A 38-year-old woman comes to the clinic complaining of worsening fatigue, a 4-kg (8.8-lb) … — USMLE Step 2 CK

A $38$ -year-old woman comes to the clinic complaining of worsening fatigue, a $4$ -kg ( $8.8$ -lb) weight gain, and amenorrhea for the past $8$ months. She also reports a persistent dry cough and mild shortness of breath on exertion for the past year. She has no significant past medical history and takes no medications. Vital signs are within normal limits. Physical examination reveals bilateral, tender, violaceous subcutaneous nodules on her anterior shins. Laboratory studies show the following:

Test	Result	Normal Range
Thyroid-stimulating hormone (TSH)	$1.1$ $\mu U/mL$	$0.4-4.0$ $\mu U/mL$
Free thyroxine (T4)	$0.4$ ng/dL	$0.9-2.4$ ng/dL
Prolactin	$65$ ng/mL	$4-23$ ng/mL
Human chorionic gonadotropin (hCG)	Negative	Negative

Which of the following is the most likely pathophysiologic mechanism underlying this patient's endocrine abnormalities?

A
Autoimmune destruction of thyroid follicular cells
B
Autonomous overproduction of hormone by a pituitary lactotroph adenoma
Granulomatous infiltration of the hypothalamic-pituitary axisAnswer
D
Ischemic necrosis of the anterior pituitary gland
E
Impaired peripheral deiodination of thyroxine

Answer

Granulomatous infiltration of the hypothalamic-pituitary axis

The correct answer identifies the underlying pathology as neurosarcoidosis. The patient's laboratory profile demonstrates central hypothyroidism (inappropriately normal TSH with a low free T4) combined with mild hyperprolactinemia. This combination is the hallmark of the 'stalk effect'—disruption of the hypothalamic-pituitary portal system. The disruption prevents Thyrotropin-Releasing Hormone (TRH) from reaching the pituitary (causing low TSH/T4) and prevents dopamine from reaching the pituitary (causing loss of lactotroph inhibition and subsequent mild hyperprolactinemia). The clinical clues of a dry cough and erythema nodosum point directly to sarcoidosis as the systemic granulomatous disease infiltrating the axis.

Step-by-Step Solution

Interpret the thyroid laboratory findings.

The patient has a low free T4 with an inappropriately normal TSH.

This pattern indicates central (secondary or tertiary) hypothyroidism, meaning the defect lies in the pituitary or hypothalamus, not the thyroid gland itself.

Interpret the prolactin level in the context of central hypothyroidism.

Prolactin is mildly elevated (

65

ng/mL).

A mass or infiltrative lesion compressing the pituitary stalk disrupts the delivery of dopamine from the hypothalamus to the anterior pituitary. Because dopamine normally inhibits prolactin secretion, this 'stalk effect' results in mild hyperprolactinemia.

Correlate the endocrine findings with the patient's systemic physical exam findings.

The patient has a chronic dry cough and erythema nodosum (tender shins).

These findings are classic for sarcoidosis. When sarcoidosis involves the central nervous system (neurosarcoidosis), it has a predilection for the basilar meninges and the hypothalamic-pituitary axis, leading to the observed endocrine profile.

Key Concept

Patients with central hypothyroidism (normal/low TSH and low T4) and mild hyperprolactinemia should be evaluated for a compressive or infiltrative lesion affecting the pituitary stalk, such as neurosarcoidosis, which disrupts dopaminergic inhibition.

Estimated Time:1m 30s

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