Thyroid Disorders

Question 1

What are the tests of autoimmunity? (3)

Which 2 are commonly found in Hashimoto’s disease?

Which are specific and confirmatory for Graves’ disease?

Answer 1

1. ATgA: thyroglobulin Ab
2. TPO: thyroperoxidase Ab
3. TRAb: thyrotropin receptor lgG Ab ($$$)

ATgA and TPO found in 95% of Hashimoto’s disease

TRAb is specific and confirmatory for Graves’ disease

Question 2

Compelling indications for screening of thyroid disorders? (8)

Answer 2

• Presence of autoimmune disease (eg T1DM, cystic fibrosis)
• First-degree relative with autoimmune thyroid disease
• Psychiatric disorders
• Taking amiodarone/ lithium
• Pts who come in for AFib
• Hx of head/ neck radiation for malignancies
• S/sx of hypothyroidism/ hyperthyroidism
• Pediatric pts and pregnant women

Question 3

How is T3 and T4 levels affected by estrogen and pregnancy?

In a normal state, how does the body compensate for this change?

Answer 3

Estrogen and pregnancy causes elevated Thyroxine Binding Globulin (TBG) levels

In normal individuals: FT3 and FT4 levels will ↓ as more T3 and T4 will bind to extra TBG → TSH released to instruct thyroid gland to release more THs → FT3 and FT4 levels return back to normal

Question 4

3 primary causes of hypothyroidism?

Answer 4

1. Iodine deficiency (MOST common)
2. Hashimoto disease (autoimmune)
3. Iatrogenic (thyroid resection/ radioiodine ablative Tx for hyperthyroidism)

Question 5

2 secondary causes of hypothyroidism?

Answer 5

• Central hypothyroidism (hypothalamus/ pituitary gland unable to secrete TRH/ TSH respectively)
• Drug-induced (amiodarone, lithium)

Question 6

Effects of hypothyroidism on pregnancy?

Answer 6

• Miscarriage, spontaneous abortion
• Congenital defects, impaired cognitive development

Question 7

Clinical manifestations of hypothyroidism?** (5)

Answer 7

• ↑ total cholesterol, LDL, TGs
• ↑ atherosclerosis, MI risk
• ↑ creatinine phosphokinase (CPK) levels
• ↑ miscarriage risk
• Impaired fetal cognitive development

Question 8

How do we diagnose hypothyroidism?

Answer 8

S/sx OR screening

PLUS

Primary hypothyroidism
- ↑ TSH, ↓ T4
- Positive ATgA and TPO Ab

OR

Central hypothyroidism
- ↓ TSH, ↓ T4

Question 9

Goals of Tx? (4)

Answer 9

1. Minimise or eliminate s/sx
2. Minimise long-term damage to organs (myxedema coma, heart disease)
3. Prevent neurologic deficits in newborns and children
4. Normalise free T4 and TSH concentrations

Question 10

What is subclinical hypothyroidism?

Answer 10

Elevated TSH with normal T4, often the result of early Hashimoto disease

Question 11

When should we treat subclinical hypothyroidism?

Answer 11

• TSH > 10 mIU/L OR
• TSH 4.5-10 mIU/L AND
  s/sx of hypothyroidism or
  TPOAb present or
  Hx of CVD, HF, or risk factors

Question 12

What are the risks when TSH > 7.0 mIU/L and when TSH > 10 mIU/L?

Answer 12

• TSH > 7.0 mIU/L in older adults: ↑ risk of HF
• TSH > 10 mIU/L: ↑ risk of coronary HD

Question 13

State the pharmacotherapy for hypothyroidism

Answer 13

1. Levothyroxine (synthetic T4)
2. Liothyronine (synthetic T3)

Question 14

Dosing for levothyroxine hypothyroidism?

How about for pregnancy women?

Answer 14

• Young, healthy adults: 1.6 mcg/kg/d
• 50-60 y/o and no cardiac issues: 50 mcg daily
• With CVD: 12.5 - 25 mcg/d, titrate up slowly

Pregnancy: May need 30-50% ↑ in dosage to maintain euthyroid status

Question 15

How should we titrate levothyroxine?

Answer 15

• Depends on response → control of s/sx, normalisation of TSH and T4
• Can ↑ or ↓ in 12.5 - 25 mcg/d increments, or in 15-20% of weekly dose

Question 16

Dosing for levothyroxine for subclinical hypothyroidism?

Answer 16

Initial daily doses of 25-75 mcg recommended

Question 17

Counselling for levothyroxine? (4)

Answer 17

• Do not take with food; take 30-60 mins BEFORE breakfast or 4 hours AFTER dinner (empty stomach)
• Calcium, iron supplements, antacids → space AT LEAST 2h apart
• Takes 4-8w to observe effects (labs)
• Takes 2-3w to observe symptomatic relief

Question 18

ADEs of levothyroxine? (3)

Answer 18

• Cardiac abnormalities (tachyarrhythmias, angina, MI)
• Risk of fractures
• Hyperthyroidism s/sx

Question 19

Clinical use of liothyronine? (synthetic T3)

Answer 19

• Combination with T4 can be considered if normalised TSH but still complains of hypothyroidism s/sx
• Give IV in myxedema coma since more potent (also can give IV levothyroxine)

Question 20

ADEs of liothyronine? Is this preferred over levothyroxine?

Answer 20

ADEs similar to levothyroxin but high incidence (hence generally not recommended)

Question 21

Dosing for liothyronine?

Answer 21

• Starting: 25 mcg
• Elderly/ CVD: 5 mcg

Question 22

Monitoring for Tx for hypothyroidism? (When to monitor and TSH target?)

Answer 22

Monitor 4-8w to assess response after initiating or changing Tx

General target: TSH 0.4-4 mIU/L

Question 23

What lab results could signify non-adherence to hypothyroidism Tx?

Answer 23

Normalisation of FT4 with consistently ↑ TSH

Question 24

After euthyroid state achieved with the help of the medicines, how often are thyroid function tests (TFT) still recommended?

Answer 24

Every 6m → 1y (non-pregnant pts)

Question 25

Target TSH levels of pregnancy in the first, second and third trimester each?

Answer 25

- 1st trimester: < 2.5 mIU/L - 2nd trimester < 3.0 mIU/L - 3rd trimester < 3.5 mIU/L

Question 26

Causes of hyperthyroidism?

Answer 26

- Toxic diffuse goiter (Graves’ disease): TRAb mimics TSH binding → stimulates TH production - Adenomas: pituitary adenomas, toxic adenoma, toxic multi-nodular goiter - Drug-induced → amiodarone, lithium - Subacute thyroiditis (release of stored hormones)→ infections, drug-induced, early Hashimoto’s disease - Surgical resection (often) - Thyroidectomy (definitely)

Question 27

What are the s/sx of hyperthyroidism specifically for pregnant women?

Answer 27

- Failure to gain weight despite good appetite - Tachycardia

Question 28

How is hyperthyroidism diagnosed?

Answer 28

S/sx PLUS - Elevated free T4 serum conc - - Suppressed TSH conc (except in TSH-secreting adenomas) - Radioactive iodine uptake (RAIU) for better etiology: (1) Uptake elevated if gland actively secreting TH → Graves’ disease, TSH-secreting adenoma, toxic adenoma, multinodular goiter, (2) Uptake suppressed if thyroiditis or cancer - Positive TRAb, ATgA and TPO Ab - Biopsy

Question 29

Goals of Tx for hyperthyroidism?

Answer 29

1. Minimise or eliminate s/sx 2. Minimise long-term damage to organs (HD, arrhythmias, sudden cardiac death, bone demineralisation, fractures) 3. Normalise free T4 and TSH conc

Question 30

Pharmacotherapeutic agents used for hyperthyroidism? (4) Which is the first line? Can pregnant pts undergo this Tx?

Answer 30

First line: Radioactive iodine ablation (RAI) Tx. AVOID in pregnant women Thionamides, iodides, non-selective β-blocker

Question 31

In which type of pts do we initiate Tx for hyperthyroidism? (5)

Answer 31

- For those awaiting ablative Tx/ surgical resection - ↓ risk of post-ablation hyperthyroidism caused by thyroiditis - For those not ablative or surgical candidates & failed to normalise thyroid - Mild disease, small goiter, low or -ve Ab titers, women - Limited life expectancy

Question 32

What is subclinical hyperthyroidism? What are its risks? (2)

Answer 32

Low/ undetectable TSH with normal T4 - Elevated risk of AF in pts > 60 y/o - Elevated risk of bone fractures in postmenopausal women

Question 33

How can hyperthyroidism affect pregnancy?

Answer 33

If untreated, may result in fetal loss

Question 34

How should we treat subclinical hyperthyroidism? Can we suggest ablative Tx?

Answer 34

- Initial daily doses of PO therapy 25-75 mcg recommended (do not do ablative Tx for young patients) - β-blocker esp if AF

Question 35

Name 2 types of thionamides MOA of thionamides? What additional effects does PTU have?

Answer 35

- Inhibits iodination and synthesis of TH by acting as substrate for TPO - Additional: PTU can block T4/ T3 conversion in periphery @ high doses Carbimazole also used to control the disease before surgery

Question 36

Dosing for carbimazole (preferred) in hyperthyroidism?

Answer 36

Initial 15-60mg daily in 2-3 divided doses

Question 37

Dosing for PTU in hyperthyroidism?

Answer 37

Initial 50 - 150mg PO tds → once euthyroid, can ↓ to 50 mg bd/ tds

Question 38

ADEs of thionamides for hyperthyroidism? (4)

Answer 38

- Hepatotoxicity - Rash → risk for SJS - Agranulocytosis early in Tx (~3m) (rare) - Fever - Joint pain (carbimazole) - Embryopathy - Hypothyroidism (monitor thyroid size and TSH levels, once thyroid size reduced and normal TSH levels achieved, titrate and decrease carbimazole's dose)

Question 39

Onset of thionamides for hyperthyroidism?

Answer 39

Slow onset in reducing s/sx, maximal effect may take 4-6m

Question 40

How should we prescribe thionamides for hyperthyroidism in pregnant pts?

Answer 40

1st trimester: use PTU (Carbimazole has higher risk of congenital malformations) 2nd and 3rd trimesters: use Carbimazole as has PTU has higher risk of hepatotoxicity

Question 41

What type of iodide is used for hyperthyroidism?

Answer 41

Lugol's solution

Question 42

MOA of Lugol's solution for hyperthyroidism? (3)

Answer 42

- Inhibits release of stored THs - Minimal effect on hormone synthesis - Helps decrease vascularity and gland size

Question 43

When should iodides be used for hyperthyroidism? After how many days of therapy does it have limited efficacy?

Answer 43

- Before surgery (7-10d) to shrink gland - After ablative tx (3-7d) to inhibit thyroiditis-mediated release of stored TH (do NOT use before!) Limited efficacy after 7-14d of tx as TH release resumes

Question 44

Name the type of non-selective β-blocker used for hyperthyroidism

Answer 44

Propranolol

Question 45

What is the place in therapy for β-blockers used for hyperthyroidism?

Answer 45

- For symptomatic relief - Bridging Tx for thionamide effects to kick in/ before ablation/ surgery - PRN for high risk pts (elderly, CV disease) - Tx of thyroiditis Give for subclinical hyperthyroidism, esp if AF