Transcript Thyroid Trivia

Thyroid Trivia
MEGAN CHAN, PGY-1
UHCMC 2015
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?
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Graves’ disease (diffuse toxic goiter)—80%
Plummer’s disease (multinodular toxic goiter)—15%
Toxic thyroid adenoma (single nodule)—2%
If transient: Hashimoto’s thyroiditis, subacute thyroiditis (early
stage)
Non-Thyroid Causes of Thyrotoxicosis
 Thyroid carcinoma
 TSH-R mutation
 Exogenous hormone
 Familial gestational
 Hydatiform mole
 Choriocarcinoma
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 Excess TRH
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 TSH-oma
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 Pituitary T3 resistance
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hyperthyroidism
Amiodarone
INF-alpha induced
HIV treatment
Sunitinib therapy
 Struma ovarii
 Thyroid destruction
 Hyperemesis
http://www.thyroidmanager.org/chapter/diagnosis-and-treatment-of-graves-disease/
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
Plummer’s dz
Single nodule within atrophic gland
Toxic adenoma
Hypothyroidism Definitions
What is Primary Hypothyroidism? What are some examples?
 Failure of the thyroid gland, accounts for 95% cases
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Hashimoto’s 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
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Deficiency of TSH
What is Tertiary Hypothyroidism? What is deficient?
 2/2 hypothalamic disease
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Deficiency of TRH
What are other causes of Hypothyroidism?
 Subacute hypothyroidism
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Increased TSH production maintains T4 wnl
 Subacute thyroiditis (late stage)
Blood Work
What is the best screening test for thyroid disease?
 TSH
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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)
Conditions associated with transient ↑ Free T4
Condition
Explanation
Estrogen withdrawal
Rapid decrease in TBG level
Amphetamine abuse
Possibly induced TSH secretion(2)
Acute psychosis
Hyperemesis gravidarum
Unknown
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-and-treatment-of-graves-disease/
Blood Work
What Ab tests are positive in Graves’ disease?
 Thyroid stimulating Ab (TSI)
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~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)
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~90%, High specificity
 Anti-peroxidase/microsomal Ab (TPO)—low titier
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>95% of pts
 Anti-thyroglobulin Ab
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~50% of pts
What Ab tests are positive in Hashimoto’s disease?
 Anti-peroxidase/microsomal Ab (TPO)—high titer
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~90% of pts
Non-specific 5-10% of healthy people test positive
 Anti-thyroglobulin Ab
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~50% of pts
Blood Work
What does Thyroglobulin do?
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Makes T4/T3
When do you test for Thyroglobulin + Antithyroglobulin 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
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Free T4 is not influenced by TBG
Increased in pregnancy, hepatitis, OPCs, ASA
Decreased in glucocorticoids, nephritic syn, cirrhosis, androgens
Imaging
What is a Radionucleotide uptake scan most helpful for?
 Helps identify the cause of hyperthyroidism: diffuse uptake
(Grave’s) vs patchy (Plummer’s disease) vs hot nodule.
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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?
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Benign if nodule <1mm
Malignant: >2mm, irregular boarders, calcifications (papillary), blood
supply via dopplers
If multinodular, can perform radionucleotide uptake scan to determine
which one to biopsy
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
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FNA is incorrect 10% of the time (false + or false -)
Pocket Medicine, 4th ed.
http://intranet.tdmu.edu.ua/data/kafedra/internal/vnutrmed2/classes_stud/en/med/lik/ptn/Internal%20medicine/4%20course/06.%20Hyperthyroidism.%20Patholo
gy%20of%20parathyroid%20glands.htm
Pocket Medicine, 4th ed.
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http://www.advancedonc.com/wpcontent/themes/royal/images/Ultrasound-Guided-FNA-2.jpg
Hyperthyroid Treatment: Pharmacologic
What is the preferred treatment for Hyperthyroidism?
 Methimazole
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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)
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Inhibits thyroid hormone synthesis
Inhibits conversion of T4 to T3
For both Methimazole & PTU, what labs should you check?
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LFTs, WBC, TSH
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 iodineradiocontrast media that acutely lower serum T4 & T3
levels by preventing release and peripheral conversion
 Lugol’s solution (iodine salts) inhibits synthesis &
release of thyroid hormone + ↓ size & vascularity of
hyperplastic thyroid.
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Used for thyroid storm & in preparation for thyroid surgery due to
rapid onset of action (2-7 days) & transient effects (several weeks)
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.
Hyperthyroid Treatment: Non-Pharmacologic
When is Radioiodine 131 used?
 Elderly with Graves’ disease, solitary toxic nodule,
Graves’ disease that fails medications, recurrent
thyrotoxicosis
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Thyroid cells are the only cells in the body that absorbs iodine
Contraindicated in pregnancy & breast feeding due to risk of
cretinism
>75% 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
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e.g. permanent hypothyroidism, recurrence of hyperthyroidism,
recurrent laryngeal nerve palsy, permanent hypoparathyroidism
Hyperthyroid Treatment
Why is it important to treat Graves’ disease?
 If untreated, increased risk for systolic HTN due to
increased CO and osteoporosis
 In Grave’s disease, only 20-25% go into remission
spontaneously in the US
Should you treat subclinical hyperthyroidism?
 No evidence to treat subclinical hyperthyroidism
unless TSH <0.1 or symptomatic
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Progresses to overt hyperthyroidism ~15% in 2 years
Hypothyroid Treatment
How do you treat hypothyroidism? What is the starting dose?
 Start levothyroxine at 1.6 mcg/kg/day
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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 > 8.0-12.0 or of symptomatic
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Progresses to overt hypothyroidism ~4% per year
References
 Agabegi SS, Agabegi ED. Step-Up to Medicine, 3rd ed. 2013.
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Lippincott Williams & Wilkins. Philadelphia, PA.
DeGroot, LJ. Diagnosis and Treatment of Grave’s Disease. Feb
2012. http://www.thyroidmanager.org/chapter/diagnosis-andtreatment-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 &
Trever’s Pharmacology: Examination & Board Review, 10th ed.
2013. McGraw-Hill. New York, NY.
Weiner C, Fauci AS, Braunwald E, et al. Harrison’s 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!