Hyperthyroid on the exam: Graves, a hot nodule, thyroiditis or a pill bottle?

The labs look the same in every case: TSH low, free T4 or T3 high. The patient is irritable, tremulous and losing weight despite a good appetite. What decides the answer is the cause, because the treatments don't overlap. Methimazole helps Graves disease and does nothing for thyroiditis.

Before the cause: confirm it and treat the symptoms

TSH is the first test. If it's low, check free T4 and T3; early in hyperthyroidism only one of them may be high. A low TSH on its own isn't enough. In a very sick patient, TSH, free T4 and T3 can all be low (sick euthyroid syndrome), and that isn't hyperthyroidism. Once hyperthyroidism is confirmed, start a beta-blocker for the tremor and palpitations before ordering anything else.

Older patients often don't look hyperthyroid at all. They may have no eye signs and no nervousness, only atrial fibrillation, heart failure or muscle weakness ("apathetic" hyperthyroidism).

Then one question: is the gland making hormone, or leaking it?

Radioactive iodine uptake (RAIU) measures how much iodine the thyroid takes up to make new hormone. High uptake means the gland is overproducing. Low uptake means hormone is leaking out of an inflamed gland, or coming from somewhere other than the thyroid.

The seven at a glance

Cause	Thyroid on exam	RAIU	Clues that decide it	Next step in management
Graves disease	Diffusely enlarged, not tender	High, diffuse	Proptosis and pretibial myxedema (only Graves causes these); TSH-receptor antibodies	Beta-blocker, then methimazole; radioactive iodine or surgery are alternatives
Toxic multinodular goiter	Several nodules, usually an older patient	High, in several patches	Can be triggered by an iodine load, such as CT contrast or angiography, weeks to months earlier	Radioactive iodine or surgery
Toxic adenoma	A single nodule	One hot nodule, the rest of the gland suppressed	Hot nodules are almost always benign	Radioactive iodine or surgery
Subacute (de Quervain) thyroiditis	Painful and tender	Low	After an upper respiratory infection; fever; high ESR or CRP; no thyroid antibodies	Beta-blocker plus aspirin or NSAIDs; steroids if pain persists
Painless (silent) or postpartum thyroiditis	Not tender; may be mildly enlarged	Low	Anti-TPO antibodies; normal ESR; within a year of delivery for the postpartum form	Beta-blocker; watch for a hypothyroid phase afterward
Surreptitious thyroxine	Small, not tender	Low	Low serum thyroglobulin; weight-loss supplements or access to levothyroxine	Stop the hormone
Struma ovarii	Normal	Low in the neck	Normal or high thyroglobulin with a normal thyroid; an ovarian (dermoid) mass	Surgery for the ovarian tumor

The distinctions that decide the question

Graves or thyroiditis?

What separates these cases: uptake. Graves disease has high, diffuse uptake; thyroiditis has low uptake. Lid lag and lid retraction happen in any hyperthyroidism, but proptosis and pretibial myxedema point only to Graves.

Subacute or painless thyroiditis?

What separates these cases: pain. Subacute granulomatous thyroiditis is tender, follows a viral illness, raises the ESR and has no antibodies. Painless and postpartum thyroiditis aren't tender, the ESR is normal, and anti-TPO antibodies are positive. A memory hook: "I SAT on a giant painful granuloma" (SAT for subacute thyroiditis).

Thyroiditis, a hidden pill bottle, or struma ovarii?

All three have low uptake in the neck. Thyroglobulin separates them. What C-peptide is to insulin, thyroglobulin is to thyroid hormone: it rises when the body makes the hormone and stays low when the hormone comes from a pill.

What separates these cases: thyroglobulin is low with surreptitious thyroxine. It's normal or high in thyroiditis (with a tender gland or antibodies) and in struma ovarii (with a normal thyroid exam).

Toxic adenoma or toxic multinodular goiter?

What separates these cases: the scan pattern. One hot nodule with the rest of the gland suppressed is an adenoma; several hot areas mean a multinodular goiter.

What if the TSH is high too?

High TSH with high free T4 and T3 is central hyperthyroidism. A TSH-secreting pituitary adenoma comes with a pituitary mass, bitemporal hemianopsia and a high α-subunit to TSH ratio. Inherited resistance to thyroid hormone looks similar on the labs but has no mass.

Treatment traps

• Thyroiditis: the hormone is already made, so methimazole and radioactive iodine don't help. Give a beta-blocker while it settles.
• Pregnancy: radioactive iodine scans and treatment are contraindicated. Use a thyroid ultrasound and TSH-receptor antibodies instead. Treat with propylthiouracil in the first trimester and methimazole after it.
• After Graves surgery or radioactive iodine: TSH-receptor antibodies can persist. A mother who is euthyroid on levothyroxine can still have a baby with neonatal Graves disease.
• Side effects that come up on the exam: radioactive iodine can worsen eye disease, so severe ophthalmopathy is a contraindication. Thioamides can cause agranulocytosis, so a fever means stop the drug and check a blood count. Surgery can injure the recurrent laryngeal nerve (hoarseness) or the parathyroids (hypocalcemia).

Try these cases from the Pradis question bank

Each case below is adapted from a question in the Pradis Endocrinology chapter. Decide before you read the answer.

1. A 45-year-old woman has had months of irritability and insomnia. She has lid lag, lid retraction and a diffusely enlarged, non-tender thyroid. TSH is 0.1 and T3 is high.
Answer: Graves disease. The chronic course and the diffuse, non-tender goiter point to it; if the symptoms were acute, subacute thyroiditis would also be possible.

2. A 68-year-old man with a known multinodular goiter has coronary angiography and bypass surgery. A month later he returns with atrial fibrillation and a rapid ventricular rate. TSH is very low and T4 and T3 are high.
Answer: iodine-induced hyperthyroidism (Jod-Basedow). The contrast load switched on his autonomous nodules, and the onset can be delayed by weeks to months.

3. Four weeks after delivery, a 35-year-old woman has a week of irritability, a big appetite and weight loss. Her thyroid is mildly enlarged and not tender, and anti-thyroid peroxidase antibodies are high.
Answer: postpartum (silent) thyroiditis, in its thyrotoxic phase. Hashimoto thyroiditis rarely has one, and struma ovarii would leave the thyroid exam normal.

4. A 45-year-old man has had a painful thyroid for a few days, with a temperature of 101.4 °F and a heart rate of 110. Two weeks ago he had a cold. His thyroid is diffusely tender and enlarged.
Answer: subacute granulomatous (de Quervain) thyroiditis. Check the ESR or CRP, and treat with a beta-blocker and aspirin or an NSAID. Suppurative thyroiditis would have a higher fever and usually no thyroid hormone changes.

5. A 45-year-old woman with hyperthyroid symptoms takes an over-the-counter weight-loss product. Her thyroid is small, and the uptake scan shows diffusely low uptake. Which lab result do you expect?
Answer: low serum thyroglobulin. The pill suppresses her own thyroid, so the gland stops making thyroglobulin.

6. A 65-year-old woman has hyperthyroid symptoms, a non-tender goiter and diffusely increased uptake, but her TSH is high, and she has bitemporal hemianopsia.
Answer: a TSH-secreting pituitary adenoma. Expect a high α-subunit to TSH ratio, and image the pituitary.

7. A 65-year-old man is treated for pneumonia, and on day 3 he develops atrial fibrillation with a rapid rate. TSH is 0.2, and free T4 and T3 are both low.
Answer: sick euthyroid syndrome, not hyperthyroidism. Hyperthyroidism would pair the low TSH with a high free T4 or T3. Don't start any thyroid drug; recheck the tests about 4 to 6 weeks after he recovers.

How to study these

Sort the seven by uptake first, then by one clue each: eye signs for Graves, the scan pattern for nodules, pain for subacute thyroiditis, antibodies and the calendar for postpartum thyroiditis, and thyroglobulin for the pill bottle and the ovary. If you can say that line for each row, you can answer the question.

In Pradis, each row of a table like this is its own question with its own stars, so the pair you confuse keeps coming back until it doesn't. The Biostatistics chapter is free once you log in.

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Written for USMLE Step 2 CK and shelf exam preparation. In patient care, follow current guidelines and your institution's protocols.