A 29-year-old man is evaluated in the outpatient office due to a one-year history of worse… — USMLE Step 2 CK

A 29-year-old man is evaluated in the outpatient office due to a one-year history of worsening sluggishness, weight gain, and diminished libido. He reports feeling constantly cold even when others are comfortable. His medical history is notable for a severe closed head injury sustained in a motorcycle collision three years ago, which required a two-week stay in the intensive care unit. He currently takes no medications. Vital signs show a temperature of $36.1^\circ\text{C}$ ( $97.0^\circ\text{F}$ ), blood pressure of $105/65 \text{ mm Hg}$ , and heart rate of $56/\text{min}$ . Physical examination reveals dry skin and a delayed relaxation phase of the deep tendon reflexes. Testes are soft and measure $12 \text{ mL}$ bilaterally (normal $15-25 \text{ mL}$ ). Laboratory studies show:

Thyroid-stimulating hormone (TSH): $1.1 \text{ mU/L}$ (Reference: $0.5-5.0 \text{ mU/L}$ )
Free thyroxine (T4): $0.5 \text{ ng/dL}$ (Reference: $0.9-2.4 \text{ ng/dL}$ )
Total testosterone: $160 \text{ ng/dL}$ (Reference: $300-1000 \text{ ng/dL}$ )

Which of the following is the most likely diagnosis?

A
Autoimmune thyroiditis
B
Thyroxine-binding globulin deficiency
Anterior pituitary insufficiencyAnswer
D
Non-thyroidal illness syndrome
E
Autoimmune polyglandular syndrome type 2

Answer

Anterior pituitary insufficiency

This patient's presentation of fatigue, cold intolerance, delayed deep tendon reflexes, and low free T4 confirms a hypothyroid state. However, his TSH is strictly within normal limits. An intact hypothalamic-pituitary-thyroid axis would respond to a free T4 of

0.5 \text{ ng/dL}

with a robust elevation in TSH. The presence of a low free T4 paired with an inappropriately normal TSH indicates central (secondary) hypothyroidism. Concurrently, he has central hypogonadism (low libido, soft testes, low testosterone). Combined with his history of a severe traumatic brain injury (TBI), the most likely diagnosis is anterior pituitary insufficiency (post-traumatic hypopituitarism). TBI can cause shearing of the infundibular stalk or ischemic damage to the anterior pituitary gland, which may manifest months to years after the initial insult.

Step-by-Step Solution

Evaluate the clinical symptoms and physical exam findings.

The patient demonstrates classic signs of hypothyroidism (fatigue, cold intolerance, weight gain, bradycardia, delayed reflexes) and hypogonadism (diminished libido, small soft testes).

Identifying the affected endocrine axes guides the interpretation of the laboratory testing.

Interpret the laboratory hormone panel.

Free T4 is overtly low, but TSH is normal (

1.1 \text{ mU/L}

). Testosterone is low.

A low target hormone level with an inappropriately normal or low stimulating hormone level indicates secondary (central) failure rather than primary glandular failure.

Synthesize the laboratory pattern with the patient's medical history.

The patient has central hypothyroidism and central hypogonadism, which clinically correlates with a history of severe traumatic brain injury.

Head trauma can cause shearing forces on the hypothalamic-pituitary stalk or direct vascular injury, leading to post-traumatic hypopituitarism.

Key Concept

Secondary (central) hypothyroidism is characterized by a low free T4 in the setting of a low or inappropriately normal TSH. It can occur as a complication of severe traumatic brain injury.

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