A 28-year-old female medical resident presents to the clinic with a 4-week history of diar… — USMLE Step 3

A 28-year-old female medical resident presents to the clinic with a 4-week history of diarrhea, palpitations, heat intolerance, and a $4$ -kg ( $8.8$ -lb) weight loss. She states she has been under immense stress during her current intensive care unit rotation and admits to taking an over-the-counter "energy and metabolism booster" to help her stay awake. Her temperature is $37.2^\circ\text{C}$ ( $99.0^\circ\text{F}$ ), blood pressure is $135/85$ mmHg, and pulse is $112$ /min. Physical examination reveals a fine tremor in her outstretched hands, warm and moist skin, and brisk deep tendon reflexes. The thyroid gland is nonpalpable and non-tender. There is no proptosis or pretibial myxedema.

Laboratory studies are obtained:

Test	Result	Reference Range
Thyroid-stimulating hormone (TSH)	$0.02$ $\mu$ U/mL	$0.4 - 4.0$ $\mu$ U/mL
Free thyroxine (T4)	$2.8$ ng/dL	$0.9 - 1.7$ ng/dL
Serum thyroglobulin	Undetectable	$3 - 40$ ng/mL

A 24-hour radioactive iodine uptake (RAIU) scan demonstrates a $1\%$ uptake (reference range: $10\% - 30\%$ ).

Which of the following is the most likely diagnosis?

Exogenous thyroid hormone ingestionAnswer
B
Graves disease
C
Subacute granulomatous thyroiditis
D
Painless (silent) thyroiditis
E
Struma ovarii

Answer

Exogenous thyroid hormone ingestion

The patient presents with symptomatic thyrotoxicosis, confirmed by a suppressed TSH and elevated free T4. The initial step in formulating a differential diagnosis for thyrotoxicosis without obvious goiter or classic physical exam findings (such as exophthalmos) is a radioactive iodine uptake (RAIU) scan. A low RAIU (typically

<5\%

) indicates that the thyroid gland is not actively synthesizing new hormone, ruling out conditions like Graves disease or toxic multinodular goiter. The differential for thyrotoxicosis with a low RAIU includes thyroiditis (release of preformed hormone), ectopic production, and exogenous thyroid hormone ingestion. Serum thyroglobulin, a glycoprotein produced only by endogenous thyroid tissue, serves as the final distinguishing marker. It is elevated during active synthesis or follicular destruction but is suppressed when exogenous hormone causes negative feedback on the hypothalamic-pituitary-thyroid axis. The undetectable thyroglobulin confirms the diagnosis of exogenous thyroid hormone ingestion (factitious thyrotoxicosis), which is likely hidden in the patient's 'energy booster' supplement.

Step-by-Step Solution

Evaluate the initial thyroid function tests.

The patient has a low TSH and high Free T4.

This confirms the presence of primary thyrotoxicosis and prompts further evaluation to determine the underlying etiology.

Interpret the radioactive iodine uptake (RAIU) scan.

The uptake is diffusely decreased at 1%.

A low RAIU differentiates thyrotoxicosis caused by active hormone overproduction (which would have high uptake) from preformed hormone release, ectopic production, or exogenous intake.

Assess the serum thyroglobulin level in the context of a low RAIU.

The thyroglobulin is undetectable.

Thyroglobulin distinguishes between endogenous thyroid tissue destruction/ectopic production (high thyroglobulin) and exogenous thyroid hormone administration (low/undetectable thyroglobulin).

Key Concept

Differentiating etiologies of thyrotoxicosis using radioactive iodine uptake and serum thyroglobulin levels.

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