Thyroid Disorders

What hormone does the hypothalamus release to regulate the thyroid axis?

TRH

What hormone does the anterior pituitary release in response to TRH?

TSH

What gland does TSH act on?

Thyroid gland

What hormones are produced by the thyroid gland?

- T4 (thyroxine)

- T3 (triiodothyronine)

Where is T4 converted to T3?

In target cells (peripheral tissues)

What is the active form of thyroid hormone at the cellular level?

T3

What is primary hypothyroidism caused by?

Failure of the thyroid gland to produce enough T3 and T4

What are lab findings in primary hypothyroidism?

↑ TSH, ↓ T3/T4

What is secondary (central) hypothyroidism caused by?

Failure of the anterior pituitary to release TSH

What are lab findings in secondary hypothyroidism?

↓ TSH, ↓ T3/T4

What is tertiary (central) hypothyroidism caused by?

Failure of the hypothalamus to release TRH

What happens to TRH and TSH when T3 and T4 levels are high?

They decrease due to negative feedback

What happens to TRH and TSH when T3 and T4 levels are low?

They increase due to lack of negative feedback

What is the most common cause of primary hypothyroidism?

Autoimmune destruction (Hashimoto's thyroiditis)

What are additional causes of primary hypothyroidism?

- Surgical removal or radioiodine ablation

- Postpartum thyroiditis

- Iodine deficiency

What causes central hypothyroidism?

Pituitary or hypothalamic dysfunction

Which 2 drugs commonly cause drug-induced hypothyroidism?

- Amiodarone

- Lithium

How does Amiodarone cause hypothyroidism?

Blocks the conversion of T4 to T3 and blocks T3 receptors

How does Lithium cause hypothyroidism?

Concentrates in thyroid gland and inhibits T4/T3 secretion

What are the signs of hypothyroidism?

- Bradycardia

- Hypothermia

- Weight gain

- Goiter

- Coarse skin and hair

- Dry, pale skin

What are the symptoms of hypothyroidism?

- Fatigue

- Cold intolerance

- Depression

- Muscle cramps

- Constipation

- Slow cognition

- Hoarse voice

- Menstrual irregularities

What TSH range defines “moderate” subclinical hypothyroidism?

TSH 4-10 mIU/L

When should moderate subclinical hypothyroidism be treated?

When TSH 4-10 mIU/L PLUS specific risk factors or symptoms

Which antibody positivity supports treating subclinical hypothyroidism?

Positive thyroid peroxidase (TPO) antibodies

Which cardiovascular conditions support treating subclinical hypothyroidism?

ASCVD or cardiovascular risk factors (HTN, hyperlipidemia, diabetes, smoking)

Which cardiac condition is an indication to treat subclinical hypothyroidism?

Heart failure

When should subclinical hypothyroidism be treated in women of childbearing age?

If pregnant or planning pregnancy

At what TSH level is treatment recommended regardless of symptoms?

TSH >10 mIU/L

What defines overt hypothyroidism based on TSH?

TSH >10 mIU/L

What is the key difference in treatment approach between subclinical and overt hypothyroidism?

- Subclinical requires additional factors

- Overt is treated regardless

What are the main thyroid hormone replacement options and their components?

- Levothyroxine (Synthroid) = synthetic T4 (preferred)

- Liothyronine (Cytomel) = synthetic T3 (more active)

- Liotrix (Thyrolar) = synthetic T4+T3

- Desiccated thyroid (Armour Thyroid) = natural T4+T3

What are the key limitations of Liothyronine (T3)?

- No added efficacy vs Levothyroxine

- ↑ cardiac adverse effects (tachycardia)

- Fewer strengths available

- Requires TID dosing

What are the key limitations of Liotrix (T4 + T3)?

- No added efficacy vs levothyroxine

- Non-physiologic 4:1 T4:T3 ratio (normal ~14:1)

- ↑ cardiac adverse effects (tachycardia)

- Fewer strengths available

- Higher cost

What are the key limitations of desiccated thyroid (natural T4 + T3)?

- Less effective than Levothyroxine

- Subnormal T4 despite normal TSH

- Wide variability in bioequivalence

- Antigenic in sensitive patients

- Higher cost

What are contraindications of levothyroxine?

Overt thyrotoxicosis and untreated adrenal insufficiency

What is the black box warning for levothyroxine?

Improper use for weight reduction

What are common dose-dependent adverse effects of levothyroxine?

Weight loss, tachycardia, arrhythmias, tremor

What is the half-life of levothyroxine?

8-10 days

How should Levothyroxine be administered?

Take in the morning on an empty stomach, at least 60 minutes before food or other medications

What is the effect of taking levothyroxine in a non-fasting state and what is the key conclusion for administration?

- Non-fasting leads to variable absorption and increased TSH

- Therefore, take Levothyroxine consistently on an empty stomach

What medications decrease Levothyroxine absorption and require separation by 4 hours?

- Antacids (aluminum/calcium/magnesium) (causes chelation reaction)

- Bile Acid Sequestrants

- Iron

- Sucralfate

What is the interaction between Levothyroxine and Warfarin?

Levothyroxine increases metabolism of clotting factors which increases INR (increased bleeding)

How should Warfarin be managed when starting Levothyroxine?

Monitor INR and reduce Warfarin dose as needed

What is the initial dosing of Levothyroxine in healthy patients <50 years old based on?

Ideal Body Weight

How should Levothyroxine therapy be monitored and adjusted?

Check TSH every 4-8 weeks and adjust until euthyroid, then monitor annually

What is the TSH goal for patients on Levothyroxine?

0.4 - 4 mIU/L

What needs to be checked before adjusting the dose of Levothyroxine?

- Adherence

- Consistent Administration

- Drug interactions

How should Levothyroxine doses be adjusted?

Increase or decrease by 12.5-25 mcg/day based on TSH

How should levothyroxine be adjusted if TSH is close to goal?

Use smaller dose adjustments

How should Levothyroxine be adjusted (empirically) when pregnancy is confirmed?

Increase dose by 20-30%

How should thyroid function be monitored during pregnancy?

Check TSH every 4 weeks

What should be done with levothyroxine dosing after delivery?

Return to pre-pregnancy dose

What is myxedema coma?

A severe, life-threatening hypothyroid state with high mortality (60-70%)

What are key clinical features of myxedema coma?

- Advanced hypothyroid symptoms

- Hypothermia

- Altered mental status (delirium or coma)

How is myxedema coma treated?

- IV Levothyroxine 300-500 mcg bolus

- Hydrocortisone 100 mg IV every 8 hours

What is the clinical disease state from excess T4 in body tissues irrespective of the source?

Thyrotoxicosis

What is thyrotoxicosis from excess T4 form the thyroid gland?

Hyperthyroidism

What is the most common cause of primary hyperthyroidism?

Graves' Disease

What is the mechanism of Graves' disease?

Autoimmune disease where TSH receptor antibodies stimulate overproduction of T4

Which medications can induce hyperthyroidism?

- Amiodarone

- Iodine contrast dye

What are the signs/symptoms of hyperthyroidism?

- Anxiety

- Irritability/emotional lability

- Tachycardia

- Palpitations

- A-fib

- Weight loss

- Increased Appetite

- Increased frequency of bowel movements

- Bone Fractures

- Goiter

Which thyroid function tests are needed to monitor hyperthyroidism?

- TSH

- Free T4

- T3

- T4

What is the treatment for subacute hyperthyroidism?

No treatment, self-limiting

When is subclinical hyperthyroidism treated?

Only in young patients with significant risk factors (A. fib & bone fractures)

Is overt hyperthyroidism treated?

Yes

What are the main pharmacologic treatments for Graves’ disease?

- Radioactive iodine (RAI) = #1 treatment

- Thionamides (methimazole, PTU)

- Iodide

Which thionamides are used to treat Graves' disease?

Methimazole and propylthiouracil (PTU)

When is thyroidectomy used in Graves’ disease?

Reserved for severe cases

What are the goals of therapy in Graves' disease?

- Eliminate excess thyroid hormone

- Minimize symptoms

- Reduce long-term consequences

What is the first-line therapy for hyperthyroidism?

Radioactive Iodine

What is the MOA for radioactive iodine therapy?

- Concentrates in thyroid gland

- Disrupts hormone synthesis

- Ablates thyroid tissue

When is radioactive iodine therapy contraindicated?

Pregnancy/lactation

When is a second dose of radioactive iodine given?

If hyperthyroidism persists beyond 6 months

What are the adverse reactions of radioactive iodine?

- Hypothyroidism

- Radiation thyroiditis

- Radiation thyrotoxicosis

How is radiation thyroiditis treated?

APAP/NSAIDs

What is the primary adjunct therapy used with radioactive iodine (RAI)?

Beta-blockers

When should iodide be given in relation to RAI therapy?

3-7 days after RAI, not before

How should thionamides be managed around RAI therapy?

Hold 4 days before and after RAI

What is a common beta-blocker used in hyperthyroidism?

Propranolol 20-40 mg QID (max 480 mg/day)

What symptoms do beta-blockers relieve in hyperthyroidism?

Sympathetic autonomic symptoms (tachycardia, tremor)

What is the heart rate goal when titrating beta-blockers in hyperthyroidism?

60-90 bpm

When should beta-blockers be discontinued in hyperthyroidism?

Taper and discontinue once thyroid function normalizes

Which medications can be used if Propranolol cannot be tolerated to treat radiation thyrotoxicosis?

- Non-DHP CCB

- Clonidine

What are the uses of iodide (SSKI, Lugol’s solution) in hyperthyroidism?

- Pre-thyroidectomy

- Treatment of thyroid storm

- Adjuvant therapy after RAI

What is the mechanism of action of iodide in hyperthyroidism?

Inhibits thyroid hormone release and biosynthesis

What are common adverse effects of iodide therapy?

Salivary gland swelling and metallic taste

What are thionamides used in hyperthyroidism?

Methimazole and propylthiouracil (PTU)

What is the mechanism of action of thionamides?

- Inhibit thyroid peroxidase

- Blocking thyroid hormone synthesis

What additional mechanism is unique to PTU?

Inhibits peripheral conversion of T4 → T3

What is the most serious adverse effect of thionamides?

Agranulocytosis (rare) = stop medication immediately

Which thionamide has a black box warning and for what?

PTU = hepatotoxicity

What are common minor adverse effects of thionamides?

- GI upset

- Hypothyroidism

- Rash

- Arthralgias

What baseline labs are required before starting thionamides?

- TSH

- Free T4

- CBC

- LFTs

How often should TSH and Free T4 be monitored during thionamide titration?

Every 4-8 weeks

How often should TSH and Free T4 be monitored once stable on thionamides?

Every 2-3 months

When should clinical improvement be assessed after starting thionamides?

At 4-8 weeks

When can thionamide doses be titrated to maintenance?

After assessing response at 4-8 weeks

When should CBC and LFTs be repeated during thionamide therapy?

If adverse drug reactions are suspected (agranulocytosis and liver toxicity)

What is the duration of thionamide therapy after achieving euthyroidism?

12-24 months

When should patients be monitored for relapse after remission?

6-12 months after remission