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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
The Bottom Line
- Primary hypothyroidism = high TSH + low free T4; subclinical = high TSH + normal free T4
- Most common US cause: Hashimoto thyroiditis; worldwide: iodine deficiency
- First-line treatment: levothyroxine, titrated by TSH every 6-8 weeks
- Start low-dose levothyroxine in older adults or coronary artery disease to avoid precipitating angina or arrhythmia
- Myxedema coma = hypothermia, bradycardia, hypotension, altered mental status — treat with IV levothyroxine + stress-dose hydrocortisone
Overview
Hypothyroidism is a clinical syndrome caused by inadequate thyroid hormone production or action. Primary hypothyroidism arises from thyroid gland failure and is characterized by elevated TSH with low free T4. Secondary or central hypothyroidism arises from pituitary or hypothalamic dysfunction and shows low or inappropriately normal TSH with low free T4. Hashimoto thyroiditis is the most common cause in iodine-sufficient areas and is associated with anti-thyroid peroxidase antibodies.
Epidemiology
Hypothyroidism is more common in women and increases with age. Risk factors include autoimmune disease, family history, prior thyroid surgery, radioactive iodine therapy, external neck radiation, medications such as amiodarone and lithium, postpartum thyroiditis, and iodine imbalance. Screening asymptomatic nonpregnant adults remains controversial, but Step 2 CK commonly tests targeted evaluation in symptomatic patients, pregnancy, infertility, goiter, hyperlipidemia, and autoimmune comorbidity.
Clinical Features
Symptoms
Fatigue, lethargy, slowed thinking, depression
Cold intolerance, weight gain, constipation
Menorrhagia, infertility, decreased libido
Hoarseness, dry skin, hair loss, brittle nails
Severe somnolence or confusion suggesting myxedema coma
Signs
Bradycardia, delayed relaxation phase of deep tendon reflexes
Nonpitting periorbital edema and coarse facial features
Cool dry skin, thinning lateral eyebrows
Goiter in Hashimoto thyroiditis or iodine deficiency
Hypothermia, hypotension, hypoventilation, hyponatremia in myxedema coma
Investigations
First-line
TSHBest initial test for suspected primary hypothyroidism; elevated in primary hypothyroidism
Free T4Low in overt hypothyroidism; normal in subclinical hypothyroidism
Anti-thyroid peroxidase antibodiesSupports Hashimoto thyroiditis and predicts progression from subclinical to overt disease
Second-line
Lipid panelHypothyroidism can cause hyperlipidemia and should be considered in secondary dyslipidemia
CBC and CMPMay show normocytic or macrocytic anemia, hyponatremia, elevated CK, or mild transaminase elevation
Pregnancy test when relevantPregnancy changes levothyroxine requirements and requires tighter TSH targets
Specialist
Pituitary evaluationIf low free T4 with low/inappropriately normal TSH, assess central hypothyroidism and other pituitary hormone axes
Thyroid ultrasoundNot routinely needed for hypothyroidism unless palpable nodule, goiter, or suspicious structural finding
1
Standard replacement
- Levothyroxine once daily on an empty stomach, separated from calcium, iron, bile acid sequestrants, and proton pump inhibitors when possible
- Healthy young adult full replacement: ~1.6 mcg/kg/day
- Recheck TSH every 6-8 weeks after initiation or dose change; once stable, every 6-12 months
2
Older adults or coronary artery disease
- Start low, often 12.5-25 mcg/day, and titrate gradually
- Avoid rapid correction because increased myocardial oxygen demand can precipitate angina, MI, or atrial fibrillation
3
Subclinical hypothyroidism
- Treat if TSH >=10 mIU/L, pregnancy, symptomatic, positive TPO antibodies, goiter, infertility, or high cardiovascular risk
- Observation with repeat TSH is reasonable for mild asymptomatic elevations
4
Pregnancy
- Increase levothyroxine dose as soon as pregnancy is confirmed in known hypothyroidism
- Monitor TSH every 4 weeks in first half of pregnancy and adjust to trimester-specific targets
5
Myxedema coma
- ICU care, passive rewarming, ventilatory and hemodynamic support
- IV levothyroxine plus stress-dose hydrocortisone until adrenal insufficiency is excluded
- Treat precipitant: infection, cold exposure, sedatives, MI, stroke, or medication nonadherence
Complications
- Myxedema coma: Rare but life-threatening decompensated hypothyroidism with hypothermia and altered mental status
- Hyperlipidemia and atherosclerotic risk: LDL may rise with untreated hypothyroidism
- Infertility and pregnancy complications: Miscarriage, preeclampsia, preterm delivery, impaired fetal neurodevelopment
- Pericardial effusion: Usually slowly accumulating and rarely causes tamponade
- Iatrogenic hyperthyroidism: Over-replacement increases atrial fibrillation and osteoporosis risk
USMLE Step 2 CK Exam Tips
- 1Primary hypothyroidism = high TSH, low free T4. Central hypothyroidism = low free T4 with low or normal TSH
- 2Delayed relaxation of ankle reflexes is the classic physical exam clue
- 3Hashimoto: painless goiter + anti-TPO antibodies; may initially have transient hyperthyroidism
- 4Start low-dose levothyroxine in elderly or CAD — do not give full replacement immediately
- 5Myxedema coma: give hydrocortisone before or with thyroid hormone because thyroid hormone can precipitate adrenal crisis
- 6Calcium and iron reduce levothyroxine absorption; separate dosing by several hours
- 7Amiodarone can cause hypo- or hyperthyroidism because of high iodine content and thyroid toxicity
practicetest your knowledge on hypothyroidismApply what you've learnt with USMLE Step 2 CK-style questions from the iatroX Q-Bank — endocrine and beyond.
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