs iodine
• Contraindicated in pregnancy breast feeding due
  to risk of cretinism
• gt75 become hypothyroid
• When is surgical subtotal thyroidectomy
  performed?
• Mostly used in those with obstructive goiter
• Very effective but rarely used (only 1 of pts)
  due to high risk of side effects
• e.g. permanent hypothyroidism, recurrence of
  hyperthyroidism, recurrent laryngeal nerve palsy,
  permanent hypoparathyroidism

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Hyperthyroid Treatment

• Why is it important to treat Graves disease?
• If untreated, increased risk for systolic HTN due
  to increased CO and osteoporosis
• In Graves disease, only 20-25 go into remission
  spontaneously in the US
• Should you treat subclinical hyperthyroidism?
• No evidence to treat subclinical hyperthyroidism
  unless TSH lt0.1 or symptomatic
• Progresses to overt hyperthyroidism 15 in 2
  years

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Hypothyroid Treatment

• How do you treat hypothyroidism? What is the
  starting dose?
• Start levothyroxine at 1.6 mcg/kg/day
• Can start at lower dose (0.3-0.5) if increased
  risk for arrhythmia (e.g. Afib) or ischemic heart
  disease
• May need increased doses with pregnancy (30 ?
  by wk 8), estrogen replacement, poor GI
  absorption (concomitant Fe or Ca, PPI,
  sucralfate, celiac dz, IBD)
• How long does it take to see effects? When should
  you recheck TSH?
• Start to see effects in 2-4 weeks
• Recheck TSH Free T4 in 6 weeks
• Why is it important to treat Hypothyroidism?
• If untreated, increased risk for diastolic HTN
  due to stiffened arteries hyperlipidemia (?LDL,
  ?HDL)
• Should you treat subclinical hypothyroidism?
• Treat subclinical hypothyroidism if TSH gt
  8.0-12.0 or of symptomatic
• Progresses to overt hypothyroidism 4 per year

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References

• Agabegi SS, Agabegi ED. Step-Up to Medicine, 3rd
  ed. 2013. Lippincott Williams Wilkins.
  Philadelphia, PA.
• DeGroot, LJ. Diagnosis and Treatment of Graves
  Disease. Feb 2012. http//www.thyroidmanager.org/c
  hapter/diagnosis-and-treatment-of-graves-disease/
• Sabatine MS. Pocket medicine, 4th ed. 2011.
  Lippincott Williams Wilkins. Philadelphia, PA.
• Trevor AJ, Katzung BG, Kruidering-Hall M, et al.
  Katzung Trevers Pharmacology Examination
  Board Review, 10th ed. 2013. McGraw-Hill. New
  York, NY.
• Weiner C, Fauci AS, Braunwald E, et al.
  Harrisons Principles of Internal Medicine
  Self-Assessment Board Review, 17th ed 18th
  ed. 2008, 2012. Lippincott Williams Wilkins.
  Philadelphia, PA.
• Special thanks to Dr. Sood for the inspiration!