A 42-year-old man comes to the clinic reporting a 4-month history of worsening fatigue, ge… — USMLE Step 2 CK

A 42-year-old man comes to the clinic reporting a 4-month history of worsening fatigue, generalized weakness, and cold intolerance. The patient has gained $6$ kg ( $13.2$ lb) during this time despite no changes in his diet. He also mentions decreased libido. His past medical history is significant for a severe traumatic brain injury following a motorcycle collision 3 years ago, which required a 4-week stay in the intensive care unit. His only current medication is ibuprofen as needed for occasional headaches. Vital signs show a blood pressure of $110/70$ mm Hg and a pulse of $54$ /min. Physical examination reveals pale, dry skin, sparse axillary hair, and delayed relaxation of the deep tendon reflexes. Laboratory evaluation shows:

Test	Result	Reference Range
Thyroid-stimulating hormone (TSH)	$1.8$ $\mu U/mL$	$0.4-4.0$ $\mu U/mL$
Free thyroxine (T4)	$0.5$ $ng/dL$	$0.9-1.7$ $ng/dL$

Which of the following is the most likely underlying mechanism for this patient's current condition?

A
Autoimmune destruction of thyroid follicles
B
Impaired peripheral conversion of thyroxine to triiodothyronine
Inadequate pituitary secretion of thyrotropinAnswer
D
Decreased tissue responsiveness to thyroid hormone
E
Antibody-mediated stimulation of thyrotropin receptors

Answer

Inadequate pituitary secretion of thyrotropin

This patient has classic symptoms of hypothyroidism (fatigue, weight gain, cold intolerance, bradycardia, delayed reflexes). Laboratory testing confirms a low free T4 level. However, the thyroid-stimulating hormone (TSH) level is inappropriately normal. In primary hypothyroidism (due to primary thyroid failure), the low free T4 removes negative feedback on the pituitary, resulting in a markedly elevated TSH. The presence of a low free T4 with a normal (or low) TSH indicates central (secondary) hypothyroidism, representing inadequate pituitary secretion of thyrotropin. The patient's history of severe traumatic brain injury is a classic risk factor for hypopituitarism, which can manifest months or years after the initial insult.

Step-by-Step Solution

Analyze the clinical presentation.

The patient presents with classic symptoms of hypothyroidism, including fatigue, weight gain, cold intolerance, bradycardia, and delayed deep tendon reflexes. The history of traumatic brain injury raises suspicion for hypopituitarism.

Identifying the clinical syndrome guides the interpretation of the laboratory data.

Interpret the thyroid function tests.

The free T4 level is low (

0.5

ng/dL

), confirming clinical hypothyroidism. The TSH level is within the normal range (

1.8

\mu U/mL

Confirming the diagnosis and localizing the source of the defect.

Synthesize the findings to determine the etiology.

In the setting of low free T4, a normal TSH is inappropriate and indicates a failure of the pituitary gland to mount a compensatory response. This points to central (secondary) hypothyroidism, likely caused by prior traumatic brain injury.

Primary hypothyroidism would feature an elevated TSH. The combination of low T4 and non-elevated TSH confirms central hypothyroidism.

Key Concept

Central (secondary) hypothyroidism is characterized by a low free T4 and an inappropriately normal or low TSH. Traumatic brain injury is a recognized cause of pituitary dysfunction.

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