1. Thyroid Trivia
Megan Chan, PGY-1
UHCMC 2015

2. Diagnosis of Thyroid disease includes…
3 Aspects:
Functional aspect
Pathological aspect
Anatomical aspect
Example: Euthyroid Graves’ disease with Goiter

3. 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%
Plummer’s disease (multinodular toxic goiter)—15%
Toxic thyroid adenoma (single nodule)—2%
If transient: Hashimoto’s thyroiditis, subacute thyroiditis (early stage)
Plummer’s disease = hyperfunctioning areas that produce high T4 & T3, rest of thyroid is not functioning (atrophy)

4. 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

5. 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

6. Hypothyroidism Definitions
What is Primary Hypothyroidism? What are some examples?
Failure of the thyroid gland, accounts for 95% cases
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
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)

7. 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)

8. Conditions associated with transient ↑ Free T4
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
Propranolol (large doses)
Inhibition of T4 to T3 conversion
Prednisone (rarely)
High altitude exposure
Possibly hypothalamic activation
Selenium deficiency
Decreased T4 to T3 conversion

9. 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
>95% of pts
Anti-thyroglobulin Ab
~50% of pts
What Ab tests are positive in Hashimoto’s disease?
Anti-peroxidase/microsomal Ab (TPO)—high titer
~90% of pts
Non-specific 5-10% of healthy people test positive

10. 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

11. 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.
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 <1mm
Malignant: >2mm, irregular boarders, calcifications (papillary), blood supply via dopplers
If multinodular, can perform radionucleotide uptake scan to determine which one to biopsy
Hypoechoic = lots of blood

12. 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 -)

13. Pocket Medicine, 4th ed.

14. http://intranet. tdmu. edu

15. Pocket Medicine, 4th ed.

16. 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 conversion of T4 to T3
For both Methimazole & PTU, what labs should you check?
LFTs, WBC, TSH
Thionamides: Methimazole, PTU

17. 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
Lugol’s 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)

18. Thioamides= Methimazole & PTU
Amiodarone can cause hypothyroidism by blocking peripheral conversion of T4 to T3. However it can also cause hyperthyroidism through an iodine-induced mechanism in persons with underlying thyroid disease (e.g. multinodular goiter) or through an inflammatory mechanism that causes leakage of thyroid hormone into the circulation. Treat amiodarone-associated hypothyroidism with thyroid hormone. Iodine-associated hyperthyroidism with thioamides. Inflammatory-associated hyperthyroidism with steriods.
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.

19. 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
>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
e.g. permanent hypothyroidism, recurrence of hyperthyroidism, recurrent laryngeal nerve palsy, permanent hypoparathyroidism

20. 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
Progresses to overt hyperthyroidism ~15% in 2 years

21. 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 ( ) 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 > or of symptomatic
Progresses to overt hypothyroidism ~4% per year

22. References
Agabegi SS, Agabegi ED. Step-Up to Medicine, 3rd ed Lippincott Williams & Wilkins. Philadelphia, PA.
DeGroot, LJ. Diagnosis and Treatment of Grave’s Disease. Feb
Sabatine MS. Pocket medicine, 4th ed Lippincott Williams & Wilkins. Philadelphia, PA.
Trevor AJ, Katzung BG, Kruidering-Hall M, et al. Katzung & Trever’s Pharmacology: Examination & Board Review, 10th ed 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, Lippincott Williams & Wilkins. Philadelphia, PA.
Special thanks to Dr. Sood for the inspiration!