MEGAN CHAN, PGY-1UHCMC 2015

Thyroid Trivia

Diagnosis of Thyroid disease includes…

3 Aspects:Functional aspectPathological

aspectAnatomical aspect

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Example: Euthyroid Graves’ disease with Goiter

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)

Non-Thyroid Causes of Thyrotoxicosis

Thyroid carcinomaExogenous hormoneHydatiform moleChoriocarcinomaExcess TRHTSH-omaPituitary T3

resistanceStruma ovariiThyroid destructionHyperemesis

TSH-R mutationFamilial gestational

hyperthyroidismAmiodaroneINF-alpha inducedHIV treatmentSunitinib therapy

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

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 wnlSubacute thyroiditis (late stage)

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)

Conditions associated with transient ↑ Free T4

Condition ExplanationEstrogen withdrawal Rapid decrease in TBG level

Amphetamine abuse Possibly induced TSH secretion(2)

Acute psychosis UnknownHyperemesis 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 conversionhttp://www.thyroidmanager.org/chapter/diagnosis-and-treatment-of-graves-disease/

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

Anti-thyroglobulin Ab ~50% of pts

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 caseWhat 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

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 goiterIf you feel and enlargement or thyroid noduleWhat 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

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 -)

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.%20Pathology%20of%20parathyroid%20glands.htm

Pocket Medicine, 4th ed.

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http://www.advancedonc.com/wp-content/themes/royal/images/Ultrasound-Guided-FNA-2.jpg

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

What agents do you use for acute treatment of hyperthyroidism?Beta blockers for sxs control & partially inhibits T4

T3 conversionSodium 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)

Thioamides= Methimazole & PTUThiocynate (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 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 goiterVery 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

Hyperthyroid Treatment

Why is it important to treat Graves’ disease?If untreated, increased risk for systolic HTN

due to increased CO and osteoporosisIn Grave’s disease, only 20-25% go into

remission spontaneously in the USShould you treat subclinical hyperthyroidism?No evidence to treat subclinical

hyperthyroidism unless TSH <0.1 or symptomatic 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

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

Progresses to overt hypothyroidism ~4% per year

References

Agabegi SS, Agabegi ED. Step-Up to Medicine, 3rd ed. 2013. Lippincott Williams & Wilkins. Philadelphia, PA.

DeGroot, LJ. Diagnosis and Treatment of Grave’s Disease. Feb 2012. http://www.thyroidmanager.org/chapter/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 & 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!