A 58-year-old man is receiving ipilimumab and nivolumab for metastatic melanoma. Thyroid tests 4 weeks ago were normal (TSH 1.9 mIU/L, free T4 16 pmol/L). He now has severe headache, fatigue and dizziness, and he is an outpatient with no infection. Results: TSH 0.12 mIU/L (reference 0.4-4.0), free T4 7.5 pmol/L (0.58 ng/dL; reference 12-22), 08:00 cortisol 48 nmol/L (1.7 µg/dL; reference 140-690), ACTH 1.0 pmol/L (4.5 pg/mL; reference 1.6-13.9), sodium 129 mmol/L (reference 135-145) and potassium 4.3 mmol/L. What is the best interpretation?

Hypophysitis with central hypothyroidism

Nonthyroidal illness from his cancer

Thyrotoxic phase of a painless thyroiditis

Primary hypothyroidism from thyroiditis

A 46-year-old woman with primary hypothyroidism has taken levothyroxine 125 µg daily for 5 years, with TSH between 1 and 2 mIU/L until last year. Today's clinic results are TSH 15.8 mIU/L (reference 0.4-4.0), free T4 27 pmol/L (2.1 ng/dL; reference 12-22) and free T3 5.9 pmol/L (3.8 pg/mL; reference 3.1-6.8). She has no symptoms. Pharmacy records show she collected tablets for only about half of the past 3 months. After 6 weeks of supervised daily dosing, TSH is 2.0 mIU/L and free T4 17 pmol/L. What best explains the first results?

Erratic intake with recent catch-up doses

Heterophile antibody raising the TSH

Inherited resistance to thyroid hormone

A TSH-secreting pituitary adenoma

A 34-year-old woman with Graves disease has taken carbimazole for 18 months and feels well; her dose has not been reduced in the last year. Before stopping the drug, her endocrinologist asks the laboratory to comment on today's results: TSH 1.3 mIU/L (reference 0.4-4.0), free T4 15 pmol/L (1.2 ng/dL; reference 12-22), free T3 4.9 pmol/L (3.2 pg/mL; reference 3.1-6.8), TSH receptor antibody 12.4 IU/L (positive above 1.75 IU/L; 19.0 IU/L at diagnosis) and TPO antibody 260 IU/mL (positive above 34). What do the results suggest?

High relapse risk if carbimazole is stopped

Remission, because TSH and free T4 are normal

Hashimoto disease, shown by the TPO antibody

Overtreatment that needs a lower dose

In suspected primary hypothyroidism, measuring T3 adds little because:

T3 stays normal until late in the disease

T3 cannot be measured by immunoassay

T3 falls well before the TSH begins to rise

T3 is mostly secreted by the thyroid

Thyroid function testing

26 DOH Abu Dhabi (HAAD) lab licensing practice questions on Thyroid function testing, part of Clinical Chemistry. The first 25 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

Question 1 · Hard
A 58-year-old man is receiving ipilimumab and nivolumab for metastatic melanoma. Thyroid tests 4 weeks ago were normal (TSH 1.9 mIU/L, free T4 16 pmol/L). He now has severe headache, fatigue and dizziness, and he is an outpatient with no infection. Results: TSH 0.12 mIU/L (reference 0.4-4.0), free T4 7.5 pmol/L (0.58 ng/dL; reference 12-22), 08:00 cortisol 48 nmol/L (1.7 µg/dL; reference 140-690), ACTH 1.0 pmol/L (4.5 pg/mL; reference 1.6-13.9), sodium 129 mmol/L (reference 135-145) and potassium 4.3 mmol/L. What is the best interpretation?
1. ANonthyroidal illness from his cancer
2. BThyrotoxic phase of a painless thyroiditis
3. CPrimary hypothyroidism from thyroiditis
4. DHypophysitis with central hypothyroidism
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Answer: D · Hypophysitis with central hypothyroidism
A low free T4 with a low, not raised, TSH means the pituitary is failing to drive the thyroid, which is central hypothyroidism. The low cortisol with an inappropriately low ACTH shows corticotroph failure as well, and the headache fits pituitary inflammation; ipilimumab, an anti-CTLA-4 antibody, is a well-known cause of hypophysitis. Thyroiditis from checkpoint inhibitors gives either a high free T4 in its thyrotoxic phase or a high TSH in its hypothyroid phase, and his tests were normal 4 weeks ago. Nonthyroidal illness does not explain ACTH deficiency in a well outpatient. Glucocorticoid replacement must start before levothyroxine, because thyroxine alone can precipitate an adrenal crisis.
- A: He is not acutely ill, and nonthyroidal illness does not explain the low ACTH and cortisol.
- B: A thyrotoxic phase gives a high free T4, not a low one.
- C: Primary hypothyroidism raises TSH; here TSH is low.
Question 2 · Hard
A 46-year-old woman with primary hypothyroidism has taken levothyroxine 125 µg daily for 5 years, with TSH between 1 and 2 mIU/L until last year. Today's clinic results are TSH 15.8 mIU/L (reference 0.4-4.0), free T4 27 pmol/L (2.1 ng/dL; reference 12-22) and free T3 5.9 pmol/L (3.8 pg/mL; reference 3.1-6.8). She has no symptoms. Pharmacy records show she collected tablets for only about half of the past 3 months. After 6 weeks of supervised daily dosing, TSH is 2.0 mIU/L and free T4 17 pmol/L. What best explains the first results?
1. AHeterophile antibody raising the TSH
2. BInherited resistance to thyroid hormone
3. CErratic intake with recent catch-up doses
4. DA TSH-secreting pituitary adenoma
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Answer: C · Erratic intake with recent catch-up doses
TSH reflects thyroid hormone exposure over the previous several weeks, whereas free T4 rises within hours to days of taking tablets. A high TSH together with a high free T4 in a patient on levothyroxine therefore fits weeks of missed doses followed by several tablets taken in the days before the test. The incomplete pharmacy collection and the return to normal on supervised daily dosing confirm it. A TSH-secreting adenoma, resistance to thyroid hormone and assay interference would all persist on regular dosing and would not fit years of normal results on the same dose.
- A: An interfering antibody would not disappear once dosing became regular.
- B: Inherited resistance is lifelong and does not fit years of normal results on the same dose.
- D: An adenoma would not resolve after six weeks of supervised dosing.
Question 3 · Hard
A 34-year-old woman with Graves disease has taken carbimazole for 18 months and feels well; her dose has not been reduced in the last year. Before stopping the drug, her endocrinologist asks the laboratory to comment on today's results: TSH 1.3 mIU/L (reference 0.4-4.0), free T4 15 pmol/L (1.2 ng/dL; reference 12-22), free T3 4.9 pmol/L (3.2 pg/mL; reference 3.1-6.8), TSH receptor antibody 12.4 IU/L (positive above 1.75 IU/L; 19.0 IU/L at diagnosis) and TPO antibody 260 IU/mL (positive above 34). What do the results suggest?
1. AHigh relapse risk if carbimazole is stopped
2. BRemission, because TSH and free T4 are normal
3. CHashimoto disease, shown by the TPO antibody
4. DOvertreatment that needs a lower dose
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Answer: A · High relapse risk if carbimazole is stopped
Antithyroid drugs block hormone synthesis but do not remove the stimulating TSH receptor antibodies that cause Graves disease. Normal thyroid tests on carbimazole therefore show good control by the drug, not remission. A TSH receptor antibody still well above the cut-off after 18 months means the autoimmune drive persists, and relapse is likely soon after the drug is stopped, so treatment is often continued or definitive therapy considered. TPO antibodies are found in most patients with Graves disease and do not mean a second disorder. A falling but persistent TSH receptor antibody also matters in pregnancy, because it crosses the placenta.
- B: Normal results on carbimazole show control by the drug, not loss of the antibody.
- C: TPO antibodies are common in Graves disease and do not mean a new disorder.
- D: TSH and free T4 are both within range, so the dose is not too high.
Question 4 · Medium
In suspected primary hypothyroidism, measuring T3 adds little because:
1. AT3 cannot be measured by immunoassay
2. BT3 stays normal until late in the disease
3. CT3 falls well before the TSH begins to rise
4. DT3 is mostly secreted by the thyroid
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Answer: B · T3 stays normal until late in the disease
As the thyroid fails, the rising TSH drives the remaining tissue to favor T3 secretion, and deiodinase activity increases the conversion of T4 to T3 in tissues. Serum T3 therefore stays normal in many patients even when free T4 is already low. TSH and free T4 are the tests for diagnosing hypothyroidism and monitoring levothyroxine. T3 is more useful in hyperthyroidism, where it can be the only raised hormone.
- A: Total and free T3 are measured routinely by immunoassay.
- C: TSH rises first; T3 is usually the last value to fall.
- D: About 80% of circulating T3 comes from peripheral conversion of T4.
Question 5 · Easy
A third-generation TSH assay has a functional sensitivity of about:
1. A0.01 to 0.02 mIU/L
2. B0.001 to 0.002 mIU/L
3. C0.1 to 0.2 mIU/L
4. D0.4 to 4.0 mIU/L
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Answer: A · 0.01 to 0.02 mIU/L
Functional sensitivity is the lowest concentration an assay measures with a between-run CV of 20% or less. Each TSH assay generation improved it about tenfold: about 1-2 mIU/L for the first, 0.1-0.2 for the second and 0.01-0.02 mIU/L for the third. Third-generation sensitivity is needed to separate a fully suppressed TSH, as in overt hyperthyroidism, from a low but detectable TSH in subclinical disease or illness. Modern automated TSH immunoassays meet this standard.
- B: 0.001 to 0.002 mIU/L is the range claimed for fourth-generation assays.
- C: 0.1 to 0.2 mIU/L is the functional sensitivity of second-generation assays.
- D: 0.4 to 4.0 mIU/L is a typical adult reference interval, not a detection limit.
Question 6 · Medium
A TSH receptor antibody assay that measures inhibition of labeled TSH binding (TBII):
1. ADetects only receptor-stimulating antibodies
2. BMeasures cAMP production in cultured cells
3. CDetects both stimulating and blocking types
4. DMeasures antibodies to thyroid peroxidase
Answer and explanation in LearnFree account
Question 7 · Medium
Long-term lithium therapy most often produces which thyroid test pattern?
1. ANormal TSH with high total T4
2. BHigh TSH with low or normal free T4
3. CLow TSH with high free T4
4. DLow TSH with low free T4
Answer and explanation in LearnFree account
Question 8 · Medium
A newborn screening dried blood spot collected at 48 hours shows a TSH well above the program's cut-off. What should happen next?
1. ARepeat the dried blood spot at 6 weeks
2. BRecall the baby for serum TSH and free T4
3. CReport it as the expected postnatal TSH surge
4. DTest the mother for TPO antibodies
Answer and explanation in LearnFree account
Question 9 · Hard
Results: TSH < 0.01 mIU/L (reference 0.4-4.0), free T4 7 pmol/L (0.5 ng/dL; reference 12-22 pmol/L), free T3 14 pmol/L (9.1 pg/mL; reference 3.1-6.8 pmol/L), thyroglobulin undetectable. Which cause best fits these results?
1. AIngestion of liothyronine (T3)
2. BT3 toxicosis from a toxic nodule
3. CCentral hypothyroidism
4. DNonthyroidal illness
Answer and explanation in LearnFree account
Question 10 · Hard
A woman with primary hypothyroidism had TSH 1.8 mIU/L on levothyroxine before conceiving. At 8 weeks of pregnancy her TSH is 5.4 mIU/L (laboratory first-trimester reference 0.1-3.5) with a low-normal free T4. What best explains the rise?
1. ARising hCG stimulating the thyroid
2. BFalling TBG during pregnancy
3. CGraves disease starting in pregnancy
4. DGreater levothyroxine need in pregnancy
Answer and explanation in LearnFree account
Question 11 · Hard
A man on hemodialysis has thyroid tests drawn just after the heparin bolus at the start of his session. Free T4 is 30 pmol/L (2.3 ng/dL; reference 12-22 pmol/L), TSH 2.1 mIU/L (reference 0.4-4.0), and he has no symptoms. The most likely explanation is:
1. AA TSH-secreting pituitary adenoma
2. BReduced renal clearance of free T4
3. CHeparin-induced fatty acid release
4. DResistance to thyroid hormone
Answer and explanation in LearnFree account
Question 12 · Hard
A 36-year-old woman has a painful, tender thyroid and fever two weeks after a sore throat. Results: TSH < 0.01 mIU/L (reference 0.4-4.0), free T4 41 pmol/L (3.2 ng/dL; reference 12-22 pmol/L), ESR 85 mm/h, thyroglobulin raised, TSH receptor antibodies negative, radioiodine uptake very low. The most likely diagnosis is:
1. ASubacute granulomatous thyroiditis
2. BToxic adenoma
3. CFactitious levothyroxine ingestion
4. DGraves disease
Answer and explanation in LearnFree account
Question 13 · Hard
A newborn has confirmed congenital hypothyroidism: serum TSH 85 mIU/L (reference < 10) and a low free T4, with a normally placed thyroid on ultrasound. The mother takes levothyroxine for atrophic (non-goitrous) autoimmune hypothyroidism, and her TSH receptor binding antibody level is very high. The most likely cause in the baby is:
1. ATransplacental TSH receptor-blocking antibodies
2. BTransplacental thyroid peroxidase antibodies
3. CThyroid dysgenesis (ectopic or absent gland)
4. DAn inherited defect of hormone synthesis
Answer and explanation in LearnFree account
Question 14 · Hard
Results: TSH 3.9 mIU/L (reference 0.4-4.0), free T4 32 pmol/L (2.5 ng/dL; reference 12-22 pmol/L), free T3 9.5 pmol/L (6.2 pg/mL; reference 3.1-6.8 pmol/L). A first-degree relative has the same pattern, pituitary MRI and the alpha subunit are normal, and a second method gives the same results. These findings best fit:
1. ANonthyroidal illness
2. BTSH-secreting pituitary adenoma
3. CGraves disease
4. DResistance to thyroid hormone
Answer and explanation in LearnFree account
Question 15 · Medium
Results in a woman with no symptoms: TSH 0.08 mIU/L (reference 0.4-4.0), free T4 17 pmol/L (1.3 ng/dL; reference 12-22 pmol/L), free T3 5.0 pmol/L (3.3 pg/mL; reference 3.1-6.8 pmol/L). These results are best described as:
1. ACentral hypothyroidism
2. BSubclinical hyperthyroidism
3. COvert hyperthyroidism
4. DT3 thyrotoxicosis
Answer and explanation in LearnFree account
Question 16 · Medium
Compared with a pre-dose sample, blood drawn 2 hours after a patient's usual morning levothyroxine tablet most likely shows:
1. AA suppressed TSH, with free T4 unchanged
2. BA higher free T4, with TSH unchanged
3. CNo change in free T4 or in TSH
4. DA lower free T4 and a higher TSH
Answer and explanation in LearnFree account
Question 17 · Easy
Which plasma protein carries most of the circulating thyroxine (T4)?
1. AThyroxine-binding globulin
2. BTransthyretin
3. CSex hormone-binding globulin
4. DAlbumin
Answer and explanation in LearnFree account
Question 18 · Medium
In central (pituitary) hypothyroidism treated with levothyroxine, which test is used to adjust the dose?
1. ATSH
2. BTotal T3
3. CFree T4
4. DThyroglobulin
Answer and explanation in LearnFree account
Question 19 · Hard
Two weeks after leaving intensive care, where he was treated for pneumonia, a 66-year-old man has TSH 8.4 mIU/L (reference 0.4-4.0), free T4 13 pmol/L (1.0 ng/dL; reference 12-22 pmol/L) and negative TPO antibodies. During the illness his TSH was low-normal. What is the best interpretation?
1. ACentral hypothyroidism; test pituitary function
2. BHashimoto thyroiditis; test thyroglobulin antibodies
3. CNew primary hypothyroidism; start levothyroxine
4. DRecovery from nonthyroidal illness; repeat later
Answer and explanation in LearnFree account
Question 20 · Easy
A woman with a firm, painless goiter and a raised TSH is most likely to have which antibody?
1. AThyroid peroxidase antibodies
2. BParietal cell antibodies
3. CAntimitochondrial antibodies
4. DTSH receptor-stimulating antibodies
Answer and explanation in LearnFree account
Question 21 · Hard
Four months after delivery, a 29-year-old woman has palpitations and a small painless goiter. Results: TSH 0.02 mIU/L (reference 0.4-4.0), free T4 28 pmol/L (2.2 ng/dL; reference 12-22 pmol/L), TPO antibodies strongly positive, TSH receptor antibodies negative. What is the most likely diagnosis?
1. AGestational transient thyrotoxicosis
2. BGraves disease
3. CSubacute granulomatous thyroiditis
4. DPostpartum thyroiditis
Answer and explanation in LearnFree account
Question 22 · Easy
Which technique is a reference method for measuring free T4?
1. AAnalog (one-step) immunoassay
2. BEquilibrium dialysis, then LC-MS/MS
3. CFree T4 index from a T uptake test
4. DTotal T4 corrected for albumin
Answer and explanation in LearnFree account
Question 23 · Medium
In subclinical hypothyroidism (raised TSH, normal free T4 on repeat testing), which additional result most increases the risk of progression to overt hypothyroidism?
1. AFree T3 near the top of its reference range
2. BPositive thyroid peroxidase antibodies
3. CPositive antinuclear antibodies
4. DRaised serum thyroglobulin
Answer and explanation in LearnFree account
Question 24 · Hard
A 52-year-old woman had TSH around 1.5 mIU/L on the same levothyroxine dose for years. Three months ago she started ferrous sulfate and calcium carbonate, which she takes with her levothyroxine at breakfast. TSH is now 9.6 mIU/L (reference 0.4-4.0) and free T4 13 pmol/L (1.0 ng/dL; reference 12-22 pmol/L). The most likely cause is:
1. AProgression of autoimmune thyroiditis
2. BReduced absorption of levothyroxine
3. CA new TSH-secreting pituitary adenoma
4. DIron interference in the TSH assay
Answer and explanation in LearnFree account
Question 25 · Medium
Refer to the reflex thyroid testing algorithm shown. The test that belongs in the dashed box is:
Figure: MedExams
1. AFree T3
2. BThyroglobulin
3. CAnti-TPO antibody
4. DTSH receptor antibody
Answer and explanation in LearnFree account

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Study Clinical Chemistry

Thyroid function testing

In suspected primary hypothyroidism, measuring T3 adds little because:

A third-generation TSH assay has a functional sensitivity of about:

A TSH receptor antibody assay that measures inhibition of labeled TSH binding (TBII):

Long-term lithium therapy most often produces which thyroid test pattern?

A newborn screening dried blood spot collected at 48 hours shows a TSH well above the program's cut-off. What should happen next?

Results: TSH < 0.01 mIU/L (reference 0.4-4.0), free T4 7 pmol/L (0.5 ng/dL; reference 12-22 pmol/L), free T3 14 pmol/L (9.1 pg/mL; reference 3.1-6.8 pmol/L), thyroglobulin undetectable. Which cause best fits these results?

A woman with primary hypothyroidism had TSH 1.8 mIU/L on levothyroxine before conceiving. At 8 weeks of pregnancy her TSH is 5.4 mIU/L (laboratory first-trimester reference 0.1-3.5) with a low-normal free T4. What best explains the rise?

A man on hemodialysis has thyroid tests drawn just after the heparin bolus at the start of his session. Free T4 is 30 pmol/L (2.3 ng/dL; reference 12-22 pmol/L), TSH 2.1 mIU/L (reference 0.4-4.0), and he has no symptoms. The most likely explanation is:

Results in a woman with no symptoms: TSH 0.08 mIU/L (reference 0.4-4.0), free T4 17 pmol/L (1.3 ng/dL; reference 12-22 pmol/L), free T3 5.0 pmol/L (3.3 pg/mL; reference 3.1-6.8 pmol/L). These results are best described as:

Compared with a pre-dose sample, blood drawn 2 hours after a patient's usual morning levothyroxine tablet most likely shows:

Which plasma protein carries most of the circulating thyroxine (T4)?

In central (pituitary) hypothyroidism treated with levothyroxine, which test is used to adjust the dose?

Two weeks after leaving intensive care, where he was treated for pneumonia, a 66-year-old man has TSH 8.4 mIU/L (reference 0.4-4.0), free T4 13 pmol/L (1.0 ng/dL; reference 12-22 pmol/L) and negative TPO antibodies. During the illness his TSH was low-normal. What is the best interpretation?

A woman with a firm, painless goiter and a raised TSH is most likely to have which antibody?

Four months after delivery, a 29-year-old woman has palpitations and a small painless goiter. Results: TSH 0.02 mIU/L (reference 0.4-4.0), free T4 28 pmol/L (2.2 ng/dL; reference 12-22 pmol/L), TPO antibodies strongly positive, TSH receptor antibodies negative. What is the most likely diagnosis?

Which technique is a reference method for measuring free T4?

In subclinical hypothyroidism (raised TSH, normal free T4 on repeat testing), which additional result most increases the risk of progression to overt hypothyroidism?

Refer to the reflex thyroid testing algorithm shown. The test that belongs in the dashed box is: