STEPTRACKERENDOCRINE | PATHOLOGY + IMMUNOLOGY + PHARMACOLOGY | HIGH-YIELD REVIEW

Hyperthyroidism

Too much thyroid hormone — from a stimulating antibody, autonomous nodules, leaking follicles or a pill bottle — and how to tell which.

FOCUS ON
Graves: TSH-receptor stimulating IgG (type II), diffuse goiter, ophthalmopathy and pretibial myxedema, diffuse ↑ uptake. Toxic multinodular goiter: older, patchy uptake. Toxic adenoma: one hot nodule. Low uptake = thyroiditis, exogenous hormone (↓ thyroglobulin), iodine load. Thyroid storm: β-blocker + PTU + steroids.
DISORDER · TOPIC
MECHANISM
FEATURES
CLUE · TREATMENT
Thyrotoxicosis — features
↑ T3 → ↑ Na⁺/K⁺-ATPase, BMR, β-adrenergic receptor number
Heat intolerance, weight loss with ↑ appetite, tremor, tachycardia, atrial fibrillation, diarrhea, anxiety, lid lag, proximal myopathy, osteoporosis
↓ TSH, ↑ free T4/T3 (primary)
Graves disease
most common cause
Thyroid-stimulating immunoglobulin (IgG) binds and activates the TSH receptor — type II hypersensitivity
Women 20–40; diffuse goiter with bruit; tall columnar cells, scalloped colloid
Diffuse ↑ radioiodine uptake · HLA-DR3, B8
Graves ophthalmopathy & dermopathy
T cells + TSI activate orbital and pretibial fibroblasts → glycosaminoglycans, fat, edema
Exophthalmos, periorbital edema, diplopia; pretibial myxedema; thyroid acropachy
Only in Graves · worsened by radioiodine, smoking
Toxic multinodular goiter
Autonomous nodules (activating TSH receptor mutations)
Older adults; nodular goiter; patchy uptake (hot nodules, cold background)
Iodine load can trigger (Jod-Basedow)
Toxic adenoma
Single autonomous follicular adenoma
One hot nodule, suppressed remainder
Rarely malignant · radioiodine or surgery
Thyroiditis (destructive)
Follicles damaged → stored hormone leaks out
Transient thyrotoxicosis with low uptake (subacute, painless, postpartum)
β-blockers only; antithyroid drugs useless
Exogenous (factitious) thyrotoxicosis
Taking thyroid hormone
Low uptake, small gland, ↓ thyroglobulin
Weight-loss attempts, health workers
Other causes
TSH-secreting adenoma (↑ TSH), hCG (molar pregnancy), struma ovarii, amiodarone, iodinated contrast
Struma ovarii: low neck uptake, pelvic uptake
↑ TSH + ↑ T4 = central cause
Thyroid storm
Stress (surgery, infection, childbirth, iodine) in uncontrolled hyperthyroidism
High fever, tachyarrhythmia, agitation, delirium, vomiting, diarrhea, heart failure
Propranolol + PTU + steroids, then iodine
Thionamides
Block thyroid peroxidase (organification, coupling); PTU also blocks peripheral 5′-deiodinase
Methimazole first-line (teratogen in 1st trimester); PTU in 1st trimester and storm
Both: agranulocytosis · PTU: liver failure
Thyrotoxic periodic paralysis
T3 ↑ Na⁺/K⁺-ATPase → K⁺ shifts into cells
Sudden weakness with hypokalemia, often after carbohydrate meal; Asian men
β-blocker, potassium

Mechanism — Graves disease

AutoimmunityHLA-DR3, smoking, stress
→
TSI (IgG)Stimulates TSH receptor
→
ThyroidHyperplasia, ↑ T4/T3
Orbit + skinFibroblast GAGs → exophthalmos, myxedema

TSI crosses the placenta → transient neonatal hyperthyroidism.

Radioiodine uptake

PATTERN
CAUSE
CLUE
Diffuse ↑
Graves
Eye disease, TSI
Patchy ↑
Toxic multinodular goiter
Older, nodules
Single hot nodule
Toxic adenoma
Rest suppressed
↓ with ↑ thyroglobulin
Thyroiditis, iodine load
Tender (subacute) or painless
↓ with ↓ thyroglobulin
Exogenous hormone
Factitious

How it's tested

COMMON CONFUSIONAny hyperthyroid patient can have lid lag and stare (sympathetic). True exophthalmos, pretibial myxedema and acropachy happen only in Graves.
THE TRAPAntithyroid drugs don't help thyroiditis — the gland isn't making new hormone, it's leaking stored hormone. Use a β-blocker and wait.
YOUR APPROACHTSH and free T4 → uptake scan → thyroglobulin if low uptake → specific features (eyes, nodules, pain, postpartum) → treatment and drug safety (pregnancy, agranulocytosis).

If you see… think…

Young woman with exophthalmos, diffuse goiter, ↓ TSH → Graves disease
Antibody in Graves → TSH-receptor stimulating IgG (type II)
Thickened orange-peel skin on the shins → pretibial myxedema
Older man with nodular goiter and patchy uptake → toxic multinodular goiter
Hyperthyroid nurse with low uptake and low thyroglobulin → factitious thyrotoxicosis
Fever, AF, delirium after surgery in a hyperthyroid patient → thyroid storm
Antithyroid drug in the first trimester → PTU
Sore throat and fever on methimazole → agranulocytosis — check ANC
Hyperthyroidism with ↑ TSH → TSH-secreting pituitary adenoma
Sudden paralysis with K⁺ 2.1 in a hyperthyroid man → thyrotoxic periodic paralysis