Graves vs Hashimoto. Hot vs cold. The axis that boards love to test and students love to mix up.
Before we start — can you get this?
A 35-year-old woman presents with weight loss, tremor, heat intolerance, and a diffuse non-tender goiter. TSH is 0.01 mIU/L. Free T4 is elevated. What confirms the diagnosis?
Good instinct if you picked RAIU — that characterizes hyperthyroidism (diffuse uptake = Graves, patchy = toxic multinodular). But the question asked what confirms the diagnosis.
TSH receptor antibodies (TRAb) are pathognomonic for Graves disease. They're autoantibodies that stimulate the TSH receptor — telling the thyroid to keep making hormones even though TSH is already bottomed out. No other condition produces them.
RAIU is the next step if TRAb is negative and you need to distinguish Graves from other causes of hyperthyroidism.
The HPT Axis — One Rule to Rule Them All
TSH and T3/T4 move in opposite directions. Always. That's the whole trick.
Hypothalamus
→ TRH →
Anterior Pituitary
→ TSH →
Thyroid
T4 (mostly) + T3
→ ⊖ negative feedback →
Pituitary shuts off TSH
The Board Rule: TSH is the screening test. It moves first and moves opposite to thyroid hormones. If the thyroid is making too much → pituitary slams the brakes → TSH ↓. If the thyroid is failing → pituitary screams louder → TSH ↑.
Condition
TSH
Free T4
Free T3
Why
Primary Hyperthyroid
↓↓
↑
↑
Thyroid overproducing → feedback suppresses TSH
Primary Hypothyroid
↑↑
↓
↓
Thyroid failing → pituitary compensates with more TSH
Subclinical Hyper
↓
Normal
Normal
TSH drops first — T4 hasn't risen enough to measure yet
Subclinical Hypo
↑
Normal
Normal
TSH rises first — thyroid still compensating, barely
Central Hypothyroid
↓ or Normal
↓
↓
Pituitary broken → can't make TSH → thyroid starves
The Trap: Central hypothyroidism has low TSH with low T4. The numbers move together instead of opposite. That's the giveaway — when feedback is broken, the pattern flips. Boards test this because students automatically associate low TSH with hyperthyroidism.
Hyper vs Hypo — The Mirror Image
Everything is opposite. Metabolism up vs down. Heat vs cold. Weight loss vs gain. Tap to compare.
Everything is revved up. The body is burning fuel faster than it can replace it.
Metabolism
Weight loss despite increased appetite. BMR through the roof.
Temperature
Heat intolerance. Sweaty, flushed, prefers cold.
Heart
Tachycardia, palpitations, AFib in elderly. Widened pulse pressure.
Neuro
Fine tremor, hyperreflexia, anxiety, insomnia. Wired and jittery.
GI
Hyperdefecation (frequent loose stools, not true diarrhea).
Skin/Hair
Warm, moist skin. Fine hair. OnycholysisNail separation from nail bed. Excess thyroid hormone disrupts keratin — the same protein in nails and hair..
Repro
Oligomenorrhea (light/infrequent periods). Can cause infertility.
Eyes
Lid lag, stare (all hyperthyroid). Exophthalmos = Graves only.
Everything is slowed down. The body is conserving fuel it doesn't have.
Metabolism
Weight gain despite decreased appetite. BMR crashes.
Temperature
Cold intolerance. Always bundled up. Hypothermia in severe cases.
Constipation. Everything is slower, including the gut.
Skin/Hair
Cool, dry, rough skin. Coarse hair. MyxedemaMucopolysaccharides (glycosaminoglycans) accumulate in the dermis → non-pitting edema. "Myxedema" literally means "mucous swelling." It's the hallmark of severe hypothyroidism. — non-pitting edema.
Repro
Menorrhagia (heavy periods). Can cause infertility and miscarriage.
Both autoimmune. Both involve thyroid antibodies. But the antibodies do opposite things.
The Core Distinction: Graves has stimulating antibodies (TRAb/TSI) that activate the TSH receptor → hyperthyroidism. Hashimoto has destructive antibodies (anti-TPO, anti-thyroglobulin) that destroy thyroid tissue → hypothyroidism.
Middle-age women (40-60). Most common cause of hypothyroidism (in iodine-sufficient areas).
Treatment
Levothyroxine (T4 replacement). Lifelong. Monitor TSH every 6-8 weeks initially.
Trick: Hashimoto can cause a BRIEF hyperthyroid phase early on (hashitoxicosis) as thyroid cells die and dump stored hormone. Boards love this. The giveaway: it's transient, and TRAb is negative.
Decision Tree — What's Causing the Thyroid Dysfunction?
TSH is abnormal. Now what? Walk through it.
Step 1: What's the TSH?
You got labs back. The TSH is abnormal. Which direction?
Step 2: TSH is low → Check Free T4
Low TSH means the pituitary is being suppressed. But is it primary hyperthyroidism or central hypothyroidism? Free T4 tells you.
Step 3: Confirmed Hyperthyroid → What's the RAIU?
Radioactive iodine uptake tells you WHERE the excess hormone is coming from. Is the thyroid making too much, or is stored hormone leaking out?
Step 4: Low RAIU — Why Isn't the Gland Picking Up Iodine?
The thyroid is NOT actively making hormone, but thyroid hormone levels are high. Something is releasing pre-made hormone or the patient is getting it from outside.
Step 2: TSH is high → Check Free T4
High TSH means the pituitary is screaming for more thyroid hormone. Is the thyroid responding?
Step 3: Primary Hypothyroidism — What's the Cause?
The thyroid is failing. Why?
The Emergencies — Thyroid Storm vs Myxedema Coma
One is the thyroid at maximum overdrive. The other is the thyroid at complete shutdown. Both kill.
Thyroid Storm
Trigger
Surgery, infection, trauma in uncontrolled hyperthyroid patient
Vitals
Fever > 104°F, tachycardia > 140, hypertension
Neuro
Agitation → delirium → seizures → coma
Cardiac
AFib, high-output heart failure
GI
Nausea, vomiting, diarrhea, jaundice (ominous)
Treatment Order
PTU first (blocks synthesis AND T4→T3 conversion), then iodine 1 hour later (blocks release — Wolff-Chaikoff). Beta-blockers. Steroids. Cooling blankets.
Board Trap
PTU before iodine. If you give iodine first, the thyroid uses it to make MORE hormone. PTU blocks synthesis first, then iodine blocks release.
Myxedema Coma
Trigger
Infection, cold exposure, sedatives in uncontrolled hypothyroid patient
Vitals
Hypothermia, bradycardia, hypotension
Neuro
Altered mental status → stupor → coma
Cardiac
Pericardial effusion, low voltage EKG
Labs
Hyponatremia (SIADH-like), hypoglycemia, elevated CK
Treatment
IV levothyroxine (T4). Stress-dose steroids (rule out adrenal crisis first — give hydrocortisone BEFORE T4). Passive rewarming.
Board Trap
Steroids before levothyroxine. If the patient has concurrent adrenal insufficiency (Schmidt syndrome), giving T4 first increases cortisol metabolism and can precipitate adrenal crisis.
Memory Hooks
Tap to reveal. Max 2, both high-yield.
🔑"Graves is GREEDY" — the stimulating antibody mnemonic
tap to reveal
Graves is Greedy — the antibodies grab the TSH receptor and won't let go. They keep stimulating it, telling the thyroid to make more, more, more. The thyroid obeys because it can't tell the difference between real TSH and the antibody.
Hashimoto is the opposite — the antibodies hate the thyroid. Hashimoto Hates. Anti-TPO and anti-thyroglobulin destroy thyroid cells. Graves grabs. Hashimoto hates. One builds. One burns.
🔑"PTU Before Iodine" — the thyroid storm treatment order
tap to reveal
Think of it like shutting down a factory. PTU = turn off the machines (stop making new hormone). Iodine = lock the warehouse doors (stop releasing stored hormone). If you lock the doors first without turning off the machines, the factory fills up with product it can't ship — and eventually it bursts through. Always shut down production first.
Wait one hour between PTU and iodine. That's real. Boards will offer "PTU and iodine simultaneously" as a tempting answer.
Drug-Thyroid Interactions — The Board Favorites
Drug
Effect
Why
Amiodarone
Can cause hyper OR hypo
37% iodine by weight. Type 1: excess iodine → excess synthesis (Jod-Basedow). Type 2: direct thyroid destruction → release of stored hormone.
Lithium
Hypothyroid
Blocks thyroid hormone release. Similar to Wolff-Chaikoff effect. Monitor TSH in all lithium patients.
Levothyroxine
Absorption decreased by:
Calcium, iron, PPIs, cholestyramine, soy. Take on empty stomach, 30-60 min before food.
Methimazole
First-line for Graves
Blocks TPO → blocks T4 synthesis. Preferred over PTU except in 1st trimester and thyroid storm.
PTU
Reserved for special cases
Blocks synthesis AND peripheral T4→T3 conversion. Hepatotoxic. Use only in: 1st trimester pregnancy, thyroid storm.
Pregnancy rules: PTU in the first trimester (methimazole is teratogenic — aplasia cutis). Switch to methimazole in 2nd/3rd trimester (PTU hepatotoxicity risk). Boards LOVE this switch.
Clinical Vignettes
Board-style questions. 4 random from a pool of 11.