A 58-year-old man is evaluated in the clinic for severe fatigue, nausea, and a mild headac… — USMLE Step 2 CK

A $58$ -year-old man is evaluated in the clinic for severe fatigue, nausea, and a mild headache that has progressively worsened over the past two weeks. His medical history is significant for metastatic melanoma, for which he began treatment with intravenous nivolumab $12$ weeks ago. His blood pressure is $90/60$ mmHg seated and $82/50$ mmHg upon standing. His pulse is $92$ /min seated and $110$ /min standing. Physical examination reveals no skin hyperpigmentation, rashes, or mucosal lesions. Visual fields are normal to confrontation. Laboratory results are as follows:

Test	Result	Reference Range
Serum sodium	$131$ mEq/L	$136$ - $145$ mEq/L
Serum potassium	$4.2$ mEq/L	$3.5$ - $5.0$ mEq/L
Thyroid-stimulating hormone (TSH)	$0.1$ $\mu$ U/mL	$0.4$ - $4.0$ $\mu$ U/mL
Free thyroxine (T4)	$0.4$ ng/dL	$0.9$ - $1.7$ ng/dL

Which of the following is the most likely additional laboratory finding in this patient?

Decreased early morning serum cortisolCevap
B
Decreased serum aldosterone
C
Elevated serum potassium
D
Elevated serum prolactin greater than $200$ ng/mL
E
Elevated serum thyroid peroxidase antibodies

Cevap

The most likely additional finding is a decreased early morning serum cortisol level.

The correct answer identifies a decreased early morning serum cortisol level. This patient is presenting with symptoms of hypophysitis, a known immune-related adverse effect of checkpoint inhibitors like nivolumab. The laboratory findings of low TSH and proportionately low free T4 confirm central hypothyroidism. Inflammation of the pituitary gland typically leads to multiple anterior pituitary hormone deficiencies, most notably adrenocorticotropic hormone (ACTH), resulting in central adrenal insufficiency. A low early morning serum cortisol level is expected and explains the patient's orthostatic hypotension and hyponatremia (which occurs due to the loss of cortisol's suppressive effect on antidiuretic hormone release).

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Interpret the patient's thyroid function tests in the context of his medical history.

The low TSH and low free T4 indicate central hypothyroidism. The recent use of nivolumab (a PD-1 inhibitor) suggests immune checkpoint inhibitor-induced hypophysitis as the etiology.

Accurate interpretation of the pituitary-thyroid axis is required to localize the lesion to the pituitary gland rather than the thyroid.

Determine the physiological consequences of pituitary inflammation (hypophysitis).

Hypophysitis causes multiple anterior pituitary hormone deficiencies (panhypopituitarism), including a decrease in adrenocorticotropic hormone (ACTH), leading to central adrenal insufficiency.

Understanding the widespread effects of hypophysitis allows prediction of concurrent endocrine deficits, such as low cortisol, which explains the patient's hypotension and hyponatremia.

Differentiate between central and primary adrenal insufficiency to predict mineralocorticoid levels.

Central adrenal insufficiency (low ACTH) results in low cortisol but spares aldosterone secretion, which is regulated independently by the renin-angiotensin-aldosterone system. Therefore, potassium and aldosterone levels remain normal.

This distinction eliminates distractors related to hyperkalemia and low aldosterone, which are hallmarks of primary adrenal insufficiency (Addison's disease).

Anahtar Kavram

Immune checkpoint inhibitors can cause hypophysitis, leading to central hypothyroidism and central adrenal insufficiency. In central adrenal insufficiency, cortisol is low, but aldosterone and potassium levels remain normal because the renin-angiotensin-aldosterone system is intact.

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