Evaluation in the primary care clinic is requested for a 32-year-old woman who has experie… — USMLE Step 3

Evaluation in the primary care clinic is requested for a $32$ -year-old woman who has experienced palpitations, diaphoresis, and an unintentional $4$ -kg ( $8.8$ -lb) weight loss over the past month. She reports no recent viral illnesses, neck pain, or changes in bowel habits. She has no significant past medical history and takes no prescription medications, though she recently started consuming an over-the-counter "metabolism-boosting" dietary supplement. Her blood pressure is $142/85$ mm Hg, and her pulse is $110$ /min. Physical examination reveals warm, moist skin and a fine bilateral tremor of the outstretched hands. There is no exophthalmos, and her thyroid gland is normal in size and non-tender on palpation.

Laboratory studies show the following:

Laboratory Test	Result	Reference Range
Thyroid-stimulating hormone (TSH)	$<0.01$ $\mu$ U/mL	$0.4-4.0$ $\mu$ U/mL
Free thyroxine (T4)	$3.8$ ng/dL	$0.8-1.8$ ng/dL
Total triiodothyronine (T3)	$240$ ng/dL	$80-200$ ng/dL
Thyroglobulin	$<1$ ng/mL	$3-40$ ng/mL
Thyroid-stimulating immunoglobulins	Negative	Negative

A $24$ -hour radioactive iodine uptake scan demonstrates an uptake of $1$ \% (Ref: $10$ \%- $30$ \%).

Based on the provided data, which of the following is the most likely diagnosis?

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

Answer

Exogenous thyroid hormone ingestion

The correct diagnosis is exogenous thyroid hormone ingestion. The patient has clinical and biochemical thyrotoxicosis (low TSH, high T4/T3). The low radioactive iodine uptake (RAIU) indicates an absence of de novo hormone synthesis in the thyroid gland. The critical distinguishing factor is the nearly undetectable thyroglobulin level. Because thyroglobulin is produced exclusively by thyroid tissue, any endogenous cause of thyrotoxicosis (such as follicular destruction in thyroiditis or ectopic production in struma ovarii) would release thyroglobulin into the bloodstream. A low thyroglobulin level in the setting of thyrotoxicosis and a low RAIU is pathognomonic for an exogenous source of thyroid hormone, which in this case is likely hidden in the patient's 'metabolism-boosting' supplement.

Step-by-Step Solution

Interpret the basic thyroid panel (TSH, free T4, total T3).

The patient has a suppressed TSH and elevated T4/T3.

This confirms a state of primary thyrotoxicosis (hyperthyroidism), necessitating further workup to determine the etiology.

Evaluate the mechanism of thyrotoxicosis using the radioactive iodine uptake (RAIU) scan.

The RAIU is low (1%).

A low uptake indicates that the thyroid gland is suppressed and not actively synthesizing hormone de novo, effectively ruling out Graves disease and toxic nodular disease.

Differentiate the causes of low-uptake thyrotoxicosis by assessing the serum thyroglobulin level.

The thyroglobulin level is profoundly low (<1 ng/mL).

Thyroglobulin is co-secreted with thyroid hormones from endogenous thyroid tissue. Elevated levels suggest endogenous destruction (thyroiditis) or ectopic production (struma ovarii). Suppressed levels confirm the hormone is coming from an exogenous source, such as a supplement.

Key Concept

The serum thyroglobulin level is the critical laboratory test used to differentiate exogenous thyroid hormone ingestion (low thyroglobulin) from endogenous destructive thyroiditis or ectopic hormone production (high thyroglobulin) in a patient with thyrotoxicosis and a low radioactive iodine uptake.

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