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

Thyroid Disorders Flashcards by Natalie Foo

What are the tests of autoimmunity? (3)

Which 2 are commonly found in Hashimoto’s disease?

Which are specific and confirmatory for Graves’ disease?

ATgA: thyroglobulin Ab
TPO: thyroperoxidase Ab
TRAb: thyrotropin receptor lgG Ab ($$$)

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

TRAb is specific and confirmatory for Graves’ disease

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Compelling indications for screening of thyroid disorders? (8)

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

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

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

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

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3 primary causes of hypothyroidism?

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

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2 secondary causes of hypothyroidism?

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

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Effects of hypothyroidism on pregnancy?

Miscarriage, spontaneous abortion
Congenital defects, impaired cognitive development

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Clinical manifestations of hypothyroidism?** (5)

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

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How do we diagnose hypothyroidism?

S/sx OR screening

PLUS

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

Central hypothyroidism
- ↓ TSH, ↓ T4

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Goals of Tx? (4)

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

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What is subclinical hypothyroidism?

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

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When should we treat subclinical hypothyroidism?

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

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

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

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State the pharmacotherapy for hypothyroidism

Levothyroxine (synthetic T4)
Liothyronine (synthetic T3)

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Dosing for levothyroxine hypothyroidism?

How about for pregnancy women?

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

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How should we titrate levothyroxine?

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

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Dosing for levothyroxine for subclinical hypothyroidism?

Initial daily doses of 25-75 mcg recommended

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Counselling for levothyroxine? (4)

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

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ADEs of levothyroxine? (3)

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

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Clinical use of liothyronine? (synthetic T3)

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)

ADEs of liothyronine? Is this preferred over levothyroxine?

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

Dosing for liothyronine?

Starting: 25 mcg
Elderly/ CVD: 5 mcg

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

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

General target: TSH 0.4-4 mIU/L

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

Normalisation of FT4 with consistently ↑ TSH

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

Every 6m → 1y (non-pregnant pts)

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

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

Causes of hyperthyroidism?

- 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)

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

- Failure to gain weight despite good appetite - Tachycardia

How is hyperthyroidism diagnosed?

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

Goals of Tx for hyperthyroidism?

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

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

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

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

- 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

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

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

How can hyperthyroidism affect pregnancy?

If untreated, may result in fetal loss

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

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

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

- 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

Dosing for carbimazole (preferred) in hyperthyroidism?

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

Dosing for PTU in hyperthyroidism?

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

ADEs of thionamides for hyperthyroidism? (4)

- 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)

Onset of thionamides for hyperthyroidism?

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

How should we prescribe thionamides for hyperthyroidism in pregnant pts?

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

What type of iodide is used for hyperthyroidism?

Lugol's solution

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

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

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

- 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

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

Propranolol

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

- 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