Thyroid

Question 1

Where are thyroid hormone (T3) receptors located?

Answer 1

Nucleus

Question 2

What is the function of calcitonin? Where is it produced

Answer 2

• Inhibits bone resorption
• Important clinical tumor marker for medullary thyroid cancer
• Parafollicular C cells of thyroid gland

Question 3

Where can ectopic thyroid tissue be found?

Answer 3

Anywhere along thyroglossal duct, tongue base (lingual), mediastinum

Question 4

What is the recommended daily intake for iodine? What happens if you don’t have enough?

Answer 4

• Adults: 150 micrograms
• Pregnant women: 200 micrograms
• Children: 90 micrograms
• <100: iodine deficiency
• <50: will result in goiter and hypothyroidism

Question 5

List the steps to thyroid hormone synthesis

Answer 5

1. Active transport of iodide across basement membrane of thyroid cell via NaI sypmporter
2. Oxidation of iodide and iodination of tyrosyl residues in TG (organification)
3. Linking pairs of iodotyrosine molecules within TG to form iodothyronines T3 and T4 (coupling)
4. Pinocytosis and then proteolysis of TG with release of free T3/T4 into circulation
5. Deiodination of iodotyrosines within thyroid cell, with conservation of the iodide
6. Intrathyroidal 5’ deiodination of T4 to T3

Question 6

Draw thyroid hormone production

Answer 6

Question 7

How does the Na-I symporter derive its energy?

Answer 7

From the Na-K ATPase creating the ion gradient

Question 8

What other tissues express NIS?

Answer 8

Salivary, gastric, breast (may light up on radioiodine scans or cause sialadenitis and gastritis with radioactive iodine treatment)

Question 9

Mutations in pendrin (PDS or SLC26A4 gene) cause ___

Answer 9

Congetnial hypothyroidism (dyshormonogenesis) and hearing loss.

Question 10

How do PTU and methimazole work?

Answer 10

• How do PTU and methimazole work?
• PTU also decreases peripheral conversion of T4 to T3

Question 11

What conditions cause increased thyroglobulin?

Answer 11

• Thyroiditis
• Nodular goiter
• Graves
• Papillary and follicular thyroid cancer (useful tumor marker)

Question 12

How does excess iodide inhibit thyroid hormone production?

Answer 12

• Inhibits iodide trapping
• Inhibits TG iodination (Wolff-Chaikoff effect)
• Inhibits thyroid hormone release from glands
• Note: these actions are transient and the normal thyroid gland escapes after 10-14 days. Excess iodine can be used to prevent thyroid gland exposure to radiation injury (ex. after nuclear power accidents)

Question 13

What is the Jod-Basedow effect?

Answer 13

Iodine load inducing hyperthyroidism in some patients with multinodular goiter, latent Graves disease and rarely in those with normal thyroid glands

Question 14

What proteins carry thyroid hormone around in circulation?

Answer 14

• Thyroid binding globulin (TBG)
• Transthyretic (previously thyroxine-binding prealbumin)
• Albumin

Question 15

Name 3 conditions that can increase thyroxine binding globulin

Answer 15

1. Estrogen (pregnancy, estrogen therapy)
2. Hepatitis
3. Drugs: tamoxifen, 5-fluorouracil, methadone, heroin

Question 16

Name 2 conditions that can decrease thyroxine binding globulin

Answer 16

1. Inherited
2. Androgens
3. Drugs: danazol, L-asparginase
4. Increased clearance: nephrotic syndrome, severe liver disease, protein-losing enteropathy

Question 17

List the deiodinase enzymes and their functions

Answer 17

• D1: most abundant, converts T4 to T3, expressed in liver, kidney, periphery
• D2: very sensitive to low T4, converts T4 to T3 in brain/pituitary gland
• D3: inactivates T4 to rT3

Question 18

The alpha subunit of TSH is common to what other hormones?

Answer 18

• LH
• FSH
• placental hormone hCG

Question 19

How does chronic illness impact thyroid hormones

Answer 19

1. Decreased conversion of T4 to T3
2. Rise in serum rT3
3. Decrease in total and free T4
4. Suppression of TSH

Question 20

List 2 indications for measuring thyroglobulin

Answer 20

1. Detection of residual or recurrent epithelial thyroid cancers (papillary, follicular, Hurthle cell)
2. Differentiating hyperthyroidism due to exogenous thyroid hormone (TG suppressed) vs. endogenous forms such as Graves (TG elevated or normal)

Question 21

List 4 indications for testing TSI

Answer 21

1. Pregnant women to define risk of neonatal hyperthyroidism
2. To differentiate Graves vs. postpartum thyroiditis in women who are breastfeeding (and cannot have radionucleotide scan)
3. To diagnosed Graves in euthyroid patietns with thyroid-related ophthalmopathy
4. To predict if Graves patients will relapse after antithyroid drugs are discontinued

Question 22

Describe physical exam findings of the thyroid gland in of Hashimoto thyroiditis

Answer 22

• Enlarged
• Firm
• Finely nodular surface

Question 23

Describe physical exam findings of the thyroid gland in of Graves disease

Answer 23

• Enlarged
• Smooth
• Rubbery
• May have a bruit

Question 24

List the differential diagnosis for hypothyroidism

Answer 24

• Hashimoto thyroiditis
• Radioactive iodine therapy
• Subtotal thyroidectomy for Graves/nodules/cancer
• Excessive iodide intake (kelp, radiocontrast dyes)
• Subacute thyroiditis (usually transient)
• Iodide deficiency (rare in North America)
• Inborn errors of thyroid hormone synthesis
• Drugs: lithium, amiodarone, interferon-alpha
• Secondary: hypopituitarism (adenoma, pituitary ablative therapy, pituitary destruction)
• Tertiary: hypothalamic dysfunction

Question 25

List the signs of hypothyroidism in newborns

Answer 25

* Respiratory difficulty * Cyanosis * Jaundice * Poor feeding * Hoarse cry * Umbilical hernia * Retardation of bone maturation (ex. absence of proximal tibial and distal femoral epiphysis in a full term infant with BW \>2500 g)

Question 26

List 4 ways which hypothyroidism may contribute to anemia

Answer 26

* Impaired hemoglobin synthesis as a result of T4 deficiency * Iron deficiency from menorrhagia * Folate deficiency from impaired intestinal absorption of folate * Pernicious anemia (associated autoimmune disease)

Question 27

List a differential diagnosis for hyperthyroidism

Answer 27

* Graves disease (diffuse toxic goiter) * Toxic adenoma (Plummer disease) * Toxic multinodular goiter * Subacute thyroiditis * Silent thyroiditis * Factitious thyrotoxicosis * Rare forms: ovarian struma, metastatic thyroid carcinoma (follicular), hydatiform mole, hamburger thyrotoxicosis, TSH-secreting pituitary tumor, pituitary resistance to T3 and T4

Question 28

List the classification of eye changes in Graves disease

Answer 28

* NO SPECS * 0: No signs or symptoms * 1: Only signs, no symptoms (upper lid, retraction, stare, lid lag) * 2: Soft tissue involvement * 3: Proptosis * 4: Extraocular muscle involvement * 5: Corneal involvement * 6: Sight loss (optic nerve involvement)

Question 29

List the side effects of methimazole. When do they usually occur?

Answer 29

* Pruritic rash (5%) * Agranulocytosis * Cholestatic jaundice * Acute arthritis * Usually in the first 3 months (?liver disease and agran are idiosyncratic)

Question 30

List 2 complications of thyroid surgery

Answer 30

* Hypoparathyroidism * Recurrent laryngeal nerve injury

Question 31

Why is PTU preferable to methimazole in thyroid storm?

Answer 31

* Also blocks conversion of T4 to T3 * However still contraindicated in children

Question 32

List 3 teratogenic effects of methimazole

Answer 32

1. Aplasia cutis 2. Choanal atresia 3. TEF

Question 33

List 4 ultrasound characteristics of malignant thyroid nodules

Answer 33

* Microcalcifications * Irregular borders * Hypoechoic * Increased intranodular vascularity * Taller than wide

Question 34

List 5 risks associated with hyperthyroidism during pregnancy (mom or fetus)

Answer 34

* IUGR/SGA * Preterm delivery * Early spontaneous abortion * Preeclampsia * Neonatal graves * Weight loss * Weak muscles * Atrial fibrillation

Question 35

List 4 poor outcomes associated with neonatal Graves

Answer 35

* Thrombocytopenia * HSM * Jaundice * Hypoprothrombinemia * Heart failure * Death * Irritability, flushing * Tachycardia, hypertension * Poor weight gain * Thyroid enlargement and exophthalmos

Question 36

List a differential diagnosis for congenital hypothyroidism with ABSENT uptake on scan (salivary glands only)

Answer 36

* Thyroid agenesis (genes: TTF1, TTF2, PAX8) * TSH receptor defect * Iodide trapping deects * TSH receptor blockade by maternal blocking antibodies or anti-thyroid meds * Iodine excess (iodine contrast, iodide containing meds)