During a routine health maintenance visit, a 48-year-old male construction worker describe… — USMLE Step 2 CK

During a routine health maintenance visit, a $48$ -year-old male construction worker describes a gradual decline in his energy levels and libido over the past $14$ months. He has also developed a pervasive feeling of being cold, even during summer months, alongside chronic, dull pain in the joints of his hands. He has no significant past medical history and takes no medications.

Vital signs include a blood pressure of $112/74$ mmHg and a heart rate of $58$ /min. Physical examination reveals a slate-gray to bronze discoloration of the skin, which is most prominent in sun-exposed areas and old scars. Palpation of the abdomen reveals a firm, non-tender liver edge $3$ cm below the right costal margin. Testicular volume is reduced bilaterally. The relaxation phase of the deep tendon reflexes is noticeably delayed.

Laboratory evaluation demonstrates:

Laboratory Test	Result	Reference Range
Fasting serum glucose	$162$ mg/dL	$< 100$ mg/dL
Thyroid-stimulating hormone (TSH)	$1.4$ $\mu$ U/mL	$0.4-4.2$ $\mu$ U/mL
Free thyroxine (T4)	$0.5$ ng/dL	$0.9-1.7$ ng/dL
Total testosterone	$125$ ng/dL	$300-1000$ ng/dL
Luteinizing hormone (LH)	$1.2$ mIU/mL	$2-9$ mIU/mL
Prolactin	$7$ ng/mL	$2-18$ ng/mL
Morning serum cortisol	$15$ $\mu$ g/dL	$5-25$ $\mu$ g/dL

Based on the patient's presentation and laboratory findings, which of the following is the most appropriate next step in diagnostic evaluation?

Measurement of serum transferrin saturation and ferritinAnswer
B
Assay for serum thyroid peroxidase antibodies
C
Magnetic resonance imaging of the pituitary gland
D
Cosyntropin (synthetic ACTH) stimulation testing
E
Measurement of fasting serum insulin-like growth factor 1

Answer

The most appropriate next diagnostic step is the measurement of serum transferrin saturation and ferritin to evaluate for hereditary hemochromatosis.

This patient's presentation is a classic, though advanced, manifestation of hereditary hemochromatosis. The excessive intestinal iron absorption leads to systemic iron deposition. The triad of skin hyperpigmentation, diabetes mellitus (fasting glucose

\ge 126

mg/dL), and hepatomegaly is historically referred to as 'bronze diabetes.' Importantly, the anterior pituitary is highly susceptible to iron deposition. Iron preferentially accumulates in gonadotrophs and thyrotrophs, leading to central hypogonadism (low testosterone with inappropriately low/normal LH) and central hypothyroidism (low free T4 with inappropriately normal TSH). The corticotrophs and lactotrophs are relatively spared, which explains his normal cortisol and prolactin levels. The most appropriate initial screening test for hereditary hemochromatosis is the measurement of serum transferrin saturation (typically

>45\%

in affected individuals) and serum ferritin levels, followed by confirmatory HFE gene mutation analysis.

Step-by-Step Solution

Analyze the thyroid and gonadal laboratory findings.

The patient has a low free T4 with an inappropriately normal TSH, and low testosterone with an inappropriately normal LH.

This specific pattern indicates secondary (central) hypothyroidism and secondary (central) hypogonadism, pointing to anterior pituitary dysfunction rather than primary glandular failure.

Evaluate the remaining endocrine laboratories and clinical signs.

Morning cortisol and prolactin are completely normal, ruling out Addison disease and making a large structural pituitary adenoma less likely. Fasting glucose is elevated, indicating new-onset diabetes mellitus.

Combining central endocrinopathy with new-onset diabetes, hepatomegaly, distinctive skin pigmentation, and arthropathy requires a unifying systemic diagnosis.

Identify the unifying underlying pathophysiology.

The clinical picture represents hereditary hemochromatosis ('bronze diabetes'), an iron overload disorder.

Excess iron systematically deposits in the liver (hepatomegaly), pancreas (diabetes), skin (hyperpigmentation), joints (arthropathy), and anterior pituitary (predominantly affecting gonadotrophs and thyrotrophs).

Select the best initial diagnostic test for this condition.

Measurement of serum transferrin saturation and ferritin is indicated.

These are the highly sensitive initial screening markers for systemic iron overload before proceeding to HFE gene mutation analysis or liver biopsy.

Key Concept

Hereditary hemochromatosis can present with complex multiorgan manifestations, including anterior pituitary infiltration that causes central hypogonadism and central hypothyroidism.

Question

Answer

Step-by-Step Solution

Key Concept

Common Mistakes

Topics

More questions from this topic